Creatine

Creatine has more RCT support than almost any other supplement, mostly in athletic contexts. Its longevity relevance is that muscle mass and function in older adults strongly predict mortality, and creatine reliably augments strength training adaptations. Sarcopenia (age-related muscle loss) is one of the most preventable major aging outcomes.

Beyond muscle, creatine has replicated evidence for modest cognitive benefit, particularly under conditions of sleep deprivation or metabolic stress. Effects on memory and reasoning in healthy adults are small but real. In vegetarians and older adults, whose baseline creatine stores are lower, the cognitive effect is more consistent.

Emerging evidence supports bone density effects when creatine is combined with resistance training, particularly at the femoral neck in postmenopausal women.

Dosing is settled: 3-5 g/day of creatine monohydrate, taken daily, with no cycling needed. Loading phases (20 g/day for 5 days) are not required for most people. Timing does not meaningfully matter, though post-workout may be marginally better.

Creatine monohydrate remains the gold standard form. Marketed alternatives (HCl, ethyl ester, magnesium chelate, buffered) offer no proven advantage and typically cost more per gram. Micronized monohydrate improves mixability but not efficacy.

Safety is thoroughly established. No kidney damage in healthy people despite persistent myths. Slight water weight gain (1-2 kg) is intramuscular water, not fat.

Dose by goal, not one number. The 3 to 5 g/day figure comes from muscle physiology and saturates skeletal muscle; it was never derived from a brain endpoint [1]. For cognition in healthy, well-rested young omnivores, higher doses do not rescue it: a dose-response trial of 10 g/day versus 20 g/day versus placebo for 6 weeks in 30 adults was null on every domain, with processing speed p=0.17, episodic memory p=0.95 and executive function p=0.59 [4]. The groups that do respond are the ones starting lower. In vegetarians, 5 g/day for 6 weeks improved backward digit span and Raven's matrices at p<0.0001 [5]. In older adults, a meta-analysis of 10 randomized trials put pooled memory at SMD 0.88 in the 66 to 76 age band versus SMD 0.03 in those aged 11 to 31 [6], and a 2026 re-analysis correcting a unit-of-analysis error left older adults as the only surviving subgroup [7].

Brain uptake needs 20 g/day for weeks. Magnetic resonance spectroscopy data summarized by Fabiano and Candow show 20 g/day for 4 weeks raising total brain creatine 8.7%, p=0.0008, with thalamus up 14.6% and white matter up 11.5%, while a single 20 g dose moved it a non-significant 3 to 7.7% and about 25 g/day for 7 days changed brain phosphocreatine by only -0.7% to +3.9% [8]. Brain creatine typically rises only 5 to 15% at best. Raising brain creatine and improving cognition remain two separate claims.

Acute sleep loss is a single bolus, not a daily dose. Fifteen adults kept awake 21 hours took one 0.35 g/kg dose, roughly 24.5 g at 70 kg, which reversed deficits in word memory, digit span and processing speed with the maximum effect at 4 hours and measurable effects to 9 hours [9]. A 29-person crossover replicated the result at 0.2 g/kg, mean 14.1 g [10].

Where creatine does not work. The largest trial ever run, NET-PD LS-1, randomized 1,741 patients with early treated Parkinson's disease to 10 g/day or placebo across 45 sites and was stopped early for futility after a median 4 years [11]. In depression, creatine is an adjunct rather than a treatment: 5 g/day for 8 weeks alongside escitalopram in 52 women produced greater HAM-D improvement from week 2 [12]. The hair-loss claim traces to a single 2009 study of 20 rugby players and has not been replicated [13]. Kidney-function studies span 1 to 80 g/day for 5 days to 60 months with no impairment on estimated GFR, creatinine, urea, proteinuria or albuminuria, though the cohorts were mostly healthy young men and anyone with reduced kidney function should be assessed with cystatin C or direct GFR [14]. Split anything above 5 g: a single 10 g dose produced diarrhea in 55.6% of participants versus 28.6% on split 5 g doses, p<0.05 [14].

A 2024 meta-analysis of 16 randomized trials (492 adults) tested creatine for cognition. Memory improved with a standardized mean difference of 0.31, and attention and processing time improved. Overall cognition and executive function showed no significant effect. Most included trials used around 5 g/day. The pattern is domain-specific: memory and processing speed respond, broader executive measures do not.

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