Title: 25(OH)D half-life as a marker of vitamin D expenditure and function
Funder: Department of Health (England)

Abstract: Background Vitamin D is important for calcium homeostasis and skeletal metabolism and in other areas of health and disease prevention. Recently the IOM updated their recommendations, but recognised that there are uncertainties about how and what amount of vitamin D is needed to achieve the plasma concentrations of 25-hydroxyvitamin D (25(OH)D) associated with optimal health outcomes in different population groups. The plasma concentration of 25(OH)D is used to assess vitamin D status. However, the relationships between intake, plasma 25(OH)D and vitamin D function are not well understood and are influenced by physiological factors including baseline 25(OHD, life-stage and body composition. New biomarkers to assess vitamin D expenditure and function are needed. Aims in relation to the issue to be addressed This study aims to assess the 25(OH)D half-life, reflecting the expenditure of 25(OH)D, and its relationship with determinants such as vitamin D supply, age, kidney function and body composition. We plan to measure 25(OH)D3 half-life in three groups of older people (study a) and one group of young people (study b). After mathematical modelling, data modelling will be performed using data from national surveys (study c). Study (a) This study is an ancillary study to a vitamin D intervention trial in the elderly (VDOP). Half-life studies will be performed twice in each individual, before and after supplementation with three different levels of vitamin D for 12 months. Study (b) We plan to complement existing data on the 25(OH)D3 half-life of 18 young adults. These data will be compared with those in study (a) to investigate differences in relation to age. Study (c) Existing data from the National Diet and Nutrition Surveys will be used to further develop models to predict vitamin D expenditure and requirements of different population groups. Research plan and methods of investigation We will measure the plasma half-life using an oral dose of stable isotope labelled 25(OH)D3 as a tracer. The 25(OH)D3 half-life will be calculated from the terminal slope of the plasma disappearance curve of the tracer as measured by LC-MS/MS . Anthropometrical data and biochemical measures of vitamin D, calcium and bone metabolism and kidney function will be collected. Statistical analyses will include analysis of covariance, multiple regression analysis and mathematical modelling. Research team The 25(OH)D half-life study will be coordinated by dr Schoenmakers, who is also a co-applicant of VDOP. The study will be carried out together with dr Kerry Jones, plus a research assistant, analytical and statistical support. Sample and statistical analysis will take place at MRC HNR. dr Schoenmakers is an expert in research of calcium, phosphate and vitamin D in relation to bone health, specialising in the endocrine and biochemical aspects of this research area. dr Jones has 10 years experience of using stable isotope tracers and mass spectrometry in human studies in different populations to investigate nutrient metabolism. Mss Harnpanich has experience in the conduct of field studies with volunteers. All analysis will be performed at MRC HNR by experienced laboratory personal. The study in the elderly will be performed in Newcastle and the study in young women in Cambridge. Potential impact/influence on the relevant policy field, users and wider stakeholders This study will identify sub-groups of the population at risk of a poor vitamin D status and increased vitamin D requirements. It will contribute to the evidence base on the dose-response to vitamin D supplementation and the factors influencing this relationship. It will contribute to the evidence base of the definition of vitamin D sufficiency and will inform the determination of vitamin D requirements and of setting dietary reference values.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: METABOLIC AND ENDOCRINE