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Background: Serum 25-hydroxyvitamin D (25-[OH]D) is considered the best biomarker of clinical vitamin D status.
Objective: To determine the effect of increasing oral doses of vitamin D3 on serum 25-(OH)D and serum parathyroid hormone (PTH) levels in postmenopausal white women with vitamin D insufficiency (defined as a 25-[OH]D level ≤50 nmol/L) in the presence of adequate calcium intake. These results can be used as a guide to estimate the Recommended Dietary Allowance (RDA) (defined as meeting the needs of 97.5% of the population) for vitamin D3.
Design: Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00472823)
Setting: Creighton University Medical Center, Omaha, Nebraska.
Participants: 163 healthy postmenopausal white women with vitamin D insufficiency enrolled in the winter or spring of 2007 to 2008 and followed for 1 year.
Intervention: Participants were randomly assigned to receive placebo or vitamin D3, 400, 800, 1600, 2400, 3200, 4000, or 4800 IU once daily. Daily calcium supplements were provided to increase the total daily calcium intake to 1200 to 1400 mg.
Measurements: The primary outcomes were 25-(OH)D and PTH levels at 6 and 12 months.
Results: The mean baseline 25-(OH)D level was 39 nmol/L. The dose response was curvilinear and tended to plateau at approximately 112 nmol/L in patients receiving more than 3200 IU/d of vitamin D3. The RDA of vitamin D3 to achieve a 25-(OH)D level greater than 50 nmol/L was 800 IU/d. A mixed-effects model predicted that 600 IU of vitamin D3 daily could also meet this goal. Compared with participants with a normal body mass index (<25 kg/m2), obese women (≥30 kg/m2) had a 25-(OH)D level that was 17.8 nmol/L lower. Parathyroid hormone levels at 12 months decreased with an increasing dose of vitamin D3 (P = 0.012). Depending on the criteria used, hypercalcemia occurred in 2.8% to 9.0% and hypercalciuria in 12.0% to 33.0% of participants; events were unrelated to dose.
Limitation: Findings may not be generalizable to other age groups or persons with substantial comorbid conditions.
Conclusion: A vitamin D3 dosage of 800 IU/d increased serum 25-(OH)D levels to greater than 50 nmol/L in 97.5% of women; however, a model predicted the same response with a vitamin D3 dosage of 600 IU/d. These results can be used as a guide for the RDA of vitamin D3, but prospective trials are needed to confirm the clinical significance of these results.
Primary Funding Source: National Institute on Aging.