Nutrient chapter

Lipoic acid

109 recorded mechanisms · 9 availability situations · 6 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

The lipoyl cofactor is attached through an amide linkage to a conserved carrier-protein lysine side chain.
Protein-bound oxidized lipoyl-lysine → Human glycine-cleavage H-protein / GCSH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/40640146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23", "start_char": 0, "end_char": 953, "text_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23"}
experimental_model
X-ray structures of catalytic stages with human lipoyl synthase
exposure
Structural trapping of sulfur-insertion intermediates
limitations
Structural snapshots establish reaction intermediates, not clinical nutrient requirements.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human recombinant proteins
plain_language
The enzyme uses a tethered cofactor; free supplement molecules are a different pool.
primary_references
[ala-p40640146] Structural basis for catalysis by human lipoyl synthase. (2025). https://pubmed.ncbi.nlm.nih.gov/40640146/ DOI: 10.1038/s41467-025-61393-x
tissue_or_cell_type
LIAS and H-protein substrate
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 247–258
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structures of catalytic stages with human lipoyl synthase · source_derived_draft · unverified_draft
### ala-lipoyl-lysine-anchor The lipoyl cofactor is attached through an amide linkage to a conserved carrier-protein lysine side chain. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme uses a tethered cofactor; free supplement molecules are a different pool. organism: Human recombinant proteins tissue_or_cell_type: LIAS and H-protein substrate experimental_model: X-ray structures of catalytic stages with human lipoyl synthase limitations: Structural snapshots establish reaction intermediates, not clinical nutrient requirements. exposure: Structural trapping of sulfur-insertion intermediates evidence_span: {"source_cache": "artifacts/ala-research/40640146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23", "start_char": 0, "end_char": 953, "text_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23"} [ala-p40640146] Structural basis for catalysis by human lipoyl synthase. (2025). https://pubmed.ncbi.nlm.nih.gov/40640146/ DOI: 10.1038/s41467-025-61393-x
Complete structured claim and evidence
Purified mouse Lipt2 transferred octanoyl groups from E. coli ACP to human GCSH.
Mouse octanoyltransferase / Lipt2 → Human octanoyl-GCSH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/29987032.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0569075b59128ea021be6077596127d1c7aae1f9ac6b0acfd2ebcb268b650d3", "start_char": 16562, "end_char": 20381, "text_sha256": "34c5cb398fa99661566112ccf850c1fe0e4a5e74e3aa5b355b1695d12cb7b24d"}
experimental_model
Purified enzymes and bacterial pathway reconstruction
exposure
Recombinant proteins and radiolabeled substrates
limitations
Human and mouse constructs must not be conflated. Recombinant reconstruction establishes chemistry, not supplementation efficacy.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human proteins; mouse Lipt2 in purified transfer assays; E. coli host
plain_language
The first assembly step loads an eight-carbon precursor onto GCSH.
primary_references
[ala-p29987032] Protein moonlighting elucidates the essential human pathway catalyzing lipoic acid assembly on its cognate enzymes. (2018). https://pubmed.ncbi.nlm.nih.gov/29987032/ DOI: 10.1073/pnas.1805862115
tissue_or_cell_type
Lipoyl assembly pathway
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 221–232
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzymes and bacterial pathway reconstruction · source_derived_draft · unverified_draft
### ala-mouse-lipt2-octanoyl-transfer Purified mouse Lipt2 transferred octanoyl groups from E. coli ACP to human GCSH. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The first assembly step loads an eight-carbon precursor onto GCSH. organism: Human proteins; mouse Lipt2 in purified transfer assays; E. coli host tissue_or_cell_type: Lipoyl assembly pathway experimental_model: Purified enzymes and bacterial pathway reconstruction limitations: Human and mouse constructs must not be conflated. Recombinant reconstruction establishes chemistry, not supplementation efficacy. exposure: Recombinant proteins and radiolabeled substrates evidence_span: {"source_cache": "artifacts/ala-research/29987032.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0569075b59128ea021be6077596127d1c7aae1f9ac6b0acfd2ebcb268b650d3", "start_char": 16562, "end_char": 20381, "text_sha256": "34c5cb398fa99661566112ccf850c1fe0e4a5e74e3aa5b355b1695d12cb7b24d"} [ala-p29987032] Protein moonlighting elucidates the essential human pathway catalyzing lipoic acid assembly on its cognate enzymes. (2018). https://pubmed.ncbi.nlm.nih.gov/29987032/ DOI: 10.1073/pnas.1805862115
Complete structured claim and evidence
LIAS installs sulfur at carbon 6 and carbon 8 of an octanoyl-lysyl residue on GCSH.
Lipoic acid synthetase / LIAS → LIAS sulfur insertion into octanoyl-GCSH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/40640146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23", "start_char": 0, "end_char": 953, "text_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23"}
experimental_model
X-ray structures of catalytic stages with human lipoyl synthase
exposure
Structural trapping of sulfur-insertion intermediates
limitations
Structural snapshots establish reaction intermediates, not clinical nutrient requirements.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human recombinant proteins
plain_language
LIAS turns the attached precursor into a sulfur-bearing working cofactor.
primary_references
[ala-p40640146] Structural basis for catalysis by human lipoyl synthase. (2025). https://pubmed.ncbi.nlm.nih.gov/40640146/ DOI: 10.1038/s41467-025-61393-x
tissue_or_cell_type
LIAS and H-protein substrate
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 260–271
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structures of catalytic stages with human lipoyl synthase · source_derived_draft · unverified_draft
### ala-lias-sulfur-installation LIAS installs sulfur at carbon 6 and carbon 8 of an octanoyl-lysyl residue on GCSH. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: LIAS turns the attached precursor into a sulfur-bearing working cofactor. organism: Human recombinant proteins tissue_or_cell_type: LIAS and H-protein substrate experimental_model: X-ray structures of catalytic stages with human lipoyl synthase limitations: Structural snapshots establish reaction intermediates, not clinical nutrient requirements. exposure: Structural trapping of sulfur-insertion intermediates evidence_span: {"source_cache": "artifacts/ala-research/40640146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23", "start_char": 0, "end_char": 953, "text_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23"} [ala-p40640146] Structural basis for catalysis by human lipoyl synthase. (2025). https://pubmed.ncbi.nlm.nih.gov/40640146/ DOI: 10.1038/s41467-025-61393-x
Complete structured claim and evidence
Reconstituted LIPT1 transfers the lipoyl group from GCSH to dehydrogenase E2 lipoyl domains.
Human lipoyl amidotransferase / LIPT1 → Human lipoyl-GCSH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/29987032.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3fc07be493a0d6e22ea55c9509cb2d727180f5921d588a52d2d9300a25aa49a2", "start_char": 0, "end_char": 989, "text_sha256": "3fc07be493a0d6e22ea55c9509cb2d727180f5921d588a52d2d9300a25aa49a2"}
experimental_model
Purified enzymes and bacterial pathway reconstruction
exposure
Recombinant proteins and radiolabeled substrates
limitations
Human and mouse constructs must not be conflated. Recombinant reconstruction establishes chemistry, not supplementation efficacy.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human proteins; mouse Lipt2 in purified transfer assays; E. coli host
plain_language
GCSH carries the cofactor before LIPT1 passes it to energy-processing enzymes.
primary_references
[ala-p29987032] Protein moonlighting elucidates the essential human pathway catalyzing lipoic acid assembly on its cognate enzymes. (2018). https://pubmed.ncbi.nlm.nih.gov/29987032/ DOI: 10.1073/pnas.1805862115
tissue_or_cell_type
Lipoyl assembly pathway
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 208–219
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzymes and bacterial pathway reconstruction · source_derived_draft · unverified_draft
### ala-lipt1-gcsh-transfer Reconstituted LIPT1 transfers the lipoyl group from GCSH to dehydrogenase E2 lipoyl domains. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: GCSH carries the cofactor before LIPT1 passes it to energy-processing enzymes. organism: Human proteins; mouse Lipt2 in purified transfer assays; E. coli host tissue_or_cell_type: Lipoyl assembly pathway experimental_model: Purified enzymes and bacterial pathway reconstruction limitations: Human and mouse constructs must not be conflated. Recombinant reconstruction establishes chemistry, not supplementation efficacy. exposure: Recombinant proteins and radiolabeled substrates evidence_span: {"source_cache": "artifacts/ala-research/29987032.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3fc07be493a0d6e22ea55c9509cb2d727180f5921d588a52d2d9300a25aa49a2", "start_char": 0, "end_char": 989, "text_sha256": "3fc07be493a0d6e22ea55c9509cb2d727180f5921d588a52d2d9300a25aa49a2"} [ala-p29987032] Protein moonlighting elucidates the essential human pathway catalyzing lipoic acid assembly on its cognate enzymes. (2018). https://pubmed.ncbi.nlm.nih.gov/29987032/ DOI: 10.1073/pnas.1805862115
Complete structured claim and evidence
Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD.
DLD → Protein-bound reduced dihydrolipoyl-lysine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction.
evidence
[{"paper_key": "brautigam-2005-dld", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human DLD crystallography with NAD+ and NADH.
limitations
Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover.
primary_references
[brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014
tissue_or_cell_type
Purified enzyme
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 717–729
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DLD crystallography with NAD+ and NADH. · source_derived_draft · unverified_draft
### b1-dld-fad-nad-lipoyl-regeneration Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Human DLD crystallography with NAD+ and NADH. limitations: Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency. evidence: [{"paper_key": "brautigam-2005-dld", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction. nutrient: Thiamine (vitamin B1) [brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014
Complete structured claim and evidence
Human AMT transfers the aminomethyl-lipoyl intermediate's carbon to tetrahydrofolate, yielding 5,10-methylene-THF, ammonia and reduced H-protein.
Human aminomethyltransferase / glycine-cleavage T-protein → 5,10-Methylenetetrahydrofolate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6-dependent GLDC precedes lipoyl-carrier transfer and folate-dependent AMT chemistry.
experimental_model
Purified human AMT structures and mutational analyses
limitations
AMT is the directly examined human enzyme; this study did not test dietary B6 depletion or the entire pathway flux.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Glycine cleavage connects its B6-dependent first step to a separate folate-dependent step.
primary_references
[b6-amt-2005] Crystal structure of human T-protein of glycine cleavage system at 2.0 A resolution and its implication for understanding non-ketotic hyperglycinemia. (2005). https://pubmed.ncbi.nlm.nih.gov/16051266/ DOI: 10.1016/j.jmb.2005.06.056
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 682–692
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human AMT structures and mutational analyses · source_derived_draft · unverified_draft
### b6-met-amt-onecarbon Human AMT transfers the aminomethyl-lipoyl intermediate's carbon to tetrahydrofolate, yielding 5,10-methylene-THF, ammonia and reduced H-protein. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glycine cleavage connects its B6-dependent first step to a separate folate-dependent step. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human AMT structures and mutational analyses limitations: AMT is the directly examined human enzyme; this study did not test dietary B6 depletion or the entire pathway flux. cross_nutrient: B6-dependent GLDC precedes lipoyl-carrier transfer and folate-dependent AMT chemistry. [b6-amt-2005] Crystal structure of human T-protein of glycine cleavage system at 2.0 A resolution and its implication for understanding non-ketotic hyperglycinemia. (2005). https://pubmed.ncbi.nlm.nih.gov/16051266/ DOI: 10.1016/j.jmb.2005.06.056
Complete structured claim and evidence
Human SMVT cryo-EM complexes placed pantothenate, biotin and oxidized lipoate in substantially overlapping positions within one central substrate-binding pocket.
Human sodium-dependent multivitamin transporter / SLC5A6 → Pantothenate (vitamin B5) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells
exposure
SMVTEM/NbALFA complexes incubated with 2 mM D-pantothenic acid, 4 mM biotin or 22 mM oxidized alpha-lipoic acid for separate structures.
limitations
Engineered, purified transporter structure supports a binding mechanism; it does not establish nutritional competition severity in vivo. The structural construct has altered biotin transport kinetics relative to wild type. These are separate ligand-bound complexes, not simultaneous occupancy.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
B5, biotin and free lipoate use the same binding pocket in SMVT.
primary_references
[b5-trans-structure2026] Structural basis for multivitamin recognition and transport by human SMVT. (2026). https://pubmed.ncbi.nlm.nih.gov/42364996/ DOI: 10.1038/s41467-026-74948-3
tissue_or_cell_type
Purified human SMVT; HEK293-derived expression system
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 405–416
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells · source_derived_draft · unverified_draft
### b5-trans-shared-substrate-site Human SMVT cryo-EM complexes placed pantothenate, biotin and oxidized lipoate in substantially overlapping positions within one central substrate-binding pocket. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: B5, biotin and free lipoate use the same binding pocket in SMVT. organism: Homo sapiens tissue_or_cell_type: Purified human SMVT; HEK293-derived expression system experimental_model: Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells limitations: Engineered, purified transporter structure supports a binding mechanism; it does not establish nutritional competition severity in vivo. The structural construct has altered biotin transport kinetics relative to wild type. These are separate ligand-bound complexes, not simultaneous occupancy. exposure: SMVTEM/NbALFA complexes incubated with 2 mM D-pantothenic acid, 4 mM biotin or 22 mM oxidized alpha-lipoic acid for separate structures. cross_nutrient: true [b5-trans-structure2026] Structural basis for multivitamin recognition and transport by human SMVT. (2026). https://pubmed.ncbi.nlm.nih.gov/42364996/ DOI: 10.1038/s41467-026-74948-3
Complete structured claim and evidence
Oxidized alpha-lipoic acid inhibited human SMVT-mediated radiolabeled biotin uptake with an IC50 of 9.1 micromolar in the 2026 HEK293T assay.
Lipoic acid → Cellular biotin uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells
exposure
Biotin uptake assay: 5 micromolar unlabeled biotin plus [3H]biotin at a 300:1 molar ratio; 30 degrees C for ten minutes; inhibitor concentration varied.
limitations
In-vitro IC50 depends on tracer/substrate concentration and expression conditions; it is not a human supplement dose, affinity constant, or threshold for biotin deficiency.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
Oxidized alpha-lipoic acid competed with biotin uptake in the SMVT cell assay.
primary_references
[b5-trans-structure2026] Structural basis for multivitamin recognition and transport by human SMVT. (2026). https://pubmed.ncbi.nlm.nih.gov/42364996/ DOI: 10.1038/s41467-026-74948-3
tissue_or_cell_type
HEK293T cells expressing human SMVT
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 444–455
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells · source_derived_draft · unverified_draft
### b5-trans-lipoate-inhibits-biotin Oxidized alpha-lipoic acid inhibited human SMVT-mediated radiolabeled biotin uptake with an IC50 of 9.1 micromolar in the 2026 HEK293T assay. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Oxidized alpha-lipoic acid competed with biotin uptake in the SMVT cell assay. organism: Homo sapiens tissue_or_cell_type: HEK293T cells expressing human SMVT experimental_model: Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells limitations: In-vitro IC50 depends on tracer/substrate concentration and expression conditions; it is not a human supplement dose, affinity constant, or threshold for biotin deficiency. exposure: Biotin uptake assay: 5 micromolar unlabeled biotin plus [3H]biotin at a 300:1 molar ratio; 30 degrees C for ten minutes; inhibitor concentration varied. cross_nutrient: true [b5-trans-structure2026] Structural basis for multivitamin recognition and transport by human SMVT. (2026). https://pubmed.ncbi.nlm.nih.gov/42364996/ DOI: 10.1038/s41467-026-74948-3
Complete structured claim and evidence
Erythrocytes from a G6PD-deficient person failed to reduce lipoic acid in the assay; pharmacological G6PD inhibition also prevented reduction.
Glucose-6-phosphate dehydrogenase / G6PD → Erythrocyte reduction of free lipoic acid source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/7632170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ebbc851e5279e646bc7c892645c931a3fd2993830c3f4405379839cbbd6e707", "start_char": 0, "end_char": 1863, "text_sha256": "2ebbc851e5279e646bc7c892645c931a3fd2993830c3f4405379839cbbd6e707"}
experimental_model
Human erythrocytes, one G6PD-deficient donor and purified-enzyme assays
exposure
Lipoic acid with glucose/2-deoxyglucose and G6PD inhibition
limitations
The deficient-donor finding is small and mechanistic; it is not a clinical safety or efficacy trial in G6PD deficiency.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
Providing the oxidized molecule did not overcome the missing reducing capacity.
primary_references
[ala-p7632170] Reduction and transport of lipoic acid by human erythrocytes. (1995). https://pubmed.ncbi.nlm.nih.gov/7632170/ DOI: 10.1016/0006-2952(95)00084-d
tissue_or_cell_type
Erythrocytes and glutathione reductase
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 728–739
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocytes, one G6PD-deficient donor and purified-enzyme assays · source_derived_draft · unverified_draft
### ala-g6pd-reduction-failure Erythrocytes from a G6PD-deficient person failed to reduce lipoic acid in the assay; pharmacological G6PD inhibition also prevented reduction. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing the oxidized molecule did not overcome the missing reducing capacity. organism: Human tissue_or_cell_type: Erythrocytes and glutathione reductase experimental_model: Human erythrocytes, one G6PD-deficient donor and purified-enzyme assays limitations: The deficient-donor finding is small and mechanistic; it is not a clinical safety or efficacy trial in G6PD deficiency. exposure: Lipoic acid with glucose/2-deoxyglucose and G6PD inhibition evidence_span: {"source_cache": "artifacts/ala-research/7632170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ebbc851e5279e646bc7c892645c931a3fd2993830c3f4405379839cbbd6e707", "start_char": 0, "end_char": 1863, "text_sha256": "2ebbc851e5279e646bc7c892645c931a3fd2993830c3f4405379839cbbd6e707"} [ala-p7632170] Reduction and transport of lipoic acid by human erythrocytes. (1995). https://pubmed.ncbi.nlm.nih.gov/7632170/ DOI: 10.1016/0006-2952(95)00084-d
Complete structured claim and evidence
Cell-derived DHLA reduced extracellular cystine to cysteine in the tested cultures.
Free dihydrolipoic acid / DHLA → Cystine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/9288403.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2", "start_char": 0, "end_char": 1497, "text_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2"}
experimental_model
Cell-culture thiol transport and glutathione experiments
exposure
Lipoic acid/DHLA treatment and extracellular thiol measurements
limitations
Cell-type and extracellular-substrate dependence; no demonstration of general methylation-vitamin depletion.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human, rat and mouse cells as specified
plain_language
Reduced lipoic acid made a glutathione building block more available.
primary_references
[ala-p9288403] Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. (1997). https://pubmed.ncbi.nlm.nih.gov/9288403/ DOI: 10.1002/biof.5520060303
tissue_or_cell_type
Human lymphocytes, Jurkat cells and erythrocytes; rat C6 and mouse NB41A3 cells
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 793–804
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-culture thiol transport and glutathione experiments · source_derived_draft · unverified_draft
### ala-dhla-cystine-cysteine Cell-derived DHLA reduced extracellular cystine to cysteine in the tested cultures. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reduced lipoic acid made a glutathione building block more available. organism: Human, rat and mouse cells as specified tissue_or_cell_type: Human lymphocytes, Jurkat cells and erythrocytes; rat C6 and mouse NB41A3 cells experimental_model: Cell-culture thiol transport and glutathione experiments limitations: Cell-type and extracellular-substrate dependence; no demonstration of general methylation-vitamin depletion. exposure: Lipoic acid/DHLA treatment and extracellular thiol measurements evidence_span: {"source_cache": "artifacts/ala-research/9288403.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2", "start_char": 0, "end_char": 1497, "text_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2"} [ala-p9288403] Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. (1997). https://pubmed.ncbi.nlm.nih.gov/9288403/ DOI: 10.1002/biof.5520060303
Complete structured claim and evidence
Lipoic acid supplementation did not improve the reported clinical course or restore deficient PDH, OGDH and leucine-catabolic function in LIPT2-deficient fibroblasts.
Lipoic acid → Human pyruvate dehydrogenase complex source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/28757203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f", "start_char": 0, "end_char": 1639, "text_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f"}
experimental_model
Three affected children from two families and patient-derived fibroblasts
exposure
Biallelic LIPT2 variants; wild-type gene rescue and lipoic acid supplementation
limitations
Rare inherited disease; not evidence for common dietary lipoic-acid deficiency.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
More free lipoic acid did not bypass the broken assembly step.
primary_references
[ala-p28757203] Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy. (2017). https://pubmed.ncbi.nlm.nih.gov/28757203/ DOI: 10.1016/j.ajhg.2017.07.001
tissue_or_cell_type
Patient cells and clinical phenotype
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 442–453
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three affected children from two families and patient-derived fibroblasts · source_derived_draft · unverified_draft
### ala-lipt2-supplement-no-rescue Lipoic acid supplementation did not improve the reported clinical course or restore deficient PDH, OGDH and leucine-catabolic function in LIPT2-deficient fibroblasts. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: More free lipoic acid did not bypass the broken assembly step. organism: Human tissue_or_cell_type: Patient cells and clinical phenotype experimental_model: Three affected children from two families and patient-derived fibroblasts limitations: Rare inherited disease; not evidence for common dietary lipoic-acid deficiency. exposure: Biallelic LIPT2 variants; wild-type gene rescue and lipoic acid supplementation evidence_span: {"source_cache": "artifacts/ala-research/28757203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f", "start_char": 0, "end_char": 1639, "text_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f"} [ala-p28757203] Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy. (2017). https://pubmed.ncbi.nlm.nih.gov/28757203/ DOI: 10.1016/j.ajhg.2017.07.001
Complete structured claim and evidence
In SYDNEY 2, TSS fell by 4.9, 4.5 and 4.7 points in the 600-, 1200- and 1800-mg groups versus 2.9 with placebo over five weeks.
Lipoic acid → Diabetic polyneuropathy Total Symptom Score / TSS source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/17065669.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a54016cad3453fec96e99aa5906435793d7baaddaf5254d5ce335aac5bb4519", "start_char": 0, "end_char": 1756, "text_sha256": "3a54016cad3453fec96e99aa5906435793d7baaddaf5254d5ce335aac5bb4519"}
experimental_model
SYDNEY 2 randomized double-blind placebo-controlled trial
exposure
Oral ALA 600, 1200 or 1800 mg/day for five weeks
limitations
Short-term symptom endpoint; no proof of nerve regeneration, lifelong benefit or correction of a nutritional deficiency.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
This short trial found greater symptom-score improvement with ALA.
primary_references
[ala-p17065669] Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. (2006). https://pubmed.ncbi.nlm.nih.gov/17065669/ DOI: 10.2337/dc06-1216
tissue_or_cell_type
181 participants with diabetic distal symmetric polyneuropathy
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1118–1129
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SYDNEY 2 randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### ala-sydney2-tss In SYDNEY 2, TSS fell by 4.9, 4.5 and 4.7 points in the 600-, 1200- and 1800-mg groups versus 2.9 with placebo over five weeks. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: This short trial found greater symptom-score improvement with ALA. organism: Human tissue_or_cell_type: 181 participants with diabetic distal symmetric polyneuropathy experimental_model: SYDNEY 2 randomized double-blind placebo-controlled trial limitations: Short-term symptom endpoint; no proof of nerve regeneration, lifelong benefit or correction of a nutritional deficiency. exposure: Oral ALA 600, 1200 or 1800 mg/day for five weeks evidence_span: {"source_cache": "artifacts/ala-research/17065669.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a54016cad3453fec96e99aa5906435793d7baaddaf5254d5ce335aac5bb4519", "start_char": 0, "end_char": 1756, "text_sha256": "3a54016cad3453fec96e99aa5906435793d7baaddaf5254d5ce335aac5bb4519"} [ala-p17065669] Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. (2006). https://pubmed.ncbi.nlm.nih.gov/17065669/ DOI: 10.2337/dc06-1216
Complete structured claim and evidence
Full-length human LIPT2 complemented the E. coli lipB/lplA deletion strain, supporting its octanoyltransferase assignment.
Human octanoyltransferase / LIPT2 → Mitochondrial protein lipoylation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/29987032.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0569075b59128ea021be6077596127d1c7aae1f9ac6b0acfd2ebcb268b650d3", "start_char": 31198, "end_char": 31564, "text_sha256": "967fbdc21edbac2bfd27e7c9c92a2ffe8a0b167c96d55f1095e429241be9463f"}
experimental_model
Purified enzymes and bacterial pathway reconstruction
exposure
Recombinant proteins and radiolabeled substrates
limitations
Bacterial complementation; the purified donor-transfer assay used mouse Lipt2. This is not direct flux measurement in a human mitochondrion.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human proteins; mouse Lipt2 in purified transfer assays; E. coli host
plain_language
Human LIPT2 restored the missing pathway function in a bacterial test.
primary_references
[ala-p29987032] Protein moonlighting elucidates the essential human pathway catalyzing lipoic acid assembly on its cognate enzymes. (2018). https://pubmed.ncbi.nlm.nih.gov/29987032/ DOI: 10.1073/pnas.1805862115
tissue_or_cell_type
Lipoyl assembly pathway
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 234–245
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzymes and bacterial pathway reconstruction · source_derived_draft · unverified_draft
### ala-human-lipt2-complementation Full-length human LIPT2 complemented the E. coli lipB/lplA deletion strain, supporting its octanoyltransferase assignment. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human LIPT2 restored the missing pathway function in a bacterial test. organism: Human proteins; mouse Lipt2 in purified transfer assays; E. coli host tissue_or_cell_type: Lipoyl assembly pathway experimental_model: Purified enzymes and bacterial pathway reconstruction limitations: Bacterial complementation; the purified donor-transfer assay used mouse Lipt2. This is not direct flux measurement in a human mitochondrion. exposure: Recombinant proteins and radiolabeled substrates evidence_span: {"source_cache": "artifacts/ala-research/29987032.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0569075b59128ea021be6077596127d1c7aae1f9ac6b0acfd2ebcb268b650d3", "start_char": 31198, "end_char": 31564, "text_sha256": "967fbdc21edbac2bfd27e7c9c92a2ffe8a0b167c96d55f1095e429241be9463f"} [ala-p29987032] Protein moonlighting elucidates the essential human pathway catalyzing lipoic acid assembly on its cognate enzymes. (2018). https://pubmed.ncbi.nlm.nih.gov/29987032/ DOI: 10.1073/pnas.1805862115
Complete structured claim and evidence
Crystallography captured LIAS cross-linked to its H-protein substrate through a 6-mercaptooctanoyl ligand at a [3Fe-4S] cluster.
Lipoic acid synthetase / LIAS → LIAS-GCSH 6-mercaptooctanoyl [3Fe-4S] intermediate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/40640146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23", "start_char": 0, "end_char": 953, "text_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23"}
experimental_model
X-ray structures of catalytic stages with human lipoyl synthase
exposure
Structural trapping of sulfur-insertion intermediates
limitations
Structural snapshots establish reaction intermediates, not clinical nutrient requirements.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human recombinant proteins
plain_language
One sulfur-insertion intermediate temporarily links the enzyme, its iron-sulfur cluster and its substrate.
primary_references
[ala-p40640146] Structural basis for catalysis by human lipoyl synthase. (2025). https://pubmed.ncbi.nlm.nih.gov/40640146/ DOI: 10.1038/s41467-025-61393-x
tissue_or_cell_type
LIAS and H-protein substrate
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 273–284
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structures of catalytic stages with human lipoyl synthase · source_derived_draft · unverified_draft
### ala-lias-trapped-intermediate Crystallography captured LIAS cross-linked to its H-protein substrate through a 6-mercaptooctanoyl ligand at a [3Fe-4S] cluster. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: One sulfur-insertion intermediate temporarily links the enzyme, its iron-sulfur cluster and its substrate. organism: Human recombinant proteins tissue_or_cell_type: LIAS and H-protein substrate experimental_model: X-ray structures of catalytic stages with human lipoyl synthase limitations: Structural snapshots establish reaction intermediates, not clinical nutrient requirements. exposure: Structural trapping of sulfur-insertion intermediates evidence_span: {"source_cache": "artifacts/ala-research/40640146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23", "start_char": 0, "end_char": 953, "text_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23"} [ala-p40640146] Structural basis for catalysis by human lipoyl synthase. (2025). https://pubmed.ncbi.nlm.nih.gov/40640146/ DOI: 10.1038/s41467-025-61393-x
Complete structured claim and evidence
LIAS cleaves SAM to generate a 5-deoxyadenosyl radical that initiates hydrogen abstraction from the octanoyl substrate.
S-Adenosyl-L-methionine → LIAS sulfur insertion into octanoyl-GCSH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"}
experimental_model
Purified human LIAS turnover and cluster-transfer assays
exposure
LIAS with candidate iron-sulfur cluster donors
limitations
Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human recombinant proteins
plain_language
SAM supplies radical chemistry here; this reaction is not methyl-group transfer.
primary_references
[ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
tissue_or_cell_type
Mitochondrial lipoyl synthesis machinery
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 286–297
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human LIAS turnover and cluster-transfer assays · source_derived_draft · unverified_draft
### ala-lias-sam-radical LIAS cleaves SAM to generate a 5-deoxyadenosyl radical that initiates hydrogen abstraction from the octanoyl substrate. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: SAM supplies radical chemistry here; this reaction is not methyl-group transfer. organism: Human recombinant proteins tissue_or_cell_type: Mitochondrial lipoyl synthesis machinery experimental_model: Purified human LIAS turnover and cluster-transfer assays limitations: Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells. exposure: LIAS with candidate iron-sulfur cluster donors evidence_span: {"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"} [ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
Complete structured claim and evidence
LIAS has distinct radical-SAM and auxiliary [4Fe-4S] clusters; the latter supplies sulfur during lipoyl synthesis.
Lipoic acid synthetase / LIAS → [4Fe-4S] iron-sulfur cluster source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"}
experimental_model
Purified human LIAS turnover and cluster-transfer assays
exposure
LIAS with candidate iron-sulfur cluster donors
limitations
Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human recombinant proteins
plain_language
Two iron-sulfur clusters perform different jobs in the same enzyme.
primary_references
[ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
tissue_or_cell_type
Mitochondrial lipoyl synthesis machinery
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 299–310
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human LIAS turnover and cluster-transfer assays · source_derived_draft · unverified_draft
### ala-lias-two-clusters LIAS has distinct radical-SAM and auxiliary [4Fe-4S] clusters; the latter supplies sulfur during lipoyl synthesis. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two iron-sulfur clusters perform different jobs in the same enzyme. organism: Human recombinant proteins tissue_or_cell_type: Mitochondrial lipoyl synthesis machinery experimental_model: Purified human LIAS turnover and cluster-transfer assays limitations: Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells. exposure: LIAS with candidate iron-sulfur cluster donors evidence_span: {"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"} [ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
Complete structured claim and evidence
Without auxiliary-cluster restoration, sulfur extraction degrades the LIAS auxiliary cluster and limits turnover.
LIAS auxiliary [4Fe-4S] site → LIAS catalytic turnover source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"}
experimental_model
Purified human LIAS turnover and cluster-transfer assays
exposure
LIAS with candidate iron-sulfur cluster donors
limitations
Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human recombinant proteins
plain_language
The sulfur-supplying part must be rebuilt for continued work.
primary_references
[ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
tissue_or_cell_type
Mitochondrial lipoyl synthesis machinery
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 312–323
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human LIAS turnover and cluster-transfer assays · source_derived_draft · unverified_draft
### ala-aux-cluster-consumed Without auxiliary-cluster restoration, sulfur extraction degrades the LIAS auxiliary cluster and limits turnover. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The sulfur-supplying part must be rebuilt for continued work. organism: Human recombinant proteins tissue_or_cell_type: Mitochondrial lipoyl synthesis machinery experimental_model: Purified human LIAS turnover and cluster-transfer assays limitations: Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells. exposure: LIAS with candidate iron-sulfur cluster donors evidence_span: {"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"} [ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
Complete structured claim and evidence
NFU1 forms a tight complex with LIAS and efficiently restores its auxiliary cluster during turnover in vitro.
Human NFU1 iron-sulfur cluster carrier → LIAS auxiliary [4Fe-4S] site source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"}
experimental_model
Purified human LIAS turnover and cluster-transfer assays
exposure
LIAS with candidate iron-sulfur cluster donors
limitations
Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human recombinant proteins
plain_language
NFU1 replenishes the sulfur-supplying cluster.
primary_references
[ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
tissue_or_cell_type
Mitochondrial lipoyl synthesis machinery
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 325–336
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human LIAS turnover and cluster-transfer assays · source_derived_draft · unverified_draft
### ala-nfu1-aux-repair NFU1 forms a tight complex with LIAS and efficiently restores its auxiliary cluster during turnover in vitro. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: NFU1 replenishes the sulfur-supplying cluster. organism: Human recombinant proteins tissue_or_cell_type: Mitochondrial lipoyl synthesis machinery experimental_model: Purified human LIAS turnover and cluster-transfer assays limitations: Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells. exposure: LIAS with candidate iron-sulfur cluster donors evidence_span: {"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"} [ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
Complete structured claim and evidence
BOLA3 did not directly enhance Fe-S cluster transfer from NFU1 or GLRX5 to LIAS in the purified assay.
Human BOLA3 → LIAS catalytic turnover source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"}
experimental_model
Purified human LIAS turnover and cluster-transfer assays
exposure
LIAS with candidate iron-sulfur cluster donors
limitations
Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human recombinant proteins
plain_language
A protein can be essential in cells without stimulating this isolated transfer step.
primary_references
[ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
tissue_or_cell_type
Mitochondrial lipoyl synthesis machinery
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 338–349
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human LIAS turnover and cluster-transfer assays · source_derived_draft · unverified_draft
### ala-bola3-direct-assay-null BOLA3 did not directly enhance Fe-S cluster transfer from NFU1 or GLRX5 to LIAS in the purified assay. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A protein can be essential in cells without stimulating this isolated transfer step. organism: Human recombinant proteins tissue_or_cell_type: Mitochondrial lipoyl synthesis machinery experimental_model: Purified human LIAS turnover and cluster-transfer assays limitations: Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells. exposure: LIAS with candidate iron-sulfur cluster donors evidence_span: {"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"} [ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
Complete structured claim and evidence
ISCA1 and ISCA2 produced only limited enhancement of LIAS turnover in this donor comparison.
Human ISCA1 → LIAS catalytic turnover source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"}
experimental_model
Purified human LIAS turnover and cluster-transfer assays
exposure
LIAS with candidate iron-sulfur cluster donors
limitations
Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human recombinant proteins
plain_language
Not every iron-sulfur carrier restores repeated activity equally well.
primary_references
[ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
tissue_or_cell_type
Mitochondrial lipoyl synthesis machinery
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 351–362
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human LIAS turnover and cluster-transfer assays · source_derived_draft · unverified_draft
### ala-isca-limited-turnover ISCA1 and ISCA2 produced only limited enhancement of LIAS turnover in this donor comparison. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Not every iron-sulfur carrier restores repeated activity equally well. organism: Human recombinant proteins tissue_or_cell_type: Mitochondrial lipoyl synthesis machinery experimental_model: Purified human LIAS turnover and cluster-transfer assays limitations: Cell-free transfer distinguishes direct donor activity from upstream functions in intact cells. exposure: LIAS with candidate iron-sulfur cluster donors evidence_span: {"source_cache": "artifacts/ala-research/36281303.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f", "start_char": 0, "end_char": 1732, "text_sha256": "29a716d2027786ee1eefa5380aca1ddc035ec330409162f3d4e61db20015780f"} [ala-p36281303] In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1. (2022). https://pubmed.ncbi.nlm.nih.gov/36281303/ DOI: 10.1021/acsbiomedchemau.2c00020
Complete structured claim and evidence
An NFU1-ISCA1 heterodimer delivers a [4Fe-4S] cluster to the radical-SAM site of LIAS.
Human NFU1-ISCA1 complex → LIAS radical-SAM [4Fe-4S] site source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/35343688.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689", "start_char": 0, "end_char": 670, "text_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689"}
experimental_model
Recombinant protein interaction and cluster-insertion analysis
exposure
NFU1-ISCA1 donor complex
limitations
Loading the radical-SAM site is distinct from recycling the auxiliary sulfur-donor site.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human proteins
plain_language
A separate assembly route equips the radical-generating site.
primary_references
[ala-p35343688] Protein-Interaction Affinity Gradient Drives [4Fe-4S] Cluster Insertion in Human Lipoyl Synthase. (2022). https://pubmed.ncbi.nlm.nih.gov/35343688/ DOI: 10.1021/jacs.1c13626
tissue_or_cell_type
LIAS radical-SAM site
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 364–375
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant protein interaction and cluster-insertion analysis · source_derived_draft · unverified_draft
### ala-nfu1-isca1-radical-site An NFU1-ISCA1 heterodimer delivers a [4Fe-4S] cluster to the radical-SAM site of LIAS. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate assembly route equips the radical-generating site. organism: Human proteins tissue_or_cell_type: LIAS radical-SAM site experimental_model: Recombinant protein interaction and cluster-insertion analysis limitations: Loading the radical-SAM site is distinct from recycling the auxiliary sulfur-donor site. exposure: NFU1-ISCA1 donor complex evidence_span: {"source_cache": "artifacts/ala-research/35343688.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689", "start_char": 0, "end_char": 670, "text_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689"} [ala-p35343688] Protein-Interaction Affinity Gradient Drives [4Fe-4S] Cluster Insertion in Human Lipoyl Synthase. (2022). https://pubmed.ncbi.nlm.nih.gov/35343688/ DOI: 10.1021/jacs.1c13626
Complete structured claim and evidence
The NFU1 C-domain guides cluster transfer along increasing interaction affinity from ISCA1 toward LIAS.
Human NFU1 iron-sulfur cluster carrier → Lipoic acid synthetase / LIAS source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/35343688.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689", "start_char": 0, "end_char": 670, "text_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689"}
experimental_model
Recombinant protein interaction and cluster-insertion analysis
exposure
NFU1-ISCA1 donor complex
limitations
Loading the radical-SAM site is distinct from recycling the auxiliary sulfur-donor site.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human proteins
plain_language
Protein-to-protein recognition helps deliver the cluster to the correct destination.
primary_references
[ala-p35343688] Protein-Interaction Affinity Gradient Drives [4Fe-4S] Cluster Insertion in Human Lipoyl Synthase. (2022). https://pubmed.ncbi.nlm.nih.gov/35343688/ DOI: 10.1021/jacs.1c13626
tissue_or_cell_type
LIAS radical-SAM site
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 377–388
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant protein interaction and cluster-insertion analysis · source_derived_draft · unverified_draft
### ala-nfu1-affinity-gradient The NFU1 C-domain guides cluster transfer along increasing interaction affinity from ISCA1 toward LIAS. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Protein-to-protein recognition helps deliver the cluster to the correct destination. organism: Human proteins tissue_or_cell_type: LIAS radical-SAM site experimental_model: Recombinant protein interaction and cluster-insertion analysis limitations: Loading the radical-SAM site is distinct from recycling the auxiliary sulfur-donor site. exposure: NFU1-ISCA1 donor complex evidence_span: {"source_cache": "artifacts/ala-research/35343688.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689", "start_char": 0, "end_char": 670, "text_sha256": "62b2b8ddcff12b7264515cd251238a0f0e4dbe086fa72830ebff6e88f5db0689"} [ala-p35343688] Protein-Interaction Affinity Gradient Drives [4Fe-4S] Cluster Insertion in Human Lipoyl Synthase. (2022). https://pubmed.ncbi.nlm.nih.gov/35343688/ DOI: 10.1021/jacs.1c13626
Complete structured claim and evidence
[2Fe-2S]-loaded human ISCU and ISCA2 reconstituted catalytically active human LIAS in vitro.
Human ISCU → Lipoic acid synthetase / LIAS source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/33562493.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4261f63098ce640cc87368d3f23f294441fdfa2a3f9b271086821fc1196bb3ac", "start_char": 0, "end_char": 1544, "text_sha256": "4261f63098ce640cc87368d3f23f294441fdfa2a3f9b271086821fc1196bb3ac"}
experimental_model
Recombinant human LIAS cluster reconstitution, EPR and LC-MS
exposure
[2Fe-2S]-loaded ISCU or ISCA2 donors
limitations
In vitro donor capacity does not establish a unique physiological donor or exclude other routes.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human proteins
plain_language
These carrier proteins can help rebuild active enzyme under assay conditions.
primary_references
[ala-p33562493] Characterization and Reconstitution of Human Lipoyl Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered Mechanism of Cluster Assembly. (2021). https://pubmed.ncbi.nlm.nih.gov/33562493/ DOI: 10.3390/ijms22041598
tissue_or_cell_type
Two LIAS iron-sulfur sites
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 390–401
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human LIAS cluster reconstitution, EPR and LC-MS · source_derived_draft · unverified_draft
### ala-iscu-isca2-reconstitution [2Fe-2S]-loaded human ISCU and ISCA2 reconstituted catalytically active human LIAS in vitro. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: These carrier proteins can help rebuild active enzyme under assay conditions. organism: Human proteins tissue_or_cell_type: Two LIAS iron-sulfur sites experimental_model: Recombinant human LIAS cluster reconstitution, EPR and LC-MS limitations: In vitro donor capacity does not establish a unique physiological donor or exclude other routes. exposure: [2Fe-2S]-loaded ISCU or ISCA2 donors evidence_span: {"source_cache": "artifacts/ala-research/33562493.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4261f63098ce640cc87368d3f23f294441fdfa2a3f9b271086821fc1196bb3ac", "start_char": 0, "end_char": 1544, "text_sha256": "4261f63098ce640cc87368d3f23f294441fdfa2a3f9b271086821fc1196bb3ac"} [ala-p33562493] Characterization and Reconstitution of Human Lipoyl Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered Mechanism of Cluster Assembly. (2021). https://pubmed.ncbi.nlm.nih.gov/33562493/ DOI: 10.3390/ijms22041598
Complete structured claim and evidence
EPR comparisons supported auxiliary-cluster insertion before radical-SAM-cluster insertion during the tested LIAS reconstitution.
LIAS auxiliary [4Fe-4S] site → LIAS radical-SAM [4Fe-4S] site source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/33562493.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4261f63098ce640cc87368d3f23f294441fdfa2a3f9b271086821fc1196bb3ac", "start_char": 0, "end_char": 1544, "text_sha256": "4261f63098ce640cc87368d3f23f294441fdfa2a3f9b271086821fc1196bb3ac"}
experimental_model
Recombinant human LIAS cluster reconstitution, EPR and LC-MS
exposure
[2Fe-2S]-loaded ISCU or ISCA2 donors
limitations
In vitro donor capacity does not establish a unique physiological donor or exclude other routes.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human proteins
plain_language
The experimental rebuild suggested an order for loading the two sites.
primary_references
[ala-p33562493] Characterization and Reconstitution of Human Lipoyl Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered Mechanism of Cluster Assembly. (2021). https://pubmed.ncbi.nlm.nih.gov/33562493/ DOI: 10.3390/ijms22041598
tissue_or_cell_type
Two LIAS iron-sulfur sites
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 403–414
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human LIAS cluster reconstitution, EPR and LC-MS · source_derived_draft · unverified_draft
### ala-cluster-order EPR comparisons supported auxiliary-cluster insertion before radical-SAM-cluster insertion during the tested LIAS reconstitution. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The experimental rebuild suggested an order for loading the two sites. organism: Human proteins tissue_or_cell_type: Two LIAS iron-sulfur sites experimental_model: Recombinant human LIAS cluster reconstitution, EPR and LC-MS limitations: In vitro donor capacity does not establish a unique physiological donor or exclude other routes. exposure: [2Fe-2S]-loaded ISCU or ISCA2 donors evidence_span: {"source_cache": "artifacts/ala-research/33562493.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4261f63098ce640cc87368d3f23f294441fdfa2a3f9b271086821fc1196bb3ac", "start_char": 0, "end_char": 1544, "text_sha256": "4261f63098ce640cc87368d3f23f294441fdfa2a3f9b271086821fc1196bb3ac"} [ala-p33562493] Characterization and Reconstitution of Human Lipoyl Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered Mechanism of Cluster Assembly. (2021). https://pubmed.ncbi.nlm.nih.gov/33562493/ DOI: 10.3390/ijms22041598
Complete structured claim and evidence
Patient LIPT2 defects reduced mitochondrial protein lipoylation; wild-type LIPT2 expression restored it.
Human octanoyltransferase / LIPT2 → Mitochondrial protein lipoylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/28757203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f", "start_char": 0, "end_char": 1639, "text_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f"}
experimental_model
Three affected children from two families and patient-derived fibroblasts
exposure
Biallelic LIPT2 variants; wild-type gene rescue and lipoic acid supplementation
limitations
Rare inherited disease; not evidence for common dietary lipoic-acid deficiency.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
Repairing the assembly enzyme restored attachment of the cofactor.
primary_references
[ala-p28757203] Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy. (2017). https://pubmed.ncbi.nlm.nih.gov/28757203/ DOI: 10.1016/j.ajhg.2017.07.001
tissue_or_cell_type
Patient cells and clinical phenotype
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 416–427
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three affected children from two families and patient-derived fibroblasts · source_derived_draft · unverified_draft
### ala-lipt2-lipoylation-loss Patient LIPT2 defects reduced mitochondrial protein lipoylation; wild-type LIPT2 expression restored it. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Repairing the assembly enzyme restored attachment of the cofactor. organism: Human tissue_or_cell_type: Patient cells and clinical phenotype experimental_model: Three affected children from two families and patient-derived fibroblasts limitations: Rare inherited disease; not evidence for common dietary lipoic-acid deficiency. exposure: Biallelic LIPT2 variants; wild-type gene rescue and lipoic acid supplementation evidence_span: {"source_cache": "artifacts/ala-research/28757203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f", "start_char": 0, "end_char": 1639, "text_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f"} [ala-p28757203] Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy. (2017). https://pubmed.ncbi.nlm.nih.gov/28757203/ DOI: 10.1016/j.ajhg.2017.07.001
Complete structured claim and evidence
LIPT2-deficient fibroblasts had reduced PDH and OGDH activities, oxygen consumption and leucine catabolic flux.
Human octanoyltransferase / LIPT2 → Human pyruvate dehydrogenase complex source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/28757203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f", "start_char": 0, "end_char": 1639, "text_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f"}
experimental_model
Three affected children from two families and patient-derived fibroblasts
exposure
Biallelic LIPT2 variants; wild-type gene rescue and lipoic acid supplementation
limitations
Rare inherited disease; not evidence for common dietary lipoic-acid deficiency.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
One early assembly failure disrupts carbohydrate and amino-acid processing.
primary_references
[ala-p28757203] Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy. (2017). https://pubmed.ncbi.nlm.nih.gov/28757203/ DOI: 10.1016/j.ajhg.2017.07.001
tissue_or_cell_type
Patient cells and clinical phenotype
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 429–440
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three affected children from two families and patient-derived fibroblasts · source_derived_draft · unverified_draft
### ala-lipt2-multienzyme-failure LIPT2-deficient fibroblasts had reduced PDH and OGDH activities, oxygen consumption and leucine catabolic flux. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: One early assembly failure disrupts carbohydrate and amino-acid processing. organism: Human tissue_or_cell_type: Patient cells and clinical phenotype experimental_model: Three affected children from two families and patient-derived fibroblasts limitations: Rare inherited disease; not evidence for common dietary lipoic-acid deficiency. exposure: Biallelic LIPT2 variants; wild-type gene rescue and lipoic acid supplementation evidence_span: {"source_cache": "artifacts/ala-research/28757203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f", "start_char": 0, "end_char": 1639, "text_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f"} [ala-p28757203] Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy. (2017). https://pubmed.ncbi.nlm.nih.gov/28757203/ DOI: 10.1016/j.ajhg.2017.07.001
Complete structured claim and evidence
The LIPT1 case showed deficient PDH and OGDH E2 lipoylation with rescue by wild-type LIPT1.
Human lipoyl amidotransferase / LIPT1 → Mitochondrial protein lipoylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/24256811.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2", "start_char": 0, "end_char": 1749, "text_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2"}
experimental_model
Affected patient, biochemical testing and complementation
exposure
Compound-heterozygous LIPT1 variants
limitations
Single rare inherited case; enzyme deficits are not interchangeable with nutritional deficiency.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
The cofactor was not reaching the dehydrogenase machinery.
primary_references
[ala-p24256811] Mutations in the lipoyltransferase LIPT1 gene cause a fatal disease associated with a specific lipoylation defect of the 2-ketoacid dehydrogenase complexes. (2014). https://pubmed.ncbi.nlm.nih.gov/24256811/ DOI: 10.1093/hmg/ddt585
tissue_or_cell_type
Patient-derived cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 455–466
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Affected patient, biochemical testing and complementation · source_derived_draft · unverified_draft
### ala-lipt1-e2-loss The LIPT1 case showed deficient PDH and OGDH E2 lipoylation with rescue by wild-type LIPT1. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cofactor was not reaching the dehydrogenase machinery. organism: Human tissue_or_cell_type: Patient-derived cells experimental_model: Affected patient, biochemical testing and complementation limitations: Single rare inherited case; enzyme deficits are not interchangeable with nutritional deficiency. exposure: Compound-heterozygous LIPT1 variants evidence_span: {"source_cache": "artifacts/ala-research/24256811.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2", "start_char": 0, "end_char": 1749, "text_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2"} [ala-p24256811] Mutations in the lipoyltransferase LIPT1 gene cause a fatal disease associated with a specific lipoylation defect of the 2-ketoacid dehydrogenase complexes. (2014). https://pubmed.ncbi.nlm.nih.gov/24256811/ DOI: 10.1093/hmg/ddt585
Complete structured claim and evidence
Despite LIPT1 deficiency, H-protein lipoylation, glycine-cleavage activity and glycine concentrations were normal in this case.
Human lipoyl amidotransferase / LIPT1 → Glycine cleavage flux source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/24256811.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2", "start_char": 0, "end_char": 1749, "text_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2"}
experimental_model
Affected patient, biochemical testing and complementation
exposure
Compound-heterozygous LIPT1 variants
limitations
Single rare inherited case; enzyme deficits are not interchangeable with nutritional deficiency.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
The glycine pathway can keep working when a later transfer step fails.
primary_references
[ala-p24256811] Mutations in the lipoyltransferase LIPT1 gene cause a fatal disease associated with a specific lipoylation defect of the 2-ketoacid dehydrogenase complexes. (2014). https://pubmed.ncbi.nlm.nih.gov/24256811/ DOI: 10.1093/hmg/ddt585
tissue_or_cell_type
Patient-derived cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 468–479
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Affected patient, biochemical testing and complementation · source_derived_draft · unverified_draft
### ala-lipt1-glycine-spared Despite LIPT1 deficiency, H-protein lipoylation, glycine-cleavage activity and glycine concentrations were normal in this case. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The glycine pathway can keep working when a later transfer step fails. organism: Human tissue_or_cell_type: Patient-derived cells experimental_model: Affected patient, biochemical testing and complementation limitations: Single rare inherited case; enzyme deficits are not interchangeable with nutritional deficiency. exposure: Compound-heterozygous LIPT1 variants evidence_span: {"source_cache": "artifacts/ala-research/24256811.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2", "start_char": 0, "end_char": 1749, "text_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2"} [ala-p24256811] Mutations in the lipoyltransferase LIPT1 gene cause a fatal disease associated with a specific lipoylation defect of the 2-ketoacid dehydrogenase complexes. (2014). https://pubmed.ncbi.nlm.nih.gov/24256811/ DOI: 10.1093/hmg/ddt585
Complete structured claim and evidence
Lipoic-acid exposure lowered lactate release from the studied LIPT1-deficient fibroblasts, while control-cell lactate increased.
Lipoic acid → Fibroblast lactate release source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/24341803.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "44f3fc89f065e58c1deb82f02c93a3654504f002fbc051d00a7703d3fbe6764b", "start_char": 19977, "end_char": 20689, "text_sha256": "3a495a2251965512793b341794c86b5caedc8525754344b8bba51281e7802a79"}
experimental_model
LIPT1 patient fibroblasts with supplementation and genetic complementation
exposure
Lipoic acid 10 or 100 micromolar for three weeks
limitations
Partial biochemical changes do not establish restored lipoylation or clinical efficacy. Historical pathway speculation is not imported as current enzymology.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
The same exposure changed this marker in opposite directions depending on the cells.
primary_references
[ala-p24341803] Mutations in human lipoyltransferase gene LIPT1 cause a Leigh disease with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase. (2013). https://pubmed.ncbi.nlm.nih.gov/24341803/ DOI: 10.1186/1750-1172-8-192
tissue_or_cell_type
Patient and control fibroblasts
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 481–492
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · LIPT1 patient fibroblasts with supplementation and genetic complementation · source_derived_draft · unverified_draft
### ala-lipt1-lactate-partial-response Lipoic-acid exposure lowered lactate release from the studied LIPT1-deficient fibroblasts, while control-cell lactate increased. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same exposure changed this marker in opposite directions depending on the cells. organism: Human tissue_or_cell_type: Patient and control fibroblasts experimental_model: LIPT1 patient fibroblasts with supplementation and genetic complementation limitations: Partial biochemical changes do not establish restored lipoylation or clinical efficacy. Historical pathway speculation is not imported as current enzymology. exposure: Lipoic acid 10 or 100 micromolar for three weeks evidence_span: {"source_cache": "artifacts/ala-research/24341803.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "44f3fc89f065e58c1deb82f02c93a3654504f002fbc051d00a7703d3fbe6764b", "start_char": 19977, "end_char": 20689, "text_sha256": "3a495a2251965512793b341794c86b5caedc8525754344b8bba51281e7802a79"} [ala-p24341803] Mutations in human lipoyltransferase gene LIPT1 cause a Leigh disease with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase. (2013). https://pubmed.ncbi.nlm.nih.gov/24341803/ DOI: 10.1186/1750-1172-8-192
Complete structured claim and evidence
In those LIPT1-deficient fibroblasts, PDH activity increased only moderately, OGDH showed no increase, and the leucine-flux assay showed no BCKDH rescue.
Lipoic acid → Human pyruvate dehydrogenase complex source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/24341803.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "44f3fc89f065e58c1deb82f02c93a3654504f002fbc051d00a7703d3fbe6764b", "start_char": 19977, "end_char": 20689, "text_sha256": "3a495a2251965512793b341794c86b5caedc8525754344b8bba51281e7802a79"}
experimental_model
LIPT1 patient fibroblasts with supplementation and genetic complementation
exposure
Lipoic acid 10 or 100 micromolar for three weeks
limitations
Partial biochemical changes do not establish restored lipoylation or clinical efficacy. Historical pathway speculation is not imported as current enzymology.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
A lower lactate measurement did not mean all affected enzyme systems were repaired.
primary_references
[ala-p24341803] Mutations in human lipoyltransferase gene LIPT1 cause a Leigh disease with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase. (2013). https://pubmed.ncbi.nlm.nih.gov/24341803/ DOI: 10.1186/1750-1172-8-192
tissue_or_cell_type
Patient and control fibroblasts
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 494–505
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · LIPT1 patient fibroblasts with supplementation and genetic complementation · source_derived_draft · unverified_draft
### ala-lipt1-enzyme-partial-response In those LIPT1-deficient fibroblasts, PDH activity increased only moderately, OGDH showed no increase, and the leucine-flux assay showed no BCKDH rescue. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A lower lactate measurement did not mean all affected enzyme systems were repaired. organism: Human tissue_or_cell_type: Patient and control fibroblasts experimental_model: LIPT1 patient fibroblasts with supplementation and genetic complementation limitations: Partial biochemical changes do not establish restored lipoylation or clinical efficacy. Historical pathway speculation is not imported as current enzymology. exposure: Lipoic acid 10 or 100 micromolar for three weeks evidence_span: {"source_cache": "artifacts/ala-research/24341803.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "44f3fc89f065e58c1deb82f02c93a3654504f002fbc051d00a7703d3fbe6764b", "start_char": 19977, "end_char": 20689, "text_sha256": "3a495a2251965512793b341794c86b5caedc8525754344b8bba51281e7802a79"} [ala-p24341803] Mutations in human lipoyltransferase gene LIPT1 cause a Leigh disease with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase. (2013). https://pubmed.ncbi.nlm.nih.gov/24341803/ DOI: 10.1186/1750-1172-8-192
Complete structured claim and evidence
The reported NFU1 splice-disrupting variant eliminated detectable mature mitochondrial NFU1 and accompanied lipoate-synthesis and 2-oxoacid dehydrogenase defects.
Human NFU1 iron-sulfur cluster carrier → Mitochondrial protein lipoylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/21944046.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9cdfbbaf37dfadc160222f6b2205256e42d430569b731140b1d6f3132b157f44", "start_char": 0, "end_char": 1658, "text_sha256": "9cdfbbaf37dfadc160222f6b2205256e42d430569b731140b1d6f3132b157f44"}
experimental_model
Two families with Fe-S disorders and fibroblast gene complementation
exposure
NFU1 and BOLA3 pathogenic variants; isoform-specific rescue
limitations
Broader Fe-S defects can affect respiratory complexes as well as lipoylation; not direct proof of a BOLA3-to-LIAS transfer reaction.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
The cofactor pathway depends on correctly assembled iron-sulfur machinery.
primary_references
[ala-p21944046] Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes. (2011). https://pubmed.ncbi.nlm.nih.gov/21944046/ DOI: 10.1016/j.ajhg.2011.08.011
tissue_or_cell_type
Fibroblasts and mitochondrial enzymes
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 507–518
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two families with Fe-S disorders and fibroblast gene complementation · source_derived_draft · unverified_draft
### ala-nfu1-patient-defect The reported NFU1 splice-disrupting variant eliminated detectable mature mitochondrial NFU1 and accompanied lipoate-synthesis and 2-oxoacid dehydrogenase defects. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cofactor pathway depends on correctly assembled iron-sulfur machinery. organism: Human tissue_or_cell_type: Fibroblasts and mitochondrial enzymes experimental_model: Two families with Fe-S disorders and fibroblast gene complementation limitations: Broader Fe-S defects can affect respiratory complexes as well as lipoylation; not direct proof of a BOLA3-to-LIAS transfer reaction. exposure: NFU1 and BOLA3 pathogenic variants; isoform-specific rescue evidence_span: {"source_cache": "artifacts/ala-research/21944046.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9cdfbbaf37dfadc160222f6b2205256e42d430569b731140b1d6f3132b157f44", "start_char": 0, "end_char": 1658, "text_sha256": "9cdfbbaf37dfadc160222f6b2205256e42d430569b731140b1d6f3132b157f44"} [ala-p21944046] Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes. (2011). https://pubmed.ncbi.nlm.nih.gov/21944046/ DOI: 10.1016/j.ajhg.2011.08.011
Complete structured claim and evidence
BOLA3 deficiency caused combined respiratory and 2-oxoacid dehydrogenase defects; expression of the appropriate BOLA3 isoform restored function.
Human BOLA3 → Cellular mitochondrial respiration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/21944046.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9cdfbbaf37dfadc160222f6b2205256e42d430569b731140b1d6f3132b157f44", "start_char": 0, "end_char": 1658, "text_sha256": "9cdfbbaf37dfadc160222f6b2205256e42d430569b731140b1d6f3132b157f44"}
experimental_model
Two families with Fe-S disorders and fibroblast gene complementation
exposure
NFU1 and BOLA3 pathogenic variants; isoform-specific rescue
limitations
Broader Fe-S defects can affect respiratory complexes as well as lipoylation; not direct proof of a BOLA3-to-LIAS transfer reaction.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
The intact cell needs BOLA3 even though its precise role differs from a purified donor assay.
primary_references
[ala-p21944046] Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes. (2011). https://pubmed.ncbi.nlm.nih.gov/21944046/ DOI: 10.1016/j.ajhg.2011.08.011
tissue_or_cell_type
Fibroblasts and mitochondrial enzymes
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 520–531
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two families with Fe-S disorders and fibroblast gene complementation · source_derived_draft · unverified_draft
### ala-bola3-patient-defect BOLA3 deficiency caused combined respiratory and 2-oxoacid dehydrogenase defects; expression of the appropriate BOLA3 isoform restored function. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The intact cell needs BOLA3 even though its precise role differs from a purified donor assay. organism: Human tissue_or_cell_type: Fibroblasts and mitochondrial enzymes experimental_model: Two families with Fe-S disorders and fibroblast gene complementation limitations: Broader Fe-S defects can affect respiratory complexes as well as lipoylation; not direct proof of a BOLA3-to-LIAS transfer reaction. exposure: NFU1 and BOLA3 pathogenic variants; isoform-specific rescue evidence_span: {"source_cache": "artifacts/ala-research/21944046.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9cdfbbaf37dfadc160222f6b2205256e42d430569b731140b1d6f3132b157f44", "start_char": 0, "end_char": 1658, "text_sha256": "9cdfbbaf37dfadc160222f6b2205256e42d430569b731140b1d6f3132b157f44"} [ala-p21944046] Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes. (2011). https://pubmed.ncbi.nlm.nih.gov/21944046/ DOI: 10.1016/j.ajhg.2011.08.011
Complete structured claim and evidence
GLRX5-associated cases showed deficient protein lipoylation and glycine-cleavage activity with elevated glycine.
Human mitochondrial glutaredoxin 5 / GLRX5 → Glycine accumulation in lipoylation disorders source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/24334290.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2", "start_char": 0, "end_char": 2342, "text_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2"}
experimental_model
Variant nonketotic hyperglycinemia cohort and cell complementation
exposure
LIAS, BOLA3 or GLRX5 variants; lipoate and mitochondrially targeted lipoate in cells
limitations
Phenotypes varied; respiratory-chain function was preserved in this series, unlike some other Fe-S disorders.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
A cofactor-assembly defect can mimic a defect in the glycine-cleavage enzymes themselves.
primary_references
[ala-p24334290] Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. (2014). https://pubmed.ncbi.nlm.nih.gov/24334290/ DOI: 10.1093/brain/awt328
tissue_or_cell_type
Eight genetically explained patients within an eleven-person group
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 533–544
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Variant nonketotic hyperglycinemia cohort and cell complementation · source_derived_draft · unverified_draft
### ala-glrx5-glycine-failure GLRX5-associated cases showed deficient protein lipoylation and glycine-cleavage activity with elevated glycine. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A cofactor-assembly defect can mimic a defect in the glycine-cleavage enzymes themselves. organism: Human tissue_or_cell_type: Eight genetically explained patients within an eleven-person group experimental_model: Variant nonketotic hyperglycinemia cohort and cell complementation limitations: Phenotypes varied; respiratory-chain function was preserved in this series, unlike some other Fe-S disorders. exposure: LIAS, BOLA3 or GLRX5 variants; lipoate and mitochondrially targeted lipoate in cells evidence_span: {"source_cache": "artifacts/ala-research/24334290.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2", "start_char": 0, "end_char": 2342, "text_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2"} [ala-p24334290] Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. (2014). https://pubmed.ncbi.nlm.nih.gov/24334290/ DOI: 10.1093/brain/awt328
Complete structured claim and evidence
Neither lipoate nor mitochondrially targeted lipoate corrected the studied cellular lipoylation deficiency.
Lipoic acid → Mitochondrial protein lipoylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/24334290.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2", "start_char": 0, "end_char": 2342, "text_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2"}
experimental_model
Variant nonketotic hyperglycinemia cohort and cell complementation
exposure
LIAS, BOLA3 or GLRX5 variants; lipoate and mitochondrially targeted lipoate in cells
limitations
Phenotypes varied; respiratory-chain function was preserved in this series, unlike some other Fe-S disorders.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
Delivering the molecule nearer mitochondria was still insufficient in these models.
primary_references
[ala-p24334290] Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. (2014). https://pubmed.ncbi.nlm.nih.gov/24334290/ DOI: 10.1093/brain/awt328
tissue_or_cell_type
Eight genetically explained patients within an eleven-person group
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 546–557
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Variant nonketotic hyperglycinemia cohort and cell complementation · source_derived_draft · unverified_draft
### ala-variant-lipoate-no-rescue Neither lipoate nor mitochondrially targeted lipoate corrected the studied cellular lipoylation deficiency. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Delivering the molecule nearer mitochondria was still insufficient in these models. organism: Human tissue_or_cell_type: Eight genetically explained patients within an eleven-person group experimental_model: Variant nonketotic hyperglycinemia cohort and cell complementation limitations: Phenotypes varied; respiratory-chain function was preserved in this series, unlike some other Fe-S disorders. exposure: LIAS, BOLA3 or GLRX5 variants; lipoate and mitochondrially targeted lipoate in cells evidence_span: {"source_cache": "artifacts/ala-research/24334290.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2", "start_char": 0, "end_char": 2342, "text_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2"} [ala-p24334290] Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. (2014). https://pubmed.ncbi.nlm.nih.gov/24334290/ DOI: 10.1093/brain/awt328
Complete structured claim and evidence
Engineered LplA restored lipoylation in MECR-, BOLA3-, FDX1-, LIAS- and LIPT1-knockout cell models.
Engineered bacterial LplA targeted to mammalian mitochondria → Mitochondrial protein lipoylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/39547509.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd", "start_char": 0, "end_char": 1884, "text_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd"}
experimental_model
Engineered bacterial ligase in human knockout cells and a modeled patient allele
exposure
Mitochondrially targeted engineered LplA expression
limitations
Experimental genetic engineering, not ordinary supplementation and not a treated-patient efficacy trial.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human cells with bacterial enzyme engineering
plain_language
Adding a new enzyme created a route that free supplementation alone did not supply.
primary_references
[ala-p39547509] Engineered bacterial lipoate protein ligase A (lplA) restores lipoylation in cell models of lipoylation deficiency. (2024). https://pubmed.ncbi.nlm.nih.gov/39547509/ DOI: 10.1016/j.jbc.2024.107995
tissue_or_cell_type
Lipoylation-null cell models and K562 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 559–570
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Engineered bacterial ligase in human knockout cells and a modeled patient allele · source_derived_draft · unverified_draft
### ala-lpla-lipoylation-rescue Engineered LplA restored lipoylation in MECR-, BOLA3-, FDX1-, LIAS- and LIPT1-knockout cell models. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding a new enzyme created a route that free supplementation alone did not supply. organism: Human cells with bacterial enzyme engineering tissue_or_cell_type: Lipoylation-null cell models and K562 cells experimental_model: Engineered bacterial ligase in human knockout cells and a modeled patient allele limitations: Experimental genetic engineering, not ordinary supplementation and not a treated-patient efficacy trial. exposure: Mitochondrially targeted engineered LplA expression evidence_span: {"source_cache": "artifacts/ala-research/39547509.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd", "start_char": 0, "end_char": 1884, "text_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd"} [ala-p39547509] Engineered bacterial lipoate protein ligase A (lplA) restores lipoylation in cell models of lipoylation deficiency. (2024). https://pubmed.ncbi.nlm.nih.gov/39547509/ DOI: 10.1016/j.jbc.2024.107995
Complete structured claim and evidence
Engineered LplA restored cellular respiration and growth in low glucose in lipoylation-null cells, including a K562 model of a patient LIPT1 allele.
Engineered bacterial LplA targeted to mammalian mitochondria → Growth of lipoylation-deficient cells in low glucose source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/39547509.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd", "start_char": 0, "end_char": 1884, "text_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd"}
experimental_model
Engineered bacterial ligase in human knockout cells and a modeled patient allele
exposure
Mitochondrially targeted engineered LplA expression
limitations
Experimental genetic engineering, not ordinary supplementation and not a treated-patient efficacy trial.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human cells with bacterial enzyme engineering
plain_language
The engineered bypass improved measured cellular function, not just a cofactor stain.
primary_references
[ala-p39547509] Engineered bacterial lipoate protein ligase A (lplA) restores lipoylation in cell models of lipoylation deficiency. (2024). https://pubmed.ncbi.nlm.nih.gov/39547509/ DOI: 10.1016/j.jbc.2024.107995
tissue_or_cell_type
Lipoylation-null cell models and K562 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 572–583
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Engineered bacterial ligase in human knockout cells and a modeled patient allele · source_derived_draft · unverified_draft
### ala-lpla-functional-rescue Engineered LplA restored cellular respiration and growth in low glucose in lipoylation-null cells, including a K562 model of a patient LIPT1 allele. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The engineered bypass improved measured cellular function, not just a cofactor stain. organism: Human cells with bacterial enzyme engineering tissue_or_cell_type: Lipoylation-null cell models and K562 cells experimental_model: Engineered bacterial ligase in human knockout cells and a modeled patient allele limitations: Experimental genetic engineering, not ordinary supplementation and not a treated-patient efficacy trial. exposure: Mitochondrially targeted engineered LplA expression evidence_span: {"source_cache": "artifacts/ala-research/39547509.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd", "start_char": 0, "end_char": 1884, "text_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd"} [ala-p39547509] Engineered bacterial lipoate protein ligase A (lplA) restores lipoylation in cell models of lipoylation deficiency. (2024). https://pubmed.ncbi.nlm.nih.gov/39547509/ DOI: 10.1016/j.jbc.2024.107995
Complete structured claim and evidence
Lias-null mouse embryos died before embryonic day 9.5.
Mouse lipoyl synthase / Lias → Survival of Lias-null mouse embryos source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/16135825.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1750e4eb7b27e8b28bf973a3683d88c6ad9d639acc10f3f4c5df6077fb384da", "start_char": 0, "end_char": 1393, "text_sha256": "b1750e4eb7b27e8b28bf973a3683d88c6ad9d639acc10f3f4c5df6077fb384da"}
experimental_model
Targeted Lias knockout and maternal supplementation
exposure
Lias-null embryos; high maternal lipoic-acid intake
limitations
Embryonic genetic loss is not a dietary depletion model in humans.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Mouse
plain_language
The developing embryo required its own cofactor-synthesis machinery.
primary_references
[ala-p16135825] Endogenous production of lipoic acid is essential for mouse development. (2005). https://pubmed.ncbi.nlm.nih.gov/16135825/ DOI: 10.1128/mcb.25.18.8387-8392.2005
tissue_or_cell_type
Embryos and pregnant dams
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 585–596
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted Lias knockout and maternal supplementation · source_derived_draft · unverified_draft
### ala-lias-embryonic-loss Lias-null mouse embryos died before embryonic day 9.5. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The developing embryo required its own cofactor-synthesis machinery. organism: Mouse tissue_or_cell_type: Embryos and pregnant dams experimental_model: Targeted Lias knockout and maternal supplementation limitations: Embryonic genetic loss is not a dietary depletion model in humans. exposure: Lias-null embryos; high maternal lipoic-acid intake evidence_span: {"source_cache": "artifacts/ala-research/16135825.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1750e4eb7b27e8b28bf973a3683d88c6ad9d639acc10f3f4c5df6077fb384da", "start_char": 0, "end_char": 1393, "text_sha256": "b1750e4eb7b27e8b28bf973a3683d88c6ad9d639acc10f3f4c5df6077fb384da"} [ala-p16135825] Endogenous production of lipoic acid is essential for mouse development. (2005). https://pubmed.ncbi.nlm.nih.gov/16135825/ DOI: 10.1128/mcb.25.18.8387-8392.2005
Complete structured claim and evidence
The tested high maternal lipoic-acid supplementation did not rescue Lias-null embryos.
Lipoic acid → Survival of Lias-null mouse embryos source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/16135825.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1750e4eb7b27e8b28bf973a3683d88c6ad9d639acc10f3f4c5df6077fb384da", "start_char": 0, "end_char": 1393, "text_sha256": "b1750e4eb7b27e8b28bf973a3683d88c6ad9d639acc10f3f4c5df6077fb384da"}
experimental_model
Targeted Lias knockout and maternal supplementation
exposure
Lias-null embryos; high maternal lipoic-acid intake
limitations
Embryonic genetic loss is not a dietary depletion model in humans.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Mouse
plain_language
Maternal intake did not bypass the embryo’s missing synthesis enzyme.
primary_references
[ala-p16135825] Endogenous production of lipoic acid is essential for mouse development. (2005). https://pubmed.ncbi.nlm.nih.gov/16135825/ DOI: 10.1128/mcb.25.18.8387-8392.2005
tissue_or_cell_type
Embryos and pregnant dams
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 598–609
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted Lias knockout and maternal supplementation · source_derived_draft · unverified_draft
### ala-maternal-lipoate-no-rescue The tested high maternal lipoic-acid supplementation did not rescue Lias-null embryos. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Maternal intake did not bypass the embryo’s missing synthesis enzyme. organism: Mouse tissue_or_cell_type: Embryos and pregnant dams experimental_model: Targeted Lias knockout and maternal supplementation limitations: Embryonic genetic loss is not a dietary depletion model in humans. exposure: Lias-null embryos; high maternal lipoic-acid intake evidence_span: {"source_cache": "artifacts/ala-research/16135825.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1750e4eb7b27e8b28bf973a3683d88c6ad9d639acc10f3f4c5df6077fb384da", "start_char": 0, "end_char": 1393, "text_sha256": "b1750e4eb7b27e8b28bf973a3683d88c6ad9d639acc10f3f4c5df6077fb384da"} [ala-p16135825] Endogenous production of lipoic acid is essential for mouse development. (2005). https://pubmed.ncbi.nlm.nih.gov/16135825/ DOI: 10.1128/mcb.25.18.8387-8392.2005
Complete structured claim and evidence
Caco-2 lipoic-acid transport was energy dependent, increased at acidic pH and was inhibited by tested monocarboxylates.
Lipoic acid → Intestinal monocarboxylate-sensitive-lipoate transport source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/17536819.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d777a0163a5cb3c8de0edf282cca050a720098f5ee7b0f4e22f9a0b3275c5b7c", "start_char": 0, "end_char": 863, "text_sha256": "d777a0163a5cb3c8de0edf282cca050a720098f5ee7b0f4e22f9a0b3275c5b7c"}
experimental_model
Caco-2 intestinal transport model
exposure
Lipoic acid transport across pH and competing-monocarboxylate conditions
limitations
Cell model suggests proton-linked monocarboxylate transport but does not identify a specific SLC16 isoform or quantify whole-person absorption.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human cell line
plain_language
Absorption behavior depended on acidity and competing molecules in this cell model.
primary_references
[ala-p17536819] Transepithelial transport of alpha-lipoic acid across human intestinal Caco-2 cell monolayers. (2007). https://pubmed.ncbi.nlm.nih.gov/17536819/ DOI: 10.1021/jf063624i
tissue_or_cell_type
Intestinal epithelial monolayer
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 611–622
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Caco-2 intestinal transport model · source_derived_draft · unverified_draft
### ala-intestinal-ph-transport Caco-2 lipoic-acid transport was energy dependent, increased at acidic pH and was inhibited by tested monocarboxylates. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Absorption behavior depended on acidity and competing molecules in this cell model. organism: Human cell line tissue_or_cell_type: Intestinal epithelial monolayer experimental_model: Caco-2 intestinal transport model limitations: Cell model suggests proton-linked monocarboxylate transport but does not identify a specific SLC16 isoform or quantify whole-person absorption. exposure: Lipoic acid transport across pH and competing-monocarboxylate conditions evidence_span: {"source_cache": "artifacts/ala-research/17536819.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d777a0163a5cb3c8de0edf282cca050a720098f5ee7b0f4e22f9a0b3275c5b7c", "start_char": 0, "end_char": 863, "text_sha256": "d777a0163a5cb3c8de0edf282cca050a720098f5ee7b0f4e22f9a0b3275c5b7c"} [ala-p17536819] Transepithelial transport of alpha-lipoic acid across human intestinal Caco-2 cell monolayers. (2007). https://pubmed.ncbi.nlm.nih.gov/17536819/ DOI: 10.1021/jf063624i
Complete structured claim and evidence
DHLA formed during lipoic-acid transport in the Caco-2 experiments.
Lipoic acid → Free dihydrolipoic acid / DHLA source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/17536819.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d777a0163a5cb3c8de0edf282cca050a720098f5ee7b0f4e22f9a0b3275c5b7c", "start_char": 0, "end_char": 863, "text_sha256": "d777a0163a5cb3c8de0edf282cca050a720098f5ee7b0f4e22f9a0b3275c5b7c"}
experimental_model
Caco-2 intestinal transport model
exposure
Lipoic acid transport across pH and competing-monocarboxylate conditions
limitations
Cell model suggests proton-linked monocarboxylate transport but does not identify a specific SLC16 isoform or quantify whole-person absorption.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human cell line
plain_language
The transported molecule can change redox state during passage through intestinal cells.
primary_references
[ala-p17536819] Transepithelial transport of alpha-lipoic acid across human intestinal Caco-2 cell monolayers. (2007). https://pubmed.ncbi.nlm.nih.gov/17536819/ DOI: 10.1021/jf063624i
tissue_or_cell_type
Intestinal epithelial monolayer
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 624–635
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Caco-2 intestinal transport model · source_derived_draft · unverified_draft
### ala-intestinal-dhla-formation DHLA formed during lipoic-acid transport in the Caco-2 experiments. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The transported molecule can change redox state during passage through intestinal cells. organism: Human cell line tissue_or_cell_type: Intestinal epithelial monolayer experimental_model: Caco-2 intestinal transport model limitations: Cell model suggests proton-linked monocarboxylate transport but does not identify a specific SLC16 isoform or quantify whole-person absorption. exposure: Lipoic acid transport across pH and competing-monocarboxylate conditions evidence_span: {"source_cache": "artifacts/ala-research/17536819.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d777a0163a5cb3c8de0edf282cca050a720098f5ee7b0f4e22f9a0b3275c5b7c", "start_char": 0, "end_char": 863, "text_sha256": "d777a0163a5cb3c8de0edf282cca050a720098f5ee7b0f4e22f9a0b3275c5b7c"} [ala-p17536819] Transepithelial transport of alpha-lipoic acid across human intestinal Caco-2 cell monolayers. (2007). https://pubmed.ncbi.nlm.nih.gov/17536819/ DOI: 10.1021/jf063624i
Complete structured claim and evidence
Compared with solution, the tested tablets produced R-lipoic-acid peak concentrations of 36–43% and exposure areas of 64–79%.
R,S-alpha-lipoic acid mixture → Plasma exposure to free alpha-lipoic acid source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/25506250.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "539058a215e046b23d352d40f72f6e4fd9259b6e746770584d8852d650990973", "start_char": 0, "end_char": 2050, "text_sha256": "539058a215e046b23d352d40f72f6e4fd9259b6e746770584d8852d650990973"}
experimental_model
Randomized four-way crossover pharmacokinetic study in 24 healthy volunteers
exposure
Single 600-mg racemic oral formulations: solution and tablets
limitations
Exposure differences are formulation specific; plasma pharmacokinetics does not establish clinical efficacy or mitochondrial attachment.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
Different formulations delivered different amounts into blood.
primary_references
[ala-p25506250] Enantiomer-selective pharmacokinetics, oral bioavailability, and sex effects of various alpha-lipoic acid dosage forms. (2014). https://pubmed.ncbi.nlm.nih.gov/25506250/ DOI: 10.2147/cpaa.s71574
tissue_or_cell_type
Plasma
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 637–648
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized four-way crossover pharmacokinetic study in 24 healthy volunteers · source_derived_draft · unverified_draft
### ala-oral-formulation-exposure Compared with solution, the tested tablets produced R-lipoic-acid peak concentrations of 36–43% and exposure areas of 64–79%. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different formulations delivered different amounts into blood. organism: Human tissue_or_cell_type: Plasma experimental_model: Randomized four-way crossover pharmacokinetic study in 24 healthy volunteers limitations: Exposure differences are formulation specific; plasma pharmacokinetics does not establish clinical efficacy or mitochondrial attachment. exposure: Single 600-mg racemic oral formulations: solution and tablets evidence_span: {"source_cache": "artifacts/ala-research/25506250.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "539058a215e046b23d352d40f72f6e4fd9259b6e746770584d8852d650990973", "start_char": 0, "end_char": 2050, "text_sha256": "539058a215e046b23d352d40f72f6e4fd9259b6e746770584d8852d650990973"} [ala-p25506250] Enantiomer-selective pharmacokinetics, oral bioavailability, and sex effects of various alpha-lipoic acid dosage forms. (2014). https://pubmed.ncbi.nlm.nih.gov/25506250/ DOI: 10.2147/cpaa.s71574
Complete structured claim and evidence
Median peak times for both lipoic-acid enantiomers were approximately 0.33–0.5 hours across the studied formulations.
R,S-alpha-lipoic acid mixture → Plasma exposure to free alpha-lipoic acid source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/25506250.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "539058a215e046b23d352d40f72f6e4fd9259b6e746770584d8852d650990973", "start_char": 0, "end_char": 2050, "text_sha256": "539058a215e046b23d352d40f72f6e4fd9259b6e746770584d8852d650990973"}
experimental_model
Randomized four-way crossover pharmacokinetic study in 24 healthy volunteers
exposure
Single 600-mg racemic oral formulations: solution and tablets
limitations
Exposure differences are formulation specific; plasma pharmacokinetics does not establish clinical efficacy or mitochondrial attachment.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
Blood levels rose quickly after these single doses.
primary_references
[ala-p25506250] Enantiomer-selective pharmacokinetics, oral bioavailability, and sex effects of various alpha-lipoic acid dosage forms. (2014). https://pubmed.ncbi.nlm.nih.gov/25506250/ DOI: 10.2147/cpaa.s71574
tissue_or_cell_type
Plasma
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 650–661
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized four-way crossover pharmacokinetic study in 24 healthy volunteers · source_derived_draft · unverified_draft
### ala-rapid-enantiomer-peaks Median peak times for both lipoic-acid enantiomers were approximately 0.33–0.5 hours across the studied formulations. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blood levels rose quickly after these single doses. organism: Human tissue_or_cell_type: Plasma experimental_model: Randomized four-way crossover pharmacokinetic study in 24 healthy volunteers limitations: Exposure differences are formulation specific; plasma pharmacokinetics does not establish clinical efficacy or mitochondrial attachment. exposure: Single 600-mg racemic oral formulations: solution and tablets evidence_span: {"source_cache": "artifacts/ala-research/25506250.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "539058a215e046b23d352d40f72f6e4fd9259b6e746770584d8852d650990973", "start_char": 0, "end_char": 2050, "text_sha256": "539058a215e046b23d352d40f72f6e4fd9259b6e746770584d8852d650990973"} [ala-p25506250] Enantiomer-selective pharmacokinetics, oral bioavailability, and sex effects of various alpha-lipoic acid dosage forms. (2014). https://pubmed.ncbi.nlm.nih.gov/25506250/ DOI: 10.2147/cpaa.s71574
Complete structured claim and evidence
The R-versus-racemate pilot found substantial exposure variability, especially in older adults, rather than a uniform formulation advantage.
Free R-alpha-lipoic acid → Plasma exposure to free alpha-lipoic acid source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/22609537.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bfd228f5a8102a99fecaf7c6de8d1cb910afacd695cb3947c60987f54da431fa", "start_char": 0, "end_char": 1645, "text_sha256": "bfd228f5a8102a99fecaf7c6de8d1cb910afacd695cb3947c60987f54da431fa"}
experimental_model
Small crossover pharmacokinetic pilot in younger and older adults
exposure
500 mg R-lipoic acid versus 500 mg racemic lipoic acid
limitations
Small groups and unequal R-content across equal total-mass doses; substantial individual variability.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
A higher exposure in a few participants did not establish that one form works better for everyone.
primary_references
[ala-p22609537] Age and gender dependent bioavailability of R- and R,S-α-lipoic acid: a pilot study. (2012). https://pubmed.ncbi.nlm.nih.gov/22609537/ DOI: 10.1016/j.phrs.2012.05.002
tissue_or_cell_type
Plasma
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 663–674
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Small crossover pharmacokinetic pilot in younger and older adults · source_derived_draft · unverified_draft
### ala-enantiomer-pk-variability The R-versus-racemate pilot found substantial exposure variability, especially in older adults, rather than a uniform formulation advantage. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A higher exposure in a few participants did not establish that one form works better for everyone. organism: Human tissue_or_cell_type: Plasma experimental_model: Small crossover pharmacokinetic pilot in younger and older adults limitations: Small groups and unequal R-content across equal total-mass doses; substantial individual variability. exposure: 500 mg R-lipoic acid versus 500 mg racemic lipoic acid evidence_span: {"source_cache": "artifacts/ala-research/22609537.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bfd228f5a8102a99fecaf7c6de8d1cb910afacd695cb3947c60987f54da431fa", "start_char": 0, "end_char": 1645, "text_sha256": "bfd228f5a8102a99fecaf7c6de8d1cb910afacd695cb3947c60987f54da431fa"} [ala-p22609537] Age and gender dependent bioavailability of R- and R,S-α-lipoic acid: a pilot study. (2012). https://pubmed.ncbi.nlm.nih.gov/22609537/ DOI: 10.1016/j.phrs.2012.05.002
Complete structured claim and evidence
Plasma glutathione did not change during the pilot’s three-hour sampling period.
Lipoic acid → Plasma glutathione concentration, assay pool unspecified source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/22609537.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bfd228f5a8102a99fecaf7c6de8d1cb910afacd695cb3947c60987f54da431fa", "start_char": 0, "end_char": 1645, "text_sha256": "bfd228f5a8102a99fecaf7c6de8d1cb910afacd695cb3947c60987f54da431fa"}
experimental_model
Small crossover pharmacokinetic pilot in younger and older adults
exposure
500 mg R-lipoic acid versus 500 mg racemic lipoic acid
limitations
The indexed abstract does not specify reduced versus total glutathione assay pool; retain that uncertainty. A three-hour blood measurement is not a test of all intracellular pools.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
An acute blood measurement did not reproduce every cell-culture glutathione result.
primary_references
[ala-p22609537] Age and gender dependent bioavailability of R- and R,S-α-lipoic acid: a pilot study. (2012). https://pubmed.ncbi.nlm.nih.gov/22609537/ DOI: 10.1016/j.phrs.2012.05.002
tissue_or_cell_type
Plasma
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 676–687
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Small crossover pharmacokinetic pilot in younger and older adults · source_derived_draft · unverified_draft
### ala-acute-plasma-gsh-null Plasma glutathione did not change during the pilot’s three-hour sampling period. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: An acute blood measurement did not reproduce every cell-culture glutathione result. organism: Human tissue_or_cell_type: Plasma experimental_model: Small crossover pharmacokinetic pilot in younger and older adults limitations: The indexed abstract does not specify reduced versus total glutathione assay pool; retain that uncertainty. A three-hour blood measurement is not a test of all intracellular pools. exposure: 500 mg R-lipoic acid versus 500 mg racemic lipoic acid evidence_span: {"source_cache": "artifacts/ala-research/22609537.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bfd228f5a8102a99fecaf7c6de8d1cb910afacd695cb3947c60987f54da431fa", "start_char": 0, "end_char": 1645, "text_sha256": "bfd228f5a8102a99fecaf7c6de8d1cb910afacd695cb3947c60987f54da431fa"} [ala-p22609537] Age and gender dependent bioavailability of R- and R,S-α-lipoic acid: a pilot study. (2012). https://pubmed.ncbi.nlm.nih.gov/22609537/ DOI: 10.1016/j.phrs.2012.05.002
Complete structured claim and evidence
600 mg R-lipoic acid and 1200 mg racemate yielded bioequivalent R-enantiomer exposure in this crossover study.
Free R-alpha-lipoic acid → R,S-alpha-lipoic acid mixture source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/32212340.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "44984e6b01b34f66b48a24660a08befba9fc1691954a6832010d6ec01df29220", "start_char": 0, "end_char": 1654, "text_sha256": "44984e6b01b34f66b48a24660a08befba9fc1691954a6832010d6ec01df29220"}
experimental_model
Crossover study in 20 people with progressive multiple sclerosis
exposure
600 mg R-lipoic acid versus 1200 mg racemic lipoic acid over 7–10 days
limitations
Equal nominal R content but different total doses; short tolerability/PK study, not an efficacy comparison.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
Matching the amount of the R form produced similar measured R exposure.
primary_references
[ala-p32212340] Gastrointestinal Tolerability and Absorption of R- Versus R,S-Lipoic Acid in Progressive Multiple Sclerosis: A Randomized Crossover Trial. (2020). https://pubmed.ncbi.nlm.nih.gov/32212340/ DOI: 10.1002/jcph.1605
tissue_or_cell_type
Plasma and gastrointestinal symptom reports
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 689–700
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crossover study in 20 people with progressive multiple sclerosis · source_derived_draft · unverified_draft
### ala-r-racemate-exposure 600 mg R-lipoic acid and 1200 mg racemate yielded bioequivalent R-enantiomer exposure in this crossover study. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Matching the amount of the R form produced similar measured R exposure. organism: Human tissue_or_cell_type: Plasma and gastrointestinal symptom reports experimental_model: Crossover study in 20 people with progressive multiple sclerosis limitations: Equal nominal R content but different total doses; short tolerability/PK study, not an efficacy comparison. exposure: 600 mg R-lipoic acid versus 1200 mg racemic lipoic acid over 7–10 days evidence_span: {"source_cache": "artifacts/ala-research/32212340.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "44984e6b01b34f66b48a24660a08befba9fc1691954a6832010d6ec01df29220", "start_char": 0, "end_char": 1654, "text_sha256": "44984e6b01b34f66b48a24660a08befba9fc1691954a6832010d6ec01df29220"} [ala-p32212340] Gastrointestinal Tolerability and Absorption of R- Versus R,S-Lipoic Acid in Progressive Multiple Sclerosis: A Randomized Crossover Trial. (2020). https://pubmed.ncbi.nlm.nih.gov/32212340/ DOI: 10.1002/jcph.1605
Complete structured claim and evidence
The R-only period had fewer gastrointestinal event reports than the racemate period; the mean symptom-score difference was not statistically significant.
Free R-alpha-lipoic acid → R,S-alpha-lipoic acid mixture source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/32212340.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "44984e6b01b34f66b48a24660a08befba9fc1691954a6832010d6ec01df29220", "start_char": 0, "end_char": 1654, "text_sha256": "44984e6b01b34f66b48a24660a08befba9fc1691954a6832010d6ec01df29220"}
experimental_model
Crossover study in 20 people with progressive multiple sclerosis
exposure
600 mg R-lipoic acid versus 1200 mg racemic lipoic acid over 7–10 days
limitations
Equal nominal R content but different total doses; short tolerability/PK study, not an efficacy comparison.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
One tolerability measure favored R-only, but the score comparison was inconclusive.
primary_references
[ala-p32212340] Gastrointestinal Tolerability and Absorption of R- Versus R,S-Lipoic Acid in Progressive Multiple Sclerosis: A Randomized Crossover Trial. (2020). https://pubmed.ncbi.nlm.nih.gov/32212340/ DOI: 10.1002/jcph.1605
tissue_or_cell_type
Plasma and gastrointestinal symptom reports
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 702–713
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crossover study in 20 people with progressive multiple sclerosis · source_derived_draft · unverified_draft
### ala-r-racemate-gi The R-only period had fewer gastrointestinal event reports than the racemate period; the mean symptom-score difference was not statistically significant. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: One tolerability measure favored R-only, but the score comparison was inconclusive. organism: Human tissue_or_cell_type: Plasma and gastrointestinal symptom reports experimental_model: Crossover study in 20 people with progressive multiple sclerosis limitations: Equal nominal R content but different total doses; short tolerability/PK study, not an efficacy comparison. exposure: 600 mg R-lipoic acid versus 1200 mg racemic lipoic acid over 7–10 days evidence_span: {"source_cache": "artifacts/ala-research/32212340.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "44984e6b01b34f66b48a24660a08befba9fc1691954a6832010d6ec01df29220", "start_char": 0, "end_char": 1654, "text_sha256": "44984e6b01b34f66b48a24660a08befba9fc1691954a6832010d6ec01df29220"} [ala-p32212340] Gastrointestinal Tolerability and Absorption of R- Versus R,S-Lipoic Acid in Progressive Multiple Sclerosis: A Randomized Crossover Trial. (2020). https://pubmed.ncbi.nlm.nih.gov/32212340/ DOI: 10.1002/jcph.1605
Complete structured claim and evidence
Human erythrocytes reduced lipoic acid to DHLA with glucose but not with 2-deoxyglucose, supporting NADPH dependence.
Lipoic acid → Erythrocyte reduction of free lipoic acid source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/7632170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ebbc851e5279e646bc7c892645c931a3fd2993830c3f4405379839cbbd6e707", "start_char": 0, "end_char": 1863, "text_sha256": "2ebbc851e5279e646bc7c892645c931a3fd2993830c3f4405379839cbbd6e707"}
experimental_model
Human erythrocytes, one G6PD-deficient donor and purified-enzyme assays
exposure
Lipoic acid with glucose/2-deoxyglucose and G6PD inhibition
limitations
The deficient-donor finding is small and mechanistic; it is not a clinical safety or efficacy trial in G6PD deficiency.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
The cell must supply reducing power to make DHLA.
primary_references
[ala-p7632170] Reduction and transport of lipoic acid by human erythrocytes. (1995). https://pubmed.ncbi.nlm.nih.gov/7632170/ DOI: 10.1016/0006-2952(95)00084-d
tissue_or_cell_type
Erythrocytes and glutathione reductase
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 715–726
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocytes, one G6PD-deficient donor and purified-enzyme assays · source_derived_draft · unverified_draft
### ala-rbc-glucose-reduction Human erythrocytes reduced lipoic acid to DHLA with glucose but not with 2-deoxyglucose, supporting NADPH dependence. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cell must supply reducing power to make DHLA. organism: Human tissue_or_cell_type: Erythrocytes and glutathione reductase experimental_model: Human erythrocytes, one G6PD-deficient donor and purified-enzyme assays limitations: The deficient-donor finding is small and mechanistic; it is not a clinical safety or efficacy trial in G6PD deficiency. exposure: Lipoic acid with glucose/2-deoxyglucose and G6PD inhibition evidence_span: {"source_cache": "artifacts/ala-research/7632170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ebbc851e5279e646bc7c892645c931a3fd2993830c3f4405379839cbbd6e707", "start_char": 0, "end_char": 1863, "text_sha256": "2ebbc851e5279e646bc7c892645c931a3fd2993830c3f4405379839cbbd6e707"} [ala-p7632170] Reduction and transport of lipoic acid by human erythrocytes. (1995). https://pubmed.ncbi.nlm.nih.gov/7632170/ DOI: 10.1016/0006-2952(95)00084-d
Complete structured claim and evidence
Purified human glutathione reductase reduced free lipoic acid to DHLA in vitro.
Glutathione reductase / GSR → Lipoic acid source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/7632170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ebbc851e5279e646bc7c892645c931a3fd2993830c3f4405379839cbbd6e707", "start_char": 0, "end_char": 1863, "text_sha256": "2ebbc851e5279e646bc7c892645c931a3fd2993830c3f4405379839cbbd6e707"}
experimental_model
Human erythrocytes, one G6PD-deficient donor and purified-enzyme assays
exposure
Lipoic acid with glucose/2-deoxyglucose and G6PD inhibition
limitations
The deficient-donor finding is small and mechanistic; it is not a clinical safety or efficacy trial in G6PD deficiency.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
An enzyme associated with glutathione recycling can also reduce free lipoic acid.
primary_references
[ala-p7632170] Reduction and transport of lipoic acid by human erythrocytes. (1995). https://pubmed.ncbi.nlm.nih.gov/7632170/ DOI: 10.1016/0006-2952(95)00084-d
tissue_or_cell_type
Erythrocytes and glutathione reductase
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 741–752
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocytes, one G6PD-deficient donor and purified-enzyme assays · source_derived_draft · unverified_draft
### ala-gsr-free-lipoate Purified human glutathione reductase reduced free lipoic acid to DHLA in vitro. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme associated with glutathione recycling can also reduce free lipoic acid. organism: Human tissue_or_cell_type: Erythrocytes and glutathione reductase experimental_model: Human erythrocytes, one G6PD-deficient donor and purified-enzyme assays limitations: The deficient-donor finding is small and mechanistic; it is not a clinical safety or efficacy trial in G6PD deficiency. exposure: Lipoic acid with glucose/2-deoxyglucose and G6PD inhibition evidence_span: {"source_cache": "artifacts/ala-research/7632170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ebbc851e5279e646bc7c892645c931a3fd2993830c3f4405379839cbbd6e707", "start_char": 0, "end_char": 1863, "text_sha256": "2ebbc851e5279e646bc7c892645c931a3fd2993830c3f4405379839cbbd6e707"} [ala-p7632170] Reduction and transport of lipoic acid by human erythrocytes. (1995). https://pubmed.ncbi.nlm.nih.gov/7632170/ DOI: 10.1016/0006-2952(95)00084-d
Complete structured claim and evidence
Purified mammalian thioredoxin reductases, including enzyme from human placenta, catalyzed NADPH-dependent lipoic-acid reduction.
Mammalian thioredoxin reductases, isoform unspecified → Lipoic acid source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/8769129.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9ba6524ef04fdc03c0a6d108325b8a96fe7ad0748be4d7056e694b5afa2a8499", "start_char": 0, "end_char": 1307, "text_sha256": "9ba6524ef04fdc03c0a6d108325b8a96fe7ad0748be4d7056e694b5afa2a8499"}
experimental_model
Purified mammalian thioredoxin reductase assays
exposure
NADPH-dependent lipoate/lipoamide reduction
limitations
Isoform identity was not resolved as a specific human TXNRD gene in the indexed abstract; assay rate comparisons are not tissue-wide flux rankings.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human placenta, calf tissues and rat liver
plain_language
The thioredoxin system provides another route to DHLA.
primary_references
[ala-p8769129] Efficient reduction of lipoamide and lipoic acid by mammalian thioredoxin reductase. (1996). https://pubmed.ncbi.nlm.nih.gov/8769129/ DOI: 10.1006/bbrc.1996.1165
tissue_or_cell_type
Purified thioredoxin reductases
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 754–765
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified mammalian thioredoxin reductase assays · source_derived_draft · unverified_draft
### ala-thioredoxin-reductase-dhla Purified mammalian thioredoxin reductases, including enzyme from human placenta, catalyzed NADPH-dependent lipoic-acid reduction. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The thioredoxin system provides another route to DHLA. organism: Human placenta, calf tissues and rat liver tissue_or_cell_type: Purified thioredoxin reductases experimental_model: Purified mammalian thioredoxin reductase assays limitations: Isoform identity was not resolved as a specific human TXNRD gene in the indexed abstract; assay rate comparisons are not tissue-wide flux rankings. exposure: NADPH-dependent lipoate/lipoamide reduction evidence_span: {"source_cache": "artifacts/ala-research/8769129.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9ba6524ef04fdc03c0a6d108325b8a96fe7ad0748be4d7056e694b5afa2a8499", "start_char": 0, "end_char": 1307, "text_sha256": "9ba6524ef04fdc03c0a6d108325b8a96fe7ad0748be4d7056e694b5afa2a8499"} [ala-p8769129] Efficient reduction of lipoamide and lipoic acid by mammalian thioredoxin reductase. (1996). https://pubmed.ncbi.nlm.nih.gov/8769129/ DOI: 10.1006/bbrc.1996.1165
Complete structured claim and evidence
The tested lipoamide dehydrogenase reduced R-lipoic acid about 28 times faster than S-lipoic acid.
Mitochondrial lipoamide dehydrogenases, species unspecified → Free R-alpha-lipoic acid source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/8573188.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7631d83a60fe421318384db96c5b92458c21b0e3aeadaff85c7ae60223e40976", "start_char": 0, "end_char": 809, "text_sha256": "7631d83a60fe421318384db96c5b92458c21b0e3aeadaff85c7ae60223e40976"}
experimental_model
Purified mitochondrial lipoamide dehydrogenase stereoselectivity assays
exposure
R/S lipoic acid and metabolites
limitations
Do not equate the enzyme-family result with a specific human DLD preparation or whole-person clinical superiority.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Species not identified in indexed abstract
plain_language
The two mirror-image forms were not equivalent substrates for this enzyme.
primary_references
[ala-p8573188] Reduction of lipoic acid by lipoamide dehydrogenase. (1996). https://pubmed.ncbi.nlm.nih.gov/8573188/ DOI: 10.1016/0006-2952(95)02124-8
tissue_or_cell_type
Purified mitochondrial enzyme
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 767–778
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified mitochondrial lipoamide dehydrogenase stereoselectivity assays · source_derived_draft · unverified_draft
### ala-lipdh-r-selectivity The tested lipoamide dehydrogenase reduced R-lipoic acid about 28 times faster than S-lipoic acid. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two mirror-image forms were not equivalent substrates for this enzyme. organism: Species not identified in indexed abstract tissue_or_cell_type: Purified mitochondrial enzyme experimental_model: Purified mitochondrial lipoamide dehydrogenase stereoselectivity assays limitations: Do not equate the enzyme-family result with a specific human DLD preparation or whole-person clinical superiority. exposure: R/S lipoic acid and metabolites evidence_span: {"source_cache": "artifacts/ala-research/8573188.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7631d83a60fe421318384db96c5b92458c21b0e3aeadaff85c7ae60223e40976", "start_char": 0, "end_char": 809, "text_sha256": "7631d83a60fe421318384db96c5b92458c21b0e3aeadaff85c7ae60223e40976"} [ala-p8573188] Reduction of lipoic acid by lipoamide dehydrogenase. (1996). https://pubmed.ncbi.nlm.nih.gov/8573188/ DOI: 10.1016/0006-2952(95)02124-8
Complete structured claim and evidence
S-lipoic acid inhibited R-lipoic-acid reduction only at high concentrations in the enzyme assay.
Free S-alpha-lipoic acid → Free R-alpha-lipoic acid source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/8573188.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7631d83a60fe421318384db96c5b92458c21b0e3aeadaff85c7ae60223e40976", "start_char": 0, "end_char": 809, "text_sha256": "7631d83a60fe421318384db96c5b92458c21b0e3aeadaff85c7ae60223e40976"}
experimental_model
Purified mitochondrial lipoamide dehydrogenase stereoselectivity assays
exposure
R/S lipoic acid and metabolites
limitations
Do not equate the enzyme-family result with a specific human DLD preparation or whole-person clinical superiority.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Species not identified in indexed abstract
plain_language
Competition appeared under particular assay conditions, not as proof that ordinary racemic supplements block the pathway.
primary_references
[ala-p8573188] Reduction of lipoic acid by lipoamide dehydrogenase. (1996). https://pubmed.ncbi.nlm.nih.gov/8573188/ DOI: 10.1016/0006-2952(95)02124-8
tissue_or_cell_type
Purified mitochondrial enzyme
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 780–791
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified mitochondrial lipoamide dehydrogenase stereoselectivity assays · source_derived_draft · unverified_draft
### ala-s-high-concentration-inhibition S-lipoic acid inhibited R-lipoic-acid reduction only at high concentrations in the enzyme assay. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Competition appeared under particular assay conditions, not as proof that ordinary racemic supplements block the pathway. organism: Species not identified in indexed abstract tissue_or_cell_type: Purified mitochondrial enzyme experimental_model: Purified mitochondrial lipoamide dehydrogenase stereoselectivity assays limitations: Do not equate the enzyme-family result with a specific human DLD preparation or whole-person clinical superiority. exposure: R/S lipoic acid and metabolites evidence_span: {"source_cache": "artifacts/ala-research/8573188.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7631d83a60fe421318384db96c5b92458c21b0e3aeadaff85c7ae60223e40976", "start_char": 0, "end_char": 809, "text_sha256": "7631d83a60fe421318384db96c5b92458c21b0e3aeadaff85c7ae60223e40976"} [ala-p8573188] Reduction of lipoic acid by lipoamide dehydrogenase. (1996). https://pubmed.ncbi.nlm.nih.gov/8573188/ DOI: 10.1016/0006-2952(95)02124-8
Complete structured claim and evidence
Increased extracellular cysteine supported cellular uptake and glutathione synthesis, bypassing dependence on cystine transport in the studied cells.
Cellular cysteine uptake → Cellular reduced-glutathione pool source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/9288403.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2", "start_char": 0, "end_char": 1497, "text_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2"}
experimental_model
Cell-culture thiol transport and glutathione experiments
exposure
Lipoic acid/DHLA treatment and extracellular thiol measurements
limitations
Cell-type and extracellular-substrate dependence; no demonstration of general methylation-vitamin depletion.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human, rat and mouse cells as specified
plain_language
The cells could import ready-to-use cysteine instead of relying on cystine uptake.
primary_references
[ala-p9288403] Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. (1997). https://pubmed.ncbi.nlm.nih.gov/9288403/ DOI: 10.1002/biof.5520060303
tissue_or_cell_type
Human lymphocytes, Jurkat cells and erythrocytes; rat C6 and mouse NB41A3 cells
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 806–817
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-culture thiol transport and glutathione experiments · source_derived_draft · unverified_draft
### ala-cysteine-gsh-route Increased extracellular cysteine supported cellular uptake and glutathione synthesis, bypassing dependence on cystine transport in the studied cells. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cells could import ready-to-use cysteine instead of relying on cystine uptake. organism: Human, rat and mouse cells as specified tissue_or_cell_type: Human lymphocytes, Jurkat cells and erythrocytes; rat C6 and mouse NB41A3 cells experimental_model: Cell-culture thiol transport and glutathione experiments limitations: Cell-type and extracellular-substrate dependence; no demonstration of general methylation-vitamin depletion. exposure: Lipoic acid/DHLA treatment and extracellular thiol measurements evidence_span: {"source_cache": "artifacts/ala-research/9288403.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2", "start_char": 0, "end_char": 1497, "text_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2"} [ala-p9288403] Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. (1997). https://pubmed.ncbi.nlm.nih.gov/9288403/ DOI: 10.1002/biof.5520060303
Complete structured claim and evidence
In peripheral blood lymphocytes, lipoic-acid treatment mainly restored a low-thiol subpopulation rather than raising all cells above physiological thiol levels.
Lipoic acid → Cellular reduced-glutathione pool source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/9288403.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2", "start_char": 0, "end_char": 1497, "text_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2"}
experimental_model
Cell-culture thiol transport and glutathione experiments
exposure
Lipoic acid/DHLA treatment and extracellular thiol measurements
limitations
Cell-type and extracellular-substrate dependence; no demonstration of general methylation-vitamin depletion.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human, rat and mouse cells as specified
plain_language
The response depended on the cells’ starting condition.
primary_references
[ala-p9288403] Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. (1997). https://pubmed.ncbi.nlm.nih.gov/9288403/ DOI: 10.1002/biof.5520060303
tissue_or_cell_type
Human lymphocytes, Jurkat cells and erythrocytes; rat C6 and mouse NB41A3 cells
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 819–830
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-culture thiol transport and glutathione experiments · source_derived_draft · unverified_draft
### ala-lymphocyte-thiol-subset In peripheral blood lymphocytes, lipoic-acid treatment mainly restored a low-thiol subpopulation rather than raising all cells above physiological thiol levels. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response depended on the cells’ starting condition. organism: Human, rat and mouse cells as specified tissue_or_cell_type: Human lymphocytes, Jurkat cells and erythrocytes; rat C6 and mouse NB41A3 cells experimental_model: Cell-culture thiol transport and glutathione experiments limitations: Cell-type and extracellular-substrate dependence; no demonstration of general methylation-vitamin depletion. exposure: Lipoic acid/DHLA treatment and extracellular thiol measurements evidence_span: {"source_cache": "artifacts/ala-research/9288403.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2", "start_char": 0, "end_char": 1497, "text_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2"} [ala-p9288403] Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. (1997). https://pubmed.ncbi.nlm.nih.gov/9288403/ DOI: 10.1002/biof.5520060303
Complete structured claim and evidence
Older rat liver showed lower GCLC/GCLM expression and about 53% lower GCL activity than young liver.
Rat glutamate-cysteine ligase catalytic subunit / Gclc → Rat hepatic glutamate-cysteine ligase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/14985508.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13", "start_char": 0, "end_char": 1696, "text_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13"}
experimental_model
Aging-rat liver biochemistry and R-lipoic-acid intervention
exposure
R-lipoic acid 40 mg/kg intraperitoneally; time course up to 48 hours
limitations
Animal injection study; changes in enzyme expression are distinct from direct radical scavenging and human clinical efficacy.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Rat
plain_language
Aging changed the machinery that makes glutathione in this model.
primary_references
[ala-p14985508] Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. (2004). https://pubmed.ncbi.nlm.nih.gov/14985508/ DOI: 10.1073/pnas.0400282101
tissue_or_cell_type
Liver
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 832–843
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Aging-rat liver biochemistry and R-lipoic-acid intervention · source_derived_draft · unverified_draft
### ala-aging-gcl-capacity Older rat liver showed lower GCLC/GCLM expression and about 53% lower GCL activity than young liver. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Aging changed the machinery that makes glutathione in this model. organism: Rat tissue_or_cell_type: Liver experimental_model: Aging-rat liver biochemistry and R-lipoic-acid intervention limitations: Animal injection study; changes in enzyme expression are distinct from direct radical scavenging and human clinical efficacy. exposure: R-lipoic acid 40 mg/kg intraperitoneally; time course up to 48 hours evidence_span: {"source_cache": "artifacts/ala-research/14985508.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13", "start_char": 0, "end_char": 1696, "text_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13"} [ala-p14985508] Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. (2004). https://pubmed.ncbi.nlm.nih.gov/14985508/ DOI: 10.1073/pnas.0400282101
Complete structured claim and evidence
Injected R-lipoic acid increased nuclear Nrf2 and antioxidant-response-element binding in aged rat liver.
Free R-alpha-lipoic acid → Rat hepatic Nrf2 nuclear accumulation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/14985508.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13", "start_char": 0, "end_char": 1696, "text_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13"}
experimental_model
Aging-rat liver biochemistry and R-lipoic-acid intervention
exposure
R-lipoic acid 40 mg/kg intraperitoneally; time course up to 48 hours
limitations
Animal injection study; changes in enzyme expression are distinct from direct radical scavenging and human clinical efficacy.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Rat
plain_language
The intervention changed a gene-regulating response, beyond any direct antioxidant reaction.
primary_references
[ala-p14985508] Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. (2004). https://pubmed.ncbi.nlm.nih.gov/14985508/ DOI: 10.1073/pnas.0400282101
tissue_or_cell_type
Liver
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 845–856
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Aging-rat liver biochemistry and R-lipoic-acid intervention · source_derived_draft · unverified_draft
### ala-rla-nrf2-rat Injected R-lipoic acid increased nuclear Nrf2 and antioxidant-response-element binding in aged rat liver. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The intervention changed a gene-regulating response, beyond any direct antioxidant reaction. organism: Rat tissue_or_cell_type: Liver experimental_model: Aging-rat liver biochemistry and R-lipoic-acid intervention limitations: Animal injection study; changes in enzyme expression are distinct from direct radical scavenging and human clinical efficacy. exposure: R-lipoic acid 40 mg/kg intraperitoneally; time course up to 48 hours evidence_span: {"source_cache": "artifacts/ala-research/14985508.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13", "start_char": 0, "end_char": 1696, "text_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13"} [ala-p14985508] Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. (2004). https://pubmed.ncbi.nlm.nih.gov/14985508/ DOI: 10.1073/pnas.0400282101
Complete structured claim and evidence
R-lipoic-acid treatment increased GCLC and GCL activity at the later measured time point in aged rat liver.
Free R-alpha-lipoic acid → Rat hepatic glutamate-cysteine ligase activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/14985508.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13", "start_char": 0, "end_char": 1696, "text_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13"}
experimental_model
Aging-rat liver biochemistry and R-lipoic-acid intervention
exposure
R-lipoic acid 40 mg/kg intraperitoneally; time course up to 48 hours
limitations
Animal injection study; changes in enzyme expression are distinct from direct radical scavenging and human clinical efficacy.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Rat
plain_language
The liver increased part of its glutathione-making capacity.
primary_references
[ala-p14985508] Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. (2004). https://pubmed.ncbi.nlm.nih.gov/14985508/ DOI: 10.1073/pnas.0400282101
tissue_or_cell_type
Liver
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 858–869
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Aging-rat liver biochemistry and R-lipoic-acid intervention · source_derived_draft · unverified_draft
### ala-rla-gcl-rat R-lipoic-acid treatment increased GCLC and GCL activity at the later measured time point in aged rat liver. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The liver increased part of its glutathione-making capacity. organism: Rat tissue_or_cell_type: Liver experimental_model: Aging-rat liver biochemistry and R-lipoic-acid intervention limitations: Animal injection study; changes in enzyme expression are distinct from direct radical scavenging and human clinical efficacy. exposure: R-lipoic acid 40 mg/kg intraperitoneally; time course up to 48 hours evidence_span: {"source_cache": "artifacts/ala-research/14985508.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13", "start_char": 0, "end_char": 1696, "text_sha256": "a43d83e66af102cc530c2cb2da20c79749ab5c85c815e573e9797f9fc6645d13"} [ala-p14985508] Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. (2004). https://pubmed.ncbi.nlm.nih.gov/14985508/ DOI: 10.1073/pnas.0400282101
Complete structured claim and evidence
Lipoic-acid exposure increased nuclear Nrf2 and reduced KEAP1 protein in HL-60 cells.
Lipoic acid → Human HL-60 Nrf2 nuclear accumulation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/18813798.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814", "start_char": 0, "end_char": 1245, "text_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814"}
experimental_model
Human HL-60 leukemia cell biochemical study
exposure
Alpha-lipoic-acid exposure
limitations
Association of Nrf2/KEAP1 changes with NQO1 induction does not by itself establish genetic dependency or clinical cancer benefit.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human cell line
plain_language
A cellular stress-response regulator changed location while its inhibitor decreased.
primary_references
[ala-p18813798] Control of cellular redox status and upregulation of quinone reductase NQO1 via Nrf2 activation by alpha-lipoic acid in human leukemia HL-60 cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18813798/ DOI: 10.3892/ijo_00000071
tissue_or_cell_type
HL-60 cells
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 871–882
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HL-60 leukemia cell biochemical study · source_derived_draft · unverified_draft
### ala-hl60-nrf2-keap1 Lipoic-acid exposure increased nuclear Nrf2 and reduced KEAP1 protein in HL-60 cells. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A cellular stress-response regulator changed location while its inhibitor decreased. organism: Human cell line tissue_or_cell_type: HL-60 cells experimental_model: Human HL-60 leukemia cell biochemical study limitations: Association of Nrf2/KEAP1 changes with NQO1 induction does not by itself establish genetic dependency or clinical cancer benefit. exposure: Alpha-lipoic-acid exposure evidence_span: {"source_cache": "artifacts/ala-research/18813798.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814", "start_char": 0, "end_char": 1245, "text_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814"} [ala-p18813798] Control of cellular redox status and upregulation of quinone reductase NQO1 via Nrf2 activation by alpha-lipoic acid in human leukemia HL-60 cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18813798/ DOI: 10.3892/ijo_00000071
Complete structured claim and evidence
NQO1 protein and enzyme activity increased after lipoic-acid treatment in HL-60 cells.
Lipoic acid → Human NAD(P)H quinone dehydrogenase 1 / NQO1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/18813798.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814", "start_char": 0, "end_char": 1245, "text_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814"}
experimental_model
Human HL-60 leukemia cell biochemical study
exposure
Alpha-lipoic-acid exposure
limitations
Association of Nrf2/KEAP1 changes with NQO1 induction does not by itself establish genetic dependency or clinical cancer benefit.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human cell line
plain_language
The response included more activity of a specific quinone-processing enzyme.
primary_references
[ala-p18813798] Control of cellular redox status and upregulation of quinone reductase NQO1 via Nrf2 activation by alpha-lipoic acid in human leukemia HL-60 cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18813798/ DOI: 10.3892/ijo_00000071
tissue_or_cell_type
HL-60 cells
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 884–895
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HL-60 leukemia cell biochemical study · source_derived_draft · unverified_draft
### ala-hl60-nqo1 NQO1 protein and enzyme activity increased after lipoic-acid treatment in HL-60 cells. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response included more activity of a specific quinone-processing enzyme. organism: Human cell line tissue_or_cell_type: HL-60 cells experimental_model: Human HL-60 leukemia cell biochemical study limitations: Association of Nrf2/KEAP1 changes with NQO1 induction does not by itself establish genetic dependency or clinical cancer benefit. exposure: Alpha-lipoic-acid exposure evidence_span: {"source_cache": "artifacts/ala-research/18813798.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814", "start_char": 0, "end_char": 1245, "text_sha256": "bcc2d2fa7c8f550c53af52dfcd88a1e84bee38f98b85cb72e723eba495b01814"} [ala-p18813798] Control of cellular redox status and upregulation of quinone reductase NQO1 via Nrf2 activation by alpha-lipoic acid in human leukemia HL-60 cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18813798/ DOI: 10.3892/ijo_00000071
Complete structured claim and evidence
Lipoic acid increased PI3K and Akt1 activities in L6 myotubes; wortmannin inhibited these responses.
Lipoic acid → Rat phosphoinositide 3-kinase enzymes source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/11375349.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "971e4224c0ff09f05d25fe64359a3c65d50f2187fd781840c55821c47d2ed111", "start_char": 0, "end_char": 1734, "text_sha256": "971e4224c0ff09f05d25fe64359a3c65d50f2187fd781840c55821c47d2ed111"}
experimental_model
Signaling, transporter localization and glucose-uptake assays
exposure
2.5 mmol/L lipoic acid; PI3K and p38 inhibitors
limitations
High cell-culture exposure; pharmacological inhibitors can have off-target effects; not a plasma target or patient dose.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Rat
plain_language
A high experimental exposure engaged part of the insulin-signaling pathway.
primary_references
[ala-p11375349] The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11375349/ DOI: 10.2337/diabetes.50.6.1464
tissue_or_cell_type
L6 myotubes
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 897–908
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Signaling, transporter localization and glucose-uptake assays · source_derived_draft · unverified_draft
### ala-myotube-pi3k-akt Lipoic acid increased PI3K and Akt1 activities in L6 myotubes; wortmannin inhibited these responses. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A high experimental exposure engaged part of the insulin-signaling pathway. organism: Rat tissue_or_cell_type: L6 myotubes experimental_model: Signaling, transporter localization and glucose-uptake assays limitations: High cell-culture exposure; pharmacological inhibitors can have off-target effects; not a plasma target or patient dose. exposure: 2.5 mmol/L lipoic acid; PI3K and p38 inhibitors evidence_span: {"source_cache": "artifacts/ala-research/11375349.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "971e4224c0ff09f05d25fe64359a3c65d50f2187fd781840c55821c47d2ed111", "start_char": 0, "end_char": 1734, "text_sha256": "971e4224c0ff09f05d25fe64359a3c65d50f2187fd781840c55821c47d2ed111"} [ala-p11375349] The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11375349/ DOI: 10.2337/diabetes.50.6.1464
Complete structured claim and evidence
Lipoic acid increased surface GLUT4 in L6 myotubes.
Lipoic acid → Rat GLUT4 translocation to the cell surface source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/11375349.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "971e4224c0ff09f05d25fe64359a3c65d50f2187fd781840c55821c47d2ed111", "start_char": 0, "end_char": 1734, "text_sha256": "971e4224c0ff09f05d25fe64359a3c65d50f2187fd781840c55821c47d2ed111"}
experimental_model
Signaling, transporter localization and glucose-uptake assays
exposure
2.5 mmol/L lipoic acid; PI3K and p38 inhibitors
limitations
High cell-culture exposure; pharmacological inhibitors can have off-target effects; not a plasma target or patient dose.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Rat
plain_language
More glucose transporters reached the cell surface.
primary_references
[ala-p11375349] The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11375349/ DOI: 10.2337/diabetes.50.6.1464
tissue_or_cell_type
L6 myotubes
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 910–921
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Signaling, transporter localization and glucose-uptake assays · source_derived_draft · unverified_draft
### ala-myotube-glut4 Lipoic acid increased surface GLUT4 in L6 myotubes. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: More glucose transporters reached the cell surface. organism: Rat tissue_or_cell_type: L6 myotubes experimental_model: Signaling, transporter localization and glucose-uptake assays limitations: High cell-culture exposure; pharmacological inhibitors can have off-target effects; not a plasma target or patient dose. exposure: 2.5 mmol/L lipoic acid; PI3K and p38 inhibitors evidence_span: {"source_cache": "artifacts/ala-research/11375349.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "971e4224c0ff09f05d25fe64359a3c65d50f2187fd781840c55821c47d2ed111", "start_char": 0, "end_char": 1734, "text_sha256": "971e4224c0ff09f05d25fe64359a3c65d50f2187fd781840c55821c47d2ed111"} [ala-p11375349] The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11375349/ DOI: 10.2337/diabetes.50.6.1464
Complete structured claim and evidence
p38 inhibitors reduced lipoic-acid-stimulated glucose uptake without blocking GLUT4 translocation in L6 myotubes.
Rat p38 MAP kinase enzymes → Rat myotube glucose uptake source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/11375349.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "971e4224c0ff09f05d25fe64359a3c65d50f2187fd781840c55821c47d2ed111", "start_char": 0, "end_char": 1734, "text_sha256": "971e4224c0ff09f05d25fe64359a3c65d50f2187fd781840c55821c47d2ed111"}
experimental_model
Signaling, transporter localization and glucose-uptake assays
exposure
2.5 mmol/L lipoic acid; PI3K and p38 inhibitors
limitations
High cell-culture exposure; pharmacological inhibitors can have off-target effects; not a plasma target or patient dose.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Rat
plain_language
Transporter location and actual glucose movement were separable measurements.
primary_references
[ala-p11375349] The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11375349/ DOI: 10.2337/diabetes.50.6.1464
tissue_or_cell_type
L6 myotubes
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 923–934
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Signaling, transporter localization and glucose-uptake assays · source_derived_draft · unverified_draft
### ala-p38-uptake-localization p38 inhibitors reduced lipoic-acid-stimulated glucose uptake without blocking GLUT4 translocation in L6 myotubes. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Transporter location and actual glucose movement were separable measurements. organism: Rat tissue_or_cell_type: L6 myotubes experimental_model: Signaling, transporter localization and glucose-uptake assays limitations: High cell-culture exposure; pharmacological inhibitors can have off-target effects; not a plasma target or patient dose. exposure: 2.5 mmol/L lipoic acid; PI3K and p38 inhibitors evidence_span: {"source_cache": "artifacts/ala-research/11375349.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "971e4224c0ff09f05d25fe64359a3c65d50f2187fd781840c55821c47d2ed111", "start_char": 0, "end_char": 1734, "text_sha256": "971e4224c0ff09f05d25fe64359a3c65d50f2187fd781840c55821c47d2ed111"} [ala-p11375349] The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11375349/ DOI: 10.2337/diabetes.50.6.1464
Complete structured claim and evidence
Lipoic-acid treatment increased intracellular oxidant signals, reduced insulin-receptor thiol reactivity and increased receptor phosphorylation.
Lipoic acid → Mouse adipocyte insulin-receptor autophosphorylation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/12948866.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0440cb8edaf0213af3824367ee799d1a1916ed2340c9da99588d83c7581804b9", "start_char": 0, "end_char": 1489, "text_sha256": "0440cb8edaf0213af3824367ee799d1a1916ed2340c9da99588d83c7581804b9"}
experimental_model
Protein-thiol, phosphorylation and glucose-uptake assays
exposure
Alpha-lipoic-acid stimulation with redox/thiol inhibitors
limitations
Cell-culture redox signaling; not proof that lipoic acid invariably lowers oxidation in all settings.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Mouse
plain_language
A local oxidant signal accompanied insulin-receptor activation.
primary_references
[ala-p12948866] Alpha-lipoic acid decreases thiol reactivity of the insulin receptor and protein tyrosine phosphatase 1B in 3T3-L1 adipocytes. (2003). https://pubmed.ncbi.nlm.nih.gov/12948866/ DOI: 10.1016/s0006-2952(03)00395-2
tissue_or_cell_type
3T3-L1 adipocytes
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 936–947
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein-thiol, phosphorylation and glucose-uptake assays · source_derived_draft · unverified_draft
### ala-adipocyte-insr-redox Lipoic-acid treatment increased intracellular oxidant signals, reduced insulin-receptor thiol reactivity and increased receptor phosphorylation. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A local oxidant signal accompanied insulin-receptor activation. organism: Mouse tissue_or_cell_type: 3T3-L1 adipocytes experimental_model: Protein-thiol, phosphorylation and glucose-uptake assays limitations: Cell-culture redox signaling; not proof that lipoic acid invariably lowers oxidation in all settings. exposure: Alpha-lipoic-acid stimulation with redox/thiol inhibitors evidence_span: {"source_cache": "artifacts/ala-research/12948866.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0440cb8edaf0213af3824367ee799d1a1916ed2340c9da99588d83c7581804b9", "start_char": 0, "end_char": 1489, "text_sha256": "0440cb8edaf0213af3824367ee799d1a1916ed2340c9da99588d83c7581804b9"} [ala-p12948866] Alpha-lipoic acid decreases thiol reactivity of the insulin receptor and protein tyrosine phosphatase 1B in 3T3-L1 adipocytes. (2003). https://pubmed.ncbi.nlm.nih.gov/12948866/ DOI: 10.1016/s0006-2952(03)00395-2
Complete structured claim and evidence
Lipoic acid reduced phosphatase activity and PTP1B thiol reactivity in 3T3-L1 cells.
Lipoic acid → Mouse protein tyrosine phosphatase 1B / Ptpn1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/12948866.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0440cb8edaf0213af3824367ee799d1a1916ed2340c9da99588d83c7581804b9", "start_char": 0, "end_char": 1489, "text_sha256": "0440cb8edaf0213af3824367ee799d1a1916ed2340c9da99588d83c7581804b9"}
experimental_model
Protein-thiol, phosphorylation and glucose-uptake assays
exposure
Alpha-lipoic-acid stimulation with redox/thiol inhibitors
limitations
Cell-culture redox signaling; not proof that lipoic acid invariably lowers oxidation in all settings.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Mouse
plain_language
The exposure weakened a phosphatase brake on phosphorylation signaling.
primary_references
[ala-p12948866] Alpha-lipoic acid decreases thiol reactivity of the insulin receptor and protein tyrosine phosphatase 1B in 3T3-L1 adipocytes. (2003). https://pubmed.ncbi.nlm.nih.gov/12948866/ DOI: 10.1016/s0006-2952(03)00395-2
tissue_or_cell_type
3T3-L1 adipocytes
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 949–960
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein-thiol, phosphorylation and glucose-uptake assays · source_derived_draft · unverified_draft
### ala-adipocyte-ptp1b Lipoic acid reduced phosphatase activity and PTP1B thiol reactivity in 3T3-L1 cells. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The exposure weakened a phosphatase brake on phosphorylation signaling. organism: Mouse tissue_or_cell_type: 3T3-L1 adipocytes experimental_model: Protein-thiol, phosphorylation and glucose-uptake assays limitations: Cell-culture redox signaling; not proof that lipoic acid invariably lowers oxidation in all settings. exposure: Alpha-lipoic-acid stimulation with redox/thiol inhibitors evidence_span: {"source_cache": "artifacts/ala-research/12948866.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0440cb8edaf0213af3824367ee799d1a1916ed2340c9da99588d83c7581804b9", "start_char": 0, "end_char": 1489, "text_sha256": "0440cb8edaf0213af3824367ee799d1a1916ed2340c9da99588d83c7581804b9"} [ala-p12948866] Alpha-lipoic acid decreases thiol reactivity of the insulin receptor and protein tyrosine phosphatase 1B in 3T3-L1 adipocytes. (2003). https://pubmed.ncbi.nlm.nih.gov/12948866/ DOI: 10.1016/s0006-2952(03)00395-2
Complete structured claim and evidence
Lipoic acid increased glucose uptake in 3T3-L1 adipocytes; intracellular thiol modification or inhibition of the upstream oxidant response blocked stimulation.
Lipoic acid → Mouse adipocyte glucose uptake source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/12948866.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0440cb8edaf0213af3824367ee799d1a1916ed2340c9da99588d83c7581804b9", "start_char": 0, "end_char": 1489, "text_sha256": "0440cb8edaf0213af3824367ee799d1a1916ed2340c9da99588d83c7581804b9"}
experimental_model
Protein-thiol, phosphorylation and glucose-uptake assays
exposure
Alpha-lipoic-acid stimulation with redox/thiol inhibitors
limitations
Cell-culture redox signaling; not proof that lipoic acid invariably lowers oxidation in all settings.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Mouse
plain_language
The glucose response depended on the cell’s redox-signaling machinery.
primary_references
[ala-p12948866] Alpha-lipoic acid decreases thiol reactivity of the insulin receptor and protein tyrosine phosphatase 1B in 3T3-L1 adipocytes. (2003). https://pubmed.ncbi.nlm.nih.gov/12948866/ DOI: 10.1016/s0006-2952(03)00395-2
tissue_or_cell_type
3T3-L1 adipocytes
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 962–973
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein-thiol, phosphorylation and glucose-uptake assays · source_derived_draft · unverified_draft
### ala-adipocyte-glucose Lipoic acid increased glucose uptake in 3T3-L1 adipocytes; intracellular thiol modification or inhibition of the upstream oxidant response blocked stimulation. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The glucose response depended on the cell’s redox-signaling machinery. organism: Mouse tissue_or_cell_type: 3T3-L1 adipocytes experimental_model: Protein-thiol, phosphorylation and glucose-uptake assays limitations: Cell-culture redox signaling; not proof that lipoic acid invariably lowers oxidation in all settings. exposure: Alpha-lipoic-acid stimulation with redox/thiol inhibitors evidence_span: {"source_cache": "artifacts/ala-research/12948866.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0440cb8edaf0213af3824367ee799d1a1916ed2340c9da99588d83c7581804b9", "start_char": 0, "end_char": 1489, "text_sha256": "0440cb8edaf0213af3824367ee799d1a1916ed2340c9da99588d83c7581804b9"} [ala-p12948866] Alpha-lipoic acid decreases thiol reactivity of the insulin receptor and protein tyrosine phosphatase 1B in 3T3-L1 adipocytes. (2003). https://pubmed.ncbi.nlm.nih.gov/12948866/ DOI: 10.1016/s0006-2952(03)00395-2
Complete structured claim and evidence
Lipoic acid suppressed hypothalamic AMPK activity in the rodent experiments.
Lipoic acid → Rodent hypothalamic AMPK activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/15195087.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6fcce42055285979267d9a0f58b3c7e9fb221b549db47d2f508b3fb2112ad493", "start_char": 0, "end_char": 1001, "text_sha256": "6fcce42055285979267d9a0f58b3c7e9fb221b549db47d2f508b3fb2112ad493"}
experimental_model
Rodent feeding, energy expenditure and hypothalamic AMPK manipulation
exposure
Alpha-lipoic acid with central AMPK manipulation
limitations
Central effects must not be generalized to AMPK in all tissues or to human weight-loss outcomes.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Rodents
plain_language
The brain’s feeding-control AMPK response decreased in this setting.
primary_references
[ala-p15195087] Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase. (2004). https://pubmed.ncbi.nlm.nih.gov/15195087/ DOI: 10.1038/nm1061
tissue_or_cell_type
Hypothalamus and whole-animal energy balance
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 975–986
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rodent feeding, energy expenditure and hypothalamic AMPK manipulation · source_derived_draft · unverified_draft
### ala-hypothalamic-ampk Lipoic acid suppressed hypothalamic AMPK activity in the rodent experiments. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The brain’s feeding-control AMPK response decreased in this setting. organism: Rodents tissue_or_cell_type: Hypothalamus and whole-animal energy balance experimental_model: Rodent feeding, energy expenditure and hypothalamic AMPK manipulation limitations: Central effects must not be generalized to AMPK in all tissues or to human weight-loss outcomes. exposure: Alpha-lipoic acid with central AMPK manipulation evidence_span: {"source_cache": "artifacts/ala-research/15195087.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6fcce42055285979267d9a0f58b3c7e9fb221b549db47d2f508b3fb2112ad493", "start_char": 0, "end_char": 1001, "text_sha256": "6fcce42055285979267d9a0f58b3c7e9fb221b549db47d2f508b3fb2112ad493"} [ala-p15195087] Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase. (2004). https://pubmed.ncbi.nlm.nih.gov/15195087/ DOI: 10.1038/nm1061
Complete structured claim and evidence
Reactivating hypothalamic AMPK reversed lipoic-acid effects on food intake and energy expenditure.
Rodent hypothalamic AMPK activity → Rodent food intake source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/15195087.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6fcce42055285979267d9a0f58b3c7e9fb221b549db47d2f508b3fb2112ad493", "start_char": 0, "end_char": 1001, "text_sha256": "6fcce42055285979267d9a0f58b3c7e9fb221b549db47d2f508b3fb2112ad493"}
experimental_model
Rodent feeding, energy expenditure and hypothalamic AMPK manipulation
exposure
Alpha-lipoic acid with central AMPK manipulation
limitations
Central effects must not be generalized to AMPK in all tissues or to human weight-loss outcomes.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Rodents
plain_language
Manipulating the brain pathway changed the feeding response.
primary_references
[ala-p15195087] Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase. (2004). https://pubmed.ncbi.nlm.nih.gov/15195087/ DOI: 10.1038/nm1061
tissue_or_cell_type
Hypothalamus and whole-animal energy balance
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 988–999
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rodent feeding, energy expenditure and hypothalamic AMPK manipulation · source_derived_draft · unverified_draft
### ala-hypothalamic-feeding Reactivating hypothalamic AMPK reversed lipoic-acid effects on food intake and energy expenditure. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Manipulating the brain pathway changed the feeding response. organism: Rodents tissue_or_cell_type: Hypothalamus and whole-animal energy balance experimental_model: Rodent feeding, energy expenditure and hypothalamic AMPK manipulation limitations: Central effects must not be generalized to AMPK in all tissues or to human weight-loss outcomes. exposure: Alpha-lipoic acid with central AMPK manipulation evidence_span: {"source_cache": "artifacts/ala-research/15195087.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6fcce42055285979267d9a0f58b3c7e9fb221b549db47d2f508b3fb2112ad493", "start_char": 0, "end_char": 1001, "text_sha256": "6fcce42055285979267d9a0f58b3c7e9fb221b549db47d2f508b3fb2112ad493"} [ala-p15195087] Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase. (2004). https://pubmed.ncbi.nlm.nih.gov/15195087/ DOI: 10.1038/nm1061
Complete structured claim and evidence
Lipoic acid spared intracellular ascorbate under basal and menadione-challenged conditions in endothelial cells.
Lipoic acid → Human endothelial intracellular ascorbate pool source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/18026819.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a", "start_char": 0, "end_char": 1329, "text_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a"}
experimental_model
Human endothelial-cell and extracellular LDL oxidation experiments
exposure
40–80 micromolar lipoic acid; menadione or copper/LDL challenge
limitations
Compartment and oxidant matter; intracellular vitamin C and LDL vitamin E are distinct readouts.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human cell line and human LDL
plain_language
Vitamin C was preserved under some cellular conditions.
primary_references
[ala-p18026819] alpha-Lipoic acid and ascorbate prevent LDL oxidation and oxidant stress in endothelial cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18026819/ DOI: 10.1007/s11010-007-9650-z
tissue_or_cell_type
EA.hy926 endothelial cells; extracellular LDL
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1001–1012
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human endothelial-cell and extracellular LDL oxidation experiments · source_derived_draft · unverified_draft
### ala-endothelial-ascorbate-sparing Lipoic acid spared intracellular ascorbate under basal and menadione-challenged conditions in endothelial cells. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C was preserved under some cellular conditions. organism: Human cell line and human LDL tissue_or_cell_type: EA.hy926 endothelial cells; extracellular LDL experimental_model: Human endothelial-cell and extracellular LDL oxidation experiments limitations: Compartment and oxidant matter; intracellular vitamin C and LDL vitamin E are distinct readouts. exposure: 40–80 micromolar lipoic acid; menadione or copper/LDL challenge evidence_span: {"source_cache": "artifacts/ala-research/18026819.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a", "start_char": 0, "end_char": 1329, "text_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a"} [ala-p18026819] alpha-Lipoic acid and ascorbate prevent LDL oxidation and oxidant stress in endothelial cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18026819/ DOI: 10.1007/s11010-007-9650-z
Complete structured claim and evidence
Lipoic acid blunted copper-driven LDL oxidation and associated vitamin E consumption in the endothelial-cell experiment.
Lipoic acid → LDL vitamin E consumption during oxidation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/18026819.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a", "start_char": 0, "end_char": 1329, "text_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a"}
experimental_model
Human endothelial-cell and extracellular LDL oxidation experiments
exposure
40–80 micromolar lipoic acid; menadione or copper/LDL challenge
limitations
Compartment and oxidant matter; intracellular vitamin C and LDL vitamin E are distinct readouts.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human cell line and human LDL
plain_language
The extracellular lipoprotein compartment showed less oxidative damage.
primary_references
[ala-p18026819] alpha-Lipoic acid and ascorbate prevent LDL oxidation and oxidant stress in endothelial cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18026819/ DOI: 10.1007/s11010-007-9650-z
tissue_or_cell_type
EA.hy926 endothelial cells; extracellular LDL
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1014–1025
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human endothelial-cell and extracellular LDL oxidation experiments · source_derived_draft · unverified_draft
### ala-ldl-vitamin-e-sparing Lipoic acid blunted copper-driven LDL oxidation and associated vitamin E consumption in the endothelial-cell experiment. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The extracellular lipoprotein compartment showed less oxidative damage. organism: Human cell line and human LDL tissue_or_cell_type: EA.hy926 endothelial cells; extracellular LDL experimental_model: Human endothelial-cell and extracellular LDL oxidation experiments limitations: Compartment and oxidant matter; intracellular vitamin C and LDL vitamin E are distinct readouts. exposure: 40–80 micromolar lipoic acid; menadione or copper/LDL challenge evidence_span: {"source_cache": "artifacts/ala-research/18026819.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a", "start_char": 0, "end_char": 1329, "text_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a"} [ala-p18026819] alpha-Lipoic acid and ascorbate prevent LDL oxidation and oxidant stress in endothelial cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18026819/ DOI: 10.1007/s11010-007-9650-z
Complete structured claim and evidence
Lipoic acid did not prevent intracellular ascorbate loss caused by the extracellular copper/LDL challenge in the same study.
Lipoic acid → Human endothelial intracellular ascorbate pool source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/18026819.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a", "start_char": 0, "end_char": 1329, "text_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a"}
experimental_model
Human endothelial-cell and extracellular LDL oxidation experiments
exposure
40–80 micromolar lipoic acid; menadione or copper/LDL challenge
limitations
Compartment and oxidant matter; intracellular vitamin C and LDL vitamin E are distinct readouts.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human cell line and human LDL
plain_language
Protection of LDL did not guarantee protection of intracellular vitamin C.
primary_references
[ala-p18026819] alpha-Lipoic acid and ascorbate prevent LDL oxidation and oxidant stress in endothelial cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18026819/ DOI: 10.1007/s11010-007-9650-z
tissue_or_cell_type
EA.hy926 endothelial cells; extracellular LDL
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1027–1038
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human endothelial-cell and extracellular LDL oxidation experiments · source_derived_draft · unverified_draft
### ala-copper-challenge-ascorbate-null Lipoic acid did not prevent intracellular ascorbate loss caused by the extracellular copper/LDL challenge in the same study. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Protection of LDL did not guarantee protection of intracellular vitamin C. organism: Human cell line and human LDL tissue_or_cell_type: EA.hy926 endothelial cells; extracellular LDL experimental_model: Human endothelial-cell and extracellular LDL oxidation experiments limitations: Compartment and oxidant matter; intracellular vitamin C and LDL vitamin E are distinct readouts. exposure: 40–80 micromolar lipoic acid; menadione or copper/LDL challenge evidence_span: {"source_cache": "artifacts/ala-research/18026819.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a", "start_char": 0, "end_char": 1329, "text_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a"} [ala-p18026819] alpha-Lipoic acid and ascorbate prevent LDL oxidation and oxidant stress in endothelial cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18026819/ DOI: 10.1007/s11010-007-9650-z
Complete structured claim and evidence
DHLA delayed copper-driven LDL oxidation, whereas oxidized lipoic acid did not protect in this cell-free assay.
Free dihydrolipoic acid / DHLA → Copper-driven LDL oxidation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/9680174.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1", "start_char": 0, "end_char": 2034, "text_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1"}
experimental_model
Cell-free human LDL oxidation and electron-spin-resonance assays
exposure
Copper 5 micromolar; DHLA 0–20 micromolar; oxygen and pH varied
limitations
Metal binding, reduction and radical production depend on ratio, oxygen and pH; not evidence for human metal-detoxification efficacy.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human LDL; cell-free chemistry
plain_language
Reduced and oxidized forms behaved differently in the same chemical test.
primary_references
[ala-p9680174] Thiol chelation of Cu2+ by dihydrolipoic acid prevents human low density lipoprotein peroxidation. (1998). https://pubmed.ncbi.nlm.nih.gov/9680174/ DOI: 10.1016/s0891-5849(98)00048-3
tissue_or_cell_type
LDL and copper/DHLA solutions
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1040–1051
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free human LDL oxidation and electron-spin-resonance assays · source_derived_draft · unverified_draft
### ala-dhla-ldl-protection DHLA delayed copper-driven LDL oxidation, whereas oxidized lipoic acid did not protect in this cell-free assay. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reduced and oxidized forms behaved differently in the same chemical test. organism: Human LDL; cell-free chemistry tissue_or_cell_type: LDL and copper/DHLA solutions experimental_model: Cell-free human LDL oxidation and electron-spin-resonance assays limitations: Metal binding, reduction and radical production depend on ratio, oxygen and pH; not evidence for human metal-detoxification efficacy. exposure: Copper 5 micromolar; DHLA 0–20 micromolar; oxygen and pH varied evidence_span: {"source_cache": "artifacts/ala-research/9680174.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1", "start_char": 0, "end_char": 2034, "text_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1"} [ala-p9680174] Thiol chelation of Cu2+ by dihydrolipoic acid prevents human low density lipoprotein peroxidation. (1998). https://pubmed.ncbi.nlm.nih.gov/9680174/ DOI: 10.1016/s0891-5849(98)00048-3
Complete structured claim and evidence
DHLA favored copper reduction when copper was in excess and chelation when DHLA was in excess.
Free dihydrolipoic acid / DHLA → Copper(II) ion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/9680174.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1", "start_char": 0, "end_char": 2034, "text_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1"}
experimental_model
Cell-free human LDL oxidation and electron-spin-resonance assays
exposure
Copper 5 micromolar; DHLA 0–20 micromolar; oxygen and pH varied
limitations
Metal binding, reduction and radical production depend on ratio, oxygen and pH; not evidence for human metal-detoxification efficacy.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human LDL; cell-free chemistry
plain_language
Whether copper was bound or chemically reduced depended on the relative amounts.
primary_references
[ala-p9680174] Thiol chelation of Cu2+ by dihydrolipoic acid prevents human low density lipoprotein peroxidation. (1998). https://pubmed.ncbi.nlm.nih.gov/9680174/ DOI: 10.1016/s0891-5849(98)00048-3
tissue_or_cell_type
LDL and copper/DHLA solutions
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1053–1064
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free human LDL oxidation and electron-spin-resonance assays · source_derived_draft · unverified_draft
### ala-dhla-copper-ratio DHLA favored copper reduction when copper was in excess and chelation when DHLA was in excess. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Whether copper was bound or chemically reduced depended on the relative amounts. organism: Human LDL; cell-free chemistry tissue_or_cell_type: LDL and copper/DHLA solutions experimental_model: Cell-free human LDL oxidation and electron-spin-resonance assays limitations: Metal binding, reduction and radical production depend on ratio, oxygen and pH; not evidence for human metal-detoxification efficacy. exposure: Copper 5 micromolar; DHLA 0–20 micromolar; oxygen and pH varied evidence_span: {"source_cache": "artifacts/ala-research/9680174.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1", "start_char": 0, "end_char": 2034, "text_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1"} [ala-p9680174] Thiol chelation of Cu2+ by dihydrolipoic acid prevents human low density lipoprotein peroxidation. (1998). https://pubmed.ncbi.nlm.nih.gov/9680174/ DOI: 10.1016/s0891-5849(98)00048-3
Complete structured claim and evidence
Oxidation destabilized DHLA-copper complexes near physiological pH, with renewed LDL oxidation and radical detection in the model.
Dihydrolipoic acid-copper complexes → Copper-driven LDL oxidation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/9680174.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1", "start_char": 0, "end_char": 2034, "text_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1"}
experimental_model
Cell-free human LDL oxidation and electron-spin-resonance assays
exposure
Copper 5 micromolar; DHLA 0–20 micromolar; oxygen and pH varied
limitations
Metal binding, reduction and radical production depend on ratio, oxygen and pH; not evidence for human metal-detoxification efficacy.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human LDL; cell-free chemistry
plain_language
Metal binding was not a permanent guarantee against oxidation.
primary_references
[ala-p9680174] Thiol chelation of Cu2+ by dihydrolipoic acid prevents human low density lipoprotein peroxidation. (1998). https://pubmed.ncbi.nlm.nih.gov/9680174/ DOI: 10.1016/s0891-5849(98)00048-3
tissue_or_cell_type
LDL and copper/DHLA solutions
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1066–1077
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free human LDL oxidation and electron-spin-resonance assays · source_derived_draft · unverified_draft
### ala-dhla-copper-oxygen Oxidation destabilized DHLA-copper complexes near physiological pH, with renewed LDL oxidation and radical detection in the model. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Metal binding was not a permanent guarantee against oxidation. organism: Human LDL; cell-free chemistry tissue_or_cell_type: LDL and copper/DHLA solutions experimental_model: Cell-free human LDL oxidation and electron-spin-resonance assays limitations: Metal binding, reduction and radical production depend on ratio, oxygen and pH; not evidence for human metal-detoxification efficacy. exposure: Copper 5 micromolar; DHLA 0–20 micromolar; oxygen and pH varied evidence_span: {"source_cache": "artifacts/ala-research/9680174.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1", "start_char": 0, "end_char": 2034, "text_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1"} [ala-p9680174] Thiol chelation of Cu2+ by dihydrolipoic acid prevents human low density lipoprotein peroxidation. (1998). https://pubmed.ncbi.nlm.nih.gov/9680174/ DOI: 10.1016/s0891-5849(98)00048-3
Complete structured claim and evidence
Lipoic acid reduced pharmacological ascorbate-generated hydrogen peroxide in the tested cell experiments.
Lipoic acid → Extracellular hydrogen peroxide generated by pharmacological ascorbate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/39493360.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9bd9ced1ace4214d80aad8e15ca5d61f8e4063f4e5838054b93e8c07a9550266", "start_char": 0, "end_char": 1935, "text_sha256": "9bd9ced1ace4214d80aad8e15ca5d61f8e4063f4e5838054b93e8c07a9550266"}
experimental_model
Cancer-cell combinations and human-tumor xenograft experiments
exposure
Millimolar cell exposures; injected ALA/ascorbate combinations in mice
limitations
Pharmacological ascorbate and animal injection exposures are not dietary vitamin C; no clinical combination trial.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human cancer cells and mice
plain_language
Reducing an oxidant can oppose a treatment that relies on that oxidant.
primary_references
[ala-p39493360] Combination of High-Dose Parenteral Ascorbate (Vitamin C) and Alpha-Lipoic Acid Failed to Enhance Tumor-Inhibitory Effect But Increased Toxicity in Preclinical Cancer Models. (2024). https://pubmed.ncbi.nlm.nih.gov/39493360/ DOI: 10.1177/11795549241283421
tissue_or_cell_type
Six cell lines; MDA-MB-231 xenografts
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1079–1090
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cancer-cell combinations and human-tumor xenograft experiments · source_derived_draft · unverified_draft
### ala-ascorbate-peroxide-antagonism Lipoic acid reduced pharmacological ascorbate-generated hydrogen peroxide in the tested cell experiments. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing an oxidant can oppose a treatment that relies on that oxidant. organism: Human cancer cells and mice tissue_or_cell_type: Six cell lines; MDA-MB-231 xenografts experimental_model: Cancer-cell combinations and human-tumor xenograft experiments limitations: Pharmacological ascorbate and animal injection exposures are not dietary vitamin C; no clinical combination trial. exposure: Millimolar cell exposures; injected ALA/ascorbate combinations in mice evidence_span: {"source_cache": "artifacts/ala-research/39493360.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9bd9ced1ace4214d80aad8e15ca5d61f8e4063f4e5838054b93e8c07a9550266", "start_char": 0, "end_char": 1935, "text_sha256": "9bd9ced1ace4214d80aad8e15ca5d61f8e4063f4e5838054b93e8c07a9550266"} [ala-p39493360] Combination of High-Dose Parenteral Ascorbate (Vitamin C) and Alpha-Lipoic Acid Failed to Enhance Tumor-Inhibitory Effect But Increased Toxicity in Preclinical Cancer Models. (2024). https://pubmed.ncbi.nlm.nih.gov/39493360/ DOI: 10.1177/11795549241283421
Complete structured claim and evidence
Lower tested lipoic-acid doses attenuated tumor-growth inhibition from high-dose ascorbate in the mouse model; the highest dose did not enhance it.
Lipoic acid → Mouse human-cancer xenograft growth source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/39493360.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9bd9ced1ace4214d80aad8e15ca5d61f8e4063f4e5838054b93e8c07a9550266", "start_char": 0, "end_char": 1935, "text_sha256": "9bd9ced1ace4214d80aad8e15ca5d61f8e4063f4e5838054b93e8c07a9550266"}
experimental_model
Cancer-cell combinations and human-tumor xenograft experiments
exposure
Millimolar cell exposures; injected ALA/ascorbate combinations in mice
limitations
Pharmacological ascorbate and animal injection exposures are not dietary vitamin C; no clinical combination trial.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human cancer cells and mice
plain_language
The combination did not provide a universal antioxidant synergy.
primary_references
[ala-p39493360] Combination of High-Dose Parenteral Ascorbate (Vitamin C) and Alpha-Lipoic Acid Failed to Enhance Tumor-Inhibitory Effect But Increased Toxicity in Preclinical Cancer Models. (2024). https://pubmed.ncbi.nlm.nih.gov/39493360/ DOI: 10.1177/11795549241283421
tissue_or_cell_type
Six cell lines; MDA-MB-231 xenografts
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1092–1103
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cancer-cell combinations and human-tumor xenograft experiments · source_derived_draft · unverified_draft
### ala-ascorbate-tumor-response Lower tested lipoic-acid doses attenuated tumor-growth inhibition from high-dose ascorbate in the mouse model; the highest dose did not enhance it. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The combination did not provide a universal antioxidant synergy. organism: Human cancer cells and mice tissue_or_cell_type: Six cell lines; MDA-MB-231 xenografts experimental_model: Cancer-cell combinations and human-tumor xenograft experiments limitations: Pharmacological ascorbate and animal injection exposures are not dietary vitamin C; no clinical combination trial. exposure: Millimolar cell exposures; injected ALA/ascorbate combinations in mice evidence_span: {"source_cache": "artifacts/ala-research/39493360.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9bd9ced1ace4214d80aad8e15ca5d61f8e4063f4e5838054b93e8c07a9550266", "start_char": 0, "end_char": 1935, "text_sha256": "9bd9ced1ace4214d80aad8e15ca5d61f8e4063f4e5838054b93e8c07a9550266"} [ala-p39493360] Combination of High-Dose Parenteral Ascorbate (Vitamin C) and Alpha-Lipoic Acid Failed to Enhance Tumor-Inhibitory Effect But Increased Toxicity in Preclinical Cancer Models. (2024). https://pubmed.ncbi.nlm.nih.gov/39493360/ DOI: 10.1177/11795549241283421
Complete structured claim and evidence
The study reported toxicity with prolonged lipoic-acid exposure and increased toxicity with tested ascorbate combinations in mice.
Lipoic acid → Toxicity of alpha-lipoic acid/ascorbate exposures in tumor-bearing mice source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/39493360.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9bd9ced1ace4214d80aad8e15ca5d61f8e4063f4e5838054b93e8c07a9550266", "start_char": 0, "end_char": 1935, "text_sha256": "9bd9ced1ace4214d80aad8e15ca5d61f8e4063f4e5838054b93e8c07a9550266"}
experimental_model
Cancer-cell combinations and human-tumor xenograft experiments
exposure
Millimolar cell exposures; injected ALA/ascorbate combinations in mice
limitations
Pharmacological ascorbate and animal injection exposures are not dietary vitamin C; no clinical combination trial.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human cancer cells and mice
plain_language
The combination’s tolerability also needed measurement.
primary_references
[ala-p39493360] Combination of High-Dose Parenteral Ascorbate (Vitamin C) and Alpha-Lipoic Acid Failed to Enhance Tumor-Inhibitory Effect But Increased Toxicity in Preclinical Cancer Models. (2024). https://pubmed.ncbi.nlm.nih.gov/39493360/ DOI: 10.1177/11795549241283421
tissue_or_cell_type
Six cell lines; MDA-MB-231 xenografts
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1105–1116
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cancer-cell combinations and human-tumor xenograft experiments · source_derived_draft · unverified_draft
### ala-ascorbate-ala-toxicity The study reported toxicity with prolonged lipoic-acid exposure and increased toxicity with tested ascorbate combinations in mice. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The combination’s tolerability also needed measurement. organism: Human cancer cells and mice tissue_or_cell_type: Six cell lines; MDA-MB-231 xenografts experimental_model: Cancer-cell combinations and human-tumor xenograft experiments limitations: Pharmacological ascorbate and animal injection exposures are not dietary vitamin C; no clinical combination trial. exposure: Millimolar cell exposures; injected ALA/ascorbate combinations in mice evidence_span: {"source_cache": "artifacts/ala-research/39493360.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9bd9ced1ace4214d80aad8e15ca5d61f8e4063f4e5838054b93e8c07a9550266", "start_char": 0, "end_char": 1935, "text_sha256": "9bd9ced1ace4214d80aad8e15ca5d61f8e4063f4e5838054b93e8c07a9550266"} [ala-p39493360] Combination of High-Dose Parenteral Ascorbate (Vitamin C) and Alpha-Lipoic Acid Failed to Enhance Tumor-Inhibitory Effect But Increased Toxicity in Preclinical Cancer Models. (2024). https://pubmed.ncbi.nlm.nih.gov/39493360/ DOI: 10.1177/11795549241283421
Complete structured claim and evidence
Nausea, vomiting and vertigo increased with dose in SYDNEY 2.
Lipoic acid → Gastrointestinal adverse events during lipoic-acid exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/17065669.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a54016cad3453fec96e99aa5906435793d7baaddaf5254d5ce335aac5bb4519", "start_char": 0, "end_char": 1756, "text_sha256": "3a54016cad3453fec96e99aa5906435793d7baaddaf5254d5ce335aac5bb4519"}
experimental_model
SYDNEY 2 randomized double-blind placebo-controlled trial
exposure
Oral ALA 600, 1200 or 1800 mg/day for five weeks
limitations
Short-term symptom endpoint; no proof of nerve regeneration, lifelong benefit or correction of a nutritional deficiency.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
Higher studied doses did not simply mean a better tolerated response.
primary_references
[ala-p17065669] Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. (2006). https://pubmed.ncbi.nlm.nih.gov/17065669/ DOI: 10.2337/dc06-1216
tissue_or_cell_type
181 participants with diabetic distal symmetric polyneuropathy
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1131–1142
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SYDNEY 2 randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### ala-sydney2-adverse-events Nausea, vomiting and vertigo increased with dose in SYDNEY 2. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Higher studied doses did not simply mean a better tolerated response. organism: Human tissue_or_cell_type: 181 participants with diabetic distal symmetric polyneuropathy experimental_model: SYDNEY 2 randomized double-blind placebo-controlled trial limitations: Short-term symptom endpoint; no proof of nerve regeneration, lifelong benefit or correction of a nutritional deficiency. exposure: Oral ALA 600, 1200 or 1800 mg/day for five weeks evidence_span: {"source_cache": "artifacts/ala-research/17065669.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3a54016cad3453fec96e99aa5906435793d7baaddaf5254d5ce335aac5bb4519", "start_char": 0, "end_char": 1756, "text_sha256": "3a54016cad3453fec96e99aa5906435793d7baaddaf5254d5ce335aac5bb4519"} [ala-p17065669] Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. (2006). https://pubmed.ncbi.nlm.nih.gov/17065669/ DOI: 10.2337/dc06-1216
Complete structured claim and evidence
ALADIN III found no significant between-group TSS change at day 19 or after seven months, although an early daily-score area-under-curve analysis favored ALA.
Lipoic acid → Diabetic polyneuropathy Total Symptom Score / TSS source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/10480774.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d28f04985ace61dd6036ea4d08d84e59c47ba587cea6438b7851e036abc1c673", "start_char": 0, "end_char": 2880, "text_sha256": "d28f04985ace61dd6036ea4d08d84e59c47ba587cea6438b7851e036abc1c673"}
experimental_model
ALADIN III multicenter randomized placebo-controlled trial
exposure
Three weeks intravenous treatment followed by six months oral ALA 600 mg three times daily or comparator sequences
limitations
Different route, duration and design from SYDNEY 2; preserve daily-score AUC and final-visit findings separately.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
The result depended partly on which symptom analysis and time point were examined.
primary_references
[ala-p10480774] Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. (1999). https://pubmed.ncbi.nlm.nih.gov/10480774/ DOI: 10.2337/diacare.22.8.1296
tissue_or_cell_type
509 people with type 2 diabetes and symptomatic polyneuropathy
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1144–1155
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ALADIN III multicenter randomized placebo-controlled trial · source_derived_draft · unverified_draft
### ala-aladin3-final-tss-null ALADIN III found no significant between-group TSS change at day 19 or after seven months, although an early daily-score area-under-curve analysis favored ALA. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The result depended partly on which symptom analysis and time point were examined. organism: Human tissue_or_cell_type: 509 people with type 2 diabetes and symptomatic polyneuropathy experimental_model: ALADIN III multicenter randomized placebo-controlled trial limitations: Different route, duration and design from SYDNEY 2; preserve daily-score AUC and final-visit findings separately. exposure: Three weeks intravenous treatment followed by six months oral ALA 600 mg three times daily or comparator sequences evidence_span: {"source_cache": "artifacts/ala-research/10480774.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d28f04985ace61dd6036ea4d08d84e59c47ba587cea6438b7851e036abc1c673", "start_char": 0, "end_char": 2880, "text_sha256": "d28f04985ace61dd6036ea4d08d84e59c47ba587cea6438b7851e036abc1c673"} [ala-p10480774] Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. (1999). https://pubmed.ncbi.nlm.nih.gov/10480774/ DOI: 10.2337/diacare.22.8.1296
Complete structured claim and evidence
ALADIN III found an early NIS improvement, while the seven-month comparison of continued ALA versus placebo did not reach conventional significance.
Lipoic acid → Neuropathy Impairment Score / NIS source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/10480774.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d28f04985ace61dd6036ea4d08d84e59c47ba587cea6438b7851e036abc1c673", "start_char": 0, "end_char": 2880, "text_sha256": "d28f04985ace61dd6036ea4d08d84e59c47ba587cea6438b7851e036abc1c673"}
experimental_model
ALADIN III multicenter randomized placebo-controlled trial
exposure
Three weeks intravenous treatment followed by six months oral ALA 600 mg three times daily or comparator sequences
limitations
Different route, duration and design from SYDNEY 2; preserve daily-score AUC and final-visit findings separately.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
An early examination-score signal did not establish durable benefit.
primary_references
[ala-p10480774] Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. (1999). https://pubmed.ncbi.nlm.nih.gov/10480774/ DOI: 10.2337/diacare.22.8.1296
tissue_or_cell_type
509 people with type 2 diabetes and symptomatic polyneuropathy
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1157–1168
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ALADIN III multicenter randomized placebo-controlled trial · source_derived_draft · unverified_draft
### ala-aladin3-nis ALADIN III found an early NIS improvement, while the seven-month comparison of continued ALA versus placebo did not reach conventional significance. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: An early examination-score signal did not establish durable benefit. organism: Human tissue_or_cell_type: 509 people with type 2 diabetes and symptomatic polyneuropathy experimental_model: ALADIN III multicenter randomized placebo-controlled trial limitations: Different route, duration and design from SYDNEY 2; preserve daily-score AUC and final-visit findings separately. exposure: Three weeks intravenous treatment followed by six months oral ALA 600 mg three times daily or comparator sequences evidence_span: {"source_cache": "artifacts/ala-research/10480774.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d28f04985ace61dd6036ea4d08d84e59c47ba587cea6438b7851e036abc1c673", "start_char": 0, "end_char": 2880, "text_sha256": "d28f04985ace61dd6036ea4d08d84e59c47ba587cea6438b7851e036abc1c673"} [ala-p10480774] Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. (1999). https://pubmed.ncbi.nlm.nih.gov/10480774/ DOI: 10.2337/diacare.22.8.1296
Complete structured claim and evidence
NATHAN 1 did not show a significant ALA effect on its prespecified NIS-LL plus seven-test primary composite at four years (P=0.105).
Lipoic acid → NATHAN 1 NIS-LL plus seven neurophysiological-test composite source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/21775755.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "39d87bd4d8c5b80564bce0fd04c3c62d00b5c76e8edac29d94ff176b97bcc1f9", "start_char": 0, "end_char": 1839, "text_sha256": "39d87bd4d8c5b80564bce0fd04c3c62d00b5c76e8edac29d94ff176b97bcc1f9"}
experimental_model
NATHAN 1 randomized placebo-controlled trial
exposure
ALA 600 mg/day for four years
limitations
Primary endpoint and secondary analyses must remain distinct; lack of expected placebo deterioration complicated interpretation.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
The long trial did not meet its main efficacy endpoint.
primary_references
[ala-p21775755] Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. (2011). https://pubmed.ncbi.nlm.nih.gov/21775755/ DOI: 10.2337/dc11-0503
tissue_or_cell_type
460 people with mild-to-moderate diabetic polyneuropathy
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1170–1181
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · NATHAN 1 randomized placebo-controlled trial · source_derived_draft · unverified_draft
### ala-nathan1-primary-null NATHAN 1 did not show a significant ALA effect on its prespecified NIS-LL plus seven-test primary composite at four years (P=0.105). Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The long trial did not meet its main efficacy endpoint. organism: Human tissue_or_cell_type: 460 people with mild-to-moderate diabetic polyneuropathy experimental_model: NATHAN 1 randomized placebo-controlled trial limitations: Primary endpoint and secondary analyses must remain distinct; lack of expected placebo deterioration complicated interpretation. exposure: ALA 600 mg/day for four years evidence_span: {"source_cache": "artifacts/ala-research/21775755.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "39d87bd4d8c5b80564bce0fd04c3c62d00b5c76e8edac29d94ff176b97bcc1f9", "start_char": 0, "end_char": 1839, "text_sha256": "39d87bd4d8c5b80564bce0fd04c3c62d00b5c76e8edac29d94ff176b97bcc1f9"} [ala-p21775755] Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. (2011). https://pubmed.ncbi.nlm.nih.gov/21775755/ DOI: 10.2337/dc11-0503
Complete structured claim and evidence
NATHAN 1 reported improvement in selected secondary impairment scores despite the nonsignificant primary endpoint.
Lipoic acid → Neuropathy Impairment Score / NIS source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/21775755.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "39d87bd4d8c5b80564bce0fd04c3c62d00b5c76e8edac29d94ff176b97bcc1f9", "start_char": 0, "end_char": 1839, "text_sha256": "39d87bd4d8c5b80564bce0fd04c3c62d00b5c76e8edac29d94ff176b97bcc1f9"}
experimental_model
NATHAN 1 randomized placebo-controlled trial
exposure
ALA 600 mg/day for four years
limitations
Primary endpoint and secondary analyses must remain distinct; lack of expected placebo deterioration complicated interpretation.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
Some examination measures favored treatment, but they do not replace the main result.
primary_references
[ala-p21775755] Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. (2011). https://pubmed.ncbi.nlm.nih.gov/21775755/ DOI: 10.2337/dc11-0503
tissue_or_cell_type
460 people with mild-to-moderate diabetic polyneuropathy
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1183–1194
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · NATHAN 1 randomized placebo-controlled trial · source_derived_draft · unverified_draft
### ala-nathan1-secondary-nis NATHAN 1 reported improvement in selected secondary impairment scores despite the nonsignificant primary endpoint. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some examination measures favored treatment, but they do not replace the main result. organism: Human tissue_or_cell_type: 460 people with mild-to-moderate diabetic polyneuropathy experimental_model: NATHAN 1 randomized placebo-controlled trial limitations: Primary endpoint and secondary analyses must remain distinct; lack of expected placebo deterioration complicated interpretation. exposure: ALA 600 mg/day for four years evidence_span: {"source_cache": "artifacts/ala-research/21775755.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "39d87bd4d8c5b80564bce0fd04c3c62d00b5c76e8edac29d94ff176b97bcc1f9", "start_char": 0, "end_char": 1839, "text_sha256": "39d87bd4d8c5b80564bce0fd04c3c62d00b5c76e8edac29d94ff176b97bcc1f9"} [ala-p21775755] Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. (2011). https://pubmed.ncbi.nlm.nih.gov/21775755/ DOI: 10.2337/dc11-0503
Complete structured claim and evidence
The exploratory clamp trial found a 27% greater change in glucose-disposal clearance versus placebo after pooling ALA groups.
Lipoic acid → Insulin-stimulated glucose disposal source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/10468203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "06f09aa0ad208b561612e62d5ce388b90205f8e767f1cf96545162ec2bf24a9a", "start_char": 0, "end_char": 2007, "text_sha256": "06f09aa0ad208b561612e62d5ce388b90205f8e767f1cf96545162ec2bf24a9a"}
experimental_model
Exploratory randomized placebo-controlled glucose-clamp pilot
exposure
600, 1200 or 1800 mg/day oral ALA for four weeks
limitations
Active doses were pooled after no dose effect was detected; exploratory design and surrogate outcome, not long-term diabetes complications.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
Insulin sensitivity improved in this small short-term experiment.
primary_references
[ala-p10468203] Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. (1999). https://pubmed.ncbi.nlm.nih.gov/10468203/ DOI: 10.1016/s0891-5849(99)00089-1
tissue_or_cell_type
74 participants with type 2 diabetes
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1196–1207
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Exploratory randomized placebo-controlled glucose-clamp pilot · source_derived_draft · unverified_draft
### ala-clamp-insulin-sensitivity The exploratory clamp trial found a 27% greater change in glucose-disposal clearance versus placebo after pooling ALA groups. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Insulin sensitivity improved in this small short-term experiment. organism: Human tissue_or_cell_type: 74 participants with type 2 diabetes experimental_model: Exploratory randomized placebo-controlled glucose-clamp pilot limitations: Active doses were pooled after no dose effect was detected; exploratory design and surrogate outcome, not long-term diabetes complications. exposure: 600, 1200 or 1800 mg/day oral ALA for four weeks evidence_span: {"source_cache": "artifacts/ala-research/10468203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "06f09aa0ad208b561612e62d5ce388b90205f8e767f1cf96545162ec2bf24a9a", "start_char": 0, "end_char": 2007, "text_sha256": "06f09aa0ad208b561612e62d5ce388b90205f8e767f1cf96545162ec2bf24a9a"} [ala-p10468203] Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. (1999). https://pubmed.ncbi.nlm.nih.gov/10468203/ DOI: 10.1016/s0891-5849(99)00089-1
Complete structured claim and evidence
R-lipoic acid did not reduce the primary fasting-triglyceride outcome in this 24-week trial.
Free R-alpha-lipoic acid → Fasting triglyceride concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/32692358.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4054eff822014466ea739125fd4000ba2a5852e5f9818487f0b32b7be2b8d076", "start_char": 0, "end_char": 2088, "text_sha256": "4054eff822014466ea739125fd4000ba2a5852e5f9818487f0b32b7be2b8d076"}
experimental_model
Randomized placebo-controlled R-lipoic-acid trial
exposure
R-lipoic acid 600 mg/day for 24 weeks
limitations
Primary triglyceride outcome was null; BMI was secondary and subgroup findings are exploratory.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
The trial’s main blood-fat target did not improve.
primary_references
[ala-p32692358] A Randomized Controlled Trial of Long-Term (R)-α-Lipoic Acid Supplementation Promotes Weight Loss in Overweight or Obese Adults without Altering Baseline Elevated Plasma Triglyceride Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/32692358/ DOI: 10.1093/jn/nxaa203
tissue_or_cell_type
81 overweight adults with elevated triglycerides
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1209–1220
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled R-lipoic-acid trial · source_derived_draft · unverified_draft
### ala-triglyceride-primary-null R-lipoic acid did not reduce the primary fasting-triglyceride outcome in this 24-week trial. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The trial’s main blood-fat target did not improve. organism: Human tissue_or_cell_type: 81 overweight adults with elevated triglycerides experimental_model: Randomized placebo-controlled R-lipoic-acid trial limitations: Primary triglyceride outcome was null; BMI was secondary and subgroup findings are exploratory. exposure: R-lipoic acid 600 mg/day for 24 weeks evidence_span: {"source_cache": "artifacts/ala-research/32692358.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4054eff822014466ea739125fd4000ba2a5852e5f9818487f0b32b7be2b8d076", "start_char": 0, "end_char": 2088, "text_sha256": "4054eff822014466ea739125fd4000ba2a5852e5f9818487f0b32b7be2b8d076"} [ala-p32692358] A Randomized Controlled Trial of Long-Term (R)-α-Lipoic Acid Supplementation Promotes Weight Loss in Overweight or Obese Adults without Altering Baseline Elevated Plasma Triglyceride Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/32692358/ DOI: 10.1093/jn/nxaa203
Complete structured claim and evidence
BMI decreased more with R-lipoic acid than placebo, by approximately 0.8 kg/m² between groups, as a secondary outcome.
Free R-alpha-lipoic acid → Body mass index source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/32692358.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4054eff822014466ea739125fd4000ba2a5852e5f9818487f0b32b7be2b8d076", "start_char": 0, "end_char": 2088, "text_sha256": "4054eff822014466ea739125fd4000ba2a5852e5f9818487f0b32b7be2b8d076"}
experimental_model
Randomized placebo-controlled R-lipoic-acid trial
exposure
R-lipoic acid 600 mg/day for 24 weeks
limitations
Primary triglyceride outcome was null; BMI was secondary and subgroup findings are exploratory.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
A modest weight-related signal accompanied a negative primary result.
primary_references
[ala-p32692358] A Randomized Controlled Trial of Long-Term (R)-α-Lipoic Acid Supplementation Promotes Weight Loss in Overweight or Obese Adults without Altering Baseline Elevated Plasma Triglyceride Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/32692358/ DOI: 10.1093/jn/nxaa203
tissue_or_cell_type
81 overweight adults with elevated triglycerides
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1222–1233
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled R-lipoic-acid trial · source_derived_draft · unverified_draft
### ala-bmi-secondary-effect BMI decreased more with R-lipoic acid than placebo, by approximately 0.8 kg/m² between groups, as a secondary outcome. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A modest weight-related signal accompanied a negative primary result. organism: Human tissue_or_cell_type: 81 overweight adults with elevated triglycerides experimental_model: Randomized placebo-controlled R-lipoic-acid trial limitations: Primary triglyceride outcome was null; BMI was secondary and subgroup findings are exploratory. exposure: R-lipoic acid 600 mg/day for 24 weeks evidence_span: {"source_cache": "artifacts/ala-research/32692358.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4054eff822014466ea739125fd4000ba2a5852e5f9818487f0b32b7be2b8d076", "start_char": 0, "end_char": 2088, "text_sha256": "4054eff822014466ea739125fd4000ba2a5852e5f9818487f0b32b7be2b8d076"} [ala-p32692358] A Randomized Controlled Trial of Long-Term (R)-α-Lipoic Acid Supplementation Promotes Weight Loss in Overweight or Obese Adults without Altering Baseline Elevated Plasma Triglyceride Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/32692358/ DOI: 10.1093/jn/nxaa203
Complete structured claim and evidence
The pilot found less annualized brain-volume loss with ALA than placebo, approximately 0.21% versus 0.65%.
Lipoic acid → Brain-volume loss in progressive multiple sclerosis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/28680916.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fc584ca455d8a40e4ce91513974752b282425a74267d5b1d45db6275a51c2f5d", "start_char": 0, "end_char": 1904, "text_sha256": "fc584ca455d8a40e4ce91513974752b282425a74267d5b1d45db6275a51c2f5d"}
experimental_model
Two-year randomized placebo-controlled progressive-MS pilot
exposure
Oral lipoic acid 1200 mg/day
limitations
Small imaging-focused trial; brain volume is a surrogate and the walking comparison was not statistically significant.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
The imaging result favored treatment in this small study.
primary_references
[ala-p28680916] Lipoic acid in secondary progressive MS: A randomized controlled pilot trial. (2017). https://pubmed.ncbi.nlm.nih.gov/28680916/ DOI: 10.1212/nxi.0000000000000374
tissue_or_cell_type
51 randomized participants with secondary progressive multiple sclerosis
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1235–1246
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-year randomized placebo-controlled progressive-MS pilot · source_derived_draft · unverified_draft
### ala-ms-pilot-atrophy The pilot found less annualized brain-volume loss with ALA than placebo, approximately 0.21% versus 0.65%. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The imaging result favored treatment in this small study. organism: Human tissue_or_cell_type: 51 randomized participants with secondary progressive multiple sclerosis experimental_model: Two-year randomized placebo-controlled progressive-MS pilot limitations: Small imaging-focused trial; brain volume is a surrogate and the walking comparison was not statistically significant. exposure: Oral lipoic acid 1200 mg/day evidence_span: {"source_cache": "artifacts/ala-research/28680916.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fc584ca455d8a40e4ce91513974752b282425a74267d5b1d45db6275a51c2f5d", "start_char": 0, "end_char": 1904, "text_sha256": "fc584ca455d8a40e4ce91513974752b282425a74267d5b1d45db6275a51c2f5d"} [ala-p28680916] Lipoic acid in secondary progressive MS: A randomized controlled pilot trial. (2017). https://pubmed.ncbi.nlm.nih.gov/28680916/ DOI: 10.1212/nxi.0000000000000374
Complete structured claim and evidence
The pilot’s timed-walking comparison did not reach conventional statistical significance (P=0.06).
Lipoic acid → Timed walking speed in progressive multiple sclerosis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/28680916.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fc584ca455d8a40e4ce91513974752b282425a74267d5b1d45db6275a51c2f5d", "start_char": 0, "end_char": 1904, "text_sha256": "fc584ca455d8a40e4ce91513974752b282425a74267d5b1d45db6275a51c2f5d"}
experimental_model
Two-year randomized placebo-controlled progressive-MS pilot
exposure
Oral lipoic acid 1200 mg/day
limitations
Small imaging-focused trial; brain volume is a surrogate and the walking comparison was not statistically significant.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
A favorable scan result did not establish improved walking.
primary_references
[ala-p28680916] Lipoic acid in secondary progressive MS: A randomized controlled pilot trial. (2017). https://pubmed.ncbi.nlm.nih.gov/28680916/ DOI: 10.1212/nxi.0000000000000374
tissue_or_cell_type
51 randomized participants with secondary progressive multiple sclerosis
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1248–1259
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-year randomized placebo-controlled progressive-MS pilot · source_derived_draft · unverified_draft
### ala-ms-pilot-walking-null The pilot’s timed-walking comparison did not reach conventional statistical significance (P=0.06). Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A favorable scan result did not establish improved walking. organism: Human tissue_or_cell_type: 51 randomized participants with secondary progressive multiple sclerosis experimental_model: Two-year randomized placebo-controlled progressive-MS pilot limitations: Small imaging-focused trial; brain volume is a surrogate and the walking comparison was not statistically significant. exposure: Oral lipoic acid 1200 mg/day evidence_span: {"source_cache": "artifacts/ala-research/28680916.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fc584ca455d8a40e4ce91513974752b282425a74267d5b1d45db6275a51c2f5d", "start_char": 0, "end_char": 1904, "text_sha256": "fc584ca455d8a40e4ce91513974752b282425a74267d5b1d45db6275a51c2f5d"} [ala-p28680916] Lipoic acid in secondary progressive MS: A randomized controlled pilot trial. (2017). https://pubmed.ncbi.nlm.nih.gov/28680916/ DOI: 10.1212/nxi.0000000000000374
Complete structured claim and evidence
The larger phase 2 trial found no improvement in timed walking speed or other reported clinical outcomes at 24 months.
Lipoic acid → Timed walking speed in progressive multiple sclerosis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/41397213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fbea8d712bb6bea0dd8b7cfde3133b06d70a6eb881917767f4385f61c8d27ba", "start_char": 0, "end_char": 3010, "text_sha256": "7fbea8d712bb6bea0dd8b7cfde3133b06d70a6eb881917767f4385f61c8d27ba"}
experimental_model
Phase 2 randomized placebo-controlled progressive-MS trial; online December 2025, 2026 issue
exposure
Oral ALA 1200 mg/day for 24 months
limitations
Primary timed-walking result was null; imaging interpretation complicated by T2 lesion volume and differential discontinuation.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
The later study did not establish functional benefit.
primary_references
[ala-p41397213] Lipoic Acid for Treatment of Progressive Multiple Sclerosis: A Phase 2 Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/41397213/ DOI: 10.1212/wnl.0000000000214454
tissue_or_cell_type
115 participants, 54 ALA and 61 placebo
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1261–1272
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phase 2 randomized placebo-controlled progressive-MS trial; online December 2025, 2026 issue · source_derived_draft · unverified_draft
### ala-ms-phase2-walking-null The larger phase 2 trial found no improvement in timed walking speed or other reported clinical outcomes at 24 months. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The later study did not establish functional benefit. organism: Human tissue_or_cell_type: 115 participants, 54 ALA and 61 placebo experimental_model: Phase 2 randomized placebo-controlled progressive-MS trial; online December 2025, 2026 issue limitations: Primary timed-walking result was null; imaging interpretation complicated by T2 lesion volume and differential discontinuation. exposure: Oral ALA 1200 mg/day for 24 months evidence_span: {"source_cache": "artifacts/ala-research/41397213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fbea8d712bb6bea0dd8b7cfde3133b06d70a6eb881917767f4385f61c8d27ba", "start_char": 0, "end_char": 3010, "text_sha256": "7fbea8d712bb6bea0dd8b7cfde3133b06d70a6eb881917767f4385f61c8d27ba"} [ala-p41397213] Lipoic Acid for Treatment of Progressive Multiple Sclerosis: A Phase 2 Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/41397213/ DOI: 10.1212/wnl.0000000000214454
Complete structured claim and evidence
Whole-brain and deep-gray volumes appeared more stable with ALA, but increased T2 lesion volume complicated interpretation.
Lipoic acid → Brain-volume loss in progressive multiple sclerosis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/41397213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fbea8d712bb6bea0dd8b7cfde3133b06d70a6eb881917767f4385f61c8d27ba", "start_char": 0, "end_char": 3010, "text_sha256": "7fbea8d712bb6bea0dd8b7cfde3133b06d70a6eb881917767f4385f61c8d27ba"}
experimental_model
Phase 2 randomized placebo-controlled progressive-MS trial; online December 2025, 2026 issue
exposure
Oral ALA 1200 mg/day for 24 months
limitations
Primary timed-walking result was null; imaging interpretation complicated by T2 lesion volume and differential discontinuation.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
Changes on scans need to be understood alongside lesions and clinical function.
primary_references
[ala-p41397213] Lipoic Acid for Treatment of Progressive Multiple Sclerosis: A Phase 2 Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/41397213/ DOI: 10.1212/wnl.0000000000214454
tissue_or_cell_type
115 participants, 54 ALA and 61 placebo
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1274–1285
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phase 2 randomized placebo-controlled progressive-MS trial; online December 2025, 2026 issue · source_derived_draft · unverified_draft
### ala-ms-phase2-imaging Whole-brain and deep-gray volumes appeared more stable with ALA, but increased T2 lesion volume complicated interpretation. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changes on scans need to be understood alongside lesions and clinical function. organism: Human tissue_or_cell_type: 115 participants, 54 ALA and 61 placebo experimental_model: Phase 2 randomized placebo-controlled progressive-MS trial; online December 2025, 2026 issue limitations: Primary timed-walking result was null; imaging interpretation complicated by T2 lesion volume and differential discontinuation. exposure: Oral ALA 1200 mg/day for 24 months evidence_span: {"source_cache": "artifacts/ala-research/41397213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fbea8d712bb6bea0dd8b7cfde3133b06d70a6eb881917767f4385f61c8d27ba", "start_char": 0, "end_char": 3010, "text_sha256": "7fbea8d712bb6bea0dd8b7cfde3133b06d70a6eb881917767f4385f61c8d27ba"} [ala-p41397213] Lipoic Acid for Treatment of Progressive Multiple Sclerosis: A Phase 2 Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/41397213/ DOI: 10.1212/wnl.0000000000214454
Complete structured claim and evidence
Proteinuria during ALA treatment prompted closer urine monitoring in the phase 2 trial; discontinuation was higher with ALA.
Lipoic acid → Proteinuria during progressive-MS trial treatment source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/41397213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fbea8d712bb6bea0dd8b7cfde3133b06d70a6eb881917767f4385f61c8d27ba", "start_char": 0, "end_char": 3010, "text_sha256": "7fbea8d712bb6bea0dd8b7cfde3133b06d70a6eb881917767f4385f61c8d27ba"}
experimental_model
Phase 2 randomized placebo-controlled progressive-MS trial; online December 2025, 2026 issue
exposure
Oral ALA 1200 mg/day for 24 months
limitations
Primary timed-walking result was null; imaging interpretation complicated by T2 lesion volume and differential discontinuation.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
The trial identified a kidney-related safety signal as well as tolerability concerns.
primary_references
[ala-p41397213] Lipoic Acid for Treatment of Progressive Multiple Sclerosis: A Phase 2 Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/41397213/ DOI: 10.1212/wnl.0000000000214454
tissue_or_cell_type
115 participants, 54 ALA and 61 placebo
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1287–1298
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phase 2 randomized placebo-controlled progressive-MS trial; online December 2025, 2026 issue · source_derived_draft · unverified_draft
### ala-ms-phase2-proteinuria Proteinuria during ALA treatment prompted closer urine monitoring in the phase 2 trial; discontinuation was higher with ALA. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The trial identified a kidney-related safety signal as well as tolerability concerns. organism: Human tissue_or_cell_type: 115 participants, 54 ALA and 61 placebo experimental_model: Phase 2 randomized placebo-controlled progressive-MS trial; online December 2025, 2026 issue limitations: Primary timed-walking result was null; imaging interpretation complicated by T2 lesion volume and differential discontinuation. exposure: Oral ALA 1200 mg/day for 24 months evidence_span: {"source_cache": "artifacts/ala-research/41397213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7fbea8d712bb6bea0dd8b7cfde3133b06d70a6eb881917767f4385f61c8d27ba", "start_char": 0, "end_char": 3010, "text_sha256": "7fbea8d712bb6bea0dd8b7cfde3133b06d70a6eb881917767f4385f61c8d27ba"} [ala-p41397213] Lipoic Acid for Treatment of Progressive Multiple Sclerosis: A Phase 2 Randomized Clinical Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/41397213/ DOI: 10.1212/wnl.0000000000214454
Complete structured claim and evidence
A reported patient developed hypoglycemia with high insulin autoantibodies after lipoic-acid exposure.
Lipoic acid → Hypoglycemia associated with insulin autoimmunity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/17329919.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "966bd02f0d270b1b8ab0e6ae7403fdeb0360e0cc0ceca34dfa4eef3e30204411", "start_char": 0, "end_char": 608, "text_sha256": "966bd02f0d270b1b8ab0e6ae7403fdeb0360e0cc0ceca34dfa4eef3e30204411"}
experimental_model
Insulin autoimmune syndrome case report
exposure
Lipoic-acid exposure preceding symptoms
limitations
Temporal case association; does not establish incidence, universal HLA susceptibility or a proved molecular antigen mechanism.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
Rare immune-mediated hypoglycemia is different from ordinary insulin sensitization.
primary_references
[ala-p17329919] Insulin Autoimmune Syndrome possibly caused by alpha lipoic acid. (2007). https://pubmed.ncbi.nlm.nih.gov/17329919/ DOI: 10.2169/internalmedicine.46.1893
tissue_or_cell_type
55-year-old person with hypoglycemia and insulin autoantibodies
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1300–1311
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Insulin autoimmune syndrome case report · source_derived_draft · unverified_draft
### ala-insulin-autoimmune-case A reported patient developed hypoglycemia with high insulin autoantibodies after lipoic-acid exposure. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Rare immune-mediated hypoglycemia is different from ordinary insulin sensitization. organism: Human tissue_or_cell_type: 55-year-old person with hypoglycemia and insulin autoantibodies experimental_model: Insulin autoimmune syndrome case report limitations: Temporal case association; does not establish incidence, universal HLA susceptibility or a proved molecular antigen mechanism. exposure: Lipoic-acid exposure preceding symptoms evidence_span: {"source_cache": "artifacts/ala-research/17329919.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "966bd02f0d270b1b8ab0e6ae7403fdeb0360e0cc0ceca34dfa4eef3e30204411", "start_char": 0, "end_char": 608, "text_sha256": "966bd02f0d270b1b8ab0e6ae7403fdeb0360e0cc0ceca34dfa4eef3e30204411"} [ala-p17329919] Insulin Autoimmune Syndrome possibly caused by alpha lipoic acid. (2007). https://pubmed.ncbi.nlm.nih.gov/17329919/ DOI: 10.2169/internalmedicine.46.1893
Complete structured claim and evidence
The case carried HLA-DRB1*0406 and had marked hypoglycemia, providing genetic context for the observed insulin autoimmunity.
Insulin-binding autoantibodies → Hypoglycemia associated with insulin autoimmunity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/17329919.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "966bd02f0d270b1b8ab0e6ae7403fdeb0360e0cc0ceca34dfa4eef3e30204411", "start_char": 0, "end_char": 608, "text_sha256": "966bd02f0d270b1b8ab0e6ae7403fdeb0360e0cc0ceca34dfa4eef3e30204411"}
experimental_model
Insulin autoimmune syndrome case report
exposure
Lipoic-acid exposure preceding symptoms
limitations
Temporal case association; does not establish incidence, universal HLA susceptibility or a proved molecular antigen mechanism.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
Susceptibility may matter, but one case cannot define everyone’s risk.
primary_references
[ala-p17329919] Insulin Autoimmune Syndrome possibly caused by alpha lipoic acid. (2007). https://pubmed.ncbi.nlm.nih.gov/17329919/ DOI: 10.2169/internalmedicine.46.1893
tissue_or_cell_type
55-year-old person with hypoglycemia and insulin autoantibodies
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1313–1324
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Insulin autoimmune syndrome case report · source_derived_draft · unverified_draft
### ala-ias-hla-context The case carried HLA-DRB1*0406 and had marked hypoglycemia, providing genetic context for the observed insulin autoimmunity. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Susceptibility may matter, but one case cannot define everyone’s risk. organism: Human tissue_or_cell_type: 55-year-old person with hypoglycemia and insulin autoantibodies experimental_model: Insulin autoimmune syndrome case report limitations: Temporal case association; does not establish incidence, universal HLA susceptibility or a proved molecular antigen mechanism. exposure: Lipoic-acid exposure preceding symptoms evidence_span: {"source_cache": "artifacts/ala-research/17329919.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "966bd02f0d270b1b8ab0e6ae7403fdeb0360e0cc0ceca34dfa4eef3e30204411", "start_char": 0, "end_char": 608, "text_sha256": "966bd02f0d270b1b8ab0e6ae7403fdeb0360e0cc0ceca34dfa4eef3e30204411"} [ala-p17329919] Insulin Autoimmune Syndrome possibly caused by alpha lipoic acid. (2007). https://pubmed.ncbi.nlm.nih.gov/17329919/ DOI: 10.2169/internalmedicine.46.1893
Complete structured claim and evidence
The LIAS Arg249His patient had depleted protein-bound lipoyl signal and reduced PDH activity/pyruvate oxidation in investigated muscle and fibroblast preparations.
LIAS Arg249His → Human pyruvate dehydrogenase complex source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Endogenous lipoate synthesis is a separate requirement of the thiamine-dependent PDH pathway.
evidence
[{"paper_key": "mayr-2011-lias", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Patient biochemical analysis.
limitations
Single patient; no proof of thiamine-treatment failure mechanism.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
A B1-dependent pathway can fail because its lipoyl machinery is defective. This case does not show that adding thiamine corrects the defect.
primary_references
[mayr-2011-lias] Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation (2011). https://pubmed.ncbi.nlm.nih.gov/22152680/ DOI: 10.1016/j.ajhg.2011.11.011
tissue_or_cell_type
Muscle and cultured fibroblasts
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 759–771
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient biochemical analysis. · source_derived_draft · unverified_draft
### b1-lias-defect-reduces-pdh The LIAS Arg249His patient had depleted protein-bound lipoyl signal and reduced PDH activity/pyruvate oxidation in investigated muscle and fibroblast preparations. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A B1-dependent pathway can fail because its lipoyl machinery is defective. This case does not show that adding thiamine corrects the defect. organism: Homo sapiens tissue_or_cell_type: Muscle and cultured fibroblasts experimental_model: Patient biochemical analysis. limitations: Single patient; no proof of thiamine-treatment failure mechanism. evidence: [{"paper_key": "mayr-2011-lias", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Endogenous lipoate synthesis is a separate requirement of the thiamine-dependent PDH pathway. nutrient: Thiamine (vitamin B1) [mayr-2011-lias] Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation (2011). https://pubmed.ncbi.nlm.nih.gov/22152680/ DOI: 10.1016/j.ajhg.2011.11.011
Complete structured claim and evidence
Mitochondrial ACP knockdown in HEK293T cells reduced the proportion of mitochondrial proteins recognized as lipoylated before later respiratory defects.
Human mitochondrial acyl carrier protein / NDUFAB1 → Mitochondrial protein lipoylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Abstract, earliest phenotypic changes; Fig. 2 caption
experimental_model
Mitochondrial ACP siRNA in HEK293T cells
exposure
ACP mRNA and protein reduced by more than 85% within 24 hours; later measurements followed knockdown.
limitations
Antibody-based lipoylation readout; not a measurement of dietary lipoic acid or pantothenate shortage. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
Loss of the mitochondrial carrier impaired attachment of the lipoate cofactor to proteins.
primary_references
[b5-met-acp2009] Down-regulation of mitochondrial acyl carrier protein in mammalian cells compromises protein lipoylation and respiratory complex I and results in cell death. (2009). https://pubmed.ncbi.nlm.nih.gov/19221180/ DOI: 10.1074/jbc.m806991200
tissue_or_cell_type
HEK293T mitochondrial proteins
trigger_kind
machinery_impairment Imported condition classification; unverified.
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 823–835
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mitochondrial ACP siRNA in HEK293T cells · source_derived_draft · unverified_draft
### b5-met-mtacp-lipoylation Mitochondrial ACP knockdown in HEK293T cells reduced the proportion of mitochondrial proteins recognized as lipoylated before later respiratory defects. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of the mitochondrial carrier impaired attachment of the lipoate cofactor to proteins. organism: Homo sapiens tissue_or_cell_type: HEK293T mitochondrial proteins experimental_model: Mitochondrial ACP siRNA in HEK293T cells limitations: Antibody-based lipoylation readout; not a measurement of dietary lipoic acid or pantothenate shortage. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: ACP mRNA and protein reduced by more than 85% within 24 hours; later measurements followed knockdown. cross_nutrient: true evidence_location: Abstract, earliest phenotypic changes; Fig. 2 caption [b5-met-acp2009] Down-regulation of mitochondrial acyl carrier protein in mammalian cells compromises protein lipoylation and respiratory complex I and results in cell death. (2009). https://pubmed.ncbi.nlm.nih.gov/19221180/ DOI: 10.1074/jbc.m806991200
Complete structured claim and evidence
Adding lipoic acid to the culture medium did not reverse the protein-lipoylation defect caused by mitochondrial ACP knockdown in HEK293T cells.
Lipoic acid → Mitochondrial protein lipoylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Abstract, lipoic-acid supplementation result
experimental_model
Mitochondrial ACP siRNA in HEK293T cells
exposure
Lipoic-acid supplementation of ACP-knockdown cultures; concentration not extracted.
limitations
Lipoic acid offered some oxidative-damage protection, but that is a different endpoint; result is not a universal statement about every lipoylation disorder. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
External lipoic acid did not bypass this carrier-protein defect.
primary_references
[b5-met-acp2009] Down-regulation of mitochondrial acyl carrier protein in mammalian cells compromises protein lipoylation and respiratory complex I and results in cell death. (2009). https://pubmed.ncbi.nlm.nih.gov/19221180/ DOI: 10.1074/jbc.m806991200
tissue_or_cell_type
HEK293T cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 851–863
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mitochondrial ACP siRNA in HEK293T cells · source_derived_draft · unverified_draft
### b5-met-lipoate-nonrescue Adding lipoic acid to the culture medium did not reverse the protein-lipoylation defect caused by mitochondrial ACP knockdown in HEK293T cells. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: External lipoic acid did not bypass this carrier-protein defect. organism: Homo sapiens tissue_or_cell_type: HEK293T cells experimental_model: Mitochondrial ACP siRNA in HEK293T cells limitations: Lipoic acid offered some oxidative-damage protection, but that is a different endpoint; result is not a universal statement about every lipoylation disorder. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Lipoic-acid supplementation of ACP-knockdown cultures; concentration not extracted. cross_nutrient: true evidence_location: Abstract, lipoic-acid supplementation result [b5-met-acp2009] Down-regulation of mitochondrial acyl carrier protein in mammalian cells compromises protein lipoylation and respiratory complex I and results in cell death. (2009). https://pubmed.ncbi.nlm.nih.gov/19221180/ DOI: 10.1074/jbc.m806991200
Complete structured claim and evidence
In the recombinant hybrid NFS1–ISD11–ACP structure, the phosphopantetheine-linked acyl group of E. coli ACP occupies the hydrophobic core of human ISD11.
Escherichia coli acylated phosphopantetheinyl-AcpP → Human ISD11 / LYRM4 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Abstract; primary Results: Identification of the ACP–Lipid–ISD11 Motif
experimental_model
Hybrid recombinant human NFS1–ISD11 plus native E. coli ACP; X-ray/EM structure
exposure
Coexpression and structural analysis; no nutrient restriction.
limitations
This is not an all-human ACP structure. The bound PLP and acyl-ACP show cofactor coexistence; dietary B6/B5 dependency or repletion was not tested. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens proteins; Escherichia coli ACP
plain_language
The CoA-derived carrier arm holds a fatty-acid chain that helps form the iron–sulfur complex interface.
primary_references
[b5-met-cory2017] Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions. (2017). https://pubmed.ncbi.nlm.nih.gov/28634302/ DOI: 10.1073/pnas.1702849114
tissue_or_cell_type
Purified recombinant Fe–S assembly subcomplex
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 935–947
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hybrid recombinant human NFS1–ISD11 plus native E. coli ACP; X-ray/EM structure · source_derived_draft · unverified_draft
### b5-met-acyl-acp-isd11-interface In the recombinant hybrid NFS1–ISD11–ACP structure, the phosphopantetheine-linked acyl group of E. coli ACP occupies the hydrophobic core of human ISD11. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The CoA-derived carrier arm holds a fatty-acid chain that helps form the iron–sulfur complex interface. organism: Homo sapiens proteins; Escherichia coli ACP tissue_or_cell_type: Purified recombinant Fe–S assembly subcomplex experimental_model: Hybrid recombinant human NFS1–ISD11 plus native E. coli ACP; X-ray/EM structure limitations: This is not an all-human ACP structure. The bound PLP and acyl-ACP show cofactor coexistence; dietary B6/B5 dependency or repletion was not tested. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Coexpression and structural analysis; no nutrient restriction. cross_nutrient: true evidence_location: Abstract; primary Results: Identification of the ACP–Lipid–ISD11 Motif [b5-met-cory2017] Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions. (2017). https://pubmed.ncbi.nlm.nih.gov/28634302/ DOI: 10.1073/pnas.1702849114
Complete structured claim and evidence
Ndufab1 siRNA in mouse C2C12 myoblasts reduced mitochondrial Nfs1, Isd11 and Iscu2 protein abundance.
Mouse mitochondrial acyl carrier protein / Ndufab1 → Mouse cysteine desulfurase / Nfs1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Full text line 117; Fig. 3C
experimental_model
Pooled Ndufab1 siRNA versus scrambled control
exposure
Ndufab1-targeting siRNA; immunoblot of isolated mitochondria.
limitations
The mammalian intact Nfs1–Isd11 complex could not be resolved by the authors with BN-PAGE; the direct mammalian result is subunit abundance. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Mus musculus
plain_language
The iron–sulfur machinery also became less stable after carrier depletion in mouse muscle cells.
primary_references
[b5-met-acp2016] The mitochondrial acyl carrier protein (ACP) coordinates mitochondrial fatty acid synthesis with iron sulfur cluster biogenesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27540631/ DOI: 10.7554/elife.17828
tissue_or_cell_type
C2C12 myoblast mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 921–933
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pooled Ndufab1 siRNA versus scrambled control · source_derived_draft · unverified_draft
### b5-met-mouse-acp-isu-stability Ndufab1 siRNA in mouse C2C12 myoblasts reduced mitochondrial Nfs1, Isd11 and Iscu2 protein abundance. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The iron–sulfur machinery also became less stable after carrier depletion in mouse muscle cells. organism: Mus musculus tissue_or_cell_type: C2C12 myoblast mitochondria experimental_model: Pooled Ndufab1 siRNA versus scrambled control limitations: The mammalian intact Nfs1–Isd11 complex could not be resolved by the authors with BN-PAGE; the direct mammalian result is subunit abundance. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Ndufab1-targeting siRNA; immunoblot of isolated mitochondria. cross_nutrient: true evidence_location: Full text line 117; Fig. 3C [b5-met-acp2016] The mitochondrial acyl carrier protein (ACP) coordinates mitochondrial fatty acid synthesis with iron sulfur cluster biogenesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27540631/ DOI: 10.7554/elife.17828
Complete structured claim and evidence
Recombinant human E1 transferred radiolabel from pyruvate to the lipoylated DLAT L2 domain, directly measuring reductive acetylation.
Human pyruvate dehydrogenase E1 → Dihydrolipoyl acetyltransferase / DLAT source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Thiamine-dependent carbon chemistry requires the separate protein-bound lipoyl carrier; free lipoic-acid supplementation was not tested.
evidence
[{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-19", "p-25"], "locator": "incorporation", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human recombinant proteins; radiolabeled pyruvate assay.
limitations
Purified-system evidence; nutritional response was not tested.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The B1-dependent enzyme passes pyruvate-derived carbon to a lipoyl arm on a different protein. Protein-bound lipoate therefore links E1 chemistry to the next reaction.
primary_references
[kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010
tissue_or_cell_type
Purified proteins
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 676–688
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant proteins; radiolabeled pyruvate assay. · source_derived_draft · unverified_draft
### b1-pdh-lipoyl-acetyl-transfer Recombinant human E1 transferred radiolabel from pyruvate to the lipoylated DLAT L2 domain, directly measuring reductive acetylation. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The B1-dependent enzyme passes pyruvate-derived carbon to a lipoyl arm on a different protein. Protein-bound lipoate therefore links E1 chemistry to the next reaction. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Human recombinant proteins; radiolabeled pyruvate assay. limitations: Purified-system evidence; nutritional response was not tested. evidence: [{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-19", "p-25"], "locator": "incorporation", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Thiamine-dependent carbon chemistry requires the separate protein-bound lipoyl carrier; free lipoic-acid supplementation was not tested. nutrient: Thiamine (vitamin B1) [kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010
Complete structured claim and evidence
The human DLAT catalytic core contains a channel for the acetylated lipoyl group and CoA; substrate modeling positions CoA for acetyl-CoA formation.
Dihydrolipoyl acetyltransferase / DLAT → Coenzyme A source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B1-dependent E1 and B5-derived CoA participate in different sequential steps.
evidence
[{"paper_key": "jiang-2018-pdh-core", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-32"], "locator": "acetyl-accepting CoA", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human DLAT cryo-EM; bacterial ligand poses used for modeling.
limitations
Ligand positions were modeled, not directly resolved in a human substrate-bound structure; no intake experiment.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
After B1 acts at E1, the E2 protein transfers the acetyl group onto CoA, a vitamin B5-derived carrier.
primary_references
[jiang-2018-pdh-core] Atomic Structure of the E2 Inner Core of Human Pyruvate Dehydrogenase Complex (2018). https://pubmed.ncbi.nlm.nih.gov/29608861/ DOI: 10.1021/acs.biochem.8b00357
tissue_or_cell_type
Purified catalytic core
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 690–702
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DLAT cryo-EM; bacterial ligand poses used for modeling. · source_derived_draft · unverified_draft
### b1-pdh-dlat-coa-acetylation The human DLAT catalytic core contains a channel for the acetylated lipoyl group and CoA; substrate modeling positions CoA for acetyl-CoA formation. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: After B1 acts at E1, the E2 protein transfers the acetyl group onto CoA, a vitamin B5-derived carrier. organism: Homo sapiens tissue_or_cell_type: Purified catalytic core experimental_model: Human DLAT cryo-EM; bacterial ligand poses used for modeling. limitations: Ligand positions were modeled, not directly resolved in a human substrate-bound structure; no intake experiment. evidence: [{"paper_key": "jiang-2018-pdh-core", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-32"], "locator": "acetyl-accepting CoA", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1-dependent E1 and B5-derived CoA participate in different sequential steps. nutrient: Thiamine (vitamin B1) [jiang-2018-pdh-core] Atomic Structure of the E2 Inner Core of Human Pyruvate Dehydrogenase Complex (2018). https://pubmed.ncbi.nlm.nih.gov/29608861/ DOI: 10.1021/acs.biochem.8b00357
Complete structured claim and evidence
Human OGDH, lipoylated DLST and DLD assembled into an active complex coupling 2-oxoglutarate oxidation to NADH production in the CoA-containing assay.
2-Oxoglutarate dehydrogenase complex → Succinyl-CoA source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B1, B5-derived CoA, B2-derived FAD and niacin-related NAD act at different steps of one complex.
evidence
[{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-28"], "locator": "The reaction medium contained the following in 1.0 ml", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Reconstituted human multienzyme assay.
limitations
NADH assay measures overall complex turnover, not every intermediate independently.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
B1-dependent E1 feeds a lipoyl/CoA transfer pathway, and E3 transfers the resulting reducing equivalents to NAD.
primary_references
[nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073
tissue_or_cell_type
Purified enzyme complex
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 855–867
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted human multienzyme assay. · source_derived_draft · unverified_draft
### b1-ogdh-complex-couples-succinyl-nadh Human OGDH, lipoylated DLST and DLD assembled into an active complex coupling 2-oxoglutarate oxidation to NADH production in the CoA-containing assay. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1-dependent E1 feeds a lipoyl/CoA transfer pathway, and E3 transfers the resulting reducing equivalents to NAD. organism: Homo sapiens tissue_or_cell_type: Purified enzyme complex experimental_model: Reconstituted human multienzyme assay. limitations: NADH assay measures overall complex turnover, not every intermediate independently. evidence: [{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-28"], "locator": "The reaction medium contained the following in 1.0 ml", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1, B5-derived CoA, B2-derived FAD and niacin-related NAD act at different steps of one complex. nutrient: Thiamine (vitamin B1) [nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073
Complete structured claim and evidence
Human BCKDH E1 decarboxylates a branched-chain alpha-ketoacid using ThDP and reductively acylates the lipoylated DBT domain.
Human branched-chain ketoacid dehydrogenase E1 → Dihydrolipoyl branched-chain transacylase / DBT source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Thiamine and protein-bound lipoate connect branched-chain amino-acid catabolism; CoA and DLD act later.
evidence
[{"paper_key": "li-2004-bckdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Recombinant human E1b and E2b lipoyl domain assays.
limitations
Purified-system evidence; nutritional response was not tested.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
B1 helps process ketoacids formed from branched-chain amino acids; the acyl fragment then moves to a lipoyl carrier on E2.
primary_references
[li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200
tissue_or_cell_type
Purified proteins
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 773–785
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human E1b and E2b lipoyl domain assays. · source_derived_draft · unverified_draft
### b1-bckdh-ketoacid-acylation Human BCKDH E1 decarboxylates a branched-chain alpha-ketoacid using ThDP and reductively acylates the lipoylated DBT domain. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 helps process ketoacids formed from branched-chain amino acids; the acyl fragment then moves to a lipoyl carrier on E2. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Recombinant human E1b and E2b lipoyl domain assays. limitations: Purified-system evidence; nutritional response was not tested. evidence: [{"paper_key": "li-2004-bckdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Thiamine and protein-bound lipoate connect branched-chain amino-acid catabolism; CoA and DLD act later. nutrient: Thiamine (vitamin B1) [li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200
Complete structured claim and evidence
Apo/holo human E1b structures showed that ThDP binding orders the phosphorylation loop needed to recognize the lipoylated E2b domain.
Thiamine diphosphate → Human branched-chain ketoacid dehydrogenase E1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
ThDP occupancy enables interaction with the lipoylated E2 carrier.
evidence
[{"paper_key": "li-2004-bckdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human apo/holo E1b crystallography and lipoyl-domain binding.
limitations
Preparation-specific structural/kinetic mechanism; not a human thiamine-dose response.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
B1 binding changes the enzyme shape so it can receive its lipoyl partner.
primary_references
[li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200
tissue_or_cell_type
Purified proteins
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 787–799
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human apo/holo E1b crystallography and lipoyl-domain binding. · source_derived_draft · unverified_draft
### b1-bckdh-thdp-orders-loop Apo/holo human E1b structures showed that ThDP binding orders the phosphorylation loop needed to recognize the lipoylated E2b domain. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 binding changes the enzyme shape so it can receive its lipoyl partner. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Human apo/holo E1b crystallography and lipoyl-domain binding. limitations: Preparation-specific structural/kinetic mechanism; not a human thiamine-dose response. evidence: [{"paper_key": "li-2004-bckdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: ThDP occupancy enables interaction with the lipoylated E2 carrier. nutrient: Thiamine (vitamin B1) [li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200
Complete structured claim and evidence
DHTKD1 with DLST and DLD supports oxidative decarboxylation of 2-oxoadipate to glutaryl-CoA, with NADH and carbon dioxide formation.
2-Oxoadipate → Glutaryl-CoA source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human DHTKD1 and DLST; structural and biochemical assays; Two human patients; fibroblast isotope tracing and genetic complementation
limitations
DHTKD1 is the E1 component, not a stand-alone enzyme performing every complex reaction.
organism
Homo sapiens
plain_language
A three-enzyme complex converts the carbon skeleton into glutaryl-CoA.
primary_references
[bezerra2020] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC7340257/ DOI: 10.1107/S205225252000696X [danhauser2012] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3516599/ DOI: 10.1016/j.ajhg.2012.10.006
tissue_or_cell_type
Mitochondrial matrix
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 125–134
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human DHTKD1 and DLST; structural and biochemical assays; Two human patients; fibroblast isotope tracing and genetic complementation · source_derived_draft · unverified_draft
### oxoadipate-dehydrogenase-complex DHTKD1 with DLST and DLD supports oxidative decarboxylation of 2-oxoadipate to glutaryl-CoA, with NADH and carbon dioxide formation. Plain language: A three-enzyme complex converts the carbon skeleton into glutaryl-CoA. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial matrix experimental_model: Recombinant human DHTKD1 and DLST; structural and biochemical assays; Two human patients; fibroblast isotope tracing and genetic complementation limitations: DHTKD1 is the E1 component, not a stand-alone enzyme performing every complex reaction. [bezerra2020] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC7340257/ DOI: 10.1107/S205225252000696X [danhauser2012] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3516599/ DOI: 10.1016/j.ajhg.2012.10.006
Complete structured claim and evidence
Human DHTKD1 supported 2-oxoadipate dehydrogenase activity when combined with the DLST and DLD components also used by OGDH.
DHTKD1 → 2-Oxoadipate dehydrogenase complex source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B1-dependent lysine catabolism converges on the same lipoyl, CoA and NAD/FAD machinery used in OGDH.
evidence
[{"paper_key": "nemeria-2018-oadh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human recombinant component reconstitution.
limitations
Reconstituted proteins; sharing does not establish competition for limiting subunits in vivo.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Lysine-related carbon disposal uses a different B1-dependent E1, while sharing the downstream E2 and E3 proteins with a TCA-cycle enzyme.
primary_references
[nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018
tissue_or_cell_type
Purified complex
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 869–881
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant component reconstitution. · source_derived_draft · unverified_draft
### b1-dhtkd1-recruits-shared-dlst-dld Human DHTKD1 supported 2-oxoadipate dehydrogenase activity when combined with the DLST and DLD components also used by OGDH. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lysine-related carbon disposal uses a different B1-dependent E1, while sharing the downstream E2 and E3 proteins with a TCA-cycle enzyme. organism: Homo sapiens tissue_or_cell_type: Purified complex experimental_model: Human recombinant component reconstitution. limitations: Reconstituted proteins; sharing does not establish competition for limiting subunits in vivo. evidence: [{"paper_key": "nemeria-2018-oadh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1-dependent lysine catabolism converges on the same lipoyl, CoA and NAD/FAD machinery used in OGDH. nutrient: Thiamine (vitamin B1) [nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018
Complete structured claim and evidence
DLD protein abundance decreased in riboflavin-depleted human 143B cells, while many other mitochondrial matrix flavoproteins did not decline.
Riboflavin (vitamin B2) → DLD source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Connects B2-dependent DLD abundance to the canonical B1-dependent mitochondrial complexes; this study does not demonstrate failure of thiamine treatment.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}]
experimental_model
Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions.
exposure
Riboflavin-free medium compared with matched replete medium.
limitations
No direct PDH/OGDH flux or thiamine-response experiment; selective loss must not be generalized to all flavoproteins.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
B2 withdrawal destabilized selected flavoproteins, including the shared DLD enzyme.
primary_references
[curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001
tissue_or_cell_type
143B cell proteomics
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 622–634
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. · source_derived_draft · unverified_draft
### b2-met-depletion-dld DLD protein abundance decreased in riboflavin-depleted human 143B cells, while many other mitochondrial matrix flavoproteins did not decline. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: B2 withdrawal destabilized selected flavoproteins, including the shared DLD enzyme. organism: Homo sapiens tissue_or_cell_type: 143B cell proteomics experimental_model: Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. limitations: No direct PDH/OGDH flux or thiamine-response experiment; selective loss must not be generalized to all flavoproteins. exposure: Riboflavin-free medium compared with matched replete medium. cross_nutrient: Connects B2-dependent DLD abundance to the canonical B1-dependent mitochondrial complexes; this study does not demonstrate failure of thiamine treatment. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}] [curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001
Complete structured claim and evidence
Purified human DLD I12T retained about 0.15 FAD per monomer versus approximately one in wild type, with forward and reverse activities of about 8% and 2%.
Human DLD Ile12Thr → FAD source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
DLD is reused from the B1 complexes; its flavin/NAD step is distinct from upstream thiamine diphosphate chemistry.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10341545", "locator": "XML .//body//p", "paragraph_index": 19, "char_start": 0, "char_end": 871, "evidence_access": "full-text"}]
experimental_model
Recombinant human DLD variants expressed in E. coli BL21(DE3), FAD quantification, activity, chromatography and crystallography.
exposure
I12T mutagenesis, purified-protein FAD and activity assays.
limitations
Purification instability can affect measured occupancy; correlation does not prove FAD loss alone caused all activity loss.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
This DLD variant poorly retained FAD and had very low catalytic activity.
primary_references
[szabo-2023-dld-variants] Structural and Biochemical Investigation of Selected Pathogenic Mutants of the Human Dihydrolipoamide Dehydrogenase (2023). https://pubmed.ncbi.nlm.nih.gov/37446004/ DOI: 10.3390/ijms241310826
tissue_or_cell_type
Recombinant DLD expressed in E. coli
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 847–859
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human DLD variants expressed in E. coli BL21(DE3), FAD quantification, activity, chromatography and crystallography. · source_derived_draft · unverified_draft
### b2-met-dld-i12t-fad-retention Purified human DLD I12T retained about 0.15 FAD per monomer versus approximately one in wild type, with forward and reverse activities of about 8% and 2%. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This DLD variant poorly retained FAD and had very low catalytic activity. organism: Homo sapiens tissue_or_cell_type: Recombinant DLD expressed in E. coli experimental_model: Recombinant human DLD variants expressed in E. coli BL21(DE3), FAD quantification, activity, chromatography and crystallography. limitations: Purification instability can affect measured occupancy; correlation does not prove FAD loss alone caused all activity loss. exposure: I12T mutagenesis, purified-protein FAD and activity assays. cross_nutrient: DLD is reused from the B1 complexes; its flavin/NAD step is distinct from upstream thiamine diphosphate chemistry. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10341545", "locator": "XML .//body//p", "paragraph_index": 19, "char_start": 0, "char_end": 871, "evidence_access": "full-text"}] [szabo-2023-dld-variants] Structural and Biochemical Investigation of Selected Pathogenic Mutants of the Human Dihydrolipoamide Dehydrogenase (2023). https://pubmed.ncbi.nlm.nih.gov/37446004/ DOI: 10.3390/ijms241310826
Complete structured claim and evidence
DLD activity in Slc25a32-null embryo mitochondria was about 23.9% of wild-type control.
Slc25a32-null mouse genotype → Mouse dihydrolipoamide dehydrogenase / Dld source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
DLD links B2 cofactor supply to glycine cleavage and thus folate-mediated one-carbon metabolism.
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 43, "char_start": 0, "char_end": 1215, "evidence_access": "full-text"}]
experimental_model
Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays.
exposure
Slc25a32-null versus wild-type embryos.
limitations
Knockout affects multiple flavoproteins; DLD-specific genetic rescue was not performed.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Mus musculus
plain_language
A defect in mitochondrial flavin supply impaired the shared DLD enzyme.
primary_references
[peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0
tissue_or_cell_type
Embryo mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 874–886
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. · source_derived_draft · unverified_draft
### b2-met-mouse-null-dld-activity DLD activity in Slc25a32-null embryo mitochondria was about 23.9% of wild-type control. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A defect in mitochondrial flavin supply impaired the shared DLD enzyme. organism: Mus musculus tissue_or_cell_type: Embryo mitochondria experimental_model: Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. limitations: Knockout affects multiple flavoproteins; DLD-specific genetic rescue was not performed. exposure: Slc25a32-null versus wild-type embryos. cross_nutrient: DLD links B2 cofactor supply to glycine cleavage and thus folate-mediated one-carbon metabolism. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 43, "char_start": 0, "char_end": 1215, "evidence_access": "full-text"}] [peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0
Complete structured claim and evidence
Phosphorylated human site-1-only E1 lacked detectable lipoylated-L2 binding and reductive acetylation, despite high ThDP in the binding assay.
PDH E1 phosphorylated at alpha Ser264 → Dihydrolipoyl acetyltransferase / DLAT source_derived_draftungraded
Experimental context and source evidence
evidence
[{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-51"], "locator": "absence of L2 binding", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Engineered human site-1-only E1; phosphorylation, ITC and kinetics.
limitations
Normal regulatory phosphorylation studied in an engineered construct; not a dietary deficiency or clinical nonresponse experiment.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Loading B1 cannot by itself undo this tested regulatory block: the phosphorylated enzyme fails to engage its lipoyl partner.
primary_references
[kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010
tissue_or_cell_type
Purified proteins
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 704–715
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Engineered human site-1-only E1; phosphorylation, ITC and kinetics. · source_derived_draft · unverified_draft
### b1-pdh-phosphorylation-blocks-lipoyl-recognition Phosphorylated human site-1-only E1 lacked detectable lipoylated-L2 binding and reductive acetylation, despite high ThDP in the binding assay. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loading B1 cannot by itself undo this tested regulatory block: the phosphorylated enzyme fails to engage its lipoyl partner. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Engineered human site-1-only E1; phosphorylation, ITC and kinetics. limitations: Normal regulatory phosphorylation studied in an engineered construct; not a dietary deficiency or clinical nonresponse experiment. evidence: [{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-51"], "locator": "absence of L2 binding", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010
Complete structured claim and evidence
Expression of cloned human SLC5A6 in HRPE cells conferred sodium-dependent uptake of lipoate.
Human sodium-dependent multivitamin transporter / SLC5A6 → Cellular free lipoate uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes
exposure
Human SMVT cDNA expression; substrate concentrations not specified in the abstract.
limitations
Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens (protein and HRPE expression cells)
plain_language
SMVT carries lipoate into cells using sodium-dependent transport.
primary_references
[b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875
tissue_or_cell_type
HRPE cell plasma membrane
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 184–195
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes · source_derived_draft · unverified_draft
### b5-trans-smvt-lipoate Expression of cloned human SLC5A6 in HRPE cells conferred sodium-dependent uptake of lipoate. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: SMVT carries lipoate into cells using sodium-dependent transport. organism: Homo sapiens (protein and HRPE expression cells) tissue_or_cell_type: HRPE cell plasma membrane experimental_model: Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes limitations: Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition. exposure: Human SMVT cDNA expression; substrate concentrations not specified in the abstract. cross_nutrient: true [b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875
Complete structured claim and evidence
Expression of cloned human SLC5A6 in HRPE cells conferred sodium-dependent uptake of pantothenate.
Human sodium-dependent multivitamin transporter / SLC5A6 → Cellular pantothenate uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes
exposure
Human SMVT cDNA expression; substrate concentrations not specified in the abstract.
limitations
Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens (protein and HRPE expression cells)
plain_language
SMVT carries pantothenate into cells using sodium-dependent transport.
primary_references
[b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875
tissue_or_cell_type
HRPE cell plasma membrane
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 158–169
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes · source_derived_draft · unverified_draft
### b5-trans-smvt-pantothenate Expression of cloned human SLC5A6 in HRPE cells conferred sodium-dependent uptake of pantothenate. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: SMVT carries pantothenate into cells using sodium-dependent transport. organism: Homo sapiens (protein and HRPE expression cells) tissue_or_cell_type: HRPE cell plasma membrane experimental_model: Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes limitations: Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition. exposure: Human SMVT cDNA expression; substrate concentrations not specified in the abstract. cross_nutrient: true [b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875
Complete structured claim and evidence
Expression of cloned human SLC5A6 in HRPE cells conferred sodium-dependent uptake of biotin.
Human sodium-dependent multivitamin transporter / SLC5A6 → Cellular biotin uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes
exposure
Human SMVT cDNA expression; substrate concentrations not specified in the abstract.
limitations
Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens (protein and HRPE expression cells)
plain_language
SMVT carries biotin into cells using sodium-dependent transport.
primary_references
[b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875
tissue_or_cell_type
HRPE cell plasma membrane
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 171–182
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes · source_derived_draft · unverified_draft
### b5-trans-smvt-biotin Expression of cloned human SLC5A6 in HRPE cells conferred sodium-dependent uptake of biotin. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: SMVT carries biotin into cells using sodium-dependent transport. organism: Homo sapiens (protein and HRPE expression cells) tissue_or_cell_type: HRPE cell plasma membrane experimental_model: Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes limitations: Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition. exposure: Human SMVT cDNA expression; substrate concentrations not specified in the abstract. cross_nutrient: true [b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

Sulfur insertion stops when the auxiliary cluster cannot be restored

Condition: machinery_impairment · Purified LIAS turns over without a cluster-restoration system.

Normal role: LIAS draws sulfur from an auxiliary cluster that can be replenished.

Recorded consequence: Cluster consumption limits continued cofactor production.

Scope: Purified human LIAS; not a dietary iron threshold.

An early assembly defect affects several enzyme systems

Condition: machinery_impairment · Biallelic pathogenic LIPT2 variants.

Normal role: LIPT2 initiates cofactor assembly on GCSH.

Recorded consequence: Protein lipoylation, PDH/OGDH activity, respiration and leucine catabolism are impaired.

Scope: Affected patients and their fibroblasts.

A transfer defect can spare glycine cleavage

Condition: machinery_impairment · Biallelic pathogenic LIPT1 variants.

Normal role: LIPT1 transfers assembled cofactor from GCSH to dehydrogenases.

Recorded consequence: PDH/OGDH lipoylation fails while GCSH lipoylation and glycine cleavage can remain intact.

Scope: Reported LIPT1 patient.

Iron-sulfur assembly defects can block lipoate-dependent enzymes

Condition: machinery_impairment · Pathogenic NFU1 or BOLA3 variants.

Normal role: Fe-S machinery supports lipoyl synthesis and other mitochondrial proteins.

Recorded consequence: Combined 2-oxoacid dehydrogenase and respiratory-chain defects.

Scope: Patient fibroblasts in two families.

Glycine can accumulate because its cofactor is missing

Condition: machinery_impairment · LIAS, BOLA3 or GLRX5 pathogenic variants.

Normal role: Lipoylated GCSH supports glycine cleavage.

Recorded consequence: Reduced protein lipoylation and glycine cleavage with elevated glycine.

Scope: Variant nonketotic hyperglycinemia cohort.

A foreign ligase can create a bypass in cultured cells

Condition: machinery_impairment · Experimental loss of MECR, BOLA3, FDX1, LIAS or LIPT1.

Normal role: Human cells normally use their endogenous lipoyl assembly pathway.

Recorded consequence: Engineered bacterial LplA restores lipoylation and cellular function.

Scope: Engineered human cell models only.

Maternal supplementation does not replace embryonic synthesis

Condition: machinery_impairment · Homozygous Lias disruption.

Normal role: Embryos synthesize their own lipoyl cofactor.

Recorded consequence: Early embryonic death despite tested maternal supplementation.

Scope: Mouse knockout model.

Low reducing capacity can limit DHLA formation

Condition: machinery_impairment · G6PD deficiency in the tested donor or experimental G6PD inhibition.

Normal role: Erythrocytes use glucose-derived reducing power to reduce free lipoic acid.

Recorded consequence: Impaired conversion of lipoic acid to DHLA.

Scope: Human erythrocytes; limited donor evidence.

Age-associated glutathione synthesis capacity can change

Condition: machinery_impairment · Comparison of old and young rats.

Normal role: Nrf2 and GCL expression support glutathione production.

Recorded consequence: Older rat liver had lower GCL subunits/activity and altered Nrf2; an injected intervention increased selected measures.

Scope: Rat liver; not diagnosed dietary lipoic-acid deficiency.

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
L-Lysine: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Diabetic neuropathy: short-term symptom benefit versus a longer negative symptom endpointSYDNEY 2 reported greater TSS improvement with oral ALA over five weeks; ALADIN III did not show a significant final TSS advantage at seven months. These are divergent clinical findings about symptomatic benefit, not a reversed chemical label. Route, duration, trial population, placebo response and analysis differ; their causal contribution is not established.Read the recorded disagreement

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Does a clinically useful human free-lipoate salvage intervention exist without engineering a foreign ligase?The cell-engineering rescue is promising but does not establish ordinary supplement rescue or clinical gene-therapy efficacy.
Which Fe-S donor route dominates in each intact human tissue?Purified loading, auxiliary-cluster repair and inherited-disease phenotypes interrogate different layers; donor capacity is not a universal in-vivo ranking.
Which patients, if any, obtain durable neuropathy benefit and why do symptom trials differ?The positive short trial and the longer final-score null do not establish a responder mechanism, durable nerve repair or a nutritional-deficiency diagnosis.
Can a human clinical regimen reproduce the preclinical glutathione, glucose-signaling or ascorbate-combination mechanisms?Exposure, formulation, tissue and endpoint differ markedly; connecting graph nodes is hypothesis generation, not clinical validation.
Does ALA supplementation deplete thiamine or other B vitamins in humans?The shared enzyme dependencies do not prove depletion. No direct primary depletion experiment was established in this curation; thiamine deficiency and lipoylation disorders remain separate causes of impaired flux.
Does shared SLC5A6 transport cause clinically meaningful biotin or pantothenate deficiency with typical lipoic-acid supplementation?Transport competition is demonstrated in vitro; that alone does not establish depleted stores, symptoms or a preventive co-supplement regimen.
Can plasma lipoic-acid concentration diagnose an intracellular lipoylation defect?The reviewed studies do not establish a universal plasma threshold for mitochondrial cofactor adequacy.
Can free-lipoate redox effects predict the direction of a clinical combination effect?Cellular signaling, metal chemistry and pharmacological ascorbate illustrate context dependence; a shared antioxidant label cannot determine the outcome.
What is the specific human thioredoxin-reductase isoform contribution to free-lipoate reduction in each tissue?The older purified-enzyme report does not establish a TXNRD1/TXNRD2 flux map or selenium-supplement synergy.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Lipoic acid

The mechanisms

The lipoyl cofactor is attached through an amide linkage to a conserved carrier-protein lysine side chain.

Purified mouse Lipt2 transferred octanoyl groups from E. coli ACP to human GCSH.

LIAS installs sulfur at carbon 6 and carbon 8 of an octanoyl-lysyl residue on GCSH.

Reconstituted LIPT1 transfers the lipoyl group from GCSH to dehydrogenase E2 lipoyl domains.

Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD.

Human AMT transfers the aminomethyl-lipoyl intermediate's carbon to tetrahydrofolate, yielding 5,10-methylene-THF, ammonia and reduced H-protein.

Human SMVT cryo-EM complexes placed pantothenate, biotin and oxidized lipoate in substantially overlapping positions within one central substrate-binding pocket.

Oxidized alpha-lipoic acid inhibited human SMVT-mediated radiolabeled biotin uptake with an IC50 of 9.1 micromolar in the 2026 HEK293T assay.

Erythrocytes from a G6PD-deficient person failed to reduce lipoic acid in the assay; pharmacological G6PD inhibition also prevented reduction.

Cell-derived DHLA reduced extracellular cystine to cysteine in the tested cultures.

Lipoic acid supplementation did not improve the reported clinical course or restore deficient PDH, OGDH and leucine-catabolic function in LIPT2-deficient fibroblasts.

In SYDNEY 2, TSS fell by 4.9, 4.5 and 4.7 points in the 600-, 1200- and 1800-mg groups versus 2.9 with placebo over five weeks.

Full-length human LIPT2 complemented the E. coli lipB/lplA deletion strain, supporting its octanoyltransferase assignment.

Crystallography captured LIAS cross-linked to its H-protein substrate through a 6-mercaptooctanoyl ligand at a [3Fe-4S] cluster.

LIAS cleaves SAM to generate a 5-deoxyadenosyl radical that initiates hydrogen abstraction from the octanoyl substrate.

LIAS has distinct radical-SAM and auxiliary [4Fe-4S] clusters; the latter supplies sulfur during lipoyl synthesis.

Without auxiliary-cluster restoration, sulfur extraction degrades the LIAS auxiliary cluster and limits turnover.

NFU1 forms a tight complex with LIAS and efficiently restores its auxiliary cluster during turnover in vitro.

BOLA3 did not directly enhance Fe-S cluster transfer from NFU1 or GLRX5 to LIAS in the purified assay.

ISCA1 and ISCA2 produced only limited enhancement of LIAS turnover in this donor comparison.

An NFU1-ISCA1 heterodimer delivers a [4Fe-4S] cluster to the radical-SAM site of LIAS.

The NFU1 C-domain guides cluster transfer along increasing interaction affinity from ISCA1 toward LIAS.

[2Fe-2S]-loaded human ISCU and ISCA2 reconstituted catalytically active human LIAS in vitro.

EPR comparisons supported auxiliary-cluster insertion before radical-SAM-cluster insertion during the tested LIAS reconstitution.

Patient LIPT2 defects reduced mitochondrial protein lipoylation; wild-type LIPT2 expression restored it.

LIPT2-deficient fibroblasts had reduced PDH and OGDH activities, oxygen consumption and leucine catabolic flux.

The LIPT1 case showed deficient PDH and OGDH E2 lipoylation with rescue by wild-type LIPT1.

Despite LIPT1 deficiency, H-protein lipoylation, glycine-cleavage activity and glycine concentrations were normal in this case.

Lipoic-acid exposure lowered lactate release from the studied LIPT1-deficient fibroblasts, while control-cell lactate increased.

In those LIPT1-deficient fibroblasts, PDH activity increased only moderately, OGDH showed no increase, and the leucine-flux assay showed no BCKDH rescue.

The reported NFU1 splice-disrupting variant eliminated detectable mature mitochondrial NFU1 and accompanied lipoate-synthesis and 2-oxoacid dehydrogenase defects.

BOLA3 deficiency caused combined respiratory and 2-oxoacid dehydrogenase defects; expression of the appropriate BOLA3 isoform restored function.

GLRX5-associated cases showed deficient protein lipoylation and glycine-cleavage activity with elevated glycine.

Neither lipoate nor mitochondrially targeted lipoate corrected the studied cellular lipoylation deficiency.

Engineered LplA restored lipoylation in MECR-, BOLA3-, FDX1-, LIAS- and LIPT1-knockout cell models.

Engineered LplA restored cellular respiration and growth in low glucose in lipoylation-null cells, including a K562 model of a patient LIPT1 allele.

Lias-null mouse embryos died before embryonic day 9.5.

The tested high maternal lipoic-acid supplementation did not rescue Lias-null embryos.

Caco-2 lipoic-acid transport was energy dependent, increased at acidic pH and was inhibited by tested monocarboxylates.

DHLA formed during lipoic-acid transport in the Caco-2 experiments.

Compared with solution, the tested tablets produced R-lipoic-acid peak concentrations of 36–43% and exposure areas of 64–79%.

Median peak times for both lipoic-acid enantiomers were approximately 0.33–0.5 hours across the studied formulations.

The R-versus-racemate pilot found substantial exposure variability, especially in older adults, rather than a uniform formulation advantage.

Plasma glutathione did not change during the pilot’s three-hour sampling period.

600 mg R-lipoic acid and 1200 mg racemate yielded bioequivalent R-enantiomer exposure in this crossover study.

The R-only period had fewer gastrointestinal event reports than the racemate period; the mean symptom-score difference was not statistically significant.

Human erythrocytes reduced lipoic acid to DHLA with glucose but not with 2-deoxyglucose, supporting NADPH dependence.

Purified human glutathione reductase reduced free lipoic acid to DHLA in vitro.

Purified mammalian thioredoxin reductases, including enzyme from human placenta, catalyzed NADPH-dependent lipoic-acid reduction.

The tested lipoamide dehydrogenase reduced R-lipoic acid about 28 times faster than S-lipoic acid.

S-lipoic acid inhibited R-lipoic-acid reduction only at high concentrations in the enzyme assay.

Increased extracellular cysteine supported cellular uptake and glutathione synthesis, bypassing dependence on cystine transport in the studied cells.

In peripheral blood lymphocytes, lipoic-acid treatment mainly restored a low-thiol subpopulation rather than raising all cells above physiological thiol levels.

Older rat liver showed lower GCLC/GCLM expression and about 53% lower GCL activity than young liver.

Injected R-lipoic acid increased nuclear Nrf2 and antioxidant-response-element binding in aged rat liver.

R-lipoic-acid treatment increased GCLC and GCL activity at the later measured time point in aged rat liver.

Lipoic-acid exposure increased nuclear Nrf2 and reduced KEAP1 protein in HL-60 cells.

NQO1 protein and enzyme activity increased after lipoic-acid treatment in HL-60 cells.

Lipoic acid increased PI3K and Akt1 activities in L6 myotubes; wortmannin inhibited these responses.

Lipoic acid increased surface GLUT4 in L6 myotubes.

p38 inhibitors reduced lipoic-acid-stimulated glucose uptake without blocking GLUT4 translocation in L6 myotubes.

Lipoic-acid treatment increased intracellular oxidant signals, reduced insulin-receptor thiol reactivity and increased receptor phosphorylation.

Lipoic acid reduced phosphatase activity and PTP1B thiol reactivity in 3T3-L1 cells.

Lipoic acid increased glucose uptake in 3T3-L1 adipocytes; intracellular thiol modification or inhibition of the upstream oxidant response blocked stimulation.

Lipoic acid suppressed hypothalamic AMPK activity in the rodent experiments.

Reactivating hypothalamic AMPK reversed lipoic-acid effects on food intake and energy expenditure.

Lipoic acid spared intracellular ascorbate under basal and menadione-challenged conditions in endothelial cells.

Lipoic acid blunted copper-driven LDL oxidation and associated vitamin E consumption in the endothelial-cell experiment.

Lipoic acid did not prevent intracellular ascorbate loss caused by the extracellular copper/LDL challenge in the same study.

DHLA delayed copper-driven LDL oxidation, whereas oxidized lipoic acid did not protect in this cell-free assay.

DHLA favored copper reduction when copper was in excess and chelation when DHLA was in excess.

Oxidation destabilized DHLA-copper complexes near physiological pH, with renewed LDL oxidation and radical detection in the model.

Lipoic acid reduced pharmacological ascorbate-generated hydrogen peroxide in the tested cell experiments.

Lower tested lipoic-acid doses attenuated tumor-growth inhibition from high-dose ascorbate in the mouse model; the highest dose did not enhance it.

The study reported toxicity with prolonged lipoic-acid exposure and increased toxicity with tested ascorbate combinations in mice.

Nausea, vomiting and vertigo increased with dose in SYDNEY 2.

ALADIN III found no significant between-group TSS change at day 19 or after seven months, although an early daily-score area-under-curve analysis favored ALA.

ALADIN III found an early NIS improvement, while the seven-month comparison of continued ALA versus placebo did not reach conventional significance.