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There’s been buzz for years around using creatine to support and maintain muscle growth, including suggestions that it can be a helpful supplement for women in menopause. But new research finds that creatine might have untapped potential as a treatment for depression, too.

The systematic review, which was published in the Canadian Journal of Psychiatry, doesn’t suggest that the supplement is a slam-dunk treatment for depression. But it did find enough of a link between creatine use and improved symptoms in women with major depressive disorder to make a case for at least considering this. Here’s what the research found, plus what psychologists think you should take away from the data.

Meet the experts: Nicholas Fabiano, MD, a study co-author and resident in theDepartment of Psychiatry at the University of Ottawa; Hillary Ammon, PsyD, a clinical psychologist at the Center for Anxiety and Women’s EmotionalWellness; and Thea Gallagher, PsyD, a clinical associate professor at NYU Langone Health and co-host of the Mind in View podcast.

What did the study find?

For the systematic review, researchers reviewed data from five randomized controlled trials where 238 participants either took creatine or a placebo. The study participants had an average age of 36 and were mostly women (in fact, two of the studies only enrolled women).

Two of the five trials found that taking creatine was linked to a drop in symptoms of depression. In one study, women who took five grams of creatine a day, along with the antidepressant escitalopram, had a bigger drop in symptoms of depression after eight weeks compared to those who took escitalopram with a placebo.

In the second study, both male and female participants underwent cognitive behavioral therapy and either took creatine or a placebo. Again, those who took creatine had greater improvements in symptoms of depression compared to those who took the placebo.

Here’s where things get complicated: The other three trials found no meaningful boost in symptom relief when participants took creatine. These trials included a study of five and 10 grams of creatine in people who didn’t respond to medication for depression, a study of teen girls, and a trial of people with bipolar disorder. It’s also worth flagging that two people in the bipolar disorder study who took creatine developed hypomania or mania.

What’s behind the link?

It’s not entirely clear. “We do not yet know definitively how creatine may lower symptoms of depression,” says Nicholas Fabiano, MD, a study co-author and resident in theDepartment of Psychiatry at the University of Ottawa. But, he says, because depression can alter the brain’s metabolism, there may be something about creatine that helps.

“Creatine is typically known for its ability to aid in preserving muscle and improving strength,” says Hillary Ammon, PsyD, a clinical psychologist at the Center for Anxiety and Women’s Emotional Wellness. “It also produces ATP, which is one of the body’s primary sources of energy.”

The brain uses large amounts of ATP, points out Thea Gallagher, PsyD, clinical associate professor at NYU Langone Health and co-host of the Mind in View podcast. “ATP is essentially the fuel our brain cells use to function,” Gallagher says.

When you take creatine supplements, your body may increase ATP production. That can then provide more “energy currency” for your brain, Ammon says. “In turn, these brain changes could improve symptoms of depression,” she adds.

Why were there more women in these trials?

There are actually a few reasons for this. “Biologically, women tend to have lower total creatine stores than men, largely due to differences in muscle mass, and some evidence suggests they may also have lower creatine levels in certain brain regions,” Dr. Fabiano says. “There’s also preclinical data showing sex-specific effects where creatine appears to have more consistent antidepressant-like benefits in female animals.”

Depression is also twice as common in women as in men, he says, which makes it easier to recruit women for these kinds of studies.

How much creatine should people take for depression?

There’s not enough data to give a prescriptive dose or exact recommendation, but the featured studies had participants taking anywhere from two to 10 grams of creatine.

What’s the takeaway?

We can’t ignore the fact that most of the studies didn’t find a benefit in taking creatine for symptoms of depression (although, to be fair, one of those studies was specifically in people with bipolar disorder). It’s important not to overstate where the science is,” Gallagher says. “The research is promising, but it’s still early, and the studies have generally been small.”

Ammon agrees that more research is needed. “It could be possible that female hormones could be playing a role in how a female’s brain positively responds to creatine,” she says. This isn’t designed to replace therapy or antidepressants, though. “Instead, it may eventually become another tool in our treatment toolbox as we continue to learn who is most likely to benefit,” Gallagher says.

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