Scientists have explored creatine’s potential to alleviate depressive symptoms, presenting a comprehensive systematic review and meta-analysis published recently in theBritish Journal of Nutrition.Depression affects nearly 280 million people globally, with many facing inadequate treatment options that are often slow to take effect and burdened by adverse effects. Creatine, widely known for its role in enhancing physical performance, has drawn interest for its central involvement in brain energy metabolism—areas disrupted in depression. Creatine supports brain energy homeostasis and neurotransmitter regulation, with lower brain creatine levels linked to depression and treatment resistance. Dietary creatine intake correlates inversely with depression prevalence, hinting at its therapeutic promise. Despite encouraging preclinical and clinical data, creatine is not yet included in major depression treatment guidelines. The meta-analysis assessed randomized controlled trials (RCTs) comparing oral creatine supplementation to placebo, including studies with co-interventions like antidepressants or psychotherapy. Researchers pooled data using robust statistical models, evaluating risk of bias and the quality of evidence via GRADE criteria, and performed subgroup analyses by diagnosis and study bias risk. From 11 eligible RCTs (mostly small, with fewer than 100 participants), creatine at a median dose of 5 grams daily was associated with a statistically significant but small reduction in depression symptom scores. However, study heterogeneity was substantial, and the overall certainty of evidence was very low. Higher-quality studies reported no effect, and correcting for publication bias further diminished the significance, suggesting possible overestimation of benefit. Subgroup analyses indicated a larger effect in affective disorder populations versus healthy participants. Side effects were generally mild, mostly gastrointestinal, and a few trials reported slight increases in serum creatinine. One trial showed no quality-of-life improvement over five years. While creatine supplementation may modestly reduce depressive symptoms, current evidence is inconclusive and likely biased. The observed effects fall below clinical significance thresholds, indicating they might not be detectable in practice. The authors call for larger, well-designed trials with rigorous blinding and minimal co-interventions to definitively assess creatine’s antidepressant efficacy, aiming to clarify its potential as a safe, adjunctive treatment for depression. REFERENCE: Eckert I, Lima J, Dariva AA (2025). Creatine supplementation for treating symptoms of depression: a systematic review and meta-analysis. British Journal of Nutrition, 1-37. DOI: 10.1017/S0007114525105588, https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/creatine-supplementation-for-treating-symptoms-of-depression-a-systematic-review-and-metaanalysis/32402D649A44771955050ED518B6E564