Vitamin D and the Immune System
By Dr. Alyssa Dweck, MS MD FACOG, practicing gynecologist in Westchester County, New York, and Tru Niagen Partner
What Is Vitamin D?
Also called calciferol, vitamin D is a well-known fat-soluble nutrient involved in maintaining healthy bone mineral density. Its two main forms are cholecalciferol (also known as vitamin D3), and ergocalciferol (aka vitamin D2). It regulates calcium and phosphate metabolism by acting on the small intestine, kidneys, and bone.[1]
When vitamin D is ingested through diet or synthesized in the skin from sunlight, it’s converted into the active forms in the liver and kidneys, respectively. It promotes calcium absorption in the gut and supports adequate serum calcium and phosphate concentration to allow normal bone mineralization and prevent low serum calcium leading to tetany (involuntary contraction of muscles causing cramps and spasms).
Why Is Vitamin D Important?
Vitamin D and Immune Health
Vitamin D is also a hormone that helps regulate the immune system.[2] Studies show vitamin D plays an important role in both the innate and adaptive immune systems.
Suggestions linking vitamin D and immune function in part originate from observations of disease occurrence based on geographic location. Vitamin D is primarily obtained through synthesis in the skin following sun exposure, and levels of UV light vary according to latitude (distance from the equator). Higher latitude is often an indicator of lower levels of UV exposure and lower vitamin D status. The incidence or prevalence of a disease increases with increasing distance from the equator.[3]
Innate and Adaptive Immune Systems
Research has shown vitamin D is involved in the innate and adaptive immune systems. Several cell types of the immune system, including T cells, B cells, neutrophils, and macrophages express the Vitamin D Receptor (VDR), symbolic of their capacity to be decreased by vitamin D signaling. Vitamin D is involved in antimicrobial activities of macrophages and monocytes[2,4] and antiviral activity against many respiratory viruses[5,6].
Vitamin D and its metabolites exert multiple phenotypic effects on the vascular endothelium via multiple pathways that are protective against vascular dysfunction and tissue injury[1]. Furthermore, multiple studies have shown that vitamin D plays a role in gut integrity and intestinal homeostasis between host and gut microbiota. Signaling vitamin D increases the viability of intestinal cells and eases intestinal damage from bacteria that activate the immune system.
Vitamin D’s role in the innate immune system has important clinical implications, made evident by the increase in vitamin D-deficient individuals resulting in the increased susceptibility to bacterial infection[1].
Adaptive Immunity
While vitamin D enhances the innate immune system, it suppresses adaptive immunity by suppressing the response of type 1 helper (Th1) cells that are capable of producing inflammatory cytokines.[3]
Vitamin D’s role in the adaptive immune system can have consequences for the occurrence of autoimmune diseases with uncontrolled adaptive immune activation. Geographically, the incidence of multiple sclerosis (MS) or inflammatory bowel disease (IBD) are almost unknown on the equator because of the ability to make vitamin D from UV light, the most favorable source. Vitamin D deficiency is associated with an increased incidence of MS and IBD.[3] Research indicates the importance of active vitamin D (1,25(OH)2 D3) as a regulator of primary components of the immune system.
Vitamin D and Bone Health
We often think of vitamin D as beneficial to bone health. Vitamin D is crucial to calcium and phosphorus homeostasis and subsequent bone metabolism. Vitamin D promotes calcium absorption in the gut and maintains adequate serum calcium and phosphate levels to enable normal bone mineralization. Normal bone mineralization is a result of highly specialized cells. Bone growth occurs via bone-building cells called osteoblasts. Bone remodeling occurs through osteoclasts—cells that break down bone. These cells work synergistically with one another to constantly remodel bone.
Along with calcium, vitamin D helps to protect against osteoporosis, or brittle bones. Women are at substantial risk for osteoporosis and subsequent bone fracture during menopause, because estrogen levels decline significantly during this time, leaving bone strength vulnerable. Estrogen exposure protects bone integrity.
As an aside, some younger women can also be at risk for bone loss and fracture, including those who fail to menstruate due to an eating disorder and excessive weight loss. These women also have limited estrogen exposure as a risk factor. Vitamin D may help to reduce risk of fractures and loss of bone density.
Vitamin D Deficiency
In the past, severe vitamin D deficiency presented as rickets, which is now a rare bone disease in children. Those who lack adequate sun exposure, have conditions of malabsorption, or diets poor in fortified foods are at risk for low vitamin D. Vitamin D deficiency can be diagnosed with a simple blood test, and supplementation can be suggested based on results.
Older adults are at increased risk of developing vitamin D insufficiency, partly because the skin’s ability to synthesize vitamin D declines with age. In addition, older adults are likely to spend more time than younger people indoors, and they might have inadequate dietary intakes.
Sources of Vitamin D
The primary source of vitamin D is through synthesis in the skin from sunlight and ultraviolet (UV) light exposure. Synthesis is dependent on multiple factors. Season, time of day, length of day and light exposure, cloud cover, smog, skin melanin content, and sunscreen can all affect UV light exposure and vitamin D synthesis. Older people and people with dark skin are less able to produce vitamin D from sunlight and are thus more at risk for deficiency. It’s also worth noting that UV light is not absorbed through glass.
Vitamin D in Food
Vitamin D is difficult to find in food. Vitamin D3 is found in fatty fish such as trout, salmon, tuna, and fish liver oils. Smaller amounts are found in beef liver, cheese, and egg yolks. Mushrooms provide varying amounts of vitamin D2 naturally. Some mushrooms have been treated with UV light to enhance the level of vitamin D2. Foods that have been fortified with vitamin D provide the majority of dietary vitamin D in America. Fortified foods include dairy milk and yogurt, infant formula, orange juice, and breakfast cereal.
Vitamin D Supplementation
Vitamin D supplements contain vitamin D2 or D3. Vitamin D2 is the plant-based source of vitamin D and is produced using UV irradiation of ergosterol in yeast. Vitamin D3 is manufactured through irradiation of 7-dehydrocholesterol from lanolin found in sheep’s wool. Lichen offers an animal-free source of vitamin D3.[4]. The vegan vitamin D3 found in Tru Niagen Immune is derived from algae.
Recommended Vitamin D Intake
The recommended daily allowance (RDA) of vitamin D for people aged 1 through 70 is 600IU (15mcg) daily, and 800IU (20mcg) is recommended for those over 70. Vitamin D status in individuals is monitored with serum 25 (OH) D levels. Optimal levels vary based on stage of life, age, gender, race, and ethnicity. The Food and Nutrition Board of the National Academies (formerly the Institute of Medicine [IOM]) established an upper limit for vitamin D intake of 4,000IU (100mcg)/day. In some cases, higher doses may be suggested based on individual needs.
Vitamin D in Excess
Excess amounts of vitamin D can be toxic, which results in marked hypercalcemia because vitamin D increases calcium absorption in the GI tract.[7] Extreme cases of vitamin D toxicity can cause renal failure, calcification of soft tissues throughout the body (including coronary vessels and heart valves), cardiac arrhythmia and even death. Toxicity may be caused by vitamin D supplements that have high doses of vitamin D that were taken excessively or incorrectly.[7] The Food and Nutrition Board established upper limits (UL) for vitamin D in 2010 acknowledging that symptoms of toxicity are unlikely at daily intakes <10,000 IU (250 mcg). Their recommendation for serum vitamin D levels is lower than 125-150 nmol/L (50-60 ng/ml).[8]
Summarizing Vitamin D and the Immune System
The immune system is complex and involves many nutrients in addition to vitamin D to function optimally. The information above highlights that vitamin D has a wide range of impact on the immune system, including modulation of immune response, inflammation, and the gut microbiome. This information suggests vitamin D supplementation may be beneficial for supporting immune health. It is recommended to speak to your healthcare provider when deciding whether to supplement with vitamin D.
Citations:
1. Charoenngam, N. & Holick, M. F. Immunologic Effects of Vitamin D on Human Health and Disease. Nutrients 12, 2097 (2020).
2. Prietl, B., Treiber, G., Pieber, T. R. & Amrein, K. Vitamin D and Immune Function. Nutrients 5, 2502–2521 (2013).
3. Wei, R. & Christakos, S. Mechanisms Underlying the Regulation of Innate and Adaptive Immunity by Vitamin D. Nutrients 7, 8251–8260 (2015).
4. Holick, M. F. Vitamin D Deficiency. N. Engl. J. Med. 357, 266–281 (2007).
5. Barlow, P. G. et al. Antiviral Activity and Increased Host Defense against Influenza Infection Elicited by the Human Cathelicidin LL-37. Plos One 6, e25333 (2011).
6. Tripathi, S. et al. The human cathelicidin LL-37 inhibits influenza A viruses through a mechanism distinct from that of surfactant protein D or defensins. J Gen Virol 94, 40–49 (2013).
7. Galior, K., Grebe, S. & Singh, R. Development of Vitamin D Toxicity from Overcorrection of Vitamin D Deficiency: A Review of Case Reports. Nutrients 10, 953 (2018).
8. Ross & AC. Institute of Medicine (US) Committee to Review DRIs for Vitamin D and Calcium. (2011).
Additional References:
https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
Moyer, VA. Vitamin, mineral, and multivitamin supplements for the primary prevention of cardiovascular disease and cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2014;160:558-64.
Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251419/
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2265.2011.04261.x
https://www.mayoclinicproceedings.org/article/S0025-6196(13)00404-7/fulltext
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