Creatine Might Also Be Fighting Depression.

Creatine is one of the most widely used sports supplements in the world, taken by millions of people primarily to boost strength and muscle performance, but a new systematic review published in the journal Brain Medicine suggests it may have a second and far more surprising application: helping to treat depression. Researchers at the University of Ottawa led by Bassam Jeryous Fares analyzed five randomized controlled trials involving 238 participants across South Korea, the United States, Brazil, Israel, and India, in which participants received either creatine or a placebo without knowing which one, and the results of the five studies point in two different directions at once. Two of the trials, both of which enrolled only women with major depressive disorder, found meaningful benefits. In one, participants taking five grams of creatine daily alongside the antidepressant escitalopram showed significantly greater reductions in depressive symptoms after eight weeks than those on the antidepressant alone, with more participants reaching full remission and an effect size that clinicians would consider large. A second study found similar advantages when creatine was combined with cognitive behavioral therapy. The remaining three trials, however, found no benefit at all.

The biological rationale for why creatine might affect the brain is more grounded than it might initially appear. The brain is one of the most energy-demanding organs in the body, and creatine plays a direct role in the cellular energy system that fuels it, helping neurons replenish the energy currency they use to fire signals. Research has shown that people with depression often have impaired energy metabolism in the brain, and the hypothesis is that supplementing creatine could help restore some of that metabolic function in patients whose depressive symptoms are connected to that deficit. The researchers emphasize that the review's mixed results and small sample sizes mean the evidence is promising rather than persuasive, and that the studies differed substantially enough in design that combining their data into a single conclusion was not scientifically appropriate. They also noted an important safety flag: two participants with bipolar disorder who received creatine developed hypomania or mania, suggesting the supplement should be approached with significant caution in that population. For people with major depressive disorder, particularly women whose symptoms have not fully responded to standard treatment alone, the researchers say the early signals are worth pursuing in larger and more rigorous future trials.

Source:https://www.sciencedaily.com/releases/2026/06/260630020231.htm