More Evidence Links Low Vitamin D to Depression

Megan Brooks

February 13, 2012

February 13, 2012 — A large cross-sectional study of adults suggests a link between low vitamin D levels and depressive symptoms, particularly in individuals with a history of depression.

Because the relationship between low vitamin D levels and depression was stronger in those with a prior history of depression, "it may be more of a marker for relapse than for new-onset," senior investigator E. Sherwood Brown, MD, PhD, head of the psychoneuroendocrine research program at the University of Texas Southwestern Medical Center, Dallas, told Medscape Medical News.

Dr. E. Sherwood Brown

"Our findings suggest that screening for vitamin D levels in depressed patients — and perhaps screening for depression in people with low vitamin D levels — might be useful," Dr. Brown added in a university-issued statement.

The study was published in the November 2011 issue of Mayo Clinic Proceedings. It involved 12,594 participants (4005 women and 8595 men) from the prospective Cooper Center Longitudinal Study (CCLS). Participants' mean age was 51.7 years. A total of 1563 participants had a history of depression; 11,031 did not.

All participants completed baseline examinations that included measurement of serum 25-hydroxyvitamin D [25(OH)D] levels and an assessment using the Center for Epidemiologic Studies Depression Scale (CES-D). A CES-D score of 10 or higher was defined as evidence of depression.

According to the investigators, low vitamin D levels were common in the sample as a whole, with 50.7% of participants having levels in either the deficient range [25(OH]D < 20 ng/mL], according to Institute of Medicine recommendations, or the insufficient range [25(OH)D < 30 ng/mL]. Mean vitamin D levels did not differ significantly between those with and without a history of depression.

Biologically Plausible

In the overall sample, higher vitamin D levels were associated with a decreased risk for current depression, based on CES-D scores. The odds ratio [OR] was 0.92 (95% confidence interval [CI], 0.87 - 0.97; P < .002) for each 10 ng/mL increase in 25(OH)D.

When study participants with and without a history of depression were analyzed separately, the link was stronger in those with a prior history of depression (OR, 0.90; 95% CI, 0.82 - 0.98; P = .02) and was not significant in those without such a history (OR, 0.95; 95% CI, 0.89 - 1.02; P = .17).

It is biologically plausible that vitamin D could have a role in depression, Dr. Brown and colleagues note in their article. Vitamin D "appears to be important for brain health and may be involved in the pathogenesis of depression." Yet, studies to date have yielded conflicting results.

Three small clinical studies found an association between low 25(OH)D levels and depression, whereas the 5 population-based studies that have explored the association yielded more mixed results.

Positive studies include 1 involving 1282 older adults from Amsterdam that found 14% lower 25(OH)D levels in those with major and minor depression relative to control participants (Hoogendijk et al, Arch Gen Psych, 2008;65:508-512).

A British national survey of older adults showed clinical vitamin D deficiency [25(OH)D level < 10 ng/mL] was significantly associated with depressive symptoms, independent of age, sex, social class, physical health status, and season. Milder states of vitamin D deficiency were not strongly associated with depression in older adults (Psychosom Med , 2010;72:608-612.)

Largest Data Set to Date

Negative studies include 1 from China involving 3262 adults aged 50 to 70 years. In this study, depressive symptoms were less prevalent in those in the top tertile of 25(OH)D concentrations compared with those in the lowest tertile. The association disappeared, however, after controlling for geographic location (Pan et al, J Affect Disord, 2009;118:608-612).

Additionally, a study in 527 Japanese adults aged 21 to 67 years found no significant association between CES-D scores and 25(OH)D levels (Nanri et al, Eur J Clin Nutr, 2009;63:1444-1447).

A study of 3916 adults in the United States showed that 25(OH)D levels and parathyroid hormone levels were not significantly associated with depressive symptoms after adjusting for several potential confounding factors (Zhao et al, Br J Nutr, 20120;104:1696-1702).

The current study, Dr. Brown told Medscape Medical News, represents the largest data set to investigate this issue and, importantly, unlike prior studies, it included a subanalysis by history of depression.

"This subset analysis may shed light on why there were conflicting results in earlier studies because the populations were not assessed on the basis of prior history of depression," he and his colleagues write.

Nonetheless, he points out that "it's a cross-sectional study, and the old saying is true that correlation does not mean causation." Additional research is needed to determine the nature and direction of the association. "Right now, we don't really know whether low vitamin D makes you depressed or whether being depressed makes you have low vitamin D," Dr. Brown said.

"Studies looking at vitamin D supplementation in depressed people with low vitamin D to see if that in itself would help with depressive symptoms would help answer some of those questions," Dr. Brown commented.

Slow Acting

Vijay K. Ganji, PhD, RD, of the College of Health and Human Sciences, Georgia State University in Atlanta, who was not involved in the study, agrees. "We need more randomized trials to see if taking vitamin D really helps lowering the episodes of depression," he told Medscape Medical News.

To date, there have been only a few small trials of vitamin D supplementation in various depressed populations, with mixed results. In 2008, a placebo-controlled study from Norway found that supplementation with high doses of vitamin D (20,000 or 40,000 IU vitamin D per week) for 1 year seemed to ameliorate depressive symptoms in adults (Jorde et al, J Intern Med, 2008;264:599-609).

In 2009, in a study of 9 women with depressive symptoms and serum vitamin D levels < 40 ng/mL, vitamin D3 supplementation was associated with an increase in serum vitamin D levels (by 27 ng/mL on average) and a decline in depressive symptoms, as measured using the Beck Depression Inventory–II, of an average of 10 points (Shipowick et al, Appl Nurs Res, 2009).

Last year, however, as reported by Medscape Medical News, in a large study of women aged 70 years and older, those who received a high dose of vitamin D3 (500,000 IU) once a year for up to 5 years did not show any improvement in symptoms of depression (Sanders et al, Br J Psychiatry, 2011;198:357-364).

"One thing that complicates trials is that if you give someone vitamin D, it takes a long time for it to have much effect, as vitamin D levels go up and down very slowly; it probably wouldn't be a fast antidepressant," said Dr. Brown.

Dr. Brown reports that he has received research support from the National Heart, Lung, and Blood Institute, the National Institute of Mental Health, the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, the Stanley Medical Research Institute, and AstraZeneca. Dr. Ganji has disclosed no relevant financial relationships.

Mayo Clin Proc. 2011;86:1050-1055. Abstract