Dose response to vitamin D supplementation in postmenopausal women: a randomized trial.
Level 2 - randomized trial
Individual randomized controlled trial.
PubMed 22431675 · doi:10.7326/0003-4819-156-6-201203200-00005
What was done
A 1-year randomized, placebo-controlled trial evaluated 163 healthy postmenopausal white women with vitamin D insufficiency (serum 25-[OH]D ≤ 50 nmol/L) in Omaha, Nebraska. Participants received daily calcium supplementation (aiming for 1200–1400 mg total daily intake) and were randomized to daily oral vitamin D3 doses of 0 (placebo), 400, 800, 1600, 2400, 3200, 4000, or 4800 IU. The primary outcomes were serum 25-(OH)D and parathyroid hormone (PTH) levels at 6 and 12 months.
What was found
Mean baseline 25-(OH)D was 39 nmol/L. Serum 25-(OH)D showed a curvilinear dose response, plateauing at approximately 112 nmol/L at doses above 3200 IU/day. Supplementation at 800 IU/day achieved a 25-(OH)D level greater than 50 nmol/L in 97.5% of participants (a mixed-effects model predicted 600 IU/day would achieve the same). Obese women (BMI ≥ 30 kg/m²) had 25-(OH)D levels 17.8 nmol/L lower than women with normal BMI (<25 kg/m²). PTH at 12 months decreased with higher vitamin D3 doses (P = 0.012). Hypercalcemia occurred in 2.8% to 9.0% and hypercalciuria in 12.0% to 33.0% of participants across groups, with rates unrelated to vitamin D dose.
Why it matters
The study provides empirical dose-response data directly supporting a Recommended Dietary Allowance of 600 to 800 IU/day to correct vitamin D insufficiency in the vast majority of postmenopausal women.
Limits
The study was conducted at a single medical center and restricted entirely to healthy postmenopausal white women, limiting generalizability to men, other racial or ethnic groups, younger ages, and populations with significant comorbidities. Clinical endpoints (such as fractures or falls) were not measured.
Cited by
- supports Supplementation with approximately 4,000 IU of vitamin D per day can raise deficient individuals to sufficient levels above 30 or 40 ng/mL.