Importance of Vitamin D for Adult Health

By Michael F. Holick, PhD, MD

Vitamin D is taken for granted and its role in health is underappreciated by both physicians and patients. Health care practitioners may be aware that vitamin D is associated with bone health in growing children, but little attention has been paid to the important role that vitamin D plays in maximizing and maintaining bone health in adults. Additionally, vitamin D ingestion may have implications for the prevention of many common cancers, hypertension, and Type 1 diabetes.1

Unlike most fat-soluble and water-soluble vitamins that are plentiful in a healthy diet, very few foods naturally contain vitamin D. Consumption of oily fish, such as salmon or mackerel, three to four times a week, or ingestion of cod liver oil on a daily basis provides vitamin D from natural sources. Some foods, including milk, some breads, and some cereals, also are fortified with vitamin D. A majority of our vitamin D requirement (80-95%) comes not from dietary sources but from sunlight exposure.1,2

Prevalence of Vitamin D Deficiency

Vitamin D deficiency is extremely common in the U.S. adult population.1-7 In the epidermis, concentrations of provitamin D3 are inversely related to age. Not surprisingly, more than half of elders (both free-living and those in nursing homes) are deficient in vitamin D. It has been assumed that young and middle-aged adults are not at risk for vitamin D deficiency. However, the lifestyle of many young and middle-aged adults is such that they are constantly at work indoors.

In addition, heightened awareness about sun exposure and skin cancer has resulted in the use of a sunscreen before exposure to sunlight. A sunscreen with an SPF of 8 will reduce vitamin D synthesis by 97.5%.8 The CDC recently reported that 41% of African-American women ages 15-49 years throughout the United States were vitamin D deficient at the end of the winter.9,10 Thirty-two percent of medical students and residents at our hospital were found to be vitamin D deficient at the end of the winter.6

Consequences of Vitamin D Deficiency

Chronic vitamin D deficiency has subtle and insidious consequences for both bone health and overall health and well-being. Vitamin D deficiency results in decreased efficiency of intestinal calcium absorption. The body responds by increasing the production of parathyroid hormone, which in turn mobilizes precious calcium stores from the skeleton. Thus, vitamin D deficiency can precipitate and exacerbate osteoporosis. In addition, vitamin D deficiency causes osteomalacia, a mineralization defect of the skeleton. Unlike osteoporosis, which is a silent disease, osteomalacia often presents as isolated or generalized muscle aches, muscle weakness, and bone pain. It has been estimated that upward of 60% of patients with symptoms consistent with fibromyalgia (i.e., muscle and bone aches and pains) actually may have vitamin D deficiency.1,11,12

Exposure to tanning bed radiation resulting in a more than 100% increase in circulating concentrations of 25-hydroxyvitamin D [25(OH)D] was effective in treating hypertension.13 It now is recognized that 1,25-dihy-droxyvitamin D (the biologically active form of vitamin D) can down-regulate the renin-angiotensin system. It also is recognized that most organs in the body have vitamin D receptors (VDRs),11-16 and that 1,25(OH)2D is a potent down-regulator of cell growth. Furthermore, the prostate, colon, and breast, as well as other tissues, can make 1,25(OH)2D3; the most likely purpose is for regulating cell growth.17-19 There is strong evidence that vitamin D deficiency, especially in those who live at higher latitudes, increases the risk of death from many common cancers, including colon, breast, prostate, and ovarian cancer.20-22 Garland et al observe that the risk of death from colon cancer was reduced by 50% if 25(OH)D was greater than 20 ng/mL.20

Vitamin D deficiency may predispose children to diabetes. The ß-islet cells of the pancreas have VDRs, and a recent study reported that the risk of developing Type 1 diabetes decreased by 80% in children who received vitamin D supplementation.23

The best method to determine vitamin D deficiency is to measure circulating concentrations of 25(OH)D. Patients who are vitamin D deficient will have a normal serum calcium due to their secondary hyperparathyroidism. Thus, the only measure of vitamin D status is a 25(OH)D level. 1,25(OH)2D is of no value and indeed can be low, normal, or even elevated in a vitamin D insufficient patient.1

Treatment of Vitamin D Deficiency

The best method to treat vitamin D deficiency is to fill the vitamin D tank quickly by giving the patient 50,000 IU of vitamin D once a week for eight weeks.8 A repeat 25(OH)D after the therapy often shows an increase of at least 100%. However, if this does not occur, the treatment should be repeated for an additional eight weeks. For those who cannot absorb vitamin D due to chronic malabsorption syndromes (e.g., chronic liver disease, cystic fibrosis, Crohn’s disease, Whipple’s disease, sprue), exposure to natural sunlight or tanning bed radiation24,25 that has a component of ultraviolet-B radiation is suggested.26,27

The National Academy of Sciences recently recommended that the adequate intake of vitamin D be increased in middle-aged adults and elders. Current recommended dietary allowances are 200 IU for ages 1-50, 400 IU for ages 51-70, and 600 IU for those older than 70 years. We, and others, have estimated that in the absence of exposure to sunlight, the requirement is closer to 1,000 IU of vitamin D daily.1,28-31 The goal is to maintain circulating concentrations of 25(OH)D of at least 20 ng/mL and preferably, between 30 and 50 ng/mL.

Because vitamin D deficiency is so common, I have recommended that as a preventive health measure, similar to measuring blood lipids, it is reasonable to check 25(OH)D annually. This will ensure that patients are vitamin D sufficient, thus maximizing their bone health, as well as their overall health and well-being.1,32,33

Dr. Holick is Director of the Bone Health Care Clinic, Director of the General Clinical Research Center, and Professor of Medicine, Dermatology, Physiology, and Biophysics, Boston University Medical Center, Boston, MA.

References

1. Holick MF. Vitamin D: The underappreciated D-lightful hormone that is important for skeletal and cellular health. Curr Opin Endocrinol Diabetes 2002;9:87-98.

2. Holick MF. McCollum Award Lecture, 1994: Vitamin D—New horizons for the 21st century. Am J Clin Nutr 1994;60:619-630.

3. Harris SS, et al. Vitamin D insufficiency and hyperparathyroidism in a low income, multiracial, elderly population. J Clin Endocrinol Metab 2001;85: 4125-4130.

4. Malabanan A, et al. Redefining vitamin D insufficiency. Lancet 1998;351:805-806.

5. Holick MF. Sunlight D’ilemma: Risk of skin cancer or bone disease and muscle weakness. Lancet 2001; 357:4-6.

6. Tangpricha V, et al. Vitamin D insufficiency among free-living healthy young adults. Am J Med 2002;112: 659-662.

7. Harris SS, et al. Plasma 25-hydroxyvitamin D responses of younger and older men to three weeks of supplementation with 1800 IU/day of vitamin D. J Am Coll Nutr 1999;18:470-474.

8. Matsuoka LY, et al. Sunscreens suppress cutaneous vitamin D3 synthesis. J Clin Endocrinol Metab 1987; 64:1165-1168.

9. Nesby-O’Dell S, 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. Am J Clin Nutr 2002;76:187-192.

10. Holick MF. Too little vitamin D in premenopausal women: Why should we care? Am J Clin Nutr 2002; 76:3-4.

11. Glerup H, et al. Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. J Intern Med 2000;247:260-268.

12. Malabanan A, et al. Severe generalized bone pain and osteoporosis in a premenopausal black female: Effect of vitamin D replacement. J Clin Densitometr 1998;1: 201-204.

13. Krause R, et al. Ultraviolet B and blood pressure. Lancet 1998;352:709-710.

14. Stumpf WE, et al. Target cells for 1,25-dihydroxyvitamin D3 in intestinal tract, stomach, kidney, skin, pituitary, and parathyroid. Science 1979;206:1188-1190.

15. Feldman D, et al. Vitamin D and prostate cancer. Endocrinology 2000;141:5-9.

16. Li YC, et al. 1,25-Dihydroxyvitamin D3 is a negative regulator of renin-angiotensin system. J Clin Invest 2002;110:229-238.

17. Schwartz GG, et al. Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3. Cancer Epidemiol Biomarkers Prev 1998;7:391-395.

18. Cross HS, et al. 25-Hydroxyvitamin D3-1alpha- hydroxylase and vitamin D receptor gene expression in human colonic mucosa is elevated during early carcinogenesis. Steroids 2001;66:287-292.

19. Tangpricha V, et al. 25-Hydroxyvitamin D-1alpha-hydroxylase in normal and malignant colon tissue. Lancet 2001;357:1673-1674.

20. Garland CF, et al. Can colon cancer incidence and death rates be reduced with calcium and vitamin D? Am J Clin Nutr 1991;54:193S-201S.

21. Hanchette CL, Schwartz GG. Geographic patterns of prostate cancer mortality. Evidence for a protective effect of ultraviolet radiation. Cancer 1992;70: 2861-2869.

22. Ahonen MH, et al. Prostate cancer risk and prediognostic serum 25-hydroxyvitamin D levels. Cancer Causes Controls 2000;11:847-852.

23. Hypponen E, et al. Intake of vitamin D and risk of type 1 diabetes: A birth-cohort study. Lancet 2001; 358:1500-1503.

24. Reid IR, et al. Prophylaxis against vitamin D deficiency in the elderly by regular sunlight exposure. Age Ageing 1986;15:35-40.

25. Webb AR, 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. J Clin Endo-crinol Metab 1988;67:373-378.

26. Chuck A, et al. Subliminal ultraviolet-B irradiation for the prevention of vitamin D deficiency in the elderly: A feasibility study. Photodermatol Photoimmunol Photomed 2001;17:168-171.

27. Adams JS, et al. Vitamin-D synthesis and metabolism after ultraviolet radiation of normal and vitamin-D-deficient subjects. N Engl J Med 1982;306:722-725.

28. Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: Consequences for bone loss and fractures and therapeutic implications. Endocr Rev 2001;22:477-501.

29. Vieth R, et al. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am J Clin Nutr 2001;73:288-294.

30. Holick MF. Vitamin D requirements for humans of all ages: New increased requirements for women and men 50 years and older. Osteoporos Int 1998;8(Suppl): S24-S29.

31. Heaney RP, et al. Calcium absorptive effects of vitamin D and its major metabolites. J Clin Endocrinol Metab 1997;82:4111-4116.

32. McGrath J. Does imprinting’ with low prenatal vitamin D contribute to the risk of various adult disorders? Med Hypotheses 2001;56:367-371.

33. Grant WB. An estimate of premature cancer mortality in the U.S. due to inadquate doses of solar ultraviolet-B radiation. Cancer 2002;94:1867-1875.