Scientists Clarify Controversial Link Between Supplements and Depression

The “food-mood” connection grows even more complex.

The idea that something as simple as diet could be the answer to preventing depression before it strikes is tantalizing — and not completely unfounded. Past studies have highlighted a food-mood connection, even going so far as to suggest that the Mediterranean diet is a promising treatment for patients with depression. But on Tuesday, the results of a large clinical trial on nutrition and depression provide a reason not to believe the hype just yet.

In a study published in JAMA, a team of scientists from England and the Netherlands reported they were unable to find that nutritional supplementation had any effects on individuals who were at risk for depression. These results come from the European MooDFOOD trial, a long-term study on 1,025 obese individuals who had an “elevated risk” for developing depression. It is the largest clinical trial yet to investigate how nutritional supplements might prevent major depression.

A previous meta-analysis suggested that people who adhere to a Mediterranean diet develop less depressive symptoms. 


Marjolein Visser, Ph.D., the study’s corresponding author, tells Inverse she was surprised they didn’t see supplements have some effect on the development of depression. However, her team’s negative result still adds crucial context to the ongoing debate around nutrition and depression, part of a field that is sometimes referred to as “nutritional psychiatry.”

“At the start of the project, there was a lot of conflicting evidence on the role of diet and nutrients in depression, and, in particular, little was known about whether these factors could contribute to the prevention of depression,” Visser tells Inverse. It’s important to note that another author of the paper disclosed funding from several pharmaceutical companies: Lundbeck, Janssen Pharmaceutica, Servier, Bayer Pharma, and Medice.

Visser’s study pulled out all the stops to add clarity to the conversation around supplements and depression. Her team hand-selected a cocktail of supplements that earlier studies had suggested may impact mood, including omega-3 supplements, vitamin D3 plus calcium, and folic acid. She also included a food therapy intervention that encouraged her participants to adhere to a Mediterranean diet and be more thoughtful about their food choices. That way, she would be able to measure the effect of the supplements against other interventions intended to curb depression.

“Although we hypothesized that the two nutritional strategies could prevent depression, it was timely and important to address this in a randomized clinical trial to obtain the evidence whether this was indeed true,” Visser says.

Finally, she divided her participants into four nearly equal groups: 256 of them got supplements and therapy, 256 got supplements alone, 256 got placebo supplements and therapy, and 257 of them got placebos and no therapy.

Over the course of a year, there were no significant differences in depression development among the groups — in fact, the placebos actually out-performed the supplements by a small margin. Those 10.5 percent who received supplements developed depression compared to 9.9 percent of those who received placebos. In terms of the therapy group, they noted slightly lower rates of depression in those who received therapy compared to those who didn’t — but still, the results weren’t statistically significant.

In response to her results, Visser feels confident saying that supplements really aren’t going to prevent depression before it strikes.

“Although we have not investigated the effects of multi-nutrient supplements on other conditions, physicians can explain to their patient population that there is no evidence to support the use of these supplements for the prevention of depression,” she says.

Can Diet Help Treat Depression?

This study is just one more in an increasingly confusing research landscape around nutrition and depression that, as Visser points out, is laden with “conflicting evidence.” While this study seems to suggest that supplements won’t prevent depression, other researchers in the field of nutritional psychiatry hold out hope that dietary interventions may be viable treatments for depression. An accompanying commentary published in JAMA on Tuesday goes to great lengths to point this out.

Nutritional psychiatry is a field that looks to use diet to treat depression and other mood disorders. 


The commentary, written by Michael Berk, Ph.D., a professor at the Deakin University School of Medicine who specializes in psychiatric disorders, and Felice Jacka, Ph.D., the director of the Food and Mood Center and a professor of nutritional and epidemiological psychiatry also at Deakin University, highlights several trials that do show dietary interventions improve mental health. They point to their own clinical trial showing that a dietary intervention drastically improved outcomes in patients with depression. However they did receive some pushback regarding their methods from additional reviewers.

Berk and Jacka both disclose funding from numerous pharmaceutical and food companies. Nevertheless, they also drive home an important point about studies that investigate diet and depression. There are so many factors that contribute to depression itself, from genetics to insomnia, that it’s hard to make a definitive statement about what will and will not prevent it.

In that sense, they suggest that we shouldn’t give up on investigating the relationship between diet and depression based on the results of this trial. But they do concede it’s unlikely that diet alone will have any effect on preventing depression. Instead, they argue that diet could be part of an “integrated care package” that involves therapy, physical activity, and other interventions.

Going forward, Visser indicates she’s thinking along the same lines. “Whether other strategies, or perhaps combined lifestyle strategies, could prevent depression should be explored in further research,” she adds.

Still, Visser’s results seem to make it clear that popping a few supplement pills can’t protect against a threatening psychological condition. But that’s not to say there isn’t more to learn when it comes to new avenues of heading the condition off at the pass.

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