Vitamin D Does Not Reduce Risk of Depression in Adults

Summary: Vitamin D3 supplements do not help to lift mood in those who suffer from depression. Researchers say there is no significant benefit for vitamin D supplements to help prevent depression or to improve mood.

Source: Mass General

Vitamin D supplementation does not protect against depression in middle-age or older adulthood according results from one of the largest ever studies of its kind. This is a longstanding question that has likely encouraged some people to take the vitamin.

In this study, however, “There was no significant benefit from the supplement for this purpose. It did not prevent depression or improve mood,” says Olivia I. Okereke, MD, MS, of Massachusetts General Hospital (MGH’s Psychiatry Department.

Okereke is the lead author of the report and principal investigator of this study, which will be published in JAMA on Aug. 4. It included more than 18,000 men and women aged 50 years or older. Half the participants received vitamin D3 (cholecalciferol) supplementation for an average of five years, and the other half received a matching placebo for the same duration.

Vitamin D is sometimes called the “sunshine vitamin” because the skin can naturally create it when exposed to sunlight. Numerous prior studies showed that low blood levels of vitamin D (25-hydroxy vitamin D) were associated with higher risk for depression in later life, but there have been few large-scale randomized trials necessary to determine causation. Now Okereke and her colleagues have delivered what may be the definitive answer to this question.

“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 development of depression,” Okereke explains. “With nearly 20,000 people, our study was statistically powered to address this issue.”

This study, called VITAL-DEP (Depression Endpoint Prevention in the Vitamin D and Omega-3 Trial), was an ancillary study to VITAL, a randomized clinical trial of cardiovascular disease and cancer prevention among nearly 26,000 people in the US.

This shows a depressed man
Among the 18,353 randomized participants, the researchers found the risk of depression or clinically relevant depressive symptoms was not significantly different between those receiving active vitamin D3 supplements and those on placebo, and there were no significant differences were seen between treatment groups in mood scores over time. Image is in the public domain.

From that group, Okereke and her colleagues studied the 18,353 men and women who did not already have any indication of clinical depression to start with, and then tested whether vitamin D3 prevented them from becoming depressed.”

The results were clear. Among the 18,353 randomized participants, the researchers found the risk of depression or clinically relevant depressive symptoms was not significantly different between those receiving active vitamin D3 supplements and those on placebo, and there were no significant differences were seen between treatment groups in mood scores over time.

“It’s not time to throw out your vitamin D yet though, at least not without your doctor’s advice,” says Okereke. Some people take it for reasons other than to elevate mood.

“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,” said the paper’s senior author, JoAnn Manson, MD, DrPH, at Brigham and Women’s Hospital.

The other authors include researchers from the Psychiatry Department at UPMC and University of Pittsburgh School of Medicine, and from the VA Boston Healthcare System.”

About this depression research article

Source:
Mass General
Media Contacts:
Noah Brown – Mass General
Image Source:
The image is in the public domain.

Original Research: Closed access
“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” by Olivia I. Okereke, MD, SM; Charles F. Reynolds III, MD; David Mischoulon, MD, PhD; Grace Chang, MD, MPH; Chirag M. Vyas, MBBS, MPH; Nancy R. Cook, ScD; Alison Weinberg, MA; Vadim Bubes, PhD; Trisha Copeland, MS, RD; Georgina Friedenberg, MPH; I-Min Lee, MBBS, ScD; Julie E. Buring, ScD; JoAnn E. Manson, MD, DrPH. JAMA.


Abstract

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

Importance
Low levels of 25-hydroxyvitamin D have been associated with higher risk for depression later in life, but there have been few long-term, high-dose large-scale trials.

Objective
To test the effects of vitamin D3 supplementation on late-life depression risk and mood scores.

Design, Setting, and Participants
There were 18 353 men and women aged 50 years or older in the VITAL-DEP (Vitamin D and Omega-3 Trial-Depression Endpoint Prevention) ancillary study to VITAL, a randomized clinical trial of cardiovascular disease and cancer prevention among 25 871 adults in the US. There were 16 657 at risk for incident depression (ie, no depression history) and 1696 at risk for recurrent depression (ie, depression history but no treatment for depression within the past 2 years). Randomization occurred from November 2011 through March 2014; randomized treatment ended on December 31, 2017, and this was the final date of follow-up.

Intervention
Randomized assignment in a 2 × 2 factorial design to vitamin D3 (2000 IU/d of cholecalciferol) and fish oil or placebo; 9181 were randomized to vitamin D3 and 9172 were randomized to matching placebo.

Main Outcomes and Measures
The primary outcomes were the risk of depression or clinically relevant depressive symptoms (total of incident and recurrent cases) and the mean difference in mood scores (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).

Results
Among the 18 353 randomized participants (mean age, 67.5 [SD, 7.1] years; 49.2% women), the median treatment duration was 5.3 years and 90.5% completed the trial (93.5% among those alive at the end of the trial). Risk of depression or clinically relevant depressive symptoms was not significantly different between the vitamin D3 group (609 depression or clinically relevant depressive symptom events; 12.9/1000 person-years) and the placebo group (625 depression or clinically relevant depressive symptom events; 13.3/1000 person-years) (hazard ratio, 0.97 [95% CI, 0.87 to 1.09]; P = .62); there were no significant differences between groups in depression incidence or recurrence. No significant differences were observed between treatment groups for change in mood scores over time; mean change in PHQ-8 score was not significantly different from zero (mean difference for change in mood scores, 0.01 points [95% CI, −0.04 to 0.05 points]).

Conclusions and Relevance
Among adults aged 50 years or older without clinically relevant depressive symptoms at baseline, treatment with vitamin D3 compared with placebo did not result in a statistically significant difference in the incidence and recurrence of depression or clinically relevant depressive symptoms or for change in mood scores over a median follow-up of 5.3 years. These findings do not support the use of vitamin D3 in adults to prevent depression.

Trial Registration
ClinicalTrials.gov Identifiers: NCT01169259 and NCT01696435

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