Creatine may be beneficial as more than just a muscle-building supplement, as new research is investigating whether the popular compound could hold promise as a treatment for depression.
The University of Ottawa’s Bassam Jeryous Fares led the new studies, described in a recent paper in Brain Research, examining how creatine affects brain chemistry, particularly involving depression.
As one of the most popular workout supplements today, creatine has been well studied for its effects on muscle growth. However, the new findings suggest that its cognitive impact may have remained underappreciated.
Hidden in the Data
For their research, the University of Ottawa team did not conduct new clinical trials. Instead, they reexamined existing data from a new perspective. The researchers identified five randomized controlled studies, published across six papers, in which neither participants nor physicians knew who received creatine or a placebo.
Together, the studies enrolled nearly 240 participants, evenly divided between the placebo and creatine groups. While most participants were women, the studies included individuals from South Korea, the United States, Brazil, India, and Israel.
The studies were focused on the mental impacts of creatine, with four looking at major depressive disorder and one at bipolar individuals enduring a major depressive episode, yet they varied widely in design. Due to these differences, the University of Ottawa researchers opted to summarize the trials separately rather than create a single set of statistics across them.
Uneven Depression Results
The results between the studies did not tell a single, cohesive story. In two of the studies, researchers reported significant positive results on major depressive disorder by combining five grams of creatine with the antidepressant escitalopram daily. Similarly, another trial combining creatine with cognitive behavioral therapy showed a greater reduction in symptoms than the placebo group.
However, the remaining studies found no measurable benefit. One focused on individuals who had previously failed to respond to depression medications and likewise found that creatine did not improve their symptoms. Similarly, a study involving adolescent girls with major depressive disorder and another involving women with bipolar disorder reported no improvement. In the bipolar group, creatine not only failed to show benefits but also induced hypomania or mania in two participants.
Brain Power and Depression
The key to the discussion is a molecule called adenosine triphosphate, which carries energy to fuel biological processes. Creatine helps replenish that molecule in muscles, and since the brain uses more energy by volume than any other part of the body, it stands to reason that creatine would have a major impact on the brain.
Existing research into mood disorders has commonly identified changes in the brain’s creatine metabolism, leading to the suggestion that reduced energy production in the brain causes depression. Additionally, some speculate that creatine activates the same pathways targeted by antidepressants, but all links between mood and creatine remain correlational.
“The signal is interesting, but it is not a verdict,” said lead author Bassam Jeryous Fares, a student in the Faculty of Medicine at the University of Ottawa. “Two trials pointed one way, and three pointed another. 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.”
According to the researchers, their findings suggest creatine may represent a promising avenue for future depression research. However, they emphasize that these studies are only an early step, and much more work is needed to determine whether the supplement can play a meaningful role in treating mood disorders.
The paper, “Creatine as a Treatment for Depression,” appeared in Brain Medicine on June 30, 2026.
Ryan Whalen covers science and technology for The Debrief. He holds an MA in History and a Master of Library and Information Science with a certificate in Data Science. He can be contacted at ryan@thedebrief.org, and follow him on Twitter @mdntwvlf.