Creatine

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

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

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

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

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

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

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

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

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

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

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

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

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/

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/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

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

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

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

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

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

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

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

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

evidence_span

{"source_cache": "artifacts/cold-research/26496606.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f2d52dfe935e633b9d69280d707a124080d6f6c4d650f94bc8cf6a00f26e43e7", "start_char": 0, "end_char": 1097, "text_sha256": "f2d52dfe935e633b9d69280d707a124080d6f6c4d650f94bc8cf6a00f26e43e7"}

experimental_model

Quantitative mitochondrial proteomics of brown and beige fat with pharmacological creatine reduction

exposure

Cold exposure, beta-3 agonist administration, and creatine depletion

limitations

Identifies a UCP1-independent route. Pharmacological creatine reduction is a blunt tool, and the compensatory induction in UCP1-deficient mice is an expression finding.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Mouse

plain_language

A second heat route runs a creatine cycle that burns energy on purpose.

primary_references

[cold-p26496606] A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat. (2015). https://pubmed.ncbi.nlm.nih.gov/26496606/ DOI: 10.1016/j.cell.2015.09.035

tissue_or_cell_type

Beige and brown adipose tissue

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 442–453

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantitative mitochondrial proteomics of brown and beige fat with pharmacological creatine reduction · source_derived_draft · unverified_draft

### cold-creatine-cycle Creatine enhanced respiration in beige-fat mitochondria when ADP was limiting, and cold exposure stimulated mitochondrial creatine kinase activity and induced coordinated expression of creatine metabolism genes in murine beige fat. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: A second heat route runs a creatine cycle that burns energy on purpose. organism: Mouse tissue_or_cell_type: Beige and brown adipose tissue experimental_model: Quantitative mitochondrial proteomics of brown and beige fat with pharmacological creatine reduction limitations: Identifies a UCP1-independent route. Pharmacological creatine reduction is a blunt tool, and the compensatory induction in UCP1-deficient mice is an expression finding. exposure: Cold exposure, beta-3 agonist administration, and creatine depletion evidence_span: {"source_cache": "artifacts/cold-research/26496606.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f2d52dfe935e633b9d69280d707a124080d6f6c4d650f94bc8cf6a00f26e43e7", "start_char": 0, "end_char": 1097, "text_sha256": "f2d52dfe935e633b9d69280d707a124080d6f6c4d650f94bc8cf6a00f26e43e7"} [cold-p26496606] A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat. (2015). https://pubmed.ncbi.nlm.nih.gov/26496606/ DOI: 10.1016/j.cell.2015.09.035

evidence_access

Primary abstract

experimental_model

Nine healthy men; six-day creatine loading 0.5 g/kg/day, with or without caffeine 5 mg/kg/day; intermittent knee-extensor testing.

limitations

Small protocol-specific trial. Creatine accumulation and performance were separate endpoints.

nutrient_topic

Caffeine collection; salts, coffee, species and coexposure contexts retain their identities. · Caffeine

plain_language

Caffeine did not block the measured phosphocreatine increase.

primary_references

Caffeine counteracts the ergogenic action of muscle creatine loading. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8929583/ · DOI 10.1152/jappl.1996.80.2.452

Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18) · lines 444–450

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Nine healthy men; six-day creatine loading 0.5 g/kg/day, with or without caffeine 5 mg/kg/day; intermittent knee-extensor testing. · source_derived_draft · unverified_draft

## caf-creatine-pcr Caffeine did not block the measured phosphocreatine increase. Creatine alone and creatine plus caffeine each increased muscle phosphocreatine by 4–6%; measured ATP stayed constant. Model: Nine healthy men; six-day creatine loading 0.5 g/kg/day, with or without caffeine 5 mg/kg/day; intermittent knee-extensor testing. Limitations: Small protocol-specific trial. Creatine accumulation and performance were separate endpoints. Evidence access: Primary abstract Caffeine counteracts the ergogenic action of muscle creatine loading. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8929583/ · DOI 10.1152/jappl.1996.80.2.452

evidence_access

Primary abstract

experimental_model

Ten men; double-blind crossover; creatine 20 g/day; electrically stimulated quadriceps.

limitations

No direct measurement of calcium-pump mediation.

nutrient_topic

Caffeine collection; salts, coffee, species and coexposure contexts retain their identities. · Caffeine

plain_language

Creatine altered a muscle-relaxation measurement.

primary_references

Opposite actions of caffeine and creatine on muscle relaxation time in humans. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11796658/ · DOI 10.1152/japplphysiol.00255.2001

Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18) · lines 460–466

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Ten men; double-blind crossover; creatine 20 g/day; electrically stimulated quadriceps. · source_derived_draft · unverified_draft

## caf-relax-creatine Creatine altered a muscle-relaxation measurement. Four days of creatine shortened stimulated-muscle relaxation time by about 5%. Model: Ten men; double-blind crossover; creatine 20 g/day; electrically stimulated quadriceps. Limitations: No direct measurement of calcium-pump mediation. Evidence access: Primary abstract Opposite actions of caffeine and creatine on muscle relaxation time in humans. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11796658/ · DOI 10.1152/japplphysiol.00255.2001

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

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

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

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

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

evidence_access

Primary full text; Figure 4A

experimental_model

Human recombinant kinases; radiolabeled ATP and TLC; annelid taurocyamine kinase positive control.

limitations

The experimental result does not exclude every reaction at other conditions, but does not support replacing creatine.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Related guanidino compounds are not automatically interchangeable energy buffers.

primary_references

Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 212–218

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant kinases; radiolabeled ATP and TLC; annelid taurocyamine kinase positive control. · source_derived_draft · unverified_draft

## agmatine-sulfate-creatine-specificity Related guanidino compounds are not automatically interchangeable energy buffers. Four purified human creatine-kinase isoforms phosphorylated creatine but not taurocyamine, guanidinobutyrate or guanidinopropionate at 10 mM test substrate. Model: Human recombinant kinases; radiolabeled ATP and TLC; annelid taurocyamine kinase positive control. Limitations: The experimental result does not exclude every reaction at other conditions, but does not support replacing creatine. Evidence access: Primary full text; Figure 4A Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

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

{"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

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

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

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

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

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

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

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

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/

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

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

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

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

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

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

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

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

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

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

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

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/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

evidence_access

Primary abstract

experimental_model

Nine healthy men; six-day creatine loading 0.5 g/kg/day, with or without caffeine 5 mg/kg/day; intermittent knee-extensor testing.

limitations

Small protocol-specific trial. Creatine accumulation and performance were separate endpoints.

nutrient_topic

Caffeine collection; salts, coffee, species and coexposure contexts retain their identities. · Caffeine

plain_language

The same stored-energy increase did not guarantee the same performance response.

primary_references

Caffeine counteracts the ergogenic action of muscle creatine loading. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8929583/ · DOI 10.1152/jappl.1996.80.2.452

Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18) · lines 452–458

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Nine healthy men; six-day creatine loading 0.5 g/kg/day, with or without caffeine 5 mg/kg/day; intermittent knee-extensor testing. · source_derived_draft · unverified_draft

## caf-creatine-torque The same stored-energy increase did not guarantee the same performance response. Creatine increased dynamic torque by 10–23%, whereas the creatine-plus-caffeine regimen did not improve torque. Model: Nine healthy men; six-day creatine loading 0.5 g/kg/day, with or without caffeine 5 mg/kg/day; intermittent knee-extensor testing. Limitations: Small protocol-specific trial. Creatine accumulation and performance were separate endpoints. Evidence access: Primary abstract Caffeine counteracts the ergogenic action of muscle creatine loading. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8929583/ · DOI 10.1152/jappl.1996.80.2.452

evidence_access

Primary abstract

experimental_model

12 active men; creatine 0.3 g/kg/day followed by caffeine 6 mg/kg; six 10-second sprints.

limitations

Different sequence, task and outcomes from repeated coadministration; not evidence of synergy across all sprints or users.

nutrient_topic

Caffeine collection; salts, coffee, species and coexposure contexts retain their identities. · Caffeine

plain_language

A different sequence produced better performance in selected sprints.

primary_references

Effect of caffeine ingestion after creatine supplementation on intermittent high-intensity sprint performance. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21207054/ · DOI 10.1007/s00421-010-1792-0

Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18) · lines 476–482

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · 12 active men; creatine 0.3 g/kg/day followed by caffeine 6 mg/kg; six 10-second sprints. · source_derived_draft · unverified_draft

## caf-postload-caffeine A different sequence produced better performance in selected sprints. A single caffeine dose after five days of creatine loading increased mean and peak cycling power over creatine-plus-placebo during sprints 1 and 2. Model: 12 active men; creatine 0.3 g/kg/day followed by caffeine 6 mg/kg; six 10-second sprints. Limitations: Different sequence, task and outcomes from repeated coadministration; not evidence of synergy across all sprints or users. Evidence access: Primary abstract Effect of caffeine ingestion after creatine supplementation on intermittent high-intensity sprint performance. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21207054/ · DOI 10.1007/s00421-010-1792-0

evidence_access

Primary abstract

experimental_model

Same ten-man muscle-stimulation experiment.

limitations

Relaxation is a candidate explanation for performance differences, not proof of a universal creatine interaction.

nutrient_topic

Caffeine collection; salts, coffee, species and coexposure contexts retain their identities. · Caffeine

plain_language

Repeated and single-dose caffeine did not have the same measured effect.

primary_references

Opposite actions of caffeine and creatine on muscle relaxation time in humans. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11796658/ · DOI 10.1152/japplphysiol.00255.2001

Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18) · lines 468–474

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Same ten-man muscle-stimulation experiment. · source_derived_draft · unverified_draft

## caf-relax-caffeine Repeated and single-dose caffeine did not have the same measured effect. Three days of caffeine 5 mg/kg/day prolonged relaxation time by about 10%; acute caffeine and the creatine/caffeine combination did not significantly change it. Model: Same ten-man muscle-stimulation experiment. Limitations: Relaxation is a candidate explanation for performance differences, not proof of a universal creatine interaction. Evidence access: Primary abstract Opposite actions of caffeine and creatine on muscle relaxation time in humans. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11796658/ · DOI 10.1152/japplphysiol.00255.2001