Guanidinoacetate

evidence_access

Primary abstract

experimental_model

Human SLC6A6 structural study.

limitations

Binding structures alone do not quantify net transport or competition in a living human.

nutrient_topic

Taurine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Taurine

plain_language

A creatine precursor also connects to this transporter.

primary_references

Molecular basis of human taurine transporter uptake and inhibition. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40789850/ · DOI 10.1038/s41467-025-62857-w

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 137–143

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human SLC6A6 structural study. · source_derived_draft · unverified_draft

## taurine-taut-guanidinoacetate A creatine precursor also connects to this transporter. The human TauT study captured guanidinoacetate-bound transporter structures as part of its substrate-recognition analysis. Model: Human SLC6A6 structural study. Limitations: Binding structures alone do not quantify net transport or competition in a living human. Evidence access: Primary abstract Molecular basis of human taurine transporter uptake and inhibition. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40789850/ · DOI 10.1038/s41467-025-62857-w

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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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

evidence_span

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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

evidence_span

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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

evidence_span

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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

evidence_span

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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

evidence_span

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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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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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

evidence_span

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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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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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/

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

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

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

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

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

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

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