title: Free 25-hydroxyvitamin D is low in obesity, but there are no adverse associations with bone health.
abstract: The mechanism and clinical significance of low circulating 25-hydroxyvitamin D [25(OH)D] in obese people are unknown. Low total 25(OH)D may be due to low vitamin D-binding proteins (DBPs) or faster metabolic clearance. However, obese people have a higher bone mineral density (BMD), which suggests that low 25(OH)D may not be associated with adverse consequences for bone.
  
  
  
  We sought to determine whether 1) vitamin D metabolism and 2) its association with bone health differ by body weight.
  
  
  
  We conducted a cross-sectional observational study of 223 normal-weight, overweight, and obese men and women aged 25-75 y in South Yorkshire, United Kingdom, in the fall and spring. A subgroup of 106 subjects was also assessed in the winter. We used novel techniques, including an immunoassay for free 25(OH)D, a stable isotope for the 25(OH)D3 half-life, and high-resolution quantitative tomography, to make a detailed assessment of vitamin D physiology and bone health.
  
  
  
  Serum total 25(OH)D was lower in obese and overweight subjects than in normal-weight subjects in the fall and spring (geometric means: 45.0 and 40.8 compared with 58.6 nmol/L, respectively; P < 0.001) but not in the winter. Serum 25(OH)D was inversely correlated with body mass index (BMI) in the fall and spring and in the winter. Free 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)2D] were lower in obese subjects. DBP, the DBP genotype, and the 25(OH)D3 half-life did not differ between BMI groups. Bone turnover was lower, and bone density was higher, in obese people.
  
  
  
  Total and free 25(OH)D and 1,25(OH)2D are lower at higher BMI, which cannot be explained by lower DBP or the shorter half-life of 25(OH)D3 We speculate that low 25(OH)D in obesity is due to a greater pool of distribution. Lower 25(OH)D may not reflect at-risk skeletal health in obese people, and BMI should be considered when interpreting serum 25(OH)D as a marker of vitamin D status.
authors.affiliation: Academic Unit of Bone Metabolism and j.walsh@sheffield.ac.uk.
authors.forename: Jennifer S
authors.identifier: 0000-0002-7122-2650
authors.initials: JS
authors.lastname: Walsh
authors.affiliation: Academic Unit of Bone Metabolism and.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Evans
authors.affiliation: Academic Unit of Bone Metabolism and.
authors.forename: Simon
authors.initials: S
authors.lastname: Bowles
authors.affiliation: Academic Unit of Bone Metabolism and.
authors.forename: Kim E
authors.initials: KE
authors.lastname: Naylor
authors.affiliation: Medical Research Council Human Nutrition Research, Cambridge, United Kingdom.
authors.forename: Kerry S
authors.identifier: 0000-0002-7380-9797
authors.initials: KS
authors.lastname: Jones
authors.affiliation: Medical Research Council Human Nutrition Research, Cambridge, United Kingdom.
authors.forename: Inez
authors.initials: I
authors.lastname: Schoenmakers
authors.affiliation: School of Health and Related Research, University of Sheffield, United Kingdom; and.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Jacques
authors.affiliation: Academic Unit of Bone Metabolism and.
authors.forename: Richard
authors.identifier: 0000-0002-0323-3366
authors.initials: R
authors.lastname: Eastell
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D015519:Bone Density; D016723:Bone Remodeling; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000503:physiopathology; D050177:Overweight / Q000097:blood / Q000503:physiopathology; D012621:Seasons; D006113:United Kingdom; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014809:Vitamin D-Binding Protein / Q000097:blood / Q000235:genetics
chemical_list: D014809:Vitamin D-Binding Protein; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; C104450:25-hydroxyvitamin D
keywords: bone density; bone turnover; half-life; obesity; vitamin D; vitamin D–binding protein