Vitamin D3 Found Ineffective at Preventing Depression

High-dose vitamin D3 supplements do not appear to be effective at preventing depression in older adults, according to a large, placebo-controlled study published August 4 in JAMA.

Observational studies have suggested that people with lower blood levels of vitamin D are at higher risk of late-life depression, while other research has found that vitamin D deficiency may be involved in seasonal depressive disorder. But to date prospective studies of people taking vitamin D supplements have yielded little evidence that adding vitamin D protects against depression.

It is possible that previous supplement studies examined vitamin D doses that were too low and/or the studies were too short in duration. This new study addressed previous shortcomings by evaluating over 18,000 older adults across the United States for over five years.

The adults were participants in the Vitamin D and Omega-3 Trial (VITAL), a randomized study examining the effects of daily vitamin D3 and/or fish oil supplements on the prevention of cancer and cardiovascular disease. As an ancillary part of the study (VITAL-DEP), participants were also given the eight-item Patient Health Questionnaire (PHQ-8) during their periodic assessments to screen for depressive symptoms. Participants who were currently receiving treatment for depression or had another psychiatric or neurological condition were excluded from this ancillary analysis.

The final sample included 9,181 adults who took 2,000 IU/d of vitamin D3 daily for an average of 5.3 years and 9,172 adults who took placebo for the same average time. By the end of the study, 609 adults taking vitamin D3 and 625 taking placebo received a diagnosis of depression or developed clinically relevant depressive symptoms (a PHQ-8 score of ≥10)—which the authors noted was not a significant difference between the groups.

There was also no significant difference between the two groups in overall mood over time; average PHQ-8 scores rose by 0.20 points in the vitamin D3 group and 0.16 points in the placebo group.

“By no means is this study a verdict on vitamin D as a supplement in general,” said study author Olivia Okereke, M.D., the director of geriatric psychiatry at Massachusetts General Hospital and an associate professor of psychiatry and epidemiology at Harvard Medical School. “This vitamin is important for bone health and immune health and potentially other conditions.”

She continued, “The findings indicate that for an average adult, taking vitamin D3 supplements for the purpose of improving mood will provide no benefit.”

Okereke and colleagues also looked at data on various subgroups in the study to see whether there might be a population that experienced a positive effect from vitamin D3. However, vitamin D3 did not appear to prevent depression in any of the tested subgroups, including grouping by sex, ethnicity, age group, and depression history.

“Now, there was one interesting signal that showed adults with normal body weight [body mass index score of 25 or less] might be gaining some protection from depression,” Okereke noted. This signal mirrored some data seen in the main VITAL study, which was published last year in the New England Journal of Medicine. This study found that while vitamin D3 supplements did not prevent cancer or major cardiovascular events in the general population, the supplements did appear to reduce the risk of cancer in adults with low body mass index.

Okereke cautioned that the findings on obesity are still preliminary, but if there was one variable worth pursuing with further research, that would be it.

The VITAL-DEP researchers are reviewing data related to fish oil and depression and hope to release those findings soon.

VITAL-DEP was supported by a grant from the National Institute of Mental Health. The main VITAL study was supported by grants from the National Cancer Institute; the National Heart, Lung, and Blood Institute; the National Institute of Neurological Disorders and Stroke; the National Center for Complementary and Integrative Health; and the Office of Dietary Supplements. Pharmavite LLC and Pronova BioPharma/ BASF donated the vitamin D3 and fish oil for the study, respectively. ■

“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 posted here.

The parent VITAL study, “Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease” is posted here.