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Vitamin D: past, present and future perspectives in the prevention of chronic diseases

European Journal of Clinical Nutrition volume 72, pages 1221–1225 (2018)Cite this article

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Vitamin D is considered the sunshine vitamin and it has been produced on the earth for more than 500 million years [1]. The main role of vitamin D is to ensure the efficient intestinal calcium absorption from dietary sources and it is of paramount importance for the development and maintenance of a calcified mammalian skeleton [2]. Adequate vitamin D levels from either sunlight or diet are critical for skeletal homeostasis in most vertebrates [1, 3,4,5]. The production of vitamin D occurs during sun exposure when 7-dehydrocholesterol in the skin absorbs UV B radiation and is converted to previtamin D3 which in turn is converted into vitamin D3 [6, 7]. Both previtamin D3 and vitamin D3 have the property to absorb UV B radiation and to be converted into a variety of photoproducts that have been reported to have unique biologic properties. However, the production of vitamin D is influenced by several variables such as season, time of day, latitude, altitude, air pollution, skin pigmentation, sunscreen use, and aging [6, 7]. After the synthesis vitamin D is metabolized in the liver where it is converted in 25-hydroxyvitamin D, which is the major circulating form of vitamin D that is used by clinicians to measure vitamin D status [8, 9]. 25(OH)D is suddenly metabolized in the kidneys by the mitochondrial enzyme 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) to be converted into the systemically circulating active form, 1,25-dihydroxyvitamin D [1,25(OH)2D] [9,10,11]. The renal synthesis of 1,25(OH)2D is modulated by several factors such as serum phosphorus, calcium, fibroblast growth factor 23 (FGF-23), parathormone (PTH), and itself [8]. However, the production of 1,25(OH)2D can also occur in a multitude of tissues [11, 12], including bone, placenta, prostate, keratinocytes, macrophages, T-lymphocytes, dendritic cells, several cancer cells [13], and the parathyroid gland [14], where CYP27B1 is expressed extrarenally. A minimum amount of vitamin D is introduced through the foods. The number of foods naturally containing vitamin D in significant amounts is very limited, and they include oily fish such as salmon, sardines and tuna, and oils of the liver of some fish such as cod as well as sun-exposed mushrooms. Vitamin D sufficiency plays a pivotal role in the maintainance of skeletal health. In fact vitamin D takes part to skeletal development both in utero [15] and in childhood [16] and contribute to the maintainance of bone health in adulthood [17]. The main mechanism of vitamin D is to lead to an adequate calcium-phosphorus product (Ca2+ × HPO42−) resulting in an effective bone mineralization [16]. The importance of vitamin D has been well established as regards bone health. In fact bone diseases represent the only condition for which is reccomended vitamin D supplementation. Vitamin D deficiency has been associated to a defect of bone mineralization, leading to rickets in children and osteomalacia in adults. The mechanism through which vitamin D mainly preserves bone health has been linked to active calcium absorption from the intestine than to locally stimulate mineralization of the newly formed bone matrix, the osteoid. In fact the active vitamin D metabolite, 1,25(OH)2D, binds to vitamin D receptor (VDR) in intestinal cells and stimulates formation of calbindin, which binds calcium and influences the calcium channels. It has been hypothesized that bone mineralization is a passive process that occurs when adequate calcium and phosphate are available. [17].

Over time, vitamin D has evolved into a hormone having numerous extraskeletal effects by regulating up to estimated 2000 genes [18–20]. As a result 1,25-dihydroxyvitamin D influences a large number of biologic pathways, which may help explain association studies relating vitamin D deficiency and living at higher latitudes with increased risk for several chronic diseases including autoimmune diseases, cancer, cardiovascular (CV) disease, infectious disease, schizophrenia, and type 2 diabetes. The increased appreciation of the pleiotropic effects of vitamin D, and the high prevalence of hypovitaminosis D in the general healthy population has generated very high interest in vitamin D among researchers, clinicians, and the lay public. Thus, the research community is currently focused on studying the association and the physiopathological mechanisms that link vitamin D and chronic diseases in order to investigate if vitamin D supplementation could have a role in the prevention/treatment of these diseases. The most investigated diseases which have been hypothesized to be influenced by vitamin D levels are cancer, cardiovascular diseases, and diabetes The evidence for a link of vitamin D and cancer has been suggested by a single-country geographical ecological studies, observational studies of cancer incidence, and survival according to solar UVB dose or exposure, serum 25(OH)D concentrations, studies of mechanisms, and clinical trials of vitamin D supplementation. Further, an inverse correlation between solar UVB doses and incidence and/or mortality rate for 15–20 types of cancer has been found. Although several risk-modifying factors have been hypothesized to explained these findings, no mechanism other than vitamin D production has been suggested. The anticancer properties of vitamin D are due to the inibition of angiogenesis around cancer cells, the promotion of apoptosis in old or abnormal cells, and differentiation of cancer cells. Further, vitamin D has been reported to inhibit invasiveness of cancer cells, metastasis, and proliferation [20]. Vitamin D deficiency has been also associated to an increased risk of developing autoimmune diseases such as type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease. In animal models affected by type 1 diabetes, systemic lupus erythematosus, inflammatory bowel disease and autoimmune uveitis, administration of calcitriol either prevented or improved autoimmunity. Studies with vitamin D deficient or VDR knock-out animals reported an increased inflammation and susceptibility to type 1 diabetes and Crohn’s disease, disturbed T cell homing, and lack of host protection from bacterial invasion and infection. Thus, this positive findings in animals studies raised the question if vitamin D could have the same beneficial effect in humans [21]. A recent systematic review analyzed results from 219 published studies and concluded that vitamin D seems to play a beneficial role in the prevention of autoimmunity, but however randomized controlled clinical trials are still lacking [22].

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  1. Department of Clinical Medicine and Surgery, University “Federico II”, Naples, Italy

    Giovanna Muscogiuri

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Muscogiuri, G. Vitamin D: past, present and future perspectives in the prevention of chronic diseases. Eur J Clin Nutr 72, 1221–1225 (2018). https://doi.org/10.1038/s41430-018-0261-4

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