Title: The value of 25 hydroxyvitamin D as a biomarker in obesity
Funder: Department of Health (England)

Abstract: Background: Low 25(OH)D and high parathyroid hormone (PTH) have been observed in people with high adiposity (obesity). The potential causes of low 25(OH)D levels include an inadequate supply of vitamin D (by reduced sunlight exposure or poor nutrition), the large pool size of adipose tissue or increased metabolic clearance rate. Overall aims: We will determine 1) the causes of low 25(OH)D in obesity, 2) the consequences of low 25(OH)D in obesity 3) the influence of gender and age on 25(OH)D in obesity. Research plan: We will perform two related studies in male and female pre- and post pubertal children, younger and older adults to determine 1) the relationship between obesity and 25(OH)D, 2) the impact of low 25(OH)D in obesity on bone structure, density and turnover, 3) the causes of low 25(OH)D in obesity (reduced intake/production, increased pool size or increased metabolic clearance rate). The studies will make use of existing longitudinal and case-control studies of male and female children and adults, ages 8 to 75. In study 1 we will examine the relationship between 25(OH)D and adiposity (measured by quantitative computed tomography (QCT) of the abdomen, DXA and BMI). We will examine the consequences of the low 25(OH)D in obesity by studying the effect of BMI and body fat on PTH and bone health. We will assess the influence of 25(OH)D on bone health and examine for interactions with adiposity, age and gender. We will also study the importance of sunlight exposure and diet on 25(OH)D. In study 2 , we will assess the influence of adiposity, diet and sunlight exposure on vitamin D metabolites and urinary calcium, and in adults we will examine the kinetics of 25(OH)D using stable isotope techniques to establish whether obesity affects pool size or metabolic clearance rate. Research team: Eastell is experienced in vitamin D kinetic experiments, measurement of bone turnover, bone density and structure. Walsh is the Principal Investigator (PI) on the study of fat and bone in adults and Dimitri is the PI on the study of fat and bone in children, both are experienced in the measurement of bone turnover, density and structure. Naylor is experienced in bone biochemistry; Barker is an expert in nutritional assessments. Campbell is an experienced medical statistician. Schoenmakers is an experienced scientist with expertise in vitamin D kinetics. Impact: If 25(OH)D deficiency in obesity is related to poorer skeletal health and is due to increased clearance of 25(OH)D or large pool size, then total requirements, and hence supplementation requirements, would be larger than for lean individuals. If 25(OH)D deficiency in obesity is related to poorer skeletal health and is due to reduced dietary intake or sunlight exposure, and metabolic clearance and pool size are the same as lean individuals, then total requirements will be the same for lean and obese people, but obese people may need to meet more of their requirement through supplementation.. If low 25(OH)D in obesity is not associated with poorer skeletal health, there may not be a need for specific supplementation advice for obese people.


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