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Vitamin D: Essential for Lifelong Health in Women

Veronica Piziak, MD, PhD

After years of emphasizing calcium intake to maintain bone health in women, researchers are recognizing that vitamin D plays an equally important role—and that bone health is only the beginning.

Vitamin D is critically important to women’s health. It is an essential steroid hormone that controls calcium and phosphorus homeostasis and the development and preservation of bone integrity. However, vitamin D intake among US women is low, and insufficiency and deficiency are common.

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REQUIREMENTS

The recommended intake of most vitamins can be satisfied with a balanced diet, but vitamin D is fat-soluble and occurs naturally in very few foods—such that the bulk of its dietary intake is from fortified foods (Table 1).1 Vitamin D is produced naturally with exposure to sunlight when ultraviolet B (UVB) rays penetrate the skin and are absorbed by 7-dehydrocholesterol, which is transformed into vitamin D3. Sunscreens that absorb UVB radiation reduce vitamin D synthesis; the sun protection factor (SPF) need only be 8 to effectively prevent vitamin D synthesis, and many skin products such as moisturizers exceed this level of UVB protection. Moreover, latitudes above 35°N also receive less UVB light during the winter, leading to lower vitamin D production.2 Aging and hyperpigmentation also decrease dermal vitamin D production. Early in the 20th century, lack of sun exposure in children in the northern United States and Europe caused an increase in the prevalence of the bone disease rickets. Fortification of foods has all but eliminated this condition in the United States, but it is still seen occasionally in dark-skinned children who are breastfed without additional vitamin D supplementation.

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TABLE 1. Dietary Sources of Vitamin D

Recommended requirements for vitamin D have recently been increased as widespread deficiency has emerged. The requirement for both breastfed infants and nonbreastfed/weaned infants has been set at 400 IU/d, with the latter also consuming 1,000 mL/d of fortified milk.1 Children and adolescents are likewise advised to receive 400 IU/d of vitamin D in fortified milk or as a supplement.1 The general recommendation for adults is 800 to 1,000 IU/d in the absence of significant sun exposure.3 Requirements during pregnancy have been established at 200 IU/d, but studies are underway to evaluate whether higher doses could substantially improve the vitamin D status of the mother and the fetus.

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PHYSIOLOGY

Whether produced by sunlight or absorbed from foods, vitamin D is not active until it is hydroxylated by the liver and kidneys to produce the active hormone. It is then disseminated throughout the circulation, most commonly bound to vitamin-D–binding protein. It subsequently passes into the cells at the cell membrane and binds to the vitamin D receptors. This complex enters the nucleus, where it interacts with the DNA to influence gene expression and cellular activity such as protein synthesis and cellular differentiation.

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EVALUATION

Vitamin D status is determined by calculating the sum of 25-hydroxy [25(OH)] vitamin D2 and D3 levels. Vitamin D deficiency is defined as a 25(OH)D level of less then 10 ng/mL, resulting in rising parathyroid hormone (PTH) values, impaired mineralization of bone, and an increased risk of fracture and osteomalacia.4 Vitamin D insufficiency is defined as a 25(OH)D level of 10 to 30 ng/mL. There is some controversy about levels between 20 and 30 ng/mL, but PTH values may be elevated in up to 33% of patients with vitamin D values below 30 ng/mL, leading to increased bone resorption and loss of bone mineral density (BMD), particularly in the hip.5 Vitamin D levels of 30 to 80 ng/mL are considered normal. Toxicity may occur with levels in excess of 80 ng/mL, with possible hypercalcemia.6

Vitamin D insufficiency and deficiency are common in the adult US population, even in those with sufficient exposure to sunlight. For example, even in Florida, 40% of adults with a mean age of more than 55 years who were screened at a health fair proved to have 25(OH)D levels of less then 20 ng/mL.7 Among 1,536 community-dwelling postmenopausal women receiving therapy for osteoporosis including calcium and vitamin D, 52% had 25(OH)D levels below 30 ng/mL that were associated with an average intake of less than 400 IU/d.8

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SCREENING

In clinical practice, it is helpful to screen female populations at high risk for vitamin D deficiency (Table 2). This includes women with pancreatic insufficiency, liver disease, and inflammatory bowel disease. Elderly institutionalized women frequently have poor dietary intake of vitamin D and little sun exposure, and are also at high risk for deficiency. In obese individuals, vitamin D tends to be sequestered in the fatty tissue, necessitating a higher intake. Women who have undergone gastric bypass surgery may develop hyperparathyroidism and osteomalacia because of nonadherence to vitamin supplements after the modern Roux-en-Y procedure and malabsorption after other bypass procedures. Women with fibromyalgia should also be screened, as myalgias can be associated with vitamin D deficiency.1 States of high bone turnover (eg, Paget disease, primary hyperparathyroidism) are likewise associated with low vitamin D levels. In addition, it is wise to check vitamin D levels before administering intravenous bisphosphonates for osteoporosis to prevent hypocalcemia.

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TABLE 2. Conditions Predisposing to Vitamin D Deficiency

Medications may also interfere with vitamin D absorption or metabolism. Glucocorticoids such as prednisone not only reduce calcium absorption, but may accelerate vitamin D metabolism as well. The weight-loss drug orlistat decreases absorption of fat and fat-soluble vitamins. Bile-acid-binding resins used to treat hypercholesterolemia also reduce absorption of fat-soluble vitamins. The anticonvulsant, phenytoin, hastens hepatic metabolism of vitamin D.1 Patients with chronic renal disease need periodic monitoring of 25(OH)D levels; as renal function deteriorates, 1,25-dihydroxy-vitamin D3 values may be assessed to determine if this supplement is needed.

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SUPPLEMENTATION

When vitamin D insufficiency or deficiency is diagnosed, supplementation should be provided to raise the 25(OH)D level to at least 30 ng/mL. For patients with 25(OH)D levels greater than 20 ng/mL, supplementation with 1,000 to 2,000 IU/d of vitamin D2 or D3 is generally sufficient. For patients with lower levels or actual deficiency, 50,000 IU/week of vitamin D2 or D3 for 6 to 8 weeks is usually effective and well tolerated. A patient can generally take up to 10,000 IU/d of vitamin D without adverse effects.6 Vitamin D2 and D3 are equally effective in raising and maintaining 25(OH)D levels.9 Levels of 25(OH)D should be measured at 8 weeks after initiating therapy to confirm repletion, after which 1,000 IU/d may be used to maintain values at 30 ng/mL in most patients.1

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SKELETAL EFFECTS

Vitamin D regulates calcium homeostasis via the intestines, bones, kidneys, and parathyroid glands. Vitamin D enhances intestinal absorption of calcium and phosphorus and facilitates calcium resorption by the kidney’s proximal tubules, thus providing calcium for bone building. Vitamin D decreases the production and release of PTH and so regulates bone turnover to avoid excess bone destruction. Vitamin D deficiency results in a decrease in BMD and defective bone mineralization or osteomalacia.

Inadequate levels of calcium and vitamin D are thought to be associated with age-related osteoporosis. However, the role of vitamin D and its interaction with calcium in the prevention of fragility fractures is controversial, and it is difficult to find studies in which 25(OH)D levels were measured prospectively. In a meta-analysis of 7 trials involving 9,820 women with a mean age of 79, higher-dose vitamin D supplementation (700 to 800 IU/d) significantly reduced hip fractures, whereas doses of 400 IU/d or less had no effect.10 By contrast, 36,000 women in the Women’s Health Initiative with a mean age of 62.4 years had no reduction in fracture risk with 1,000 mg/d of calcium and 400 IU/d of vitamin D.11 However, hip fractures were reduced significantly in women who adhered to supplements 80% of the time. The preponderance of evidence demonstrates that 800 to 1,000 IU/d of vitamin D is necessary to protect against fractures in most postmenopausal women. It has also been shown that calcium and vitamin D supplementation can prevent stress fractures in young women who exercise strenuously.12

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EXTRASKELETAL FUNCTIONS

Vitamin D is also necessary for the maintenance of muscle function. Patients with osteomalacia have a decrease in type II muscle fibers, which are involved in quick movements—eg, the types of movements used to prevent falling. Controlled trials have demonstrated improved movement and decreased falls in elderly patients who take 700 to 1,000 IU/d of vitamin D.13

Higher 25(OH)D levels have been associated with a decrease in colon cancer, while suboptimal vitamin D values were linked with an increased risk of breast cancer occurrence.14,15 Additionally, a meta-analysis showed that vitamin D supplementation in elderly patients at high risk for fractures resulted in a reduction in all-cause mortality.16

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CONCLUSION

Vitamin D plays an important role in a woman’s health throughout her life. Low levels increase the risk of many diseases—particularly osteomalacia—and predispose to hip fracture. Adequate levels of vitamin D not only preserve skeletal integrity, but may also decrease the risk of certain cancers and prolong life. Data suggest that women older than 50 years of age should consume at least 1,000 IU/d of vitamin D to take full advantage of these benefits.

The author reports no actual or potential conflicts of interest in relation to this article.

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Veronica Piziak, MD, PhD, is Professor of Medicine and Endocrinology, Department of Internal Medicine, Texas A&M Health Science Center College of Medicine; and Director, Department of Endocrinology, Scott & White, Temple, TX.

References

1. Office of Dietary Supplements. Dietary Supplement Fact Sheet: Vitamin D. National Institutes of Health. http://ods.od.nih.gov/factsheets/vitamind.asp. Accessed January 2009.
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