James Greenblatt, M.D.
Vitamin D was thought to be of use only in preventing rickets and osteomalacia. Accumulating evidence, however, has demonstrated that vitamin D does much more, influencing the health and function of tissues and organs throughout the body. Vitamin D is an important nutrient for our physical health, but many people are unaware of how critical this vitamin is for maintaining our mental health. In this article, we will explore the evidence-based research on vitamin D and depression. The next article will explore the effects of vitamin D on psychosis and schizophrenia.
Vitamin D is categorized as a hormone because of its paracrine, autocrine, and endocrine functions, and it can be acquired through food or exposure to the sun. Vitamin D can be found in high amounts in fatty fish and also in milk, yogurt, orange juice and cereals, and dietary supplements. A sufficient amount of vitamin D can also be produced from 5-15 minutes of daily exposure to sunlight.
Vitamin D2, or ergocalciferol, is only made by plants and vitamin D3, or cholecalciferol, is created when ultraviolet light hitting the skin photochemically converts cholesterol to vitamin D. Serum 25-hydroxyvitamin D [25(OH)D] is a biological marker used to reliably measure the levels of both forms of vitamin D. Among its many functions, vitamin D is important for absorbing calcium, maintaining calcium homeostasis in tissues, growth of bones and teeth, properly functioning neurons and glial cells, preventing rickets and osteomalacia, influencing tissues and organs, preventing psoriasis, muscle pain, weakness, elevated blood pressure, some forms of cancer, and autoimmune disease, and preserving mental health.
Recent studies have advanced our understanding of vitamin D and its effect on the brain. There are vitamin D receptors in neurons and glial cells in the brain. Specifically, research suggests vitamin D may act on particular regions of the brain important in the development of depression, including the prefrontal cortex, hippocampus, cingulate gyrus, thalamus, hypothalamus, and substantia nigra. Moreover, it has also been discovered that genetic variations of vitamin D receptors are associated with depression. Recent research shows vitamin D controls the transcription of over one thousand genes involved in neurotrophic and neuroprotective effects, including the maintenance and development of neurons. In addition, vitamin D may also stimulate the release of neurotrophins, a family of proteins that function to protect and stimulate the growth of neurons.
In a recent study, Polak et al. investigated the association between vitamin D levels and depressive symptoms in 615 young adults. Subjects in the lowest quartile of vitamin D levels were more likely to report having symptoms of depression than those in the highest quartile, suggesting that vitamin D deficiency is a potential predictor of depression. Similarly, in a study on previously deployed military personnel who committed suicide, Umhau et al. found that subjects in the lowest octile of vitamin D levels had the highest risk of suicide. Milaneschi et al. found a comparable effect in the elderly population, with low levels of vitamin D correlating with a significantly higher risk of developing depression. In another study with adolescent participants, Toppanen et al. measured vitamin D levels and depressive symptoms in the same group of children at 9.8, 10.6, and 13.8 years old. Interestingly, higher levels of vitamin D at age 9.8 predicted lower levels of depression at age 13.8, suggesting an association between low levels of vitamin D and early onset depression.
Bertone-Johnson et al., performed a cross-sectional study on 81,189 older women and found an inverse association between vitamin D levels and depressive symptoms in the postmenopausal women. In another study, Lee et al. found that lower vitamin D levels were associated with depression in a population of 3,369 European men. A study by Black et al. came to the same results in a population of young adult males.
Vitamin D supplements have also been found to enhance positive moods. In a study by Allen et al., healthy subjects were given 800 IU, 400 IU, or no vitamin D during five days of winter. The results of their study showed that vitamin D was able to significantly enhance positive affect and also reduce negative affect. Taken together, these diverse studies suggest an indisputable connection between vitamin D deficiency and depression across all age groups and genders.
Biochemical individuality plays a substantial role in vitamin D status. Although environmental factors, such as nutrition and sun exposure, are considered the major determinants of vitamin D status, genetics are responsible for a large portion of the variation seen in serum 25-hydroxyvitamin D. A Swedish study involving 204 same-sex twins between the ages of thirty-nine and eighty-five years living at northern latitude 60 degrees found that genetic factors were responsible for one-fourth of the variation in serum 25-hydroxyvitamin D, independent of season. During the summer season alone, genetics was responsible for half of the variability in 25-hydroxyvitamin D.
Vitamin D levels between 20 and 30 ng/mL have been traditionally accepted as normal and healthy. We now know that this range is too low, and even people who were thought to be safely in the middle of range may need vitamin D supplementation. Given the quirks of biochemical individuality, some people in the upper reaches may need even more. I prefer to see a 25-hydroxyvitamin D between 40 and 60 ng/mL in my patients. The best way to determine vitamin D deficiency is through serum blood testing which should also be done twice a year.
Research literature supports a link between vitamin D and depression; however, the exact mechanisms are unclear. The research has not yet established whether low levels of vitamin D cause depression, or whether depression causes low levels of vitamin D. New research is continually emerging on the importance of vitamin D in sustaining mental health. In one 2012 study, adolescents in a mental health facility who were vitamin D deficient were 3½ times more likely to have psychotic features when compared to those with sufficient vitamin D levels. We'll explore the exciting research implicating vitamin D's role in other mental illnesses such as psychosis and schizophrenia in the next newsletter.
- Anglin R, Samaan Z, Walter S et al. Vitamin D deficiency and depression in adults: systematic review and meta analysis. British Journal of Psychiatry, 2013.
- Bertone-Johnson ER, Powers SI, Spangler L et al. Vitamin D Supplementation and Depression in the Women's Health Initiative Calcium and Vitamin D Trial. Am J Epidemiol 2012; 176(1):1-13.
- Bertone-Johnson ER, Powers SI, Spangler L, et al. Vitamin D intake from foods and supplements and depressive symptoms in a diverse population of older women. Am J Clin Nutr. 2011 Oct;94(4):1104-12.
- Bertone-Johnson ER. Vitamin D and the occurrence of depression: causal association or circumstantial evidence? Nutr Rev. 2009 Aug;67(8):481-92.
- Black LJ, Jacoby P, Allen KL, et al. Low vitamin D levels are associated with symptoms of depression in young adult males. Aust N Z J Psychiatry 2014 May;48(5):464-71.
- Dean A J, Bellgrove M A, Hall T et al. Effects of vitamin D supplementation on cognitive and emotional functioning in young adults–a randomised controlled trial. PLoS One. 2011;6(11):e25966
- Gracious, BL, Finucane, TL, Friedman-Campbell, M. et al. Vitamin D deficiency and psychotic features in mentally ill adolescents: A cross-sectional study. BMC Psychiatr. 2012; 12: 38.
- Han B, Lyu Y, Sun Y et al. Low serum levels of vitamin D are associated with post-stroke depression. European Journal of Neurology Dec 2014. [E-pub ahead of print].
- Jorde, M. Sneve, Y. Figenschau, J et al. 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.
- Lansdowne AT & Provost SC. Vitamin D3 enhances mood in healthy subjects during winter. Psychopharmacology (Berl) 1998 Feb;135(4):319-23
- Lee DM, Tajar A, O'Neill TW, et al. Lower vitamin D levels are associated with depression among community-dwelling European men. J Psychopharmacol 2011 Oct;25(10):1320-8.
- Polak MA, Houghton LA, Reeder AI, et al. Serum 25-hydroxyvitamin D concentrations and depressive symptoms among young adult men and women. Nutrients 2014 Oct 28;6(11):4720-30.
- Toffanello ED, Sergi G, Veronese N, et al. Serum 25-hydroxyvitamin d and the onset of late-life depressive mood in older men and women: the Pro.V.A. study. J Gerontol A Biol Sci Med Sci 2014 Dec;69(12):1554-61.
- Tolppanen AM, Sayers A, Fraser WD, et al. The association of serum 25-hydroxyvitamin D3 and D2 with depressive symptoms in childhood--a prospective cohort study. J Child Psychol Psychiatry 2012 Jul;53(7):757-66.
- Umhau JC, George DT, Heaney RP, et al. Low Vitamin D Status and Suicide: A Case-Control Study of Active Duty Military Service Members. PLoS One 2013;8(1):e51543.
- Yue W, Xiang L, Zhang YJ, et al. Association of serum 25-hydroxyvitamin D with symptoms of depression after 6 months in stroke patients. Neurochem Res. 2014 Nov;39(11):2218-24.