The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention

Vitamin D deficiency and insufficiency is a global health issue that afflicts more than one billion children and adults worldwide. The consequences of vitamin D deficiency cannot be under estimated. There has been an association of vitamin D deficiency with a myriad of acute and chronic illnesses including preeclampsia, childhood dental caries, periodontitis, autoimmune disorders, infectious diseases, cardiovascular disease, deadly cancers, type 2 diabetes and neurological disorders. This review is to put into perspective the controversy surrounding the definition for vitamin D deficiency and insufficiency as well as providing guidance for how to treat and prevent vitamin D deficiency.

[1]  M. Cogswell,et al.  Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. , 2002, The American journal of clinical nutrition.

[2]  M. Holick,et al.  Size of the exposed body surface area, skin erythema and body mass index predict skin production of vitamin D. , 2015, Journal of photochemistry and photobiology. B, Biology.

[3]  R. McKenzie,et al.  Europe’s darker atmosphere in the UV-B , 2008, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[4]  A. Kashyap,et al.  Case 3-2009: a 9-month-old boy with seizures. , 2009, The New England journal of medicine.

[5]  I. Holm,et al.  Hypervitaminosis D associated with drinking milk. , 1992, The New England journal of medicine.

[6]  C. Barth,et al.  Atmospheric scattering of the solar flux in the middle ultraviolet. , 1967, Applied optics.

[7]  T. Key,et al.  Plasma concentrations of 25-hydroxyvitamin D in meat eaters, fish eaters, vegetarians and vegans: results from the EPIC–Oxford study , 2010, Public Health Nutrition.

[8]  G. Amadi Maternal Versus Infant Vitamin D Supplementation During Lactation: A Randomized Controlled Trial , 2018 .

[9]  J. Devogelaer,et al.  Urban tropospheric ozone increases the prevalence of vitamin D deficiency among Belgian postmenopausal women with outdoor activities during summer. , 2008, The Journal of clinical endocrinology and metabolism.

[10]  A. Webb,et al.  Concurrent beneficial (vitamin D production) and hazardous (cutaneous DNA damage) impact of repeated low‐level summer sunlight exposures† , 2016, The British journal of dermatology.

[11]  N. Shah,et al.  High prevalence of hypovitaminosis D in young healthy adults from the western part of India , 2011, Postgraduate Medical Journal.

[12]  Stefan Pilz,et al.  Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence. , 2013, Autoimmunity reviews.

[13]  M. Holick,et al.  Sunscreens suppress cutaneous vitamin D3 synthesis. , 1987, The Journal of clinical endocrinology and metabolism.

[14]  P. Delmas,et al.  Healthy elderly French women living at home have secondary hyperparathyroidism and high bone turnover in winter. EPIDOS Study Group. , 1996, The Journal of clinical endocrinology and metabolism.

[15]  I. Kema,et al.  Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l , 2012, British Journal of Nutrition.

[16]  M. Holick Vitamin D Is Not as Toxic as Was Once Thought: A Historical and an Up-to-Date Perspective. , 2015, Mayo Clinic proceedings.

[17]  P. Vestergaard,et al.  Vitamin D status and its adequacy in healthy Danish perimenopausal women: relationships to dietary intake, sun exposure and serum parathyroid hormone , 2001, British Journal of Nutrition.

[18]  C. Gordon,et al.  Treatment of hypovitaminosis D in infants and toddlers. , 2008, The Journal of clinical endocrinology and metabolism.

[19]  M. Holick,et al.  Biological Effects of Sunlight, Ultraviolet Radiation, Visible Light, Infrared Radiation and Vitamin D for Health. , 2016, Anticancer research.

[20]  J. Adams,et al.  INCREASED SKIN PIGMENT REDUCES THE CAPACITY OF SKIN TO SYNTHESISE VITAMIN D3 , 1982, The Lancet.

[21]  R. Vieth,et al.  Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. , 1999, The American journal of clinical nutrition.

[22]  T. Travison,et al.  Treatment with 50,000 IU vitamin D₂ every other week and effect on serum 25-hydroxyvitamin D₂, 25-hydroxyvitamin D₃, and total 25-hydroxyvitamin D in a clinical setting. , 2012, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[23]  M. Holick Vitamin D deficiency. , 2007, The New England journal of medicine.

[24]  C. Gordon,et al.  Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. , 2011, The Journal of clinical endocrinology and metabolism.

[25]  Michael F. Holick,et al.  Case 3-2009 , 2009 .

[26]  Recommendations Abstracted from the American Geriatrics Society Consensus Statement on Vitamin D for Prevention of Falls and Their Consequences , 2014, Journal of the American Geriatrics Society.

[27]  J. Shao,et al.  High prevalence of vitamin D deficiency among children aged 1 month to 16 years in Hangzhou, China , 2012, BMC Public Health.

[28]  M. Holick,et al.  Decreased bioavailability of vitamin D in obesity. , 2000, The American journal of clinical nutrition.

[29]  M. Holick,et al.  Photobiology of vitamin D in mushrooms and its bioavailability in humans , 2013, Dermato-endocrinology.

[30]  C. Wagner,et al.  Vitamin D supplementation during pregnancy: Double‐blind, randomized clinical trial of safety and effectiveness , 2011, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[31]  M. Holick,et al.  Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. , 2005, The Journal of clinical endocrinology and metabolism.

[32]  Min‐ge Xie,et al.  Temporal Relationship between Vitamin D Status and Parathyroid Hormone in the United States , 2015, PloS one.

[33]  J. Richards,et al.  25-Hydroxyvitamin D in Canadian adults: biological, environmental, and behavioral correlates , 2011, Osteoporosis International.

[34]  R. Vieth CHAPTER 61 – The Pharmacology of Vitamin D, Including Fortification Strategies , 2005 .

[35]  T. Chen,et al.  Vitamin D intoxication associated with an over-the-counter supplement. , 2001, The New England journal of medicine.

[36]  C. Sempos,et al.  Vitamin D status: United States, 2001-2006. , 2011, NCHS data brief.

[37]  K. Nielsen,et al.  Avoidance of sun exposure as a risk factor for major causes of death: a competing risk analysis of the Melanoma in Southern Sweden cohort , 2016, Journal of internal medicine.

[38]  M. Holick,et al.  Treatment of vitamin D deficiency with UV light in patients with malabsorption syndromes: a case series , 2007, Photodermatology, photoimmunology & photomedicine.

[39]  M. Holick,et al.  The effect of ultraviolet radiation from a novel portable fluorescent lamp on serum 25‐hydroxyvitamin D3 levels in healthy adults with Fitzpatrick skin types II and III , 2012, Photodermatology, photoimmunology & photomedicine.

[40]  Prevalence of Vitamin D Inadequacy among Postmenopausal North American Women Receiving Osteoporosis Therapy , 2005 .

[41]  C. Apovian,et al.  Serum 25‐hydroxyvitamin D levels and metabolic health status in extremely obese individuals , 2014, Obesity.

[42]  J. Moan,et al.  At what time should one go out in the sun? , 2008, Advances in experimental medicine and biology.

[43]  B. Hollis,et al.  Vitamin D2 is much less effective than vitamin D3 in humans. , 2004, The Journal of clinical endocrinology and metabolism.

[44]  R. Heaney,et al.  All-source basal vitamin D inputs are greater than previously thought and cutaneous inputs are smaller. , 2013, The Journal of nutrition.

[45]  M. Holick,et al.  Vitamin D2 treatment for vitamin D deficiency and insufficiency for up to 6 years. , 2009, Archives of internal medicine.

[46]  B. Clarke,et al.  Bone Mineralization Defects and Vitamin D Deficiency: Histomorphometric Analysis of Iliac Crest Bone Biopsies and Circulating 25-Hydroxyvitamin D in 675 Patients , 2010 .

[47]  V. Ganji,et al.  Serum 25-hydroxyvitamin D concentrations and prevalence estimates of hypovitaminosis D in the U.S. population based on assay-adjusted data. , 2012, The Journal of nutrition.

[48]  R. Vieth,et al.  Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. , 1998, The American journal of clinical nutrition.

[49]  T. Chen,et al.  Treatment of vitamin D deficiency due to Crohn's disease with tanning bed ultraviolet B radiation. , 2001, Gastroenterology.

[50]  J. Moan,et al.  Addressing the health benefits and risks, involving vitamin D or skin cancer, of increased sun exposure , 2008, Proceedings of the National Academy of Sciences.

[51]  M. Ferrari,et al.  Vitamin D status among adolescents in Europe: the Healthy Lifestyle in Europe by Nutrition in Adolescence study , 2011, British Journal of Nutrition.

[52]  M. Holick,et al.  Fortification of orange juice with vitamin D(2) or vitamin D(3) is as effective as an oral supplement in maintaining vitamin D status in adults. , 2010, The American journal of clinical nutrition.

[53]  Looker Ac,et al.  Hypovitaminosis D in medical inpatients. , 1998 .

[54]  M. Holick,et al.  Can you have your cake and eat it too? The sunlight D‐lema , 2016, The British journal of dermatology.

[55]  M. Holick,et al.  Chronic sunscreen use decreases circulating concentrations of 25-hydroxyvitamin D. A preliminary study. , 1988, Archives of dermatology.

[56]  R. Recker,et al.  Vitamin D(3) is more potent than vitamin D(2) in humans. , 2011, The Journal of clinical endocrinology and metabolism.

[57]  A. Litonjua,et al.  Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. , 2007, The American journal of clinical nutrition.

[58]  J. Pettifor,et al.  Pediatric vitamin D and calcium nutrition in developing countries , 2008, Reviews in Endocrine and Metabolic Disorders.

[59]  S. Mallya,et al.  Differential Responses to Vitamin D2 and Vitamin D3 Are Associated With Variations in Free 25-Hydroxyvitamin D. , 2016, Endocrinology.

[60]  J. Shaw,et al.  Prevalence of vitamin D deficiency and its determinants in Australian adults aged 25 years and older: a national, population‐based study , 2012, Clinical endocrinology.

[61]  Sahana K.R,et al.  Sunlight and vitamin D; A global perspective for health. , 2019 .

[62]  H. Bauchner,et al.  Association between vitamin D deficiency and primary cesarean section. , 2009, The Journal of clinical endocrinology and metabolism.

[63]  Sudhaker D. Rao,et al.  Effects of age and serum 25-OH-vitamin D on serum parathyroid hormone levels. , 2012, The Journal of clinical endocrinology and metabolism.

[64]  Christine L. Taylor,et al.  IOM committee members respond to Endocrine Society vitamin D guideline. , 2012, The Journal of clinical endocrinology and metabolism.

[65]  R. Vieth,et al.  Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial. , 2006, The Journal of clinical endocrinology and metabolism.

[66]  M. Holick,et al.  Sunlight and Vitamin D: Necessary for Public Health , 2015, Journal of the American College of Nutrition.

[67]  J. Bouwes Bavinck,et al.  The influence of painful sunburns and lifetime sun exposure on the risk of actinic keratoses, seborrheic warts, melanocytic nevi, atypical nevi, and skin cancer. , 2003, The Journal of investigative dermatology.

[68]  E. Horton,et al.  Vitamin D in the Persian Gulf: Integrative Physiology and Socioeconomic Factors , 2011, Current osteoporosis reports.

[69]  T. Travison,et al.  Serum concentrations of 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 in response to vitamin D2 and vitamin D3 supplementation. , 2013, The Journal of clinical endocrinology and metabolism.

[70]  H. Bauchner,et al.  Widespread Vitamin D Deficiency in Urban Massachusetts Newborns and Their Mothers , 2010, Pediatrics.

[71]  B. Astor,et al.  25-Hydroxyvitamin D Levels and the Risk of Mortality in the General Population , 2008 .

[72]  D. Naughton,et al.  Vitamin D in health and disease: Current perspectives , 2010, Nutrition journal.

[73]  R. Brodell,et al.  Obesity as a risk factor for malignant melanoma and non-melanoma skin cancer , 2016, Reviews in Endocrine and Metabolic Disorders.

[74]  M. Holick,et al.  Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe - recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency. , 2013, Endokrynologia Polska.

[75]  M. Holick,et al.  Vitamin D Deficiency in a Healthy Group of Mothers and Newborn Infants , 2007, Clinical pediatrics.

[76]  M. Holick,et al.  Vitamin D for health: a global perspective. , 2013, Mayo Clinic proceedings.

[77]  M. Holick,et al.  Vitamin D intoxication with severe hypercalcemia due to manufacturing and labeling errors of two dietary supplements made in the United States. , 2011, The Journal of clinical endocrinology and metabolism.

[78]  M. Seijo,et al.  Vitamin D3 seems more appropriate than D2 to sustain adequate levels of 25OHD: a pharmacokinetic approach , 2015, European Journal of Clinical Nutrition.

[79]  S. Hailpern,et al.  Prevalence and Associations of 25-Hydroxyvitamin D Deficiency in US Children: NHANES 2001–2004 , 2009, Pediatrics.

[80]  E. Goodman,et al.  Vitamin D deficiency, adiposity, and cardiometabolic risk in urban schoolchildren. , 2011, The Journal of pediatrics.

[81]  M. Holick,et al.  Randomized trial of fortified milk and supplements to raise 25-hydroxyvitamin D concentrations in schoolchildren in Mongolia. , 2011, The American journal of clinical nutrition.

[82]  M. Holick,et al.  Redefining vitamin D insufficiency , 1998, The Lancet.

[83]  M. Holick,et al.  Solar UV Doses of Adult Americans and Vitamin D3 Production , 2011, Dermato-endocrinology.

[84]  Barbara A Gilchrest,et al.  The vitamin D questions: how much do you need and how should you get it? , 2006, Journal of the American Academy of Dermatology.

[85]  E. Giovannucci,et al.  The Importance of Body Weight for the Dose Response Relationship of Oral Vitamin D Supplementation and Serum 25-Hydroxyvitamin D in Healthy Volunteers , 2014, PloS one.

[86]  M. Holick,et al.  Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. , 2003, The American journal of clinical nutrition.

[87]  C. A. Koch,et al.  Vitamin D Deficiency and the Risk of Preeclampsia and Eclampsia in Bangladesh , 2013, Hormone and Metabolic Research.

[88]  O. Franco,et al.  Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies , 2014, BMJ : British Medical Journal.

[89]  M. Holick,et al.  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. , 1988, The Journal of clinical endocrinology and metabolism.

[90]  R. Scragg,et al.  Is outdoor recreational activity an independent predictor of cardiovascular disease mortality - NHANES III? , 2015, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[91]  P. Lips,et al.  Worldwide vitamin D status. , 2011, Best practice & research. Clinical endocrinology & metabolism.

[92]  M. Holick,et al.  Vitamin D deficiency: a worldwide problem with health consequences. , 2008, The American journal of clinical nutrition.

[93]  C. Gordon,et al.  Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited. , 2012, The Journal of clinical endocrinology and metabolism.

[94]  C. Annweiler,et al.  Do studies reporting ‘U’-shaped serum 25-hydroxyvitamin D–health outcome relationships reflect adverse effects? , 2016, Dermato-endocrinology.