Vitamin D describes a group of fat-soluble chemical compounds that promote normal growth and development, with vitamin D2 and D3 being the most important for humans. While essential vitamins cannot be synthesized by humans, vitamin D can be. The major natural source of vitamin D is a chemical reaction dependent on sun exposure that results in its synthesis in the lower layers of the skin.
Alternative sources of vitamin D include certain foods, such as mushrooms, fatty fish and some milks that are fortified with vitamin D, as well as manufactured supplements. Despite this, a large proportion of the world population (~7%) do not take or have access to normal doses of vitamin D. When considering the potential health benefits of vitamin D, this raises several concerns that will be discussed in this article.
Biology of Vitamin D
Whether it be ingested or generated from sun exposure in the skin, vitamin D remains inactive until it reaches the liver. To be used in the body, vitamin D must be activated through two enzymatic steps, the first of which is in the liver and the second is in the kidneys, into calcitriol and 25hydroxyergocalciferol. These two compounds make up the biologically active forms of vitamin D that can be used to promote healthy tissue function and growth in humans.
Impact of Vitamin D on Health and Disease
One of the most well-known benefits of vitamin D is its role in calcium homeostasis and metabolism to maintain skeletal health. In addition to calcium absorption, vitamin D also improves the intestinal absorption of nutrients such as phosphate and magnesium, which are necessary in the blood for improved metabolism and bone health. It is well understood that children deficient in vitamin D can experience nutritional rickets, a disease that results in bone pain, delayed motor development and bending of the bones. Further, supplementation with vitamin D and calcium in older adults have been shown to decrease risk of hip fractures and other fractures by approximately 20%.
The impact of vitamin D on extra-skeletal tissues and organs are more controversial. Vitamin D deficiency has been shown to increase the risk and/or severity of various infectious diseases, including tuberculosis, HIV, and more recently COVID19. There is also strong evidence that supports a causal association between low serum vitamin D levels and increased risk of autoimmune diseases, particularly multiple sclerosis. However, vitamin D supplementation provides only a modest decrease in cancer mortality and no effects on the incidence of cardiovascular events.
Despite these controversial findings, the vitamin D receptor and the enzyme involved in producing the active form of vitamin D are widely expressed in tissues not involved in calcium, phosphate, or magnesium transport. As such, the importance of vitamin D in health and disease likely extend beyond skeletal health. Furthermore, many diseases in humans are reportedly associated with low serum vitamin D levels, as such, it is important to investigate whether vitamin D plays a causal role in the development of specific diseases.
Until we better understand the role of vitamin D in disease development, it is important that vitamin D be used wisely and provided to populations of people that are not taking enough to maintain a healthy nutritional status.
1.Anthony W Norman, From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health, The American Journal of Clinical Nutrition, Volume 88, Issue 2, August 2008, Pages 491S–499S, https://doi.org/10.1093/ajcn/88.2.491S
4.Bouillon, R., Manousaki, D., Rosen, C., Trajanoska, K., Rivadeneira, F., & Richards, J. B. (2022). The health effects of vitamin D supplementation: Evidence from human studies. Nature Reviews Endocrinology, 18(2), 96-110.
5.Lips, P., Bilezikian, J. P., & Bouillon, R. (2020). Vitamin D: giveth to those who needeth. JBMR plus, 4(1), e10232.
6.Pereira, M., Dantas Damascena, A., Galvão Azevedo, L. M., de Almeida Oliveira, T., & da Mota Santana, J. (2022). Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis. Critical reviews in food science and nutrition, 62(5), 1308-1316.
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