Creatine & Phosphocreatine System — References

Mirrored Reference Dossier

Parent Topic: Creatine & Phosphocreatine System | References Hub: 02 - Compounds & Molecules References MOC

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Landmark Peer-Reviewed Studies

1. Kreider et al. (2017) — Journal of the International Society of Sports Nutrition

• Citation: Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., Candow, D. G., Kleiner, S. M., Almada, A. L., & Lopez, H. L. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14, 18.
• Identifiers: PMID: 28615996 (PubMed · Europe PMC) | PMCID: PMC5469049 (PMC Full Text) | DOI: 10.1186/s12970-017-0173-z (DOI · SciDB · Scholar)
• Study Design & Sample Size: Comprehensive systematic review and consensus position stand synthesizing $>1,000$ peer-reviewed clinical and physiological trials.
• Key Quantitative Outcomes: Confirmed that $3\text{–}5\text{ g/day}$ (or $0.3\text{ g/kg/day}$ loading for 5–7 days) increases intramuscular creatine and phosphocreatine (PCr) stores by $+15\text{–}40\%$, improves high-intensity exercise capacity and maximal strength by $+5\text{–}15\%$, and shows zero evidence of renal dysfunction, hepatic toxicity, or musculoskeletal cramping in healthy or clinical populations up to $30\text{ g/day}$ for 5 years.

2. Gordji-Nejad et al. (2024) — Scientific Reports (Nature Portfolio)

• Citation: Gordji-Nejad, A., Matusch, A., Kleedörfer, S., Patel, H. J., Drzezga, A., Elmenhorst, D., Binkofski, F., & Bauer, A. (2024). Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. Scientific Reports, 14(1), 4937.
• Identifiers: PMID: 38418482 (PubMed · Europe PMC) | DOI: 10.1038/s41598-024-54249-9 (DOI · SciDB · Scholar)
• Study Design & Sample Size: Randomized, double-blind, placebo-controlled crossover neuroimaging trial ($N=15$) utilizing ${}^{31}\text{P-MRS}$ and ${}^1\text{H-MRS}$ magnetic resonance spectroscopy across 21 hours of acute sleep deprivation.
• Key Quantitative Outcomes: A single high dose of creatine monohydrate ($0.35\text{ g/kg}$, $\sim 25\text{–}30\text{ g}$) significantly increased total brain creatine ($t\text{Cr}/t\text{NAA}$, $p=0.03$), prevented the sleep-deprivation-induced drop in cerebral $\text{PCr/Pi}$ (phosphocreatine to inorganic phosphate ratio, $p<0.01$), prevented intracellular cerebral pH acidification, and improved processing speed, numeric working memory, and word memory recall peaking at 4 hours post-ingestion ($p<0.01$).

3. Rae et al. (2003) — Proceedings of the Royal Society B: Biological Sciences

• Citation: Rae, C., Digney, A. L., McEwan, S. R., & Bates, T. C. (2003). Oral creatine monohydrate supplementation improves brain performance: a double–blind, placebo–controlled, cross–over trial. Proceedings of the Royal Society of London. Series B: Biological Sciences, 270(1529), 2147–2150.
• Identifiers: PMID: 14561278 (PubMed · Europe PMC) | DOI: 10.1098/rspb.2003.2492 (DOI · SciDB · Scholar)
• Study Design & Sample Size: 6-week randomized, double-blind, placebo-controlled crossover trial with a 6-week washout in vegetarian/vegan young adults ($N=45$).
• Key Quantitative Outcomes: Supplementation with $5\text{ g/day}$ creatine monohydrate for 6 weeks significantly enhanced Raven’s Advanced Progressive Matrices (fluid intelligence/abstract reasoning) scores by $+20.7\%$ ($p<0.0001$) and Backward Digit Span (working memory capacity) from $7.05$ to $8.50$ items ($+20.5\%,p<0.0001$).

4. Korzun et al. (2016) / Stead et al. (2001) — American Journal of Clinical Nutrition

• Citation: Korzun, W. J., et al. (2016) / Stead, L. M., Au, K. P., Jacobs, R. L., Brosnan, M. E., & Brosnan, J. T. (2001). Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. The American Journal of Clinical Nutrition / American Journal of Physiology, 281(5), E1095–E1100.
• Identifiers: PMID: 11595668 (PubMed · Europe PMC) | DOI: 10.1152/ajpendo.2001.281.5.E1095 (DOI · SciDB · Scholar)
• Study Design & Sample Size: Metabolic flux and clinical methylation sparing investigation.
• Key Quantitative Outcomes: Demonstrated that endogenous creatine synthesis via Guanidinoacetate N-Methyltransferase (GAMT) consumes $\sim 40\%$ of all S-Adenosylmethionine (SAMe)-derived methyl groups; exogenous dietary creatine downregulates renal AGAT expression by $-83\%$ and reduces plasma homocysteine concentration by $-25\text{ to }-27\%$ ($p<0.05$).