Overview

Creatine (as creatine monohydrate) is a naturally occurring compound that buffers cellular energy by regenerating ATP via the phosphocreatine (PCr) system. Beyond muscle, the brain contains a dedicated creatine/PCr pool used to stabilize energy supply during high demand (intense cognitive work, sleep loss, hypoxia). Goldmind:Drive uses pure creatine monohydrate in research-aligned dosing of 5 g daily. Five grams of creatine monohydrate daily is among the most researched -- and safest -- supplements on the market. While it is better known for its boosts to physical performance, there is a growing, robust literature on the cognitive enhancing effects of this supplement.

On ingestion, creatine monohydrate gets converted into phosphocreatine–an endogenous energy buffer we already make high concentrations of ourselves and get nutritionally from red meat and fish. Oral supplementation “tops up” our cellular supply. Five grams per day saturates our muscle stores of creatine, but emerging research is exploring using higher doses 10-20g per day to increase brain and bone stores of creatine. Phosphocreatine donates phosphates to regenerate ATP, buffering energy during demand-spikes.

The brain is an extremely energy hungry organ–it is 2% of body weight but uses 20% of total energy at rest–and creatine functions similarly in neurons as it does in skeletal muscle: it allows rapid increases in ATP during high-cognitive-load “mental sprints.” The brain holds 5-10% of the body's total creatine and with four weeks of supplementation this brain phosphocreatine pool can be increased by 5-10%. Multiple randomized trials have shown creatine improves memory, processing speed and general cognition (effect size 0.3-0.6), with stronger gains in sleep deprived adults. It’s also neuroprotective and improves mood (effect size 0.3 for mood elevation in non-depressed adults, up to 0.69 for adults with major depressive disorder taking creatine as an adjunctive with an SSRI or CBT). Personally, I’ve used creatine monohydrate 5-10g/day for years without issue. Skip the loading protocols–GI discomfort is the only issue I’ve encountered often when starting people on creatine, which is worse when you dose too high too quickly. At 5g/day, most gut issues resolve quickly.

Many creatine myths persist–almost all are unfounded. One excellent review debunks these–for example, creatine supplementation does not harm your kidneys though you should avoid it in advanced renal disease. Expect a mild rise in serum creatinine–creatinine is simply the breakdown product of creatine. By supplementing, you increase creatine turnover and creatinine will naturally go up. Numerous studies have demonstrated creatine does not impair kidney function at standard dosing. If you are concerned, please ask your doctor to order a cystatin C blood test. This is a protein made by all nucleated cells at a constant rate and filtered freely by the kidneys. Research shows stable cystatin C levels on creatine, demonstrating preserved renal function.

More in-depth mechanisms of action:

• PCr→ATP recycling: Creatine kinase shuttles high-energy phosphates from mitochondria to synapses/ion pumps, sustaining ATP during peak neural activity and under sleep loss or hypoxia.
• Neuroenergetic reserve: Supplementation increases brain PCr and alters high-energy phosphate dynamics, observed with 31P-MRS, consistent with improved cognitive endurance during stress.
• Neurotransmission under load: By stabilizing ATP, creatine supports Na⁺/K⁺-ATPase, vesicle recycling, and glutamatergic signaling—processes tied to working memory, reaction speed, and sustained attention.
• Mood/stress circuitry: Augmentation trials suggest creatine can accelerate antidepressant response or enhance psychotherapy outcomes, likely via improved prefrontal energy metabolism.

Clinical studies supporting use (focus-relevant populations)

[Effect-size note: When variance data are incomplete, effects are conservatively described as small-to-moderate (≈0.2–0.4) based on reported outcomes.]

A) Healthy or stressed adults

Rae C, et al. Proc Biol Sci. 2003.
• Population/design/duration: Young adult vegetarians; double-blind, placebo-controlled, cross-over; ~6 weeks.
• Dose/form: Creatine monohydrate ~5 g/day.
• Endpoints: Working memory (backward digit span), abstract reasoning (Raven’s matrices).
• Result: Significant improvements vs placebo; larger effects in those with lower baseline dietary creatine.
• Estimated effect size: g ≈ 0.3–0.4 (memory/reasoning).

McMorris T, et al. Psychopharmacology. 2006.
• Population/design: Adults exposed to sleep deprivation with mild exercise; placebo-controlled.
• Dose: Short loading protocol (high-dose creatine).
• Endpoints: Choice reaction time, balance/psychomotor tasks, mood and catecholamines/cortisol.
• Result: Creatine attenuated sleep-loss decrements in cognitive and psychomotor performance versus placebo.
• Estimated effect size: g ≈ 0.2–0.3 on speed/accuracy under sleep loss.

Gordji-Nejad A, et al. Sci Rep. 2024.
• Population/design: Adults undergoing sleep deprivation; randomized, placebo-controlled, single-dose study with 31P-MRS.
• Dose: Single oral dose creatine monohydrate.
• Endpoints: Cognitive battery and cerebral high-energy phosphates.
• Result: Improved cognitive performance during sleep loss with concurrent shifts in brain PCr/ATP dynamics.
• Estimated effect size: small-to-moderate acute benefit under sleep deprivation.

Xu Chen, et al. Frontiers in Nutrition. 2024 (Systematic review & meta-analysis).
• Scope: Adult RCTs of creatine and cognition across conditions.
• Main finding: Positive effects are most consistent in stressed states (sleep loss, hypoxia) and in lower-baseline groups (e.g., vegetarians), with small-to-moderate improvements in tasks requiring speed/working memory.

B) Mood/stress domain (relevance to cognitive steadiness)

Lyoo IK, et al. Am J Psychiatry. 2012.
• Design: Double-blind RCT; women with major depressive disorder on SSRI ± creatine (8 weeks).
• Dose: 5 g/day creatine monohydrate.
• Result: Faster and greater antidepressant response with creatine augmentation; supports improved prefrontal bioenergetics.

Sherpa NN, et al. Eur Neuropsychopharmacol. 2025.
• Design: Double-blind, randomized add-on to CBT in depression (pilot feasibility).
• Result: Acceptable safety with signals for enhanced symptom improvement versus placebo.

C) Additional adult data
• Forbes SC, et al. Ann Nutr Metab. 2022. In older adults, higher creatine doses combined with resistance training were required to augment bone indices.
• Antonio J, et al. J Int Soc Sports Nutr. 2021. Evidence-based review dispelling misconceptions: creatine monohydrate is safe, effective, and does not harm kidneys in healthy individuals at studied doses.

Dose-relationships:
• Common research doses — Maintenance 3–5 g/day; acute or loading protocols use higher intakes (e.g., divided ~20 g/day for ~5–7 days) when rapid saturation is desired.
• Goldmind:Drive — Uses creatine monohydrate and is designed to be compatible with the 3–5 g/day evidence-based maintenance zone using 5 g/day.

Safety
• Tolerability: Creatine monohydrate is one of the most studied supplements; typical effects are mild (transient GI upset if taken without food or adequate water).
• Renal/hepatic: RCTs and position papers report no adverse renal effects in healthy individuals at customary doses; those with kidney disease should consult a clinician.
• Practical use: Split doses with meals (e.g., 3–5 g/day maintenance). Short loading (e.g., ~20 g/day in divided doses for 5–7 days) can fill stores faster but is optional and not recommended.

References
• Gordji-Nejad A, et al. Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. Sci Rep. 2024;14:4937.
• Forbes SC, et al. A High Dose of Creatine Combined with Resistance Training Appears to Be Required to Augment Indices of Bone Health in Older Adults. Ann Nutr Metab. 2022;78(3):183-186.
• Raichle ME, Gusnard DA. Appraising the brain’s energy budget. Proc Natl Acad Sci USA. 2002;99(16):10237-10239.
• Rae C, et al. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc Biol Sci. 2003;270(1529):2147-2150.
• Chen X, et al. The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis. Front Nutr. 2024 Jul 12;11:1424972. 
• McMorris T, et al. Creatine supplementation and sleep deprivation with mild exercise: effects on cognitive/psychomotor performance, mood, and hormones. Psychopharmacology (Berl). 2006;185(1):93-103.
• Lyoo IK, et al. Creatine augmentation of SSRI in women with major depression: randomized, double-blind trial. Am J Psychiatry. 2012;169(9):937-945.
• Sherpa NN, et al. Oral creatine monohydrate add-on to CBT in depression: double-blind randomized feasibility trial. Eur Neuropsychopharmacol. 2025;90:28-35.
• Antonio J, Candow DG, Forbes SC, et al. Common questions and misconceptions about creatine supplementation. J Int Soc Sports Nutr. 2021;18:13.