Vitamin D deficiency: Beyond bone health
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At a glance
Over the past several years, there has been much talk about vitamin D deficiency, with the debate centering around optimal levels of vitamin D; who should be screened; and, after screening, how to treat. In the past, vitamin D deficiency was associated with persons who had inadequate exposure to sunlight or who lacked access to sufficient amounts of foods containing calcium, resulting in rickets.
Over the past decade, information in the literature suggests that vitamin D deficiency may be more prevalent than first suspected and that the adverse health effects of low vitamin D levels may be far-reaching.
Vitamin D has been implicated in a variety of health-related disorders. Although the primary indication for vitamin D is maintenance of bone health, vitamin D also factors into a number of physiologic processes, such as immunity, calcium absorption, and homeostasis of various organs. Adults whose low vitamin D levels remain unresolved may experience muscle weakness, osteoporosis, osteomalacia, and increased risk of falls. Decreased vitamin D intake and lower levels of serum vitamin D have been associated with some autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, type 1 diabetes, systemic lupus erythematosus, and psoriasis. In addition, low serum vitamin D levels have been linked to increased risk of hypertension, MI, and death due to cardiovascular disease (CVD).¹ Table 1 presents a list of diseases in which vitamin D has been implicated.2 According to the Institute of Medicine (IOM), however, the evidence related to these diseases has been inconsistent and further research is needed. While the investigative work continues, any adverse effects of vitamin D deficiency can be avoided if persons at risk are identified, screened, and treated appropriately in a timely fashion.
Vitamin D was discovered in 1922 during the quest to cure rickets. Originally classified as a vitamin, vitamin D is actually a prohormone in the endocrine system of the skin. Vitamin D comprises a group of fat-soluble sterol compounds that includes ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). Vitamin D2 can be obtained from UV irradiation of the yeast sterol ergosterol. It is found naturally in sun-exposed mushrooms and may be ingested from plant or fish sources. Vitamin D3 is synthesized by the skin from cholesterol under the influence of UV light and is present in oil-rich fish, such as mackerel and salmon.3 In the liver, vitamin D is hydroxylated to 25-hydroxyvitamin D (25[OH]D), or calcidiol. In the kidney, calcidiol is hyroxylated to 1,25-dihydroxyvitamin D (1,25[OH]2D), or calcitriol. In turn, calcitriol increases intestinal absorption of calcium, enchances bone resorption, and decreases renal calcium and phosphate excretion. The function of vitamin D is to promote absorption of calcium in the intestine and to maintain adequate serum phosphate and calcium concentration in order to ensure normal bone mineralization. Without vitamin D, only 10%-15% of dietary calcium and only 60% of phosphorus is absorbed. When the level of vitamin D is sufficient, these amounts increase to 30%-40% for calcium and 80% for phosphorus. Vitamin D is also needed for bone growth and remodeling by osteoblasts and osteoclasts. The vitamin D content of various foods is presented in Table 2.
Definition and prevalence
The diagnostic test used to assess for vitamin D deficiency is a serum 25[OH]D determination. Deficiency has been defined as a serum 25(OH)D level of <20 ng/mL and insufficiency is defined as a serum 25(OH)D level of 21-29 ng/mL. According to recent estimates reported by The Endocrine Society, 20%-100% of U.S., Canadian, and European elderly men and women have vitamin D deficiency, 50% of Hispanic and black adolescents in Boston are deficient, 48% of white preadolescent girls in Maine have vitamin D levels <20 ng/mL, and 42% of black females aged 15-49 years have levels of <15 ng/mL by the end of winter.3 Other levels of vitamin D and the associated health implications are shown in Table 3.
The primary cause of vitamin D deficiency is lack of exposure to sunlight, with exposure defined as sun shining on the arms and legs for five to 30 minutes between the hours of 10 AM and 3 PM twice a week. Keep in mind that application of sunscreen with a sun protective factor (SPF) of 30 decreases the synthesis of vitamin D by 95%. Other causes of vitamin D deficiency include obesity (BMI >30), fat malabsorption syndromes, nephrotic syndrome, hyperparathyroidism, some lymphomas, and HIV/AIDS.
Among the primary benefits of adequate amounts of vitamin D are decreased risk of fracture and prevention of falls in older adults. According to research from Canada, inadequate levels of vitamin D (levels <20 ng/mL) have been linked an increased risk (30%-50%) of colon, breast, and prostate cancer.4
Guidelines for evaluation of vitamin D deficiency
In 2009, the Agency for Healthcare Research and Quality (AHRQ) published guidelines on the evaluation and treatment of vitamin D deficiency,5 and in 2011, The Endocrine Society provided its own recommendations that also included prevention of vitamin D deficiency.3 Both organizations provided comprehensive guidelines on which patients to screen. However, a side-by-side comparison of these recommendations (Table 4) reveals some distinct differences. Also included in Table 4 are this author's recommendations of which of the patients seen in general practice should be screened. The AHRQ included in its recommendations the assessments that comprise an appropriate physical examination. These include general appearance, height and weight, vital signs, overall skin evaluation, skin color, and assessment of bone pain by pressing on the area over the sternum or shin. In addition to a serum 25(OH)D level, other laboratory studies that should be obtained to assess general bone health include a comprehensive metabolic panel, liver function tests, and thyroid-stimulating hormone, calcium phosphorus, protein, intact parathyroid hormone, albumin, alkaline phosphatase, creatinine, total testosterone, serum C-telopeptide, urinary N-telopeptide, and serum osteocalcin determinations.