Large Review Finds Only 4 Supplements Have Substantive Evidence for Depression
- A massive new review of clinical trials suggests that only four dietary supplements possess substantive scientific evidence to help manage depression in adults under age 60.
- Led by Rachael Frost, PhD, a senior lecturer in health and social care at Liverpool John Moores University in England and a Western herbal practitioner, the research aimed...
- John's wort—an invasive, wild, flowering plant—was evaluated in a total of 37 trials.
A massive new review of clinical trials suggests that only four dietary supplements possess substantive scientific evidence to help manage depression in adults under age 60. According to a scoping review published by researchers, out of 64 over-the-counter products investigated across 209 trials, only St. John’s wort, saffron, probiotics, and vitamin D met the threshold of having more than 10 clinical trials backing their effectiveness.
Evaluating 64 Supplements Across 209 Trials
Led by Rachael Frost, PhD, a senior lecturer in health and social care at Liverpool John Moores University in England and a Western herbal practitioner, the research aimed to provide an overview of available clinical trials for a wide range of over-the-counter mental health products. Previous research typically focused on single products, which prevented investigators from comparing different treatments and identifying research gaps. To map out the existing literature, researchers evaluated randomized controlled trials—considered the gold standard of clinical evidence—though they did not assess the individual quality or size of those trials. Out of the 64 supplements examined, researchers found that 41 were supported by only a single study. Only four supplements crossed the threshold of substantive evidence by appearing in more than 10 trials. Alex Dimitriu, MD, a psychiatrist, sleep medicine physician, and founder of Menlo Park Psychiatry and Sleep Medicine in Menlo Park, California, noted that the research is highly relevant because many individuals experiment with supplements before ever seeking professional help.
The Four Supplements With Substantive Evidence
According to Frost, St. John’s wort—an invasive, wild, flowering plant—was evaluated in a total of 37 trials. More of these trials showed positive effects against a placebo than no effects, with results similar to or better than antidepressants. Saffron was investigated in 18 trials, which demonstrated effects comparable to prescription antidepressants and, in some cases, greater effects than a placebo. Probiotics appeared in 16 trials and were shown to be more effective than a placebo, potentially boosting gut health and mood stability. Vitamin D was tested in 14 trials and proved effective compared with a placebo, though Frost noted it was not effective when compared directly against antidepressants. Vitamin D plays a recognized role in thyroid regulation, sleep, and mood.
Limited Evidence and Mixed Results for Other Products
Beyond the top four treatments, the review identified limited evidence suggesting possible benefits for depressive symptoms from several other products. These include lavender, lemon balm, chamomile, tryptophan, rhodiola, zinc, and folic acid. Meanwhile, the review yielded mixed results for melatonin, magnesium, cinnamon, vitamin C, and several additional compounds. Frost emphasized that the findings call for additional clinical trials into products with promising evidence, noting that efficacy varies by product rather than being a binary issue of herbs or supplements working or failing. Researchers encourage individuals to thoroughly investigate any product they plan to take, keeping in mind that the reviewed studies involved a variety of dosages and trial sizes ranging from large, well-conducted studies to small pilot projects.
