Vitamin D does not reduce risk of depression or mood changes

Vitamin D has been found to benefit health in various ways. As a consequence, this "sunshine" vitamin has been used as a supplement in several health conditions. There have been reports of the mental health benefits of this vitamin in reducing the risk of depression. Now, a new study shows that there may not be any specific benefit provided by vitamin D supplementation in reducing the risk of depression. The study titled, "Effect of Long-term Vitamin D3 Supplementation vs. Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial," is published in the latest issue of the Journal of American Medical Association (JAMA).

What was this study about?

Several studies have shown that those with Vitamin D deficiency also have symptoms of depressive illness. The authors wrote, "Low levels of 25-hydroxyvitamin D have been associated with a higher risk for depression later in life, but there have been few long-term, high-dose large-scale trials." The authors wanted to answer the question if long term supplementation of vitamin D3 could prevent depression among adults.

What was done?

For this large study, the team recruited 18,353 individuals aged 50 years or older. The trial was named "VITAL-DEP (Vitamin D and Omega-3 Trial-Depression Endpoint Prevention)" and was part of the extensive study VITAL. The VITAL study is a large study with 25,871 American adults to see if this vitamin reduced their risk of heart disease and cancer.

In this ancillary study on depression risk, the team noted that 16,657 individuals did not have a previous history of diagnosed depressive illness. However, these individuals were said to be at risk of developing new-onset depression during the study. The other 1,696 individuals had a history of depression and were considered to be at risk of developing recurrent depression during the course of this study. Those with a history of depression were defined as "depression history but no treatment for depression within the past 2 years".

The participants were recruited between November 2011 and March 2014. Treatment was continued till December 31, 2017, which was the last follow up date of the participants. The participants were divided into two groups in a randomized fashion;

  • 9,181 participants were given vitamin D3 (2000 IU/d of cholecalciferol) and fish oil
  • 9,172 participants were given placebo pills

The researchers looked at the risk of depression or symptoms of depression that could be clinically measured among the participants. Both new and recurrent cases of depression among the participants were checked. In addition, mood score changes with time were also checked. For this, the tool used was the "8-item Patient Health Questionnaire depression scale [PHQ-8]; score range, 0 points [least symptoms] to 24 points [most symptoms]; the minimal clinically important difference for change in scores was 0.5 points".

What was found?

This large study showed that compared to placebo treatment, vitamin D3 supplementation did not result in significant differences in new cases of depression or recurrence of depressive symptoms among the participants over five years of treatment.

The average age of the participants was around 67.5 years, and nearly half of them were women. A total of 90.5 percent of the participants completed the trial, with 93.5 percent alive at the end of the trial.

The authors wrote that among the vitamin D3 group, there were 609 cases of depression or with clinically detectable depressive symptoms. The incidence was 12.9 per thousand person-years. Among the placebo group, there were 625 cases of depression with an incidence of 13.3 per thousand person-years. The hazard ratio was 0.97, and the team wrote, "there were no significant differences between groups in depression incidence or recurrence."

Checking on mood scores, they noted that there were no significant changes in mood scores with time among both treatment and placebo groups from baseline on the PHQ-8 score. The average change in mood scores was 0.01 points, the team found.

Conclusions and implications

The authors concluded that treatment with vitamin D3 for five years compared with the placebo does not reduce the risk of developing depressive symptoms among adults aged 50 or older. Dr. Olivia I. Okereke of Massachusetts General Hospital's Psychiatry Department and lead author of the study, in her statement, said, "There was no significant benefit from the supplement for this purpose. It did not prevent depression or improve mood." She added that these findings were reasonably reliable due to the large number of study subjects. She said, "One scientific issue is that you actually need a very large number of study participants to tell whether or not a treatment is helping to prevent the development of depression...With nearly 20,000 people, our study was statistically powered to address this issue."

Co-author of the study Dr. JoAnn Manson of Brigham and Women's Hospital, said in her statement, "Vitamin D is known to be essential for bone and metabolic health, but randomized trials have cast doubt on many of the other presumed benefits." Okereke added, "It's not time to throw out your vitamin D yet, though, at least not without your doctor's advice."

Authors wrote in conclusion, "These [study] findings do not support the use of vitamin D3 in adults to prevent depression."

Journal reference:
  • Okereke OI, Reynolds CF, Mischoulon D, et al. Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial. JAMA. 2020;324(5):471–480. doi:10.1001/jama.2020.10224,
Dr. Ananya Mandal

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.


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