he Importance of Vitamin D

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editorial

The Importance of Vitamin D

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hen I was in medical school and during residency training in the 1970s and early 1980s, we were taught that osteomalacia and rickets were bone diseases caused by defective bone mineralization due to a lack of vitamin D.1 Today, vitamin D deficiency is recognized as a pandemic. It is estimated that there are more than 1 billion people worldwide with vitamin D deficiency.2 More recently, vitamin D has been shown to be of great importance in the prevention of diseases. There is strong evidence in the current medical literature that a number of significant medical problems affecting patients, such as cancer, respiratory diseases, diabetes mellitus, cardiovascular diseases, immunology, and neurology are all affected by vitamin D. There are more diseases and disorders that are linked to low vitamin D levels, including possibly autism spectrum disorder, but I am limited in discussing these by the amount of space for this editorial. Vitamin D2, known as ergocalciferol, and vitamin D3, known as cholecalciferol, are both produced when ultraviolet B irradiation from sunlight reaches the epidermis, with vitamin D3 being made in the skin and consisting of approximately 90% of all vitamin D.3 We also get vitamin D3 (cholecalciferol) from food, especially egg yolk, fatty fish, and enriched dairy products. Vitamin D2 (ergocalciferol) comes from plants. Of the two, vitamin D3 is more efficiently metabolized.4,5 When measuring vitamin D in patients, we look at levels in the serum of 25-hydroxyvitamin D (25[OH] D), which shows the overall vitamin D level from diet and sunlight exposure. It is stable in the blood and is a good indication of vitamin D stores.6 NEUROLOGY There are a number of important areas in neurology where vitamin D supplementation can be very helpful. An important one is in cognitive impairment, which includes Alzheimer’s disease (AD), vascular dementia, Lewy body dementia, and other conditions that develop due to brain cell malfunction or cell death. AD is increasingly becoming a public health problem: it affects one in eight people 65 years old and older. In those

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aged 85 and older, AD affects 45% of the population and is the leading cause of death.7 We know that in communitydwelling elderly or in institutionalized elderly, low vitamin D is common, regardless of latitude.8 In addition, low vitamin D levels are associated with increased cognitive impairment.9,10 Another study done in the United States showed an inverse relationship between vitamin D levels and cognitive function.11 We can therefore conclude that supplementation in the elderly with vitamin D is important and may prevent cognitive decline. CARDIOVASCULAR DISEASES An analysis of the data from a large retrospective data analysis of more than 13 000 adults in the National Health and Nutrition Examination Survey (NHANES) III shows those with 25(OH)D levels < 10 ng/mL had 1.5 times increased risk of cardiovascular mortality when compared to those with 25(OH)D > 40 ng/mL. In this same study, participants with 37 ng/mL of 25(OH)D.12 In another large retrospective analysis of 1700 participants of the Framingham study, those with 25(OH)D levels < 15 ng/mL had a 62% greater risk of cardiovascular events when compared to those with 25(OH)D > 15 ng/mL. There are more studies that I can bring to our readers’ attention; however, the above shows clearly and conclusively that higher levels of vitamin D reduce important cardiovascular risks in adult patients. DIABETES MELLITUS A well-done report regarding 10 000 adults followed from birth for approximately 31 years shows the epidemiological link between exposure to vitamin D in early life and the development of type 1 diabetes mellitus. Starting in infancy, supplementation with 2000 IU of vitamin D reduced the risk of developing type 1 diabetes mellitus later in life by 30% as compared to those who received less vitamin D.13 Looking at type 2 diabetes mellitus (t2DM), in a recent meta-analysis of 11 prospective studies, those participants Campbell—Vitamin D


with 25(OH)D levels > 32 ng/mL had a 40% lower risk of developing t2DM than those with 25(OH)D levels < 19.6 ng/ mL.14 In another very interesting study of 1226 participants from Spain, those individuals who had levels of 25(OH)D > 30 ng/mL did not develop t2DM. Those with 25(OH)D > 18.5 ng/mL had 80% less risk of t2DM than those with 25(OH)D < 18.5 ng/mL.15 Reviewing the Nurses’ Health Study, there was a positive correlation with vitamin D with added calcium. When vitamin D > 800 IU was taken with calcium > 1200 mg, there was a 33% lower risk of t2DM compared to those who took 400 IU of vitamin D and 548 IU and calcium > 1366 mg.17 In another study of more than 1100 postmenopausal women followed for over 4 years, there was a reduction in the risk of all cancers compared to placebo in those who took 1100 IU of vitamin D3 (cholecalciferol) and 1500 mg of calcium daily.18,19 In the NHANES III study of more than 16 000 adults, those with 25(OH)D levels > 32 ng/mL had a 72% less risk of colorectal cancer related mortality when compared to those with 32.1 ng/mL.26 Vitamin D deficiency was an independent strong predictor of all cause death in a study of 11 000 adults, and supplementation with vitamin D was significantly associated with better survival.27 Globally speaking, increasing serum levels of 25(OH)D is a very cost effective way to reduce global mortality rates. It would reduce mortality for European females by 17.3% and African women by 7.6% in all cause mortality rates. CONCLUSION From the above, we can readily see the importance in the prevention of diseases by measuring levels of vitamin D in the serum and recommending vitamin D supplementation to our patients. Levels of 25(OH)D between 40 to 50 ng/mL are what we would like to see in our patients from the data available in the large studies mentioned above. The dosages of vitamin D3 at 4000 to 5000 IU raise the levels in the serum to this range. There are numerous studies about dosage, including mega bolus of cholecalciferol, but I am limited by space in delving into that interesting aspect of supplementation. Let us help our patients by reviewing their serum levels of vitamin D and recommending supplementation with cholecalciferol when appropriate. Let us also remember that health insurance carriers pay for the testing of vitamin D levels.

Andrew W. Campbell, MD Editor in Chief

REFERENCES

1. Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metab. 2010;95(2):471-478. 2. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87(4):1080S-1086S. 3. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006;81(3):353–373. 4. Bjelacovic G, Gludd LL, Nikolova D, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. July 2011;(7):CD007470. doi: 10.1002/14651858.CD007470.pub2.

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5. 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 Metab. 2011;96(1):53-58. 6. Kulie T, Groff A, Redmer J, Hounshell J, Schrager S. Vitamin D: an evidencebased review. J Am Board Fam Med. 2009;22(6):698-706. 7. Alzheimer’s Association. 2012 Alzheimer’s disease facts and figures. Alzheim Dement. 2012;8(2):131-168. doi: 10.1016/j.jalz.2012.02.001. 8. Leif M. Vitamin D and the elderly. Clin Endocrin. 2005;62:265-281. 9. Llewellyn DJ, Langa KM, Lang IA. Serum 25-hydroxyvitamin D concentration and cognitive impairment. J Geriatr Psychiatry Neurol. 2009;22(3):188-195. 10. Annweiler C, Allali G, Allain P, et al. Vitamin D and cognitive performance in adults: a systematic review. Eur J Neurol. 2009;16(10):1083-1089. 11. Llewellyn DJ, Lang IA, Langa KM, Melzer D. Vitamin D and cognitive impairment in the elderly U.S. population. J Gerontol A Biol Sci Med Sci. 2011;66(1):5965. 12. Ginde AA, Scragg R, Schwartz RS, Camargo CA Jr. Prospective study of serum 25-hydroxyvitamin D level, cardiovascular disease mortality, and all-cause mortality in older U.S. adults. J Am Geriatr Soc. 2009;57(9):1595-1603. 13. 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(9292):15001503. 14. Forouhi NG, Ye Z, Rickard AP, et al. Circulating 25-hydroxyvitamin D concentration and the risk of type 2 diabetes: results from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort and updated meta-analysis of prospective studies. Diabetologia. 2012;55(8):2173-2182. 15. González-Molero I, Rojo-Martínez G, Morcillo S, et al. Vitamin D and incidence of diabetes: a prospective cohort study. Clin Nutr. 2012;31(4):571-573. 16. Samuel S, Sitrin MD. Vitamin D’s role in cell proliferation and differentiation. Nutr Rev. 2008;66(10) (suppl 2):S116-S124. 17. Lin J, Manson JE, Lee IM, Cook NR, Buring JE, Zhang SM. Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med. 2007;167(10):1050-1059. 18. Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H. Meta-analysis: serum vitamin D and breast cancer risk. Eur J Cancer. 2010;46(12):2196-2205. 19. Avenell A, MacLennan GS, Jenkinson DJ, et al. Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium (RECORD trial). J Clin Endocrinol Metab. 2012;97(2):614-622. 20. Freedman DM, Looker AC, Chang SC, Graubard BI. Prospective study of serum vitamin D and cancer mortality in the United States. J Natl Cancer Inst. 2007;99(21):1594-1602. 21. Janssens W, Bouillon R, Claes B. Vitamin D deficiency is highly prevalent in COPD and correlates with variants in the vitamin D-binding gene. Thorax. 2010;65(3):215-220. 22. Laaksi I, Ruohola JP, Tuohimaa P, et al. An association of serum vitamin D concentrations < 40 nmol/L with acute respiratory tract infection in young Finnish men. Am J Clin Nutr. 2007;86(3):714-717. 23. Ginde AA, Mansbach JM, Camargo CA Jr. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009;169(4):384390. 24. Sutherland ER, Goleva E, Jackson LP, Stevens AD, Leung DY. Vitamin D levels, lung function, and steroid response in adult asthma. Am J Respir Crit Care Med. 2010;181(7):699-704.) 25. Leow L, Simpson T, Cursons R, Karalus N, Hancox RJ. Vitamin D, innate immunity and outcomes in community acquired pneumonia. Respirology. 2011;16(4):611-616. 26. 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(15):16291637. 27. Vacek JL, Vanga SR, Good M, Lai SM, Lakkireddy D, Howard PA. Vitamin D deficiency and supplementation and relation to cardiovascular health. Am J Cardiol. 2012;109(3):359-363.

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Campbell—Vitamin D