Evaluation, treatment and prevention of vitamin D deficiency

The Endocrine Society, 8401 Connecticut Avenue, Suite 900, Chevy Chase, MD, USA.

“Summary of recommendations:

Diagnostic procedure

• We recommend screening for vitamin D deficiency in individuals at risk for deficiency. We do not recommend population screening for vitamin D deficiency in individuals who are not at risk.
• We recommend using the serum circulating 25-hydroxyvitamin D [25(OH)D] level, measured by a reliable assay, to evaluate vitamin D status in patients who are at risk for vitamin D deficiency. Vitamin D deficiency is defined as a 25(OH)D below 20 ng/ml (50 nmol/liter).

Recommended dietary intakes of vitamin D

• We suggest that infants and children aged 0–1 year require at least 400 IU /day (IU = 25ng) of vitamin D and children 1 year and older require at least 600 IU /day to maximize bone health. Whether 400 and
  600 IU /day for children aged 0–1 years and 1–18 years, respectively, are enough to provide all the potential non-skeletal health benefits associated with vitamin D to maximize bone health and muscle function is not known at this time. However, to raise the blood level of 25(OH)D consistently above
  30 ng/ml (75 nmol/liter) may require at least 1,000 IU /day of vitamin D.
• We suggest that adults aged 19–50 years require at least 600 IU /day of vitamin D to maximize bone health and muscle function. It is unknown whether 600 IU /day is enough to provide all the potential nonskeletal health benefits associated with vitamin D. However, to raise the blood level of 25(OH)D consistently above 30 ng/ml, at least 1,500–2,000 IU /day of vitamin D may be required.
• We suggest that all adults aged 50–70 and 70+ years require at least 600 and 800 IU /day , respectively, of vitamin D. Whether 600 and 800 IU /day of vitamin D are enough to provide all of the potential nonskeletal health benefits associated with vitamin D is not known at this time. However, to raise the blood level of
  25(OH)D above 30 ng/ml may require at least 1’500–2’000 IU /day of supplemental vitamin D.
• We suggest that pregnant and lactating women require at least 600 IU /day of vitamin D and recognize that at least 1’500–2’000 IU /day of vitamin D may be needed to maintain a blood level of 25(OH)D above
  30 ng/ml.
• We suggest that obese children and adults and children and adults on anticonvulsant medications, gluco-corticoids, antifungals such as ketoconazole, and medications for AIDS be given at least two to three times more vitamin D for their age group to satisfy their body’s vitamin D requirement.
• We suggest that the maintenance tolerable upper limits (UL) of vitamin D, which is not to be exceeded without medical supervision, should be1,000 IU /d for infants up to 6 months, 1,500 IU /day for infants from 6 months to 1 year, at least 2,500 IU /day for children aged 1–3 years, 3,000 IU /day for children aged 4–8 years, and 4,000 IU /day for everyone over 8 years. However, higher levels of 2,000 IU /day for children
  0–1 year, 4,000 IU /day for children 1–18 years, and 10,000 IU /day for children and adults 19 years and older may be needed to correct vitamin D deficiency.

Treatment and prevention strategies

• We suggest using either vitamin D2 or vitamin D3 for the treatment and prevention of vitamin D deficiency.
• For infants and toddlers aged 0–1 years who are vitamin D deficient, we suggest treatment with 2,000 IU / day of vitamin D2 or vitamin D3, or with 50,000 IU of vitamin D2 or vitamin D3 once weekly for 6 weeks to achieve a blood level of 25(OH)D above 30 ng/ml, followed by maintenance therapy of 400-1,000 IU /day .
• For children aged 1–18 years who are vitamin D deficient, we suggest treatment with 2,000 IU /day of vitamin D2 or vitamin D3 for at least 6 weeks or with 50,000 IU of vitamin D2 once a week for at least 6 weeks to achieve a blood level of 25(OH)D above 30 ng/ml, followed by maintenance therapy of 600-1,000 IU /day.
• We suggest that all adults who are vitamin D deficient be treated with 50,000 IU of vitamin D2 or vitamin D3 once a week for 8 weeks or its equivalent of 6,000 IU of vitamin D2 or vitamin D3 daily to achieve a blood level of 25(OH)D above 30 ng/ml, followed by maintenance therapy of 1,500–2,000 IU /day.
• In obese patients, patients with malabsorption syndromes, and patients on medications affecting vitamin D metabolism, we suggest a higher dose (two to three times higher; at least 6,000–10,000 IU /day ) of vitamin D to treat vitamin D deficiency and maintain a 25(OH)D level above 30 ng/ml, followed by maintenance therapy of 3,000–6,000 IU /d.
• In patients with extrarenal production of 1,25(OH)2D, we suggest serial monitoring of 25(OH)D levels and serum calcium levels during treatment with vitamin D to prevent hypercalcemia.
• For patients with primary hyperparathyroidism and vitamin D deficiency, we suggest treatment with vitamin D as needed. Serum calcium levels should be monitored.

Vitamin D deficiency has been historically defined and recently recommended by the Institute of Medicine (IOM) as a 25(OH)D of less than 20 ng/ml. Vitamin D insufficiency has been defined as a 25(OH)D of 21–29 ng/ml. In accordance with these definitions, it has been estimated that 20–100% of U.S., Canadian, and European elderly men and women still living in the community are vitamin D deficient. Children and young and middle-aged adults are at equally high risk for vitamin D deficiency and insufficiency worldwide. Vitamin D deficiency is common in Australia, the Middle East, India, Africa, and South America. In the United States, more than 50% of Hispanic and African-American adolescents in Boston and 48% of white preadolescent girls in Maine had 25(OH)D below 20 ng/ml. In addition, 42% of African-American girls and women aged 15–49 years throughout the United States had a blood level of 25(OH)D below 15 ng/ml at the end of the winter, and 32% of healthy students and physicians at a Boston hospital had 25(OH)D below 20 ng/ml. Pregnant and lactating women who take a prenatal vitamin and a calcium supplement with vitamin D remain at high risk for vitamin D deficiency.

The major source of vitamin D for children and adults is exposure to natural sunlight. Very few foods naturally contain or are fortified with vitamin D. In the United States and Canada, milk is fortified with vitamin D, as are some bread products, orange juices, cereals, yogurts, and cheeses. In Europe, most countries do not fortify milk. However, Sweden and Finland now fortify milk, and many European countries add vitamin D to cereals, breads, and margarine. Multivitamin preparations contain 400-1,000 IU of vitamin D2 or vitamin D3.

The major cause of vitamin D deficiency is inadequate exposure to sunlight. Vitamin D deficiency results in abnormalities in calcium, phosphorus, and bone metabolism. Specifically, vitamin D deficiency causes a decrease in the efficiency of intestinal calcium and phosphorus absorption of dietary calcium and phosphorus, resulting in an increase in parathyroid hormone (PTH) levels. The PTH-mediated increase in bone resorption activity creates local foci of bone weakness and causes a generalized decrease in bone mineral density, resulting in osteopenia and osteoporosis. In young children, who have little of this mineral in their skeleton, this defect results in a variety of skeletal deformities classically known as rickets. Vitamin D deficiency also causes muscle weakness; affected children have difficulty standing and walking, whereas the elderly may begin to sway and experience more frequent falls, thereby increasing their risk of fracture.

In conclusion, considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommends supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggests the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D2 or vitamin D3 is recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the non-calcemic benefit for cardiovascular protection.”

June 2011