Related Compounds
Compounds connected by the same goals, effects, or research topics.
Compound Profile
Creatine
Creatine monohydrate has strong human evidence for selected high intensity exercise outcomes and can modestly support lean mass and strength, particularly alongside resistance training.
Use extra caution — Safety evidence: systematic review evidence shows a small serum creatinine increase without a significant decline in glomerular filtration in studied users. Details
Last reviewed: •4 sources citedReport a correctionProfile-wide ·D Preliminary
Verdict: CreatineYes
Bottom line
One of the safest, best-evidenced supplements there is — long established for training, and increasingly interesting for cognition under stress and sleep loss.
- Evidence confidence
- Strong for muscle; emerging and promising for cognition
- Expected onset
- Days to a few weeks (tissue saturation)
- Give it
- 2–4 weeks
Safety: Very well tolerated; stay hydrated. Discuss with a clinician if you have kidney disease.
On the evidence: Extensive evidence for physical performance; cognitive evidence is newer but growing.
Best for
- Cognitive support under sleep deprivation
- Strength and training output
- A high-safety daily staple
Not ideal for
- A same-day focus stimulant
- Anyone expecting a fast mental "lift"
How strong is the evidence?Strong for training; emerging for cognition
Why not higher
- The cognitive evidence is newer and mostly under stress or sleep deprivation
- It is not a same-day mental "lift"
Why not lower
- One of the most-studied supplements, with extensive safety and performance data
- A clear energy-metabolism mechanism, plus growing cognitive trials
Practical takeaway: A very safe daily staple. Expect reliable training benefits; treat the cognitive upside — clearest when sleep-deprived — as a promising bonus.
Quick stats
- Evidence level
- Preliminary evidence
- Typical onset
- Varies by prep
- Safety rating
- Use extra caution: Use caution
- Best for
- ATP Regeneration, Muscle Cells, Phosphocreatine ATP
Safety
Safety & Cautions
Elevated caution
Caution level: Elevated. One caution category applies — read it before use.
- Pregnancy/Breastfeeding CautionPregnancy or breastfeeding caution language is present.
- Safety evidence
- systematic review evidence shows a small serum-creatinine increase without a significant decline in glomerular filtration in studied users
- Who should avoid this?
- No specific evidence-backed contraindication is documented for this profile. This is not the same as established safety.
- Talk to a professional if
- you are pregnant or breastfeeding, you have a condition named in this safety summary.
Evidence in pre-existing kidney disease, pregnancy, breastfeeding, and long-term use remains limited; serum creatinine should be interpreted in context.
Evidence Summary
Profile-wide ·D PreliminaryEvidence lens
Early signal that needs stronger human replication before practical claims.
PreliminaryPreliminary evidence
Human clinical evidence: Present in source signals
Mechanistic / preclinical: Mechanism mapped — Oxidative Stress Modulation · Mitochondrial Support · Neuroprotective Activity
Research maturity: Preliminary research — Early findings are not treated as established consumer benefit.
Safety boundary: Safety note available — Safety evidence: systematic review evidence shows a small serum creatinine increase without a significant decline in glomerular filtration in studied users.
This profile cites 4 human studies.
Evidence Strength
Confidence estimate based on the design quality and consistency of published clinical trials.
Creatine has a preliminary evidence rating.
AdaptogenStress & MoodRecoveryLongevity
Citation density
4.0
Sources
12
Effects
3
Research recency
Mixed recency
Evidence Grade
Grade D: Preliminary / Theoretical Evidence
Evaluation of methodological rigor, population reach, and evidence alignment.
- Design Match
- Meta analysis
- Risk of Bias
- Low
- Consistency
- Consistent
Strongest recorded design is a meta analysis, drawn from 18 recorded studies, 16 in people. No disagreement is recorded across them.
How evidence grades work
Each grade reflects the strength and consistency of published human evidence — not marketing claims. Grades are based on study count, design quality, effect size, consistency, and recency.
- Strong
- Multiple RCTs, consistent direction, adequate effect size
- Moderate
- Some RCTs or consistent observational data in humans
- Preliminary / Mixed
- Animal or in-vitro only, or conflicting human data
- Traditional / Theoretical
- Traditional use only; no controlled human trials
Clinical Study Summaries (12)10 human evidence sources · 5 human trials · ~492 participants across 1 human evidence source with reported N · Consistency not yet classifiable
Filter by study class
Showing 12 of 12 studies.
What the evidence actually shows
This table contains 12 structured sources, including 10 human evidence sources; 5 are human trials. Across 1 human evidence source with a reported sample size, the approximate participant total is 492; overlapping publications may include some of the same people.
| Study | Design | N | Dose | Duration | Population | Outcome | Result & magnitude | Source |
|---|---|---|---|---|---|---|---|---|
Xu et al. · Frontiers in Nutrition · 2024 Background | Systematic review Uses a predefined method to find and evaluate relevant studies, but may or may not pool their results statistically. | n=492 | — | — | — | — | — | PubMed → |
Creatine and Cognition in Aging: A Systematic Review of Evidence in Older Adults Background | Systematic review Uses a predefined method to find and evaluate relevant studies, but may or may not pool their results statistically. | — | — | — | — | — | Five of six studies reported a positive creatine-cognition relationship, especially for memory/attention, but study quality was often weak. | Five of six studies reported a positive association between creatine and cognition, particularly memory and attention. | PubMed → |
Background | Systematic review Uses a predefined method to find and evaluate relevant studies, but may or may not pool their results statistically. | — | — | — | — | — | Some adult major-depression trials found adjunctive benefit, while adolescent depression and bipolar-depression augmentation findings were null. | Adult MDD trials showed promise for creatine augmentation of escitalopram (one trial, Cohen's d=1.13 at 8 weeks) and CBT; other trials, including female adolescents and bipolar depression, did not show a placebo difference. | PubMed → |
Background | Systematic review Uses a predefined method to find and evaluate relevant studies, but may or may not pool their results statistically. | — | — | — | — | — | Early studies show a possible cognitive-performance benefit during acute sleep deprivation, but effects vary by cognitive domain. | PubMed → |
Background | Systematic review Uses a predefined method to find and evaluate relevant studies, but may or may not pool their results statistically. | — | — | — | — | — | Creatine can increase brain creatine content, but cognitive effects were equivocal rather than consistently beneficial. | PubMed → |
Background | Randomized controlled trial Randomly assigns participants to interventions or controls, reducing many sources of bias when the trial is conducted well. | — | — | — | — | — | Creatine improved subjective sleep quality (d=0.81, p=0.009), digit-cancellation cognitive performance (d=0.77, p=0.013), high-intensity exercise output, and muscle soreness. | PubMed → |
Show 6 more studies
Background | Randomized controlled trial Randomly assigns participants to interventions or controls, reducing many sources of bias when the trial is conducted well. | — | — | — | — | — | Creatine provided additional benefits in antioxidant/inflammatory markers and selected strength/function outcomes when combined with training; creatine alone reduced F2-isoprostanes and TNF-alpha and improved perceived health versus placebo. | PubMed → |
Background | Randomized controlled trial Randomly assigns participants to interventions or controls, reducing many sources of bias when the trial is conducted well. | — | — | — | — | — | The 1,500 mg/day creatine HCl group outperformed placebo for reaction-time improvement and increased frontal brain creatine; serum lipid profiles also improved. | PubMed → |
Cognitive effects of creatine ethyl ester supplementation PubMed · Behav Pharmacol · 2009 Background | Controlled trial Compares an intervention with a control group but may lack random assignment or other safeguards of a strong randomized trial. | — | — | — | — | — | — | PubMed → |
PubMed · Psychopharmacology (Berl) · 2006 Background | Controlled trial Compares an intervention with a control group but may lack random assignment or other safeguards of a strong randomized trial. | — | — | — | — | — | — | PubMed → |
PubMed · J Int Soc Sports Nutr · 2017 Background | Narrative review Summarizes selected literature without the full prespecified search and selection methods of a systematic review. | — | — | — | — | — | — | PubMed → |
Background | Narrative review Summarizes selected literature without the full prespecified search and selection methods of a systematic review. | — | — | — | — | — | Evidence did not support a general cognitive-function health claim; isolated acute working-memory findings at 20 g/day were not consistently reproduced at lower doses or longer use. | PubMed → |
How Creatine Works
Simplified mechanism pathway based on preclinical and pharmacological evidence. Does not confirm clinical efficacy.
Mechanism Pathway — How Creatine Works
CompoundTarget / ReceptorMechanismEffect / Outcome
Dosing
- No standardized dose
- Creatine monohydrate; adult RCT evidence; domain specific cognition outcomes. Use studied dose table; do not invent one universal cognitive dose from meta analysis alone.
Mechanisms & biological pathways
Preclinical mechanism details from scientific profiles; these represent plausible pathways but do not guarantee clinical efficacy in humans.
- Oxidative Stress Modulation
- Mitochondrial Support
- Neuroprotective Activity
Guides that use Creatine
Goal guides
Continue exploring
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Compare & Sourcing
Compare side-by-side tradeoffs or verify active marker guidelines.
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Tradeoffs
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Sourcing options
Creatine product picks
Recommendation status
Product recommendations are not shown for this profile because the current site safety and monetization policy does not permit them.
Product form & quality guidelines
When sourcing Creatine, verify the label for:
- Standardized Extract: Confirm active content percentages on the supplement facts panel (e.g. standardized to specific marker compounds) rather than simple raw herb weights.
- Third-Party Testing: Look for independent purity labels (USP, NSF, ConsumerLab, or Eurofins) to ensure the product is free from heavy metals, solvents, and contaminants.
- Form Bioavailability: Ensure the form matches evidence-supported configurations (e.g. chelated bisglycinate/glycinate for magnesium, micronized monohydrate for creatine) for optimal onset and digestion tolerance.
Safety first · Harm reduction
This information is educational and not medical advice. Start low, avoid risky combinations, and consult a licensed clinician before making health decisions—especially if you use medications, have diagnosed conditions, or are pregnant/breastfeeding.
Learn how we evaluate confidence, safety, and intensity on the methodology page.
Editorial Review
Checked against primary sources, cited evidence, and contraindication language before publication. Evidence claims, safety language, and affiliate modules are reviewed independently. Not personal medical advice.
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