title: Cross-sectional and prospective associations between dietary and plasma vitamin C, heel bone ultrasound, and fracture risk in men and women in the European Prospective Investigation into Cancer in Norfolk cohort.
abstract: BACKGROUND
  Vitamin C sufficiency may help prevent osteoporosis and fractures by mediating osteoclastogenesis, osteoblastogenesis, and bone collagen synthesis.
  
  
  OBJECTIVE
  We determined whether dietary intakes and plasma concentrations of vitamin C were associated with a heel ultrasound and hip and spine fracture risks in older men and women.
  
  
  METHODS
  Participants were recruited from the European Prospective Investigation into Cancer in Norfolk study with 7-d diet diary estimates of vitamin C intake and plasma concentrations. A random subset (4000 of 25,639 subjects) was available for the cross-sectional (ultrasound) study of broadband ultrasound attenuation (BUA) and velocity of sound (VOS), which were determined during the second health examination. The prospective (fracture) study was a case-cohort sample of all participants with a fracture up to March 2009 and the random subset (n = 5319). ANCOVA-determined associations between quintiles of vitamin C intake and plasma status with adjusted BUA and VOS and adjusted Prentice-weighted Cox proportional HRs were calculated for fracture risk.
  
  
  RESULTS
  Women were 58% of the population (39-79 y old), and the median follow-up was 12.6 y (range: 0-16 y). Positive associations across all quintiles of vitamin C intake but not plasma status were significant for VOS in men (β = 2.47 m/s, P = 0.008) and BUA in women (β = 0.82 dB/MHz, P = 0.004). Vitamin C intake was not associated with fracture risk, but there was an inverse association with plasma concentrations in men, with quintile 4 having significantly lower risks of hip fractures (HR: 0.35; 95% CI: 0.16, 0.80) and spine fractures (HR: 0.26; 95% CI: 0.10, 0.69) than quintile 1.
  
  
  CONCLUSIONS
  Higher vitamin C intake was significantly associated with higher heel ultrasound measures in men and women, and higher plasma vitamin C concentrations were significantly associated with reduced fracture risk in men only. Our findings that vitamin C intake and status were inconsistently associated with bone health variables suggest that additional research is warranted.
authors.affiliation: Departments of Population Health and Primary Care.
authors.forename: Henriette
authors.initials: H
authors.lastname: Finck
authors.affiliation: Medicine, and.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hart
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratories, Cambridge, United Kingdom.
authors.forename: Marleen A H
authors.initials: MA
authors.lastname: Lentjes
authors.affiliation: Nutrition, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, United Kingdom; and.
authors.forename: Amy
authors.initials: A
authors.lastname: Jennings
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratories, Cambridge, United Kingdom.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Luben
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratories, Cambridge, United Kingdom.
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.affiliation: Departments of Population Health and Primary Care, a.welch@uea.ac.uk.
authors.forename: Ailsa A
authors.identifier: http://orcid.org/0000-0002-6702-3704
authors.initials: AA
authors.lastname: Welch
mesh_terms: D000328:Adult; D000368:Aged; D001205:Ascorbic Acid / Q000097:blood* / Q000627:therapeutic use; D001206:Ascorbic Acid Deficiency / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D015519:Bone Density; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004032:Diet / Q000009:adverse effects*; D015930:Diet Records; D004739:England / Q000453:epidemiology; D005260:Female; D006620:Hip Fractures / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D010024:Osteoporosis / Q000097:blood / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D058866:Osteoporotic Fractures / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D016103:Spinal Fractures / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control
chemical_list: D001205:Ascorbic Acid
keywords: ascorbic acid; collagen; fracture risk; osteoporosis; vitamin C