The role of vitamin D in autoimmunity and mood
Vitamin D is known as the “sunshine vitamin” because it is generated within the skin upon exposure to ultraviolet B (UVB) rays, the rays responsible for suntans. Vitamin D is essential for strong bones, immunity, and many other bodily functions.,, In the absence of sun exposure, however, it is necessary to obtain vitamin D solely from the diet and supplementation.
Many variables affect sun exposure and therefore influence vitamin D levels in the body: the latitude at which one resides, the season (winter vs. summer), time of day, cloud cover, air pollution (which filters out UVB), skin melanin content (which absorbs UVB), age, and sunscreen use (which blocks UVB).,,, Public health organizations recommend the use of sunscreen, because prolonged sun exposure damages the skin and increases the risk for skin cancer. Unfortunately, the use of sunscreen also inhibits vitamin D synthesis.
Diet is considered a relatively unreliable source of vitamin D because vitamin D is found naturally in only a few foods, namely dairy products, eggs, fish, and cod liver oil. Some foods (milk, various brands of cereal, yogurt, and orange juice) are fortified with vitamin D, but the levels are not enough to prevent deficiency.,,,,
Insufficient vitamin D causes a decrease in bone mineral density as we age, which increases the risk of osteoporosis, falling, and bone fractures in the elderly. Vitamin D insufficiency is also associated with diabetes, heart disease, respiratory infections, and some cancers.,,, Compelling evidence suggests that vitamin D insufficiency also plays a role in mood disturbances and autoimmune diseases, as discussed below.
How does vitamin D influence mood?
Vitamin D’s reputation as the sunshine vitamin is well deserved for another reason: vitamin D influences mood.,,, The well-known phenomenon of seasonal depression may be due in part to lower vitamin D levels in winter, especially in Northern climates.,
“Effective detection and treatment of inadequate vitamin D levels in persons with depression and other mental disorders may be an easy and cost-effective therapy which could improve patients’ long-term health outcomes as well as their quality of life.”
In placebo-controlled clinical trials, supplementation with vitamin D significantly improved mood in various groups: overweight and obese individuals, women with type 2 diabetes, older adults, individuals with osteoarthritis, and adolescents experiencing depression. Scientists studying the connection between vitamin D and mood discovered that the vitamin helps regulate dopamine transport in the so-called “reward center” of the brain, a region closely linked to our ability to feel pleasure.
One research group states: “Effective detection and treatment of inadequate vitamin D levels in persons with depression and other mental disorders may be an easy and cost-effective therapy which could improve patients’ long-term health outcomes as well as their quality of life.”
How does vitamin D influence autoimmunity?
More than 100 human diseases are classified as autoimmune conditions, in which the immune system attacks the body’s own healthy cells and tissues. Autoimmune diseases are caused by genetic, environmental, and hormonal factors, and vitamin D is thought to be the environmental factor that most strongly influences autoimmune disease development.,, Supplementation to correct low vitamin D levels may significantly benefit individuals with autoimmune conditions. For example:
Multiple Sclerosis. In multiple sclerosis (MS), the immune system attacks the protective myelin sheath that coats nerve fibers, causing inflammation that disrupts communication between the brain and the rest of the body. Low levels of vitamin D are associated with disease progression and disability.,
“Given the prominent reduction in the quarterly relapse rate in late winter/early spring, our data indicate a beneficial effect of supplementing MS patients with vitamin D.”
One key study showed that supplementation with vitamin D (18,950 IU per week, equivalent to about 2700 IU per day) eliminated seasonal variation in vitamin D levels, and cut the relapse rate in half. The authors wrote, “Given the prominent reduction in the quarterly relapse rate in late winter/early spring, our data indicate a beneficial effect of supplementing MS patients with vitamin D, especially during this period of the year.”
Rheumatoid Arthritis. Up to 80% of all patients with rheumatoid arthritis (RA) have insufficient vitamin D levels,,, and a meta-analysis of studies involving 215,757 participants suggests that low vitamin D intake is associated with an elevated risk of RA development. Furthermore, individuals with the highest total vitamin D intakes had a less severe disease course than those with lower intakes.,,, The authors of a 2018 study conclude: “Vitamin D deficiency is associated with the clinical activity of the disease. The quantification of serum 25 (OH) D levels and, consequently, vitamin D supplementation, should be considered in the management of patients with RA.”
“The quantification of serum 25 (OH) D levels and, consequently, vitamin D supplementation, should be considered in the management of patients with RA.”
Diabetes.The incidence of diabetes mellitus (type 1 diabetes, or T1D) peaks in the winter and spring, coinciding with low seasonal levels of vitamin D. In Finland, which has one of the highest rates of T1D in the world, supplementation with vitamin D during the first year of life is associated with a lower risk of T1D., The benefits of vitamin D are most apparent if supplementation is initiated in the earliest phases of the disease, rather than at later stages.,
“Advising patients with higher HbA1c to test their vitamin D level and correct any deficiency will result in better blood glucose control and benefit the patient’s overall health.”
Type 2 diabetes (T2D) is characterized by insulin resistance and an inadequate compensatory insulin secretion. Vitamin D supplementation was shown to reduce blood levels of hemoglobin A1c (HbA1c), a marker of diabetes, in vitamin D-deficient patients with T2D and/or prediabetes.,,, The authors of a recent meta-analysis of controlled clinical trials, representing more than 3,800 participants, concluded: “Advising patients with higher HbA1c to test their vitamin D level and correct any deficiency will result in better blood glucose control and benefit the patient’s overall health.”
New research also suggests that supplementation with vitamin D prior to pregnancy may help lower the risk of gestational diabetes mellitus (GDM) in pregnant women. The authors concluded, “Pre-pregnancy supplemental vitamin D intake was significantly and inversely associated with risk of GDM. This study indicates potential benefits of increasing vitamin D intake from supplements in the prevention of GDM in women of reproductive age.”
How much vitamin D do we need?
The only way to assure you are getting enough vitamin D is to have your blood tested for the 25-hydroxy form of the vitamin, or 25(OH)D. One frequently asked question is, “What 25(OH)D level should I have?” There is considerable controversy on the subject, briefly summarized here:
- The Institute of Medicine (IOM) guidelines, used by many laboratories for analyzing test results, classify blood 25(OH)D levels as follows: < 30 nmol/L as “deficient”; 30–50 nmol/L as “insufficient”; and 50–75 nmol/L as “sufficient.”
- However, many experts believe the IOM recommendations for 25(OH)D are too low. They argue that the level indicating sufficiency should be 75 nmol/L (30 ng/mL) or higher.,,,,,,
- The average 25(OH)D concentration in the Maasai people, who live a pastoral lifestyle in East Africa, is about 115 nmol/L (46 ng/mL). This may be the “natural” 25(OH)D level experienced by our Paleolithic ancestors, who lived near the equator and wore minimal clothing.
Individuals with limited sun exposure will likely need to take a vitamin D supplement to meet their needs. The recommended dietary allowance (RDA) is 600 IU of vitamin D per day for adults up to age 70, and 800 IU daily thereafter. However, 800 IU per day is not sufficient to correct pre-existing vitamin D deficiencies.,,
To reach a 25(OH)D blood level of at least 75 nmol/L (30 ng/mL) – the level advised by many experts, as discussed above – requires at least 1,000–2,000 IU per day of supplemental vitamin D, or even more in some individuals.,,,,,, Supplemental vitamin D doses up to 4,000 IU per day are considered safe for adults.
The form of vitamin D is also important: the studies cited herein mainly utilized vitamin D3 (cholecalciferol), which is superior to vitamin D2 (ergocalciferol). Cholecalciferol raises blood levels more effectively and is more active biologically than ergocalciferol.
In sum, supplementation to correct vitamin D deficiency can help reduce age-related bone loss, prevent seasonal mood fluctuations, and support better health in individuals with autoimmune conditions. So for optimal health, consider having your blood tested for vitamin D, and grab a little sunshine – whether from the sun or from a bottle!
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 Wacker M, Holick MF. Sunlight and vitamin D: a global perspective for health. Dermatoendocrinol. 2013 Jan 1;5(1):51-108.
 Nair R, Maseeh A. Vitamin D: the “sunshine” vitamin. J Pharmacol Pharmacother. 2012 Apr;3(2):118-26.
 Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266-81.
 Baggerly CA, et al. Sunlight and vitamin D: necessary for public health. J Am Coll Nutr. 2015;34(4):359-65.
 de Jongh RT, et al. Changes in vitamin D endocrinology during aging in adults. Mol Cell Endocrinol. 2017 Sep 15;453:144-50.
 Grant WB, et al. Seasonal variations of U.S. mortality rates: roles of solar ultraviolet-B doses, vitamin D, gene expression, and infections. J Steroid Biochem Mol Biol. 2017 Oct;173:5-12.
 Webb AR, et al. Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab. 1988 Aug;67(2):373-8.
 Pilz S, et al. Rationale and plan for vitamin D food fortification: a review and guidance paper. Front Endocrinol (Lausanne). 2018 Jul 17;9:373.
 Bischoff-Ferrari H, Willett W. Comment on the IOM vitamin D and calcium recommendations [Internet]. Boston (MA): Harvard School of Public Health; 2010 [cited 2018 Nov 13]. Available from: https://www.hsph.harvard.edu/nutritionsource/2010/12/25/comment-on-the-iom-vitamin-d-and-calcium-recommendations/
 Ginde AA, et al. Vitamin D insufficiency in pregnant and nonpregnant women of childbearing age in the United States. Am J Obstet Gynecol. 2010 May;202(5):436.
 Holick MF. The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord. 2017 Jun;18(2):153-65.
 Gebreegziabher T, Stoecker BJ. Vitamin D insufficiency in a sunshine-sufficient area: southern Ethiopia. Food Nutr Bull. 2013 Dec;34(4):429-33.
 Ensrud KE, et al. Circulating 25-hydroxyvitamin D levels and frailty status in older women. J Clin Endocrinol Metab. 2010 Dec;95(12):5266-73.
 Zitterman A, et al. Vitamin D and airway infections: a European perspective. Eur J Med Res. 2016 Mar 24;21:14.
 Mirhosseini N, et al. Vitamin D supplementation, serum 25(OH)D concentrations and cardiovascular disease risk factors: a systematic review and meta-analysis. Front Cardiovasc Med. 2018 Jul 12;5:87.
 Umar M, et al. Role of vitamin D beyond the skeletal function: a review of the molecular and clinical studies. Int J Mol Sci. 2018 May 30;19(6).
 Sarkar S. Vitamin D for depression with a seasonal pattern: an effective treatment strategy. Int Phys Med Rehab J. 2017;1(4):91‒9.
 Jorde R, et al. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. J Intern Med. 2008 Dec;264(6):599-609.
 Aghajafari F, et al. Vitamin D Deficiency and antenatal and postpartum depression: a systematic review. Nutrients. 2018 Apr 12;10(4).
 Spedding S. Vitamin D and depression: a systematic review and meta-analysis comparing studies with and without biological flaws. Nutrients. 2014 Apr 11;6(4):1501-18.
 Imai CM, et al. Depression and serum 25-hydroxyvitamin D in older adults living at northern latitudes – AGES-Reykjavik Study. J Nutr Sci. 2015 Nov 20;4:e37.
 Kurata Y, et al. Seasonality in mood and behaviors of Japanese residents in high-latitude regions: transnational cross-sectional study. Biopsychosoc Med. 2016 Dec 5;10:33.
 Penckofer S, et al. Vitamin D and depression: where is all the sunshine? Issues Ment Health Nurs. 2010 Jun;31(6):385-93.
 Alavi NM, et al. Effect of vitamin D supplementation on depression in elderly patients: A randomized clinical trial. Clin Nutr. 2018 Sep 19.
 Zheng S, et al. Effect of vitamin D supplementation on depressive symptoms in patients with knee osteoarthritis. J Am Med Dir Assoc. 2018 Nov 3.
 Högberg G, et al. Depressed adolescents in a case-series were low in vitamin D and depression was ameliorated by vitamin D supplementation. Acta Paediatr. 2012 Jul;101(7):779-83.
 Sedaghat A, et al. Mesolimbic dopamine system and its modulation by vitamin D in a chronic mild stress model of depression in the rat. Behav Brain Res. 2019 Jan 1;356:156-69.
 Blumberg RS, et al. Unraveling the autoimmune translational research process layer by layer. Nat Med. 2012 Jan 6; 18(1):35-41.
 Hayes CE, et al. Vitamin D actions on CD4(+) T cells in autoimmune disease. Front Immunol. 2015 Mar 18;6:100.
 Vanherwegen AS, et al. Regulation of immune function by vitamin D and its use in diseases of immunity. Endocrinol Metab Clin North Am. 2017 Dec;46(4):1061-94.
 Dankers W, et al. Vitamin D in autoimmunity: molecular mechanisms and therapeutic potential. Front Immunol. 2017 Jan 20;7:697.
 Mowry EM, et al. Vitamin D status predicts new brain magnetic resonance imaging activity in multiple sclerosis. Ann Neurol. 2012 Aug;72(2):234-40.
 Fitzgerald KC, et al. Association of vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon beta-1b. JAMA Neurol. 2015 Dec;72(12):1458-65.
 Miclea A, et al. Vitamin D supplementation differentially affects seasonal multiple sclerosis disease activity. Brain Behav. 2017 Jul 11;7(8):e00761.
 Raczkiewicz A, et al. Vitamin D status and its association with quality of life, physical activity, and disease activity in rheumatoid arthritis patients. J Clin Rheumatol. 2015 Apr;21(3):126-30.
 Hajjaj-Hassouni N, et al. Evaluation of vitamin D status in rheumatoid arthritis and its association with disease activity across 15 countries: “The COMORA Study.” Int J Rheumatol. 2017;2017:5491676.
 Meena N, et al. Assessment of vitamin D in rheumatoid arthritis and its correlation with disease activity. J Nat Sci Biol Med. 2018 Jan-Jun;9(1):54-8.
 Song GG, et al. Association between vitamin D intake and the risk of rheumatoid arthritis: a meta-analysis. Clin Rheumatol. 2012 Dec;31(12):1733-9.
 Di Franco M, et al. Hypovitaminosis D in recent onset rheumatoid arthritis is predictive of reduced response to treatment and increased disease activity: a 12 month follow-up study. BMC Musculoskelet Disord. 2015 Mar 15;16:53.
 Quintana-Duque MA, et al. The role of 25-hydroxyvitamin D as a predictor of clinical and radiological outcomes in early onset rheumatoid arthritis. J Clin Rheumatol. 2017 Jan;23(1):33-9.
 Garcia de Veas Silva JL, et al. A-385 – Vitamin D and disease activity in patients with rheumatoid arthritis. American Association for Clinical Chemistry: 31 Jul 2018 [cited 13 Nov 2018]. Available from: http://www.abstractsonline.com/pp8/#!/4647/presentation/429
 Chakhtoura M, Azar ST. The role of vitamin D deficiency in the incidence, progression, and complications of type 1 diabetes mellitus. Int J Endocrinol. 2013;2013:148673.
 Hyppönen E, et al. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001 Nov 3;358(9292):1500-3.
 Li X, et al. Protective effects of 1-alpha-hydroxyvitamin D3 on residual beta-cell function in patients with adult-onset latent autoimmune diabetes (LADA). Diabetes Metab Res Rev. 2009 Jul;25(5):411-6.
 Mirhosseini N, et al. Vitamin D supplementation, glycemic control, and insulin resistance in prediabetics: a meta-analysis. J Endocr Soc. 2018 May 25;2(7):687-709.
 Wu C, et al. Vitamin D supplementation and glycemic control in type 2 diabetes patients: a systematic review and meta-analysis. Metabolism. 2017 Aug;73:67-76.
 Buhary BM, et al. Association of glycosylated hemoglobin levels with vitamin d status. J Clin Med Res. 2017 Dec;9(12):1013-8.
 Dutta D, et al. Vitamin-D supplementation in prediabetes reduced progression to type 2 diabetes and was associated with decreased insulin resistance and systemic inflammation: an open label randomized prospective study from Eastern India. Diabetes Res Clin Pract. 2014 Mar;103(3):e18-23.
 Bao W, et al. Prepregnancy habitual intake of vitamin D from diet and supplements in relation to risk of gestational diabetes mellitus: a prospective cohort study. J Diabetes. 2018 May;10(5):373-9.
 Del Valle HB, Yaktine AL, Taylor CL, Ross AC, editors. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011.
 Heaney RP. Vitamin D: criteria for safety and efficacy. Nutr Rev. 2008 Oct;66(10 Suppl 2):S178-81.
 Wagner CL, Hollis BW. The implications of vitamin D. Front Endocrinol (Lausanne). 2018 Aug 31;9:500.
 Carlsson M, et al. Older Swedish adults with high self-perceived health show optimal 25-hydroxyvitamin D levels whereas vitamin D status is low in patients with high disease burden. Nutrients. 2016 Nov 11;8(11).
 American Geriatrics Society Workgroup on Vitamin D Supplementation for Older Adults. Recommendations abstracted from the American Geriatrics Society consensus statement on vitamin D for prevention of falls and their consequences. J Am Geriatr Soc. 2014 Jan;62(1):147-52.
 Grant WB. An estimate of the global reduction in mortality rates through doubling vitamin D levels. Eur J Clin Nutr. 2011 Sep;65(9):1016-26.
 Luxwolda MF, et al. Vitamin D status indicators in indigenous populations in East Africa. Eur J Nutr. 2013 Apr;52(3):1115-25.
 National Institutes of Health, Office of Dietary Supplements. Vitamin D Fact Sheet for Health Professionals [Internet]. Bethesda (MD): US Department of Health and Human Services; 2018 [cited 2018 Jul 13]. Available from: https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
 Talwar SA, et al. Dose response to vitamin D supplementation among postmenopausal African American women. Am J Clin Nutr. 2007 Dec;86(6):1657-62.
 Vieth R, et al. The urgent need to recommend an intake of vitamin D that is effective. Am J Clin Nutr. 2007 Mar;85(3):649-50.
 Balvers MG, et al. Recommended intakes of vitamin D to optimize health, associated circulating 25-hydroxyvitamin D concentrations, and dosing regimens to treat deficiency: workshop report and overview of current literature. J Nutr Sci. 2015 May 25;4:e23.
 Holick MF, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30.
 Chao YS, et al. The importance of dose, frequency and duration of vitamin D supplementation for plasma 25-hydroxyvitamin D. Nutrients. 2013 Oct 11;5(10):4067-78.
 Sadat-Ali M, et al. Maintenance dose of vitamin D: how much is enough? J Bone Metab. 2018 Aug;25(3):161-4.
 Lukaszuk JM, et al. 25(OH)D status: effect of D3 supplement. Obes Sci Pract. 2017 Mar;3(1):99-105.
 Moss BP, et al. Wellness and the role of comorbidities in multiple sclerosis. Neurotherapeutics. 2017 Oct;14(4):999-1017.
 Veugelers PJ, Ekwaru JP. A statistical error in the estimation of the recommended dietary allowance for vitamin D. Nutrients. 2014 Oct 20;6(10):4472-5.
 Heaney R, et al. Letter to Veugelers, P.J. and Ekwaru, J.P., A statistical error in the estimation of the recommended dietary allowance for vitamin D. Nutrients. 2015 Mar 10;7(3):1688-90.
 Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. 2006;84:694–7.