The Effect of Body Weight on Vitamin D Metabolism
Condition: Osteoporosis; Obesity
MeSH terms: Osteoporosis; Body Weight
Study type: Observational

Summary: 
      There is current interest in the role of vitamin D in the prevention and treatment of many
      chronic diseases, including osteoporosis, cancer and neurological disease. The majority of
      vitamin D in the UK comes from the action of sunlight on skin, and very little from dietary
      sources. Half of the adult United Kingdom (UK) population have vitamin D insufficiency
      (according to the Institute of Medicine definition). There are still several important
      unknowns, including what the optimum levels of vitamin D are, and whether the same intake of
      vitamin D is appropriate for all sections of the population.

      Low 25(OH)D and high parathyroid hormone (PTH) have been observed in people with high
      adiposity (obesity), and the summer rise in vitamin D is blunted in 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.

      The investigators will measure metabolites of vitamin D and the kinetics of 25(OH)D using
      stable isotope techniques in lean, overweight and obese men, women and children to establish
      whether age, gender and obesity affect vitamin D metabolism and clearance rate.

      If low 25(OH)D 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 for obese people than for lean people.
    

Detailed description: 
      Part 1: Measurement of vitamin D and metabolites (adults and children) Circulating levels of
      vitamin D metabolites are influenced by calcium intake, so participants will be asked to
      complete a seven day diet diary before the first vitamin D measurement. Measured vitamin D is
      influenced by vitamin D binding protein, lipids and inflammatory cytokines, so the
      investigators will include and correct for these measurements.

      Visit 1 Consent Height and weight Diet diary instructions Urine collection instructions

      Visit 2 Return of 24h urine collection for calcium and creatinine Return of diet diary
      Fasting blood sample for vitamin D, binding protein and metabolites C reactive protein (CRP),
      lipids and creatine kinase (CK), PTH, insulin-like growth factor -1 (IGF-1), creatinine,
      calcium, albumin, phosphate

      Part 2: Measurement of vitamin D clearance rate (adults only) Kinetic studies will be
      perturbed by acute changes in vitamin D (most likely to be caused by sunlight exposure on a
      sunny day), and so the studies will all be conducted in the autumn, winter, and early spring
      when sunlight in Sheffield will not be strong enough to deliver large doses of vitamin D.

      The administration and sampling protocol for the kinetics study has been developed by
      statisticians at the Sheffield School of Health and Related Research (ScHaRR) in
      collaboration with the Medical Research Council Human Nutrition Unit, based on modelling from
      their previous use of the stable isotope tracer method.

      Visit 2 Oral administration of stable vitamin D isotope

      Visit 3 (5-7 days after visit 2) Blood sample for tracer and vitamin D metabolites

      Visit 4 (9 days ± 2 after visit 2) Blood sample for tracer and vitamin D metabolites

      Visit 5 (27 days ± 2 after visit 2) Blood sample for tracer and vitamin D metabolites

      Visit 6 (30 days ± 2 after visit 2) Blood sample for tracer and vitamin D metabolites Height
      and weight

      The effect of obesity on vitamin D metabolites will be determined by regression models of BMI
      and vitamin D measurements corrected for age and gender.

      The effects of obesity on vitamin D kinetics will be determined by modelling metabolic
      clearance rate on age, gender and BMI.

      Subjects' previous data from the 'Effects of obesity on bone structure and strength'study
      (STH 15688) and the 'Body weight and bone' study (STH16199) will be used to evaluate
      relationships between vitamin D metabolism and body fat distribution, bone density and
      structure, and bone biochemistry.
    

Observational model: Ecologic or Community
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        The total study sample will consist of 136 participants (112 adults and 24 children) who
        are lean, overweight or obese. Participants will be drawn from two previous studies; 'The
        effects of obesity on bone structure and strength' (STH 15688) and 'Body weight and bone'
        (STH16199), in which their body composition, bone strength and biochemistry have been
        documented in detail.

        All participants from the previous studies will be invited to participate, and recruitment
        will continue until 112 adults and 24 children across a range of body weights have been
        recruited.
      
Biospecimen description: 
      serum, plasma, urine, DNA
    
Keywords: Vitamin D