The rest is made by our bodies when our skin is exposed to sunlight. They were not in agreement with a cut-off level of 20 ng/ml for deficiency and recommended a lower level of 12.5 ng/ml. J Clin Endocrinol Metab. The active form of vitamin D and its analogs have been shown to upregulate cathelicidin expression in cultured keratinocytes (41, 45). The following factors may interfere with our body's ability to make vitamin D: In addition, a poor intake of vitamin D through the diet may also contribute; however, studies have shown less than 10% of the vitamin D in our body is obtained through diet, so it is not considered a major contributing factor. 2007;127(3):707-715. 2003;295(1):24-28. Mol Cell Endocrinol. 2004;89-90(1-5):567-570. Previtamin D 3 isomerizes to form vitamin D 3 (cholecalciferol), which is subsequently transported into the circulation via a binding protein (11) .  (PubMed), 34.  De Haes P, Garmyn M, Degreef H, Vantieghem K, Bouillon R, Segaert S. 1,25-Dihydroxyvitamin D3 inhibits ultraviolet B-induced apoptosis, Jun kinase activation, and interleukin-6 production in primary human keratinocytes. 1,25-dihydroxyvitamin D3 and its receptor, the VDR, have several biological functions in skin, including regulating the proliferation and differentiation of keratinocytes, hair follicle cycling, and tumor suppression.  (PubMed), 15.  Tsiaras WG, Weinstock MA. J Eur Acad Dermatol Venereol. Ligand-independent actions of the vitamin D receptor maintain hair follicle homeostasis. Best Practice Journal 2011:36, Vitamin D. Siemens Healthineers. It is also not just one substance, but five different substances, of which two have been identified as being the most important to humans. There are reports that excessive levels of vitamin D have caused kidney failure. Br J Dermatol.  (PubMed), 32.  Lee J, Youn JI.  (PubMed), 36.  Dixon KM, Deo SS, Norman AW, et al. 2009(2):CD005028. 23.  Odland GF. Group; 2001. email: lpi@oregonstate.edu, Healthcare Professional Continuing Education. Although cod liver oil had been used as a treatment for other ailments for some time, it wasn’t prescribed for rickets until 1824. Oldways. Calcitriol (1,25-dihydroxyvitamin D3) has been used topically to treat certain skin conditions, including psoriasis, a skin condition that involves a hyperproliferation of keratinocytes. Although rare in the U.S., it is common in other parts of the world, such as regions of Asia where vegetarianism coupled with low daylight hours are prevalent. The recommended daily intake of vitamin D is: The safe upper limit of vitamin D is 4,000 IU/day for adults. Factors influencing vitamin D status. Production of vitamin D via our skin is efficient and represents an easy, reliable way for most people to get enough vitamin D. Of course, how long you need to stay in the sun for depends on your age, skin type and color, the season, and the time of the day; but for most people, 10 minutes of summer skin on exposed skin, without sunblock, is considered sufficient. https://www.healthcare.siemens.com/laboratory-diagnostics/assays-by-diseases-conditions/bone-metabolism-assays/vitamin-d/types-of-vitamin-d. Vitamin D. Hormone Health Network.  (PubMed), 2.  Brunette MG, Chan M, Ferriere C, Roberts KD. Humans get vitamin D from their normal diet, dietary supplements and from exposure to sunlight.  (PubMed), 31.  Bikle DD. Subscribe to Drugs.com newsletters for the latest medication news, new drug approvals, alerts and updates. People living in higher latitudes are more at risk for vitamin D deficiency compared to those living in more equatorial latitudes because the sunlight intensity is lower. Copyright 2011-2021  Linus Pauling Institute, 1.  Holick MF. 1989;68(5):882-887. But this is significantly more than the recommended safe upper dosage of vitamin D, which is 4,000 IU/day for adults. 2011;133(3):250-252. Vitamin D deficiency is when levels of vitamin D in your body fall below those recommended as necessary to ensure all the processes in your body that rely on vitamin D can function properly. Proc Natl Acad Sci U S A. Rickets is a bone condition characterized by the softening and weakening of bones in children. Thus, several factors can have a substantial impact on body vitamin D levels through affecting the production of the vitamin in skin. Living at latitudes above 37 degrees north or below 37 degrees south of the equator over winter, although this is controversial, and studies have shown only Caucasians show a correlation with low vitamin D levels and latitude. Any symptoms reflect the fact that vitamin D impacts on your bone health, mood and immune system and may include: If the deficiency continues unresolved, then more noticeable symptoms may occur, such as bone fractures, rickets, or osteomalacia. J Biol Chem. Photoprotection by 1alpha,25-dihydroxyvitamin D and analogs: further studies on mechanisms and implications for UV-damage. Depending on the dose, UV light can lead to DNA damage, inflammatory responses, skin cell apoptosis (programmed cell death), skin aging, and skin cancer. 2012;4(2):158-166. doi:10.4161/derm.20731. It is also the most abundant form and lasts several weeks in the body. However, not everybody agrees, and some organizations suggest different cut-off values. 1986;25(7):1545-1548. A landmark study in 1922 that showed that malnourished children with rickets could be cured by the addition of whole milk or cod-liver oil in their diet, paved the way for researchers to isolate active vitamin D in the 1930s. unusual fractures, unexplained bone pain, or other symptoms suggesting metabolic bone disease. 2013;5(9):3605-16.  (PubMed), 29.  Li YC, Pirro AE, Amling M, et al. Type B UV (UVB) radiation with a wavelength of approximately 290–320 nanometers penetrates uncovered skin and converts cutaneous 7-dehydrocholesterol to previtamin D 3, which in turn becomes vitamin D 3. 2010;28(2):117-130. J Drugs Dermatol. Covering exposed skin or using sunscreen whenever outside are risk factors for vitamin D deficiency. Fortified milk or juice is more likely to contain D2 because it is cheaper to produce. 1 Vitamin D from the skin and diet is further metabolized in the liver to 25-(OH) vitamin D (or calcidiol). Solar ultraviolet-B radiation (UVB; wavelengths of 290 to 315 nanometers) stimulates the production of vitamin D3 from 7-dehydrocholesterol (7-DHC) in the epidermis of the skin (see Production in Skin) (1). low calcium or phosphate levels or an unexplained increase in serum alkaline phosphatase, unexplained limb pain near a joint in older people. D3 is better absorbed and more potent than D2. Long-term safety of topical calcitriol 3 microg g(-1) ointment. Vitamin D2, also called ergocalciferol, is found naturally in mushrooms that have been exposed to the sun. This is then irradiated to produce D3 (cholecalciferol). The University of California, San Francisco.  (PubMed), 43.  Frohm M, Agerberth B, Ahangari G, et al. Vitamine D is een groep van vet-oplosbare organische verbindingen die verantwoordelijk zijn voor de opname van calcium en fosfaat uit voeding, wat van groot belang is voor diverse biologische processen. Alshahrani F, Aljohani N. Vitamin D: deficiency, sufficiency and toxicity. 2007;103(3-5):451-456. UVB irradiation quickly converts epidermal 7-dehydrocholesterol into previtamin D3; the latter then isomerizes to vitamin D3 (cholecalciferol), which is then converted in the liver to 25- hydroxyvitamin D3 and subsequently in the kidneys to 1,25-dihydroxyvitamin D3, its active form. Br J Dermatol. During prolonged exposure to UV-B rays, precholecalciferol (previtamin D 3) is transformed into lumisterol, an inert isomer that maintains the balance of vitamin D 3 production (132, 133). Moreover, use of sunscreen effectively blocks UVB absorption and therefore vitamin D synthesis in skin: application of sunscreen with a sun protection factor (SPF) of 8 reduces production of vitamin D in skin by more than 95% (20). Aging decreases the capacity of human skin to produce vitamin D3. Upon exposure to UVB radiation, previtamin D 3 is synthesized from 7-DHC in the skin, primarily in keratinocytes of the stratum basale and stratum spinosum layers of the epidermis. Rickets is a bone disease that causes bone and growth deformities, typically in young children. Research has shown that taking 40,000-60,000 IU of vitamin D per day for several months can lead to toxicity.  (PubMed), 38.  Mason RS, Sequeira VB, Dixon KM, et al. Michael F. Holick, Neil C. Binkley, Heike A. Bischoff-Ferrari, Catherine M. Gordon, David A. Hanley, Robert P. Heaney, M. Hassan Murad, Connie M. Weaver; Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 96, Issue 7, 1 July 2011, Pages 1911–1930. J Invest Dermatol. Our skin stores a specific type of cholesterol, called 7-dehydrocholesterol, which is converted to previtamin D3 on exposure to UVB (wavelength 270-300nm). Previtamin D3 isomerizes to form vitamin D3 (cholecalciferol), which is subsequently transported into the circulation via a binding protein (11). Dermato-endocrinology. Upon entering the nucleus, 1,25-dihydroxyvitamin D3 associates with the VDR, which heterodimerizes with the retinoic acid X receptor (RXR).  (PubMed), 16.  Webb AR, Kline L, Holick MF. Upon exposure to sunlight, vitamin D3 can also be degraded to other photoproducts, including 5,6-trans-vitamin D3, suprasterol I, and suprasterol II (13). Moreover, vitamin D is known to modulate inflammation and may be involved in wound healing. Skin cancer prevention: a possible role of 1,25dihydroxyvitamin D3 and its analogs. 2005;124(5):1080-1082. Mol Cell Endocrinol. Naeem Z. Vitamin D Deficiency- An Ignored Epidemic. Vitamin D and the skin. 2011;347(1-2):80-89. Photodamage refers to skin damage induced by ultraviolet (UV) light. Supplemental D2 is cheaper to produce than supplemental D3; however, it is not as effective at raising levels of vitamin D in the blood nor as stable as synthetic vitamin D3. 2011;347(1-2):90-96. When UVB rays of the wavelength range 290 to 315nm touch 7-dehydrocholesterol, they convert it into previtamin D3. The active form of vitamin D functions as a steroid hormone. 2001;2(2):203-216. Vitamin D. National Institutes of Health. Daniel D. Bikle, M.D., Ph.D. Neonatal human foreskin keratinocytes produce 1,25-dihydroxyvitamin D3. Available for Android and iOS devices.  (PubMed), 19.  MacLaughlin J, Holick MF. Previtamin D3 can also isomerize to form the photoproducts, tachysterol3 or lumisterol3; the reaction that forms this latter compound is reversible. Rickets, Vitamin D Deficiency. April 2018. 1998;9(10):419-427. 維他命d有很多種不同的形式存在。兩種最主要的維他命d種類分別是維他命d 2 （麥角鈣化醇）和維他命d 3 （膽鈣化醇），它們統稱為鈣化醇。 1932年，研究人員闡明了維他命d 2 的結構，而人們於1936年發現了維他命d 3 ，並發現它可以由7-脫氫膽固醇經紫外線照射轉化而成 。 However, more research is needed to determine the role of vitamin D in wound healing and epidermal barrier function, and whether oral vitamin D supplementation or topical treatment with vitamin D analogs is helpful in healing surgical wounds.  (PubMed), 8.  Rizova E, Corroller M. Topical calcitriol--studies on local tolerance and systemic safety. Arch Dermatol Res. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. But in the 1940s this practice was replaced by the simpler and more effective method of adding vitamin D concentrate to milk, which continues today. Foods that naturally contain vitamin D3 include beef liver, cheese, cod liver oil, egg yolks, and fatty fish (such as mackerel, tuna, and salmon). Komaroff AL. This complex binds small sequences of DNA known as vitamin D response elements (VDREs); the binding initiates a cascade of molecular interactions that modulate the transcription of certain genes (21, 22).  (PubMed), 13.  Webb AR, DeCosta BR, Holick MF. See the flow chart above for an overview of the different forms of vitamin d. Our skin makes vitamin D when it is exposed to the sun. Trends Endocrinol Metab.  (PubMed), 11.  Holick MF, MacLaughlin JA, Clark MB, et al. Supplements obtained from lanolin are not vegan-friendly; however, a D3 supplement extracted from lichen is vegan and vegetarian-friendly. In skin, the vitamin D receptor (VDR) appears to have other roles that are independent of its association with 1,25-dihydroxyvitamin D3. Endocr Rev. Lisa A Houghton, Reinhold Vieth; The case against ergocalciferol (vitamin D2) as a vitamin supplement, The American Journal of Clinical Nutrition, Volume 84, Issue 4, 1 October 2006, Pages 694–697, Tello M. Vitamin D. What’s the right level? 1-5 Ultraviolet B irradiation of the skin drives the conversion of 7-dehydrocholesterol to previtamin D 3, which is then rapidly converted to vitamin D 3. The upper limit for children is 1000IU for infants up to 6 months; 2,500IU for toddlers up to 3 years; 3,000IU for children aged 4-8 years, and 4,000IU for those aged 9 years and older. Up until then, rickets was a common disease and rampant among poor children living in polluted and industrialized cities in the United States. International Journal of Health Sciences. It is also known as 1,25-dihydroxycholecalciferol.It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the expression of many genes. Chanterelle mushrooms contain a lot less D2 (114 IU/cup). Keratinocytes can locally convert previtamin D3 to the active form, 1,25-dihydroxyvitamin D3. Vitamin D metabolism and function in the skin. It was first recognized as a medical condition in 1650. Like the active form of vitamin D, some of the mentioned photoproducts may regulate epidermal proliferation and differentiation (14), but elucidation of their biological relevance will require further study. Time of day also influences the ability to generate vitamin D in skin, with midday solar radiation being the most intense. For a start, it is not actually a vitamin, but a prohormone, which means that it is converted into a hormone by our body. An impairment in memory and thinking skills in older adults, Cardiovascular disease, and an increased risk of dying from a stroke or a heart attack, A delay in the closure of the bones of the skull, Bead-like nodules where the bones of the rib cage join to cartilage (rachitic rosary), Bowed legs and knock-knees from the ends of the long bones becoming enlarged, Chest deformity due to the pull on the diaphragm on the ribs, Frequent infections (such as colds and flu), Vitamin D testing is considerably more expensive than supplements, No clear cut-off point for deficiency has been agreed upon. It is also better absorbed and more easily converted into active D. All forms of vitamin D2 and D3 obtained from our diet or from supplements require conversion in our liver and kidneys before being active in our body. An evaluation of the biologic activity and vitamin D receptor binding affinity of the photoisomers of vitamin D3 and previtamin D3. J Dermatol Sci. The VDR also functions as a tumor suppressor in skin (31). The vitamin D analog called calcipotriene or calcipotriol has also been used as a treatment for chronic plaque psoriasis, either alone or in combination with corticosteroids (9, 10). The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders. It is not intended as nutritional or medical advice for individual problems. Vitamin D toxicity is rare, but it can happen if you take too many supplements. Rickets most commonly occurs in children aged between six months and 36 months. Faseb J. Along with various coregulators, 1,25-dihydroxyvitamin D3 and its receptor, the VDR, regulate the abovementioned processes that replenish skin. Since D2 is cheaper to produce, it’s the most common form in fortified foods. Supplements of vitamin D3 can be made by extracting cholesterol from lanolin derived from sheep wool, then subjecting it to a series of chemical reactions to yield 7-dehydrocholesterol. 1998;18(1):11-18. Science. Cells in the stratum basale are constantly proliferating in order to produce new cells that will comprise the upper epidermal layers (23, 24). It has also been postulated that non-genomic actions of vitamin D contribute to the photoprotection (38); such effects of vitamin D involve cell-signaling cascades that open calcium channels (39). If levels are left too high for too long, bone pain, headaches, drowsiness, itching and calcium stones in the kidneys may occur.  (PubMed), 41.  Gombart AF, Borregaard N, Koeffler HP.  (PubMed), 44.  Koczulla R, von Degenfeld G, Kupatt C, et al. Acta Derm Venereol. Office of Dietary Supplements. J Invest Dermatol. Our skin stores a specific type of cholesterol, called 7-dehydrocholesterol, which is converted to previtamin D3 … Vitamin D3 enters the circulation and is transported to the liver, where it is hydroxylated to form 25-hydroxyvitamin D3 (calcidiol; the major circulating form of vitamin D). Several studies found that topical use of calcitriol (3 μg/g) ointment is safe and may be an effective treatment for plaque-type psoriasis (6-8). Consequently, parathyroid hormone (PTH) production by the parathyroid glands is increased and calcium is mobilized from bone to maintain normal serum calcium levels (see the article on Vitamin D). New York: Parthenon Pub.  (PubMed), 33.  Wong G, Gupta R, Dixon KM, et al. New York: Oxford University Press; 1991:3-62. How much vitamin D should I take? Melanin, the dark pigment in skin, competes with 7-DHC for the absorption of UV light and thus acts as a natural sunscreen, reducing the effectiveness of vitamin D production in skin. Religion or culture: People (especially women) whose beliefs require them to cover most of their skin and/or face usually do not receive adequate sunlight for their skin to make vitamin d. Avoidance of the sun and use of sunscreen: Fears of skin cancer and skin aging mean people spend less time in the sun than in the past, although only 10 minutes of direct summer sun is necessary to make an adequate daily dose of vitamin D. Medical conditions that affect absorption of vitamin D from the diet (such as, Prolonged, exclusive breastfeeding or being born to a vitamin D deficient mother, Obesity (stores of vitamin D get locked up in adipose tissue), Taking medications that affect vitamin D synthesis or degradation (such as, Frequent infections (such as colds or flu). Vitamin D2 still requires conversion in the body to become D3 active. Drisdol is another name for supplemental vitamin D2.  (PubMed), 14.  Chen TC, Persons KS, Lu Z, Mathieu JS, Holick MF. Vitamin D was first added to milk in the U.S. in the late 1930s. 2006;116(8):2062-2072. Science. For instance, the VDR is important in regulating the growth cycle of mature hair follicles (27, 28). Mol Endocrinol. Photosynthesis of previtamin D3 in human skin and the physiologic consequences. This article was underwritten, in part, by a grant from Neutrogena Corporation, Los Angeles, California. The Indian Journal of Medical Research. Fluids and other medications, such as bisphosphonates may also be prescribed. J Clin Invest. J Clin Invest. The consequences of vitamin D deficiency primarily concern bone health. 1985;76(4):1536-1538. Vitamin D deficiency. In summary, vitamin D is a prohormone that is essential for good health. Written in November 2011 by: In vivo relevance for photoprotection by the vitamin D rapid response pathway.  (PubMed), 5.  Lehmann B, Sauter W, Knuschke P, Dressler S, Meurer M. Demonstration of UVB-induced synthesis of 1 alpha,25-dihydroxyvitamin D3 (calcitriol) in human skin by microdialysis. J Steroid Biochem Mol Biol.  (PubMed), 20.  Matsuoka LY, Ide L, Wortsman J, MacLaughlin JA, Holick MF. Low blood levels of vitamin D have also been associated with: Research also suggests vitamin D may help prevent or be helpful in the management of several other conditions such as diabetes, high blood pressure, and multiple sclerosis. Documented effects in skin cells include decreased DNA damage, reduced apoptosis, increased cell survival, and decreased erythema. In latitudes around 40 degrees north or 40 degrees south (Boston is 42 degrees north), there is insufficient UVB radiation available for vitamin D synthesis from November to early March. In addition to its steroid hormone actions, vitamin D regulates biochemical steps that result in a cellular influx of calcium, which is important in cell differentiation (26). Mushrooms contain a yeast compound called ergosterol, which is converted to ergocalciferol on exposure to UV light.  (PubMed), 21.  Jones G, Strugnell SA, DeLuca HF.  (PubMed), 17.  Holick MF. Note that several members of the IOM committee publicly stated that over screening for vitamin D deficiency was a problem which typically resulted in unnecessary treatment. For example, aging reduces the capacity to synthesize vitamin D in skin since older adults have lower skin concentrations of the vitamin D precursor, 7-DHC, compared to younger individuals (19). 2010;121(1-2):164-168. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition.  (PubMed), 42.  Heilborn JD, Nilsson MF, Kratz G, et al. Liability for individual actions or omissions based upon the contents of this site is expressly disclaimed. Malabsorption syndromes or a diet low in foods containing vitamin D can also lower vitamin D levels.  (PubMed), 10.  Murphy G, Reich K. In touch with psoriasis: topical treatments and current guidelines. Most of the physiological effects of vitamin D in the body are related to the activity of 1,25-dihydroxyvitamin D3; see the article on Vitamin D. Keratinocytes in the epidermis possess hydroxylase enzymes that locally convert vitamin D to 1,25-dihydroxyvitamin D3 (3-5), the form that regulates epidermal proliferation and differentiation (see Metabolism in keratinocytes). The photoprotective effect of 1,25-dihydroxyvitamin D3 on ultraviolet light B-induced damage in keratinocyte and its mechanism of action. Sometimes surgery may be required to correct bone and muscle distortions. J Bone Miner Metab.  (PubMed), 27.  Skorija K, Cox M, Sisk JM, et al. Sunscreens suppress cutaneous vitamin D3 synthesis. Gröber U, Kisters K. Influence of drugs on vitamin D and calcium metabolism. The synthesis of active vitamin D is quite complex but involves sunlight, a specific type of cholesterol present in our skin, and modification first by our liver and then our kidneys. Vitamin D deficiency is prevalent among obese people, because greater amounts of vitamin D are locked up in their adipose tissue (fat stores), rather than in the blood where it can be used. Some cell culture and rodent studies have shown that 1,25-dihydroxyvitamin D3 exhibits photoprotective effects. Drug-vitamin D interactions: A systematic review of the literature. Nutrients. Anything that interferes with the body’s ability to make vitamin D through the skin, including liver or kidney disease, can cause deficiency. Published 2013 Sep 13. doi:10.3390/nu5093605. The process of converting 7-dehydrocholesterol into active vitamin D3, although complex, is reasonably efficient and it has been estimated that only 10 minutes of summer sun on our hands and face is required to generate our daily requirement of 10 micrograms of vitamin D3. J Invest Dermatol. Oregon State University, Reviewed in November 2011 by: The active form of cholecalciferol, 1,25-dihydroxycholecalciferol plays an important role in maintaining blood calcium and phosphorus levels and mineralization of bone. Ten degrees farther north (Edmonton, Canada) or south the “vitamin D winter” extends from October to April (16). Other studies have shown that cathelicidin modulates inflammation in skin (43), induces angiogenesis (44), and improves reepithelialization (the process of restoring the epidermal barrier to re-establish a functional barrier that protects underlying cells from environmental exposures) (42). Therefore, individuals with dark-colored skin require more time (up to ten times as long) to synthesize the same amount of previtamin D3 in skin as those with fair skin (12, 17). Site of 1,25(OH)2 vitamin D3 synthesis in the kidney. Cholecalciferol is a form of vitamin D which is naturally synthesized in skin and functions as a pro-hormone, being converted to calcitriol.This is important for maintaining calcium levels and promoting bone health and development. 2009;8(8 Suppl):s17-22. Numerous variables affect skin synthesis of vitamin D, including latitude, season, time of day, degree of skin pigmentation, age, amount of skin exposed, and sunscreen use. The processes of epidermal proliferation and differentiation are essential for normal cell growth, wound healing, and maintaining the barrier function of skin. A lack of vitamin D has been associated with: Research also suggests low vitamin D may be a factor in several other conditions such as diabetes, high blood pressure, and multiple sclerosis. 2004;173(5):2909-2912. Obese people are also less likely to eat foods naturally high in vitamin D or expose their skin to sunlight. Balasubramanian S. Vitamin D deficiency in breastfed infants & the need for routine vitamin D supplementation.  (PubMed), 22.  Jurutka PW, Whitfield GK, Hsieh JC, Thompson PD, Haussler CA, Haussler MR. Molecular nature of the vitamin D receptor and its role in regulation of gene expression. J Steroid Biochem Mol Biol. Evaluation of keratinocyte proliferation and differentiation in vitamin D receptor knockout mice.  (PubMed), 37.  Gupta R, Dixon KM, Deo SS, et al. J Clin Invest. Other fat-soluble vitamins are vitamin A, vitamin E and vitamin K. Because it is fat soluble, vitamin D toxicity can occur if too much is taken. Always talk to your doctor before taking vitamin and mineral supplements. Only 10% of the vitamin D our body needs is obtained from food.
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