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(Vitamin D Guidelines) Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline
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J Clin Endocrin Metab. First published ahead of print June 6, 2011
Michael F. Holick, Neil C. Binkley, Heike A. Bischoff-Ferrari, Catherine M. Gordon, David A. Hanley, Robert P. Heaney, M. Hassan Murad, and Connie M. Weaver
Boston University School of Medicine (M.F.H.), Boston, Massachusetts 02118; University of Wisconsin (N.C.B.), Madison, Wisconsin 53706; University Hospital Zurich (H.A.B.-F.), CH-8091 Zurich, Switzerland; Children's Hospital Boston (C.M.G.), Boston, Massachusetts 02115; University of Calgary Faculty of Medicine (D.A.H.), Calgary, Alberta, Canada T2N 1N4; Creighton University (R.P.H.), Omaha, Nebraska 68178; Mayo Clinic (M.H.M.), Rochester, Minnesota 55905; and Purdue University (C.M.W.), West Lafayette, Indiana 47907
"Increased use of clothing and sunscreen over sun-exposed areas and de- creased consumption of vitamin D-fortified milk increases the risk for vitamin D deficiency"
"In addition, age decreases the capacity of the skin to produce vitamin D3 (3). Although it has been suggested that aging may decrease the ability of the intestine to absorb dietary vitamin D, studies have revealed that aging does not alter the absorption of physiological or pharmacological doses of vitamin D (101, 104-106). The IOM report (20) suggests that 25(OH)D levels need to be at least 20 ng/ml to maintain skeletal health."
"Muscle weakness is a prominent feature of the clinical syndrome of severe vitamin D deficiency. Clinical findings in vitamin D-deficiency myopathy include proximal muscle weakness, diffuse muscle pain, and gait impairments
such as a waddling way of walking (115, 116). Double-blind RCT demonstrated that 800 IU/d vitamin D3 resulted in a 4-11% gain in lower extremity strength or function (80, 117), an up to 28% improvement in body sway (117, 118), and an up to 72% reduction in the rate of falling (119) in adults older than 65 yr after 5 months of treatment.
Several systematic reviews and meta-analyses have demonstrated a reduction in falls associated with interventions to raise 25(OH)D levels."
"We suggest that obese children and adults and children and adults on anticonvulsant medications, glucocorticoids, 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"
"Patients on multiple anticonvulsant medications, glucocorticoids, or AIDS treatment are at increased risk for vitamin D deficiency because these medications increase the catabolism of 25(OH)D (3, 42, 43)."
ABSTRACT
Objective: The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency.
Participants: The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration.
Consensus Process: Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes.
Conclusions: Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested 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 was 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 noncalcemic benefit for cardiovascular protection. (J Clin Endocrinol Metab 96: 0000-0000, 2011)
Vitamin D deficiency is defined as a 25(OH)D below 20 ng/ml (50 nmol/liter).
We recommend against using the serum 1,25-dihydroxyvita- min D [1,25(OH)2D] assay for this purpose and are in favor of using it only in monitoring certain conditions, such as acquired and inherited disorders of vitamin D and phosphate metabolism
Recommendation
1.2 We recommend using the serum circulating 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). We recommend against using the serum 1,25(OH)2D assay for this purpose and are in favor of using it only in monitoring certain conditions, such as acquired and inherited disorders of vitamin D and phosphate metabolism
Recommendation
2.3 We suggest that all adults aged 50 -70 and 70+ yr require at least 600 and 800 IU/d, respectively, of vitamin D to maximize bone health and muscle function. Whether 600 and 800 IU/d of vitamin D are enough to provide all of the potential nonskeletal health benefits associated with vi- tamin 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 1500 -2000 IU/d of supplemental vitamin D (2|QQQQ).
Recommended dietary intakes of vitamin D for patients at risk for vitamin D deficiency
2.1 We suggest that infants and children aged 0 -1 yr require at least 400 IU/d (IU = 25 ng) of vitamin D and children 1 yr and older require at least 600 IU/d to maximize bone health. Whether 400 and 600 IU/d for children aged 0 -1 yr and 1-18 yr, respectively, are enough to provide all the po- tential nonskeletal 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 1000 IU/d of vitamin D (2|QQQQ).
2.2 We suggest that adults aged 19-50 yr require at least 600 IU/d of vitamin D to maximize bone health and muscle function. It is unknown whether 600 IU/d 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 may require at least 1500 -2000 IU/d of vitamin D (2|QQQQ).
2.3 We suggest that all adults aged 50-70 and 70+ yr require at least 600 and 800 IU/d, respectively, of vitamin D. Whether 600 and 800 IU/d 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 1500 -2000 IU/d of supplemental vitamin D (2|QQQQ).
2.6 We suggest that the maintenance tolerable upper limits (UL) of vitamin D, which is not to be exceeded without medical supervision, should be 1000 IU/d for infants up to 6 months, 1500 IU/d for infants from 6 months to 1 yr, at least 2500 IU/d for children aged 1-3 yr, 3000 IU/d for children aged 4 - 8 yr, and 4000 IU/d for everyone over 8 yr. However, higher levels of 2000 IU/d for children 0 -1 yr, 4000 IU/d for children 1-18 yr, and 10,000 IU/d for children and adults 19 yr and older may be needed to correct vitamin D deficiency (2|QQQQ).
3.0 Treatment and prevention strategies
3.4 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 wk or its equivalent of 6000 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 1500-2000 IU/d (2|QQQQ).
Sources of Vitamin D
A major source of vitamin D for most humans comes from exposure of the skin to sunlight typically between 1000 h and 1500 h in the spring, summer, and fall (3-5, 7). Vitamin D produced in the skin may last at least twice as long in the blood compared with ingested vitamin D (53). When an adult wearing a bathing suit is exposed to one minimal erythemal dose of UV radiation (a slight pinkness to the skin 24 h after exposure), the amount of vitamin D produced is equivalent to ingesting between 10,000 and 25,000 IU (5). A variety of factors reduce the skin's production of vitamin D3, including increased skin pigmentation, aging, and the topical application of a sunscreen (3, 39, 40). An alteration in the zenith angle of the sun caused by a change in latitude, season of the year, or time of day dramatically influences the skin's production of vitamin D3 (3, 5). Above and below latitudes of approximately 33°, vitamin D3 synthesis in the skin is very low or absent during most of the winter.
Few foods naturally contain vitamin D2 or vitamin D3 (Table 1).
Suggested 25(OH)D levels
Vitamin D deficiency in children and adults is a clinical syndrome caused by a low circulating level of 25(OH)D (3, 10, 25, 47, 50). The blood level of 25(OH)D that is defined as vitamin D deficiency remains somewhat controversial. A provocative study in adults who received 50,000 IU of vitamin D2 once a week for 8 wk along with calcium supplementation demonstrated a significant reduction in their PTH levels when their 25(OH)D was below 20 ng/ml (16). Several, but not all, studies have reported that PTH levels are inversely associated with 25(OH)D and begin to plateau in adults who have blood levels of 25(OH)D between 30 and 40 ng/ml (20 -22, 60); these findings are consistent with the threshold for hip and nonvertebral fracture prevention from a recent meta-analysis of double-blind randomized controlled trials (RCT) with oral vitamin D (56). When postmenopausal women who had an average blood level of 25(OH)D of 20 ng/ml increased their level to 32 ng/ml, they increased the efficiency of intestinal calcium absorption by 45- 65% (17). Thus, based on these and other studies, it has been suggested that vitamin D deficiency be defined as a 25(OH)D below 20 ng/ml, insufficiency as a 25(OH)D of 21-29 ng/ml, and sufficiency as a 25(OH)D of 30 -100 ng/ml (3).
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