Creatine is a well‑known sports supplement. People use it to boost strength and muscle power. Scientists are now checking if it might also help the brain when someone feels sad.
A team of researchers looked at earlier studies instead of doing a new experiment. They found six reports that tested creatine against a fake pill (placebo) in random groups.
The trials took place in South Korea, the United States, Brazil, Israel, and India. In total, 238 volunteers started the studies. About half received creatine and the rest got placebo. The average age was 36 years, and most participants were women.
Mixed Findings
Two of the five trials, both with women who had major depression, showed good results.
In one trial, participants took five grams of creatine each day together with the antidepressant escitalopram. After eight weeks they reported much less sadness than those who took escitalopram with a placebo.
Another trial added creatine to cognitive‑behavioral therapy. The group that got creatine felt better on a standard mood questionnaire than the group that got therapy alone.
The other three trials did not see any benefit. One study found no change in people whose depression did not respond to medication, even when they took five or ten grams of creatine each day. Another trial with teenage girls showed no improvement, and a study with bipolar participants also reported no change.
Two participants with bipolar disorder who took creatine experienced a jump into a manic or hypomanic state, suggesting the supplement may affect some people differently.
Why Creatine Might Matter for the Brain
Creatine helps cells make energy quickly. The brain uses a lot of energy, so scientists think adding extra creatine could support brain function.
Research has also shown that creatine can change the levels of dopamine and serotonin, chemicals that help control mood.
"Creatine appears safe, with only mild stomach upset reported. We still cannot say for sure that it eases depression for everyone."
More Research Needed
The current evidence is small and uneven. Most participants were women, and the quality of the trials varied. Only two studies were judged to have low risk of bias.
Scientists say larger, longer studies are needed. Future research should test different doses, combine creatine with exercise, and look at both men and women.
Animal work hints that creatine may affect male and female brains differently, which could explain why the human studies with mostly women showed stronger results.
For now, creatine remains an interesting possibility, not a proven treatment, for depression.
The full peer‑reviewed article, “Creatine as a treatment for depression,” was published in Brain Medicine and is freely available from June 30, 2026.