Human Effect Matrix
Evidence-ranked outcomes from human trials only. Effect direction, strength, and tier shown for each outcome area.
| Outcome | Effect | Strength | Evidence | Key Study |
|---|---|---|---|---|
| Lean Muscle MassLean body mass gain vs placebo | ↑ +1.4kg | Strong | 500+ studies; well-replicated | |
| Strength Output1RM and peak force production | ↑ 5–15% | Strong | Upper and lower body; all ages | |
| Working MemoryShort-term memory tasks | ↑ +14% | Moderate | Human RCT | Benton & Donohoe 2011; vegetarians benefit most |
| Cognitive SpeedProcessing speed, executive function | ↑ Modest | Preliminary | Avgerinos 2018 meta-analysis | |
| Muscle RecoveryPost-exercise soreness, damage markers | ↑ Improved | Moderate | Human RCT | Creatine reduces CK elevation |
| Sarcopenia (Older Adults)Muscle preservation with aging | ↑ Improved | Moderate | Candow 2021; combine with resistance training | |
| Kidney FunctioneGFR, creatinine in healthy adults | ~ Safe | Strong | No adverse effect at 3–5g/day long-term |
Key Clinical Evidence
Spanning athletics, cognition, aging, and now longevity science
| Study / Meta-Analysis | N | Dose | Duration | Key Finding |
|---|---|---|---|---|
| Rawson & Volek (2003) — Meta-analysis | N/A (22 trials) | 3–25g/day | 4–12 weeks | +1.37kg fat-free mass; +8% strength gains vs. placebo in resistance training |
| Candow et al. (2022) — Aging review | N/A | 3–5g/day | Long-term | Preserves muscle mass, bone density, and cognitive function in older adults when combined with resistance exercise |
| Avgerinos et al. (2018) — Meta-analysis | 281 | 3–20g/day | 4–26 weeks | +14% working memory; +8% intelligence/reasoning scores in non-athletes |
| Brosnan & Brosnan (2016) | N/A | Dietary | — | Brain creatine synthesis consumes ~40% of body's arginine supply; supplementation spares this for other uses |
| Forbes et al. (2021) — Meta-analysis | N/A (15 RCTs) | 3–5g/day | Various | Creatine supplementation + resistance training → significant bone mineral density preservation in older adults vs. exercise alone |
| Nuccio et al. (2017) | N/A | 5g/day | 12 weeks | No adverse effects on renal or hepatic function in healthy adults — confirms long-term safety |
After age 30, adults lose 3–8% of muscle mass per decade. After 60, this accelerates. Low muscle mass (sarcopenia) is directly correlated with all-cause mortality — more predictive of 10-year survival than BMI. Creatine + resistance exercise is the only intervention with an A-grade evidence base for preventing sarcopenia.
Creatine serves as a phosphate buffer in the brain, maintaining ATP availability during high cognitive demand. MRS studies show brain creatine levels decline with age. Supplementation increases brain phosphocreatine by 5–15%, with measurable improvements in working memory and speed of processing in older adults.
Despite heavy marketing of creatine HCl, buffered creatine, and ethyl ester — none outperform monohydrate in head-to-head trials. Monohydrate has all 500+ studies. Buy the cheapest Creapure® (German pharmaceutical-grade) monohydrate you can find — the fancy forms offer no advantage.
Traditional loading (20g/day for 5–7 days) saturates muscle stores faster but is unnecessary for long-term use. Taking 5g/day reaches the same saturation level in 28 days with no GI discomfort. Loading causes water retention (3–5 lbs in week 1) which is misleading on the scale but harmless.
Dosing Protocol
The simplest and most evidence-backed protocol of any Tier A supplement
Evidence-Based Dosing (Creatine Monohydrate)
⚠ Safety Considerations
Creatine monohydrate is one of the most extensively safety-studied supplements ever. Long-term use (up to 5 years in athletes) shows no adverse effects on kidney or liver function in healthy individuals. Creatine can mildly elevate serum creatinine (not creatinine clearance) — do not confuse this lab artifact with renal impairment. Individuals with pre-existing kidney disease should consult a physician before use.
Best Products by Evidence
Form is identical across brands — what matters is purity certification (Creapure® preferred) and price
Dual-certified for sport — both NSF and Informed-Sport, the strictest anti-doping certifications. Creapure® is the most studied form. Ideal for professionals or anyone who wants absolute certainty of purity.
Get on Fullscript ↗Same Creapure® ingredient as Momentous at 25% of the price. For longevity supplementation, this is the rational choice — you are buying Creapure® regardless of brand at the top of the market.
Get on Fullscript ↗Thorne's NSF certification and clean manufacturing makes this the physician-recommended choice for patients asking for a trusted brand. Priced between NOW and Momentous — solid middle ground.
Get on Fullscript ↗- Candow et al. Nutrients 2021 — creatine supplementation meta-analysis
- Lanhers et al. Eur J Sport Sci 2017 — creatine and upper body strength
- Human RCTBenton & Donohoe 2011 Psychopharmacology — creatine and cognitive function RCT
- Avgerinos et al. Exp Gerontol 2018 — creatine and cognition meta-analysis
- ReviewKreider et al. J Int Soc Sports Nutr 2017 — ISSN position stand on creatine