Clinical Review

Vitamin D Deficiency

Clinician Reviews. 2008 July;18(7):13-15

References

1. Dusso AS, Brown AJ, Slatopolsky E. Vitamin D. Am J Physiol Renal Physiol. 2005;289(1):F8-F28.

2. Forman JP, Giovannucci E, Holmes MD, et al. Plasma 25-hydroxyvitamin D levels and risk of incident hypertension. Hypertension. 2007;49(5):1063-1069.

3. Gartner LM, Greer FR; Section on Breastfeeding and Committee on Nutrition, American Academy of Pediatrics. Prevention of rickets and vitamin D deficiency: new guidelines for vitamin D intake. Pediatrics. 2003;111(4 pt 1):908-910.

4. Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest. 2006;116(8):2062-2072.

5. Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr. 2004;80(6 suppl):1678S-1688S.

6. Office of Dietary Supplements, National Institutes of Health. Dietary supplement fact sheet: Vitamin D (2008). http://dietary-supplements.info.nih.gov/factsheets/vitamind.asp. Accessed June 26, 2008.

7. Vieth R, Bischoff-Ferrari H, Boucher BJ, et al. The urgent need to recommend an intake of vitamin D that is effective (editorial). Am J Clin Nutr. 2007;85(3):649-650.

8. 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(6 suppl): 1752S-1758S.

9. Gordon CM, DePeter KC, Feldman HA, et al. Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med. 2004;158(6):531-537.

10. Bodnar LM, Catov JM, Simhan HN, et al. Maternal vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab. 2007;92(9):3517-3522.

11. Dietrich T, Joshipura KJ, Dawson-Hughes B, Bischoff-Ferrari HA. Association between serum concentrations of 25-hydroxyvitamin D3 and periodontal disease in the US population. Am J Clin Nutr. 2004;80(1):108-113.

12. Bischoff-Ferrari HA. Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. Adv Exp Med Biol. 2008;624:55-71.

13. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79(3):362-371.

14. Wang TJ, Pencina MJ, Booth SL, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117(4):503-511.

15. Zittermann A, Schleithoff SS, Koerfer R. Putting cardiovascular disease and vitamin D insufficiency into perspective. Br J Nutr. 2005;94(4):483-492.

16. Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med. 2008;168(11):1174-1180.

17. Jorde R, Waterloo K, Saleh F, et al. Neuropsychological function in relation to serum parathyroid hormone and serum 25-hydroxyvitamin D levels: the Tromsø study. J Neurol. 2006;253(4):464-470.

18. Garland CF, Gorham ED, Mohr SB, et al. Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol. 2007;103(3-5):708-711.

19. Flanagan JN, Young MV, Persons KS, et al. Vitamin D metabolism in human prostate cells: implications for prostate cancer chemoprevention by vitamin D. Anticancer Res. 2006;26(4A):2567-2572.

20. Spina CS, Ton L, Yao M, et al. Selective vitamin D receptor modulators and their effects on colorectal tumor growth. J Steroid Biochem Mol Biol. 2007;103(3-5):757-762.

21. Bischoff HA, Stähelin HB, Dick W, et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res. 2003;18(2):343-351.

22. Bischoff-Ferrari HA, Dietrich T, Orav EJ, Dawson-Hughes B. Positive association between 25-hydroxy vitamin D levels and bone mineral density: a population-based study of younger and older adults. Am J Med. 2004;116(9):634-639.

23. Harris SS, Soteriades E, Coolidge JA, et al. Vitamin D insufficiency and hyperparathyroidism in a low income, multiracial, elderly population. J Clin Endocrinol Metab. 2000;85(11):4125-4130.

24. Wilkins CH, Sheline YI, Roe CM, et al. Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults. Am J Geriatr Psychiatry. 2006;14(12):1032-1040.

25. Holick MF. Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol. 2008 Mar 8; [Epub ahead of print].

26. Elliott ME, Binkley NC, Carnes M, et al. Fracture risks for women in long-term care: high prevalence of calcaneal osteoporosis and hypovitaminosis D. Pharmacotherapy. 2003;23(6):702-710.

27. Johnson JM, Maher JW, DeMaria EJ, et al. The long-term effects of gastric bypass on vitamin D metabolism. Ann Surg. 2006;243(5):701-705.

28. Wortsman J, Matsuoka LY, Chen TC, et al. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 2000;72(3):690-693.

29. Mishal AA. Effects of different dress styles on vitamin D levels in healthy young Jordanian women. Osteoporos Int. 2001;12(11):931-935.

30. McDuffie JR, Calis KA, Booth SL, et al. Effects of orlistat on fat-soluble vitamins in obese adolescents. Pharmacotherapy. 2002;22(7):814-822.

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Assessment of the patient's constitution, of course, includes vital signs and general appearance. As mentioned earlier, hypertension may coexist with vitamin D deficiency.^2,13-16 Obesity, it is also important to note, has been associated with reduced vitamin D bioavailability.²⁸ The type and coverage of the patient's clothing can provide an important clue to a potential lack of sunlight exposure and its impact on his or her vitamin D status.²⁹ As for inspection of the integument, it should be noted that darker skin pigmentation is included among the risk factors for vitamin D insufficiency, as melanin in darker skin reduces vitamin D synthesis.^9,31

Testing for Vitamin D
The most accurate means of meassuring the patient's vitamin D status is 25-hydroxyvitamin D, also known as serum 25(OH)D.^4,25 With a relative half-life of two weeks,⁴ this marker reliably indicates the body's stores of vitamin D. Some laboratories report three aspects—total serum 25(OH)D, 25[OH]D3, and 25[OH]D2—while others report only total serum 25(OH)D. Interpretation of the latter is shown in Table 2.^4,25

Additional research suggests that higher levels of serum 25(OH)D (ie, 36 to 48 ng/mL) may be desirable for the prevention of cancer.¹²

Treatment
Vitamin D insufficiency and deficiency are relatively easy and inexpensive to treat. With a target treatment goal of serum 25(OH)D greater than 30 ng/mL, the patient can be advised to increase his or her sunlight or UV exposure in moderate amounts, such as exposure of the hands and face to bright sunlight for 15 minutes daily. During winter or at northern latitudes with reduced sunlight, moderate exposure in a tanning bed (ie, one emitting 2% to 6% UVB radiation) can be helpful.^6,32 For recommended supplementation to correct vitamin D deficiency or insufficiency, see Table 3.^6,32

Oral supplementation for adults is an inexpensive, well-tolerated solution. A conscious effort to increase dietary intake of fortified dairy products and cereals or fatty fish may be adequate. OTC oral vitamin D3 supplements are available in 200, 400, and 1,000 IU for a few cents per dose. Prescription vitamin D2 ergocalciferol is also available.⁶

Infants who are exclusively breastfed or who consume less than 500 mL/d of vitamin D–fortified formula can be given a combination multivitamin containing 400 IU/mL for adequate supplementation^3,6; Hollis and Wagner⁸ recommend that breastfeeding women have 4,000 IU/d of vitamin D intake to protect both themselves and their infants. Single-source or concentrated vitamin D is not recommended for infants.³ Gartner and Greer³ recommend a vitamin D intake of 200 IU/d from childhood through adolescence.

Research indicates that higher levels of vitamin D supplementation than previously recommended are needed for most people and are safe.^7,12 Additionally, higher doses of vitamin D are not as toxic as were previously believed, as excess amounts are stored.³³ Daily doses of no less than 1,000 IU (with or without sunlight exposure and/or dietary intake) may improve the serum 25(OH)D levels in the majority of the population.¹² Results from one study suggest that a total of 3,600 to 4,200 IU/d from all sources is desirable and safe.³³

Reevaluation
The serum 25(OH)D test should be repeated after six to eight weeks to ensure adequate vitamin D absorption, targeting a level of at least 30 ng/mL. If serum 25(OH)D falls persistently below that level, the clinician should consider vitamin D in an injectable form and reassess the patient for malabsorption or other interference issues.³⁴

Conclusion
The health benefits of vitamin D are frequently overlooked in everyday practice. Screening and treatment are simple, cost-effective, and beneficial for patients' wellness.