What evidence supports creatine and vitamin B12 for improving cognition in adults?

1. What the best reviews say: small but consistent signals for creatine, mainly in older adults

Two recent systematic reviews and meta-analyses conclude creatine supplementation may improve specific cognitive domains (memory, attention, processing speed), with pooled effect sizes described as modest and authors calling for larger trials; the Frontiers/NLM review reports significant positive effects on memory (SMD ≈ 0.31) and processing speed, and urges more robust clinical trials to validate these findings ^{[1] [4] [2]}.

2. Heterogeneity and who benefits most: age and stress matter

Subgroup and individual-trial analyses indicate the cognitive gains are largest and most reproducible in older adults and in situations of metabolic stress (sleep deprivation, dementia models), while healthy young adults often show null or inconsistent effects—meta-analyses found large memory effects in older groups (SMD up to 0.88 in one review) but minimal effects in younger cohorts ^{[5] [6] [3]}.

3. Mechanisms offered by researchers: brain energy, phosphates, and neuroprotection

Investigators propose creatine boosts brain energy reserves (PCr/ATP) and reduces oxidative stress, plausibly supporting tasks with high energetic demand; human neurochemical studies during sleep deprivation showed creatine altered cerebral high-energy phosphates alongside cognitive improvement, supplying a mechanistic link though uptake into the CNS is variable and may limit effects ^{[2] [7] [3]}.

4. Experimental designs and dosing: short loading vs. chronic low doses, and variable brain uptake

Trials have used everything from single high doses to multi-week daily regimens (≈2–20 g/day), with some studies showing measurable increases in brain creatine after higher or longer dosing and others showing no change—this variability in brain creatine response likely contributes to inconsistent cognitive outcomes and points to unanswered dose–response questions ^{[3] [7] [1]}.

5. Clinical populations and early signals: Alzheimer’s and other conditions

Small pilot studies and preclinical models report promising signals: an Alzheimer’s pilot using high-dose creatine reported feasibility and preliminary cognitive improvements, and animal models show cognitive and biomarker benefits; these are hypothesis-generating rather than definitive, given single-arm designs and small samples ^{[8] [9] [10]}.

6. Safety, accessibility, and the research agenda

Creatine is widely available and generally regarded as safe in short-term trials, but large, well-powered randomized controlled trials with standardized dosing, longer follow-up, and direct measures of brain creatine are needed to confirm cognitive efficacy and long-term safety—several reviews and trialists explicitly call for these studies ^{[1] [10] [3]}.

7. Contrarian data and interpretive caution

Not all high-quality trials show benefit: the largest randomized crossover trial in young adults found at best a borderline effect on one working-memory task and no improvement on other cognitive measures, underscoring that any cognitive benefit is neither universal nor large for healthy younger populations ^{[11] [3]}. Meta-analytic corrections and corrigenda further illustrate the evolving and sometimes contradictory nature of pooled estimates ^[12].

8. What cannot be concluded from the supplied reporting: vitamin B12

The provided corpus contains no studies, reviews, or trials addressing vitamin B12 and cognition, so no evidence-based claims about B12’s effect on adult cognition can be supported here; absence of sourced information is explicitly a limitation of this report (no source).