A new assessment of studies on more than 60 supplements claiming to help depression symptoms finds that only 4 have ‘substantive’ evidence of benefits.
For the millions of Americans living with depression, there is no shortage of dietary supplements claiming to help. Some influencers are more than happy to spread the word.
Now, a new review of existing studies suggests that there is “substantive” evidence to support the benefits of only four supplements for depression: St. John’s wort, saffron, probiotics, and vitamin D.
Previous research on mental health supplements has typically focused on single products, says lead author Rachael Frost, PhD, a senior lecturer in health and social care at Liverpool John Moores University in England and a Western herbal practitioner. “This doesn’t allow us to look across the different products and see where the research is, and where the gaps are,” she says.
“We aimed to provide an overview of the clinical trials available for a large range of OTC products to show which products have the most evidence, and which have very little,” she says. “This was to help people make decisions about products they may want to try, and to help inform future research directions on this topic.”
“This research is very relevant, as so many people will try supplements before they ever even seek professional help,” says Alex Dimitriu, MD, a psychiatrist and sleep medicine physician and founder of Menlo Park Psychiatry and Sleep Medicine in Menlo Park, California.
4 Supplements Have the Most Proof They Can Help Depression
To understand the existing evidence on supplements for depression in adults under age 60, researchers conducted a “scoping review” of existing research They looked at 209 trials investigating 64 different types of supplements. For 41 of these supplements, researchers only found a single study.
Researchers found “substantive evidence” for just 4 of the 64 supplements, Dr. Frost says. “By substantive evidence, we mean that there were more than 10 trials for each product,” she explains.
Those supplements were:
St. John’s Wort St. John’s wort is an invasive, wild, flowering plant. The current review found a total of 37 trials on St. John’s wort, with more showing effects against placebo than no effects, with similar or better results than antidepressants, Frost says.
Saffron Eighteen trials on saffron showed similar effects to prescription antidepressants. Some trials showed greater effects than a placebo.
Probiotics In 16 trials, probiotics were shown to be more effective than placebo, Frost says. Probiotics may boost gut health and mood stability.
Vitamin D Tested in 14 trials, vitamin D was shown to be effective compared with a placebo, but Frost says it wasn’t effective compared with antidepressants. Vitamin D plays a role in thyroid regulation, sleep, and mood.
The evidence to support the positive impact of other supplements was limited, but did suggest possible benefits for depressive symptoms from the following:
The review yielded mixed results for: melatonin, magnesium, cinnamon, vitamin C, and several others.
“Our review really calls for carrying out more trials into those products with promising evidence,” Frost emphasizes. “It’s simply not a case of ‘Herbs or dietary supplements work or don’t work,’ but each product has levels of evidence with regards to their effectiveness. I would encourage people to look carefully into any product they are planning to take.”
The Study Has Limitations
Researchers didn’t assess the quality of the trials that were included, only the volume of clinical trials available, Frost says.
“This is because we were aiming to scope the literature and map out what evidence was available, rather than make definitive conclusions on each product,” she explains.
The review only included randomized controlled trials, considered the “gold standard of clinical evidence,” Frost adds. But some trials were large and well-conducted, while others were small pilot studies.
Another limitation is that the studies reviewed often included a variety of dosages of supplements and preparations, which makes it difficult to identify what may be most effective for individuals, she explains.
Most studies didn’t include the side effects of tested products. Frost says more research should report this information to help identify product safety issues.
Are Depression Supplements Safe?
The scoping review identified few side effects of the supplements studied, Frost says, “but people should always be cautious if they are currently taking medications or have other health conditions.”
The supplements are generally safe, but could potentially cause problems in high doses, says Robert G.G. Piccinini, DO, an osteopathic psychiatrist and president of the American Osteopathic Association.
For example, St. John’s wort may act on receptors for serotonin (a hormone associated with mood), which can affect sleep and appetite, he explains.
St. John’s wort can also interact with prescription antidepressants, Dr. Dimitriu says, so it’s a good idea to talk to your doctor before taking it, or any other supplement, for that matter.
If you want to try the four supplements that showed benefits for depression, don’t take them all at once. “A better decision would be adding one at a time to evaluate its individual effect,” Dr. Piccinini says.
Dietary supplements aren’t evaluated for safety and efficacy by the U.S. Food and Drug Administration (FDA) like prescription and over-the-counter medications are. In 2021, the FDA sent warning letters to 10 companies for “illegal selling” of products claiming to “cure, treat, mitigate, or prevent depression and other mental health disorders,” as there’s no evidence to support the claims.
Supplements Aren’t a Replacement for Mental Health Treatment
“I think the key is that the study recognizes the importance of combining psychological therapy with supplement or prescription medication,” Piccinini says.
Supplements shouldn’t be considered a replacement for mental health treatment for depression, Dimitriu says, as the condition can mask your thinking and outlook.
“It’s good to have outside guidance and oversight for the best outcomes” for depression, he says. “For anyone experiencing more debilitating symptoms of depression, I recommend against self-treatment, and instead working with a professional.”
EDITORIAL SOURCES
Everyday Health follows strict sourcing guidelines to ensure the accuracy of its content, outlined in our editorial policy. We use only trustworthy sources, including peer-reviewed studies, board-certified medical experts, patients with lived experience, and information from top institutions.
FDA Sends Warning Letters to 10 Companies for Illegally Selling Dietary Supplements Claiming to Treat Depression and Mental Illness. U.S. Food and Drug Administration. February 19, 2021.
Influencers are asked to help stop the spread of mental health misinformation. NPR. February 12, 2024.
Understanding the research landscape of over-the-counter herbal products, dietary supplements, and medications evaluated for depressive symptoms in adults: a scoping review. Frontiers in Pharmacology. July 14, 2025.
Peterson B et al. St. John's Wort. StatPearls. May 16, 2023.
Johnson KV et al. Probiotics Reduce Negative Mood Over Time: The Value of Daily Self-Reports in Detecting Effects. npj Mental Health Research. April 9, 2025.
Akpınar Ş et al. Is Vitamin D Important in Anxiety or Depression? What Is the Truth? Current Nutrition Reports. September 2022.
Tom Gavin joined Everyday Health as copy chief in 2022 after a lengthy stint as a freelance copy editor. He has a bachelor's degree in psychology from College of the Holy Cross.
Prior to working for Everyday Health, he wrote, edited, copyedited, and fact-checked for books, magazines, and digital content covering a range of topics, including women's health, lifestyle, recipes, restaurant reviews, travel, and more. His clients have included Frommer's, Time-Life, and Google, among others.
He lives in Brooklyn, New York, where he likes to spend his time making music, fixing too-old electronics, and having fun with his family and the dog who has taken up residence in their home.
Erica Sweeney has been a journalist for more than two decades. These days, she mostly covers health and wellness as a freelance writer. Her work regularly appears in The New York Times, Men’s Health, HuffPost, Self, and many other publications. She has a master’s degree in journalism from the University of Arkansas at Little Rock, where she previously worked in local media and still lives.
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