Role of Vitamin D in Depression

Question:

“Please comment further on the roles of vitamin D and its role in depression.”

Jon W. Draud, MD, MS:
This is an excellent question and in my practice checking vitamin D levels has become a standard practice. It has amazed me over the past couple of years how common this deficiency is and how correcting it can lead to mood improvements. That being said, what do we know about vitamin D and depression?

Nearly 20 years ago, Professor Walter E. Stumpf from the University of North Carolina predicted a major role for bright light therapy and vitamin D in psychiatry. ¹  We now know that bright light (without vitamin D producing UVB [ultraviolet B]) does have positive effects on mood. The question remains whether vitamin D has a separate or complementary effect on mood as do the effects of bright light alone.

This gets to the concept of seasonal affective disorder (SAD). There is evidence dating to 1998 when researchers in Australia found that cholecalciferol at both 400 IU and 800 IU significantly improved affect when given to healthy individuals. ²  Forty-four participants were given drug versus placebo in the late winter for five days in a randomized double-blinded study. Results on a self-reported measure showed a full standard delineation of improvement in enhancement of positive affect. In 1999, Gloth and colleagues ³  found that 100,000 IU of vitamin D as a single dose was superior in improvement of depression scale measures compared to bright light therapy in patients with SAD. Other researchers have found healthy controls’ average serum 25-hydroxyvitamin D levels of 46 ng/L versus depressed participants with levels averaging 37 ng/L. ⁴

Many have theorized that the rates of depression have increased over the past 100 years and ongoing in part to vitamin D deficiency. Humans have decreased their sunlight exposure due to tall buildings, pollution, cars, clothing, and mostly indoor work habits. Low vitamin D status is a widespread problem in the United States. ⁵  Additionally, research by Wagner and Greer have indicated that vitamin D levels previously thought to be sufficient for good health are actually too low. ⁶

There are numerous roles for vitamin D in disease states including cognition, depression, osteoporosis, cancer, cardiovascular disease, and diabetes. Vitamin D receptors are found prominently in amygdala regions where behavior and emotions are regulated in the limbic system, and we believe that vitamin D can exert neuroprotective effects as well. Recently, Wilkins and colleagues ⁷  showed a link between low vitamin D levels, depression, and impaired cognition in older adults. Several other authors have shown a link between vitamin D levels and depression. ^8-10  Martiny et al.  ¹¹  found that light therapy can improve depression along with antidepressants, which may, in part, be due to improved vitamin D synthesis with light therapy.

Results from various studies attempting to link vitamin D deficiency to depression have been equivocal, but recently 7,970 U.S. residents were studied in the Third National Health and Nutrition Examination Survey (NHANES III). ¹²  The participants were between the ages of 15 and 39, and we will discuss the study and results to help shed light on this issue. There was a significant association between depression and low vitamin D levels (odds ratio=1.85; P =0.021) when statistical analysis was corrected for sex, age, gender, race, poverty/income ratio, vitamin/mineral supplements, and medication use. The prevalence of suboptimal serum vitamin D concentration (≤75 nmol/L) was 50%; 20% were vitamin D deficient at <50 nmol/L and 30% were moderately deficient falling into the serum range of 50 to 75 nmol/L. Higher prevalence of vitamin D deficiency was found in women, non-Hispanic blacks, individuals with higher body mass index, individuals with lower income levels, and those living in the South and West regions and urban areas. This was surprising in terms of more deficiencies occurring in people in Southern regions, but this may have been due to the fact that NHANES III was conducted in the summer months so maybe Northern participants would have been more disadvantaged if the study had been in the fall or winter.

In contrast, a recent study by Zhao et al. ¹³  found no significant association between vitamin D levels and depression.

We are still left with conflicting results, but I believe clinicians do not doubt this association and the strength of NHANES III is primarily study size—the largest cohort ever studied.

—Jon W. Draud, MD, MS

References

1. Stumpf WE, Privette TH.  Light, vitamin D and psychiatry. Role of 1,25 dihydroxyvitamin D3 (soltriol) in etiology and therapy of seasonal affective disorder and other mental processes.  Psychopharmacology  (Berl). 1989;97(3):285-294.
2. Lansdowne AT, Provost SC.  Vitamin D3 enhances mood in healthy subjects during winter.  Psychopharmacology  (Berl). 1998;135(4):319-323.
3. Gloth FM 3rd, Alam W, Hollis B.  Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder.  J Nutr Health Aging.  1999;3(1):5-7.
4. Schneider B, Weber B, Frensch A, Stein J, Fritz J.  Vitamin D in schizophrenia, major depression and alcoholism.  J Neural Transm.  2000;107(7):839-842.
5. Holick MF.  High prevalence of vitamin D inadequacy and implications for health.  Mayo Clin Proc.  2006;81(3):353-373.
6. Wagner CL, Greer FR ; American Academy of Pediatrics Section on Breastfeeding; American Academy of Pediatrics Committee on Nutrition. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents.  Pediatrics.  2008;122(5):1142-1152.
7. Wilkins CH, Sheline YI, Roe CM, Birge SJ, Morris JC.  Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults.  Am J Geriatr Psychiatry.  2006;14(12):1032-1040.
8. Jorde R, Waterloo K, Saleh F, Haug E, Svartberg J.  Neuropsychological function in relation to serum parathyroid hormone and serum 25-hydroxyvitamin D levels. The Tromso study.  J Neurol.  2006;253(4):464-470.
9. Jorde R, Sneve M, Figenschau Y, Svartberg J, Waterloo K.  Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial.  J Intern Med.  2008;264(6):599-609.
10. Hoogendijk WJ, Lips P, Dik MG, et al.  Depression is associated with decreased 25-hydroxyvitamin D and increased parathyroid hormone levels in older adults.  Arch Gen Psychiatry.  2008;65(5):508-512.
11. Martiny K, Lunde M, Unden M, Dam H, Bech P.  Adjunctive bright light in non-seasonal major depression: results from clinician-rated depression scales.  Acta Psychiatr Scand.  2005;112(2):117-125.
12. Ganji V, Milone C, Cody MM, McCarty F, Wang YT.  Serum vitamin D concentrations are related to depression in young adult US population: the Third National Health and Nutrition Examination Survey.  Int Arch Med.  2010;3:29.
13. Zhao G, Ford ES, Li C, Balluz LS.  No associations between serum concentrations of 25-hydroxyvitamin D and parathyroid hormone and depression among US adults.  Br J Nutr.  2010;104(11):1696-1702.