Component

Lipoic acid

54 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

Human evidence only

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

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
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 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
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
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
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 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
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
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
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 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
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
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
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
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
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
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
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
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 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
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
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
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
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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
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
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
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
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
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
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
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
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
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
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

What acts on it

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

Where it participates (unsigned role)

Chicken P-protein alone catalyzed very slow glycine decarboxylation; added lipoic acid stimulated the measured decarboxylation at least 100-fold.
Chicken glycine decarboxylase → Glycine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
PLP chemistry connects with the lipoyl component of glycine cleavage.
experimental_model
Purified chicken liver mitochondrial P-protein
limitations
Free lipoic acid assay; not evidence that supplements replace the intact cleavage system.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Gallus gallus
plain_language
B6-dependent glycine cleavage also depends on its lipoyl-linked reaction partners.
primary_references
[b6-gldc-1980] The mitochondrial glycine cleavage system. Purification and properties of glycine decarboxylase from chicken liver mitochondria. (1980). https://pubmed.ncbi.nlm.nih.gov/7440562/ DOI: 10.1016/s0021-9258(19)70183-5
tissue_or_cell_type
Chicken liver mitochondrial protein
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 659–669
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified chicken liver mitochondrial P-protein · source_derived_draft · unverified_draft
### b6-met-chicken-gldc-decarboxylation Chicken P-protein alone catalyzed very slow glycine decarboxylation; added lipoic acid stimulated the measured decarboxylation at least 100-fold. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6-dependent glycine cleavage also depends on its lipoyl-linked reaction partners. organism: Gallus gallus tissue_or_cell_type: Chicken liver mitochondrial protein experimental_model: Purified chicken liver mitochondrial P-protein limitations: Free lipoic acid assay; not evidence that supplements replace the intact cleavage system. cross_nutrient: PLP chemistry connects with the lipoyl component of glycine cleavage. [b6-gldc-1980] The mitochondrial glycine cleavage system. Purification and properties of glycine decarboxylase from chicken liver mitochondria. (1980). https://pubmed.ncbi.nlm.nih.gov/7440562/ DOI: 10.1016/s0021-9258(19)70183-5
Complete structured claim and evidence
SLC25A26 mutations were associated with impaired CoQ10 and lipoic-acid biosynthesis in the functional study.
Human mitochondrial SAM transporter / SLC25A26 → CoQ10 and lipoate biosynthesis in the SLC25A26 study source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human mitochondrial disease study and functional models.
limitations
This does not demonstrate that oral methionine, SAM, CoQ10 or lipoate repairs the transporter.
nutrient_topic
L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
plain_language
One transport gate connects methyl-donor supply with other cofactors.
primary_references
Intra-mitochondrial Methylation Deficiency Due to Mutations in SLC25A26. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26522469/ · DOI 10.1016/j.ajhg.2015.09.013
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 124–130
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human mitochondrial disease study and functional models. · source_derived_draft · unverified_draft
## methionine-mitochondrial-cofactor-products One transport gate connects methyl-donor supply with other cofactors. SLC25A26 mutations were associated with impaired CoQ10 and lipoic-acid biosynthesis in the functional study. Model: Human mitochondrial disease study and functional models. Limitations: This does not demonstrate that oral methionine, SAM, CoQ10 or lipoate repairs the transporter. Evidence access: Primary abstract Intra-mitochondrial Methylation Deficiency Due to Mutations in SLC25A26. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26522469/ · DOI 10.1016/j.ajhg.2015.09.013
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
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
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
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
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
In the cardiac Ndufab1-knockout study, the measured mitochondrial protein lipoylation was not significantly changed despite respiratory defects.
Mouse 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
Full text line 47; Supplementary Fig. S4B
experimental_model
Cardiomyocyte-specific Ndufab1 knockout mice and isolated heart mitochondria
exposure
Cardiomyocyte-specific Ndufab1 deletion.
limitations
A null result for these measurements is not proof that all fatty-acid synthesis was intact. Different tissue, developmental timing and depletion conditions preclude a same-context contradiction with HEK293T cells. 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
Mouse heart respiratory failure occurred without the measured lipoylation defect seen in the cultured-cell study.
primary_references
[b5-met-ndufab2019] NDUFAB1 confers cardio-protection by enhancing mitochondrial bioenergetics through coordination of respiratory complex and supercomplex assembly. (2019). https://pubmed.ncbi.nlm.nih.gov/31366990/ DOI: 10.1038/s41422-019-0208-x
tissue_or_cell_type
Heart mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 977–989
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cardiomyocyte-specific Ndufab1 knockout mice and isolated heart mitochondria · source_derived_draft · unverified_draft
### b5-met-heart-acp-lipoylation-spared In the cardiac Ndufab1-knockout study, the measured mitochondrial protein lipoylation was not significantly changed despite 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: Mouse heart respiratory failure occurred without the measured lipoylation defect seen in the cultured-cell study. organism: Mus musculus tissue_or_cell_type: Heart mitochondria experimental_model: Cardiomyocyte-specific Ndufab1 knockout mice and isolated heart mitochondria limitations: A null result for these measurements is not proof that all fatty-acid synthesis was intact. Different tissue, developmental timing and depletion conditions preclude a same-context contradiction with HEK293T cells. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Cardiomyocyte-specific Ndufab1 deletion. cross_nutrient: true evidence_location: Full text line 47; Supplementary Fig. S4B [b5-met-ndufab2019] NDUFAB1 confers cardio-protection by enhancing mitochondrial bioenergetics through coordination of respiratory complex and supercomplex assembly. (2019). https://pubmed.ncbi.nlm.nih.gov/31366990/ DOI: 10.1038/s41422-019-0208-x
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
Yeast PPT2 deletion, preventing mitochondrial ACP phosphopantetheinylation, reduced aconitase activity; a lipoate-synthesis LIP5 deletion control retained normal activity.
Saccharomyces cerevisiae mitochondrial phosphopantetheinyl transferase / Ppt2 → Total cellular aconitase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Full text line 181; Fig. 4C–E
experimental_model
Yeast PPT2-deletion and LIP5-deletion comparison
exposure
Genetic deletion of PPT2, compared with wild type and LIP5 deletion.
limitations
Aconitase activity is the measured endpoint. The separate sulfite-reductase result is retained in the source, without duplicating it as another claim. 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
Saccharomyces cerevisiae
plain_language
Failure to install the carrier arm affected an iron–sulfur enzyme beyond the lipoate pathway.
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
Whole-cell enzyme assay; mitochondrial aconitase
trigger_kind
machinery_impairment Imported condition classification; unverified.
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 907–919
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Yeast PPT2-deletion and LIP5-deletion comparison · source_derived_draft · unverified_draft
### b5-met-yeast-ppt2-fe-s Yeast PPT2 deletion, preventing mitochondrial ACP phosphopantetheinylation, reduced aconitase activity; a lipoate-synthesis LIP5 deletion control retained normal activity. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Failure to install the carrier arm affected an iron–sulfur enzyme beyond the lipoate pathway. organism: Saccharomyces cerevisiae tissue_or_cell_type: Whole-cell enzyme assay; mitochondrial aconitase experimental_model: Yeast PPT2-deletion and LIP5-deletion comparison limitations: Aconitase activity is the measured endpoint. The separate sulfite-reductase result is retained in the source, without duplicating it as another claim. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Genetic deletion of PPT2, compared with wild type and LIP5 deletion. cross_nutrient: true evidence_location: Full text line 181; Fig. 4C–E [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
In the human SMVT–pantothenate structural model, the substrate carboxyl group interacts with backbone amino groups of Ser81/Ala84 and hydrogen-bonds to Tyr156.
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
3.7-angstrom cryo-EM pantothenate complex; molecular-dynamics support for the binding model.
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. Atom-level interactions are structural-model interpretations; no specific dietary threshold follows.
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
SMVT anchors the charged end of B5 through specific contacts in its binding pocket.
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 ligand-binding pocket
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 418–429
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-pantothenate-carboxyl-recognition In the human SMVT–pantothenate structural model, the substrate carboxyl group interacts with backbone amino groups of Ser81/Ala84 and hydrogen-bonds to Tyr156. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: SMVT anchors the charged end of B5 through specific contacts in its binding pocket. organism: Homo sapiens tissue_or_cell_type: Purified human SMVT ligand-binding pocket 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. Atom-level interactions are structural-model interpretations; no specific dietary threshold follows. exposure: 3.7-angstrom cryo-EM pantothenate complex; molecular-dynamics support for the binding model. 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
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
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
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Lipoic acid

How nutrients influence it

Other things that act on it

How nutrients reach it in more than one step

What it does

What it acts on

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

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

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.

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.

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

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 exploratory clamp trial found a 27% greater change in glucose-disposal clearance versus placebo after pooling ALA groups.

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

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

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

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

Lipoic acid suppressed hypothalamic AMPK activity in the rodent experiments.

A reported patient developed hypoglycemia with high insulin autoantibodies after lipoic-acid exposure.

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

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

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

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

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

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

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

Whole-brain and deep-gray volumes appeared more stable with ALA, but increased T2 lesion volume complicated interpretation.

Proteinuria during ALA treatment prompted closer urine monitoring in the phase 2 trial; discontinuation was higher with ALA.

The larger phase 2 trial found no improvement in timed walking speed or other reported clinical outcomes at 24 months.

The pilot found less annualized brain-volume loss with ALA than placebo, approximately 0.21% versus 0.65%.

The pilot’s timed-walking comparison did not reach conventional statistical significance (P=0.06).

Lipoic acid increased surface GLUT4 in L6 myotubes.

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

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).

NATHAN 1 reported improvement in selected secondary impairment scores despite the nonsignificant primary endpoint.

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

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

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.

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

Adding lipoic acid to the culture medium did not reverse the protein-lipoylation defect caused by mitochondrial ACP knockdown in HEK293T cells.

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

What acts on it

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.

Where it participates (unsigned role)

Chicken P-protein alone catalyzed very slow glycine decarboxylation; added lipoic acid stimulated the measured decarboxylation at least 100-fold.

SLC25A26 mutations were associated with impaired CoQ10 and lipoic-acid biosynthesis in the functional study.

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

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

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

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

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

In the cardiac Ndufab1-knockout study, the measured mitochondrial protein lipoylation was not significantly changed despite respiratory defects.

Mitochondrial ACP knockdown in HEK293T cells reduced the proportion of mitochondrial proteins recognized as lipoylated before later respiratory defects.

Yeast PPT2 deletion, preventing mitochondrial ACP phosphopantetheinylation, reduced aconitase activity; a lipoate-synthesis LIP5 deletion control retained normal activity.

In the human SMVT–pantothenate structural model, the substrate carboxyl group interacts with backbone amino groups of Ser81/Ala84 and hydrogen-bonds to Tyr156.

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

Expression of cloned human SLC5A6 in HRPE cells conferred sodium-dependent uptake of lipoate.

The events it takes part in

Situations it appears in

In the sources

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