Nutrient chapter

Creatine

Independently recorded entity or measured process. Linked claims specify compartment, assay and experimental scope.

95 recorded mechanisms · 16 availability situations · 9 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

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

AGAT catalyzes transfer of an amidino group from arginine to glycine, forming guanidinoacetate and ornithine.
Human glycine amidinotransferase AGAT / GATM → Guanidinoacetate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/9218780.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "407baedc2f982a5abb9d14a01e8ac9dc331d60115acc716604c1e6003aa12c1b", "start_char": 0, "end_char": 1112, "text_sha256": "407baedc2f982a5abb9d14a01e8ac9dc331d60115acc716604c1e6003aa12c1b"}
experimental_model
Human AGAT crystal structures and inactive-mutant substrate complex
exposure
Native, ornithine-bound and inactive mutant structures
limitations
Structures support an amidino-transfer mechanism; substrate availability in a person and effects of amino-acid supplementation were not measured.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Recombinant human enzyme
plain_language
The first synthesis step joins material from arginine and glycine to make the precursor of creatine.
primary_references
[creatine-p9218780] Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis. (1997). https://pubmed.ncbi.nlm.nih.gov/9218780/ DOI: 10.1093/emboj/16.12.3373
tissue_or_cell_type
Purified protein
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 177–188
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human AGAT crystal structures and inactive-mutant substrate complex · source_derived_draft · unverified_draft
### creatine-agat-reaction AGAT catalyzes transfer of an amidino group from arginine to glycine, forming guanidinoacetate and ornithine. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The first synthesis step joins material from arginine and glycine to make the precursor of creatine. organism: Recombinant human enzyme tissue_or_cell_type: Purified protein experimental_model: Human AGAT crystal structures and inactive-mutant substrate complex limitations: Structures support an amidino-transfer mechanism; substrate availability in a person and effects of amino-acid supplementation were not measured. exposure: Native, ornithine-bound and inactive mutant structures evidence_span: {"source_cache": "artifacts/creatine-research/9218780.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "407baedc2f982a5abb9d14a01e8ac9dc331d60115acc716604c1e6003aa12c1b", "start_char": 0, "end_char": 1112, "text_sha256": "407baedc2f982a5abb9d14a01e8ac9dc331d60115acc716604c1e6003aa12c1b"} [creatine-p9218780] Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis. (1997). https://pubmed.ncbi.nlm.nih.gov/9218780/ DOI: 10.1093/emboj/16.12.3373
Complete structured claim and evidence
GAMT transfers a methyl group from S-adenosylmethionine to guanidinoacetate, producing creatine and S-adenosylhomocysteine.
Rat guanidinoacetate methyltransferase / Gamt → Guanidinoacetate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/12079381.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f63981cbaa4b7614a24f0a637893d05f9eff2c2143991404b0a7af1ea6667c6", "start_char": 0, "end_char": 1161, "text_sha256": "4f63981cbaa4b7614a24f0a637893d05f9eff2c2143991404b0a7af1ea6667c6"}
experimental_model
SAH-bound crystal structure and mutagenesis
exposure
SAH-bound structure at 2.5 angstrom resolution
limitations
The crystallized construct lacks 36 N-terminal residues; its dimer arrangement is not assigned universally to native human GAMT.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Rat GAMT
plain_language
The second synthesis step spends one SAM methyl group to finish each creatine molecule.
primary_references
[creatine-p12079381] Crystal structure of guanidinoacetate methyltransferase from rat liver: a model structure of protein arginine methyltransferase. (2002). https://pubmed.ncbi.nlm.nih.gov/12079381/ DOI: 10.1016/s0022-2836(02)00448-5 [creatine-p11595668] Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. (2001). https://pubmed.ncbi.nlm.nih.gov/11595668/ DOI: 10.1152/ajpendo.2001.281.5.e1095
tissue_or_cell_type
Purified, N-terminally truncated enzyme
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 203–215
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SAH-bound crystal structure and mutagenesis · source_derived_draft · unverified_draft
### creatine-gamt-methyl-transfer GAMT transfers a methyl group from S-adenosylmethionine to guanidinoacetate, producing creatine and S-adenosylhomocysteine. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The second synthesis step spends one SAM methyl group to finish each creatine molecule. organism: Rat GAMT tissue_or_cell_type: Purified, N-terminally truncated enzyme experimental_model: SAH-bound crystal structure and mutagenesis limitations: The crystallized construct lacks 36 N-terminal residues; its dimer arrangement is not assigned universally to native human GAMT. exposure: SAH-bound structure at 2.5 angstrom resolution evidence_span: {"source_cache": "artifacts/creatine-research/12079381.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f63981cbaa4b7614a24f0a637893d05f9eff2c2143991404b0a7af1ea6667c6", "start_char": 0, "end_char": 1161, "text_sha256": "4f63981cbaa4b7614a24f0a637893d05f9eff2c2143991404b0a7af1ea6667c6"} [creatine-p12079381] Crystal structure of guanidinoacetate methyltransferase from rat liver: a model structure of protein arginine methyltransferase. (2002). https://pubmed.ncbi.nlm.nih.gov/12079381/ DOI: 10.1016/s0022-2836(02)00448-5 [creatine-p11595668] Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. (2001). https://pubmed.ncbi.nlm.nih.gov/11595668/ DOI: 10.1152/ajpendo.2001.281.5.e1095
Complete structured claim and evidence
Creatine kinase catalyzes reversible phosphoryl transfer between ATP and creatine to form ADP and phosphocreatine.
Torpedo californica creatine kinase → Creatine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/12437342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1", "start_char": 0, "end_char": 1625, "text_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1"}
experimental_model
X-ray structure of a creatine kinase transition-state analogue complex
exposure
ADP, magnesium, nitrate and creatine complex at 2.1 angstrom resolution
limitations
Nitrate models the transferring phosphoryl group; it is not declared a physiological substrate. Structural magnesium dependence does not establish benefit from extra oral magnesium.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Torpedo californica enzyme
plain_language
Creatine can temporarily hold a phosphate group and return it to ADP when ATP must be regenerated.
primary_references
[creatine-p12437342] The 2.1 A structure of Torpedo californica creatine kinase complexed with the ADP-Mg(2+)-NO(3)(-)-creatine transition-state analogue complex. (2002). https://pubmed.ncbi.nlm.nih.gov/12437342/ DOI: 10.1021/bi026655p
tissue_or_cell_type
Purified creatine kinase
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 334–345
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structure of a creatine kinase transition-state analogue complex · source_derived_draft · unverified_draft
### creatine-ck-reversible-phosphate Creatine kinase catalyzes reversible phosphoryl transfer between ATP and creatine to form ADP and phosphocreatine. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Creatine can temporarily hold a phosphate group and return it to ADP when ATP must be regenerated. organism: Torpedo californica enzyme tissue_or_cell_type: Purified creatine kinase experimental_model: X-ray structure of a creatine kinase transition-state analogue complex limitations: Nitrate models the transferring phosphoryl group; it is not declared a physiological substrate. Structural magnesium dependence does not establish benefit from extra oral magnesium. exposure: ADP, magnesium, nitrate and creatine complex at 2.1 angstrom resolution evidence_span: {"source_cache": "artifacts/creatine-research/12437342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1", "start_char": 0, "end_char": 1625, "text_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1"} [creatine-p12437342] The 2.1 A structure of Torpedo californica creatine kinase complexed with the ADP-Mg(2+)-NO(3)(-)-creatine transition-state analogue complex. (2002). https://pubmed.ncbi.nlm.nih.gov/12437342/ DOI: 10.1021/bi026655p
Complete structured claim and evidence
Magnesium in the transition-state analogue complex coordinated ADP, nitrate and water ligands at the creatine kinase active site.
Mg2+ → Magnesium-coordinated creatine kinase transition-state analogue complex source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/12437342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1", "start_char": 0, "end_char": 1625, "text_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1"}
experimental_model
X-ray structure of a creatine kinase transition-state analogue complex
exposure
ADP, magnesium, nitrate and creatine complex at 2.1 angstrom resolution
limitations
Nitrate models the transferring phosphoryl group; it is not declared a physiological substrate. Structural magnesium dependence does not establish benefit from extra oral magnesium.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Torpedo californica enzyme
plain_language
Magnesium helps position the phosphate-transfer chemistry; creatine is only one component of that reaction.
primary_references
[creatine-p12437342] The 2.1 A structure of Torpedo californica creatine kinase complexed with the ADP-Mg(2+)-NO(3)(-)-creatine transition-state analogue complex. (2002). https://pubmed.ncbi.nlm.nih.gov/12437342/ DOI: 10.1021/bi026655p
tissue_or_cell_type
Purified creatine kinase
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 347–358
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structure of a creatine kinase transition-state analogue complex · source_derived_draft · unverified_draft
### creatine-ck-magnesium-complex Magnesium in the transition-state analogue complex coordinated ADP, nitrate and water ligands at the creatine kinase active site. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium helps position the phosphate-transfer chemistry; creatine is only one component of that reaction. organism: Torpedo californica enzyme tissue_or_cell_type: Purified creatine kinase experimental_model: X-ray structure of a creatine kinase transition-state analogue complex limitations: Nitrate models the transferring phosphoryl group; it is not declared a physiological substrate. Structural magnesium dependence does not establish benefit from extra oral magnesium. exposure: ADP, magnesium, nitrate and creatine complex at 2.1 angstrom resolution evidence_span: {"source_cache": "artifacts/creatine-research/12437342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1", "start_char": 0, "end_char": 1625, "text_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1"} [creatine-p12437342] The 2.1 A structure of Torpedo californica creatine kinase complexed with the ADP-Mg(2+)-NO(3)(-)-creatine transition-state analogue complex. (2002). https://pubmed.ncbi.nlm.nih.gov/12437342/ DOI: 10.1021/bi026655p
Complete structured claim and evidence
Human creatine-transporter expression conferred sodium-dependent creatine uptake with Km 14.9 ± 3.0 micromolar in five experiments.
Human creatine transporter CRT / SLC6A8 → Creatine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sodium-research/7945388.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f936121279583ab698555d2a318900a9dc5a42ecbf294619ee3abcc95c9a2f0", "start_char": 0, "end_char": 910, "text_sha256": "4f936121279583ab698555d2a318900a9dc5a42ecbf294619ee3abcc95c9a2f0"}
experimental_model
Cloning and functional expression
exposure
Radiolabeled creatine uptake
limitations
This primary abstract establishes sodium dependence; no chloride stoichiometry or clinical benefit is inferred.
nutrient_topic
Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium
organism
Human SLC6A8 in COS-7 cells
plain_language
Creatine entry has its own sodium-coupled transporter.
primary_references
[sodium-p7945388] The cloning and expression of a human creatine transporter. (1994). https://pubmed.ncbi.nlm.nih.gov/7945388/ DOI: 10.1006/bbrc.1994.2475
tissue_or_cell_type
Cell plasma membrane
transport_effect
raises Expression conferred sodium-dependent creatine uptake.
transport_pool
the expressing cell Expression conferred sodium-dependent creatine uptake.
Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 629–640
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning and functional expression · source_derived_draft · unverified_draft
### sodium-creatine-transport Human creatine-transporter expression conferred sodium-dependent creatine uptake with Km 14.9 ± 3.0 micromolar in five experiments. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Creatine entry has its own sodium-coupled transporter. organism: Human SLC6A8 in COS-7 cells tissue_or_cell_type: Cell plasma membrane experimental_model: Cloning and functional expression limitations: This primary abstract establishes sodium dependence; no chloride stoichiometry or clinical benefit is inferred. exposure: Radiolabeled creatine uptake evidence_span: {"source_cache": "artifacts/sodium-research/7945388.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f936121279583ab698555d2a318900a9dc5a42ecbf294619ee3abcc95c9a2f0", "start_char": 0, "end_char": 910, "text_sha256": "4f936121279583ab698555d2a318900a9dc5a42ecbf294619ee3abcc95c9a2f0"} [sodium-p7945388] The cloning and expression of a human creatine transporter. (1994). https://pubmed.ncbi.nlm.nih.gov/7945388/ DOI: 10.1006/bbrc.1994.2475
Complete structured claim and evidence
The cloned rabbit creatine transporter mediated sodium- and chloride-dependent creatine uptake, with an apparent Km of approximately 35 micromolar.
Rabbit creatine transporter / Slc6a8 → Creatine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/8473283.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10a3e9e18054bc80e38fe289f59ba358853482082e69c87af0844ac90a6da5c7", "start_char": 0, "end_char": 1330, "text_sha256": "10a3e9e18054bc80e38fe289f59ba358853482082e69c87af0844ac90a6da5c7"}
experimental_model
Rabbit transporter cloning and heterologous uptake assay
exposure
Radiolabeled creatine uptake with ion dependence and substrate analogues
limitations
Rabbit expression assay; neither human ion stoichiometry nor a benefit from extra dietary salt is inferred.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Rabbit transporter expressed in COS-7 cells
plain_language
Creatine uptake used both sodium and chloride in this transport experiment.
primary_references
[creatine-p8473283] A Na(+)-dependent creatine transporter in rabbit brain, muscle, heart, and kidney. cDNA cloning and functional expression. (1993). https://pubmed.ncbi.nlm.nih.gov/8473283/ DOI: 10.1016/s0021-9258(18)52891-x
tissue_or_cell_type
Cell plasma membrane
transport_effect
raises Sodium- and chloride-dependent creatine uptake with an apparent Km near 35 micromolar.
transport_pool
the expressing cell Sodium- and chloride-dependent creatine uptake with an apparent Km near 35 micromolar.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 412–423
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rabbit transporter cloning and heterologous uptake assay · source_derived_draft · unverified_draft
### creatine-rabbit-sodium-chloride The cloned rabbit creatine transporter mediated sodium- and chloride-dependent creatine uptake, with an apparent Km of approximately 35 micromolar. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Creatine uptake used both sodium and chloride in this transport experiment. organism: Rabbit transporter expressed in COS-7 cells tissue_or_cell_type: Cell plasma membrane experimental_model: Rabbit transporter cloning and heterologous uptake assay limitations: Rabbit expression assay; neither human ion stoichiometry nor a benefit from extra dietary salt is inferred. exposure: Radiolabeled creatine uptake with ion dependence and substrate analogues evidence_span: {"source_cache": "artifacts/creatine-research/8473283.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10a3e9e18054bc80e38fe289f59ba358853482082e69c87af0844ac90a6da5c7", "start_char": 0, "end_char": 1330, "text_sha256": "10a3e9e18054bc80e38fe289f59ba358853482082e69c87af0844ac90a6da5c7"} [creatine-p8473283] A Na(+)-dependent creatine transporter in rabbit brain, muscle, heart, and kidney. cDNA cloning and functional expression. (1993). https://pubmed.ncbi.nlm.nih.gov/8473283/ DOI: 10.1016/s0021-9258(18)52891-x
Complete structured claim and evidence
AGAT reporter expression fell with intracellular creatine, with a reported intracellular IC50 of approximately 1–2 mM.
Intracellular creatine content → AGAT expression and synthesis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/38104212.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28686c279fa726cb1596357628d69b5d5606fbe38e0177fe7b27b1931f249936", "start_char": 0, "end_char": 1889, "text_sha256": "28686c279fa726cb1596357628d69b5d5606fbe38e0177fe7b27b1931f249936"}
experimental_model
CRISPR AGAT reporter, transporter knockout and rescue
exposure
Manipulated extracellular and intracellular creatine with intact or deleted SLC6A8
limitations
Cell-line reporter regulation; the intracellular sensor was inferred rather than molecularly identified.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Human HAP1 cells
plain_language
Cells responded to the creatine inside them when regulating the first synthesis enzyme.
primary_references
[creatine-p38104212] Evidence of an intracellular creatine-sensing mechanism that modulates creatine biosynthesis via AGAT expression in human HAP1 cells. (2023). https://pubmed.ncbi.nlm.nih.gov/38104212/ DOI: 10.1038/s41598-023-49860-1
tissue_or_cell_type
Cultured cells
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 308–319
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CRISPR AGAT reporter, transporter knockout and rescue · source_derived_draft · unverified_draft
### creatine-intracellular-feedback AGAT reporter expression fell with intracellular creatine, with a reported intracellular IC50 of approximately 1–2 mM. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cells responded to the creatine inside them when regulating the first synthesis enzyme. organism: Human HAP1 cells tissue_or_cell_type: Cultured cells experimental_model: CRISPR AGAT reporter, transporter knockout and rescue limitations: Cell-line reporter regulation; the intracellular sensor was inferred rather than molecularly identified. exposure: Manipulated extracellular and intracellular creatine with intact or deleted SLC6A8 evidence_span: {"source_cache": "artifacts/creatine-research/38104212.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28686c279fa726cb1596357628d69b5d5606fbe38e0177fe7b27b1931f249936", "start_char": 0, "end_char": 1889, "text_sha256": "28686c279fa726cb1596357628d69b5d5606fbe38e0177fe7b27b1931f249936"} [creatine-p38104212] Evidence of an intracellular creatine-sensing mechanism that modulates creatine biosynthesis via AGAT expression in human HAP1 cells. (2023). https://pubmed.ncbi.nlm.nih.gov/38104212/ DOI: 10.1038/s41598-023-49860-1
Complete structured claim and evidence
Creatine alone did not significantly lower total plasma homocysteine compared with placebo (P=0.35).
Creatine → Homocysteine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/26311810.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "055a97365d5a6d864e78eafcfa4a73bc8c425e240487580796a443cf8ef33a04", "start_char": 0, "end_char": 2160, "text_sha256": "055a97365d5a6d864e78eafcfa4a73bc8c425e240487580796a443cf8ef33a04"}
experimental_model
Twelve-week randomized placebo-controlled trial
exposure
Creatine 3 g/day, folic acid 400 micrograms/day, both, or placebo; analyzed groups 101, 153, 103 and 101 respectively
limitations
Group-average effects and exploratory within-person associations are distinct. No general claim of restored methylation or reduced disease risk.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Bangladeshi adults
plain_language
Reducing precursor production did not automatically produce a lower homocysteine result in people.
primary_references
[creatine-p26311810] Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial. (2015). https://pubmed.ncbi.nlm.nih.gov/26311810/ DOI: 10.3945/jn.115.216739
tissue_or_cell_type
Plasma metabolites
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 737–748
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve-week randomized placebo-controlled trial · source_derived_draft · unverified_draft
### creatine-human-hcy-null Creatine alone did not significantly lower total plasma homocysteine compared with placebo (P=0.35). Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing precursor production did not automatically produce a lower homocysteine result in people. organism: Bangladeshi adults tissue_or_cell_type: Plasma metabolites experimental_model: Twelve-week randomized placebo-controlled trial limitations: Group-average effects and exploratory within-person associations are distinct. No general claim of restored methylation or reduced disease risk. exposure: Creatine 3 g/day, folic acid 400 micrograms/day, both, or placebo; analyzed groups 101, 153, 103 and 101 respectively evidence_span: {"source_cache": "artifacts/creatine-research/26311810.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "055a97365d5a6d864e78eafcfa4a73bc8c425e240487580796a443cf8ef33a04", "start_char": 0, "end_char": 2160, "text_sha256": "055a97365d5a6d864e78eafcfa4a73bc8c425e240487580796a443cf8ef33a04"} [creatine-p26311810] Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial. (2015). https://pubmed.ncbi.nlm.nih.gov/26311810/ DOI: 10.3945/jn.115.216739
Complete structured claim and evidence
The AGAT-deficient sisters had low urinary guanidinoacetate, absent AGAT activity and brain creatine depletion.
Human glycine amidinotransferase AGAT / GATM → Brain total creatine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/11555793.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "89ef028281e917c6af5ac6975c05f6ff421852645e695550b737ca4eff6d78f3", "start_char": 0, "end_char": 1044, "text_sha256": "89ef028281e917c6af5ac6975c05f6ff421852645e695550b737ca4eff6d78f3"}
experimental_model
Biochemical and genetic investigation with oral replacement observations
exposure
Inherited AGAT deficiency and oral creatine substitution
limitations
Rare synthesis disorder; treatment response is not equivalent to a diagnosis of dietary creatine deficiency.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Two human sisters
plain_language
A broken first synthesis step can leave both precursor and brain creatine low.
primary_references
[creatine-p11555793] Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11555793/ DOI: 10.1086/323765
tissue_or_cell_type
Urine, brain magnetic-resonance spectroscopy and AGAT assays
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 841–852
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical and genetic investigation with oral replacement observations · source_derived_draft · unverified_draft
### creatine-agat-brain-deficiency The AGAT-deficient sisters had low urinary guanidinoacetate, absent AGAT activity and brain creatine depletion. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A broken first synthesis step can leave both precursor and brain creatine low. organism: Two human sisters tissue_or_cell_type: Urine, brain magnetic-resonance spectroscopy and AGAT assays experimental_model: Biochemical and genetic investigation with oral replacement observations limitations: Rare synthesis disorder; treatment response is not equivalent to a diagnosis of dietary creatine deficiency. exposure: Inherited AGAT deficiency and oral creatine substitution evidence_span: {"source_cache": "artifacts/creatine-research/11555793.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "89ef028281e917c6af5ac6975c05f6ff421852645e695550b737ca4eff6d78f3", "start_char": 0, "end_char": 1044, "text_sha256": "89ef028281e917c6af5ac6975c05f6ff421852645e695550b737ca4eff6d78f3"} [creatine-p11555793] Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11555793/ DOI: 10.1086/323765
Complete structured claim and evidence
The GAMT-deficient children had high brain guanidinoacetate, low blood creatine and severely deficient liver GAMT activity.
Human guanidinoacetate methyltransferase / GAMT → Brain guanidinoacetate accumulation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/8651275.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d6999ce02dd6012eefd5981a91374d6c933af0924d5e82b1447fd322e8f211de", "start_char": 0, "end_char": 706, "text_sha256": "d6999ce02dd6012eefd5981a91374d6c933af0924d5e82b1447fd322e8f211de"}
experimental_model
Biochemical diagnosis and treatment observations
exposure
GAMT deficiency with oral creatine substitution
limitations
Small case series; biochemical and neurological responses are not a universal prognosis.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Two human children
plain_language
The blocked final step left precursor behind while reducing the finished product.
primary_references
[creatine-p8651275] Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man. (1996). https://pubmed.ncbi.nlm.nih.gov/8651275/
tissue_or_cell_type
Brain spectroscopy, blood and liver enzyme assay
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 867–878
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical diagnosis and treatment observations · source_derived_draft · unverified_draft
### creatine-gamt-gaa-accumulation The GAMT-deficient children had high brain guanidinoacetate, low blood creatine and severely deficient liver GAMT activity. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The blocked final step left precursor behind while reducing the finished product. organism: Two human children tissue_or_cell_type: Brain spectroscopy, blood and liver enzyme assay experimental_model: Biochemical diagnosis and treatment observations limitations: Small case series; biochemical and neurological responses are not a universal prognosis. exposure: GAMT deficiency with oral creatine substitution evidence_span: {"source_cache": "artifacts/creatine-research/8651275.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d6999ce02dd6012eefd5981a91374d6c933af0924d5e82b1447fd322e8f211de", "start_char": 0, "end_char": 706, "text_sha256": "d6999ce02dd6012eefd5981a91374d6c933af0924d5e82b1447fd322e8f211de"} [creatine-p8651275] Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man. (1996). https://pubmed.ncbi.nlm.nih.gov/8651275/
Complete structured claim and evidence
The SLC6A8-deficient male had absent brain creatine on spectroscopy and defective fibroblast creatine uptake despite high plasma and urinary creatine and normal guanidinoacetate.
Human creatine transporter CRT / SLC6A8 → Brain total creatine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/11326334.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "95d65dd9212e917935c2c5d5c76a36a1bef2803c23be600da6b2e1c54bcd5cc9", "start_char": 0, "end_char": 739, "text_sha256": "95d65dd9212e917935c2c5d5c76a36a1bef2803c23be600da6b2e1c54bcd5cc9"}
experimental_model
Human family genetics and fibroblast transport assay
exposure
SLC6A8 loss-of-function variant
limitations
Single family; circulating creatine cannot substitute for cellular transport. No treatment failure claim is inferred from this abstract.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Human male patient and relatives
plain_language
A high blood or urine value did not mean creatine reached the brain.
primary_references
[creatine-p11326334] X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome. (2001). https://pubmed.ncbi.nlm.nih.gov/11326334/ DOI: 10.1086/320595
tissue_or_cell_type
Brain spectroscopy, plasma, urine and fibroblasts
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 906–917
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human family genetics and fibroblast transport assay · source_derived_draft · unverified_draft
### creatine-transporter-brain-loss The SLC6A8-deficient male had absent brain creatine on spectroscopy and defective fibroblast creatine uptake despite high plasma and urinary creatine and normal guanidinoacetate. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A high blood or urine value did not mean creatine reached the brain. organism: Human male patient and relatives tissue_or_cell_type: Brain spectroscopy, plasma, urine and fibroblasts experimental_model: Human family genetics and fibroblast transport assay limitations: Single family; circulating creatine cannot substitute for cellular transport. No treatment failure claim is inferred from this abstract. exposure: SLC6A8 loss-of-function variant evidence_span: {"source_cache": "artifacts/creatine-research/11326334.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "95d65dd9212e917935c2c5d5c76a36a1bef2803c23be600da6b2e1c54bcd5cc9", "start_char": 0, "end_char": 739, "text_sha256": "95d65dd9212e917935c2c5d5c76a36a1bef2803c23be600da6b2e1c54bcd5cc9"} [creatine-p11326334] X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome. (2001). https://pubmed.ncbi.nlm.nih.gov/11326334/ DOI: 10.1086/320595
Complete structured claim and evidence
TNAP localized to thermogenic adipocyte mitochondria and hydrolyzed phosphocreatine to support the futile creatine cycle.
Mouse tissue-nonspecific alkaline phosphatase / Alpl → Phosphocreatine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/33981039.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "915403423e16b5e0e5db70e99ebc6518e612bc9ef69ceb1e25da3074a8410dca", "start_char": 0, "end_char": 1400, "text_sha256": "915403423e16b5e0e5db70e99ebc6518e612bc9ef69ceb1e25da3074a8410dca"}
experimental_model
Phosphatase biochemistry, mitochondrial inhibition and adipocyte gene deletion
exposure
TNAP inhibition and adipocyte Alpl deletion
limitations
Mouse mechanism; it does not establish that creatine supplements cause weight loss in humans.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Mouse thermogenic adipocytes and mice
plain_language
This phosphatase releases the stored phosphate without making ATP, allowing continued fuel use and heat production.
primary_references
[creatine-p33981039] Mitochondrial TNAP controls thermogenesis by hydrolysis of phosphocreatine. (2021). https://pubmed.ncbi.nlm.nih.gov/33981039/ DOI: 10.1038/s41586-021-03533-z
tissue_or_cell_type
Adipocyte mitochondria
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 503–514
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phosphatase biochemistry, mitochondrial inhibition and adipocyte gene deletion · source_derived_draft · unverified_draft
### creatine-tnap-pcr-hydrolysis TNAP localized to thermogenic adipocyte mitochondria and hydrolyzed phosphocreatine to support the futile creatine cycle. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This phosphatase releases the stored phosphate without making ATP, allowing continued fuel use and heat production. organism: Mouse thermogenic adipocytes and mice tissue_or_cell_type: Adipocyte mitochondria experimental_model: Phosphatase biochemistry, mitochondrial inhibition and adipocyte gene deletion limitations: Mouse mechanism; it does not establish that creatine supplements cause weight loss in humans. exposure: TNAP inhibition and adipocyte Alpl deletion evidence_span: {"source_cache": "artifacts/creatine-research/33981039.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "915403423e16b5e0e5db70e99ebc6518e612bc9ef69ceb1e25da3074a8410dca", "start_char": 0, "end_char": 1400, "text_sha256": "915403423e16b5e0e5db70e99ebc6518e612bc9ef69ceb1e25da3074a8410dca"} [creatine-p33981039] Mitochondrial TNAP controls thermogenesis by hydrolysis of phosphocreatine. (2021). https://pubmed.ncbi.nlm.nih.gov/33981039/ DOI: 10.1038/s41586-021-03533-z
Complete structured claim and evidence
Ornithine binding to human AGAT induced movement of a flexible loop and neighboring helix at the active-site region.
L-Ornithine → Human glycine amidinotransferase AGAT / GATM source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/9218780.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "407baedc2f982a5abb9d14a01e8ac9dc331d60115acc716604c1e6003aa12c1b", "start_char": 0, "end_char": 1112, "text_sha256": "407baedc2f982a5abb9d14a01e8ac9dc331d60115acc716604c1e6003aa12c1b"}
experimental_model
Human AGAT crystal structures and inactive-mutant substrate complex
exposure
Native, ornithine-bound and inactive mutant structures
limitations
Structures support an amidino-transfer mechanism; substrate availability in a person and effects of amino-acid supplementation were not measured.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Recombinant human enzyme
plain_language
A product of the first step can bind back to the enzyme and change its working shape.
primary_references
[creatine-p9218780] Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis. (1997). https://pubmed.ncbi.nlm.nih.gov/9218780/ DOI: 10.1093/emboj/16.12.3373
tissue_or_cell_type
Purified protein
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 190–201
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human AGAT crystal structures and inactive-mutant substrate complex · source_derived_draft · unverified_draft
### creatine-ornithine-agat Ornithine binding to human AGAT induced movement of a flexible loop and neighboring helix at the active-site region. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A product of the first step can bind back to the enzyme and change its working shape. organism: Recombinant human enzyme tissue_or_cell_type: Purified protein experimental_model: Human AGAT crystal structures and inactive-mutant substrate complex limitations: Structures support an amidino-transfer mechanism; substrate availability in a person and effects of amino-acid supplementation were not measured. exposure: Native, ornithine-bound and inactive mutant structures evidence_span: {"source_cache": "artifacts/creatine-research/9218780.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "407baedc2f982a5abb9d14a01e8ac9dc331d60115acc716604c1e6003aa12c1b", "start_char": 0, "end_char": 1112, "text_sha256": "407baedc2f982a5abb9d14a01e8ac9dc331d60115acc716604c1e6003aa12c1b"} [creatine-p9218780] Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis. (1997). https://pubmed.ncbi.nlm.nih.gov/9218780/ DOI: 10.1093/emboj/16.12.3373
Complete structured claim and evidence
Methionine adenosylation supplies SAM, the methyl donor consumed when guanidinoacetate is converted to creatine.
L-Methionine → S-Adenosyl-L-methionine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/11595668.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0", "start_char": 0, "end_char": 1687, "text_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0"}
experimental_model
Rat methyl-demand feeding and hepatocyte experiments; reaction context from the primary report
exposure
Guanidinoacetate, creatine and methionine exposures
limitations
The reaction record preserves the biochemical context of this primary experiment; it does not establish a universal fraction of human methylation demand.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Rats
plain_language
Methionine must first be activated into SAM before its methyl group can finish creatine synthesis.
primary_references
[creatine-p11595668] Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. (2001). https://pubmed.ncbi.nlm.nih.gov/11595668/ DOI: 10.1152/ajpendo.2001.281.5.e1095
tissue_or_cell_type
Liver and isolated hepatocytes
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 217–228
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat methyl-demand feeding and hepatocyte experiments; reaction context from the primary report · source_derived_draft · unverified_draft
### creatine-methionine-sam-supply Methionine adenosylation supplies SAM, the methyl donor consumed when guanidinoacetate is converted to creatine. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Methionine must first be activated into SAM before its methyl group can finish creatine synthesis. organism: Rats tissue_or_cell_type: Liver and isolated hepatocytes experimental_model: Rat methyl-demand feeding and hepatocyte experiments; reaction context from the primary report limitations: The reaction record preserves the biochemical context of this primary experiment; it does not establish a universal fraction of human methylation demand. exposure: Guanidinoacetate, creatine and methionine exposures evidence_span: {"source_cache": "artifacts/creatine-research/11595668.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0", "start_char": 0, "end_char": 1687, "text_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0"} [creatine-p11595668] Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. (2001). https://pubmed.ncbi.nlm.nih.gov/11595668/ DOI: 10.1152/ajpendo.2001.281.5.e1095
Complete structured claim and evidence
Creatine feeding reduced renal AGAT activity to 26% of control in the studied rats.
Creatine → Renal AGAT enzymatic activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/6384218.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e742efaf02e310dd4a64db3d9336c23354b40d901631e61be2a0cbb9fee507", "start_char": 0, "end_char": 1077, "text_sha256": "12e742efaf02e310dd4a64db3d9336c23354b40d901631e61be2a0cbb9fee507"}
experimental_model
Controlled feeding with enzyme, protein-synthesis and functional-mRNA measurements
exposure
Diet supplemented with 0.3% creatine
limitations
Rat feedback regulation; percentages are relative to controls in this experiment, not human intake targets.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Rats
plain_language
Providing creatine reduced the kidney enzyme activity used to make its precursor.
primary_references
[creatine-p6384218] Repression of rat kidney L-arginine:glycine amidinotransferase synthesis by creatine at a pretranslational level. (1984). https://pubmed.ncbi.nlm.nih.gov/6384218/ DOI: 10.1016/s0021-9258(20)71316-5
tissue_or_cell_type
Kidney
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 230–241
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled feeding with enzyme, protein-synthesis and functional-mRNA measurements · source_derived_draft · unverified_draft
### creatine-feedback-renal-agat Creatine feeding reduced renal AGAT activity to 26% of control in the studied rats. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing creatine reduced the kidney enzyme activity used to make its precursor. organism: Rats tissue_or_cell_type: Kidney experimental_model: Controlled feeding with enzyme, protein-synthesis and functional-mRNA measurements limitations: Rat feedback regulation; percentages are relative to controls in this experiment, not human intake targets. exposure: Diet supplemented with 0.3% creatine evidence_span: {"source_cache": "artifacts/creatine-research/6384218.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e742efaf02e310dd4a64db3d9336c23354b40d901631e61be2a0cbb9fee507", "start_char": 0, "end_char": 1077, "text_sha256": "12e742efaf02e310dd4a64db3d9336c23354b40d901631e61be2a0cbb9fee507"} [creatine-p6384218] Repression of rat kidney L-arginine:glycine amidinotransferase synthesis by creatine at a pretranslational level. (1984). https://pubmed.ncbi.nlm.nih.gov/6384218/ DOI: 10.1016/s0021-9258(20)71316-5
Complete structured claim and evidence
Renal AGAT synthesis fell to 21% of control and functional AGAT mRNA to 37% with creatine feeding.
Creatine → AGAT expression and synthesis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/6384218.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e742efaf02e310dd4a64db3d9336c23354b40d901631e61be2a0cbb9fee507", "start_char": 0, "end_char": 1077, "text_sha256": "12e742efaf02e310dd4a64db3d9336c23354b40d901631e61be2a0cbb9fee507"}
experimental_model
Controlled feeding with enzyme, protein-synthesis and functional-mRNA measurements
exposure
Diet supplemented with 0.3% creatine
limitations
Rat feedback regulation; percentages are relative to controls in this experiment, not human intake targets.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Rats
plain_language
The body adjusted production of the synthesis enzyme, not merely the amount of precursor in a test tube.
primary_references
[creatine-p6384218] Repression of rat kidney L-arginine:glycine amidinotransferase synthesis by creatine at a pretranslational level. (1984). https://pubmed.ncbi.nlm.nih.gov/6384218/ DOI: 10.1016/s0021-9258(20)71316-5
tissue_or_cell_type
Kidney
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 243–254
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled feeding with enzyme, protein-synthesis and functional-mRNA measurements · source_derived_draft · unverified_draft
### creatine-feedback-agat-expression Renal AGAT synthesis fell to 21% of control and functional AGAT mRNA to 37% with creatine feeding. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The body adjusted production of the synthesis enzyme, not merely the amount of precursor in a test tube. organism: Rats tissue_or_cell_type: Kidney experimental_model: Controlled feeding with enzyme, protein-synthesis and functional-mRNA measurements limitations: Rat feedback regulation; percentages are relative to controls in this experiment, not human intake targets. exposure: Diet supplemented with 0.3% creatine evidence_span: {"source_cache": "artifacts/creatine-research/6384218.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12e742efaf02e310dd4a64db3d9336c23354b40d901631e61be2a0cbb9fee507", "start_char": 0, "end_char": 1077, "text_sha256": "12e742efaf02e310dd4a64db3d9336c23354b40d901631e61be2a0cbb9fee507"} [creatine-p6384218] Repression of rat kidney L-arginine:glycine amidinotransferase synthesis by creatine at a pretranslational level. (1984). https://pubmed.ncbi.nlm.nih.gov/6384218/ DOI: 10.1016/s0021-9258(20)71316-5
Complete structured claim and evidence
Creatinine excretion represents continuing loss from the creatine/phosphocreatine pool, which is replaced by diet and/or endogenous synthesis.
Creatinine → Creatine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/19017728.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee", "start_char": 0, "end_char": 1599, "text_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee"}
experimental_model
Rat feeding, isolated hepatocytes and in-vivo hepatic balance
exposure
Creatine-fed versus creatine-free conditions; guanidinoacetate and methionine substrate experiments
limitations
Biochemical premise of the rat synthesis paper, not a new quantitative human turnover measurement or a direct measure of tissue stores.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Rats
plain_language
The pool needs replenishment because some material continually leaves as creatinine.
primary_references
[creatine-p19017728] Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo. (2009). https://pubmed.ncbi.nlm.nih.gov/19017728/ DOI: 10.1152/ajpendo.90547.2008
tissue_or_cell_type
Kidney, liver, plasma and isolated hepatocytes
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 256–267
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat feeding, isolated hepatocytes and in-vivo hepatic balance · source_derived_draft · unverified_draft
### creatine-creatinine-loss Creatinine excretion represents continuing loss from the creatine/phosphocreatine pool, which is replaced by diet and/or endogenous synthesis. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pool needs replenishment because some material continually leaves as creatinine. organism: Rats tissue_or_cell_type: Kidney, liver, plasma and isolated hepatocytes experimental_model: Rat feeding, isolated hepatocytes and in-vivo hepatic balance limitations: Biochemical premise of the rat synthesis paper, not a new quantitative human turnover measurement or a direct measure of tissue stores. exposure: Creatine-fed versus creatine-free conditions; guanidinoacetate and methionine substrate experiments evidence_span: {"source_cache": "artifacts/creatine-research/19017728.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee", "start_char": 0, "end_char": 1599, "text_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee"} [creatine-p19017728] Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo. (2009). https://pubmed.ncbi.nlm.nih.gov/19017728/ DOI: 10.1152/ajpendo.90547.2008
Complete structured claim and evidence
Isolated rat hepatocytes synthesized creatine from guanidinoacetate but could not carry out the entire pathway from methionine, arginine and glycine under the tested conditions.
Guanidinoacetate → Hepatic synthesis of creatine from guanidinoacetate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/19017728.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee", "start_char": 0, "end_char": 1599, "text_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee"}
experimental_model
Rat feeding, isolated hepatocytes and in-vivo hepatic balance
exposure
Creatine-fed versus creatine-free conditions; guanidinoacetate and methionine substrate experiments
limitations
Interorgan division of synthesis is established here in rats; this is not proof that human tissues never synthesize both steps locally.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Rats
plain_language
In this preparation, the liver needed the precursor supplied by the earlier synthesis step.
primary_references
[creatine-p19017728] Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo. (2009). https://pubmed.ncbi.nlm.nih.gov/19017728/ DOI: 10.1152/ajpendo.90547.2008
tissue_or_cell_type
Kidney, liver, plasma and isolated hepatocytes
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 269–280
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat feeding, isolated hepatocytes and in-vivo hepatic balance · source_derived_draft · unverified_draft
### creatine-hepatocyte-gaa-conversion Isolated rat hepatocytes synthesized creatine from guanidinoacetate but could not carry out the entire pathway from methionine, arginine and glycine under the tested conditions. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this preparation, the liver needed the precursor supplied by the earlier synthesis step. organism: Rats tissue_or_cell_type: Kidney, liver, plasma and isolated hepatocytes experimental_model: Rat feeding, isolated hepatocytes and in-vivo hepatic balance limitations: Interorgan division of synthesis is established here in rats; this is not proof that human tissues never synthesize both steps locally. exposure: Creatine-fed versus creatine-free conditions; guanidinoacetate and methionine substrate experiments evidence_span: {"source_cache": "artifacts/creatine-research/19017728.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee", "start_char": 0, "end_char": 1599, "text_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee"} [creatine-p19017728] Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo. (2009). https://pubmed.ncbi.nlm.nih.gov/19017728/ DOI: 10.1152/ajpendo.90547.2008
Complete structured claim and evidence
Adding methionine increased hepatocyte SAM and creatine synthesis from guanidinoacetate.
L-Methionine → Hepatic synthesis of creatine from guanidinoacetate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/19017728.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee", "start_char": 0, "end_char": 1599, "text_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee"}
experimental_model
Rat feeding, isolated hepatocytes and in-vivo hepatic balance
exposure
Creatine-fed versus creatine-free conditions; guanidinoacetate and methionine substrate experiments
limitations
Interorgan division of synthesis is established here in rats; this is not proof that human tissues never synthesize both steps locally.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Rats
plain_language
Methionine helped supply the methyl donor needed to finish creatine.
primary_references
[creatine-p19017728] Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo. (2009). https://pubmed.ncbi.nlm.nih.gov/19017728/ DOI: 10.1152/ajpendo.90547.2008
tissue_or_cell_type
Kidney, liver, plasma and isolated hepatocytes
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 282–293
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat feeding, isolated hepatocytes and in-vivo hepatic balance · source_derived_draft · unverified_draft
### creatine-methionine-hepatic-synthesis Adding methionine increased hepatocyte SAM and creatine synthesis from guanidinoacetate. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Methionine helped supply the methyl donor needed to finish creatine. organism: Rats tissue_or_cell_type: Kidney, liver, plasma and isolated hepatocytes experimental_model: Rat feeding, isolated hepatocytes and in-vivo hepatic balance limitations: Interorgan division of synthesis is established here in rats; this is not proof that human tissues never synthesize both steps locally. exposure: Creatine-fed versus creatine-free conditions; guanidinoacetate and methionine substrate experiments evidence_span: {"source_cache": "artifacts/creatine-research/19017728.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee", "start_char": 0, "end_char": 1599, "text_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee"} [creatine-p19017728] Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo. (2009). https://pubmed.ncbi.nlm.nih.gov/19017728/ DOI: 10.1152/ajpendo.90547.2008
Complete structured claim and evidence
Creatine feeding reduced renal AGAT and circulating guanidinoacetate without reducing hepatic GAMT activity or capacity to synthesize creatine from guanidinoacetate.
Creatine → Rat guanidinoacetate methyltransferase / Gamt source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/19017728.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee", "start_char": 0, "end_char": 1599, "text_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee"}
experimental_model
Rat feeding, isolated hepatocytes and in-vivo hepatic balance
exposure
Creatine-fed versus creatine-free conditions; guanidinoacetate and methionine substrate experiments
limitations
Interorgan division of synthesis is established here in rats; this is not proof that human tissues never synthesize both steps locally.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Rats
plain_language
Feedback mainly limited precursor supply in this rat experiment; it did not switch off every synthesis step.
primary_references
[creatine-p19017728] Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo. (2009). https://pubmed.ncbi.nlm.nih.gov/19017728/ DOI: 10.1152/ajpendo.90547.2008
tissue_or_cell_type
Kidney, liver, plasma and isolated hepatocytes
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 295–306
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat feeding, isolated hepatocytes and in-vivo hepatic balance · source_derived_draft · unverified_draft
### creatine-feedback-spares-gamt-capacity Creatine feeding reduced renal AGAT and circulating guanidinoacetate without reducing hepatic GAMT activity or capacity to synthesize creatine from guanidinoacetate. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Feedback mainly limited precursor supply in this rat experiment; it did not switch off every synthesis step. organism: Rats tissue_or_cell_type: Kidney, liver, plasma and isolated hepatocytes experimental_model: Rat feeding, isolated hepatocytes and in-vivo hepatic balance limitations: Interorgan division of synthesis is established here in rats; this is not proof that human tissues never synthesize both steps locally. exposure: Creatine-fed versus creatine-free conditions; guanidinoacetate and methionine substrate experiments evidence_span: {"source_cache": "artifacts/creatine-research/19017728.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee", "start_char": 0, "end_char": 1599, "text_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee"} [creatine-p19017728] Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo. (2009). https://pubmed.ncbi.nlm.nih.gov/19017728/ DOI: 10.1152/ajpendo.90547.2008
Complete structured claim and evidence
The high-affinity component of creatine accumulation and AGAT regulation depended on SLC6A8, whereas a nonsaturable component remained without the transporter.
Human creatine transporter CRT / SLC6A8 → Intracellular creatine content source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/38104212.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28686c279fa726cb1596357628d69b5d5606fbe38e0177fe7b27b1931f249936", "start_char": 0, "end_char": 1889, "text_sha256": "28686c279fa726cb1596357628d69b5d5606fbe38e0177fe7b27b1931f249936"}
experimental_model
CRISPR AGAT reporter, transporter knockout and rescue
exposure
Manipulated extracellular and intracellular creatine with intact or deleted SLC6A8
limitations
Cell-line reporter regulation; the intracellular sensor was inferred rather than molecularly identified.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Human HAP1 cells
plain_language
The usual transporter shaped feedback, but the engineered cells also showed a separate low-affinity route.
primary_references
[creatine-p38104212] Evidence of an intracellular creatine-sensing mechanism that modulates creatine biosynthesis via AGAT expression in human HAP1 cells. (2023). https://pubmed.ncbi.nlm.nih.gov/38104212/ DOI: 10.1038/s41598-023-49860-1
tissue_or_cell_type
Cultured cells
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 321–332
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CRISPR AGAT reporter, transporter knockout and rescue · source_derived_draft · unverified_draft
### creatine-feedback-transporter-component The high-affinity component of creatine accumulation and AGAT regulation depended on SLC6A8, whereas a nonsaturable component remained without the transporter. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The usual transporter shaped feedback, but the engineered cells also showed a separate low-affinity route. organism: Human HAP1 cells tissue_or_cell_type: Cultured cells experimental_model: CRISPR AGAT reporter, transporter knockout and rescue limitations: Cell-line reporter regulation; the intracellular sensor was inferred rather than molecularly identified. exposure: Manipulated extracellular and intracellular creatine with intact or deleted SLC6A8 evidence_span: {"source_cache": "artifacts/creatine-research/38104212.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28686c279fa726cb1596357628d69b5d5606fbe38e0177fe7b27b1931f249936", "start_char": 0, "end_char": 1889, "text_sha256": "28686c279fa726cb1596357628d69b5d5606fbe38e0177fe7b27b1931f249936"} [creatine-p38104212] Evidence of an intracellular creatine-sensing mechanism that modulates creatine biosynthesis via AGAT expression in human HAP1 cells. (2023). https://pubmed.ncbi.nlm.nih.gov/38104212/ DOI: 10.1038/s41598-023-49860-1
Complete structured claim and evidence
The mitochondrial creatine kinase structure supported an octameric enzyme positioned to convert mitochondrially generated ATP into phosphocreatine.
Mitochondrial creatine kinase family → Phosphocreatine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/8692275.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dca64c2f8e71d91a83ba9bbcc8cc320c7c87e2239de6f07111efe0560ac061c6", "start_char": 0, "end_char": 1125, "text_sha256": "dca64c2f8e71d91a83ba9bbcc8cc320c7c87e2239de6f07111efe0560ac061c6"}
experimental_model
Mitochondrial creatine kinase crystal structure
exposure
Octamer architecture and electrostatic surface analysis
limitations
The abstract does not specify the organism; no human-specific structural assignment is made. Membrane binding interpretation accompanies structural data.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Mitochondrial creatine kinase preparation in the primary study
plain_language
Mitochondrial creatine kinase can load the phosphate carrier near the site of ATP production.
primary_references
[creatine-p8692275] Structure of mitochondrial creatine kinase. (1996). https://pubmed.ncbi.nlm.nih.gov/8692275/ DOI: 10.1038/381341a0
tissue_or_cell_type
Purified protein; mitochondrial membrane interface interpretation
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 360–371
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mitochondrial creatine kinase crystal structure · source_derived_draft · unverified_draft
### creatine-mitochondrial-ck-organization The mitochondrial creatine kinase structure supported an octameric enzyme positioned to convert mitochondrially generated ATP into phosphocreatine. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mitochondrial creatine kinase can load the phosphate carrier near the site of ATP production. organism: Mitochondrial creatine kinase preparation in the primary study tissue_or_cell_type: Purified protein; mitochondrial membrane interface interpretation experimental_model: Mitochondrial creatine kinase crystal structure limitations: The abstract does not specify the organism; no human-specific structural assignment is made. Membrane binding interpretation accompanies structural data. exposure: Octamer architecture and electrostatic surface analysis evidence_span: {"source_cache": "artifacts/creatine-research/8692275.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dca64c2f8e71d91a83ba9bbcc8cc320c7c87e2239de6f07111efe0560ac061c6", "start_char": 0, "end_char": 1125, "text_sha256": "dca64c2f8e71d91a83ba9bbcc8cc320c7c87e2239de6f07111efe0560ac061c6"} [creatine-p8692275] Structure of mitochondrial creatine kinase. (1996). https://pubmed.ncbi.nlm.nih.gov/8692275/ DOI: 10.1038/381341a0
Complete structured claim and evidence
Mitochondrial creatine kinase selectively recruited cardiolipin and promoted lipid clustering in the tested reconstituted membranes.
Mitochondrial creatine kinase family → Cardiolipin enrichment and clustering in a membrane source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/19289067.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3880cefa5c138a1e112b50ad2d734e8f38c70da3a545aff80969e7aa1e9a5666", "start_char": 0, "end_char": 1484, "text_sha256": "3880cefa5c138a1e112b50ad2d734e8f38c70da3a545aff80969e7aa1e9a5666"}
experimental_model
Protein–lipid monolayer and mixed-membrane experiments
exposure
Creatine kinase added to cardiolipin or mixed phospholipid films
limitations
Mitochondrial CK family record; the specific human isoform is not assigned from this abstract. Reconstituted membrane experiment; no human outcome.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Mitochondrial creatine kinase in reconstituted lipid systems
plain_language
The enzyme can help organize the membrane lipids around it.
primary_references
[creatine-p19289067] Mitochondrial creatine kinase binding to phospholipid monolayers induces cardiolipin segregation. (2009). https://pubmed.ncbi.nlm.nih.gov/19289067/ DOI: 10.1016/j.bpj.2008.12.3911
tissue_or_cell_type
Synthetic cardiolipin-containing membranes
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 373–384
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein–lipid monolayer and mixed-membrane experiments · source_derived_draft · unverified_draft
### creatine-mtck-cardiolipin Mitochondrial creatine kinase selectively recruited cardiolipin and promoted lipid clustering in the tested reconstituted membranes. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme can help organize the membrane lipids around it. organism: Mitochondrial creatine kinase in reconstituted lipid systems tissue_or_cell_type: Synthetic cardiolipin-containing membranes experimental_model: Protein–lipid monolayer and mixed-membrane experiments limitations: Mitochondrial CK family record; the specific human isoform is not assigned from this abstract. Reconstituted membrane experiment; no human outcome. exposure: Creatine kinase added to cardiolipin or mixed phospholipid films evidence_span: {"source_cache": "artifacts/creatine-research/19289067.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3880cefa5c138a1e112b50ad2d734e8f38c70da3a545aff80969e7aa1e9a5666", "start_char": 0, "end_char": 1484, "text_sha256": "3880cefa5c138a1e112b50ad2d734e8f38c70da3a545aff80969e7aa1e9a5666"} [creatine-p19289067] Mitochondrial creatine kinase binding to phospholipid monolayers induces cardiolipin segregation. (2009). https://pubmed.ncbi.nlm.nih.gov/19289067/ DOI: 10.1016/j.bpj.2008.12.3911
Complete structured claim and evidence
At 2 seconds of stimulation, phosphocreatine depletion was approximately 2.2% in MM-CK-deficient muscle versus 9.7% in wild type.
Mouse muscle creatine kinase / Ckm → Skeletal-muscle phosphocreatine content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/12419710.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e27a7cfa46bbfc4a05cb51ba54832614c64b750471ee2ea564c8232addb4bd68", "start_char": 0, "end_char": 1400, "text_sha256": "e27a7cfa46bbfc4a05cb51ba54832614c64b750471ee2ea564c8232addb4bd68"}
experimental_model
Magnetic-resonance spectroscopy and contraction experiment with kinetic modeling
exposure
5 Hz stimulation, including the first 2 seconds and an 80-second steady state
limitations
Measured metabolite changes are distinguished from model-inferred ADP and oxidative activation; knockout compensation is possible.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Ckm-knockout and wild-type mice
plain_language
Removing the muscle enzyme changed how quickly the phosphate reserve could be used.
primary_references
[creatine-p12419710] Phosphocreatine kinetics at the onset of contractions in skeletal muscle of MM creatine kinase knockout mice. (2002). https://pubmed.ncbi.nlm.nih.gov/12419710/ DOI: 10.1152/ajpcell.00210.2002
tissue_or_cell_type
Gastrocnemius muscle
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 386–397
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Magnetic-resonance spectroscopy and contraction experiment with kinetic modeling · source_derived_draft · unverified_draft
### creatine-ckm-loss-early-pcr At 2 seconds of stimulation, phosphocreatine depletion was approximately 2.2% in MM-CK-deficient muscle versus 9.7% in wild type. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing the muscle enzyme changed how quickly the phosphate reserve could be used. organism: Ckm-knockout and wild-type mice tissue_or_cell_type: Gastrocnemius muscle experimental_model: Magnetic-resonance spectroscopy and contraction experiment with kinetic modeling limitations: Measured metabolite changes are distinguished from model-inferred ADP and oxidative activation; knockout compensation is possible. exposure: 5 Hz stimulation, including the first 2 seconds and an 80-second steady state evidence_span: {"source_cache": "artifacts/creatine-research/12419710.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e27a7cfa46bbfc4a05cb51ba54832614c64b750471ee2ea564c8232addb4bd68", "start_char": 0, "end_char": 1400, "text_sha256": "e27a7cfa46bbfc4a05cb51ba54832614c64b750471ee2ea564c8232addb4bd68"} [creatine-p12419710] Phosphocreatine kinetics at the onset of contractions in skeletal muscle of MM creatine kinase knockout mice. (2002). https://pubmed.ncbi.nlm.nih.gov/12419710/ DOI: 10.1152/ajpcell.00210.2002
Complete structured claim and evidence
Resting PCr/ATP and pH did not differ, and no ATP change was detected at 2 seconds despite altered early phosphocreatine depletion.
Mouse muscle creatine kinase / Ckm → Skeletal-muscle ATP content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/12419710.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e27a7cfa46bbfc4a05cb51ba54832614c64b750471ee2ea564c8232addb4bd68", "start_char": 0, "end_char": 1400, "text_sha256": "e27a7cfa46bbfc4a05cb51ba54832614c64b750471ee2ea564c8232addb4bd68"}
experimental_model
Magnetic-resonance spectroscopy and contraction experiment with kinetic modeling
exposure
5 Hz stimulation, including the first 2 seconds and an 80-second steady state
limitations
Measured metabolite changes are distinguished from model-inferred ADP and oxidative activation; knockout compensation is possible.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Ckm-knockout and wild-type mice
plain_language
A normal resting energy measurement did not guarantee normal rapid buffering.
primary_references
[creatine-p12419710] Phosphocreatine kinetics at the onset of contractions in skeletal muscle of MM creatine kinase knockout mice. (2002). https://pubmed.ncbi.nlm.nih.gov/12419710/ DOI: 10.1152/ajpcell.00210.2002
tissue_or_cell_type
Gastrocnemius muscle
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 399–410
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Magnetic-resonance spectroscopy and contraction experiment with kinetic modeling · source_derived_draft · unverified_draft
### creatine-ckm-loss-resting-markers Resting PCr/ATP and pH did not differ, and no ATP change was detected at 2 seconds despite altered early phosphocreatine depletion. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A normal resting energy measurement did not guarantee normal rapid buffering. organism: Ckm-knockout and wild-type mice tissue_or_cell_type: Gastrocnemius muscle experimental_model: Magnetic-resonance spectroscopy and contraction experiment with kinetic modeling limitations: Measured metabolite changes are distinguished from model-inferred ADP and oxidative activation; knockout compensation is possible. exposure: 5 Hz stimulation, including the first 2 seconds and an 80-second steady state evidence_span: {"source_cache": "artifacts/creatine-research/12419710.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e27a7cfa46bbfc4a05cb51ba54832614c64b750471ee2ea564c8232addb4bd68", "start_char": 0, "end_char": 1400, "text_sha256": "e27a7cfa46bbfc4a05cb51ba54832614c64b750471ee2ea564c8232addb4bd68"} [creatine-p12419710] Phosphocreatine kinetics at the onset of contractions in skeletal muscle of MM creatine kinase knockout mice. (2002). https://pubmed.ncbi.nlm.nih.gov/12419710/ DOI: 10.1152/ajpcell.00210.2002
Complete structured claim and evidence
The increase in muscle total creatine was 60% greater with carbohydrate plus creatine than with creatine alone; urinary creatine loss was lower.
Creatine → Skeletal-muscle total creatine content source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/8944667.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb8718a42f8bcb978e6cb3ec9bed92cb32b819ec2874ed111b82ff7b1bddd270", "start_char": 0, "end_char": 1014, "text_sha256": "bb8718a42f8bcb978e6cb3ec9bed92cb32b819ec2874ed111b82ff7b1bddd270"}
experimental_model
Controlled supplementation and muscle biopsy
exposure
5 g creatine alone or followed by 93 g simple carbohydrate, four times daily for five days
limitations
Large carbohydrate exposure; increased insulin was measured, but mediation was an interpretation. Not a suggested intake regimen.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
24 male participants
plain_language
Carbohydrate changed creatine retention under this loading protocol.
primary_references
[creatine-p8944667] Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans. (1996). https://pubmed.ncbi.nlm.nih.gov/8944667/ DOI: 10.1152/ajpendo.1996.271.5.e821
tissue_or_cell_type
Skeletal muscle, urine and serum
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 425–436
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled supplementation and muscle biopsy · source_derived_draft · unverified_draft
### creatine-carbohydrate-retention The increase in muscle total creatine was 60% greater with carbohydrate plus creatine than with creatine alone; urinary creatine loss was lower. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Carbohydrate changed creatine retention under this loading protocol. organism: 24 male participants tissue_or_cell_type: Skeletal muscle, urine and serum experimental_model: Controlled supplementation and muscle biopsy limitations: Large carbohydrate exposure; increased insulin was measured, but mediation was an interpretation. Not a suggested intake regimen. exposure: 5 g creatine alone or followed by 93 g simple carbohydrate, four times daily for five days evidence_span: {"source_cache": "artifacts/creatine-research/8944667.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb8718a42f8bcb978e6cb3ec9bed92cb32b819ec2874ed111b82ff7b1bddd270", "start_char": 0, "end_char": 1014, "text_sha256": "bb8718a42f8bcb978e6cb3ec9bed92cb32b819ec2874ed111b82ff7b1bddd270"} [creatine-p8944667] Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans. (1996). https://pubmed.ncbi.nlm.nih.gov/8944667/ DOI: 10.1152/ajpendo.1996.271.5.e821
Complete structured claim and evidence
The two higher insulin infusion conditions increased muscle creatine accumulation, by approximately 4.5 and 8.3 mmol/kg dry muscle, during creatine administration.
Insulin → Skeletal-muscle total creatine content source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/9843739.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "405040e7e3d900e06a7f83a43c660ae040e7c95c53c96cd9159a766dee9fdda0", "start_char": 0, "end_char": 1214, "text_sha256": "405040e7e3d900e06a7f83a43c660ae040e7c95c53c96cd9159a766dee9fdda0"}
experimental_model
Insulin-clamp dose experiment with creatine administration
exposure
12.4 g creatine with four insulin infusion conditions
limitations
High physiological or supraphysiological insulin exposure; transport stimulation was inferred, not a direct SLC6A8 molecular assay.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Seven men
plain_language
Higher insulin increased muscle uptake in a controlled infusion experiment.
primary_references
[creatine-p9843739] Stimulatory effect of insulin on creatine accumulation in human skeletal muscle. (1998). https://pubmed.ncbi.nlm.nih.gov/9843739/ DOI: 10.1152/ajpendo.1998.275.6.e974
tissue_or_cell_type
Skeletal muscle and limb circulation
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 438–449
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Insulin-clamp dose experiment with creatine administration · source_derived_draft · unverified_draft
### creatine-insulin-uptake The two higher insulin infusion conditions increased muscle creatine accumulation, by approximately 4.5 and 8.3 mmol/kg dry muscle, during creatine administration. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Higher insulin increased muscle uptake in a controlled infusion experiment. organism: Seven men tissue_or_cell_type: Skeletal muscle and limb circulation experimental_model: Insulin-clamp dose experiment with creatine administration limitations: High physiological or supraphysiological insulin exposure; transport stimulation was inferred, not a direct SLC6A8 molecular assay. exposure: 12.4 g creatine with four insulin infusion conditions evidence_span: {"source_cache": "artifacts/creatine-research/9843739.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "405040e7e3d900e06a7f83a43c660ae040e7c95c53c96cd9159a766dee9fdda0", "start_char": 0, "end_char": 1214, "text_sha256": "405040e7e3d900e06a7f83a43c660ae040e7c95c53c96cd9159a766dee9fdda0"} [creatine-p9843739] Stimulatory effect of insulin on creatine accumulation in human skeletal muscle. (1998). https://pubmed.ncbi.nlm.nih.gov/9843739/ DOI: 10.1152/ajpendo.1998.275.6.e974
Complete structured claim and evidence
Limb blood-flow differences did not explain the insulin-associated increase in muscle creatine accumulation.
Insulin → Skeletal-muscle total creatine content source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/9843739.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "405040e7e3d900e06a7f83a43c660ae040e7c95c53c96cd9159a766dee9fdda0", "start_char": 0, "end_char": 1214, "text_sha256": "405040e7e3d900e06a7f83a43c660ae040e7c95c53c96cd9159a766dee9fdda0"}
experimental_model
Insulin-clamp dose experiment with creatine administration
exposure
12.4 g creatine with four insulin infusion conditions
limitations
High physiological or supraphysiological insulin exposure; transport stimulation was inferred, not a direct SLC6A8 molecular assay.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Seven men
plain_language
Greater delivery through the bloodstream alone did not account for the measured uptake effect.
primary_references
[creatine-p9843739] Stimulatory effect of insulin on creatine accumulation in human skeletal muscle. (1998). https://pubmed.ncbi.nlm.nih.gov/9843739/ DOI: 10.1152/ajpendo.1998.275.6.e974
tissue_or_cell_type
Skeletal muscle and limb circulation
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 451–462
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Insulin-clamp dose experiment with creatine administration · source_derived_draft · unverified_draft
### creatine-insulin-flow-boundary Limb blood-flow differences did not explain the insulin-associated increase in muscle creatine accumulation. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Greater delivery through the bloodstream alone did not account for the measured uptake effect. organism: Seven men tissue_or_cell_type: Skeletal muscle and limb circulation experimental_model: Insulin-clamp dose experiment with creatine administration limitations: High physiological or supraphysiological insulin exposure; transport stimulation was inferred, not a direct SLC6A8 molecular assay. exposure: 12.4 g creatine with four insulin infusion conditions evidence_span: {"source_cache": "artifacts/creatine-research/9843739.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "405040e7e3d900e06a7f83a43c660ae040e7c95c53c96cd9159a766dee9fdda0", "start_char": 0, "end_char": 1214, "text_sha256": "405040e7e3d900e06a7f83a43c660ae040e7c95c53c96cd9159a766dee9fdda0"} [creatine-p9843739] Stimulatory effect of insulin on creatine accumulation in human skeletal muscle. (1998). https://pubmed.ncbi.nlm.nih.gov/9843739/ DOI: 10.1152/ajpendo.1998.275.6.e974
Complete structured claim and evidence
Thermogenic stimulation induced CKB expression in human and mouse adipocytes in the study.
Human creatine kinase B / CKB → Adipocyte futile creatine cycle source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/33597756.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "90b9ec2286a126569876b65a77450dec9f600bf04cb6f3e8c4aeb43edcc34c4b", "start_char": 0, "end_char": 942, "text_sha256": "90b9ec2286a126569876b65a77450dec9f600bf04cb6f3e8c4aeb43edcc34c4b"}
experimental_model
Adipocyte biochemical experiments and conditional gene deletion
exposure
Thermogenic stimulation and adipocyte Ckb loss
limitations
Human cell induction and mouse causal phenotypes are separately scoped; no human weight-loss intervention was tested.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Human and mouse adipocytes; mice for gene deletion
plain_language
The enzyme commonly called brain-type creatine kinase also participates in thermogenic fat.
primary_references
[creatine-p33597756] Creatine kinase B controls futile creatine cycling in thermogenic fat. (2021). https://pubmed.ncbi.nlm.nih.gov/33597756/ DOI: 10.1038/s41586-021-03221-y
tissue_or_cell_type
Thermogenic adipose tissue
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 464–475
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adipocyte biochemical experiments and conditional gene deletion · source_derived_draft · unverified_draft
### creatine-ckb-thermogenic-induction Thermogenic stimulation induced CKB expression in human and mouse adipocytes in the study. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme commonly called brain-type creatine kinase also participates in thermogenic fat. organism: Human and mouse adipocytes; mice for gene deletion tissue_or_cell_type: Thermogenic adipose tissue experimental_model: Adipocyte biochemical experiments and conditional gene deletion limitations: Human cell induction and mouse causal phenotypes are separately scoped; no human weight-loss intervention was tested. exposure: Thermogenic stimulation and adipocyte Ckb loss evidence_span: {"source_cache": "artifacts/creatine-research/33597756.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "90b9ec2286a126569876b65a77450dec9f600bf04cb6f3e8c4aeb43edcc34c4b", "start_char": 0, "end_char": 942, "text_sha256": "90b9ec2286a126569876b65a77450dec9f600bf04cb6f3e8c4aeb43edcc34c4b"} [creatine-p33597756] Creatine kinase B controls futile creatine cycling in thermogenic fat. (2021). https://pubmed.ncbi.nlm.nih.gov/33597756/ DOI: 10.1038/s41586-021-03221-y
Complete structured claim and evidence
CKB trafficked to adipocyte mitochondria through an internal mitochondrial targeting sequence and supported the futile creatine cycle.
Mouse creatine kinase B / Ckb → Adipocyte futile creatine cycle source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/33597756.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "90b9ec2286a126569876b65a77450dec9f600bf04cb6f3e8c4aeb43edcc34c4b", "start_char": 0, "end_char": 942, "text_sha256": "90b9ec2286a126569876b65a77450dec9f600bf04cb6f3e8c4aeb43edcc34c4b"}
experimental_model
Adipocyte biochemical experiments and conditional gene deletion
exposure
Thermogenic stimulation and adipocyte Ckb loss
limitations
Human cell induction and mouse causal phenotypes are separately scoped; no human weight-loss intervention was tested.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Mouse adipocyte mechanistic experiments
plain_language
In fat cells, CKB can move to mitochondria and help run an energy-consuming creatine cycle.
primary_references
[creatine-p33597756] Creatine kinase B controls futile creatine cycling in thermogenic fat. (2021). https://pubmed.ncbi.nlm.nih.gov/33597756/ DOI: 10.1038/s41586-021-03221-y
tissue_or_cell_type
Thermogenic adipose tissue
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 477–488
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adipocyte biochemical experiments and conditional gene deletion · source_derived_draft · unverified_draft
### creatine-ckb-mitochondrial-trafficking CKB trafficked to adipocyte mitochondria through an internal mitochondrial targeting sequence and supported the futile creatine cycle. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: In fat cells, CKB can move to mitochondria and help run an energy-consuming creatine cycle. organism: Mouse adipocyte mechanistic experiments tissue_or_cell_type: Thermogenic adipose tissue experimental_model: Adipocyte biochemical experiments and conditional gene deletion limitations: Human cell induction and mouse causal phenotypes are separately scoped; no human weight-loss intervention was tested. exposure: Thermogenic stimulation and adipocyte Ckb loss evidence_span: {"source_cache": "artifacts/creatine-research/33597756.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "90b9ec2286a126569876b65a77450dec9f600bf04cb6f3e8c4aeb43edcc34c4b", "start_char": 0, "end_char": 942, "text_sha256": "90b9ec2286a126569876b65a77450dec9f600bf04cb6f3e8c4aeb43edcc34c4b"} [creatine-p33597756] Creatine kinase B controls futile creatine cycling in thermogenic fat. (2021). https://pubmed.ncbi.nlm.nih.gov/33597756/ DOI: 10.1038/s41586-021-03221-y
Complete structured claim and evidence
Adipocyte Ckb deletion reduced thermogenic capacity and predisposed mice to obesity and disturbed glucose handling.
Mouse creatine kinase B / Ckb → Heat production and energy expenditure by thermogenic adipocytes source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/33597756.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "90b9ec2286a126569876b65a77450dec9f600bf04cb6f3e8c4aeb43edcc34c4b", "start_char": 0, "end_char": 942, "text_sha256": "90b9ec2286a126569876b65a77450dec9f600bf04cb6f3e8c4aeb43edcc34c4b"}
experimental_model
Adipocyte biochemical experiments and conditional gene deletion
exposure
Thermogenic stimulation and adipocyte Ckb loss
limitations
Human cell induction and mouse causal phenotypes are separately scoped; no human weight-loss intervention was tested.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Mice
plain_language
Removing this enzyme weakened the heat-producing pathway in mice.
primary_references
[creatine-p33597756] Creatine kinase B controls futile creatine cycling in thermogenic fat. (2021). https://pubmed.ncbi.nlm.nih.gov/33597756/ DOI: 10.1038/s41586-021-03221-y
tissue_or_cell_type
Thermogenic adipose tissue
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 490–501
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adipocyte biochemical experiments and conditional gene deletion · source_derived_draft · unverified_draft
### creatine-fat-ckb-loss Adipocyte Ckb deletion reduced thermogenic capacity and predisposed mice to obesity and disturbed glucose handling. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing this enzyme weakened the heat-producing pathway in mice. organism: Mice tissue_or_cell_type: Thermogenic adipose tissue experimental_model: Adipocyte biochemical experiments and conditional gene deletion limitations: Human cell induction and mouse causal phenotypes are separately scoped; no human weight-loss intervention was tested. exposure: Thermogenic stimulation and adipocyte Ckb loss evidence_span: {"source_cache": "artifacts/creatine-research/33597756.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "90b9ec2286a126569876b65a77450dec9f600bf04cb6f3e8c4aeb43edcc34c4b", "start_char": 0, "end_char": 942, "text_sha256": "90b9ec2286a126569876b65a77450dec9f600bf04cb6f3e8c4aeb43edcc34c4b"} [creatine-p33597756] Creatine kinase B controls futile creatine cycling in thermogenic fat. (2021). https://pubmed.ncbi.nlm.nih.gov/33597756/ DOI: 10.1038/s41586-021-03221-y
Complete structured claim and evidence
TNAP inhibition abolished the measured futile creatine cycle in isolated thermogenic-fat mitochondria.
Mouse tissue-nonspecific alkaline phosphatase / Alpl → Adipocyte futile creatine cycle source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/33981039.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "915403423e16b5e0e5db70e99ebc6518e612bc9ef69ceb1e25da3074a8410dca", "start_char": 0, "end_char": 1400, "text_sha256": "915403423e16b5e0e5db70e99ebc6518e612bc9ef69ceb1e25da3074a8410dca"}
experimental_model
Phosphatase biochemistry, mitochondrial inhibition and adipocyte gene deletion
exposure
TNAP inhibition and adipocyte Alpl deletion
limitations
Mouse mechanism; it does not establish that creatine supplements cause weight loss in humans.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Mouse thermogenic adipocytes and mice
plain_language
Blocking phosphate release stopped the measured cycle.
primary_references
[creatine-p33981039] Mitochondrial TNAP controls thermogenesis by hydrolysis of phosphocreatine. (2021). https://pubmed.ncbi.nlm.nih.gov/33981039/ DOI: 10.1038/s41586-021-03533-z
tissue_or_cell_type
Adipocyte mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 516–527
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phosphatase biochemistry, mitochondrial inhibition and adipocyte gene deletion · source_derived_draft · unverified_draft
### creatine-tnap-inhibits-cycle TNAP inhibition abolished the measured futile creatine cycle in isolated thermogenic-fat mitochondria. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blocking phosphate release stopped the measured cycle. organism: Mouse thermogenic adipocytes and mice tissue_or_cell_type: Adipocyte mitochondria experimental_model: Phosphatase biochemistry, mitochondrial inhibition and adipocyte gene deletion limitations: Mouse mechanism; it does not establish that creatine supplements cause weight loss in humans. exposure: TNAP inhibition and adipocyte Alpl deletion evidence_span: {"source_cache": "artifacts/creatine-research/33981039.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "915403423e16b5e0e5db70e99ebc6518e612bc9ef69ceb1e25da3074a8410dca", "start_char": 0, "end_char": 1400, "text_sha256": "915403423e16b5e0e5db70e99ebc6518e612bc9ef69ceb1e25da3074a8410dca"} [creatine-p33981039] Mitochondrial TNAP controls thermogenesis by hydrolysis of phosphocreatine. (2021). https://pubmed.ncbi.nlm.nih.gov/33981039/ DOI: 10.1038/s41586-021-03533-z
Complete structured claim and evidence
Adipocyte Alpl deletion reduced energy expenditure and increased obesity susceptibility without altered feeding or movement.
Mouse tissue-nonspecific alkaline phosphatase / Alpl → Heat production and energy expenditure by thermogenic adipocytes source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/33981039.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "915403423e16b5e0e5db70e99ebc6518e612bc9ef69ceb1e25da3074a8410dca", "start_char": 0, "end_char": 1400, "text_sha256": "915403423e16b5e0e5db70e99ebc6518e612bc9ef69ceb1e25da3074a8410dca"}
experimental_model
Phosphatase biochemistry, mitochondrial inhibition and adipocyte gene deletion
exposure
TNAP inhibition and adipocyte Alpl deletion
limitations
Mouse mechanism; it does not establish that creatine supplements cause weight loss in humans.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Mouse thermogenic adipocytes and mice
plain_language
The lower energy use was not explained by eating more or moving less in these mice.
primary_references
[creatine-p33981039] Mitochondrial TNAP controls thermogenesis by hydrolysis of phosphocreatine. (2021). https://pubmed.ncbi.nlm.nih.gov/33981039/ DOI: 10.1038/s41586-021-03533-z
tissue_or_cell_type
Adipocyte mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 529–540
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phosphatase biochemistry, mitochondrial inhibition and adipocyte gene deletion · source_derived_draft · unverified_draft
### creatine-tnap-fat-loss Adipocyte Alpl deletion reduced energy expenditure and increased obesity susceptibility without altered feeding or movement. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The lower energy use was not explained by eating more or moving less in these mice. organism: Mouse thermogenic adipocytes and mice tissue_or_cell_type: Adipocyte mitochondria experimental_model: Phosphatase biochemistry, mitochondrial inhibition and adipocyte gene deletion limitations: Mouse mechanism; it does not establish that creatine supplements cause weight loss in humans. exposure: TNAP inhibition and adipocyte Alpl deletion evidence_span: {"source_cache": "artifacts/creatine-research/33981039.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "915403423e16b5e0e5db70e99ebc6518e612bc9ef69ceb1e25da3074a8410dca", "start_char": 0, "end_char": 1400, "text_sha256": "915403423e16b5e0e5db70e99ebc6518e612bc9ef69ceb1e25da3074a8410dca"} [creatine-p33981039] Mitochondrial TNAP controls thermogenesis by hydrolysis of phosphocreatine. (2021). https://pubmed.ncbi.nlm.nih.gov/33981039/ DOI: 10.1038/s41586-021-03533-z
Complete structured claim and evidence
Glycerol bound a TNAP surface pocket distant from the active site and enhanced TNAP activity.
Glycerol → Tissue-nonspecific alkaline phosphatase ALPL / TNAP source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/42020733.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd", "start_char": 0, "end_char": 1255, "text_sha256": "232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd"}
experimental_model
Structural, biochemical, cellular, physiological and human genetic experiments
exposure
Glycerol binding and glycerol-pocket disruption
limitations
Published 2026; model-specific thermogenesis and mineralization findings do not establish a dietary glycerol or creatine treatment for bone disease.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
TNAP experimental systems, mice and human variant analyses
plain_language
A molecule made during fat breakdown can adjust the phosphatase that participates in creatine cycling.
primary_references
[creatine-p42020733] Glycerol-driven TNAP activation in thermogenesis and mineralization. (2026). https://pubmed.ncbi.nlm.nih.gov/42020733/ DOI: 10.1038/s41586-026-10396-9
tissue_or_cell_type
Thermogenic adipocytes, osteoblasts and purified protein
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 542–553
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Structural, biochemical, cellular, physiological and human genetic experiments · source_derived_draft · unverified_draft
### creatine-glycerol-tnap Glycerol bound a TNAP surface pocket distant from the active site and enhanced TNAP activity. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A molecule made during fat breakdown can adjust the phosphatase that participates in creatine cycling. organism: TNAP experimental systems, mice and human variant analyses tissue_or_cell_type: Thermogenic adipocytes, osteoblasts and purified protein experimental_model: Structural, biochemical, cellular, physiological and human genetic experiments limitations: Published 2026; model-specific thermogenesis and mineralization findings do not establish a dietary glycerol or creatine treatment for bone disease. exposure: Glycerol binding and glycerol-pocket disruption evidence_span: {"source_cache": "artifacts/creatine-research/42020733.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd", "start_char": 0, "end_char": 1255, "text_sha256": "232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd"} [creatine-p42020733] Glycerol-driven TNAP activation in thermogenesis and mineralization. (2026). https://pubmed.ncbi.nlm.nih.gov/42020733/ DOI: 10.1038/s41586-026-10396-9
Complete structured claim and evidence
The TNAP glycerol pocket was required for TNAP-driven thermogenesis through the futile creatine cycle in the tested systems.
Tissue-nonspecific alkaline phosphatase ALPL / TNAP → Heat production and energy expenditure by thermogenic adipocytes source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/42020733.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd", "start_char": 0, "end_char": 1255, "text_sha256": "232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd"}
experimental_model
Structural, biochemical, cellular, physiological and human genetic experiments
exposure
Glycerol binding and glycerol-pocket disruption
limitations
Published 2026; model-specific thermogenesis and mineralization findings do not establish a dietary glycerol or creatine treatment for bone disease.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
TNAP experimental systems, mice and human variant analyses
plain_language
The same phosphatase needs a regulatory pocket to support this heat-producing pathway.
primary_references
[creatine-p42020733] Glycerol-driven TNAP activation in thermogenesis and mineralization. (2026). https://pubmed.ncbi.nlm.nih.gov/42020733/ DOI: 10.1038/s41586-026-10396-9
tissue_or_cell_type
Thermogenic adipocytes, osteoblasts and purified protein
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 555–566
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Structural, biochemical, cellular, physiological and human genetic experiments · source_derived_draft · unverified_draft
### creatine-tnap-pocket-thermogenesis The TNAP glycerol pocket was required for TNAP-driven thermogenesis through the futile creatine cycle in the tested systems. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same phosphatase needs a regulatory pocket to support this heat-producing pathway. organism: TNAP experimental systems, mice and human variant analyses tissue_or_cell_type: Thermogenic adipocytes, osteoblasts and purified protein experimental_model: Structural, biochemical, cellular, physiological and human genetic experiments limitations: Published 2026; model-specific thermogenesis and mineralization findings do not establish a dietary glycerol or creatine treatment for bone disease. exposure: Glycerol binding and glycerol-pocket disruption evidence_span: {"source_cache": "artifacts/creatine-research/42020733.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd", "start_char": 0, "end_char": 1255, "text_sha256": "232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd"} [creatine-p42020733] Glycerol-driven TNAP activation in thermogenesis and mineralization. (2026). https://pubmed.ncbi.nlm.nih.gov/42020733/ DOI: 10.1038/s41586-026-10396-9
Complete structured claim and evidence
Human missense variants in the glycerol pocket reduced TNAP-dependent mineralization in vitro and were associated with lower alkaline phosphatase activity and bone mineral density.
Tissue-nonspecific alkaline phosphatase ALPL / TNAP → Osteoblast mineralization source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/42020733.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd", "start_char": 0, "end_char": 1255, "text_sha256": "232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd"}
experimental_model
Structural, biochemical, cellular, physiological and human genetic experiments
exposure
Glycerol binding and glycerol-pocket disruption
limitations
Published 2026; model-specific thermogenesis and mineralization findings do not establish a dietary glycerol or creatine treatment for bone disease.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
TNAP experimental systems, mice and human variant analyses
plain_language
A shared protein connects the fat-energy pathway to bone biology; this is not evidence that creatine repairs those variants.
primary_references
[creatine-p42020733] Glycerol-driven TNAP activation in thermogenesis and mineralization. (2026). https://pubmed.ncbi.nlm.nih.gov/42020733/ DOI: 10.1038/s41586-026-10396-9
tissue_or_cell_type
Thermogenic adipocytes, osteoblasts and purified protein
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 568–579
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Structural, biochemical, cellular, physiological and human genetic experiments · source_derived_draft · unverified_draft
### creatine-tnap-pocket-bone Human missense variants in the glycerol pocket reduced TNAP-dependent mineralization in vitro and were associated with lower alkaline phosphatase activity and bone mineral density. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A shared protein connects the fat-energy pathway to bone biology; this is not evidence that creatine repairs those variants. organism: TNAP experimental systems, mice and human variant analyses tissue_or_cell_type: Thermogenic adipocytes, osteoblasts and purified protein experimental_model: Structural, biochemical, cellular, physiological and human genetic experiments limitations: Published 2026; model-specific thermogenesis and mineralization findings do not establish a dietary glycerol or creatine treatment for bone disease. exposure: Glycerol binding and glycerol-pocket disruption evidence_span: {"source_cache": "artifacts/creatine-research/42020733.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd", "start_char": 0, "end_char": 1255, "text_sha256": "232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd"} [creatine-p42020733] Glycerol-driven TNAP activation in thermogenesis and mineralization. (2026). https://pubmed.ncbi.nlm.nih.gov/42020733/ DOI: 10.1038/s41586-026-10396-9
Complete structured claim and evidence
Loss of Slc6a8 impaired CD8 T-cell antitumor immunity in the studied mouse models.
Mouse creatine transporter / Slc6a8 → Antitumor T-cell function in mouse models source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/31628186.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2547f09774244dc13d8bd95950b9b313b7fa625436ab778bb52913a64f2ae458", "start_char": 0, "end_char": 1076, "text_sha256": "2547f09774244dc13d8bd95950b9b313b7fa625436ab778bb52913a64f2ae458"}
experimental_model
Transporter-deficient T cells, tumor models and supplementation experiments
exposure
Slc6a8 deletion; creatine administration with or without checkpoint blockade
limitations
Preclinical tumor immunity; no human cancer efficacy or universal tumor effect is inferred.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Mice
plain_language
Having creatine available outside cells did not replace the missing transporter.
primary_references
[creatine-p31628186] Creatine uptake regulates CD8 T cell antitumor immunity. (2019). https://pubmed.ncbi.nlm.nih.gov/31628186/ DOI: 10.1084/jem.20182044
tissue_or_cell_type
CD8 T cells and transplanted tumor models
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 581–592
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter-deficient T cells, tumor models and supplementation experiments · source_derived_draft · unverified_draft
### creatine-tumor-transporter-loss Loss of Slc6a8 impaired CD8 T-cell antitumor immunity in the studied mouse models. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Having creatine available outside cells did not replace the missing transporter. organism: Mice tissue_or_cell_type: CD8 T cells and transplanted tumor models experimental_model: Transporter-deficient T cells, tumor models and supplementation experiments limitations: Preclinical tumor immunity; no human cancer efficacy or universal tumor effect is inferred. exposure: Slc6a8 deletion; creatine administration with or without checkpoint blockade evidence_span: {"source_cache": "artifacts/creatine-research/31628186.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2547f09774244dc13d8bd95950b9b313b7fa625436ab778bb52913a64f2ae458", "start_char": 0, "end_char": 1076, "text_sha256": "2547f09774244dc13d8bd95950b9b313b7fa625436ab778bb52913a64f2ae458"} [creatine-p31628186] Creatine uptake regulates CD8 T cell antitumor immunity. (2019). https://pubmed.ncbi.nlm.nih.gov/31628186/ DOI: 10.1084/jem.20182044
Complete structured claim and evidence
Creatine supplementation suppressed tumor growth in the tested mouse models and enhanced the effects of PD-1/PD-L1 checkpoint blockade.
Creatine → Antitumor T-cell function in mouse models source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/31628186.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2547f09774244dc13d8bd95950b9b313b7fa625436ab778bb52913a64f2ae458", "start_char": 0, "end_char": 1076, "text_sha256": "2547f09774244dc13d8bd95950b9b313b7fa625436ab778bb52913a64f2ae458"}
experimental_model
Transporter-deficient T cells, tumor models and supplementation experiments
exposure
Slc6a8 deletion; creatine administration with or without checkpoint blockade
limitations
Preclinical tumor immunity; no human cancer efficacy or universal tumor effect is inferred.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Mice
plain_language
Creatine helped in these mouse immune experiments; benefit for people with cancer was not established.
primary_references
[creatine-p31628186] Creatine uptake regulates CD8 T cell antitumor immunity. (2019). https://pubmed.ncbi.nlm.nih.gov/31628186/ DOI: 10.1084/jem.20182044
tissue_or_cell_type
CD8 T cells and transplanted tumor models
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 594–605
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter-deficient T cells, tumor models and supplementation experiments · source_derived_draft · unverified_draft
### creatine-mouse-tumor-supplement Creatine supplementation suppressed tumor growth in the tested mouse models and enhanced the effects of PD-1/PD-L1 checkpoint blockade. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Creatine helped in these mouse immune experiments; benefit for people with cancer was not established. organism: Mice tissue_or_cell_type: CD8 T cells and transplanted tumor models experimental_model: Transporter-deficient T cells, tumor models and supplementation experiments limitations: Preclinical tumor immunity; no human cancer efficacy or universal tumor effect is inferred. exposure: Slc6a8 deletion; creatine administration with or without checkpoint blockade evidence_span: {"source_cache": "artifacts/creatine-research/31628186.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2547f09774244dc13d8bd95950b9b313b7fa625436ab778bb52913a64f2ae458", "start_char": 0, "end_char": 1076, "text_sha256": "2547f09774244dc13d8bd95950b9b313b7fa625436ab778bb52913a64f2ae458"} [creatine-p31628186] Creatine uptake regulates CD8 T cell antitumor immunity. (2019). https://pubmed.ncbi.nlm.nih.gov/31628186/ DOI: 10.1084/jem.20182044
Complete structured claim and evidence
Loss of either Ckb or Slc6a8 compromised CD8 T-cell expansion in response to infection.
Mouse creatine kinase B / Ckb → CD8 T-cell expansion in response to infection source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/35235777.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81515a03473f41d52c2e13de56ac9b13ea5cd813e288d166159d517f9855958", "start_char": 0, "end_char": 1025, "text_sha256": "a81515a03473f41d52c2e13de56ac9b13ea5cd813e288d166159d517f9855958"}
experimental_model
Transporter or kinase loss, T-cell homeostasis and infection experiments
exposure
Slc6a8 or Ckb deletion
limitations
The study distinguishes TCR–mTORC1 signaling from whole-cell adenylate energy charge; it does not demonstrate clinical immune benefits of supplements.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Mice
plain_language
Both the transporter and the phosphate-transfer enzyme mattered for the immune response.
primary_references
[creatine-p35235777] Creatine transport and creatine kinase activity is required for CD8+ T cell immunity. (2022). https://pubmed.ncbi.nlm.nih.gov/35235777/ DOI: 10.1016/j.celrep.2022.110446
tissue_or_cell_type
Naive and activated CD8 T cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 607–618
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter or kinase loss, T-cell homeostasis and infection experiments · source_derived_draft · unverified_draft
### creatine-tcell-expansion-loss Loss of either Ckb or Slc6a8 compromised CD8 T-cell expansion in response to infection. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Both the transporter and the phosphate-transfer enzyme mattered for the immune response. organism: Mice tissue_or_cell_type: Naive and activated CD8 T cells experimental_model: Transporter or kinase loss, T-cell homeostasis and infection experiments limitations: The study distinguishes TCR–mTORC1 signaling from whole-cell adenylate energy charge; it does not demonstrate clinical immune benefits of supplements. exposure: Slc6a8 or Ckb deletion evidence_span: {"source_cache": "artifacts/creatine-research/35235777.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81515a03473f41d52c2e13de56ac9b13ea5cd813e288d166159d517f9855958", "start_char": 0, "end_char": 1025, "text_sha256": "a81515a03473f41d52c2e13de56ac9b13ea5cd813e288d166159d517f9855958"} [creatine-p35235777] Creatine transport and creatine kinase activity is required for CD8+ T cell immunity. (2022). https://pubmed.ncbi.nlm.nih.gov/35235777/ DOI: 10.1016/j.celrep.2022.110446
Complete structured claim and evidence
Ckb or Slc6a8 loss weakened TCR-mediated mTORC1 activation required for CD8 T-cell expansion.
Mouse creatine kinase B / Ckb → Mechanistic target of rapamycin complex 1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/35235777.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81515a03473f41d52c2e13de56ac9b13ea5cd813e288d166159d517f9855958", "start_char": 0, "end_char": 1025, "text_sha256": "a81515a03473f41d52c2e13de56ac9b13ea5cd813e288d166159d517f9855958"}
experimental_model
Transporter or kinase loss, T-cell homeostasis and infection experiments
exposure
Slc6a8 or Ckb deletion
limitations
The study distinguishes TCR–mTORC1 signaling from whole-cell adenylate energy charge; it does not demonstrate clinical immune benefits of supplements.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Mice
plain_language
The pathway also affected the signal telling T cells to expand.
primary_references
[creatine-p35235777] Creatine transport and creatine kinase activity is required for CD8+ T cell immunity. (2022). https://pubmed.ncbi.nlm.nih.gov/35235777/ DOI: 10.1016/j.celrep.2022.110446
tissue_or_cell_type
Naive and activated CD8 T cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 620–631
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter or kinase loss, T-cell homeostasis and infection experiments · source_derived_draft · unverified_draft
### creatine-tcell-mtor-loss Ckb or Slc6a8 loss weakened TCR-mediated mTORC1 activation required for CD8 T-cell expansion. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pathway also affected the signal telling T cells to expand. organism: Mice tissue_or_cell_type: Naive and activated CD8 T cells experimental_model: Transporter or kinase loss, T-cell homeostasis and infection experiments limitations: The study distinguishes TCR–mTORC1 signaling from whole-cell adenylate energy charge; it does not demonstrate clinical immune benefits of supplements. exposure: Slc6a8 or Ckb deletion evidence_span: {"source_cache": "artifacts/creatine-research/35235777.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81515a03473f41d52c2e13de56ac9b13ea5cd813e288d166159d517f9855958", "start_char": 0, "end_char": 1025, "text_sha256": "a81515a03473f41d52c2e13de56ac9b13ea5cd813e288d166159d517f9855958"} [creatine-p35235777] Creatine transport and creatine kinase activity is required for CD8+ T cell immunity. (2022). https://pubmed.ncbi.nlm.nih.gov/35235777/ DOI: 10.1016/j.celrep.2022.110446
Complete structured claim and evidence
Ckb or Slc6a8 loss impaired T-cell function without changing global adenylate energy charge in the study.
Mouse creatine kinase B / Ckb → T-cell adenylate energy charge source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/35235777.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81515a03473f41d52c2e13de56ac9b13ea5cd813e288d166159d517f9855958", "start_char": 0, "end_char": 1025, "text_sha256": "a81515a03473f41d52c2e13de56ac9b13ea5cd813e288d166159d517f9855958"}
experimental_model
Transporter or kinase loss, T-cell homeostasis and infection experiments
exposure
Slc6a8 or Ckb deletion
limitations
The study distinguishes TCR–mTORC1 signaling from whole-cell adenylate energy charge; it does not demonstrate clinical immune benefits of supplements.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Mice
plain_language
The observed signaling defect could not be reduced to a simple fall in the cell-wide energy measurement.
primary_references
[creatine-p35235777] Creatine transport and creatine kinase activity is required for CD8+ T cell immunity. (2022). https://pubmed.ncbi.nlm.nih.gov/35235777/ DOI: 10.1016/j.celrep.2022.110446
tissue_or_cell_type
Naive and activated CD8 T cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 633–644
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter or kinase loss, T-cell homeostasis and infection experiments · source_derived_draft · unverified_draft
### creatine-tcell-energy-charge Ckb or Slc6a8 loss impaired T-cell function without changing global adenylate energy charge in the study. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The observed signaling defect could not be reduced to a simple fall in the cell-wide energy measurement. organism: Mice tissue_or_cell_type: Naive and activated CD8 T cells experimental_model: Transporter or kinase loss, T-cell homeostasis and infection experiments limitations: The study distinguishes TCR–mTORC1 signaling from whole-cell adenylate energy charge; it does not demonstrate clinical immune benefits of supplements. exposure: Slc6a8 or Ckb deletion evidence_span: {"source_cache": "artifacts/creatine-research/35235777.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a81515a03473f41d52c2e13de56ac9b13ea5cd813e288d166159d517f9855958", "start_char": 0, "end_char": 1025, "text_sha256": "a81515a03473f41d52c2e13de56ac9b13ea5cd813e288d166159d517f9855958"} [creatine-p35235777] Creatine transport and creatine kinase activity is required for CD8+ T cell immunity. (2022). https://pubmed.ncbi.nlm.nih.gov/35235777/ DOI: 10.1016/j.celrep.2022.110446
Complete structured claim and evidence
CRT loss impaired epithelial barrier formation and wound healing; transporter-deficient organoids also had reduced barrier function.
Human creatine transporter CRT / SLC6A8 → Intestinal epithelial barrier integrity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/32433978.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1733708b77e75d099fa25665b9b9a9aa0af72143c985b6f0f2b931fb8f4c0887", "start_char": 0, "end_char": 2283, "text_sha256": "1733708b77e75d099fa25665b9b9a9aa0af72143c985b6f0f2b931fb8f4c0887"}
experimental_model
Transporter manipulation, intestinal organoids and human biopsy comparison
exposure
CRT knockdown/overexpression; transporter-deficient organoids; 30 Crohn disease, 27 ulcerative colitis and 30 control biopsies
limitations
Causal epithelial experiments and observational human expression findings are distinct; no human creatine treatment outcome was tested.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Human T84 cells, mouse organoids and human IBD biopsies
plain_language
Intestinal cells needed the transporter to maintain their barrier in these experiments.
primary_references
[creatine-p32433978] Creatine Transporter, Reduced in Colon Tissues From Patients With Inflammatory Bowel Diseases, Regulates Energy Balance in Intestinal Epithelial Cells, Epithelial Integrity, and Barrier Function. (2020). https://pubmed.ncbi.nlm.nih.gov/32433978/ DOI: 10.1053/j.gastro.2020.05.033
tissue_or_cell_type
Intestinal epithelium and tight junctions
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 646–657
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter manipulation, intestinal organoids and human biopsy comparison · source_derived_draft · unverified_draft
### creatine-gut-transporter-barrier CRT loss impaired epithelial barrier formation and wound healing; transporter-deficient organoids also had reduced barrier function. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Intestinal cells needed the transporter to maintain their barrier in these experiments. organism: Human T84 cells, mouse organoids and human IBD biopsies tissue_or_cell_type: Intestinal epithelium and tight junctions experimental_model: Transporter manipulation, intestinal organoids and human biopsy comparison limitations: Causal epithelial experiments and observational human expression findings are distinct; no human creatine treatment outcome was tested. exposure: CRT knockdown/overexpression; transporter-deficient organoids; 30 Crohn disease, 27 ulcerative colitis and 30 control biopsies evidence_span: {"source_cache": "artifacts/creatine-research/32433978.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1733708b77e75d099fa25665b9b9a9aa0af72143c985b6f0f2b931fb8f4c0887", "start_char": 0, "end_char": 2283, "text_sha256": "1733708b77e75d099fa25665b9b9a9aa0af72143c985b6f0f2b931fb8f4c0887"} [creatine-p32433978] Creatine Transporter, Reduced in Colon Tissues From Patients With Inflammatory Bowel Diseases, Regulates Energy Balance in Intestinal Epithelial Cells, Epithelial Integrity, and Barrier Function. (2020). https://pubmed.ncbi.nlm.nih.gov/32433978/ DOI: 10.1053/j.gastro.2020.05.033
Complete structured claim and evidence
CRT loss increased epithelial glycolytic stress and was accompanied by actin mislocalization and leaky junctions.
Human creatine transporter CRT / SLC6A8 → Intestinal epithelial glycolytic stress source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/32433978.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1733708b77e75d099fa25665b9b9a9aa0af72143c985b6f0f2b931fb8f4c0887", "start_char": 0, "end_char": 2283, "text_sha256": "1733708b77e75d099fa25665b9b9a9aa0af72143c985b6f0f2b931fb8f4c0887"}
experimental_model
Transporter manipulation, intestinal organoids and human biopsy comparison
exposure
CRT knockdown/overexpression; transporter-deficient organoids; 30 Crohn disease, 27 ulcerative colitis and 30 control biopsies
limitations
Causal epithelial experiments and observational human expression findings are distinct; no human creatine treatment outcome was tested.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Human T84 cells, mouse organoids and human IBD biopsies
plain_language
The transporter defect changed both energy handling and the cell structures that seal the barrier.
primary_references
[creatine-p32433978] Creatine Transporter, Reduced in Colon Tissues From Patients With Inflammatory Bowel Diseases, Regulates Energy Balance in Intestinal Epithelial Cells, Epithelial Integrity, and Barrier Function. (2020). https://pubmed.ncbi.nlm.nih.gov/32433978/ DOI: 10.1053/j.gastro.2020.05.033
tissue_or_cell_type
Intestinal epithelium and tight junctions
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 659–670
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter manipulation, intestinal organoids and human biopsy comparison · source_derived_draft · unverified_draft
### creatine-gut-transporter-stress CRT loss increased epithelial glycolytic stress and was accompanied by actin mislocalization and leaky junctions. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The transporter defect changed both energy handling and the cell structures that seal the barrier. organism: Human T84 cells, mouse organoids and human IBD biopsies tissue_or_cell_type: Intestinal epithelium and tight junctions experimental_model: Transporter manipulation, intestinal organoids and human biopsy comparison limitations: Causal epithelial experiments and observational human expression findings are distinct; no human creatine treatment outcome was tested. exposure: CRT knockdown/overexpression; transporter-deficient organoids; 30 Crohn disease, 27 ulcerative colitis and 30 control biopsies evidence_span: {"source_cache": "artifacts/creatine-research/32433978.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1733708b77e75d099fa25665b9b9a9aa0af72143c985b6f0f2b931fb8f4c0887", "start_char": 0, "end_char": 2283, "text_sha256": "1733708b77e75d099fa25665b9b9a9aa0af72143c985b6f0f2b931fb8f4c0887"} [creatine-p32433978] Creatine Transporter, Reduced in Colon Tissues From Patients With Inflammatory Bowel Diseases, Regulates Energy Balance in Intestinal Epithelial Cells, Epithelial Integrity, and Barrier Function. (2020). https://pubmed.ncbi.nlm.nih.gov/32433978/ DOI: 10.1053/j.gastro.2020.05.033
Complete structured claim and evidence
Intestinal CRT transcript expression was lower in the Crohn disease and ulcerative colitis biopsy groups than in controls.
Human creatine transporter CRT / SLC6A8 → Intestinal creatine transporter expression source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/32433978.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1733708b77e75d099fa25665b9b9a9aa0af72143c985b6f0f2b931fb8f4c0887", "start_char": 0, "end_char": 2283, "text_sha256": "1733708b77e75d099fa25665b9b9a9aa0af72143c985b6f0f2b931fb8f4c0887"}
experimental_model
Transporter manipulation, intestinal organoids and human biopsy comparison
exposure
CRT knockdown/overexpression; transporter-deficient organoids; 30 Crohn disease, 27 ulcerative colitis and 30 control biopsies
limitations
Causal epithelial experiments and observational human expression findings are distinct; no human creatine treatment outcome was tested.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Humans
plain_language
The human tissue comparison found an association; it did not show that reduced creatine intake caused bowel disease.
primary_references
[creatine-p32433978] Creatine Transporter, Reduced in Colon Tissues From Patients With Inflammatory Bowel Diseases, Regulates Energy Balance in Intestinal Epithelial Cells, Epithelial Integrity, and Barrier Function. (2020). https://pubmed.ncbi.nlm.nih.gov/32433978/ DOI: 10.1053/j.gastro.2020.05.033
tissue_or_cell_type
Intestinal biopsies
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 672–683
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter manipulation, intestinal organoids and human biopsy comparison · source_derived_draft · unverified_draft
### creatine-ibd-crt-expression Intestinal CRT transcript expression was lower in the Crohn disease and ulcerative colitis biopsy groups than in controls. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The human tissue comparison found an association; it did not show that reduced creatine intake caused bowel disease. organism: Humans tissue_or_cell_type: Intestinal biopsies experimental_model: Transporter manipulation, intestinal organoids and human biopsy comparison limitations: Causal epithelial experiments and observational human expression findings are distinct; no human creatine treatment outcome was tested. exposure: CRT knockdown/overexpression; transporter-deficient organoids; 30 Crohn disease, 27 ulcerative colitis and 30 control biopsies evidence_span: {"source_cache": "artifacts/creatine-research/32433978.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1733708b77e75d099fa25665b9b9a9aa0af72143c985b6f0f2b931fb8f4c0887", "start_char": 0, "end_char": 2283, "text_sha256": "1733708b77e75d099fa25665b9b9a9aa0af72143c985b6f0f2b931fb8f4c0887"} [creatine-p32433978] Creatine Transporter, Reduced in Colon Tissues From Patients With Inflammatory Bowel Diseases, Regulates Energy Balance in Intestinal Epithelial Cells, Epithelial Integrity, and Barrier Function. (2020). https://pubmed.ncbi.nlm.nih.gov/32433978/ DOI: 10.1053/j.gastro.2020.05.033
Complete structured claim and evidence
Guanidinoacetate feeding raised plasma homocysteine by approximately 50% in the rat experiment.
Guanidinoacetate → Homocysteine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/11595668.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0", "start_char": 0, "end_char": 1687, "text_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0"}
experimental_model
Two-week feeding and isolated hepatocyte experiments
exposure
Guanidinoacetate or creatine feeding; guanidinoacetate plus methionine in hepatocytes
limitations
Animal methyl-demand experiment; effect sizes do not predict human homocysteine responses.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Rats
plain_language
Providing more precursor increased the load on the methylation step in these rats.
primary_references
[creatine-p11595668] Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. (2001). https://pubmed.ncbi.nlm.nih.gov/11595668/ DOI: 10.1152/ajpendo.2001.281.5.e1095
tissue_or_cell_type
Plasma and liver cells
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 685–696
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-week feeding and isolated hepatocyte experiments · source_derived_draft · unverified_draft
### creatine-gaa-homocysteine Guanidinoacetate feeding raised plasma homocysteine by approximately 50% in the rat experiment. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing more precursor increased the load on the methylation step in these rats. organism: Rats tissue_or_cell_type: Plasma and liver cells experimental_model: Two-week feeding and isolated hepatocyte experiments limitations: Animal methyl-demand experiment; effect sizes do not predict human homocysteine responses. exposure: Guanidinoacetate or creatine feeding; guanidinoacetate plus methionine in hepatocytes evidence_span: {"source_cache": "artifacts/creatine-research/11595668.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0", "start_char": 0, "end_char": 1687, "text_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0"} [creatine-p11595668] Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. (2001). https://pubmed.ncbi.nlm.nih.gov/11595668/ DOI: 10.1152/ajpendo.2001.281.5.e1095
Complete structured claim and evidence
Creatine feeding lowered plasma homocysteine by approximately 25% in the rat experiment.
Creatine → Homocysteine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/11595668.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0", "start_char": 0, "end_char": 1687, "text_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0"}
experimental_model
Two-week feeding and isolated hepatocyte experiments
exposure
Guanidinoacetate or creatine feeding; guanidinoacetate plus methionine in hepatocytes
limitations
Animal methyl-demand experiment; effect sizes do not predict human homocysteine responses.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Rats
plain_language
Supplying the finished product reduced a methylation-related blood marker in this animal setting.
primary_references
[creatine-p11595668] Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. (2001). https://pubmed.ncbi.nlm.nih.gov/11595668/ DOI: 10.1152/ajpendo.2001.281.5.e1095
tissue_or_cell_type
Plasma and liver cells
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 698–709
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-week feeding and isolated hepatocyte experiments · source_derived_draft · unverified_draft
### creatine-creatine-rat-homocysteine Creatine feeding lowered plasma homocysteine by approximately 25% in the rat experiment. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Supplying the finished product reduced a methylation-related blood marker in this animal setting. organism: Rats tissue_or_cell_type: Plasma and liver cells experimental_model: Two-week feeding and isolated hepatocyte experiments limitations: Animal methyl-demand experiment; effect sizes do not predict human homocysteine responses. exposure: Guanidinoacetate or creatine feeding; guanidinoacetate plus methionine in hepatocytes evidence_span: {"source_cache": "artifacts/creatine-research/11595668.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0", "start_char": 0, "end_char": 1687, "text_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0"} [creatine-p11595668] Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. (2001). https://pubmed.ncbi.nlm.nih.gov/11595668/ DOI: 10.1152/ajpendo.2001.281.5.e1095
Complete structured claim and evidence
Guanidinoacetate increased homocysteine export from methionine-supplied rat hepatocytes, whereas added creatine did not.
Guanidinoacetate → Homocysteine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/11595668.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0", "start_char": 0, "end_char": 1687, "text_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0"}
experimental_model
Two-week feeding and isolated hepatocyte experiments
exposure
Guanidinoacetate or creatine feeding; guanidinoacetate plus methionine in hepatocytes
limitations
Animal methyl-demand experiment; effect sizes do not predict human homocysteine responses.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Rats
plain_language
The precursor and finished creatine were metabolically different in liver cells.
primary_references
[creatine-p11595668] Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. (2001). https://pubmed.ncbi.nlm.nih.gov/11595668/ DOI: 10.1152/ajpendo.2001.281.5.e1095
tissue_or_cell_type
Plasma and liver cells
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 711–722
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-week feeding and isolated hepatocyte experiments · source_derived_draft · unverified_draft
### creatine-gaa-hepatocyte-hcy-export Guanidinoacetate increased homocysteine export from methionine-supplied rat hepatocytes, whereas added creatine did not. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The precursor and finished creatine were metabolically different in liver cells. organism: Rats tissue_or_cell_type: Plasma and liver cells experimental_model: Two-week feeding and isolated hepatocyte experiments limitations: Animal methyl-demand experiment; effect sizes do not predict human homocysteine responses. exposure: Guanidinoacetate or creatine feeding; guanidinoacetate plus methionine in hepatocytes evidence_span: {"source_cache": "artifacts/creatine-research/11595668.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0", "start_char": 0, "end_char": 1687, "text_sha256": "b195a8b17815bf7d9223831374e2f85ae2f90d8d74117ad7aa8d94af7a9e94b0"} [creatine-p11595668] Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. (2001). https://pubmed.ncbi.nlm.nih.gov/11595668/ DOI: 10.1152/ajpendo.2001.281.5.e1095
Complete structured claim and evidence
Plasma guanidinoacetate declined 10.6% with creatine versus a 3.7% rise with placebo over 12 weeks.
Creatine → Plasma guanidinoacetate concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/26311810.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "055a97365d5a6d864e78eafcfa4a73bc8c425e240487580796a443cf8ef33a04", "start_char": 0, "end_char": 2160, "text_sha256": "055a97365d5a6d864e78eafcfa4a73bc8c425e240487580796a443cf8ef33a04"}
experimental_model
Twelve-week randomized placebo-controlled trial
exposure
Creatine 3 g/day, folic acid 400 micrograms/day, both, or placebo; analyzed groups 101, 153, 103 and 101 respectively
limitations
Group-average effects and exploratory within-person associations are distinct. No general claim of restored methylation or reduced disease risk.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Bangladeshi adults
plain_language
The human trial detected feedback on precursor production.
primary_references
[creatine-p26311810] Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial. (2015). https://pubmed.ncbi.nlm.nih.gov/26311810/ DOI: 10.3945/jn.115.216739
tissue_or_cell_type
Plasma metabolites
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 724–735
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve-week randomized placebo-controlled trial · source_derived_draft · unverified_draft
### creatine-human-gaa-feedback Plasma guanidinoacetate declined 10.6% with creatine versus a 3.7% rise with placebo over 12 weeks. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The human trial detected feedback on precursor production. organism: Bangladeshi adults tissue_or_cell_type: Plasma metabolites experimental_model: Twelve-week randomized placebo-controlled trial limitations: Group-average effects and exploratory within-person associations are distinct. No general claim of restored methylation or reduced disease risk. exposure: Creatine 3 g/day, folic acid 400 micrograms/day, both, or placebo; analyzed groups 101, 153, 103 and 101 respectively evidence_span: {"source_cache": "artifacts/creatine-research/26311810.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "055a97365d5a6d864e78eafcfa4a73bc8c425e240487580796a443cf8ef33a04", "start_char": 0, "end_char": 2160, "text_sha256": "055a97365d5a6d864e78eafcfa4a73bc8c425e240487580796a443cf8ef33a04"} [creatine-p26311810] Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial. (2015). https://pubmed.ncbi.nlm.nih.gov/26311810/ DOI: 10.3945/jn.115.216739
Complete structured claim and evidence
Homocysteine fell 23.4% with folic acid alone and 21.0% with creatine plus folic acid; the difference was not significant (P=0.41).
Folic acid → Homocysteine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/26311810.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "055a97365d5a6d864e78eafcfa4a73bc8c425e240487580796a443cf8ef33a04", "start_char": 0, "end_char": 2160, "text_sha256": "055a97365d5a6d864e78eafcfa4a73bc8c425e240487580796a443cf8ef33a04"}
experimental_model
Twelve-week randomized placebo-controlled trial
exposure
Creatine 3 g/day, folic acid 400 micrograms/day, both, or placebo; analyzed groups 101, 153, 103 and 101 respectively
limitations
Group-average effects and exploratory within-person associations are distinct. No general claim of restored methylation or reduced disease risk.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Bangladeshi adults
plain_language
Adding creatine did not improve the average homocysteine reduction achieved by folic acid in this trial.
primary_references
[creatine-p26311810] Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial. (2015). https://pubmed.ncbi.nlm.nih.gov/26311810/ DOI: 10.3945/jn.115.216739
tissue_or_cell_type
Plasma metabolites
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 750–761
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve-week randomized placebo-controlled trial · source_derived_draft · unverified_draft
### creatine-folate-creatine-hcy Homocysteine fell 23.4% with folic acid alone and 21.0% with creatine plus folic acid; the difference was not significant (P=0.41). Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding creatine did not improve the average homocysteine reduction achieved by folic acid in this trial. organism: Bangladeshi adults tissue_or_cell_type: Plasma metabolites experimental_model: Twelve-week randomized placebo-controlled trial limitations: Group-average effects and exploratory within-person associations are distinct. No general claim of restored methylation or reduced disease risk. exposure: Creatine 3 g/day, folic acid 400 micrograms/day, both, or placebo; analyzed groups 101, 153, 103 and 101 respectively evidence_span: {"source_cache": "artifacts/creatine-research/26311810.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "055a97365d5a6d864e78eafcfa4a73bc8c425e240487580796a443cf8ef33a04", "start_char": 0, "end_char": 2160, "text_sha256": "055a97365d5a6d864e78eafcfa4a73bc8c425e240487580796a443cf8ef33a04"} [creatine-p26311810] Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial. (2015). https://pubmed.ncbi.nlm.nih.gov/26311810/ DOI: 10.3945/jn.115.216739
Complete structured claim and evidence
Guanidinoacetate inhibited complex II activity in the in-vitro striatal assays; complex II–III activity was inhibited after intrastriatal exposure.
Guanidinoacetate → Rat striatal respiratory complex II activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/17407807.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6174f6169ebf6ca7e61bc61642e38841a9089aecdd278ad8fb2f2221cf847c35", "start_char": 0, "end_char": 1929, "text_sha256": "6174f6169ebf6ca7e61bc61642e38841a9089aecdd278ad8fb2f2221cf847c35"}
experimental_model
Acute guanidinoacetate exposure with biochemical assays and antioxidant pretreatment
exposure
Intrastriatal guanidinoacetate and in-vitro assays; taurine or combined vitamins E plus C pretreatment
limitations
This scenario models a consequence relevant to a GAMT bottleneck, but the experiment administered guanidinoacetate rather than deleting GAMT. No human treatment inference.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Young rats and rat striatal preparations
plain_language
The accumulated precursor can affect mitochondrial enzyme measurements in this model.
primary_references
[creatine-p17407807] Evidence that the inhibitory effects of guanidinoacetate on the activities of the respiratory chain, Na+,K+-ATPase and creatine kinase can be differentially prevented by taurine and vitamins E and C administration in rat striatum in vivo. (2007). https://pubmed.ncbi.nlm.nih.gov/17407807/ DOI: 10.1016/j.bbadis.2007.02.005
tissue_or_cell_type
Striatum
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 763–774
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute guanidinoacetate exposure with biochemical assays and antioxidant pretreatment · source_derived_draft · unverified_draft
### creatine-gaa-complex-ii Guanidinoacetate inhibited complex II activity in the in-vitro striatal assays; complex II–III activity was inhibited after intrastriatal exposure. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The accumulated precursor can affect mitochondrial enzyme measurements in this model. organism: Young rats and rat striatal preparations tissue_or_cell_type: Striatum experimental_model: Acute guanidinoacetate exposure with biochemical assays and antioxidant pretreatment limitations: This scenario models a consequence relevant to a GAMT bottleneck, but the experiment administered guanidinoacetate rather than deleting GAMT. No human treatment inference. exposure: Intrastriatal guanidinoacetate and in-vitro assays; taurine or combined vitamins E plus C pretreatment evidence_span: {"source_cache": "artifacts/creatine-research/17407807.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6174f6169ebf6ca7e61bc61642e38841a9089aecdd278ad8fb2f2221cf847c35", "start_char": 0, "end_char": 1929, "text_sha256": "6174f6169ebf6ca7e61bc61642e38841a9089aecdd278ad8fb2f2221cf847c35"} [creatine-p17407807] Evidence that the inhibitory effects of guanidinoacetate on the activities of the respiratory chain, Na+,K+-ATPase and creatine kinase can be differentially prevented by taurine and vitamins E and C administration in rat striatum in vivo. (2007). https://pubmed.ncbi.nlm.nih.gov/17407807/ DOI: 10.1016/j.bbadis.2007.02.005
Complete structured claim and evidence
Taurine pretreatment prevented the reported guanidinoacetate-related inhibition of complex II, complex II–III and sodium/potassium ATPase activity.
Taurine → Rat striatal respiratory complex II activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/17407807.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6174f6169ebf6ca7e61bc61642e38841a9089aecdd278ad8fb2f2221cf847c35", "start_char": 0, "end_char": 1929, "text_sha256": "6174f6169ebf6ca7e61bc61642e38841a9089aecdd278ad8fb2f2221cf847c35"}
experimental_model
Acute guanidinoacetate exposure with biochemical assays and antioxidant pretreatment
exposure
Intrastriatal guanidinoacetate and in-vitro assays; taurine or combined vitamins E plus C pretreatment
limitations
Acute experimental precursor toxicity is not a human supplement trial or proof that antioxidant treatment corrects GAMT deficiency. Vitamin E and C were combined.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Young rats and rat striatal preparations
plain_language
Taurine protected selected enzyme measurements in this rat experiment.
primary_references
[creatine-p17407807] Evidence that the inhibitory effects of guanidinoacetate on the activities of the respiratory chain, Na+,K+-ATPase and creatine kinase can be differentially prevented by taurine and vitamins E and C administration in rat striatum in vivo. (2007). https://pubmed.ncbi.nlm.nih.gov/17407807/ DOI: 10.1016/j.bbadis.2007.02.005
tissue_or_cell_type
Striatum
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 776–787
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute guanidinoacetate exposure with biochemical assays and antioxidant pretreatment · source_derived_draft · unverified_draft
### creatine-taurine-gaa-enzyme Taurine pretreatment prevented the reported guanidinoacetate-related inhibition of complex II, complex II–III and sodium/potassium ATPase activity. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Taurine protected selected enzyme measurements in this rat experiment. organism: Young rats and rat striatal preparations tissue_or_cell_type: Striatum experimental_model: Acute guanidinoacetate exposure with biochemical assays and antioxidant pretreatment limitations: Acute experimental precursor toxicity is not a human supplement trial or proof that antioxidant treatment corrects GAMT deficiency. Vitamin E and C were combined. exposure: Intrastriatal guanidinoacetate and in-vitro assays; taurine or combined vitamins E plus C pretreatment evidence_span: {"source_cache": "artifacts/creatine-research/17407807.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6174f6169ebf6ca7e61bc61642e38841a9089aecdd278ad8fb2f2221cf847c35", "start_char": 0, "end_char": 1929, "text_sha256": "6174f6169ebf6ca7e61bc61642e38841a9089aecdd278ad8fb2f2221cf847c35"} [creatine-p17407807] Evidence that the inhibitory effects of guanidinoacetate on the activities of the respiratory chain, Na+,K+-ATPase and creatine kinase can be differentially prevented by taurine and vitamins E and C administration in rat striatum in vivo. (2007). https://pubmed.ncbi.nlm.nih.gov/17407807/ DOI: 10.1016/j.bbadis.2007.02.005
Complete structured claim and evidence
Combined vitamin E plus C pretreatment prevented guanidinoacetate-associated inhibition of creatine kinase and sodium/potassium ATPase.
Vitamin E → Creatine kinase catalytic activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/17407807.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6174f6169ebf6ca7e61bc61642e38841a9089aecdd278ad8fb2f2221cf847c35", "start_char": 0, "end_char": 1929, "text_sha256": "6174f6169ebf6ca7e61bc61642e38841a9089aecdd278ad8fb2f2221cf847c35"}
experimental_model
Acute guanidinoacetate exposure with biochemical assays and antioxidant pretreatment
exposure
Intrastriatal guanidinoacetate and in-vitro assays; taurine or combined vitamins E plus C pretreatment
limitations
Acute experimental precursor toxicity is not a human supplement trial or proof that antioxidant treatment corrects GAMT deficiency. Vitamin E and C were combined.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Young rats and rat striatal preparations
plain_language
The study tested two antioxidant vitamins together; it did not establish either vitamin as an effective treatment on its own.
primary_references
[creatine-p17407807] Evidence that the inhibitory effects of guanidinoacetate on the activities of the respiratory chain, Na+,K+-ATPase and creatine kinase can be differentially prevented by taurine and vitamins E and C administration in rat striatum in vivo. (2007). https://pubmed.ncbi.nlm.nih.gov/17407807/ DOI: 10.1016/j.bbadis.2007.02.005
tissue_or_cell_type
Striatum
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 789–800
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute guanidinoacetate exposure with biochemical assays and antioxidant pretreatment · source_derived_draft · unverified_draft
### creatine-vitamins-gaa-ck Combined vitamin E plus C pretreatment prevented guanidinoacetate-associated inhibition of creatine kinase and sodium/potassium ATPase. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The study tested two antioxidant vitamins together; it did not establish either vitamin as an effective treatment on its own. organism: Young rats and rat striatal preparations tissue_or_cell_type: Striatum experimental_model: Acute guanidinoacetate exposure with biochemical assays and antioxidant pretreatment limitations: Acute experimental precursor toxicity is not a human supplement trial or proof that antioxidant treatment corrects GAMT deficiency. Vitamin E and C were combined. exposure: Intrastriatal guanidinoacetate and in-vitro assays; taurine or combined vitamins E plus C pretreatment evidence_span: {"source_cache": "artifacts/creatine-research/17407807.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6174f6169ebf6ca7e61bc61642e38841a9089aecdd278ad8fb2f2221cf847c35", "start_char": 0, "end_char": 1929, "text_sha256": "6174f6169ebf6ca7e61bc61642e38841a9089aecdd278ad8fb2f2221cf847c35"} [creatine-p17407807] Evidence that the inhibitory effects of guanidinoacetate on the activities of the respiratory chain, Na+,K+-ATPase and creatine kinase can be differentially prevented by taurine and vitamins E and C administration in rat striatum in vivo. (2007). https://pubmed.ncbi.nlm.nih.gov/17407807/ DOI: 10.1016/j.bbadis.2007.02.005
Complete structured claim and evidence
Combined vitamin E plus C pretreatment prevented the rise in the lipid-peroxidation readout after guanidinoacetate exposure.
Vitamin E → Rat striatal lipid peroxidation readout source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/17407807.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6174f6169ebf6ca7e61bc61642e38841a9089aecdd278ad8fb2f2221cf847c35", "start_char": 0, "end_char": 1929, "text_sha256": "6174f6169ebf6ca7e61bc61642e38841a9089aecdd278ad8fb2f2221cf847c35"}
experimental_model
Acute guanidinoacetate exposure with biochemical assays and antioxidant pretreatment
exposure
Intrastriatal guanidinoacetate and in-vitro assays; taurine or combined vitamins E plus C pretreatment
limitations
Acute experimental precursor toxicity is not a human supplement trial or proof that antioxidant treatment corrects GAMT deficiency. Vitamin E and C were combined.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Young rats and rat striatal preparations
plain_language
Oxidative damage markers were altered in this preparation, alongside the enzyme effects.
primary_references
[creatine-p17407807] Evidence that the inhibitory effects of guanidinoacetate on the activities of the respiratory chain, Na+,K+-ATPase and creatine kinase can be differentially prevented by taurine and vitamins E and C administration in rat striatum in vivo. (2007). https://pubmed.ncbi.nlm.nih.gov/17407807/ DOI: 10.1016/j.bbadis.2007.02.005
tissue_or_cell_type
Striatum
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 802–813
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute guanidinoacetate exposure with biochemical assays and antioxidant pretreatment · source_derived_draft · unverified_draft
### creatine-vitamins-gaa-oxidation Combined vitamin E plus C pretreatment prevented the rise in the lipid-peroxidation readout after guanidinoacetate exposure. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Oxidative damage markers were altered in this preparation, alongside the enzyme effects. organism: Young rats and rat striatal preparations tissue_or_cell_type: Striatum experimental_model: Acute guanidinoacetate exposure with biochemical assays and antioxidant pretreatment limitations: Acute experimental precursor toxicity is not a human supplement trial or proof that antioxidant treatment corrects GAMT deficiency. Vitamin E and C were combined. exposure: Intrastriatal guanidinoacetate and in-vitro assays; taurine or combined vitamins E plus C pretreatment evidence_span: {"source_cache": "artifacts/creatine-research/17407807.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6174f6169ebf6ca7e61bc61642e38841a9089aecdd278ad8fb2f2221cf847c35", "start_char": 0, "end_char": 1929, "text_sha256": "6174f6169ebf6ca7e61bc61642e38841a9089aecdd278ad8fb2f2221cf847c35"} [creatine-p17407807] Evidence that the inhibitory effects of guanidinoacetate on the activities of the respiratory chain, Na+,K+-ATPase and creatine kinase can be differentially prevented by taurine and vitamins E and C administration in rat striatum in vivo. (2007). https://pubmed.ncbi.nlm.nih.gov/17407807/ DOI: 10.1016/j.bbadis.2007.02.005
Complete structured claim and evidence
AGAT expression increased homoarginine in cells, and homoarginine was absent in AGAT-deficient mice.
Human glycine amidinotransferase AGAT / GATM → Homoarginine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/24004504.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "301113d570a67df12332ca3574aa0714c6dc3c62297e72c2dd7863b146187d6a", "start_char": 0, "end_char": 1911, "text_sha256": "301113d570a67df12332ca3574aa0714c6dc3c62297e72c2dd7863b146187d6a"}
experimental_model
Human genetic/observational analyses, cell expression and mouse gene deletion
exposure
GATM variation, AGAT expression, AGAT or GAMT deletion and homoarginine rescue
limitations
Human stroke associations are not supplementation causation. AGAT deletion disrupts more than creatine synthesis.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Humans, cultured cells and mice
plain_language
The first creatine-synthesis enzyme also helps make another metabolite, homoarginine.
primary_references
[creatine-p24004504] Homoarginine levels are regulated by L-arginine:glycine amidinotransferase and affect stroke outcome: results from human and murine studies. (2013). https://pubmed.ncbi.nlm.nih.gov/24004504/ DOI: 10.1161/circulationaha.112.000580
tissue_or_cell_type
Plasma, expressing cells and experimental stroke models
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 815–826
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human genetic/observational analyses, cell expression and mouse gene deletion · source_derived_draft · unverified_draft
### creatine-agat-homoarginine AGAT expression increased homoarginine in cells, and homoarginine was absent in AGAT-deficient mice. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The first creatine-synthesis enzyme also helps make another metabolite, homoarginine. organism: Humans, cultured cells and mice tissue_or_cell_type: Plasma, expressing cells and experimental stroke models experimental_model: Human genetic/observational analyses, cell expression and mouse gene deletion limitations: Human stroke associations are not supplementation causation. AGAT deletion disrupts more than creatine synthesis. exposure: GATM variation, AGAT expression, AGAT or GAMT deletion and homoarginine rescue evidence_span: {"source_cache": "artifacts/creatine-research/24004504.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "301113d570a67df12332ca3574aa0714c6dc3c62297e72c2dd7863b146187d6a", "start_char": 0, "end_char": 1911, "text_sha256": "301113d570a67df12332ca3574aa0714c6dc3c62297e72c2dd7863b146187d6a"} [creatine-p24004504] Homoarginine levels are regulated by L-arginine:glycine amidinotransferase and affect stroke outcome: results from human and murine studies. (2013). https://pubmed.ncbi.nlm.nih.gov/24004504/ DOI: 10.1161/circulationaha.112.000580
Complete structured claim and evidence
Homoarginine supplementation rescued the aggravated stroke phenotype in AGAT-deficient mice in this study.
Homoarginine → Cerebral damage and neurological deficits after experimental ischemic stroke in mice source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/24004504.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "301113d570a67df12332ca3574aa0714c6dc3c62297e72c2dd7863b146187d6a", "start_char": 0, "end_char": 1911, "text_sha256": "301113d570a67df12332ca3574aa0714c6dc3c62297e72c2dd7863b146187d6a"}
experimental_model
Human genetic/observational analyses, cell expression and mouse gene deletion
exposure
GATM variation, AGAT expression, AGAT or GAMT deletion and homoarginine rescue
limitations
Mouse stroke experiment; homoarginine rescue shows that AGAT deletion has a non-creatine consequence, not that homoarginine treats human stroke.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Humans, cultured cells and mice
plain_language
An AGAT-knockout effect cannot automatically be blamed entirely on creatine loss.
primary_references
[creatine-p24004504] Homoarginine levels are regulated by L-arginine:glycine amidinotransferase and affect stroke outcome: results from human and murine studies. (2013). https://pubmed.ncbi.nlm.nih.gov/24004504/ DOI: 10.1161/circulationaha.112.000580
tissue_or_cell_type
Plasma, expressing cells and experimental stroke models
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 828–839
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human genetic/observational analyses, cell expression and mouse gene deletion · source_derived_draft · unverified_draft
### creatine-agat-knockout-confounding Homoarginine supplementation rescued the aggravated stroke phenotype in AGAT-deficient mice in this study. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An AGAT-knockout effect cannot automatically be blamed entirely on creatine loss. organism: Humans, cultured cells and mice tissue_or_cell_type: Plasma, expressing cells and experimental stroke models experimental_model: Human genetic/observational analyses, cell expression and mouse gene deletion limitations: Mouse stroke experiment; homoarginine rescue shows that AGAT deletion has a non-creatine consequence, not that homoarginine treats human stroke. exposure: GATM variation, AGAT expression, AGAT or GAMT deletion and homoarginine rescue evidence_span: {"source_cache": "artifacts/creatine-research/24004504.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "301113d570a67df12332ca3574aa0714c6dc3c62297e72c2dd7863b146187d6a", "start_char": 0, "end_char": 1911, "text_sha256": "301113d570a67df12332ca3574aa0714c6dc3c62297e72c2dd7863b146187d6a"} [creatine-p24004504] Homoarginine levels are regulated by L-arginine:glycine amidinotransferase and affect stroke outcome: results from human and murine studies. (2013). https://pubmed.ncbi.nlm.nih.gov/24004504/ DOI: 10.1161/circulationaha.112.000580
Complete structured claim and evidence
Oral creatine substitution reversed the brain creatine depletion in the reported AGAT-deficient patients.
Creatine → Brain total creatine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/11555793.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "89ef028281e917c6af5ac6975c05f6ff421852645e695550b737ca4eff6d78f3", "start_char": 0, "end_char": 1044, "text_sha256": "89ef028281e917c6af5ac6975c05f6ff421852645e695550b737ca4eff6d78f3"}
experimental_model
Biochemical and genetic investigation with oral replacement observations
exposure
Inherited AGAT deficiency and oral creatine substitution
limitations
Rare synthesis disorder; treatment response is not equivalent to a diagnosis of dietary creatine deficiency.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Two human sisters
plain_language
Replacing the finished molecule could bypass this synthesis defect.
primary_references
[creatine-p11555793] Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11555793/ DOI: 10.1086/323765
tissue_or_cell_type
Urine, brain magnetic-resonance spectroscopy and AGAT assays
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 854–865
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical and genetic investigation with oral replacement observations · source_derived_draft · unverified_draft
### creatine-agat-creatine-replacement Oral creatine substitution reversed the brain creatine depletion in the reported AGAT-deficient patients. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacing the finished molecule could bypass this synthesis defect. organism: Two human sisters tissue_or_cell_type: Urine, brain magnetic-resonance spectroscopy and AGAT assays experimental_model: Biochemical and genetic investigation with oral replacement observations limitations: Rare synthesis disorder; treatment response is not equivalent to a diagnosis of dietary creatine deficiency. exposure: Inherited AGAT deficiency and oral creatine substitution evidence_span: {"source_cache": "artifacts/creatine-research/11555793.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "89ef028281e917c6af5ac6975c05f6ff421852645e695550b737ca4eff6d78f3", "start_char": 0, "end_char": 1044, "text_sha256": "89ef028281e917c6af5ac6975c05f6ff421852645e695550b737ca4eff6d78f3"} [creatine-p11555793] Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11555793/ DOI: 10.1086/323765
Complete structured claim and evidence
The reported GAMT-deficiency syndrome was responsive to oral creatine substitution.
Creatine → Neurological impairment associated with GAMT deficiency source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/8651275.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d6999ce02dd6012eefd5981a91374d6c933af0924d5e82b1447fd322e8f211de", "start_char": 0, "end_char": 706, "text_sha256": "d6999ce02dd6012eefd5981a91374d6c933af0924d5e82b1447fd322e8f211de"}
experimental_model
Biochemical diagnosis and treatment observations
exposure
GAMT deficiency with oral creatine substitution
limitations
Small case series; biochemical and neurological responses are not a universal prognosis.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Two human children
plain_language
Some manifestations improved with replacement in these cases; precursor accumulation remains a separate issue.
primary_references
[creatine-p8651275] Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man. (1996). https://pubmed.ncbi.nlm.nih.gov/8651275/
tissue_or_cell_type
Brain spectroscopy, blood and liver enzyme assay
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 880–891
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical diagnosis and treatment observations · source_derived_draft · unverified_draft
### creatine-gamt-replacement-response The reported GAMT-deficiency syndrome was responsive to oral creatine substitution. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some manifestations improved with replacement in these cases; precursor accumulation remains a separate issue. organism: Two human children tissue_or_cell_type: Brain spectroscopy, blood and liver enzyme assay experimental_model: Biochemical diagnosis and treatment observations limitations: Small case series; biochemical and neurological responses are not a universal prognosis. exposure: GAMT deficiency with oral creatine substitution evidence_span: {"source_cache": "artifacts/creatine-research/8651275.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d6999ce02dd6012eefd5981a91374d6c933af0924d5e82b1447fd322e8f211de", "start_char": 0, "end_char": 706, "text_sha256": "d6999ce02dd6012eefd5981a91374d6c933af0924d5e82b1447fd322e8f211de"} [creatine-p8651275] Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man. (1996). https://pubmed.ncbi.nlm.nih.gov/8651275/
Complete structured claim and evidence
In the GAMT registry, clinical severity improved in 13 patients, 11 became seizure-free and movement disorder resolved in four during treatment combinations.
Creatine → Neurological impairment associated with GAMT deficiency source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/29506905.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e443eeda80f65e6e7cd3b0b07a4a86b5f11b6b4feef6201ce97a99bc27af0b66", "start_char": 0, "end_char": 1609, "text_sha256": "e443eeda80f65e6e7cd3b0b07a4a86b5f11b6b4feef6201ce97a99bc27af0b66"}
experimental_model
International retrospective registry
exposure
All received creatine; 18 ornithine and 15 arginine/protein restriction
limitations
Nonrandomized combination treatment and variable diagnosis timing prevent attribution of improvements to a single component.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
22 people with GAMT deficiency
plain_language
The registry supports the importance of treating this disorder, but cannot tell us which component caused each improvement.
primary_references
[creatine-p29506905] Treatment outcome of twenty-two patients with guanidinoacetate methyltransferase deficiency: An international retrospective cohort study. (2018). https://pubmed.ncbi.nlm.nih.gov/29506905/ DOI: 10.1016/j.ejpn.2018.02.007
tissue_or_cell_type
Clinical outcomes
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 893–904
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · International retrospective registry · source_derived_draft · unverified_draft
### creatine-gamt-combination-outcomes In the GAMT registry, clinical severity improved in 13 patients, 11 became seizure-free and movement disorder resolved in four during treatment combinations. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The registry supports the importance of treating this disorder, but cannot tell us which component caused each improvement. organism: 22 people with GAMT deficiency tissue_or_cell_type: Clinical outcomes experimental_model: International retrospective registry limitations: Nonrandomized combination treatment and variable diagnosis timing prevent attribution of improvements to a single component. exposure: All received creatine; 18 ornithine and 15 arginine/protein restriction evidence_span: {"source_cache": "artifacts/creatine-research/29506905.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e443eeda80f65e6e7cd3b0b07a4a86b5f11b6b4feef6201ce97a99bc27af0b66", "start_char": 0, "end_char": 1609, "text_sha256": "e443eeda80f65e6e7cd3b0b07a4a86b5f11b6b4feef6201ce97a99bc27af0b66"} [creatine-p29506905] Treatment outcome of twenty-two patients with guanidinoacetate methyltransferase deficiency: An international retrospective cohort study. (2018). https://pubmed.ncbi.nlm.nih.gov/29506905/ DOI: 10.1016/j.ejpn.2018.02.007
Complete structured claim and evidence
Earlier-treated AGAT-deficient patients had better developmental outcomes, while later treatment produced only partial improvement despite brain creatine repletion.
Creatine → Developmental impairment associated with AGAT deficiency source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/28148286.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "aadaba592d731ef134291139ecb131188660c23d0dcd078523704dccd6e3dee7", "start_char": 0, "end_char": 1605, "text_sha256": "aadaba592d731ef134291139ecb131188660c23d0dcd078523704dccd6e3dee7"}
experimental_model
Long-term clinical follow-up
exposure
Creatine treatment over approximately 15 years of follow-up
limitations
Small observational series with different treatment start ages; later improvement was partial and early response is not a guaranteed outcome.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Four Italian patients with AGAT deficiency
plain_language
Replacing a missing metabolite may not reverse all effects once developmental injury has occurred.
primary_references
[creatine-p28148286] Fifteen-year follow-up of Italian families affected by arginine glycine amidinotransferase deficiency. (2017). https://pubmed.ncbi.nlm.nih.gov/28148286/ DOI: 10.1186/s13023-017-0577-5
tissue_or_cell_type
Brain spectroscopy and neurodevelopment
trigger_kind
machinery_impairment Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 919–930
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Long-term clinical follow-up · source_derived_draft · unverified_draft
### creatine-agat-treatment-timing Earlier-treated AGAT-deficient patients had better developmental outcomes, while later treatment produced only partial improvement despite brain creatine repletion. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacing a missing metabolite may not reverse all effects once developmental injury has occurred. organism: Four Italian patients with AGAT deficiency tissue_or_cell_type: Brain spectroscopy and neurodevelopment experimental_model: Long-term clinical follow-up limitations: Small observational series with different treatment start ages; later improvement was partial and early response is not a guaranteed outcome. exposure: Creatine treatment over approximately 15 years of follow-up evidence_span: {"source_cache": "artifacts/creatine-research/28148286.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "aadaba592d731ef134291139ecb131188660c23d0dcd078523704dccd6e3dee7", "start_char": 0, "end_char": 1605, "text_sha256": "aadaba592d731ef134291139ecb131188660c23d0dcd078523704dccd6e3dee7"} [creatine-p28148286] Fifteen-year follow-up of Italian families affected by arginine glycine amidinotransferase deficiency. (2017). https://pubmed.ncbi.nlm.nih.gov/28148286/ DOI: 10.1186/s13023-017-0577-5
Complete structured claim and evidence
Oral creatine loading increased muscle total creatine, with larger increases in participants with lower starting concentrations.
Creatine → Skeletal-muscle total creatine content source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/1327657.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ae0516c0f0465293ac00446b6a863fa2d791a750258a11b532c1247fdb47bd6", "start_char": 0, "end_char": 1573, "text_sha256": "3ae0516c0f0465293ac00446b6a863fa2d791a750258a11b532c1247fdb47bd6"}
experimental_model
Oral loading with muscle biopsies
exposure
5 g creatine four to six times daily for two or more days
limitations
Loading study, not evidence that everyone is deficient; the indexed abstract is truncated and no unreported exercise effect is extracted.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
17 human participants
plain_language
People with lower initial muscle stores tended to retain more in this experiment.
primary_references
[creatine-p1327657] Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. (1992). https://pubmed.ncbi.nlm.nih.gov/1327657/ DOI: 10.1042/cs0830367
tissue_or_cell_type
Skeletal muscle and blood
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 932–943
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral loading with muscle biopsies · source_derived_draft · unverified_draft
### creatine-muscle-loading Oral creatine loading increased muscle total creatine, with larger increases in participants with lower starting concentrations. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: People with lower initial muscle stores tended to retain more in this experiment. organism: 17 human participants tissue_or_cell_type: Skeletal muscle and blood experimental_model: Oral loading with muscle biopsies limitations: Loading study, not evidence that everyone is deficient; the indexed abstract is truncated and no unreported exercise effect is extracted. exposure: 5 g creatine four to six times daily for two or more days evidence_span: {"source_cache": "artifacts/creatine-research/1327657.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ae0516c0f0465293ac00446b6a863fa2d791a750258a11b532c1247fdb47bd6", "start_char": 0, "end_char": 1573, "text_sha256": "3ae0516c0f0465293ac00446b6a863fa2d791a750258a11b532c1247fdb47bd6"} [creatine-p1327657] Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. (1992). https://pubmed.ncbi.nlm.nih.gov/1327657/ DOI: 10.1042/cs0830367
Complete structured claim and evidence
Approximately 20% or more of the creatine taken up was recovered as phosphocreatine, while muscle ATP concentration did not change.
Creatine → Skeletal-muscle phosphocreatine content source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/1327657.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ae0516c0f0465293ac00446b6a863fa2d791a750258a11b532c1247fdb47bd6", "start_char": 0, "end_char": 1573, "text_sha256": "3ae0516c0f0465293ac00446b6a863fa2d791a750258a11b532c1247fdb47bd6"}
experimental_model
Oral loading with muscle biopsies
exposure
5 g creatine four to six times daily for two or more days
limitations
Loading study, not evidence that everyone is deficient; the indexed abstract is truncated and no unreported exercise effect is extracted.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
17 human participants
plain_language
More creatine expanded the phosphate reserve without simply raising resting ATP.
primary_references
[creatine-p1327657] Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. (1992). https://pubmed.ncbi.nlm.nih.gov/1327657/ DOI: 10.1042/cs0830367
tissue_or_cell_type
Skeletal muscle and blood
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 945–956
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral loading with muscle biopsies · source_derived_draft · unverified_draft
### creatine-pcr-versus-atp-loading Approximately 20% or more of the creatine taken up was recovered as phosphocreatine, while muscle ATP concentration did not change. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: More creatine expanded the phosphate reserve without simply raising resting ATP. organism: 17 human participants tissue_or_cell_type: Skeletal muscle and blood experimental_model: Oral loading with muscle biopsies limitations: Loading study, not evidence that everyone is deficient; the indexed abstract is truncated and no unreported exercise effect is extracted. exposure: 5 g creatine four to six times daily for two or more days evidence_span: {"source_cache": "artifacts/creatine-research/1327657.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ae0516c0f0465293ac00446b6a863fa2d791a750258a11b532c1247fdb47bd6", "start_char": 0, "end_char": 1573, "text_sha256": "3ae0516c0f0465293ac00446b6a863fa2d791a750258a11b532c1247fdb47bd6"} [creatine-p1327657] Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. (1992). https://pubmed.ncbi.nlm.nih.gov/1327657/ DOI: 10.1042/cs0830367
Complete structured claim and evidence
Plasma and muscle creatine declined after adoption of the vegetarian diet; the creatine-plus-beta-alanine group attenuated the decline.
Creatine → Skeletal-muscle total creatine content source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/29569535.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3f1a5c6540a84e1f679a0b16d2faefd7caa27fac1276ff53744ee25e50e498aa", "start_char": 0, "end_char": 1813, "text_sha256": "3f1a5c6540a84e1f679a0b16d2faefd7caa27fac1276ff53744ee25e50e498aa"}
experimental_model
Six-month dietary intervention with supplement/placebo groups
exposure
Continued omnivorous diet or vegetarian diet with placebo or creatine 1 g/day plus beta-alanine
limitations
The schema category nutrient_deficiency describes reduced dietary provision here, not a demonstrated clinical deficiency syndrome. Combined supplementation limits causal attribution.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
40 initially omnivorous women
plain_language
Endogenous production did not fully maintain the previous measured stores in this study.
primary_references
[creatine-p29569535] Changing to a vegetarian diet reduces the body creatine pool in omnivorous women, but appears not to affect carnitine and carnosine homeostasis: a randomised trial. (2018). https://pubmed.ncbi.nlm.nih.gov/29569535/ DOI: 10.1017/s000711451800017x
tissue_or_cell_type
Plasma and skeletal muscle
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 958–969
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month dietary intervention with supplement/placebo groups · source_derived_draft · unverified_draft
### creatine-vegetarian-stores Plasma and muscle creatine declined after adoption of the vegetarian diet; the creatine-plus-beta-alanine group attenuated the decline. Condition category: nutrient_deficiency nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Endogenous production did not fully maintain the previous measured stores in this study. organism: 40 initially omnivorous women tissue_or_cell_type: Plasma and skeletal muscle experimental_model: Six-month dietary intervention with supplement/placebo groups limitations: The schema category nutrient_deficiency describes reduced dietary provision here, not a demonstrated clinical deficiency syndrome. Combined supplementation limits causal attribution. exposure: Continued omnivorous diet or vegetarian diet with placebo or creatine 1 g/day plus beta-alanine evidence_span: {"source_cache": "artifacts/creatine-research/29569535.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3f1a5c6540a84e1f679a0b16d2faefd7caa27fac1276ff53744ee25e50e498aa", "start_char": 0, "end_char": 1813, "text_sha256": "3f1a5c6540a84e1f679a0b16d2faefd7caa27fac1276ff53744ee25e50e498aa"} [creatine-p29569535] Changing to a vegetarian diet reduces the body creatine pool in omnivorous women, but appears not to affect carnitine and carnosine homeostasis: a randomised trial. (2018). https://pubmed.ncbi.nlm.nih.gov/29569535/ DOI: 10.1017/s000711451800017x
Complete structured claim and evidence
Bench-press and squat gains were greater with creatine than placebo during training: approximately 24% versus 16% and 32% versus 24%, respectively.
Creatine → Muscle strength response to resistance training source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/10449017.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "945065c1e6c32f344bfc4092d1306d6ebed2354e688efe65bd73702af096729e", "start_char": 0, "end_char": 1770, "text_sha256": "945065c1e6c32f344bfc4092d1306d6ebed2354e688efe65bd73702af096729e"}
experimental_model
Twelve-week randomized resistance-training trial
exposure
25 g/day creatine for one week then 5 g/day, with standardized resistance training
limitations
Small male training study; mechanistic explanations for greater training adaptation are hypotheses, not directly established signaling pathways.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
19 resistance-trained men
plain_language
Creatine improved the measured training response in this group.
primary_references
[creatine-p10449017] Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. (1999). https://pubmed.ncbi.nlm.nih.gov/10449017/ DOI: 10.1097/00005768-199908000-00011
tissue_or_cell_type
Muscle performance and muscle biopsies
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 971–982
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve-week randomized resistance-training trial · source_derived_draft · unverified_draft
### creatine-training-strength Bench-press and squat gains were greater with creatine than placebo during training: approximately 24% versus 16% and 32% versus 24%, respectively. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Creatine improved the measured training response in this group. organism: 19 resistance-trained men tissue_or_cell_type: Muscle performance and muscle biopsies experimental_model: Twelve-week randomized resistance-training trial limitations: Small male training study; mechanistic explanations for greater training adaptation are hypotheses, not directly established signaling pathways. exposure: 25 g/day creatine for one week then 5 g/day, with standardized resistance training evidence_span: {"source_cache": "artifacts/creatine-research/10449017.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "945065c1e6c32f344bfc4092d1306d6ebed2354e688efe65bd73702af096729e", "start_char": 0, "end_char": 1770, "text_sha256": "945065c1e6c32f344bfc4092d1306d6ebed2354e688efe65bd73702af096729e"} [creatine-p10449017] Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. (1999). https://pubmed.ncbi.nlm.nih.gov/10449017/ DOI: 10.1097/00005768-199908000-00011
Complete structured claim and evidence
Muscle-fiber cross-sectional area and fat-free mass increased more with creatine than placebo during the 12-week resistance program.
Creatine → Skeletal-muscle fiber cross-sectional area source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/10449017.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "945065c1e6c32f344bfc4092d1306d6ebed2354e688efe65bd73702af096729e", "start_char": 0, "end_char": 1770, "text_sha256": "945065c1e6c32f344bfc4092d1306d6ebed2354e688efe65bd73702af096729e"}
experimental_model
Twelve-week randomized resistance-training trial
exposure
25 g/day creatine for one week then 5 g/day, with standardized resistance training
limitations
Small male training study; mechanistic explanations for greater training adaptation are hypotheses, not directly established signaling pathways.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
19 resistance-trained men
plain_language
The study found tissue and body-composition changes as well as strength changes.
primary_references
[creatine-p10449017] Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. (1999). https://pubmed.ncbi.nlm.nih.gov/10449017/ DOI: 10.1097/00005768-199908000-00011
tissue_or_cell_type
Muscle performance and muscle biopsies
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 984–995
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve-week randomized resistance-training trial · source_derived_draft · unverified_draft
### creatine-training-fiber-growth Muscle-fiber cross-sectional area and fat-free mass increased more with creatine than placebo during the 12-week resistance program. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The study found tissue and body-composition changes as well as strength changes. organism: 19 resistance-trained men tissue_or_cell_type: Muscle performance and muscle biopsies experimental_model: Twelve-week randomized resistance-training trial limitations: Small male training study; mechanistic explanations for greater training adaptation are hypotheses, not directly established signaling pathways. exposure: 25 g/day creatine for one week then 5 g/day, with standardized resistance training evidence_span: {"source_cache": "artifacts/creatine-research/10449017.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "945065c1e6c32f344bfc4092d1306d6ebed2354e688efe65bd73702af096729e", "start_char": 0, "end_char": 1770, "text_sha256": "945065c1e6c32f344bfc4092d1306d6ebed2354e688efe65bd73702af096729e"} [creatine-p10449017] Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. (1999). https://pubmed.ncbi.nlm.nih.gov/10449017/ DOI: 10.1097/00005768-199908000-00011
Complete structured claim and evidence
Creatine plus exercise increased muscle GLUT4 translocation to the sarcolemma relative to placebo plus exercise.
Creatine → Human muscle GLUT4 translocation to the sarcolemma source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/20881878.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b3ba6f24e6aedc2c8220a6b50f5d315fc4f885740bc1934cf438cbe0865ace52", "start_char": 0, "end_char": 1736, "text_sha256": "b3ba6f24e6aedc2c8220a6b50f5d315fc4f885740bc1934cf438cbe0865ace52"}
experimental_model
Twelve-week randomized double-blind trial with exercise in both arms
exposure
Creatine 5 g/day plus exercise versus placebo plus exercise
limitations
Small adjunct-to-exercise trial; no replacement for diabetes treatment or isolated creatine effect without exercise is established.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
25 adults with type 2 diabetes
plain_language
More of the glucose transporter was located at the muscle-cell surface in this trial.
primary_references
[creatine-p20881878] Creatine in type 2 diabetes: a randomized, double-blind, placebo-controlled trial. (2011). https://pubmed.ncbi.nlm.nih.gov/20881878/ DOI: 10.1249/mss.0b013e3181fcee7d
tissue_or_cell_type
Blood glucose regulation and muscle GLUT4 localization
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 997–1008
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve-week randomized double-blind trial with exercise in both arms · source_derived_draft · unverified_draft
### creatine-diabetes-glut4 Creatine plus exercise increased muscle GLUT4 translocation to the sarcolemma relative to placebo plus exercise. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: More of the glucose transporter was located at the muscle-cell surface in this trial. organism: 25 adults with type 2 diabetes tissue_or_cell_type: Blood glucose regulation and muscle GLUT4 localization experimental_model: Twelve-week randomized double-blind trial with exercise in both arms limitations: Small adjunct-to-exercise trial; no replacement for diabetes treatment or isolated creatine effect without exercise is established. exposure: Creatine 5 g/day plus exercise versus placebo plus exercise evidence_span: {"source_cache": "artifacts/creatine-research/20881878.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b3ba6f24e6aedc2c8220a6b50f5d315fc4f885740bc1934cf438cbe0865ace52", "start_char": 0, "end_char": 1736, "text_sha256": "b3ba6f24e6aedc2c8220a6b50f5d315fc4f885740bc1934cf438cbe0865ace52"} [creatine-p20881878] Creatine in type 2 diabetes: a randomized, double-blind, placebo-controlled trial. (2011). https://pubmed.ncbi.nlm.nih.gov/20881878/ DOI: 10.1249/mss.0b013e3181fcee7d
Complete structured claim and evidence
The between-group HbA1c difference favored creatine plus exercise by approximately 1.1 percentage points, with a 95% confidence interval of 0.4–1.9 percentage points lower.
Creatine → Glycated hemoglobin / HbA1c source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/20881878.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b3ba6f24e6aedc2c8220a6b50f5d315fc4f885740bc1934cf438cbe0865ace52", "start_char": 0, "end_char": 1736, "text_sha256": "b3ba6f24e6aedc2c8220a6b50f5d315fc4f885740bc1934cf438cbe0865ace52"}
experimental_model
Twelve-week randomized double-blind trial with exercise in both arms
exposure
Creatine 5 g/day plus exercise versus placebo plus exercise
limitations
Small adjunct-to-exercise trial; no replacement for diabetes treatment or isolated creatine effect without exercise is established.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
25 adults with type 2 diabetes
plain_language
Average long-term glucose exposure improved in this small combined-intervention trial.
primary_references
[creatine-p20881878] Creatine in type 2 diabetes: a randomized, double-blind, placebo-controlled trial. (2011). https://pubmed.ncbi.nlm.nih.gov/20881878/ DOI: 10.1249/mss.0b013e3181fcee7d
tissue_or_cell_type
Blood glucose regulation and muscle GLUT4 localization
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 1010–1021
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve-week randomized double-blind trial with exercise in both arms · source_derived_draft · unverified_draft
### creatine-diabetes-hba1c The between-group HbA1c difference favored creatine plus exercise by approximately 1.1 percentage points, with a 95% confidence interval of 0.4–1.9 percentage points lower. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Average long-term glucose exposure improved in this small combined-intervention trial. organism: 25 adults with type 2 diabetes tissue_or_cell_type: Blood glucose regulation and muscle GLUT4 localization experimental_model: Twelve-week randomized double-blind trial with exercise in both arms limitations: Small adjunct-to-exercise trial; no replacement for diabetes treatment or isolated creatine effect without exercise is established. exposure: Creatine 5 g/day plus exercise versus placebo plus exercise evidence_span: {"source_cache": "artifacts/creatine-research/20881878.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b3ba6f24e6aedc2c8220a6b50f5d315fc4f885740bc1934cf438cbe0865ace52", "start_char": 0, "end_char": 1736, "text_sha256": "b3ba6f24e6aedc2c8220a6b50f5d315fc4f885740bc1934cf438cbe0865ace52"} [creatine-p20881878] Creatine in type 2 diabetes: a randomized, double-blind, placebo-controlled trial. (2011). https://pubmed.ncbi.nlm.nih.gov/20881878/ DOI: 10.1249/mss.0b013e3181fcee7d
Complete structured claim and evidence
Mean brain total creatine increased 8.7%, with regional and individual variability, after four weeks of supplementation; changes were reversible on follow-up.
Creatine monohydrate → Brain total creatine concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/10484486.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "91190f8691b1728904ae6d8a46b65c2c731b75fe9fe876d964e18facc61c7c9d", "start_char": 0, "end_char": 1490, "text_sha256": "91190f8691b1728904ae6d8a46b65c2c731b75fe9fe876d964e18facc61c7c9d"}
experimental_model
Before/after quantitative proton MRS with washout
exposure
20 g/day creatine monohydrate for four weeks
limitations
Small non-placebo-controlled study; total creatine includes the creatine/phosphocreatine signal and is not a direct cognition endpoint.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Six healthy human volunteers
plain_language
Brain stores rose modestly and unevenly, rather than matching the much larger changes sometimes seen in muscle.
primary_references
[creatine-p10484486] Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. (1999). https://pubmed.ncbi.nlm.nih.gov/10484486/ DOI: 10.1152/ajpregu.1999.277.3.r698
tissue_or_cell_type
Multiple brain regions
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 1023–1034
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Before/after quantitative proton MRS with washout · source_derived_draft · unverified_draft
### creatine-brain-loading Mean brain total creatine increased 8.7%, with regional and individual variability, after four weeks of supplementation; changes were reversible on follow-up. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Brain stores rose modestly and unevenly, rather than matching the much larger changes sometimes seen in muscle. organism: Six healthy human volunteers tissue_or_cell_type: Multiple brain regions experimental_model: Before/after quantitative proton MRS with washout limitations: Small non-placebo-controlled study; total creatine includes the creatine/phosphocreatine signal and is not a direct cognition endpoint. exposure: 20 g/day creatine monohydrate for four weeks evidence_span: {"source_cache": "artifacts/creatine-research/10484486.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "91190f8691b1728904ae6d8a46b65c2c731b75fe9fe876d964e18facc61c7c9d", "start_char": 0, "end_char": 1490, "text_sha256": "91190f8691b1728904ae6d8a46b65c2c731b75fe9fe876d964e18facc61c7c9d"} [creatine-p10484486] Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. (1999). https://pubmed.ncbi.nlm.nih.gov/10484486/ DOI: 10.1152/ajpregu.1999.277.3.r698
Complete structured claim and evidence
Neither primary cognitive test reached conventional statistical significance; exploratory tasks showed no indication of improvement, and vegetarians did not benefit more than omnivores.
Creatine → Cognitive performance in creatine intervention studies source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/37968687.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bf6121a3717d28c7cca0ae08a4ff612dc0f0d5fcfa610cbfb03c942a7a831798", "start_char": 0, "end_char": 1953, "text_sha256": "bf6121a3717d28c7cca0ae08a4ff612dc0f0d5fcfa610cbfb03c942a7a831798"}
experimental_model
Preregistered randomized double-blind crossover trial
exposure
5 g/day creatine for six weeks versus placebo
limitations
Backward digit span P=0.064 and Raven matrices P=0.327; Bayesian interpretation suggested a possible small effect. No established broad cognitive benefit or vegetarian-specific advantage.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
123 vegetarian and omnivorous participants
plain_language
The larger trial left a possible small benefit uncertain and did not demonstrate a broad cognitive boost.
primary_references
[creatine-p37968687] The effects of creatine supplementation on cognitive performance-a randomised controlled study. (2023). https://pubmed.ncbi.nlm.nih.gov/37968687/ DOI: 10.1186/s12916-023-03146-5
tissue_or_cell_type
Cognitive testing
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 1036–1047
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Preregistered randomized double-blind crossover trial · source_derived_draft · unverified_draft
### creatine-cognition-context Neither primary cognitive test reached conventional statistical significance; exploratory tasks showed no indication of improvement, and vegetarians did not benefit more than omnivores. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The larger trial left a possible small benefit uncertain and did not demonstrate a broad cognitive boost. organism: 123 vegetarian and omnivorous participants tissue_or_cell_type: Cognitive testing experimental_model: Preregistered randomized double-blind crossover trial limitations: Backward digit span P=0.064 and Raven matrices P=0.327; Bayesian interpretation suggested a possible small effect. No established broad cognitive benefit or vegetarian-specific advantage. exposure: 5 g/day creatine for six weeks versus placebo evidence_span: {"source_cache": "artifacts/creatine-research/37968687.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bf6121a3717d28c7cca0ae08a4ff612dc0f0d5fcfa610cbfb03c942a7a831798", "start_char": 0, "end_char": 1953, "text_sha256": "bf6121a3717d28c7cca0ae08a4ff612dc0f0d5fcfa610cbfb03c942a7a831798"} [creatine-p37968687] The effects of creatine supplementation on cognitive performance-a randomised controlled study. (2023). https://pubmed.ncbi.nlm.nih.gov/37968687/ DOI: 10.1186/s12916-023-03146-5
Complete structured claim and evidence
Creatine altered PCr/Pi, ATP and total-creatine/total-NAA measures and prevented the observed fall in brain pH during sleep deprivation.
Creatine monohydrate → Brain phosphate and pH measurements during sleep deprivation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/38418482.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b6dad9388eb7cb8986f1873e6ba9f8dd36924c7a9aa7c661059cde1012f1e3a8", "start_char": 0, "end_char": 1364, "text_sha256": "b6dad9388eb7cb8986f1873e6ba9f8dd36924c7a9aa7c661059cde1012f1e3a8"}
experimental_model
Placebo comparison with repeated phosphorus/proton MRS and cognition
exposure
Single creatine monohydrate dose 0.35 g/kg during approximately 21 hours of sleep deprivation
limitations
Acute high-dose, sleep-deprivation setting; not an everyday dose recommendation or proof of benefit in well-rested people.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Human participants during sleep deprivation
plain_language
The experiment detected changes in brain energy-related measurements under acute sleep stress.
primary_references
[creatine-p38418482] Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. (2024). https://pubmed.ncbi.nlm.nih.gov/38418482/ DOI: 10.1038/s41598-024-54249-9
tissue_or_cell_type
Brain spectroscopy and cognitive performance
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 1049–1060
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Placebo comparison with repeated phosphorus/proton MRS and cognition · source_derived_draft · unverified_draft
### creatine-sleep-deprivation-phosphates Creatine altered PCr/Pi, ATP and total-creatine/total-NAA measures and prevented the observed fall in brain pH during sleep deprivation. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The experiment detected changes in brain energy-related measurements under acute sleep stress. organism: Human participants during sleep deprivation tissue_or_cell_type: Brain spectroscopy and cognitive performance experimental_model: Placebo comparison with repeated phosphorus/proton MRS and cognition limitations: Acute high-dose, sleep-deprivation setting; not an everyday dose recommendation or proof of benefit in well-rested people. exposure: Single creatine monohydrate dose 0.35 g/kg during approximately 21 hours of sleep deprivation evidence_span: {"source_cache": "artifacts/creatine-research/38418482.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b6dad9388eb7cb8986f1873e6ba9f8dd36924c7a9aa7c661059cde1012f1e3a8", "start_char": 0, "end_char": 1364, "text_sha256": "b6dad9388eb7cb8986f1873e6ba9f8dd36924c7a9aa7c661059cde1012f1e3a8"} [creatine-p38418482] Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. (2024). https://pubmed.ncbi.nlm.nih.gov/38418482/ DOI: 10.1038/s41598-024-54249-9
Complete structured claim and evidence
The study reported improved cognitive performance and processing speed after the single high dose during sleep deprivation.
Creatine monohydrate → Cognitive performance in creatine intervention studies source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/38418482.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b6dad9388eb7cb8986f1873e6ba9f8dd36924c7a9aa7c661059cde1012f1e3a8", "start_char": 0, "end_char": 1364, "text_sha256": "b6dad9388eb7cb8986f1873e6ba9f8dd36924c7a9aa7c661059cde1012f1e3a8"}
experimental_model
Placebo comparison with repeated phosphorus/proton MRS and cognition
exposure
Single creatine monohydrate dose 0.35 g/kg during approximately 21 hours of sleep deprivation
limitations
Acute high-dose, sleep-deprivation setting; not an everyday dose recommendation or proof of benefit in well-rested people.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Human participants during sleep deprivation
plain_language
The positive result applies to this demanding sleep-loss setting.
primary_references
[creatine-p38418482] Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. (2024). https://pubmed.ncbi.nlm.nih.gov/38418482/ DOI: 10.1038/s41598-024-54249-9
tissue_or_cell_type
Brain spectroscopy and cognitive performance
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 1062–1073
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Placebo comparison with repeated phosphorus/proton MRS and cognition · source_derived_draft · unverified_draft
### creatine-sleep-deprivation-cognition The study reported improved cognitive performance and processing speed after the single high dose during sleep deprivation. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The positive result applies to this demanding sleep-loss setting. organism: Human participants during sleep deprivation tissue_or_cell_type: Brain spectroscopy and cognitive performance experimental_model: Placebo comparison with repeated phosphorus/proton MRS and cognition limitations: Acute high-dose, sleep-deprivation setting; not an everyday dose recommendation or proof of benefit in well-rested people. exposure: Single creatine monohydrate dose 0.35 g/kg during approximately 21 hours of sleep deprivation evidence_span: {"source_cache": "artifacts/creatine-research/38418482.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b6dad9388eb7cb8986f1873e6ba9f8dd36924c7a9aa7c661059cde1012f1e3a8", "start_char": 0, "end_char": 1364, "text_sha256": "b6dad9388eb7cb8986f1873e6ba9f8dd36924c7a9aa7c661059cde1012f1e3a8"} [creatine-p38418482] Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. (2024). https://pubmed.ncbi.nlm.nih.gov/38418482/ DOI: 10.1038/s41598-024-54249-9
Complete structured claim and evidence
Creatine supplementation did not significantly change tracer-measured glomerular filtration rate versus placebo over 12 weeks in postmenopausal women.
Creatine → Glomerular filtration rate measured by tracer clearance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/21574777.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f5e67ad2a24e51cb17b0a014373841762659f8c1801dd8ae65d4917123cbbb4", "start_char": 0, "end_char": 693, "text_sha256": "4f5e67ad2a24e51cb17b0a014373841762659f8c1801dd8ae65d4917123cbbb4"}
experimental_model
Randomized placebo-controlled trial with measured 51Cr-EDTA clearance
exposure
20 g/day for one week then 5 g/day through 12 weeks
limitations
No significant measured-GFR effect over 12 weeks; this does not establish safety in advanced kidney disease, all doses or lifelong exposure.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Postmenopausal women
plain_language
The study measured filtration directly rather than relying only on a creatinine-based estimate.
primary_references
[creatine-p21574777] Effect of creatine supplementation on measured glomerular filtration rate in postmenopausal women. (2011). https://pubmed.ncbi.nlm.nih.gov/21574777/ DOI: 10.1139/h11-014
tissue_or_cell_type
Kidney function
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 1075–1086
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled trial with measured 51Cr-EDTA clearance · source_derived_draft · unverified_draft
### creatine-measured-gfr-21574777 Creatine supplementation did not significantly change tracer-measured glomerular filtration rate versus placebo over 12 weeks in postmenopausal women. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The study measured filtration directly rather than relying only on a creatinine-based estimate. organism: Postmenopausal women tissue_or_cell_type: Kidney function experimental_model: Randomized placebo-controlled trial with measured 51Cr-EDTA clearance limitations: No significant measured-GFR effect over 12 weeks; this does not establish safety in advanced kidney disease, all doses or lifelong exposure. exposure: 20 g/day for one week then 5 g/day through 12 weeks evidence_span: {"source_cache": "artifacts/creatine-research/21574777.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f5e67ad2a24e51cb17b0a014373841762659f8c1801dd8ae65d4917123cbbb4", "start_char": 0, "end_char": 693, "text_sha256": "4f5e67ad2a24e51cb17b0a014373841762659f8c1801dd8ae65d4917123cbbb4"} [creatine-p21574777] Effect of creatine supplementation on measured glomerular filtration rate in postmenopausal women. (2011). https://pubmed.ncbi.nlm.nih.gov/21574777/ DOI: 10.1139/h11-014
Complete structured claim and evidence
Creatine supplementation did not significantly change tracer-measured glomerular filtration rate versus placebo over 12 weeks in healthy resistance-trained people consuming at least 1.2 g protein/kg/day.
Creatine → Glomerular filtration rate measured by tracer clearance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/23680457.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "00d1d37c5f4c752fba7ffa6b1c837cd4b48e6739ca05f815df3180baa2bf3193", "start_char": 0, "end_char": 1412, "text_sha256": "00d1d37c5f4c752fba7ffa6b1c837cd4b48e6739ca05f815df3180baa2bf3193"}
experimental_model
Randomized placebo-controlled trial with measured 51Cr-EDTA clearance
exposure
20 g/day for five days then 5 g/day through 12 weeks
limitations
No significant measured-GFR effect over 12 weeks; this does not establish safety in advanced kidney disease, all doses or lifelong exposure.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Healthy resistance-trained people consuming at least 1.2 g protein/kg/day
plain_language
The study measured filtration directly rather than relying only on a creatinine-based estimate.
primary_references
[creatine-p23680457] Does long-term creatine supplementation impair kidney function in resistance-trained individuals consuming a high-protein diet? (2013). https://pubmed.ncbi.nlm.nih.gov/23680457/ DOI: 10.1186/1550-2783-10-26
tissue_or_cell_type
Kidney function
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 1088–1099
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled trial with measured 51Cr-EDTA clearance · source_derived_draft · unverified_draft
### creatine-measured-gfr-23680457 Creatine supplementation did not significantly change tracer-measured glomerular filtration rate versus placebo over 12 weeks in healthy resistance-trained people consuming at least 1.2 g protein/kg/day. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The study measured filtration directly rather than relying only on a creatinine-based estimate. organism: Healthy resistance-trained people consuming at least 1.2 g protein/kg/day tissue_or_cell_type: Kidney function experimental_model: Randomized placebo-controlled trial with measured 51Cr-EDTA clearance limitations: No significant measured-GFR effect over 12 weeks; this does not establish safety in advanced kidney disease, all doses or lifelong exposure. exposure: 20 g/day for five days then 5 g/day through 12 weeks evidence_span: {"source_cache": "artifacts/creatine-research/23680457.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "00d1d37c5f4c752fba7ffa6b1c837cd4b48e6739ca05f815df3180baa2bf3193", "start_char": 0, "end_char": 1412, "text_sha256": "00d1d37c5f4c752fba7ffa6b1c837cd4b48e6739ca05f815df3180baa2bf3193"} [creatine-p23680457] Does long-term creatine supplementation impair kidney function in resistance-trained individuals consuming a high-protein diet? (2013). https://pubmed.ncbi.nlm.nih.gov/23680457/ DOI: 10.1186/1550-2783-10-26
Complete structured claim and evidence
Serum creatinine was higher with creatine ethyl ester than with monohydrate or placebo at the measured post-baseline visits.
Creatine ethyl ester → Serum creatinine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/creatine-research/19228401.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "381c3f18fe14f7eba6ee3abe9ca81ab4f02c293c3dd4593ea27dcbb6f879a114", "start_char": 0, "end_char": 1727, "text_sha256": "381c3f18fe14f7eba6ee3abe9ca81ab4f02c293c3dd4593ea27dcbb6f879a114"}
experimental_model
Seven-week randomized double-blind comparison plus resistance training
exposure
Creatine ethyl ester, creatine monohydrate or placebo with loading and maintenance
limitations
The abstract conclusion overstates some comparisons: reported muscle total creatine did not differ significantly between formulations. This curation preserves the actual reported outcomes.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
30 previously non-resistance-trained men
plain_language
A formulation can change the creatinine marker; this trial alone does not establish the mechanism or diagnose kidney injury.
primary_references
[creatine-p19228401] The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels. (2009). https://pubmed.ncbi.nlm.nih.gov/19228401/ DOI: 10.1186/1550-2783-6-6
tissue_or_cell_type
Serum and muscle metabolites, body composition and performance
trigger_kind
biomarker_context Imported condition classification; unverified.
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 1101–1112
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Seven-week randomized double-blind comparison plus resistance training · source_derived_draft · unverified_draft
### creatine-ethyl-ester-creatinine Serum creatinine was higher with creatine ethyl ester than with monohydrate or placebo at the measured post-baseline visits. Condition category: biomarker_context nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A formulation can change the creatinine marker; this trial alone does not establish the mechanism or diagnose kidney injury. organism: 30 previously non-resistance-trained men tissue_or_cell_type: Serum and muscle metabolites, body composition and performance experimental_model: Seven-week randomized double-blind comparison plus resistance training limitations: The abstract conclusion overstates some comparisons: reported muscle total creatine did not differ significantly between formulations. This curation preserves the actual reported outcomes. exposure: Creatine ethyl ester, creatine monohydrate or placebo with loading and maintenance evidence_span: {"source_cache": "artifacts/creatine-research/19228401.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "381c3f18fe14f7eba6ee3abe9ca81ab4f02c293c3dd4593ea27dcbb6f879a114", "start_char": 0, "end_char": 1727, "text_sha256": "381c3f18fe14f7eba6ee3abe9ca81ab4f02c293c3dd4593ea27dcbb6f879a114"} [creatine-p19228401] The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels. (2009). https://pubmed.ncbi.nlm.nih.gov/19228401/ DOI: 10.1186/1550-2783-6-6
Complete structured claim and evidence
Both creatine formulations increased muscle total creatine versus placebo, with no significant difference between formulations; performance and body-composition changes did not significantly differ between groups.
Creatine ethyl ester → Skeletal-muscle total creatine content source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/19228401.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "381c3f18fe14f7eba6ee3abe9ca81ab4f02c293c3dd4593ea27dcbb6f879a114", "start_char": 0, "end_char": 1727, "text_sha256": "381c3f18fe14f7eba6ee3abe9ca81ab4f02c293c3dd4593ea27dcbb6f879a114"}
experimental_model
Seven-week randomized double-blind comparison plus resistance training
exposure
Creatine ethyl ester, creatine monohydrate or placebo with loading and maintenance
limitations
The abstract conclusion overstates some comparisons: reported muscle total creatine did not differ significantly between formulations. This curation preserves the actual reported outcomes.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
30 previously non-resistance-trained men
plain_language
Ethyl ester did not show the claimed advantage in the measured outcomes.
primary_references
[creatine-p19228401] The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels. (2009). https://pubmed.ncbi.nlm.nih.gov/19228401/ DOI: 10.1186/1550-2783-6-6
tissue_or_cell_type
Serum and muscle metabolites, body composition and performance
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 1114–1125
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Seven-week randomized double-blind comparison plus resistance training · source_derived_draft · unverified_draft
### creatine-ethyl-ester-no-superiority Both creatine formulations increased muscle total creatine versus placebo, with no significant difference between formulations; performance and body-composition changes did not significantly differ between groups. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Ethyl ester did not show the claimed advantage in the measured outcomes. organism: 30 previously non-resistance-trained men tissue_or_cell_type: Serum and muscle metabolites, body composition and performance experimental_model: Seven-week randomized double-blind comparison plus resistance training limitations: The abstract conclusion overstates some comparisons: reported muscle total creatine did not differ significantly between formulations. This curation preserves the actual reported outcomes. exposure: Creatine ethyl ester, creatine monohydrate or placebo with loading and maintenance evidence_span: {"source_cache": "artifacts/creatine-research/19228401.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "381c3f18fe14f7eba6ee3abe9ca81ab4f02c293c3dd4593ea27dcbb6f879a114", "start_char": 0, "end_char": 1727, "text_sha256": "381c3f18fe14f7eba6ee3abe9ca81ab4f02c293c3dd4593ea27dcbb6f879a114"} [creatine-p19228401] The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels. (2009). https://pubmed.ncbi.nlm.nih.gov/19228401/ DOI: 10.1186/1550-2783-6-6
Complete structured claim and evidence
Creatine did not improve survival or the decline in functional measurements in the ALS trial.
Creatine monohydrate → ALS functional progression and survival source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/12666111.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9b668ab22f36cab83a9ccca495012eeff4c953adbd62955fa0efba24a06477ed", "start_char": 0, "end_char": 1367, "text_sha256": "9b668ab22f36cab83a9ccca495012eeff4c953adbd62955fa0efba24a06477ed"}
experimental_model
Double-blind placebo-controlled clinical trial
exposure
Creatine monohydrate 10 g/day versus placebo
limitations
Negative human trial despite a preceding mouse rationale; no inference to every neurological condition.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
175 people with ALS
plain_language
An energy-related mechanism and a promising mouse model did not translate into benefit in this human trial.
primary_references
[creatine-p12666111] A randomized sequential trial of creatine in amyotrophic lateral sclerosis. (2003). https://pubmed.ncbi.nlm.nih.gov/12666111/ DOI: 10.1002/ana.10554
tissue_or_cell_type
Survival and functional progression
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 1127–1138
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind placebo-controlled clinical trial · source_derived_draft · unverified_draft
### creatine-als-negative Creatine did not improve survival or the decline in functional measurements in the ALS trial. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An energy-related mechanism and a promising mouse model did not translate into benefit in this human trial. organism: 175 people with ALS tissue_or_cell_type: Survival and functional progression experimental_model: Double-blind placebo-controlled clinical trial limitations: Negative human trial despite a preceding mouse rationale; no inference to every neurological condition. exposure: Creatine monohydrate 10 g/day versus placebo evidence_span: {"source_cache": "artifacts/creatine-research/12666111.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9b668ab22f36cab83a9ccca495012eeff4c953adbd62955fa0efba24a06477ed", "start_char": 0, "end_char": 1367, "text_sha256": "9b668ab22f36cab83a9ccca495012eeff4c953adbd62955fa0efba24a06477ed"} [creatine-p12666111] A randomized sequential trial of creatine in amyotrophic lateral sclerosis. (2003). https://pubmed.ncbi.nlm.nih.gov/12666111/ DOI: 10.1002/ana.10554
Complete structured claim and evidence
The trial was stopped for futility; creatine did not improve the primary clinical progression comparison (P=0.45).
Creatine monohydrate → Parkinson disease clinical progression source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/25668262.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f671e1277dae81047694ee994f7375030d1b744b83a5a7ffcf410b13b69cd419", "start_char": 0, "end_char": 2637, "text_sha256": "f671e1277dae81047694ee994f7375030d1b744b83a5a7ffcf410b13b69cd419"}
experimental_model
Multicenter double-blind randomized NET-PD LS-1 trial
exposure
Creatine monohydrate 10 g/day; median follow-up four years; planned five-year outcome
limitations
Stopped early for futility; distinguishes intended follow-up from actual median duration.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
1741 people with early treated Parkinson disease
plain_language
Long-term testing did not confirm the hoped-for clinical benefit for Parkinson disease.
primary_references
[creatine-p25668262] Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial. (2015). https://pubmed.ncbi.nlm.nih.gov/25668262/ DOI: 10.1001/jama.2015.120
tissue_or_cell_type
Composite clinical progression
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 1140–1151
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicenter double-blind randomized NET-PD LS-1 trial · source_derived_draft · unverified_draft
### creatine-parkinson-negative The trial was stopped for futility; creatine did not improve the primary clinical progression comparison (P=0.45). Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Long-term testing did not confirm the hoped-for clinical benefit for Parkinson disease. organism: 1741 people with early treated Parkinson disease tissue_or_cell_type: Composite clinical progression experimental_model: Multicenter double-blind randomized NET-PD LS-1 trial limitations: Stopped early for futility; distinguishes intended follow-up from actual median duration. exposure: Creatine monohydrate 10 g/day; median follow-up four years; planned five-year outcome evidence_span: {"source_cache": "artifacts/creatine-research/25668262.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f671e1277dae81047694ee994f7375030d1b744b83a5a7ffcf410b13b69cd419", "start_char": 0, "end_char": 2637, "text_sha256": "f671e1277dae81047694ee994f7375030d1b744b83a5a7ffcf410b13b69cd419"} [creatine-p25668262] Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial. (2015). https://pubmed.ncbi.nlm.nih.gov/25668262/ DOI: 10.1001/jama.2015.120
Complete structured claim and evidence
DHT rose 56% after loading and remained 40% above baseline after maintenance in the creatine condition; serum testosterone did not change.
Creatine → Serum dihydrotestosterone concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/19741313.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1a90f951d101c58728a098b31f98db2fe8c509d5811d7a08e5b2052cd930f1d3", "start_char": 0, "end_char": 1975, "text_sha256": "1a90f951d101c58728a098b31f98db2fe8c509d5811d7a08e5b2052cd930f1d3"}
experimental_model
Double-blind placebo-controlled crossover study
exposure
25 g/day creatine with glucose for seven days then 5 g/day for 14 days
limitations
DHT was measured, not hair loss; the proposed increased testosterone-to-DHT conversion was an interpretation, not an enzyme assay.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
20 college-aged male rugby players
plain_language
This small study reported a hormone change but did not measure hair loss.
primary_references
[creatine-p19741313] Three weeks of creatine monohydrate supplementation affects dihydrotestosterone to testosterone ratio in college-aged rugby players. (2009). https://pubmed.ncbi.nlm.nih.gov/19741313/ DOI: 10.1097/jsm.0b013e3181b8b52f
tissue_or_cell_type
Serum hormones
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 1153–1164
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind placebo-controlled crossover study · source_derived_draft · unverified_draft
### creatine-dht-loading-study DHT rose 56% after loading and remained 40% above baseline after maintenance in the creatine condition; serum testosterone did not change. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This small study reported a hormone change but did not measure hair loss. organism: 20 college-aged male rugby players tissue_or_cell_type: Serum hormones experimental_model: Double-blind placebo-controlled crossover study limitations: DHT was measured, not hair loss; the proposed increased testosterone-to-DHT conversion was an interpretation, not an enzyme assay. exposure: 25 g/day creatine with glucose for seven days then 5 g/day for 14 days evidence_span: {"source_cache": "artifacts/creatine-research/19741313.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1a90f951d101c58728a098b31f98db2fe8c509d5811d7a08e5b2052cd930f1d3", "start_char": 0, "end_char": 1975, "text_sha256": "1a90f951d101c58728a098b31f98db2fe8c509d5811d7a08e5b2052cd930f1d3"} [creatine-p19741313] Three weeks of creatine monohydrate supplementation affects dihydrotestosterone to testosterone ratio in college-aged rugby players. (2009). https://pubmed.ncbi.nlm.nih.gov/19741313/ DOI: 10.1097/jsm.0b013e3181b8b52f
Complete structured claim and evidence
There were no significant group-by-time differences in DHT or DHT-to-testosterone ratio after 12 weeks.
Creatine monohydrate → Serum dihydrotestosterone concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/40265319.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dede40817f51a6dbe3d53dc09cefa031cee507182056cb23c068678563dfb2bf", "start_char": 0, "end_char": 2039, "text_sha256": "dede40817f51a6dbe3d53dc09cefa031cee507182056cb23c068678563dfb2bf"}
experimental_model
Twelve-week randomized placebo-controlled trial
exposure
Creatine monohydrate 5 g/day versus maltodextrin placebo
limitations
Different dose and duration from the 2009 loading study; short follow-up cannot establish every long-term or genetically susceptible outcome.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
38 completing resistance-trained men out of 45 recruited
plain_language
A later maintenance-dose trial did not reproduce the earlier hormone signal.
primary_references
[creatine-p40265319] Does creatine cause hair loss? A 12-week randomized controlled trial. (2025). https://pubmed.ncbi.nlm.nih.gov/40265319/ DOI: 10.1080/15502783.2025.2495229
tissue_or_cell_type
Serum hormones and objective hair measurements
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 1166–1177
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve-week randomized placebo-controlled trial · source_derived_draft · unverified_draft
### creatine-dht-maintenance-study There were no significant group-by-time differences in DHT or DHT-to-testosterone ratio after 12 weeks. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A later maintenance-dose trial did not reproduce the earlier hormone signal. organism: 38 completing resistance-trained men out of 45 recruited tissue_or_cell_type: Serum hormones and objective hair measurements experimental_model: Twelve-week randomized placebo-controlled trial limitations: Different dose and duration from the 2009 loading study; short follow-up cannot establish every long-term or genetically susceptible outcome. exposure: Creatine monohydrate 5 g/day versus maltodextrin placebo evidence_span: {"source_cache": "artifacts/creatine-research/40265319.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dede40817f51a6dbe3d53dc09cefa031cee507182056cb23c068678563dfb2bf", "start_char": 0, "end_char": 2039, "text_sha256": "dede40817f51a6dbe3d53dc09cefa031cee507182056cb23c068678563dfb2bf"} [creatine-p40265319] Does creatine cause hair loss? A 12-week randomized controlled trial. (2025). https://pubmed.ncbi.nlm.nih.gov/40265319/ DOI: 10.1080/15502783.2025.2495229
Complete structured claim and evidence
Hair density, follicular unit count and cumulative hair thickness did not differ significantly between creatine and placebo over 12 weeks.
Creatine monohydrate → Hair density, follicular unit count and cumulative hair thickness source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/40265319.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dede40817f51a6dbe3d53dc09cefa031cee507182056cb23c068678563dfb2bf", "start_char": 0, "end_char": 2039, "text_sha256": "dede40817f51a6dbe3d53dc09cefa031cee507182056cb23c068678563dfb2bf"}
experimental_model
Twelve-week randomized placebo-controlled trial
exposure
Creatine monohydrate 5 g/day versus maltodextrin placebo
limitations
Different dose and duration from the 2009 loading study; short follow-up cannot establish every long-term or genetically susceptible outcome.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
38 completing resistance-trained men out of 45 recruited
plain_language
This trial measured hair directly and found no group difference over its follow-up.
primary_references
[creatine-p40265319] Does creatine cause hair loss? A 12-week randomized controlled trial. (2025). https://pubmed.ncbi.nlm.nih.gov/40265319/ DOI: 10.1080/15502783.2025.2495229
tissue_or_cell_type
Serum hormones and objective hair measurements
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 1179–1190
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve-week randomized placebo-controlled trial · source_derived_draft · unverified_draft
### creatine-hair-trial Hair density, follicular unit count and cumulative hair thickness did not differ significantly between creatine and placebo over 12 weeks. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This trial measured hair directly and found no group difference over its follow-up. organism: 38 completing resistance-trained men out of 45 recruited tissue_or_cell_type: Serum hormones and objective hair measurements experimental_model: Twelve-week randomized placebo-controlled trial limitations: Different dose and duration from the 2009 loading study; short follow-up cannot establish every long-term or genetically susceptible outcome. exposure: Creatine monohydrate 5 g/day versus maltodextrin placebo evidence_span: {"source_cache": "artifacts/creatine-research/40265319.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dede40817f51a6dbe3d53dc09cefa031cee507182056cb23c068678563dfb2bf", "start_char": 0, "end_char": 2039, "text_sha256": "dede40817f51a6dbe3d53dc09cefa031cee507182056cb23c068678563dfb2bf"} [creatine-p40265319] Does creatine cause hair loss? A 12-week randomized controlled trial. (2025). https://pubmed.ncbi.nlm.nih.gov/40265319/ DOI: 10.1080/15502783.2025.2495229
Complete structured claim and evidence
Ouabain-sensitive extrusion was approximately three sodium ions per ATP hydrolyzed in resealed erythrocyte ghosts.
Sodium-potassium ATPase complexes → Sodium-pump-mediated sodium efflux source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Sodium export couples to potassium-supported pump cycling and magnesium-dependent energy use.
experimental_model
Radiotracer sodium and ATP-hydrolysis assay.
limitations
This measurement does not itself establish an exact two-potassium ratio.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Human
plain_language
ATP consumption pays for sodium extrusion while potassium is available externally.
primary_references
[garrahan-1967-pump] The stoicheiometry of the sodium pump (1967). https://pmc.ncbi.nlm.nih.gov/articles/PMC1365482/ DOI: 10.1113/jphysiol.1967.sp008297
tissue_or_cell_type
Erythrocyte membrane
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 587–597
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiotracer sodium and ATP-hydrolysis assay. · source_derived_draft · unverified_draft
### k-pump-sodium-atp-coupling Ouabain-sensitive extrusion was approximately three sodium ions per ATP hydrolyzed in resealed erythrocyte ghosts. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP consumption pays for sodium extrusion while potassium is available externally. organism: Human tissue_or_cell_type: Erythrocyte membrane experimental_model: Radiotracer sodium and ATP-hydrolysis assay. limitations: This measurement does not itself establish an exact two-potassium ratio. cross_nutrient: Sodium export couples to potassium-supported pump cycling and magnesium-dependent energy use. [garrahan-1967-pump] The stoicheiometry of the sodium pump (1967). https://pmc.ncbi.nlm.nih.gov/articles/PMC1365482/ DOI: 10.1113/jphysiol.1967.sp008297
Complete structured claim and evidence
Pre-steady-state pig-kidney pump experiments identified Mg as an essential activator of ATP-dependent phosphorylation.
Mg2+ → Sodium-potassium ATPase phosphorylation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration.
experimental_model
Pig-kidney Na/K-ATPase rapid-mixing phosphorylation; Na-containing, K-free medium; varied ATP and MgCl2.
limitations
Na-containing, K-free assay; not the full physiological transport cycle.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Sus scrofa
plain_language
Magnesium enables the ATP-driven phosphate-transfer step of the sodium pump.
primary_references
[campos-1992-nka] Effects of magnesium and ATP on pre-steady-state phosphorylation kinetics of the Na+,K(+)-ATPase (1992). https://pubmed.ncbi.nlm.nih.gov/1314673/ DOI: 10.1016/0005-2736(92)90161-e
tissue_or_cell_type
Kidney enzyme
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 771–781
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pig-kidney Na/K-ATPase rapid-mixing phosphorylation; Na-containing, K-free medium; varied ATP and MgCl2. · source_derived_draft · unverified_draft
### mg-nka-phosphorylation-requirement Pre-steady-state pig-kidney pump experiments identified Mg as an essential activator of ATP-dependent phosphorylation. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium enables the ATP-driven phosphate-transfer step of the sodium pump. organism: Sus scrofa tissue_or_cell_type: Kidney enzyme experimental_model: Pig-kidney Na/K-ATPase rapid-mixing phosphorylation; Na-containing, K-free medium; varied ATP and MgCl2. limitations: Na-containing, K-free assay; not the full physiological transport cycle. cross_nutrient: Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration. [campos-1992-nka] Effects of magnesium and ATP on pre-steady-state phosphorylation kinetics of the Na+,K(+)-ATPase (1992). https://pubmed.ncbi.nlm.nih.gov/1314673/ DOI: 10.1016/0005-2736(92)90161-e
Complete structured claim and evidence
Adding KCl after ATP phosphorylation accelerated dephosphorylation of pig-kidney Na/K-ATPase.
Potassium ion → Sodium-potassium ATPase dephosphorylation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration.
experimental_model
Pig-kidney enzyme stopped-flow RH421 fluorescence; sequential ATP then KCl mixing.
limitations
Stopped-flow assay; no dietary or magnesium-depletion intervention.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Sus scrofa
plain_language
Potassium promotes the phosphate-removal part of the pump cycle.
primary_references
[kane-1998-nka] Dephosphorylation kinetics of pig kidney Na+,K+-ATPase (1998). https://pubmed.ncbi.nlm.nih.gov/9521778/ DOI: 10.1021/bi972813e
tissue_or_cell_type
Kidney enzyme
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 807–817
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pig-kidney enzyme stopped-flow RH421 fluorescence; sequential ATP then KCl mixing. · source_derived_draft · unverified_draft
### mg-nka-potassium-dephosphorylation Adding KCl after ATP phosphorylation accelerated dephosphorylation of pig-kidney Na/K-ATPase. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium promotes the phosphate-removal part of the pump cycle. organism: Sus scrofa tissue_or_cell_type: Kidney enzyme experimental_model: Pig-kidney enzyme stopped-flow RH421 fluorescence; sequential ATP then KCl mixing. limitations: Stopped-flow assay; no dietary or magnesium-depletion intervention. cross_nutrient: Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration. [kane-1998-nka] Dephosphorylation kinetics of pig kidney Na+,K+-ATPase (1998). https://pubmed.ncbi.nlm.nih.gov/9521778/ DOI: 10.1021/bi972813e
Complete structured claim and evidence
Combined Mg and Zn reconstituted demetalated TNAP activity; neither metal alone restored the same activity.
Mg2+ → Tissue-nonspecific alkaline phosphatase ALPL / TNAP source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium + zinc -> ALPL; connects to calcium/phosphate mineralization.
experimental_model
Recombinant TNAP metal-reconstitution assay. Activity was measured using artificial pNPP substrate.
limitations
Not an oral supplementation synergy trial. This assay does not quantify physiological pyrophosphate turnover or mineral deposition.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
This mineralization enzyme needs the right metals in different sites.
primary_references
[mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874
tissue_or_cell_type
Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1467–1477
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant TNAP metal-reconstitution assay. Activity was measured using artificial pNPP substrate. · source_derived_draft · unverified_draft
### mg-zinc-alpl-reconstitution Combined Mg and Zn reconstituted demetalated TNAP activity; neither metal alone restored the same activity. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This mineralization enzyme needs the right metals in different sites. organism: Homo sapiens tissue_or_cell_type: Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay experimental_model: Recombinant TNAP metal-reconstitution assay. Activity was measured using artificial pNPP substrate. limitations: Not an oral supplementation synergy trial. This assay does not quantify physiological pyrophosphate turnover or mineral deposition. cross_nutrient: Magnesium + zinc -> ALPL; connects to calcium/phosphate mineralization. [mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874
Complete structured claim and evidence
Human fibroblast ALPL hydrolyzed extracellular micromolar PLP at physiological pH; intact-cell and PI-PLC experiments supported lipid-anchored ecto-orientation.
Tissue-nonspecific alkaline phosphatase ALPL / TNAP → PLP source_derived_draftungraded
Experimental context and source evidence
evidence_location
Indexed abstract: intact/disrupted cells, PI-PLC and patient enzyme activity
experimental_model
Normal and hypophosphatasia human skin fibroblasts.
exposure
Extracellular PLP; intact versus disrupted cells; PI-PLC release.
limitations
Directly demonstrated in fibroblasts; does not itself measure brain entry.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Cell-surface ALPL processes PLP outside the cell.
primary_references
[fedde1990] Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase: normal and hypophosphatasia fibroblast study. (1990). https://pubmed.ncbi.nlm.nih.gov/2220817/
tissue_or_cell_type
Skin fibroblasts
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 309–320
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Normal and hypophosphatasia human skin fibroblasts. · source_derived_draft · unverified_draft
### b6-transport-alpl-ecto Human fibroblast ALPL hydrolyzed extracellular micromolar PLP at physiological pH; intact-cell and PI-PLC experiments supported lipid-anchored ecto-orientation. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cell-surface ALPL processes PLP outside the cell. organism: Homo sapiens tissue_or_cell_type: Skin fibroblasts experimental_model: Normal and hypophosphatasia human skin fibroblasts. limitations: Directly demonstrated in fibroblasts; does not itself measure brain entry. exposure: Extracellular PLP; intact versus disrupted cells; PI-PLC release. evidence_location: Indexed abstract: intact/disrupted cells, PI-PLC and patient enzyme activity [fedde1990] Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase: normal and hypophosphatasia fibroblast study. (1990). https://pubmed.ncbi.nlm.nih.gov/2220817/
Complete structured claim and evidence
The ZnT5-ZnT6 and ZnT7 complexes support TNAP conversion from apoenzyme to zinc-loaded active enzyme in the early secretory pathway.
Human ZnT5-ZnT6 heterodimer → Tissue-nonspecific alkaline phosphatase ALPL / TNAP source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation
exposure
ZnT gene disruption and transporter re-expression comparisons.
limitations
Primary abstract-level evidence in engineered chicken DT40 cells with transporter complementation. Not a human dietary deficiency or supplementation trial; assay exposure amounts and mutant-specific residue effects are not inferred.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Gallus gallus cell model with human proteins
plain_language
Specific transporter complexes deliver zinc while TNAP matures.
primary_references
[zinc-enz-znt-tnap2011] Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. (2011). https://pubmed.ncbi.nlm.nih.gov/21402707/ DOI: 10.1074/jbc.m111.227173
tissue_or_cell_type
Chicken DT40 early secretory pathway; human transporter complementation
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 768–779
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation · source_derived_draft · unverified_draft
### zinc-enz-znt-specific-maturation The ZnT5-ZnT6 and ZnT7 complexes support TNAP conversion from apoenzyme to zinc-loaded active enzyme in the early secretory pathway. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Specific transporter complexes deliver zinc while TNAP matures. organism: Gallus gallus cell model with human proteins tissue_or_cell_type: Chicken DT40 early secretory pathway; human transporter complementation experimental_model: Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation limitations: Primary abstract-level evidence in engineered chicken DT40 cells with transporter complementation. Not a human dietary deficiency or supplementation trial; assay exposure amounts and mutant-specific residue effects are not inferred. exposure: ZnT gene disruption and transporter re-expression comparisons. cross_nutrient: false [zinc-enz-znt-tnap2011] Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. (2011). https://pubmed.ncbi.nlm.nih.gov/21402707/ DOI: 10.1074/jbc.m111.227173
Complete structured claim and evidence
Extracellular zinc supplementation did not restore reduced TNAP activity in DT40 cells deficient in both ZnT5-ZnT6 and ZnT7 complexes.
Zinc(II) ion → Tissue-nonspecific alkaline phosphatase ALPL / TNAP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation
exposure
Genetic deficiency of the two specific secretory ZnT complexes, followed by zinc supplementation in culture; amount unreported in abstract.
limitations
Primary abstract-level evidence in engineered chicken DT40 cells with transporter complementation. Not a human dietary deficiency or supplementation trial; assay exposure amounts and mutant-specific residue effects are not inferred.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Gallus gallus
plain_language
More available zinc did not bypass missing enzyme-loading machinery.
primary_references
[zinc-enz-znt-tnap2011] Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. (2011). https://pubmed.ncbi.nlm.nih.gov/21402707/ DOI: 10.1074/jbc.m111.227173
tissue_or_cell_type
Chicken DT40 early secretory pathway
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 781–792
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation · source_derived_draft · unverified_draft
### zinc-enz-zinc-cannot-bypass-znt-loss Extracellular zinc supplementation did not restore reduced TNAP activity in DT40 cells deficient in both ZnT5-ZnT6 and ZnT7 complexes. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: More available zinc did not bypass missing enzyme-loading machinery. organism: Gallus gallus tissue_or_cell_type: Chicken DT40 early secretory pathway experimental_model: Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation limitations: Primary abstract-level evidence in engineered chicken DT40 cells with transporter complementation. Not a human dietary deficiency or supplementation trial; assay exposure amounts and mutant-specific residue effects are not inferred. exposure: Genetic deficiency of the two specific secretory ZnT complexes, followed by zinc supplementation in culture; amount unreported in abstract. cross_nutrient: false [zinc-enz-znt-tnap2011] Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. (2011). https://pubmed.ncbi.nlm.nih.gov/21402707/ DOI: 10.1074/jbc.m111.227173
Complete structured claim and evidence
Added TNAP restored mineralization in calcitriol-treated differentiated mouse osteoblast cultures while lowering extracellular pyrophosphate.
Tissue-nonspecific alkaline phosphatase ALPL / TNAP → Osteoblast mineralization source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin D–calcium–phosphate regulation.
evidence_locator
Figure 6 and adjacent Results: mineralization restored by TNAP
evidence_scope
D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.
experimental_model
Differentiated primary mouse osteoblasts; Alizarin red mineralization and conditioned-medium pyrophosphate assays
exposure
10^-8 M calcitriol and 1 U/mL added TNAP for 4 days; companion cultures tested 5 x 10^-6 M pyrophosphate.
limitations
Enzyme-addition culture rescue supports pyrophosphate involvement; it does not quantify human bone outcomes or establish the contribution of each calcitriol-regulated gene.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Mus musculus
plain_language
Removing the pyrophosphate brake restored mineral deposition in the treated cultures.
primary_references
[vdm-lieben2012] Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. (2012). https://pubmed.ncbi.nlm.nih.gov/22523068/ DOI: 10.1172/jci45890
tissue_or_cell_type
Osteoblast extracellular matrix
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 825–839
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated primary mouse osteoblasts; Alizarin red mineralization and conditioned-medium pyrophosphate assays · source_derived_draft · unverified_draft
### vdm-tnap-rescues-calcitriol-culture-mineralization Added TNAP restored mineralization in calcitriol-treated differentiated mouse osteoblast cultures while lowering extracellular pyrophosphate. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing the pyrophosphate brake restored mineral deposition in the treated cultures. organism: Mus musculus tissue_or_cell_type: Osteoblast extracellular matrix experimental_model: Differentiated primary mouse osteoblasts; Alizarin red mineralization and conditioned-medium pyrophosphate assays limitations: Enzyme-addition culture rescue supports pyrophosphate involvement; it does not quantify human bone outcomes or establish the contribution of each calcitriol-regulated gene. exposure: 10^-8 M calcitriol and 1 U/mL added TNAP for 4 days; companion cultures tested 5 x 10^-6 M pyrophosphate. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Figure 6 and adjacent Results: mineralization restored by TNAP nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-lieben2012] Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. (2012). https://pubmed.ncbi.nlm.nih.gov/22523068/ DOI: 10.1172/jci45890
Complete structured claim and evidence
Reconstituted human MTR transfers methylfolate-derived methyl groups through cobalamin to homocysteine, producing methionine and THF.
Cobalamin-dependent methionine synthase / MTR → L-Methionine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Folate methyl transfer requires B12.
experimental_model
Human MTR/MTRR expressed in insect cells; purified enzymes and extracts.
limitations
Chemistry, not dietary response.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
B12-dependent MTR recycles both homocysteine and folate.
primary_references
[yamada-2006] Human methionine synthase reductase is a molecular chaperone for human methionine synthase (2006). https://pubmed.ncbi.nlm.nih.gov/16769880/ DOI: 10.1073/pnas.0603694103
tissue_or_cell_type
Purified protein
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 482–492
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MTR/MTRR expressed in insect cells; purified enzymes and extracts. · source_derived_draft · unverified_draft
### folate-methyl-mtr-methyl-transfer Reconstituted human MTR transfers methylfolate-derived methyl groups through cobalamin to homocysteine, producing methionine and THF. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: B12-dependent MTR recycles both homocysteine and folate. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Human MTR/MTRR expressed in insect cells; purified enzymes and extracts. limitations: Chemistry, not dietary response. cross_nutrient: Folate methyl transfer requires B12. [yamada-2006] Human methionine synthase reductase is a molecular chaperone for human methionine synthase (2006). https://pubmed.ncbi.nlm.nih.gov/16769880/ DOI: 10.1073/pnas.0603694103
Complete structured claim and evidence
Purified human BHMT uses betaine and homocysteine in the alternative methionine-forming reaction.
Betaine-homocysteine S-methyltransferase / BHMT → L-Methionine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Betaine/choline and folate routes meet at homocysteine.
experimental_model
Recombinant human BHMT and human liver-derived BHMT.
limitations
Does not establish complete folate substitution in vivo.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
Betaine supplies another recycling route.
primary_references
[millian-1998] Human betaine-homocysteine methyltransferase is a zinc metalloenzyme (1998). https://pubmed.ncbi.nlm.nih.gov/9681996/ DOI: 10.1006/abbi.1998.0757
tissue_or_cell_type
Recombinant and liver-derived enzyme
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 610–620
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human BHMT and human liver-derived BHMT. · source_derived_draft · unverified_draft
### folate-methyl-bhmt-reaction Purified human BHMT uses betaine and homocysteine in the alternative methionine-forming reaction. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Betaine supplies another recycling route. organism: Homo sapiens tissue_or_cell_type: Recombinant and liver-derived enzyme experimental_model: Recombinant human BHMT and human liver-derived BHMT. limitations: Does not establish complete folate substitution in vivo. cross_nutrient: Betaine/choline and folate routes meet at homocysteine. [millian-1998] Human betaine-homocysteine methyltransferase is a zinc metalloenzyme (1998). https://pubmed.ncbi.nlm.nih.gov/9681996/ DOI: 10.1006/abbi.1998.0757
Complete structured claim and evidence
Chemical zinc removal inactivated human BHMT; zinc reconstitution restored its activity and metal content.
Zinc(II) ion → Betaine-homocysteine S-methyltransferase / BHMT source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc supports parallel remethylation.
experimental_model
Recombinant human BHMT and human liver-derived BHMT.
limitations
Demetallation is not dietary zinc deficiency.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
The betaine route requires a zinc-containing enzyme.
primary_references
[millian-1998] Human betaine-homocysteine methyltransferase is a zinc metalloenzyme (1998). https://pubmed.ncbi.nlm.nih.gov/9681996/ DOI: 10.1006/abbi.1998.0757
tissue_or_cell_type
Purified protein
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 622–632
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human BHMT and human liver-derived BHMT. · source_derived_draft · unverified_draft
### folate-methyl-bhmt-zinc Chemical zinc removal inactivated human BHMT; zinc reconstitution restored its activity and metal content. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The betaine route requires a zinc-containing enzyme. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Recombinant human BHMT and human liver-derived BHMT. limitations: Demetallation is not dietary zinc deficiency. cross_nutrient: Zinc supports parallel remethylation. [millian-1998] Human betaine-homocysteine methyltransferase is a zinc metalloenzyme (1998). https://pubmed.ncbi.nlm.nih.gov/9681996/ DOI: 10.1006/abbi.1998.0757
Complete structured claim and evidence
Purified recombinant human MTRR contained equimolar FAD and FMN, identifying two distinct flavin cofactors in the same reductase.
Methionine synthase reductase / MTRR → FAD source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-derived flavins form part of the B12-reactivation machinery.
evidence_location
Abstract
experimental_model
Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution.
exposure
Purified-enzyme assay
limitations
Biochemical evidence does not establish a dietary threshold or supplementation benefit.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
MTRR uses both B2-derived cofactors.
primary_references
[olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1094–1106
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. · source_derived_draft · unverified_draft
### b2-mtrr-dual-flavins Purified recombinant human MTRR contained equimolar FAD and FMN, identifying two distinct flavin cofactors in the same reductase. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: MTRR uses both B2-derived cofactors. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. limitations: Biochemical evidence does not establish a dietary threshold or supplementation benefit. exposure: Purified-enzyme assay cross_nutrient: B2-derived flavins form part of the B12-reactivation machinery. evidence_location: Abstract [olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
Complete structured claim and evidence
Reconstituted assays showed human MTRR sufficient to support NADPH-dependent activity of cobalamin-dependent methionine synthase.
Methionine synthase reductase / MTRR → Cobalamin-dependent methionine synthase / MTR source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2 flavins support reactivation of B12-dependent folate/homocysteine metabolism.
evidence_location
Abstract
experimental_model
Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution.
exposure
Purified-enzyme assay
limitations
Reconstituted biochemistry; the accessible abstract identifies human MTRR but not the target MTR species. No dietary B2/B12 synergy was tested.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
The flavin reductase helps restore an enzyme that uses B12 and methylfolate.
primary_references
[olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1122–1134
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. · source_derived_draft · unverified_draft
### b2-mtrr-mtr-reactivation Reconstituted assays showed human MTRR sufficient to support NADPH-dependent activity of cobalamin-dependent methionine synthase. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The flavin reductase helps restore an enzyme that uses B12 and methylfolate. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. limitations: Reconstituted biochemistry; the accessible abstract identifies human MTRR but not the target MTR species. No dietary B2/B12 synergy was tested. exposure: Purified-enzyme assay cross_nutrient: B2 flavins support reactivation of B12-dependent folate/homocysteine metabolism. evidence_location: Abstract [olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
Complete structured claim and evidence
Human SHMT1 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate.
SHMT1 → 5,10-Methylenetetrahydrofolate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
PLP (B6) and THF (folate) cooperate in one reaction.
experimental_model
Purified human SHMT1 and SHMT2; structures and solution oligomerization
limitations
Reaction is reversible; assembly assays do not establish flux in every cell.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The enzyme connects B6-dependent amino-acid chemistry to folate chemistry.
primary_references
[b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 602–612
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SHMT1 and SHMT2; structures and solution oligomerization · source_derived_draft · unverified_draft
### b6-met-shmt1-onecarbon Human SHMT1 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme connects B6-dependent amino-acid chemistry to folate chemistry. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human SHMT1 and SHMT2; structures and solution oligomerization limitations: Reaction is reversible; assembly assays do not establish flux in every cell. cross_nutrient: PLP (B6) and THF (folate) cooperate in one reaction. [b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
Complete structured claim and evidence
Human SHMT2 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate.
SHMT2 → 5,10-Methylenetetrahydrofolate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
PLP (B6) and THF (folate) cooperate in one reaction.
experimental_model
Purified human SHMT1 and SHMT2; structures and solution oligomerization
limitations
Reaction is reversible; assembly assays do not establish flux in every cell.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The enzyme connects B6-dependent amino-acid chemistry to folate chemistry.
primary_references
[b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 614–624
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SHMT1 and SHMT2; structures and solution oligomerization · source_derived_draft · unverified_draft
### b6-met-shmt2-onecarbon Human SHMT2 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme connects B6-dependent amino-acid chemistry to folate chemistry. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human SHMT1 and SHMT2; structures and solution oligomerization limitations: Reaction is reversible; assembly assays do not establish flux in every cell. cross_nutrient: PLP (B6) and THF (folate) cooperate in one reaction. [b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
Complete structured claim and evidence
Plasma creatine decreased 40% in both meal states; creatinine fell 9% and dimethylglycine 16% postprandially.
Vitamin B6 → Creatine source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Plasma metabolites connect B6 status with one-carbon metabolism without establishing a complete causal chain.
experimental_model
Twenty-three healthy adults; paired pre/postprandial LC-MS/MS metabolite profiling.
exposure
28 days below 0.35 mg/day B6. Related restriction research program; do not count paper totals as independent trial replications.
limitations
This does not establish exhausted SAM, impaired muscle phosphocreatine or a direct PLP requirement for creatine methylation.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
B6 restriction changed selected methylation-related metabolites.
primary_references
[b6-dasilva2013] Metabolite profile analysis reveals functional effects of 28-day vitamin B-6 restriction on one-carbon metabolism and tryptophan catabolic pathways in healthy men and women (2013). https://pubmed.ncbi.nlm.nih.gov/23966327/ DOI: 10.3945/jn.113.180588
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1423–1434
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twenty-three healthy adults; paired pre/postprandial LC-MS/MS metabolite profiling. · source_derived_draft · unverified_draft
### b6-restriction-creatine-profile Plasma creatine decreased 40% in both meal states; creatinine fell 9% and dimethylglycine 16% postprandially. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6 restriction changed selected methylation-related metabolites. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Twenty-three healthy adults; paired pre/postprandial LC-MS/MS metabolite profiling. limitations: This does not establish exhausted SAM, impaired muscle phosphocreatine or a direct PLP requirement for creatine methylation. exposure: 28 days below 0.35 mg/day B6. Related restriction research program; do not count paper totals as independent trial replications. cross_nutrient: Plasma metabolites connect B6 status with one-carbon metabolism without establishing a complete causal chain. [b6-dasilva2013] Metabolite profile analysis reveals functional effects of 28-day vitamin B-6 restriction on one-carbon metabolism and tryptophan catabolic pathways in healthy men and women (2013). https://pubmed.ncbi.nlm.nih.gov/23966327/ DOI: 10.3945/jn.113.180588
Complete structured claim and evidence

Availability and dependencies

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

The phosphate buffer can fail even when resting ATP looks normal

Condition: machinery_impairment · Muscle creatine kinase deletion

Normal role: Muscle CK rapidly exchanges phosphate between ATP and phosphocreatine.

Recorded consequence: Early phosphocreatine use is reduced despite similar resting PCr/ATP.

Scope: Mouse muscle contraction experiment

Losing the creatine-cycle kinase reduces fat thermogenesis

Condition: machinery_impairment · Adipocyte Ckb deletion

Normal role: CKB supports creatine-dependent ATP turnover in thermogenic adipocytes.

Recorded consequence: Reduced thermogenic capacity and predisposition to obesity in mice.

Scope: Mouse adipose-tissue gene deletion

The creatine cycle needs its phosphate-releasing step

Condition: machinery_impairment · TNAP inhibition or adipocyte Alpl deletion

Normal role: TNAP hydrolyzes phosphocreatine in thermogenic adipocytes.

Recorded consequence: Impaired cycling and lower energy expenditure in the mouse model.

Scope: Isolated adipocyte mitochondria and conditional knockout mice

A shared TNAP regulatory site links thermogenesis and mineralization

Condition: machinery_impairment · Disruption of the glycerol-binding pocket

Normal role: TNAP participates in both phosphate metabolism in bone and creatine cycling in fat.

Recorded consequence: Reduced TNAP-dependent mineralization in the tested variant systems.

Scope: Osteoblast experiments and human genetic associations

T cells can lose function when creatine transport is disabled

Condition: machinery_impairment · Slc6a8 deletion in the studied immune system

Normal role: SLC6A8 supplies creatine to immune cells.

Recorded consequence: Impaired antitumor immunity.

Scope: Mouse CD8 T-cell and tumor models

Creatine handling can affect signaling without lowering bulk energy charge

Condition: machinery_impairment · Slc6a8 or Ckb loss

Normal role: Transport and CKB-dependent phosphate transfer support T-cell homeostasis and activation.

Recorded consequence: Reduced expansion and weakened TCR-dependent mTORC1 activation.

Scope: Mouse CD8 T cells in infection experiments

When the creatine cycle is removed

Condition: machinery_impairment · Pharmacological creatine reduction, or adipocyte-selective deletion of the creatine-synthesising enzyme GATM.

Normal role: A futile creatine cycle in beige and brown fat dissipates energy alongside UCP1.

Recorded consequence: Energy expenditure and adipose metabolic rate fall, beta-3 activation of metabolic rate is blunted, and in UCP1-deficient mice core temperature falls.

Scope: Mouse adipose tissue

Epithelial creatine transport helps maintain the intestinal barrier

Condition: machinery_impairment · Transporter loss in epithelial preparations

Normal role: Creatine transport supports epithelial energy handling and junction organization.

Recorded consequence: Glycolytic stress and impaired barrier function.

Scope: T84 cells and mouse intestinal organoids

When fat cells cannot make their own creatine

Condition: machinery_impairment · Adipocyte-selective Gatm knockout.

Normal role: Adipocytes synthesise creatine through GATM to run the futile creatine cycle.

Recorded consequence: Diet-induced thermogenesis is suppressed and obesity follows, and dietary creatine supplementation rescues the beta-3 response.

Scope: Mouse adipose tissue

A blocked synthesis step can leave too much precursor as well as too little creatine

Condition: machinery_impairment · Experimental guanidinoacetate accumulation/exposure

Normal role: GAMT converts guanidinoacetate into creatine.

Recorded consequence: Impaired enzyme activity and oxidative-stress readouts in rat striatum.

Scope: Acute rat striatal and in-vitro experiments

Missing the first synthesis enzyme lowers precursor and brain creatine

Condition: machinery_impairment · Inherited GATM/AGAT loss

Normal role: AGAT supplies guanidinoacetate for GAMT.

Recorded consequence: Low guanidinoacetate and depleted brain creatine with developmental impairment.

Scope: Two human patients with AGAT deficiency

The second synthesis defect combines low creatine with excess precursor

Condition: machinery_impairment · Inherited GAMT deficiency

Normal role: GAMT converts guanidinoacetate to creatine using SAM.

Recorded consequence: Guanidinoacetate accumulation and creatine depletion.

Scope: Human GAMT-deficiency cases

Creatine can be high outside cells while the brain lacks it

Condition: machinery_impairment · Inherited creatine transporter dysfunction

Normal role: SLC6A8 allows creatine entry into cells.

Recorded consequence: Brain creatine depletion despite elevated plasma and urinary creatine.

Scope: Human SLC6A8-deficiency family

Restoring brain creatine does not erase every prior developmental effect

Condition: machinery_impairment · Delayed treatment of inherited AGAT deficiency

Normal role: Creatine supports brain energetics during development.

Recorded consequence: Incomplete developmental recovery despite biochemical repletion.

Scope: Four-patient long-term AGAT series

Lower dietary provision can lower measured creatine stores

Condition: nutrient_deficiency · Switch to a vegetarian diet in initially omnivorous women

Normal role: Dietary intake complements endogenous synthesis.

Recorded consequence: Lower plasma and muscle creatine by three months.

Scope: Six-month dietary intervention with combined-supplement arm

A higher creatinine result is not the same as more useful muscle creatine

Condition: biomarker_context · Creatine ethyl ester supplementation in a comparative trial

Normal role: Creatine formulations can change measured creatine and creatinine differently.

Recorded consequence: Higher serum creatinine without demonstrated superior muscle creatine or performance.

Scope: Seven-week human formulation trial

The sources

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

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

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

Open questions in this collection

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

Which intracellular molecule senses creatine to regulate human AGAT expression?The reporter study supports intracellular feedback but does not identify the sensor.
Why did the small loading study and later maintenance-dose trial report different DHT results?Different dosing, duration and populations are candidate explanations, not demonstrated mediators. Neither study proves a universal hair-loss effect.
Who experiences a clinically meaningful cognitive benefit, and under which conditions?The larger routine supplementation study and acute sleep-deprivation experiment had different designs and outcomes.
Can creatine reliably spare methyl donors in a way that improves human clinical outcomes?Rat homocysteine effects differ from the group-average human trial result; lower guanidinoacetate is not proof of improved DNA methylation or disease prevention.
Does targeting adipocyte creatine cycling improve human metabolic disease?Causal thermogenesis records are largely mouse and cellular experiments, not human treatment trials.
Do the immune and barrier mechanisms translate to a net clinical benefit in cancer or inflammatory bowel disease?Cellular and mouse mechanisms cannot determine human efficacy, tumor specificity or an effective treatment regimen.

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

Evidence, AI assistance and curation standards

Creatine

The mechanisms

AGAT catalyzes transfer of an amidino group from arginine to glycine, forming guanidinoacetate and ornithine.

GAMT transfers a methyl group from S-adenosylmethionine to guanidinoacetate, producing creatine and S-adenosylhomocysteine.

Creatine kinase catalyzes reversible phosphoryl transfer between ATP and creatine to form ADP and phosphocreatine.

Magnesium in the transition-state analogue complex coordinated ADP, nitrate and water ligands at the creatine kinase active site.

Human creatine-transporter expression conferred sodium-dependent creatine uptake with Km 14.9 ± 3.0 micromolar in five experiments.

The cloned rabbit creatine transporter mediated sodium- and chloride-dependent creatine uptake, with an apparent Km of approximately 35 micromolar.

AGAT reporter expression fell with intracellular creatine, with a reported intracellular IC50 of approximately 1–2 mM.

Creatine alone did not significantly lower total plasma homocysteine compared with placebo (P=0.35).

The AGAT-deficient sisters had low urinary guanidinoacetate, absent AGAT activity and brain creatine depletion.

The GAMT-deficient children had high brain guanidinoacetate, low blood creatine and severely deficient liver GAMT activity.

The SLC6A8-deficient male had absent brain creatine on spectroscopy and defective fibroblast creatine uptake despite high plasma and urinary creatine and normal guanidinoacetate.

TNAP localized to thermogenic adipocyte mitochondria and hydrolyzed phosphocreatine to support the futile creatine cycle.

Ornithine binding to human AGAT induced movement of a flexible loop and neighboring helix at the active-site region.

Methionine adenosylation supplies SAM, the methyl donor consumed when guanidinoacetate is converted to creatine.

Creatine feeding reduced renal AGAT activity to 26% of control in the studied rats.

Renal AGAT synthesis fell to 21% of control and functional AGAT mRNA to 37% with creatine feeding.

Creatinine excretion represents continuing loss from the creatine/phosphocreatine pool, which is replaced by diet and/or endogenous synthesis.

Isolated rat hepatocytes synthesized creatine from guanidinoacetate but could not carry out the entire pathway from methionine, arginine and glycine under the tested conditions.

Adding methionine increased hepatocyte SAM and creatine synthesis from guanidinoacetate.

Creatine feeding reduced renal AGAT and circulating guanidinoacetate without reducing hepatic GAMT activity or capacity to synthesize creatine from guanidinoacetate.

The high-affinity component of creatine accumulation and AGAT regulation depended on SLC6A8, whereas a nonsaturable component remained without the transporter.

The mitochondrial creatine kinase structure supported an octameric enzyme positioned to convert mitochondrially generated ATP into phosphocreatine.

Mitochondrial creatine kinase selectively recruited cardiolipin and promoted lipid clustering in the tested reconstituted membranes.

At 2 seconds of stimulation, phosphocreatine depletion was approximately 2.2% in MM-CK-deficient muscle versus 9.7% in wild type.

Resting PCr/ATP and pH did not differ, and no ATP change was detected at 2 seconds despite altered early phosphocreatine depletion.

The increase in muscle total creatine was 60% greater with carbohydrate plus creatine than with creatine alone; urinary creatine loss was lower.

The two higher insulin infusion conditions increased muscle creatine accumulation, by approximately 4.5 and 8.3 mmol/kg dry muscle, during creatine administration.

Limb blood-flow differences did not explain the insulin-associated increase in muscle creatine accumulation.

Thermogenic stimulation induced CKB expression in human and mouse adipocytes in the study.

CKB trafficked to adipocyte mitochondria through an internal mitochondrial targeting sequence and supported the futile creatine cycle.

Adipocyte Ckb deletion reduced thermogenic capacity and predisposed mice to obesity and disturbed glucose handling.

TNAP inhibition abolished the measured futile creatine cycle in isolated thermogenic-fat mitochondria.

Adipocyte Alpl deletion reduced energy expenditure and increased obesity susceptibility without altered feeding or movement.

Glycerol bound a TNAP surface pocket distant from the active site and enhanced TNAP activity.

The TNAP glycerol pocket was required for TNAP-driven thermogenesis through the futile creatine cycle in the tested systems.

Human missense variants in the glycerol pocket reduced TNAP-dependent mineralization in vitro and were associated with lower alkaline phosphatase activity and bone mineral density.

Loss of Slc6a8 impaired CD8 T-cell antitumor immunity in the studied mouse models.

Creatine supplementation suppressed tumor growth in the tested mouse models and enhanced the effects of PD-1/PD-L1 checkpoint blockade.

Loss of either Ckb or Slc6a8 compromised CD8 T-cell expansion in response to infection.

Ckb or Slc6a8 loss weakened TCR-mediated mTORC1 activation required for CD8 T-cell expansion.

Ckb or Slc6a8 loss impaired T-cell function without changing global adenylate energy charge in the study.

CRT loss impaired epithelial barrier formation and wound healing; transporter-deficient organoids also had reduced barrier function.

CRT loss increased epithelial glycolytic stress and was accompanied by actin mislocalization and leaky junctions.

Intestinal CRT transcript expression was lower in the Crohn disease and ulcerative colitis biopsy groups than in controls.

Guanidinoacetate feeding raised plasma homocysteine by approximately 50% in the rat experiment.

Creatine feeding lowered plasma homocysteine by approximately 25% in the rat experiment.

Guanidinoacetate increased homocysteine export from methionine-supplied rat hepatocytes, whereas added creatine did not.

Plasma guanidinoacetate declined 10.6% with creatine versus a 3.7% rise with placebo over 12 weeks.

Homocysteine fell 23.4% with folic acid alone and 21.0% with creatine plus folic acid; the difference was not significant (P=0.41).

Guanidinoacetate inhibited complex II activity in the in-vitro striatal assays; complex II–III activity was inhibited after intrastriatal exposure.

Taurine pretreatment prevented the reported guanidinoacetate-related inhibition of complex II, complex II–III and sodium/potassium ATPase activity.

Combined vitamin E plus C pretreatment prevented guanidinoacetate-associated inhibition of creatine kinase and sodium/potassium ATPase.

Combined vitamin E plus C pretreatment prevented the rise in the lipid-peroxidation readout after guanidinoacetate exposure.

AGAT expression increased homoarginine in cells, and homoarginine was absent in AGAT-deficient mice.

Homoarginine supplementation rescued the aggravated stroke phenotype in AGAT-deficient mice in this study.

Oral creatine substitution reversed the brain creatine depletion in the reported AGAT-deficient patients.

The reported GAMT-deficiency syndrome was responsive to oral creatine substitution.

In the GAMT registry, clinical severity improved in 13 patients, 11 became seizure-free and movement disorder resolved in four during treatment combinations.

Earlier-treated AGAT-deficient patients had better developmental outcomes, while later treatment produced only partial improvement despite brain creatine repletion.

Oral creatine loading increased muscle total creatine, with larger increases in participants with lower starting concentrations.

Approximately 20% or more of the creatine taken up was recovered as phosphocreatine, while muscle ATP concentration did not change.

Plasma and muscle creatine declined after adoption of the vegetarian diet; the creatine-plus-beta-alanine group attenuated the decline.

Bench-press and squat gains were greater with creatine than placebo during training: approximately 24% versus 16% and 32% versus 24%, respectively.

Muscle-fiber cross-sectional area and fat-free mass increased more with creatine than placebo during the 12-week resistance program.

Creatine plus exercise increased muscle GLUT4 translocation to the sarcolemma relative to placebo plus exercise.

The between-group HbA1c difference favored creatine plus exercise by approximately 1.1 percentage points, with a 95% confidence interval of 0.4–1.9 percentage points lower.

Mean brain total creatine increased 8.7%, with regional and individual variability, after four weeks of supplementation; changes were reversible on follow-up.

Neither primary cognitive test reached conventional statistical significance; exploratory tasks showed no indication of improvement, and vegetarians did not benefit more than omnivores.

Creatine altered PCr/Pi, ATP and total-creatine/total-NAA measures and prevented the observed fall in brain pH during sleep deprivation.

The study reported improved cognitive performance and processing speed after the single high dose during sleep deprivation.

Creatine supplementation did not significantly change tracer-measured glomerular filtration rate versus placebo over 12 weeks in postmenopausal women.

Creatine supplementation did not significantly change tracer-measured glomerular filtration rate versus placebo over 12 weeks in healthy resistance-trained people consuming at least 1.2 g protein/kg/day.

Serum creatinine was higher with creatine ethyl ester than with monohydrate or placebo at the measured post-baseline visits.

Both creatine formulations increased muscle total creatine versus placebo, with no significant difference between formulations; performance and body-composition changes did not significantly differ between groups.

Creatine did not improve survival or the decline in functional measurements in the ALS trial.

The trial was stopped for futility; creatine did not improve the primary clinical progression comparison (P=0.45).

DHT rose 56% after loading and remained 40% above baseline after maintenance in the creatine condition; serum testosterone did not change.

There were no significant group-by-time differences in DHT or DHT-to-testosterone ratio after 12 weeks.