European Journal of Dermatology

, Volume 24, Issue 4, pp 428–434 | Cite as

Review: Higher vitamin D status and supplementation may be associated with risks

  • Kaveri KorgavkarEmail author
  • Michael Xiong
  • Martin A. Weinstock
Review Article


The prevalence of low vitamin D levels and associated risks has led to an increase in supplementation. However, a “U-shaped” relationship has been suggested between vitamin D status and adverse effects, with risks observed both in low and high levels. While risks associated with low levels of vitamin D have been extensively studied, the risks of higher levels of vitamin D have not been as widely circulated. We sought to describe key observed adverse risks with vitamin D supplementation and higher serum 25(OH)-D levels in healthy adult populations.

Key words

epidemiology vitamin D 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gilchrest BA. Sun protection and Vitamin D: three dimensions of obfuscation. J Steroid Biochem Mol Biol 2007; 103: 655–63.PubMedCrossRefGoogle Scholar
  2. 2.
    Looker AC, Pfeiffer CM, Lacher DA, Schleicher RL, Picciano MF, Yetley EA. Serum 25-hydroxyvitamin D status of the US population: 1988–1994 compared with 2000–2004. Am J Clin Nutr 2008; 88: 1519–27.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Gambichler T, Bindsteiner M, Hoxtermann S. Kreuter A. Serum 25-hydroxyvitamin D serum levels in a large German cohort of patients with melanoma. Br J Dermatol 2013; 168: 625–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Orgaz-Molina J, Magro-Checa C, Arrabal-Polo MA, et al. Association of 25-hydroxyvitamin D with Metabolic Syndrome in Patients with Psoriasis: A Case-control Study. Acta Derm Venereol 2013. doi:  10.2340/00015555-1642 (In press).Google Scholar
  5. 5.
    Orgaz-Molina J, Buendia-Eisman A, Arrabal-Polo MA, Ruiz JC, Arias-Santiago S. Deficiency of serum concentration of 25-hydroxyvitamin D in psoriatic patients: a case-control study. J Am Ac Dermatol 2012; 67: 931–8.CrossRefGoogle Scholar
  6. 6.
    Gahche J, Bailey R, Burt V, et al. Dietary supplement use among U.S. adults has increased since NHANES III (1988–1994). NCHS Data Brief 2011; 61: 1–8.PubMedGoogle Scholar
  7. 7.
    Bailey RL, Dodd KW, Goldman JA, et al. Estimation of total usual calcium and vitamin D intakes in the United States. J Nutr 2010; 140: 817–22.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metabol 2011; 96: 53–8.CrossRefGoogle Scholar
  9. 9.
    Institute of Medicine Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC.: The National Academies Press; 2011.Google Scholar
  10. 10.
    Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr 2007; 85: 6–18.PubMedGoogle Scholar
  11. 11.
    Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. New Engl J Med 2006; 354: 669–83.PubMedCrossRefGoogle Scholar
  12. 12.
    Anaizi N. Rediscovering vitamin D. Libyan J Med 2010: 5.Google Scholar
  13. 13.
    Schottker B, Haug U, Schomburg L, et al. Strong associations of 25-hydroxyvitamin D concentrations with all-cause, cardiovascular, cancer, and respiratory disease mortality in a large cohort study. Am J Clin Nutr 2013; 97: 782–93.PubMedCrossRefGoogle Scholar
  14. 14.
    Scragg R. Vitamin D and public health: an overview of recent research on common diseases and mortality in adulthood. Public Health Nutr 2011; 14: 1515–32.PubMedCrossRefGoogle Scholar
  15. 15.
    Melamed ML, Michos ED, Post W, Astor B. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Int Med 2008; 168: 1629–37.CrossRefGoogle Scholar
  16. 16.
    Visser M, Deeg DJ, Puts MT, Seidell JC, Lips P. Low serum concentrations of 25-hydroxyvitamin D in older persons and the risk of nursing home admission. Am J Clin Nutr 2006; 84: 616–22 (quiz 71-2).PubMedGoogle Scholar
  17. 17.
    Jia X, Aucott LS, McNeill G. Nutritional status and subsequent allcause mortality in men and women aged 75 years or over living in the community. Br J Nutr 2007; 98: 593–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Michaelsson K, Baron JA, Snellman G, et al. Plasma vitamin D and mortality in older men: a community-based prospective cohort study. Am J Clin Nutr 2010; 92: 841–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Sempos CT, Durazo-Arvizu RA, Dawson-Hughes B, et al. Is there a Reverse J-shaped Association between 25-Hydroxyvitamin D and All-Cause Mortality? Results from the US Nationally Representative NHANES. J Clin Endocrinol Metabol 2013: 973001–9.Google Scholar
  20. 20.
    Dror Y, Giveon SM, Hoshen M, Feldhamer I, Balicer RD, Feldman BS. Vitamin d levels for preventing acute coronary syndrome and mortality: evidence of a nonlinear association. J Clin Endocrinol Metabol 2013; 98: 2160–7.CrossRefGoogle Scholar
  21. 21.
    Durup D, Jorgensen HL, Christensen J, Schwarz P, Heegaard AM, Lind B. A reverse J-shaped association of all-cause mortality with serum 25-hydroxyvitamin D in general practice: the CopD study. J Clin Endocrinol Metabol 2012; 97: 2644–52.CrossRefGoogle Scholar
  22. 22.
    Langsetmo L, Berger C, Kreiger N, et al. Calcium and Vitamin D Intake and Mortality: Results from the Canadian Multicentre Osteoporosis Study (CaMos). J Clin Endocrinol Metabol 2013; 98: 3010–8.CrossRefGoogle Scholar
  23. 23.
    Krause R, Schober-Halstenberg HJ, Edenharter G, Haas K, Roth HJ, Frei U. Vitamin D status and mortality of German hemodialysis patients. Anticancer Res 2012; 32: 391–5.PubMedGoogle Scholar
  24. 24.
    Cawthon PM, Parimi N, Barrett-Connor E, et al. Serum 25-hydroxyvitamin D, parathyroid hormone, and mortality in older men. J Clin Endocrinol Metabol 2010; 95: 4625–34.CrossRefGoogle Scholar
  25. 25.
    Freedman DM, Looker AC, Abnet CC, Linet MS, Graubard BI. Serum 25-hydroxyvitamin D and cancer mortality in the NHANES III study (1988–2006). Cancer Res 2010; 70: 8587–97.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Pilz S, Kienreich K, Tomaschitz A, et al. Vitamin d and cancer mortality: systematic review of prospective epidemiological studies. Anticancer Agents Med Chem 2013; 13: 107–17.PubMedCrossRefGoogle Scholar
  27. 27.
    Klein EA, Thompson IM Jr., Tangen CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA: J Am Medical Assoc 2011; 306: 1549–56.CrossRefGoogle Scholar
  28. 28.
    Albanes D, Heinonen OP, Huttunen JK, et al. Effects of alphatocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. Am J Clin Nutr 1995; 62: 1427S–30S.PubMedGoogle Scholar
  29. 29.
    Giovannucci E, Liu Y, Rimm EB, et al. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Nat Cancer Inst 2006; 98: 451–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Ordonez Mena JM, Schottker B, Haug U, et al. Serum 25-hydroxyvitamin D and cancer risk in older adults. Results from a large German prospective cohort study. Cancer Epidemiol Biomarkers Prev 2013; 22: 905–16.PubMedCrossRefGoogle Scholar
  31. 31.
    Giovannucci E, Liu Y, Willett WC. Cancer incidence and mortality and vitamin D in black and white male health professionals. Cancer Epidemiol, biomarkers & prevention 2006; 15: 2467–72.CrossRefGoogle Scholar
  32. 32.
    Skinner HG, Michaud DS, Giovannucci E, Willett WC, Colditz GA, Fuchs CS. Vitamin D intake and the risk for pancreatic cancer in two cohort studies. Cancer Epidemiol Biomarkers Prev 2006; 15: 1688–95.PubMedCrossRefGoogle Scholar
  33. 33.
    Wolpin BM, Ng K, Bao Y, et al. Plasma 25-hydroxyvitamin D and risk of pancreatic cancer. Cancer Epidemiol Biomarkers Prev 2012; 21: 82–91.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Stolzenberg-Solomon RZ, Jacobs EJ, Arslan AA, et al. Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol 2010; 172: 81–93.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Stolzenberg-Solomon RZ, Vieth R, Azad A, 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.PubMedCrossRefGoogle Scholar
  36. 36.
    Weinstein SJ, Stolzenberg-Solomon RZ, Kopp W, Rager H, Virtamo J, Albanes D. Impact of circulating vitamin D binding protein levels on the association between 25-hydroxyvitamin D and pancreatic cancer risk: a nested case-control study. Cancer Res 2012; 72: 1190–8.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Helzlsouer KJ, Gallicchio L. Shedding light on serum vitamin d concentrations and the risk of rarer cancers. Anticancer Agents Med Chem 2013; 13: 65–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Tuohimaa P, Tenkanen L, Ahonen M, et al. Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries. Int J Cancer 2004; 108: 104–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Brandstedt J, Almquist M, Manjer J, Malm J, Vitamin D. PTH, and calcium and the risk of prostate cancer: a prospective nested casecontrol study. Cancer Causes Control: CCC 2012; 23: 1377–85.PubMedCrossRefGoogle Scholar
  40. 40.
    Meyer HE, Robsahm TE, Bjorge T, Brustad M, Blomhoff R. Vitamin D, season, and risk of prostate cancer: a nested case-control study within Norwegian health studies. Am J Clin Nutr 2013; 97: 147–54.PubMedCrossRefGoogle Scholar
  41. 41.
    Albanes D, Mondul AM, Yu K, et al. Serum 25-hydroxy vitamin D and prostate cancer risk in a large nested case-control study. Cancer Epidemiol Biomarkers Prev 2011; 20: 1850–60.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Gandini S, Boniol M, Haukka J, et al. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer 2011; 128: 1414–24.PubMedCrossRefGoogle Scholar
  43. 43.
    van der Pols JC, Russell A, Bauer U, Neale RE, Kimlin MG, Green AC. Vitamin d status and skin cancer risk independent of time outdoors: 11-year prospective study in an Australian community. J Invest Dermatol 2013; 133: 637–41.PubMedCrossRefGoogle Scholar
  44. 44.
    Afzal S, Nordestgaard BG, Bojesen SE. Plasma 25-hydroxyvitamin d and risk of non-melanoma and melanoma skin cancer: a prospective cohort study. J Invest Dermatol 2013; 133: 629–36.PubMedCrossRefGoogle Scholar
  45. 45.
    Liang G, Nan H, Qureshi AA, Han J. Pre-diagnostic plasma 25-hydroxyvitamin D levels and risk of non-melanoma skin cancer in women. PloS one 2012; 7: e35211.CrossRefGoogle Scholar
  46. 46.
    Asgari MM, Tang J,Warton ME, et al. Association of prediagnostic serum vitamin D levels with the development of basal cell carcinoma. J Invest Dermatol 2010; 130: 1438–43.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Asgari MM, Maruti SS, Kushi LH, White E. A cohort study of vitamin D intake and melanoma risk. J Invest Dermatol 2009; 129: 1675–80.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Tang JY, Fu T, Leblanc E, et al. Calcium plus vitamin D supplementation and the risk of nonmelanoma and melanoma skin cancer: post hoc analyses of the women’s health initiative randomized controlled trial. J Clin Oncol 2011; 29: 3078–84.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Reddy KK. Vitamin d level and Basal cell carcinoma, squamous cell carcinoma, and melanoma risk. J Invest Dermatol 2013; 133: 589–92.PubMedCrossRefGoogle Scholar
  50. 50.
    Brondum-Jacobsen P, Benn M, Jensen GB, Nordestgaard BG. 25-hydroxyvitamin d levels and risk of ischemic heart disease, myocardial infarction, and early death: population-based study and meta-analyses of 18 and 17 studies. Arterioscler Thromb Vasc Biol 2012; 32: 2794–802.PubMedCrossRefGoogle Scholar
  51. 51.
    Wang TJ, Pencina MJ, Booth SL, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008; 117: 503–11.PubMedCrossRefGoogle Scholar
  52. 52.
    Linden V. Vitamin D and myocardial infarction. Br Med J 1974; 3: 647–50.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Alele JD, Luttrell LM, Hollis BW, Luttrell DK, Hunt KJ. Relationship between vitamin D status and incidence of vascular events in the Veterans Affairs Diabetes Trial. Atherosclerosis 2013; 228: 502–7.PubMedCrossRefGoogle Scholar
  54. 54.
    Rajasree S, Rajpal K, Kartha CC, et al. Serum 25-hydroxyvitamin D3 levels are elevated in South Indian patients with ischemic heart disease. Eur J Epidemiol 2001; 17: 567–71.PubMedCrossRefGoogle Scholar
  55. 55.
    Smith M. Vitamin D Excess Is Significantly Associated with Risk of Atrial Fibrillation. In: American Heart Association Meeting; 2011, 2011.Google Scholar
  56. 56.
    Freedman BI, Wagenknecht LE, Hairston KG, et al. Vitamin d, adiposity, and calcified atherosclerotic plaque in african-americans. J Clin Endocrinol Metabol 2010; 95: 1076–83.CrossRefGoogle Scholar
  57. 57.
    Shroff R, Egerton M, Bridel M, et al. A bimodal association of vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol 2008; 19: 1239–46.PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Wang H, Xia N, Yang Y, Peng DQ. Influence of vitamin D supplementation on plasma lipid profiles: a meta-analysis of randomized controlled trials. Lipids Health Dis 2012; 11: 42.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Heikkinen AM, Tuppurainen MT, Niskanen L, Komulainen M, Penttila I, Saarikoski S. Long-term vitamin D3 supplementation may have adverse effects on serum lipids during postmenopausal hormone replacement therapy. Eur J Endocrin 1997; 137: 495–502.CrossRefGoogle Scholar
  60. 60.
    Tuppurainen M, Heikkinen AM, Penttila I, Saarikoski S. Does vitamin D3 have negative effects on serum levels of lipids? A follow-up study with a sequential combination of estradiol valerate and cyproterone acetate and/or vitamin D3. Maturitas 1995; 22: 55–61.PubMedCrossRefGoogle Scholar
  61. 61.
    Jorde R, Strand Hutchinson M, Kjaergaard M, Sneve M, Grimnes G. Supplementation with High Doses of Vitamin D to Subjects without Vitamin D Deficiency May Have Negative Effects: Pooled Data from Four Intervention Trials in Tromso. ISRN Endocrin 2013; 2013: 348705.CrossRefGoogle Scholar
  62. 62.
    Sanders KM, Stuart AL, Williamson EJ, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA 2010; 303: 1815–22.PubMedCrossRefGoogle Scholar
  63. 63.
    Smith H, Anderson F, Raphael H, Maslin P, Crozier S, Cooper C. Effect of annual intramuscular vitamin D on fracture risk in elderly men and women-a population-based, randomized, double-blind, placebocontrolled trial. Rheumatology 2007; 46: 1852–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Minisola S, Colangelo L, Cilli M, Cipriani C, Pepe J, Romagnoli E. Intermittent high doses of vitamin d: a need for further studies? Calcif Tissue Int 2013; 92: 487–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Sanders KM, Nicholson GC, Ebeling PR. Is high-dose vitamin d harmful? Authors’ reply. Calcif Tissue Int 2013; 92: 491–2.PubMedCrossRefGoogle Scholar
  66. 66.
    Sanders KM, Nicholson GC, Ebeling PR. Is high dose vitamin D harmful? Calcif Tissue Int 2013; 92: 191–206.PubMedCrossRefGoogle Scholar
  67. 67.
    Eisner BH, Thavaseelan S, Sheth S, Haleblian G, Pareek G. Relationship between serum vitamin D and 24-hour urine calcium in patients with nephrolithiasis. Urology 2012; 80: 1007–10.PubMedCrossRefGoogle Scholar
  68. 68.
    Netelenbos JC, Jongen MJ, van der Vijgh WJ, Lips P, van Ginkel FC. Vitamin D status in urinary calcium stone formation. Arch Int Med 1985; 145: 681–4.CrossRefGoogle Scholar
  69. 69.
    Fallahzadeh MH, Zare J, Al-Hashemi GH, et al. Elevated serum levels of Vitamin D in infants with urolithiasis. Iranian J Kidney Dis 2012; 6: 186–91.Google Scholar
  70. 70.
    Tang J, McFann KK, Chonchol MB. Association between serum 25-hydroxyvitamin D and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988-94. Nephrol Dialysis Transplant 2012; 27: 4385–9.CrossRefGoogle Scholar
  71. 71.
    Xu L, Wan X, Huang Z, et al. Impact of vitamin d on chronic kidney diseases in non-dialysis patients: a meta-analysis of randomized controlled trials. PloS one 2013; 8: e61387.CrossRefGoogle Scholar
  72. 72.
    Cranney A, Horsley T, O’Donnell S, et al. Effectiveness and safety of vitamin D in relation to bone health. Evid Rep Technol Assess (Full Rep) 2007: 1–235.Google Scholar
  73. 73.
    Keet CA, McCormack MC, Peng RD, Matsui EC. Age- and atopydependent effects of vitamin D on wheeze and asthma. J Allergy Clin Immunol 2011; 128: 414–6, e5.PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    Mai XM, Langhammer A, Camargo CA Jr., Chen Y. Serum 25-hydroxyvitamin D levels and incident asthma in adults: the HUNT Study. Am J Epidemiol 2012; 176: 1169–76.PubMedCrossRefGoogle Scholar
  75. 75.
    Hypponen E, Sovio U, Wjst M, et al. Infant vitamin d supplementation and allergic conditions in adulthood: northern Finland birth cohort 1966. Ann New York Acad Sci 2004; 1037: 84–95.CrossRefGoogle Scholar
  76. 76.
    Back O, Blomquist HK, Hernell O, Stenberg B. Does vitamin D intake during infancy promote the development of atopic allergy? Acta Derm Venereol 2009; 89: 28–32.PubMedCrossRefGoogle Scholar
  77. 77.
    Hollams EM, Hart PH, Holt BJ, et al. Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study. Eur Resp J 2011; 38: 1320–7.CrossRefGoogle Scholar
  78. 78.
    Gale CR, Robinson SM, Harvey NC, et al. Maternal vitamin D status during pregnancy and child outcomes. Eur J Clin Nutr 2008; 62: 68–77.PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Pike KC, Inskip HM, Robinson S, et al. Maternal late-pregnancy serum 25-hydroxyvitamin D in relation to childhood wheeze and atopic outcomes. Thorax 2012; 67: 950–6.PubMedCentralPubMedCrossRefGoogle Scholar
  80. 80.
    Miyake Y, Sasaki S, Tanaka K, Hirota Y. Dairy food, calcium and vitamin D intake in pregnancy, and wheeze and eczema in infants. Eur Resp J 2010; 35: 1228–34.CrossRefGoogle Scholar
  81. 81.
    Selby PL, Davies M, Marks JS, Mawer EB. Vitamin D intoxication causes hypercalcaemia by increased bone resorption which responds to pamidronate. Clin Endocrin 1995; 43: 531–6.CrossRefGoogle Scholar
  82. 82.
    Sage RJ, Rao DS, Burke RR, Lim HW. Preventing vitamin D toxicity in patients with sarcoidosis. J Am Ac Dermatol 2011; 64: 795–6.CrossRefGoogle Scholar
  83. 83.
    Brannon PM, Yetley EA, Bailey RL, Picciano MF. Overview of the conference “Vitamin D and Health in the 21st Century: an Update”. Am J Clin Nutr 2008; 88: 483S–90S.PubMedGoogle Scholar
  84. 84.
    Weinstock MA, Moses AM. Skin cancer meets vitamin D: the way forward for dermatology and public health. J Am Ac Dermatol 2009; 61: 720–4.CrossRefGoogle Scholar

Copyright information

© John Libbey Eurotext 2014

Authors and Affiliations

  • Kaveri Korgavkar
    • 1
    • 2
    Email author
  • Michael Xiong
    • 1
    • 2
  • Martin A. Weinstock
    • 1
    • 2
    • 3
    • 4
  1. 1.Dermatoepidemiology UnitVA Medical Center514, ProvidenceUSA
  2. 2.Department of DermatologyAlpert Medical School of Brown UniversityProvidenceUSA
  3. 3.Department of EpidemiologyAlpert Medical School of Brown UniversityProvidenceUSA
  4. 4.Department of DermatologyRhode Island HospitalProvidenceUSA

Personalised recommendations