Issues around screening and treatment of vitamin D deficiency have been very controversial in recent years. The Endocrine Society recently published an evidence-based guideline aimed at helping determine who should be screened and receive vitamin D replacement.

Conclusions

The Institute of Medicine recently endorsed the historical definition of vitamin D deficiency as a 25-hydroxy vitamin D level of less than 20 ng/ml, insufficiency as 21-29 ng/ml, and sufficiency as 30-100 ng/ml.

It is estimated that at least 20%, if not a large majority, of community-dwelling seniors in the United States are vitamin D deficient, based on the IOM definition, with a high proportion of younger adults and children also likely to be vitamin D deficient. These estimates are supported by numerous epidemiologic studies in varied populations.

The principal source of vitamin D is exposure to natural sunlight. Dark skin pigmentation and sunscreens with an SPF greater than 30 reduce solar vitamin D synthesis dramatically.

Only a few foods, such as salmon, tuna, and shitake mushrooms, are naturally rich in vitamin D, so vitamin D supplementation is added to a variety of foods in the U.S. and Canada.

Obesity is associated with reduction in vitamin D levels.

Vitamin D deficiency is problematic in patients with intestinal malabsorption, including those with bariatric surgeries. Nephrotic syndrome causes increased urinary loss of bound vitamin D.

Multiple medications including corticosteroids, azole antifungals, HIV drugs, and anticonvulsants cause enhanced vitamin D catabolism and increase the risk for vitamin D deficiency.

Patients with lymphomas, granuloma-forming disorders, such as sarcoidosis, certain fungal infections, and tuberculosis have extra-renal metabolism of 25-hydroxy vitamin D to 1,25(OH)D₂ and are at high risk for vitamin D deficiency. They also are at risk of hypercalcemia with vitamin D replacement to sufficiency.

Vitamin D deficiency results in abnormal calcium/phosphate and bone metabolism at intestinal, renal and bone levels.

Implementation

• Prevention: Vitamin D2 or vitamin D3 should be used for the prevention and treatment of vitamin D deficiency.

A dose of at least 600 IU daily of vitamin D is suggested for adults 19-65 years of age, including women who are pregnant and lactating, to maximize bone and muscular function.

At least 800 IU of vitamin D daily is suggested for persons 65 years and older to maximize bone and muscle function and to reduce the risk for falls and associated fractures. The data for this dosing recommendation is stronger than that supporting dosing in younger adults.

Obese adults and those taking anticonvulsants and other medications known to interfere with vitamin D should take doses of vitamin D that are two to three times the dose of their age-matched peers.

These daily allowances may not be sufficient to raise the blood level of 25-OH vitamin D to 30 ng/ml in all persons.

The maximum daily dose of vitamin D which should be taken by adults not under the supervision of a physician, or being treated specifically for vitamin D deficiency is 4000 IU daily.

• Screening: Vitamin D screening should be restricted to patients at increased risk for deficiency. This would include patients with osteoporosis, those with malabsorption syndromes, patients taking medications interfering with vitamin D, those with chronic kidney disease and older adults. The primary circulating form of vitamin D is 25-hydroxy vitamin D and is the recommended test for assessment of deficiency in nearly all patients.

Only patients with chronic kidney disease, and other specific conditions in which vitamin D and phosphate metabolism is altered should be evaluated by 1,25(OH)D₂ level.

• Treatment: Adults who are vitamin D deficient should be treated with 50,000 IU of vitamin D2 [or D3] weekly for 8 weeks with a goal of achieving 25-OH vitamin D levels of 30 ng/ml or above, followed by maintenance therapy to maintain these levels. Alternative dosing strategies are reviewed in the full text guideline.

Evaluation for a cause of vitamin D malabsorption should be considered in patients who are adherent to replacement therapy but in whom the 25-OH vitamin D level does not increase.

Obese patients, those taking medications affecting vitamin D metabolism and those with malabsorption of vitamin D should be treated with replacement doses two- to threefold higher (6,000-10,000 IU daily) to replete their deficiency. They also require higher doses for maintenance therapy.

Patients with extrarenal production of 1,25(OH)D₂ and primary hyperparathyroidism should have serial monitoring of 25-OH vitamin D and calcium during replacement to minimize the risk for hypercalcemia.

Vitamin D receptors are located in many tissues and many potential pleiotropic effects of vitamin D have been noted by researchers, but the data to date are insufficient for firm clinical conclusions about the magnitude of these effects. A number of other questions remain unanswered regarding vitamin D and its effects.

Reference

Evaluation, Treatment, and Prevention of Vitamin D Deficiency: An Endocrine Society Clinical Practice Guideline (J. Clin. Endocrinol. Metab. 2011;96:1911-30).

Dr. Golden is professor of medicine and public health and Dr. Hopkins is program director for the internal medicine/pediatrics combined residency program at the University of Arkansas, Little Rock.

Vitamin D Deficiency: Prevention, Evaluation, Replacement