Phosphocreatine

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

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/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/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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/creatine-research/12419710.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e27a7cfa46bbfc4a05cb51ba54832614c64b750471ee2ea564c8232addb4bd68", "start_char": 0, "end_char": 1400, "text_sha256": "e27a7cfa46bbfc4a05cb51ba54832614c64b750471ee2ea564c8232addb4bd68"}

experimental_model

Magnetic-resonance spectroscopy and contraction experiment with kinetic modeling

exposure

5 Hz stimulation, including the first 2 seconds and an 80-second steady state

limitations

Measured metabolite changes are distinguished from model-inferred ADP and oxidative activation; knockout compensation is possible.

nutrient_topic

Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine

organism

Ckm-knockout and wild-type mice

plain_language

Removing the muscle enzyme changed how quickly the phosphate reserve could be used.

primary_references

[creatine-p12419710] Phosphocreatine kinetics at the onset of contractions in skeletal muscle of MM creatine kinase knockout mice. (2002). https://pubmed.ncbi.nlm.nih.gov/12419710/ DOI: 10.1152/ajpcell.00210.2002

tissue_or_cell_type

Gastrocnemius muscle

trigger_kind

machinery_impairment Imported condition classification; unverified.

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 386–397

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Magnetic-resonance spectroscopy and contraction experiment with kinetic modeling · source_derived_draft · unverified_draft

### creatine-ckm-loss-early-pcr At 2 seconds of stimulation, phosphocreatine depletion was approximately 2.2% in MM-CK-deficient muscle versus 9.7% in wild type. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing the muscle enzyme changed how quickly the phosphate reserve could be used. organism: Ckm-knockout and wild-type mice tissue_or_cell_type: Gastrocnemius muscle experimental_model: Magnetic-resonance spectroscopy and contraction experiment with kinetic modeling limitations: Measured metabolite changes are distinguished from model-inferred ADP and oxidative activation; knockout compensation is possible. exposure: 5 Hz stimulation, including the first 2 seconds and an 80-second steady state evidence_span: {"source_cache": "artifacts/creatine-research/12419710.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e27a7cfa46bbfc4a05cb51ba54832614c64b750471ee2ea564c8232addb4bd68", "start_char": 0, "end_char": 1400, "text_sha256": "e27a7cfa46bbfc4a05cb51ba54832614c64b750471ee2ea564c8232addb4bd68"} [creatine-p12419710] Phosphocreatine kinetics at the onset of contractions in skeletal muscle of MM creatine kinase knockout mice. (2002). https://pubmed.ncbi.nlm.nih.gov/12419710/ DOI: 10.1152/ajpcell.00210.2002

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/creatine-research/12419710.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e27a7cfa46bbfc4a05cb51ba54832614c64b750471ee2ea564c8232addb4bd68", "start_char": 0, "end_char": 1400, "text_sha256": "e27a7cfa46bbfc4a05cb51ba54832614c64b750471ee2ea564c8232addb4bd68"}

experimental_model

Magnetic-resonance spectroscopy and contraction experiment with kinetic modeling

exposure

5 Hz stimulation, including the first 2 seconds and an 80-second steady state

limitations

Measured metabolite changes are distinguished from model-inferred ADP and oxidative activation; knockout compensation is possible.

nutrient_topic

Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine

organism

Ckm-knockout and wild-type mice

plain_language

A normal resting energy measurement did not guarantee normal rapid buffering.

primary_references

[creatine-p12419710] Phosphocreatine kinetics at the onset of contractions in skeletal muscle of MM creatine kinase knockout mice. (2002). https://pubmed.ncbi.nlm.nih.gov/12419710/ DOI: 10.1152/ajpcell.00210.2002

tissue_or_cell_type

Gastrocnemius muscle

trigger_kind

machinery_impairment Imported condition classification; unverified.

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 399–410

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Magnetic-resonance spectroscopy and contraction experiment with kinetic modeling · source_derived_draft · unverified_draft

### creatine-ckm-loss-resting-markers Resting PCr/ATP and pH did not differ, and no ATP change was detected at 2 seconds despite altered early phosphocreatine depletion. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A normal resting energy measurement did not guarantee normal rapid buffering. organism: Ckm-knockout and wild-type mice tissue_or_cell_type: Gastrocnemius muscle experimental_model: Magnetic-resonance spectroscopy and contraction experiment with kinetic modeling limitations: Measured metabolite changes are distinguished from model-inferred ADP and oxidative activation; knockout compensation is possible. exposure: 5 Hz stimulation, including the first 2 seconds and an 80-second steady state evidence_span: {"source_cache": "artifacts/creatine-research/12419710.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e27a7cfa46bbfc4a05cb51ba54832614c64b750471ee2ea564c8232addb4bd68", "start_char": 0, "end_char": 1400, "text_sha256": "e27a7cfa46bbfc4a05cb51ba54832614c64b750471ee2ea564c8232addb4bd68"} [creatine-p12419710] Phosphocreatine kinetics at the onset of contractions in skeletal muscle of MM creatine kinase knockout mice. (2002). https://pubmed.ncbi.nlm.nih.gov/12419710/ DOI: 10.1152/ajpcell.00210.2002

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/42020733.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd", "start_char": 0, "end_char": 1255, "text_sha256": "232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd"}

experimental_model

Structural, biochemical, cellular, physiological and human genetic experiments

exposure

Glycerol binding and glycerol-pocket disruption

limitations

Published 2026; model-specific thermogenesis and mineralization findings do not establish a dietary glycerol or creatine treatment for bone disease.

nutrient_topic

Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine

organism

TNAP experimental systems, mice and human variant analyses

plain_language

A molecule made during fat breakdown can adjust the phosphatase that participates in creatine cycling.

primary_references

[creatine-p42020733] Glycerol-driven TNAP activation in thermogenesis and mineralization. (2026). https://pubmed.ncbi.nlm.nih.gov/42020733/ DOI: 10.1038/s41586-026-10396-9

tissue_or_cell_type

Thermogenic adipocytes, osteoblasts and purified protein

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 542–553

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Structural, biochemical, cellular, physiological and human genetic experiments · source_derived_draft · unverified_draft

### creatine-glycerol-tnap Glycerol bound a TNAP surface pocket distant from the active site and enhanced TNAP activity. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A molecule made during fat breakdown can adjust the phosphatase that participates in creatine cycling. organism: TNAP experimental systems, mice and human variant analyses tissue_or_cell_type: Thermogenic adipocytes, osteoblasts and purified protein experimental_model: Structural, biochemical, cellular, physiological and human genetic experiments limitations: Published 2026; model-specific thermogenesis and mineralization findings do not establish a dietary glycerol or creatine treatment for bone disease. exposure: Glycerol binding and glycerol-pocket disruption evidence_span: {"source_cache": "artifacts/creatine-research/42020733.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd", "start_char": 0, "end_char": 1255, "text_sha256": "232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd"} [creatine-p42020733] Glycerol-driven TNAP activation in thermogenesis and mineralization. (2026). https://pubmed.ncbi.nlm.nih.gov/42020733/ DOI: 10.1038/s41586-026-10396-9

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/38418482.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b6dad9388eb7cb8986f1873e6ba9f8dd36924c7a9aa7c661059cde1012f1e3a8", "start_char": 0, "end_char": 1364, "text_sha256": "b6dad9388eb7cb8986f1873e6ba9f8dd36924c7a9aa7c661059cde1012f1e3a8"}

experimental_model

Placebo comparison with repeated phosphorus/proton MRS and cognition

exposure

Single creatine monohydrate dose 0.35 g/kg during approximately 21 hours of sleep deprivation

limitations

Acute high-dose, sleep-deprivation setting; not an everyday dose recommendation or proof of benefit in well-rested people.

nutrient_topic

Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine

organism

Human participants during sleep deprivation

plain_language

The experiment detected changes in brain energy-related measurements under acute sleep stress.

primary_references

[creatine-p38418482] Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. (2024). https://pubmed.ncbi.nlm.nih.gov/38418482/ DOI: 10.1038/s41598-024-54249-9

tissue_or_cell_type

Brain spectroscopy and cognitive performance

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 1049–1060

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Placebo comparison with repeated phosphorus/proton MRS and cognition · source_derived_draft · unverified_draft

### creatine-sleep-deprivation-phosphates Creatine altered PCr/Pi, ATP and total-creatine/total-NAA measures and prevented the observed fall in brain pH during sleep deprivation. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The experiment detected changes in brain energy-related measurements under acute sleep stress. organism: Human participants during sleep deprivation tissue_or_cell_type: Brain spectroscopy and cognitive performance experimental_model: Placebo comparison with repeated phosphorus/proton MRS and cognition limitations: Acute high-dose, sleep-deprivation setting; not an everyday dose recommendation or proof of benefit in well-rested people. exposure: Single creatine monohydrate dose 0.35 g/kg during approximately 21 hours of sleep deprivation evidence_span: {"source_cache": "artifacts/creatine-research/38418482.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b6dad9388eb7cb8986f1873e6ba9f8dd36924c7a9aa7c661059cde1012f1e3a8", "start_char": 0, "end_char": 1364, "text_sha256": "b6dad9388eb7cb8986f1873e6ba9f8dd36924c7a9aa7c661059cde1012f1e3a8"} [creatine-p38418482] Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. (2024). https://pubmed.ncbi.nlm.nih.gov/38418482/ DOI: 10.1038/s41598-024-54249-9

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

nutrient_deficiency Imported condition classification; unverified.

evidence_location

Abstract

evidence_span

before the onset of neurological signs

experimental_model

Adult male Wistar rats with pyrithiamine-induced acute thiamine-deficient encephalopathy; microwave fixation and regional ATP/phosphocreatine assays before and after neurological signs.

exposure

Pyrithiamine-induced severe thiamine deficiency in rats

limitations

Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Rattus norvegicus

plain_language

Energy reserves fell early in two vulnerable brain regions.

primary_references

[aikawa-1984-brain-energy] Low energy levels in thiamine-deficient encephalopathy. (1984). https://pubmed.ncbi.nlm.nih.gov/6726285/ DOI: 10.1097/00005072-198405000-00006

tissue_or_cell_type

Diencephalon and lower brainstem

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1070–1082

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adult male Wistar rats with pyrithiamine-induced acute thiamine-deficient encephalopathy; microwave fixation and regional ATP/phosphocreatine assays before and after neurological signs. · source_derived_draft · unverified_draft

### thiamine-def-regional-energy-loss Before neurological signs, total high-energy phosphates were 89% of control in diencephalon and 91% in lower brainstem; after signs, 76% and 79%. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Energy reserves fell early in two vulnerable brain regions. organism: Rattus norvegicus tissue_or_cell_type: Diencephalon and lower brainstem experimental_model: Adult male Wistar rats with pyrithiamine-induced acute thiamine-deficient encephalopathy; microwave fixation and regional ATP/phosphocreatine assays before and after neurological signs. limitations: Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold. evidence_location: Abstract evidence_span: before the onset of neurological signs exposure: Pyrithiamine-induced severe thiamine deficiency in rats [aikawa-1984-brain-energy] Low energy levels in thiamine-deficient encephalopathy. (1984). https://pubmed.ncbi.nlm.nih.gov/6726285/ DOI: 10.1097/00005072-198405000-00006

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_location

Abstract

evidence_span

high energy phosphates were not significantly reduced

experimental_model

Adult male Wistar rats with pyrithiamine-induced acute thiamine-deficient encephalopathy; microwave fixation and regional ATP/phosphocreatine assays before and after neurological signs.

exposure

Pyrithiamine-induced severe thiamine deficiency in rats

limitations

A nonsignificant result does not prove unchanged ATP in every cell or at later stages. Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Rattus norvegicus

plain_language

A severe thiamine-deficiency model did not cause uniform energy depletion across the brain.

primary_references

[aikawa-1984-brain-energy] Low energy levels in thiamine-deficient encephalopathy. (1984). https://pubmed.ncbi.nlm.nih.gov/6726285/ DOI: 10.1097/00005072-198405000-00006

tissue_or_cell_type

Cerebral cortex and cerebellum

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1084–1096

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adult male Wistar rats with pyrithiamine-induced acute thiamine-deficient encephalopathy; microwave fixation and regional ATP/phosphocreatine assays before and after neurological signs. · source_derived_draft · unverified_draft

### thiamine-def-regional-energy-preservation Cerebral cortex and cerebellum showed no significant high-energy phosphate reduction in the same encephalopathic rats. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A severe thiamine-deficiency model did not cause uniform energy depletion across the brain. organism: Rattus norvegicus tissue_or_cell_type: Cerebral cortex and cerebellum experimental_model: Adult male Wistar rats with pyrithiamine-induced acute thiamine-deficient encephalopathy; microwave fixation and regional ATP/phosphocreatine assays before and after neurological signs. limitations: A nonsignificant result does not prove unchanged ATP in every cell or at later stages. Combined thiamine withdrawal and pyrithiamine exposure; not an estimate for mild dietary insufficiency or a human blood threshold. evidence_location: Abstract evidence_span: high energy phosphates were not significantly reduced exposure: Pyrithiamine-induced severe thiamine deficiency in rats [aikawa-1984-brain-energy] Low energy levels in thiamine-deficient encephalopathy. (1984). https://pubmed.ncbi.nlm.nih.gov/6726285/ DOI: 10.1097/00005072-198405000-00006

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

evidence_span

{"source_cache": "artifacts/phosphorus-research/38482570.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11f6599b477ce87228e00e4d562eb0c70615dceebb82a983188e9b0fcd8e730f", "start_char": 0, "end_char": 2164, "text_sha256": "11f6599b477ce87228e00e4d562eb0c70615dceebb82a983188e9b0fcd8e730f"}

experimental_model

Small cross-sectional diet-recall and 31P-MRS association study

exposure

24-hour dietary recall normalized to energy; calf-muscle MRS at rest/exercise

limitations

Observational pilot with n=13, not a controlled excess-phosphate intervention. The source uses a phosphocreatinine wording error; PCr is represented as phosphocreatine.

nutrient_topic

Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus

organism

Human

plain_language

The phosphocreatine response also differed with reported intake.

primary_references

[phosphorus-p38482570] Association between dietary phosphate intake and skeletal muscle energetics in adults without cardiovascular disease. (2024). https://pubmed.ncbi.nlm.nih.gov/38482570/ DOI: 10.1152/japplphysiol.00818.2023

tissue_or_cell_type

Thirteen adults without cardiopulmonary disease

Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1258–1269

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Small cross-sectional diet-recall and 31P-MRS association study · source_derived_draft · unverified_draft

### phosphorus-high-intake-pcr Higher reported phosphate intake was associated with greater exercise-related phosphocreatine depletion in the pilot. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The phosphocreatine response also differed with reported intake. organism: Human tissue_or_cell_type: Thirteen adults without cardiopulmonary disease experimental_model: Small cross-sectional diet-recall and 31P-MRS association study limitations: Observational pilot with n=13, not a controlled excess-phosphate intervention. The source uses a phosphocreatinine wording error; PCr is represented as phosphocreatine. exposure: 24-hour dietary recall normalized to energy; calf-muscle MRS at rest/exercise evidence_span: {"source_cache": "artifacts/phosphorus-research/38482570.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11f6599b477ce87228e00e4d562eb0c70615dceebb82a983188e9b0fcd8e730f", "start_char": 0, "end_char": 2164, "text_sha256": "11f6599b477ce87228e00e4d562eb0c70615dceebb82a983188e9b0fcd8e730f"} [phosphorus-p38482570] Association between dietary phosphate intake and skeletal muscle energetics in adults without cardiovascular disease. (2024). https://pubmed.ncbi.nlm.nih.gov/38482570/ DOI: 10.1152/japplphysiol.00818.2023