Doctor calls creatine ‘promising but not definitive’ as a complement to depression care.
A systematic review, published in Genomic Press’ Brain Medicine, found that creatine monohydrate may be beneficial as an add-on treatment for major depressive disorder, although the evidence remains preliminary.
The Canada-based researchers analyzed data from five randomized controlled trials, evaluating the impact of creatine monohydrate intake on mental health.
Four of the trials studied major depressive disorder, and another looked at bipolar disorder with a current depressive episode.
In one trial of women with depression who took 5 grams of creatine per day, plus the antidepressant escitalopram, there was greater improvement after eight weeks. Another study revealed benefit when creatine was added to cognitive behavioral therapy.
Other studies involving teen girls found no benefit from a variety of creatine dosages after eight weeks. The bipolar depression study also found no significant improvements when 6 grams of creatine was added to medication after six weeks.
In a press release, the researchers said previous studies have found that people with mood disorders process creatine differently in the brain. Because creatine helps produce energy, some scientists believe disruptions in this process may contribute to depression.
Although creatine has also been associated with boosting dopamine and serotonin, which most antidepressants target, the authors stressed that the link between brain creatine and mood “remains correlational,” as depression has “many moving parts.”
Lead study author Bassam Jeryous Fares, a student in the Faculty of Medicine at the University of Ottawa, commented in a statement that the signal is “interesting, but not a verdict.”
“Two trials pointed one way, and three pointed another,” he said. “That is not the kind of evidence on which you change clinical practice. It is the kind that tells you the question is worth further exploration.”
Nicholas Fabiano, corresponding author and a psychiatry resident at the University of Ottawa, added in the same press release that creatine “appears to be a safe intervention,” noting that side effects were limited to mild stomach pain.
“We cannot yet reliably say that creatine helps with depressive symptoms or if the findings are generalizable to everyone,” he added as a caveat. Dr. Thea Gallagher, psychologist and director of wellness programs at NYU Langone, said that although creatine is best known for supporting muscle performance, it also helps the brain produce and use energy.
“Researchers believe that some people with depression may have alterations in brain energy metabolism, and creatine could help support these energy-producing pathways,” Gallagher, who was not involved in the study, told Fox News Digital. “There is also emerging evidence that it may influence neurotransmitters and reduce oxidative stress and inflammation, although these mechanisms are still being investigated.”
The research suggests that creatine may be most helpful when combined with established depression treatments rather than as a replacement, Gallagher emphasized.
“This research is encouraging because it adds to a growing body of evidence suggesting that supporting brain energy metabolism may be another pathway for improving depression symptoms,” she said.
“It’s exciting whenever we identify another potential tool that could complement existing treatments, particularly one that is relatively inexpensive and widely available.”
Limitations and caveats
The new study is a review of prior research rather than a new clinical trial, which can pose a limitation, the researchers acknowledged, adding that “larger, well-controlled trials are still needed.”
Gallagher noted that creatine should be considered as a potentially promising addition to treatment, rather than a substitute for psychotherapy, antidepressant medication, regular exercise, or healthy sleep habits.
“While creatine has a strong safety profile for most healthy adults, it’s still important to talk with your healthcare provider before starting any supplement — particularly if you have kidney disease, are pregnant or have other medical conditions,” she advised.
For those experiencing signs of depression, Gallagher recommends seeking evidence-based mental healthcare.
The doctor noted that depression is a “highly heterogeneous condition, so we still don’t know which patients are most likely to benefit or what the optimal treatment approach looks like.”
Gallagher also cautioned that supplements have been known to generate “early enthusiasm” before larger studies have revealed “more modest effects.”
“Right now, I’d describe creatine as promising but not definitive,” she concluded. “It’s an area that deserves continued research, but it’s not something people should view as a standalone treatment for depression.”
