Dose Response to Vitamin D Supplementation in Postmenopausal Women A Randomized Trial

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 D-3 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 D-3. 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 D-3, 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/m(2)), obese women (>= 30 kg/m(2)) 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 D-3 (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 D-3 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 D-3 dosage of 600 IU/d. These results can be used as a guide for the RDA of vitamin D-3, but prospective trials are needed to confirm the clinical significance of these results.