Dozens of supplements claim to help alleviate depression, but only a few are backed by research, a new study found.
Researchers in the United Kingdom reviewed hundreds of clinical trials that evaluated how well 64 different types of over-the-counter dietary supplements—from herbs to vitamins—treated depressive symptoms.
Most of the research on supplements was limited, but five were significantly more studied than the others. Of those, four tended to outperform a placebo:
“I was interested in seeing whether this could be a solution for many people,” said the study’s lead author, Rachael Frost, an herbal practitioner and senior lecturer at Liverpool John Moores University in the United Kingdom. “The accessibility of supplements is important—they do tend to cost less and do tend to be widely available.”
Frost cautioned that she and her team did not assess the quality of the studies included. All were clinical trials—meaning they tested supplements in people—but some were large and well-designed, while others were smaller and less rigorous, she said.
With millions of social media posts from non-experts promoting products in the nearly $152 billion supplements industry, experts said it’s more important than ever to understand which are actually effective.
“This study is a really helpful snapshot of where we stand with supplements for depression. What stood out most to me is that they looked at 64 different products but found solid evidence for only four,” said De Borrah Wright, MD, medical director of child and adolescent psychiatry inpatient service at NYC Health + Hospitals – Kings County, who was not involved with the new study.
It “highlights how important it is not to assume that every supplement on the shelf is effective,” she said.
The researchers looked at 209 trials investigating magnesium, folic acid, cinnamon, vitamin C, prebiotics, and dozens of other supplements. Of these, 196 trials evaluated the supplements for depression alone. Others evaluated how well these products could alleviate depression along with other mental health conditions, such as anxiety and insomnia.
There was little research conducted on most of the products, the team’s analysis revealed. Forty-one were each only evaluated in a single trial.
Still, the new paper found that some supplements have been more extensively studied than others for their potential to ease depressive symptoms:
- Omega-3 fatty acids. These were evaluated in 39 trials—more than any other product. However, the majority of those studies found that the supplements didn’t outperform a placebo in reducing depressive symptoms.
- St. John’s wort. This herb is derived from the yellow-flowered Hypericum perforatum plant. Many trials showed that it improved symptoms compared to a placebo, and some research has even suggested that it may be as effective as prescription antidepressants.
- Saffron. Derived from a type of crocus flower, this spice was also studied more than many other supplements. Though early results show promise, “studies are small, and we still need more data before making strong recommendations,” Wright told Health.
- Probiotics and vitamin D. These also had a substantial body of research, much of it promising. For vitamin D, the benefits seem clearer in people with low levels. But “for those with normal levels, the benefit is less clear,” Wright said. A 2024 meta-analysis suggested that high levels of vitamin D may be needed to see an effect on depressive symptoms, but excess vitamin D can be toxic and affect bone health.
The following supplements had limited evidence but hinted at positive effects:
Studies have shown that some supplements, including St. John’s wort and saffron, appear to regulate serotonin and dopamine, two hormones related to depression.
As for vitamin D, research has noted that receptors for the vitamin are located in several parts of the brain thought to play a role in depression, including the prefrontal cortex, hippocampus, and thalamus.
According to Thea Gallagher, PsyD, a clinical psychologist at NYU Grossman School of Medicine and director of wellness programs at NYU Langone, probiotics are a low-risk place to start if someone would like to incorporate a supplement into their depression treatment. “That gut-brain access point, we think, is an important factor in mental health, so taking probiotics and also getting probiotics from food can be good,” she said.
If someone with mild or moderate—but not severe—depression would like to try supplements for their symptoms, Gallagher said taking them is likely low-risk. Reassuringly, there “were relatively few adverse events” in the studies her paper reviewed, Frost said.
Still, “herbs and supplements can have quite a wide range of effects across different body systems,” Frost said. “It’s important to look at the quality of the products and see if the dose you are taking aligns with the dose used in studies.”
You also want to confirm that you aren’t taking medications that could interfere with the supplement—St. John’s wort, for example, can be dangerous when mixed with birth control pills, blood thinners, and antidepressants.
Because the Food and Drug Administration doesn’t regulate most supplements for safety or efficacy, Wright recommends buying supplements with a seal from a third-party tester, such as USP or NSF.
Though some supplements show promise for reducing depressive symptoms, how well they work compared to anti-depression drugs, such as selective serotonin reuptake inhibitors (SSRIs), remains largely unknown, said Gallagher.
“It’s kind of the wild wild west with understanding supplements, and we are trying to learn a lot more about how they work and what they do,” Gallagher told Health.
It’s possible the well-documented placebo effect could be influencing some of the evidence in favor of supplements—but this isn’t necessarily a bad thing, she noted. “If supplements are part of you turning over a new leaf of taking better care of your health, that can be part and parcel good for depression,” she said.
Still, Gallagher cautioned people to be critical of what they see online. “There are a lot of influencers that are getting paid to say something has worked for them, but the problem when you come from the science and research side, we don’t find that the scientific findings are robust enough for us to recommend,” she said.
For people with even mild to moderate depression, “supplements alone are probably not going to help you,” she added. And if you’re trying to avoid prescription medication, it’s especially important to maintain healthy habits like “eating regular, substantive meals, getting good sleep, [and] getting 150 minutes of exercise per week,” she said.
