Vitamin D: The "sunshine" vitamin

Rathish Nair, Arun Maseeh, Rathish Nair, Arun Maseeh

Abstract

Vitamin D insufficiency affects almost 50% of the population worldwide. An estimated 1 billion people worldwide, across all ethnicities and age groups, have a vitamin D deficiency (VDD). This pandemic of hypovitaminosis D can mainly be attributed to lifestyle (for example, reduced outdoor activities) and environmental (for example, air pollution) factors that reduce exposure to sunlight, which is required for ultraviolet-B (UVB)-induced vitamin D production in the skin. High prevalence of vitamin D insufficiency is a particularly important public health issue because hypovitaminosis D is an independent risk factor for total mortality in the general population. Current studies suggest that we may need more vitamin D than presently recommended to prevent chronic disease. As the number of people with VDD continues to increase, the importance of this hormone in overall health and the prevention of chronic diseases are at the forefront of research. VDD is very common in all age groups. As few foods contain vitamin D, guidelines recommended supplementation at suggested daily intake and tolerable upper limit levels. It is also suggested to measure the serum 25-hydroxyvitamin D level as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D2 or vitamin D3 is recommended for deficient patients. A meta-analysis published in 2007 showed that vitamin D supplementation was associated with significantly reduced mortality. In this review, we will summarize the mechanisms that are presumed to underlie the relationship between vitamin D and understand its biology and clinical implications.

Keywords: Cancer; fat soluble vitamin; hypertension; obesity; vitamin D analogs.

Conflict of interest statement

Conflict of Interest: None declared.

Figures

Figure 1
Figure 1
Vitamin D synthesis

References

    1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81.
    1. Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ. Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med. 2004;158:531–7.
    1. Lips P, Hosking D, Lippuner K, Norquist JM, Wehren L, Maalouf G, et al. The prevalence of vitamin D inadequacy amongst women with osteoporosis: An international epidemiological investigation. J Intern Med. 2006;260:245–54.
    1. Rostand SG. Ultraviolet light may contribute to geographic and racial blood pressure differences. Hypertension. 1997;30:150–6.
    1. Melamed ML, Michos ED, Post W, Astor B. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. 2008;168:1629–37.
    1. Harvard School of Public Health Nutrition Source. Vitamin D and health. [Last accessed on 2010 Aug 30]. Available from: .
    1. Autier P, Gandini S. Vitamin D supplementation and total mortality: A meta-analysis of randomized controlled trials. Arch Intern Med. 2007;167:1730–7.
    1. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Chapter 7. Vitamin D. [Last accessed on 2010 Aug 02]. Available from: .
    1. NIH Office of Dietary Supplements. Dietary supplement fact sheet: Vitamin D. [Last accessed on 2010 Aug 04]. .
    1. Nair S. Symptoms of low vitamin D levels. [Last accessed on 2010 Sep 02]. Available from: .
    1. MedlinePlus. 25-hydroxy vitamin D test. [Last accessed on 2010 Aug 04]. Available from: .
    1. Moyad MA. Vitamin D: A rapid review: Side effects and toxicity. [Last accessed on 2010 Sep 02]. Available from: .
    1. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized trial. Am J Clin Nutr. 2007;85:1586–91.
    1. Chlebowski RT, Johnson KC, Kooperberg C, Pettinger M, Wactawski-Wende J, Rohan T, et al. J Natl Cancer Inst. 2008;100:1581–91.
    1. Stolzenberg-Solomon RZ, Vieth R, Azad A, Pietinen P, Taylor PR, Virtamo J, et al. A prospective nested case-control study of vitamin D status and pancreatic cancer risk in male smokers. Cancer Res. 2006;66:10213–9.
    1. Stolzenberg-Solomon RZ, Hayes RB, Horst RL, Anderson KE, Hollis BW, Silverman DT. Serum vitamin D and risk of pancreatic cancer in the Prostate, Lung, Colorectal, and Ovarian Screening Trial. Cancer Res. 2009;69:1439–47.
    1. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117:503–11.
    1. Heaney RP. Functional indices of vitamin D status and ramifications of vitamin D deficiency. Am J Clin Nutr. 2004;80(6 Suppl):1706S–9S.
    1. Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet. 1998;351:805–6.
    1. Heaney RP, Dowell MS, Hale CA, Bendich A. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr. 2003;22:142–6.
    1. Hansen KE, Jones AN, Lindstrom MJ, Davis LA, Engelke JA, Shafer MM. Vitamin D insufficiency: Disease or no disease? J Bone Miner Res. 2008;23:1052–60.
    1. Bischoff-Ferrari HA, Can U, Staehelin HB, Platz A, Henschkowski J, Michel BA, et al. Severe vitamin D deficiency in Swiss hip fracture patients. Bone. 2008;42:597–602.
    1. Dietary reference intakes for calcium and vitamin D. Washington DC: The National Academies Press; 2011. IOM (Institute of Medicine)
    1. Marwaha RK, Tandon N, Reddy DR, Aggarwal R, Singh R, Sawhney RC, et al. Vitamin D and bone mineral density status of healthy schoolchildren in northern India. Am J Clin Nutr. 2005;82:477–82.
    1. Thacher TD, Fischer PR, Strand MA, Pettifor JM. Nutritional rickets around the world: Causes and future directions. Ann Trop Paediatr. 2006;26:1–16.
    1. Hollis BW, Wagner CL. Vitamin D requirements during lactation: High-dose maternal supplementation as therapy to prevent hypovitaminosis D for both the mother and the nursing infant. Am J Clin Nutr. 2004;80:1752S–8S.
    1. Lee JM, Smith JR, Philipp BL, Chen TC, Mathieu J, Holick MF. Vitamin D deficiency in a healthy group of mothers and newborn infants. Clin Pediatr (Phila) 2007;46:42–4.
    1. Bodnar LM, Simhan HN, Powers RW, Frank MP, Cooperstein E, Roberts JM. High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates. J Nutr. 2007;137:447–52.
    1. Moan J, Porojnicu AC, Dahlback A, Setlow RB. Addressing the health benefits and risks, involving vitamin D or skin cancer, of increased sun exposure. Proc Natl Acad Sci USA. 2008;105:668–73.
    1. Hollis BW. Circulating 25-hydroxyvitaminDlevels indicative of vitamin D sufficiency: Implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr. 2005;135:317–22.
    1. Maeda SS, Kunii IS, Hayashi L, Lazaretti-Castro M. The effect of sun exposure on 25-hydroxyvitamin D concentrations in young healthy subjects living in the city of Sao Paulo, Brazil. Braz J Med Biol Res. 2007;40:1653–9.
    1. Brot C, Vestergaard P, Kolthoff N, Gram J, Hermann AP, Sorensen OH. Vitamin D status and its adequacy in healthy Danish peri-menopausal women: Relationships to dietary intake, sun exposure and serum parathyroid hormone. Br J Nutr. 2001;86(Suppl 1):S97–103.
    1. Holick MF, Chen TC. Vitamin D deficiency: A worldwide problem with health consequences. Am J Clin Nutr. 2008;87:1080S–6S.
    1. Holick MF, Chen TC, Sauter ER. Vitamin D and skin physiology: A D-lightful story. J Bone Miner Res. 2007;22(Suppl 2):V28–33.
    1. Looker AC, Pfeiffer CM, Lacher DA, Schleicher RL, Picciano MF, Yetley EA. Serum 25-hydroxyvitaminDstatus of the US population: 1988–1994 compared to 2000–2004. Am J Clin Nutr. 2008;88:1519–27.
    1. Matsuoka LY, Ide L, Wortsman J, MacLaughlin JA, Holick MF. Sunscreens suppress cutaneous vitamin D3 synthesis. J Clin Endocrinol Metab. 1987;64:1165–8.
    1. Clemens TL, Henderson SL, Adams JS, Holick MF. Increased skin pigment reduces the capacity of skin to synthesise vitamin D3. Lancet. 1982;1:74–6.
    1. Hintzpeter B, Scheidt-Nave C, Müller MJ, Schenk L, Mensink GB. Higher prevalence of vitamin D deficiency is associated with immigrant background among children and adolescents in Germany. J Nutr. 2008;138:1482–90.
    1. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 2000;72:690–3.
    1. Zhou C, Assem M, Tay JC, Watkins PB, Blumberg B, Schuetz EG, et al. Steroid and xenobiotic receptor and vitamin D receptor crosstalk mediates CYP24 expression and drug-induced osteomalacia. J Clin Invest. 2006;116:1703–12.
    1. Adams JS, Hewison M. Hypercalcemia caused by granuloma forming disorders. In: Favus MJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. 6th ed. Washington, DC: American Society for Bone and Mineral Research; 2006. pp. 200–2.
    1. Grey A, Lucas J, Horne A, Gamble G, Davidson JS, Reid IR. Vitamin D repletion in patients with primary hyperparathyroidism and coexistent vitamin D insufficiency. J Clin Endocrinol Metab. 2005;90:2122–6.
    1. Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT, et al. Prevalence of vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab. 2005;90:3215–24.
    1. Aaron JE, Gallagher JC, Anderson J, Stasiak L, Longton EB, Nordin BE, et al. Frequency of osteomalacia and osteoporosis in fractures of the proximal femur. Lancet. 1974;1:229–33.
    1. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006;81:353–73.
    1. Gordon CM, Williams AL, Feldman HA, May J, Sinclair L, Vasquez A, et al. Treatment of hypovitaminosis D in infants and toddlers. J Clin Endocrinol Metab. 2008;93:2716–21.
    1. Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest. 2006;116:2062–72.
    1. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: A meta-analysis of randomized controlled trials. JAMA. 2005;293:2257–64.
    1. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, Orav JE, Stuck AE, Theiler R, et al. Fall prevention with supplemental and active forms of vitamin D: A meta-analysis of randomised controlled trials. BMJ. 2009;339:b3692.
    1. Dietary Supplement Fact Sheet: Vitamin D. Office of Dietary Supplements, National Institutes of Health. 2011 Jun 24;
    1. Picciano MF. Nutrient composition of human milk. Pediatr Clin North Am. 2001;48:53–67.
    1. Wagner CL, Greer FR. American Academy of Pediatrics Section on Breastfeeding; American Academy of Pediatrics Committee on Nutrition. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics. 2008;122:1142–52.
    1. American Academy of Pediatrics Committee on Environmental Health. Ultraviolet light: A hazard to children. Pediatrics. 1999;104:328–33.
    1. Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D3: Exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab. 1988;67:373–8.
    1. Webb AR, Pilbeam C, Hanafin N, Holick MF. An evaluation of the relative contributions of exposure to sunlight and of diet to the circulating concentrations of 25-hydroxyvitamin D in an elderly nursing home population in Boston. Am J Clin Nutr. 1990;51:1075–81.
    1. Lo CW, Paris PW, Clemens TL, Nolan J, Holick MF. Vitamin D absorption in healthy subjects and in patients with intestinal malabsorption syndromes. Am J Clin Nutr. 1985;42:644–9.
    1. Holick MF. Vitamin D. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, editors. Modern Nutrition in Health and Disease. 10th ed. Philadelphia: Lippincott Williams and Wilkins; 2006.
    1. Malone M. Recommended nutritional supplements for bariatric surgery patients. Ann Pharmacother. 2008;42:1851–8.
    1. Compher CW, Badellino KO, Boullata JI. Vitamin D and the bariatric surgical patient: A review. Obes Surg. 2008;18:220–4.
    1. Holick MF. Vitamin D: A D-lightful health perspective. Nutr Rev. 2008;66(10 Suppl 2):S182–94.
    1. Haddad JG, Matsuoka LY, Hollis BW, Hu YZ, Wortsman J. Human plasma transport of vitamin D after its endogenous synthesis. J Clin Invest. 1993;91:2552–5.
    1. Lau AH, How PP. The role of the pharmacist in the identification and management of secondary hyperparathyroidism. US Pharm. 2007;32:62–72.
    1. Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, et al. Hypovitaminosis D in medical inpatients. N Engl J Med. 1998;338:777–83.
    1. Dusso AS, Brown AJ, Slatopolsky E. Vitamin D. Am J Physiol Renal Physiol. 2005;289:F8–28.
    1. Peterlik M, Cross HS. Vitamin D and calcium deficits predispose for multiple chronic diseases. Eur J Clin Invest. 2005;35:290–304.
    1. Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: Lessons from vitamin D receptor null mice. Endocr Rev. 2008;29:726–76.
    1. Medici D, Razzaque MS, Deluca S, Rector TL, Hou B, Kang K, et al. FGF-23-Klotho signaling stimulates proliferation and prevents vitamin D-induced apoptosis. J Cell Biol. 2008;182:459–65.
    1. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311:1770–3.
    1. Schauber J, Dorschner RA, Coda AB, Büchau AS, Liu PT, Kiken D, et al. Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest. 2007;117:803–11.
    1. Cannell JJ, Vieth R, Willett W, Zasloff M, Hathcock JN, White JH, et al. Cod liver oil, vitamin A toxicity, frequent respiratory infections, and the vitamin D deficiency epidemic. Ann Otol Rhinol Laryngol. 2008;117:864–70.
    1. Ahn J, Peters U, Albanes D, Purdue MP, Abnet CC, Chatterjee N, et al. Serum vitamin D concentration and prostate cancer risk: A nested case-control study. J Natl Cancer Inst. 2008;100:796–804.
    1. Anderson LN, Cotterchio M, Vieth R, Knight JA. Vitamin D and calcium intakes and breast cancer risk in pre- and postmenopausal women. Am J Clin Nutr. 2010;91:1699–707.
    1. Forman JP, Giovannucci E, Holmes MD, Bischoff-Ferrari HA, Tworoger SS, Willett WC, et al. Plasma 25-hydroxyvitamin D levels and risk of incident hypertension. Hypertension. 2007;49:1063–9.
    1. Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, ethnicity, and blood pressure in the third National Health and Nutrition Examination Survey. Am J Hypertens. 2007;20:713–9.
    1. Judd SE, Nanes MS, Ziegler TR, Wilson PW, Tangpricha V. Optimal vitamin D status attenuates the age-associated increase in systolic blood pressure in white Americans: Results from the third National Health and Nutrition Examination Survey. Am J Clin Nutr. 2008;87:136–41.
    1. Martins D, Wolf M, Pan D, Zadshir A, Tareen N, Thadhani R, et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: Data from the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2007;167:1159–65.
    1. Hintzpeter B, Mensink GB, Thierfelder W, Muller MJ, Scheidt-Nave C. Vitamin D status and health correlates among German adults. Eur J Clin Nutr. 2008;62:1079–89.
    1. Hypponen E, Boucher BJ, Berry DJ, Power C. 25-hydroxyvitamin D, IGF-1, and metabolic syndrome at 45 years of age: A cross-sectional study in the 1958 British Birth Cohort. Diabetes. 2008;57:298–305.
    1. Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, et al. Hypovitaminosis D in medical inpatients. N Engl J Med. 1998;338:777–83.
    1. Kokot F, Pietrek J, Srokowska S, Wartenberg W, Kuska J, Jedrychowska M, et al. 25-hydroxyvitamin D in patients with essential hypertension. Clin Nephrol. 1981;16:188–92.
    1. Forouhi NG, Luan J, Cooper A, Boucher BJ, Wareham NJ. Baseline serum 25-hydroxyvitamin D is predictive of future glycemic status and insulin resistance: The Medical Research Council Ely Prospective study 1990-2000. Diabetes. 2008;57:2619–25.
    1. Duprez D, de Buyzere M, de Backer T, Clement D. Relationship between vitamin D3 and the peripheral circulation in moderate arterial primary hypertension. Blood Prees Monit. 1994;3:389–93.
    1. Smotkin-Tangorra M, Purushothaman R, Gupta A, Nejati G, Anhalt H, Ten S. Prevalence of vitamin D insufficiency in obese children and adolescents. J Pediatr Endocrinol Metab. 2007;20:817–23.
    1. Gannagé-Yared MH, Chedid R, Khalife S, Azzi E, Zoghbi F, Halaby G. Vitamin D in relation to metabolic risk factors, insulin sensitivity and adiponectin in a young Middle-Eastern population. Eur J Endocrinol. 2009;160:965–71.
    1. Pilz S, Tomaschitz A, Ritz E, Pieber TR. Vitamin D status and arterial hypertension: A systematic review. Nat Rev Cardiol. 2009;6:621–30.
    1. Kulah E, Dursun A, Aktunc E, Acikgoz S, Aydin M, Can M, et al. Effects of angiotensin-converting enzyme gene polymorphism and serum vitamin D levels on ambulatory blood pressure measurement and left ventricular mass in Turkish hypertensive population. Blood Press Monit. 2007;12:207–13.
    1. Landin-Wilhelmsen K, Wilhelmsen L, Wilske J, Lappas G, Rosén T, Lindstedt G, et al. Sunlight increases serum 25(OH) vitamin D concentration whereas 1,25(OH)2D3 is unaffected. Results from a general population study in Goteborg, Sweden (the WHO MONICA project) Eur J Clin Nutr. 1995;49:400–7.
    1. Kumaravel R, de las Heras J, Chen TC. Vitamin D Status, Adiposity, and Lipids in Black American and Caucasian Children. J Clin Endocrinol Metab. 2011;96:1560–7.
    1. Mason C, Xiao L, Imayama I, Duggan CR, Bain C, Foster-Schubert KE, et al. Effects of weight loss on serum vitamin D in postmenopausal women. Am J Clin Nutr. 2011;94:95–103.
    1. Pittas AG, Harris SS, Stark PC, Dawson-Hughes B. The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care. 2007;30:980–6.
    1. Jorde R, Sneve M, Figenschau Y, Svartberg J, Waterloo K. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: Randomized double blind trial. J Intern Med. 2008;264:599–609.
    1. Llewellyn DJ, Lang IA, Langa KM, Muniz-Terrera G, Phillips CL, Cherubini A, et al. Vitamin D and risk of cognitive decline in elderly persons. Arch Intern Med. 2010;170:1135–41.
    1. Knekt P, Kilkkinen A, Rissanen H, Marniemi J, Sääksjärvi K, Heliövaara M. Serum vitamin D and the risk of Parkinson disease. Arch Neurol. 2010;67:808–11.
    1. Liebman B. From sun and sea: New study puts vitamin D and omega-3s to the test. Nutrition Action Healthletter. 2009 Nov 3-7;
    1. Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav EJ, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: A meta-analysis of randomized controlled trials. Arch Intern Med. 2009;169:551–61.
    1. Christine G. Vitamin D Supplementation: An Update. US Pharm. 2010;35:58–76.
    1. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006;296:2832–8.
    1. Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: A birth-cohort study. Lancet. 2001;358:1500–3.
    1. Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr. 2010;91:1255–60.
    1. Hensel KJ, Randis TM, Gelber SE, Ratner AJ. Pregnancy-specific association of vitamin D deficiency and bacterial vaginosis. Am J Obstet Gynecol. 2011;204(41):e1–9.
    1. Badalian SS, Rosenbaum PF. Vitamin D and pelvic floor disorders in women: Results from the National Health and Nutrition Examination Survey. Obstet Gynecol. 2010;115:795–803.
    1. Millen AE, Voland R, Sondel SA, Parekh N, Horst RL, Wallace RB, et al. Vitamin D Status and Early Age-Related Macular Degeneration in Postmenopausal Women. Arch Ophthalmol. 2011;129:481–9.
    1. Holick MF, Binkley NC, Heike A, Bischoff-Ferrari, Gordon CM, Hanley DA, et al. Evaluation, Treatment, and Prevention of Vitamin D Deficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96:1911–30.
    1. Murayama E, Miyamoto K, Kubodera N, Mori T, Matsunaga I. Synthetic studies of vitamin D3 analogues. VIII. Synthesis of 22-oxavitamin D analogues. Chem Pharm Bull. 1986;34:4410–3.
    1. Brown AJ, Slatopolsky E. Vitamin D analogs: Therapeutic applications and mechanisms for selectivity. Mol Aspects Med. 2008;29:433–52.
    1. Sjoden G, Smith C, Lindgren U, DeLuca HF. 1a-Hydroxyvitamin D2 is less toxic than 1a-hydroxyvitamin D3 in the rat. Proc Soc Exp Biol Med. 1985;178:432–6.
    1. Imanishi Y, Inaba M, Seki H, Koyama H, Nishizawa Y, Morii H, et al. Increased biological potency of hexafluorinated analogs of 1,25-dihydroxyvitamin D3 on bovine parathyroid cells. J Steroid Biochem Mol Biol. 1999;70:243–8.

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