Scientists say creatine may help fight depression

Creatine is known as a muscle-building supplement. Now, scientists are looking into whether it could also help treat depression. They believe it might do this by boosting the brain's energy supply.

A new review looked at five studies with 238 people. The results were mixed. Two studies, both with women who had major depressive disorder, found that adding creatine to their usual treatment improved symptoms. However, three other studies found no real benefit.

Reviewing the Evidence

Researchers at the University of Ottawa, led by Bassam Jeryous Fares, did not run a new experiment. Instead, they looked at existing research. They found six reports covering five randomized controlled trials. In these trials, people received either creatine or a placebo without knowing which one they got.

The studies took place in South Korea, the United States, Brazil, Israel, and India. A total of 238 people started these trials. Of them, 126 received creatine and 112 received a placebo. The average age of participants was 36, and most were women. Two studies only included women.

Four trials focused on people with major depressive disorder. One trial included people with bipolar disorder who were having a depressive episode. The studies were very different in how they were designed. Because of this, the researchers looked at each study separately instead of combining all the data.

Mixed Results

The review showed different outcomes.

Two of the five trials found that creatine helped. Both of these studies involved women with major depressive disorder. In one study, people who took five grams of creatine daily along with the antidepressant escitalopram saw bigger drops in depressive symptoms after eight weeks. This was compared to those who took escitalopram with a placebo.

This improvement was considered significant. More participants even achieved remission.

Another study combined creatine with cognitive behavioral therapy. People who received creatine showed a greater drop in depression symptoms than those who got therapy with a placebo.

However, the other three trials found no real benefit.

One study reported that neither five nor ten grams of creatine daily improved symptoms for people whose depression had not responded to medication. Another study found no advantage over placebo for adolescent girls, even with different doses. A third trial with people who had bipolar disorder also showed no improvement.

Researchers also noted a safety concern. Two participants with bipolar disorder who took creatine developed hypomania or mania. This suggests creatine might affect people differently based on their underlying health condition.

Why Creatine Might Affect the Brain

The idea that creatine could impact depression comes from how much energy the brain needs.

Creatine is best known for helping muscles quickly make adenosine triphosphate (ATP), which powers cells. The brain also relies heavily on this energy system. Past research has shown changes in brain creatine metabolism in people with mood disorders. This led scientists to wonder if problems with cellular energy production could play a role in depression.

Creatine might also affect dopamine and serotonin. These are two brain chemicals important for mood regulation. Many antidepressant medications target them.

However, the review's authors say these links are still just ideas. Current studies show connections, but they don't prove that changes in creatine metabolism directly cause depression. Depression itself involves many biological processes.

Bassam Jeryous Fares, the lead author, said the findings are "interesting, but it is not a verdict." He noted that two trials pointed one way and three pointed another. He believes this means the question is worth more study, but it's not enough to change how doctors treat patients yet.

Nicholas Fabiano, a psychiatry resident and corresponding author, also advised caution. He said creatine seems safe, with only mild stomach issues reported. But he added that they cannot yet say for sure if creatine helps with depressive symptoms or if the findings apply to everyone.

More Studies Are Needed

The researchers emphasize that there isn't enough evidence yet to recommend creatine for depression regularly.

The studies were fairly small. They also included more women than men and varied in quality. Two studies were considered low risk for bias, while three had some concerns, mainly about how participants were assigned and missing data. Because of this, the results cannot be widely applied yet.

The review calls for larger and longer studies, lasting more than eight weeks. Researchers also suggest studying creatine with exercise. They want to see if different doses work better, while also noting that higher doses might not always mean more benefits.

Animal studies might offer more clues. Experiments have shown that creatine can affect depression-like behavior differently in male and female rodents. This could help explain why the human studies with mostly women showed the strongest positive results.

For now, creatine is an interesting possibility, not a proven treatment. This supplement, long known for building muscle, is now gaining interest from scientists looking for new ways to treat depression.

The research article, "Creatine as a treatment for depression," was published in Brain Medicine.

Deep Dive & References

Creatine as a treatment for depression - Brain Medicine, 2026