Vitamin D Deficiency

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.

The Facts
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 products^4,5; 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

Widespread Effects
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}

Assessment
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