After decades of being terrified of the sun (don’t go outside without wearing SPF 99 and a flannel shirt), there seems to be a lot of vitamin D deficiency. Vitamin D3 can be formed when a chemical reaction occurs in human skin, when 7-dehydrocholesterol is broken down by the sun’s UVB light. Correctly applied sunscreen can reduce vitamin D absorption by more than 90%1. Although the media warnings seem to be about sunlight in general, we really just need to avoid sunburn.

Vitamin D Is Actually a Hormone

Vitamin D is considered a hormone because your body makes it from sunlight, processes it through organs, and uses it as a chemical messenger to control genes. Unlike true vitamins (which your body cannot make), your skin builds vitamin D when hit by sunlight. Your liver and kidneys change this raw chemical into an active form called calcitriol. It travels through your blood and binds to special receptors inside cells, just like steroid hormones such as testosterone or cortisol. Instead of acting like a basic nutrient helper, the active form turns hundreds of different genes on and off all over the body. Sunlight does not contain vitamin D. Instead, ultraviolet B (UVB) photons trigger a chemical reaction with cholesterol in your skin to create it.

Vitamin D as a Panacea

To hear some talk, vitamin D seems like a panacea. It has become a very “in” vitamin (even though it really isn’t a vitamin). It is necessary for the immune system to function, it helps keep inflammation in check, and, of course, it is necessary for healthy bones. You can get it in your diet as either D2 or D3. D2 is found in vegetable sources and breaks down faster. D3 is found in eggs and fatty fish. It binds to proteins and is in the circulation longer.

You Need Magnesium and Other Nutrients

Before we get into the virtues of vitamin D, let’s talk about another nutrient, magnesium. According to a recent study, as many as 50% of Americans taking vitamin D supplements may not get significant benefit, as the vitamin D simply gets stored in its inactive form2.

“People are taking Vitamin D supplements but don’t realize how it gets metabolized. Without magnesium, Vitamin D is not really useful or safe,” says study co-author Mohammed S. Razzaque, MBBS, PhD, a professor of pathology at Lake Erie College of Osteopathic Medicine2.

According to the American Osteopathic Association, “Consumption of vitamin D supplements can increase a person’s calcium and phosphate levels even if they remain vitamin D deficient. The problem is people may suffer from vascular calcification if their magnesium levels aren’t high enough to prevent this complication. Patients with optimum magnesium levels require less vitamin D supplementation to achieve sufficient vitamin D levels.2”

You need a balance between vitamins D and K2, calcium, and magnesium; they work together. Lack of balance between these four nutrients is why calcium supplements have become associated with increased risk of heart attack and stroke, and why some experience symptoms of vitamin D toxicity.  Excessive vitamin D in combination with lack of vitamin K2 may cause overabsorption of calcium, which in turn may result in calcium deposits in your heart and kidneys. Part of the explanation for these adverse side effects is that vitamin K2 keeps calcium in its appropriate place — in your teeth and bones and out of soft tissues and arteries. Vascular calcification is also a side effect of low magnesium, so when taking vitamin D3, you need both vitamin K2 and magnesium to make sure everything is working properly2.

Vitamin D, Immunity, and Inflammation

Vitamin D and COVID: Vitamin D is important for the immune system. Defense against uncontrolled inflammation, and against viral infection in general, is provided by T regulatory lymphocytes (Tregs). Vitmin D’s importance came to light during the COVID pandemic. Treg levels had been reported to be low in many COVID-19 patients and especially low in patients with a severe case of the disease.3

Complications related to blood clotting are common in severe cases of COVID. D dimer levels (protein fragment that’s made when a blood clot dissolves in your body) tend to be elevated in these patients. More than 50% of patients with a severe case of COVID have elevated D dimer levels. This is important because vitamin D is involved in the regulation of thrombotic pathways, and vitamin D deficiency is associated with an increase in thrombotic episodes10.

Vitamin D and Viral Infection

In general, high Treg level is associated with a lower incidence of viral respiratory disease4. Tregs can be increased by vitamin D supplementation.5,6 Low vitamin D levels have been associated with an increase in inflammatory cytokines and a significantly increased risk of pneumonia and viral upper respiratory tract infections7,8.

The relationship between inflammatory cytokines and vitamin D has been studied. One study, looking at healthy women between the ages of 25-82, found that serum vitamin D is inversely related to TNF-alpha concentrations in healthy women. The authors felt that this result, in part, may explain vitamin D’s role in the prevention and treatment of inflammatory diseases.9

Autoimmune Disease

Autoimmune diseases are increasing at a rate of about 7% per year. Multiple chemical assaults and disruption of the microbiome are at least partially responsible. These things must be addressed in any protocol. Vitamin D may play an important role in treating these patients.

Because of its role in defensins and in the microbiome, checking vitamin D levels may be important for your patients with autoimmune disease. Defensins are anti-microbial peptides that act as natural antibiotics and are part of the innate immune defense. Vitamin D stimulates the expression of defensins11, which exist in neutrophils, monocytes, natural killer (NK) cells and epithelial cells lining the respiratory tract12.

Vitamin D’s role as an immunoregulator has led to investigations on the effect of Vitamin D supplementation in various autoimmune diseases and its anti-inflammatory effects. There is some evidence that Vitamin D can regulate gastrointestinal inflammation. In addition, previous studies have shown that Vitamin D can affect the gut microbiome. One study evaluated the effect of Vitamin D on inflammatory processes, especially its relation to the inflammatory bowel disease (IBD) and gut microbiome13.

Type 1 diabetes is the result of an autoimmune attack on the beta cells of the pancreas. It is more prevalent in areas with low levels of sunlight14. Vitamin D supplementation has been shown to reduce the incidence of type 1 diabetes15.

Patients with lupus (SLE) tend to be deficient in vitamin D, partially because of photophobia16. The disease is more severe in patients with severe symptoms17,18.

Low levels of vitamin D are associated with other autoimmune diseases. One analysis found a link between vitamin D deficiency and autoimmune thyroid disease19. The authors of one review article stated, “Disorders such as systemic lupus erythematosus, rheumatoid arthritis, Behçet’s, polymyositis/dermatomyositis and systemic scleroderma have all been associated to some extent to vitamin D deficiency.20”

This is, of course, not suggesting that vitamin D be used as a stand-alone treatment for autoimmune disease. You have to look at chemical exposure, gluten, the microbiome, and other factors. Low vitamin D levels may be a contributing factor. Also, when giving vitamin D, make sure that the patient has adequate magnesium, K2, A, and E. K2 comes from a healthy GI tract, but can be supplemented. Magnesium deficiency is so prevalent that giving some magnesium (on an empty stomach, the last thing at night) is a good strategy when supplementing with vitamin D.

Bottom Line

Vitamin D is not a miracle nutrient, but it is much more than a “bone vitamin.” It plays important roles in immunity, inflammation, and many other aspects of normal physiology. If you are at risk for deficiency or have chronic health problems, ask your healthcare provider whether checking your vitamin D level makes sense. And remember, vitamin D doesn’t work alone. Magnesium, vitamin K2, and an overall healthy lifestyle are all part of the picture.

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Selected References:

  1. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004; 79:362-71
  2. Journal of the American Osteopathic Association March 2018; 118: 181-189
  3. J Clin Invest. 2020 May 1; 130(5):2620-2629. Clinical and immunological features of severe and moderate coronavirus disease 2019.
  4. Immune biomarkers predictive of respiratory viral infection in elderly nursing home residents. PLoS One. 2014; 9(9):e108481.
  5. The role of vitamin D in increasing circulating T regulatory cell numbers and modulating T regulatory cell phenotypes in patients with inflammatory disease or in healthy volunteers: A systematic review. PLoS One. 2019; 14(9):e0222313.
  6. High-dose cholecalciferol supplementation significantly increases peripheral CD4+ Tregs in healthy adults without negatively affecting the frequency of other immune cells. Eur J Nutrition 2014;53:751–9.
  7. Link between community-acquired pneumonia and vitamin D levels in older patients. Z Gerontol Geriatr. 2018 Jun; 51(4):435-439.
  8. Low serum 25-hydroxyvitamin D level and risk of upper respiratory tract infection in children and adolescents. Clin Infect Dis. 2013 Aug; 57(3):392-7.
  9. Serum tumor necrosis factor-alpha concentrations are negatively correlated with serum 25(OH)D concentrations in healthy women. J Inflamm (Lond). 2008 Jul 24; 5():10.
  10. Emerging Role of Vitamin D and its Associated Molecules in Pathways Related to Pathogenesis of Thrombosis. Biomolecules. 2019 Oct 24; 9(11)
  11. Bartley J. Vitamin D: emerging roles in infection and immunity. Expert Rev Anti Infect Ther. 2010;8:1359–1369.
  12. Ginde AA, Mansbach JM, Camargo CA., Jr Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009;169:384–390.
  13. Tabatabaeizadeh SA, Tafazoli N, Ferns GA, Avan A, Ghayour-Mobarhan M.J Res Med Sci. 2018 Aug 23;23:75 Vitamin D, the gut microbiome and inflammatory bowel disease.
  14. Staples JA, Ponsonby AL, Lim LL, McMichael AJ. Ecologic analysis of some immune-related disorders, including type 1 diabetes, in Australia: latitude, regional ultraviolet radiation, and disease prevalence. Environ Health Perspect. 2003;111:518–523.
  15. Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001;358:1500–1503.
  16. Lehmann P, Homey B. Clinic and pathophysiology of photosensitivity in lupus erythematosus. Autoimmun Rev. 2009;8:456–461
  17. Borba VZ, Vieira JG, Kasamatsu T, Radominski SC, Sato EI, Lazaretti-Castro M. Vitamin D deficiency in patients with active systemic lupus erythematosus. Osteoporos Int. 2009;20:427–433
  18. Amital H, Szekanecz Z, Szucs G, et al. Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D? Ann Rheum Dis. 2010;69:1155–1157
  19. Nutrients 2015 Apr 3;7(4):2485-98 Immunomodulatory Function of Vitamin D and Its Role in Autoimmune Thyroid Disease
  20. Autoimmun Rev. 2010 May;9(7):507-10. Vitamin D and autoimmune disease