As increasing numbers of people work in windowless environments and as computer time, gaming consoles, and TV viewing keep more of them indoors during their leisure hours, many are losing access to their natural source of vitamin D: sunshine. In response to the justifiably publicized risk of skin cancers, people avoid sunlight or take great care to cover the skin with sunscreen—minimizing the risk of sun-related skin cancer, but greatly increasing the risk of vitamin D deficiency.
The importance of vitamin D was first recognized in the prevention of rickets and its role in absorption of calcium and phosphate in the diet.1 In recent decades, however, the growing understanding of vitamin D’s influence on leukocytes, vascular smooth muscle cells, and other tissues2 has led to an increased awareness of this nutrient’s contribution to numerous processes and functions.
Considering vitamin D’s subtle but substantial impact on mental, cardiovascular, musculoskeletal, and autoimmune health (not to mention bone disorders and calcium deficiency), vitamin D deficiency is overlooked and undertreated with surprising frequency in the clinical setting, where clinicians are more likely to screen for and treat other disorders.
Exposure of the skin to sunlight or ultraviolet (UV) light is the human body’s natural way to synthesize vitamin D3.1,3 This nutrient can also be ingested in fish and fish liver oils; in the form of vitamin D2, which has been used since the 1930s in efforts to reduce rickets and other bone disorders by fortifying milk, cereals, and a variety of food products4,5; and in dietary supplements.
Unfortunately, the intake of vitamin D–fortified foods and/or supplements is often insufficient for the average person to maintain an adequate level of this essential substance.3 Fatty fish, including sardines, mackerel, tuna, and salmon,6 are among the few foods that represent a valuable source of vitamin D, but these are not commonly considered a staple in today’s American diet. Additionally, it has been questioned whether the current recommended daily allowance guidelines for vitamin D intake are adequate for most of the population.7
The impact of vitamin D deficiency or insufficiency affects patients of both genders across the life span. Exclusive breastfeeding without adequate vitamin D supplementation can result in rickets in infants, children, and adolescents.3,4,8 Research indicates that even healthy-appearing adolescents may be deficient in this nutrient.9 Inadequate intake or supplementation of vitamin D during pregnancy has been shown to increase women’s risk of preeclampsia, with potential impact on their infants’ well-being.10
Adults with inadequate levels of vitamin D are at risk for periodontal disease and other dental concerns,11,12 hypertension and cardiovascular disease,2,13-16 musculoskeletal disorders, depression,17 and malignancies of the breast,18 colon,1,19,20 and prostate.13 Older persons with insufficient levels of this essential substance are at increased risk of falls and fractures,12,21 osteoporosis,21,22 hyperparathyroidism,23 impaired cognitive function, and depression.24
Vitamin D Synthesis
Vitamin D is synthesized in the skin by UV light between wavelengths of 290 and 315 nm,4,13 converting 7-dehydrocholesterol to previtamin D3, then by thermal isomerization to vitamin D3.1,3 Both vitamin D3 and vitamin D2 are incorporated into chylomicrons and absorbed by the lymph system, then put into systemic circulation by vitamin D–binding protein.4,13
Two additional steps—one that occurs in the liver, the other in the kidneys—are needed to complete the conversion from an inert form to usable vitamin D. In the liver, the molecule is hydroxylated by enzymes called the vitamin D-25-hydroxylases to form 25-hydroxyvitamin D. Then in the kidneys, the cytochrome P-450 enzyme 25-hydroxyvitamin D-1 alpha-hydroxylase continues the hydroxylation process, converting the molecule to vitamin D’s biologically active form, 1,25-dihydroxyvitamin D.4,13,25 It is next bound to the vitamin D receptors and in an additional step is transcribed in RNA and replicated.
The known actions of vitamin D include increasing calcium and phosphorus absorption from the small bowel, enhancement of renal tubule resorption of phosphate, and maturation of osteoclasts to resorb calcium from the bones. Vitamin D also improves measurable bone mineral density.1
Who Is at Risk?
Many individuals may not recognize their risk for vitamin D deficiency or insufficiency. Clinicians must be aware of the conditions and factors that increase the risk. Many of these are identified in Table 1.3,5,6,8,10,24,26-31
Clinicians in any number of specialties may encounter patients with vitamin D deficiency or insufficiency. Thus, it is important during the interview and review of systems to ask routinely about the patient’s occupation, sun exposure, and use of sunscreen. Clinicians should also ask about dietary habits and dietary supplements, including multivitamins and supplemental vitamin D (eg, calcium with vitamin D).
The examining clinician should also key in on fatigue, bone pain, and muscle pain or weakness. While reviewing the patient’s medical history and the current problem list, the clinician should maintain an awareness of disease processes that may mimic vitamin D insufficiency. These include fibromyalgia, chronic fatigue syndrome, myositis, hyperparathyroidism, and depression.13,17,23 Comorbidities that often coexist with vitamin D deficiency include hypertension and cardiovascular disease,16 obesity, type 1 diabetes mellitus,13 multiple sclerosis,5 secondary hyperparathyroidism,13 and prostate, breast, or colorectal cancer.1,2,9,13
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
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 supplementation3,6; 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
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
The health benefits of vitamin D are frequently overlooked in everyday practice. Screening and treatment are simple, cost-effective, and beneficial for patients’ wellness.
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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.
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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.
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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].
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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.
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