High-Dose Vitamin D Does Not Prevent Depression

Fran Lowry

May 13, 2011

May 13, 2011 — Women 70 years and older who received a high dose of vitamin D3 once a year for up to 5 years did not show any improvement in symptoms of depression, according to a new study published in the May issue of the British Journal of Psychiatry.

The finding, from the Vital D trial, calls into question the hypothesis that an annual high dose of vitamin D3 is a practical intervention to prevent depressive symptoms in older individuals, the study authors, led by Kerrie M. Sanders, PhD, of the University of Melbourne, Australia, write.

About half of community-dwelling older women in Australia have vitamin D insufficiency (< 50 nmol/L), and it has been postulated that low levels of vitamin D, which are common in winter, may contribute to seasonal affective disorder and also that older adults with vitamin D deficiency are more likely to have depressed mood.

In addition, the biochemical pathways in the brain are consistent with vitamin D playing a part in mental well-being, Dr. Sanders told Medscape Medical News.

The Vital D study was a double-blind, randomized, placebo-controlled trial involving 2258 women 70 years or older who were randomized to receive either an oral dose of vitamin D3, 500,000 IU, or placebo once a year every autumn or winter for 3 to 5 years.

The primary endpoint of the study was falls and fractures, and the women were recruited on the basis of hip fracture risk. Results of that study, which were published in the Journal of the American Medical Association in 2010 and reported by Medscape Medical News at the time, showed that high-dose vitamin D was associated with an increased risk for falls and fractures.

In the present study, Dr. Sanders and her group assessed a subgroup of 150 women for the effect of vitamin D on mental health. These women completed various mental health questionnaires, including the General Health Questionnaire, the 12-item Short-Form Health Survey, the World Health Organization Well-Being Index, and the Patient Global Impression Improvement scale.

Serum 25-hydroxyvitamin D levels were measured before receiving the annual dose and again at 1 and 3 months afterward.

No Impact on Mental Health

The results showed no differences between the vitamin D and placebo groups in any of the measured outcomes of mental health, even though serum 25-hydroxyvitamin D levels in the women in the high-dose vitamin D group were 41% higher than in the placebo group when measured 1 year after their annual dose.

In an interview Dr. Sanders said she and her team were surprised by the study findings. "We considered that better vitamin D status would be associated with improved mood.

"However," she added, "the study was originally designed to show a reduction in falls and fractures in those on the vitamin D, but very surprisingly our results showed increased falls and fractures using the once-a-year large dose of vitamin D. So that unexpected outcome raised doubts that we would show benefit of mental health in the vitamin D group."

For now, people should not take large doses of vitamin D, Dr. Sanders said. However, the jury is still out on small doses.

"This is particularly important as we actually found more falls and fractures in the vitamin D group. But we must remember that the adverse results relate to annual large doses and not smaller regular doses of vitamin D,"she said.

"Having adequate vitamin D status (ie, serum 25 hydroxyvitamin D levels between 60 and 75 nmol/L) is beneficial, but people should obtain their vitamin D in smaller regular doses of 800 to 1000 IU per day."

Commenting on this study for Medscape Medical News, Glenn Currier, MD, MPH, from the University of Rochester Medical Center in New York, suggests that these findings are important but should not necessarily be extrapolated to other age groups and clinical populations.

"Findings in elderly women in high sun climates may not be relevant to younger depressed patients in the Great Lakes Cloud Belt, for example," he said.

This study was funded by the Australian National Health and Medical Research Council. Other study authors report financial relationships with Stanley Medical Research Foundation, Beyond Blue, Eli Lilly, GlaxoSmithKline, Organon, Mayne Pharma, Servia, Bristol Myers Squibb, Novartis, AstraZeneca, Janssen-Cilag, Lundbeck, Pfizer, Sanofi Synthelabo, Solvay, and Wyeth. Dr. Sanders and Dr. Currier has disclosed no relevant financial relationships.

Br J Psychiatry. 2011;198:357-364. Abstract