Estimation of the Recommended Daily Allowance (RDA) for Vitamin D Intake Using Serum 25 Hydroxyvitamin D Level of 20ng/Ml As the End Point, May Vary According to the Analytical Measurement Technique Used

Presentation Number: OR07-4
Date of Presentation: April 2nd, 2017

Lynette M Smith*1, J Christopher Gallagher2, Glenville Jones3 and Martin Kaufmann3
1University of Nebraska Medical Center, Omaha, NE, 2Creighton University Medical Center, Omaha, NE, 3Queen's University, Kingston, ON, Canada


Abstract: Serum 25-hydroxyvitamin D (25OHD) is considered to be the best biomarker of vitamin D intake. It has been suggested by the Institute of Medicine, World Health Organization and European Food Safety authority that a serum 25OHD level of 20ng/ml (50nmol/l) is an adequate level to prevent fractures. Previously we reported in a dose response study that 800IU daily would meet this requirement for 97.5% of the population. However, this was based on analysis using immunoassay (Diasorin). Since then, Liquid chromatography mass spectrometry (LC-MS/MS) has become the gold standard for 25-O-HD measurement and the original samples were reanalyzed using LC-MS/MS.

Methods: 163 healthy Caucasian postmenopausal women (at least 7 years postmenopausal, age 57-90 years, with vitamin D insufficiency–WHO definition serum 25OHD ≤ 20 ng/ml) were randomized in a double blind placebo controlled trial to one of seven vitamin D3 doses - 400, 800, 1600, 2400, 3200, 4000, 4800 IU/day or placebo for 1 year. All subjects were given calcium supplements to maintain a total calcium intake of 1200-1400 mg/d. Serum 25OHD was measured by immunoassay (Diasorin) and by LC-MS/MS. Statistical analysis employed a mixed effects model for dose response curve estimation and bootstrapping resampling methodology to determine the 95% prediction limits for the 12-month value for 25OHD. The primary outcome of this analysis was to estimate the RDA for vitamin D intake based on exceeding serum 25OHD of 20ng/ml (50nmol/l) measured by LC-MS/MS after 1-year treatment on vitamin D.

Results:  Serum 25OHD measured by both techniques were highly correlated (r=0.93), but compared to LC-MS/MS, Diasorin underestimated serum 25OHD on average by 3.7ng/ml below levels of 30ng/ml. Both assays showed a curvilinear increase in serum 25OHD with dose that best fit a quadratic model. However, the quadratic curve was systematically higher using LC-MS/MS. Bootstrap prediction intervals showed a dose of vitamin D 400 IU daily would exceed a serum 25OHD level of 20ng/ml and a vitamin D intake of 800 IU would exceed a serum 25OHD of 30ng/ml.

Conclusion: In estimating the RDA for vitamin D intake the method used for measuring serum 25-OH-D is an important consideration. Based on the Diasorin assay system the estimated RDA to exceed 20ng/ml was 800 IU daily whereas LC-MS/MS estimated that 400 IU daily would meet the RDA. This has important ramifications for public health recommendations.


Nothing to Disclose: LMS, JCG, GJ, MK