Now, a new metastudy has assessed 64 different products reviewed in hundreds of studies to shed light on how useful they are in relieving depression.

An international team of researchers reviewed 23,933 study records and 1,367 papers, homing in on 209 clinical trials that analyzed the efficacy of 64 common over-the-counter (OTC) supplements aimed at treating depression when taken consistently for more than a week. The collective data covered adults aged 18-60 years with either depression symptoms or an official diagnosis.

"Studies were not always straightforward – some tested multiple doses or products, some were in addition to antidepressants and in some trials people had a range of physical conditions in addition to depression," said study co-author Rachael Frost, a senior lecturer at Liverpool John Moores University. "We grouped our findings into products with substantive evidence (more than 10 trials), emerging evidence (between two and nine trials), and single trials only."

The most comprehensively studied products were omega-3s (39 trials), St John's wort (38), prebiotics (18) and vitamin D (14) – as well as saffron (18), which is popular in the Middle East and Asia.

As far as relieving depression symptoms, there was little conclusive evidence that omega-3 supplements had any impact; the scientists found more studies produced no effects than those that showed some, compared to a placebo. In 2021, we covered one such study that failed to show omega-3 supplements played any role in treating depression.

St John's wort and saffron had the strongest positive outcomes, with studies showing these two distinct supplements worked, compared to a placebo, and were on par with existing prescription antidepressants. And gut-health probiotics, as well as vitamin D, reduced depressive symptoms to some degree in their respective controlled trials.

But overall, the researchers found a distinct lack of multiple trials for many emerging OTC products, which shows how far the science is lagging behind as the wellbeing supplements market continues to grow. More than 40 of the 64 products had only a single clinical study completed on them to date.

"Out of a range of products with promising evidence, those most commonly used and so warranting further research were lavender, lemon balm, chamomile and echium," the scientists noted.

As for the emerging supplements with little research, some showed the most promise in early studies: Folic acid, lavender, zinc, tryptophan, rhodiola and lemon balm. Lemon balm (Melissa officinalis L.) has been growing in popularity over the last 12 months, touted as an effective sleep aid and anti-anxiety mood booster.