Popular workout supplement creatine could help fight depression, according to a systematic review from the University of Ottawa published in Genomic Press' Brain Medicine journal. The analysis of five randomized controlled trials suggests that creatine monohydrate may be a valuable additional tool for those with major depressive disorder, though researchers emphasize the evidence is preliminary and requires further study.
Review Combines Data from Five International Trials
Rather than conducting new experiments, the researchers analyzed existing data from five randomized controlled trials conducted in South Korea, the United States, Brazil, Israel, and India. The combined studies included 238 participants at baseline: 126 who received creatine and 112 who received a placebo. The average age of participants, predominantly women, was 36 years.
Four of the trials focused on major depressive disorder, while the fifth examined individuals with bipolar disorder experiencing a depressive episode. The dosages and treatment durations varied across studies, ranging from 5 to 6 grams of creatine daily over six to eight weeks.
Mixed Results Across Different Populations
One trial involving only women found that those with depression who took five grams of creatine per day alongside the antidepressant escitalopram showed greater improvement after eight weeks compared to those on escitalopram alone. Another study indicated benefits when creatine was added to cognitive behavioural therapy.
However, other studies involving teenage girls found no benefit from different dosages of creatine after eight weeks. The study of patients with bipolar depression also found no significant improvements when six grams of creatine was added to their medication after six weeks. Notably, two of the bipolar participants taking creatine developed hypomania or mania.
Brain Energy Metabolism and Depression Link
The researchers noted that previous studies have found the brains of people with mood disorders process creatine differently. Creatine helps produce energy in cells, and some scientists believe disruptions in this energy production process could contribute to depression. The authors stressed that the link between brain creatine and mood remains correlational and that depression has “many moving parts.”
They also acknowledged that due to the small size of the trials and the imbalance in sex representation, “larger, well-controlled trials are still needed.”
Researchers Call for Caution and Further Study
Lead author Bassam Jeryous Fares, a student in the University of Ottawa's Faculty of Medicine, said in a press release that the signal is “interesting, but not a verdict.” He added: “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.”
Nicholas Fabiano, corresponding author and a psychiatry resident at the University of Ottawa, emphasized that creatine “appears to be a safe intervention,” with side effects limited to mild stomach pain. However, he cautioned: “We cannot yet reliably say that creatine helps with depressive symptoms or if the findings are generalizable to everyone.”
Future Directions and Animal Research
The authors called for “more rigorous work” with larger, longer trials. They also highlighted animal research showing that creatine altered depression-like behaviour differently in male and female rodents, which may help explain why human trials with more women showed more promise. “For now, creatine remains a promising lead rather than a proven remedy,” the news release concluded. “The molecule that builds muscle has earned a closer look from the people who study the mind.”
