Review Examines Clinical Studies on Supplements for Depression

A variety of supplements, including omega-3s, St. John’s Wort, saffron, and probiotics, may have efficacy in preventing or ameliorating depressive symptoms, according to a review of 209 available clinical studies published in Frontiers in Pharmacology.

“There has been an abundance of evidence evaluating OTC products for depression over the last few years, particularly products such as St. John’s Wort and omega-3 supplements,” the authors said, and omega-3s, St. John’s Wort, and saffron “have relatively conclusive separate systematic reviews and meta-analyses.”

The researchers carried out reviews of all available studies on Medline, Embase, PsycInfo, Amed, and Central journals, from inception to December 2022, including all studies involving participants with symptoms of depression or a formal diagnosis at baseline. Reviews were then summarized by the product and volume of evidence available.

According to the authors, the largest volume of evidence that supplementation may improve depressive symptoms included omega-3s, St. John’s Wort, saffron, probiotics (mainly multi-strain), and vitamin D.

There was also promising but highly limited evidence for a number of herbs and botanicals, including lavender, lemon balm, chamomile, and Echium; however, for the 41 products reviewed, only one clinical study was available for each.

“Limited but promising evidence” was also available for folic acid, zinc, tryptophan, and Rhodiola, but more research is needed, the authors wrote.

St. John’s Wort

According to the authors, St. John’s Wort was the most commonly-studied herbal product, and the review only included studies on people formally diagnosed with depression. St. John’s Wort was compared to placebo in 26 trials, to an active drug in 10 trials, and to a lower dose in one trial.

The evidence mostly favored St. John’s Wort, with 16 positive versus 9 negative placebo-controlled trials. In studies comparing it to antidepressants, St. John’s Wort was found to have similar effects in 11 studies, greater effects in four studies, and worse effects in one study.

Saffron

The studies encompassed a range of extracts which included stigma, crocin, petals, a mix, or unspecified plant parts. Saffron was evaluated across a wider range of comorbid conditions than St. John’s Wort, including heart disease, postpartum, menopause, and type 2 diabetes.

Eight studies reported positive effects, while three studies reported negative effects when saffron was compared to a placebo. In studies comparing it to prescription medications, six studies found it had similar effects, while two studies found that different saffron products exhibited similar effects.

Probiotics

Probiotics were evaluated as multi-strain species in 13 of the 16 studies included. Eight studies were conducted on people diagnosed with depression, while the other eight included self-reported symptoms.

A range of comorbidities were included, and probiotics were evaluated as an adjunct to antidepressant therapy in seven studies. A majority of studies favored probiotics over placebo with similar results to other OTC products.

Vitamin D

Vitamin D studies involved a wide variety of dosing regimens (daily to weekly) and levels (1,000-100,000 IU).

Nine trials were conducted in people with a depression diagnosis, while six studies involved people with self-reported symptoms.

In eight of 14 cases, vitamin D was tested as an adjunct to prescription medication or cognitive behavioral therapy. It was mostly compared to a placebo (9 of 14 studies) and most studies involved people with a vitamin D deficiency. Comparisons against placebo mostly favored vitamin D (six positive versus three negative), but other types of comparisons showed mixed results.

The authors noted that they found 34 ongoing clinical studies evaluating dietary supplements in people with depression or its symptoms that have not been published – 17 involve probiotics, four involve vitamin D, and three involve omega-3s.

They noted that there were no safety issues in most of the studies involved, with just a small number of mild adverse events reported.

“What we have is relatively conclusive evidence for some products,” said Rachael Frost, first author of the study and senior lecturer at Liverpool John Moores University. “When we looked at surveys of what people commonly take, chamomile, lavender, lemon balm, and echium emerged as commonly consumed products with an emerging evidence base, which we recommend to be studied further … our study has pioneered an exploration into what research is needed to further assess such widely used health care products.”