Pairing the vital vitamin to obtain the greatest bioavailability in patients
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
To hear some talk, vitamin D seems like a panacea. 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 any significant benefit, as the vitamin D simply gets stored in its inactive form.2
“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, professor of pathology at Lake Erie College of Osteopathic Medicine.2
Vitamin D and bioavailability
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 over-absorption 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 properly.2
Immunity and inflammation
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). Treg levels have been reported to be low in many COVID-19 patients and especially low in patients with a severe case of the disease.3 In general, high Treg level is associated with a lower incidence of viral respiratory disease.4
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 infections.7,8
Vitamin D and inflammation
The relationship between inflammatory cytokines and vitamin D has been studied extensively. 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
Complications related to blood clotting are common in severe cases of COVID. D dimer levels (a 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 episodes.10
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 defensins,11 which exist in neutrophils, monocytes, natural killer (NK) cells and epithelial cells lining the respiratory tract.12
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 microbiome.13
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 sunlight.14 Vitamin D supplementation has been shown to reduce the incidence of type 1 diabetes.15 Patients with lupus (SLE) tend to be deficient in vitamin D, partially because of photophobia.16 The disease is more severe in patients with severe symptoms.17,18
Low levels of vitamin D are also associated with other autoimmune diseases. One analysis found a link between vitamin D deficiency and autoimmune thyroid disease.19 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, is 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 suggesting vitamin D, make sure 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.
PAUL VARNAS, DC, DACBN, is a graduate of the National College of Chiropractic and has had a functional medicine practice for 34 years. He is the author of several books and has taught nutrition at the National University of Health Sciences. For a free PDF of “Instantly Have a Functional Medicine Practice,” email him at email@example.com, or for a patient handout on the anti-inflammatory diet.
- Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004; 79:362-71
- Journal of the American Osteopathic Association March 2018; 118: 181-189
- J Clin Invest. 2020 May 1; 130(5):2620-2629. Clinical and immunological features of severe and moderate coronavirus disease 2019.
- Immune biomarkers predictive of respiratory viral infection in elderly nursing home residents. PLoS One. 2014; 9(9):e108481.
- 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.
- 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.
- Link between community-acquired pneumonia and vitamin D levels in older patients. Z Gerontol Geriatr. 2018 Jun; 51(4):435-439.
- 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.
- 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.
- Emerging Role of Vitamin D and its Associated Molecules in Pathways Related to Pathogenesis of Thrombosis. Biomolecules. 2019 Oct 24; 9(11)
- Bartley J. Vitamin D: emerging roles in infection and immunity. Expert Rev Anti Infect Ther. 2010;8:1359–1369.
- 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.
- 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.
- 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.
- 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.
- Lehmann P, Homey B. Clinic and pathophysiology of photosensitivity in lupus erythematosus. Autoimmun Rev. 2009;8:456–461
- 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
- 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
- Nutrients. 2015 Apr 3;7(4):2485-98 Immunomodulatory Function of Vitamin D and Its Role in Autoimmune Thyroid Disease
- Autoimmun Rev. 2010 May;9(7):507-10. Vitamin D and autoimmune disease