Creatine, a popular supplement known for its muscle-building benefits, may also have potential as an aid for depression, according to new research.

A systematic review published in Brain Medicine by Genomic Press analyzed data from five randomized controlled trials examining the effects of creatine monohydrate on mental health.

The analysis suggested that creatine monohydrate might serve as a helpful add-on treatment for major depressive disorder, though the researchers described the findings as preliminary.

The Canada-based team reviewed studies focusing on major depressive disorder and one trial on bipolar disorder during a depressive episode. Each explored how creatine supplementation affected mood outcomes.

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One study of women with depression who took 5 grams of creatine daily in addition to the antidepressant escitalopram reported greater improvement after eight weeks compared with medication alone. Another trial observed benefits when creatine was combined with cognitive behavioral therapy.

However, other studies found no significant change. Investigations involving teenage girls taking varying creatine doses over eight weeks and another trial examining bipolar depression both failed to show measurable improvements.

The researchers noted that previous work had found differences in how people with mood disorders process creatine in their brains. Because creatine contributes to energy production, some scientists theorize that energy metabolism may play a role in certain forms of depression.

Still, the authors emphasized that the relationship between brain creatine and mood remains uncertain. They noted that while creatine has been linked to changes in dopamine and serotonin levels, those associations are correlational rather than causal.

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Lead author Bassam Jeryous Fares, a University of Ottawa medical student, said in a statement that the signal from the data is “interesting, but not a verdict.” He explained that “two trials pointed one way and three pointed another,” adding that this level of evidence warrants further exploration but does not justify changes to clinical practice.

Nicholas Fabiano, a psychiatry resident at the University of Ottawa and corresponding author, described creatine as a “safe intervention,” noting that reported side effects were limited to mild stomach pain. Still, he cautioned that the data are not yet strong enough to confirm widespread benefit.

Dr. Thea Gallagher, psychologist and director of wellness programs at NYU Langone, told Fox News Digital that creatine supports cellular energy production, including in the brain. She said some people with depression may experience disruptions in energy metabolism, and creatine could help support those pathways.

Gallagher emphasized that creatine should be considered a complement to existing depression treatments rather than a replacement. She said the findings are “encouraging” because they point to a new biological pathway worth studying, calling creatine “promising but not definitive.”

She also highlighted the supplement’s accessibility, noting that creatine is relatively inexpensive and widely available, which could make it an appealing candidate for further research.

The review authors acknowledged that the analysis was based on previously published data, meaning larger and more controlled clinical trials will be needed to confirm any potential effect.

Gallagher added that people with depression should continue to seek evidence-based care, including therapy, medication, regular exercise, and healthy sleep habits.

She advised consulting a healthcare provider before beginning any supplement, especially for individuals with kidney disease, pregnancy, or other medical conditions, since responses to treatment can vary widely.

Gallagher concluded that depression remains a complex condition and that enthusiasm for new supplements should be balanced with caution until more robust evidence becomes available.

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