Many people living with depression look for relief outside of prescription medications. Whether due to side effects, stigma, or simply wanting a more natural option, vitamins, herbs, and supplements are becoming go-to choices for those hoping to manage symptoms on their own terms.
But do these over-the-counter (OTC) products actually work? A major new review led by Rachael Frost, Ph.D., an herbalist and senior lecturer at Liverpool John Moores University, set out to answer that question. Her team examined 209 clinical trials to find out which natural options show real promise — and which still need more research.
Why Natural Support Matters
Depression doesn’t just affect mood. It can reduce quality of life and increase risks for serious health issues like heart disease and diabetes. It also takes a massive toll on work, relationships, and even the global economy — costing an estimated $4.7 trillion worldwide.
While antidepressants are available, they require seeing a doctor and can have mixed results when it comes to effectiveness and side effects. So, it’s no surprise that many people try herbal products, vitamins, and minerals either before or alongside traditional treatments.
Which Natural Products Show the Most Promise?
After digging into the evidence, Dr. Frost’s team found five natural options that had the most consistent support in managing mild to moderate depression:
- Omega-3 fatty acids
- St. John’s Wort
- Saffron
- Probiotics
- Vitamin D
Each of these showed positive results in clinical trials, helping with mood and other depression-related symptoms.
Other products like lavender, chamomile, lemon balm, and Echium also showed potential benefits, but the researchers say more studies are needed to confirm their effectiveness.
What About Lesser-Known Supplements?
Some less commonly used products — such as folic acid, zinc, tryptophan, and Rhodiola — had smaller but encouraging amounts of evidence. Many were tested alongside antidepressants or therapy, rather than as stand-alone options. These may offer added support rather than a full alternative.
Are These Remedies Safe?
Good news: Most of the OTC products reviewed had no serious safety concerns, whether taken alone or with other treatments. Of the 69% of trials that reported side effects, 85% had no significant problems.
Still, researchers noted that side effect reporting could be better — more detailed, consistent tracking is needed in future studies.
What Made This Review Different?
This review stands out because it took a broad, comprehensive look at multiple OTC options instead of focusing on just one or two. It included studies from all over the world, particularly the U.S., U.K., Iran, Germany, Australia, and China. It also looked specifically at adults aged 18–60 with diagnosed depression or clear symptoms — making the results more relevant for real-world use.
Some Limitations to Keep in Mind
The review wasn’t perfect. Only 10% of studies were double-screened, which could allow for bias. Some relevant studies may have been missed, especially due to confusing product labels or limited search terms. And while non-English trials were included, some translations were done using Google Lens, which might not always be accurate.
For better results in the future, the team recommends using wider language filters and including traditional medicine systems, like those in China, which are currently underrepresented.
The Bottom Line
If you’re exploring natural ways to support your mental health, this research gives hope — but also a reminder to proceed wisely. Some supplements, like omega-3s, probiotics, and vitamin D, show real promise. Others may help, but need more scientific backing.
And most importantly, always check with your healthcare provider before starting any supplement — especially if you’re already on medication or managing other health conditions.
Natural doesn’t always mean risk-free, but with the right information, it can be part of a thoughtful, personalized approach to feeling better.