title: Serum 25-hydroxyvitamin D, mortality, and incident cardiovascular disease, respiratory disease, cancers, and fractures: a 13-y prospective population study.
abstract: BACKGROUND
  Vitamin D is associated with many health conditions, but optimal blood concentrations are still uncertain.
  
  
  OBJECTIVE
  We examined the prospective relation between serum 25-hydroxyvitamin D [25(OH)D] concentrations [which comprised 25(OH)D3 and 25(OH)D2] and subsequent mortality by the cause and incident diseases in a prospective population study.
  
  
  METHODS
  Serum vitamin D concentrations were measured in 14,641 men and women aged 42-82 y in 1997-2000 who were living in Norfolk, United Kingdom, and were followed up to 2012. Participants were categorized into 5 groups according to baseline serum concentrations of total 25(OH)D <30, 30 to <50, 50 to <70, 70 to <90, and ≥ 90 nmol/L.
  
  
  RESULTS
  The mean serum total 25(OH)D was 56.6 nmol/L, which consisted predominantly of 25(OH)D3 (mean: 56.2 nmol/L; 99% of total). The age-, sex-, and month-adjusted HRs (95% CIs) for all-cause mortality (2776 deaths) for men and women by increasing vitamin D category were 1, 0.84 (0.74, 0.94), 0.72 (0.63, 0.81), 0.71 (0.62, 0.82), and 0.66 (0.55, 0.79) (P-trend < 0.0001). When analyzed as a continuous variable and with additional adjustment for body mass index, smoking, social class, education, physical activity, alcohol intake, plasma vitamin C, history of cardiovascular disease, diabetes, or cancer, HRs for a 20-nmol/L increase in 25(OH)D were 0.92 (0.88, 0.96) (P < 0.001) for total mortality, 0.96 (0.93, 0.99) (P = 0.014) (4469 events) for cardiovascular disease, 0.89 (0.85, 0.93) (P < 0.0001) (2132 events) for respiratory disease, 0.89 (0.81, 0.98) (P = 0.012) (563 events) for fractures, and 1.02 (0.99, 1.06) (P = 0.21) (3121 events) for incident total cancers.
  
  
  CONCLUSIONS
  Plasma 25(OH)D concentrations predict subsequent lower 13-y total mortality and incident cardiovascular disease, respiratory disease, and fractures but not total incident cancers. For mortality, lowest risks were in subjects with concentrations >90 nmol/L, and there was no evidence of increased mortality at high concentrations, suggesting that a moderate increase in population mean concentrations may have potential health benefit, but <1% of the population had concentrations >120 nmol/L.
authors.affiliation: From the Department of Public Health and Primary Care, Institute of Public Health, School of Clinical Medicine (K-TK and RL) and the Medical Research Council Epidemiology Unit (NW), University of Cambridge, Cambridge, United Kingdom.
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.affiliation: From the Department of Public Health and Primary Care, Institute of Public Health, School of Clinical Medicine (K-TK and RL) and the Medical Research Council Epidemiology Unit (NW), University of Cambridge, Cambridge, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Luben
authors.affiliation: From the Department of Public Health and Primary Care, Institute of Public Health, School of Clinical Medicine (K-TK and RL) and the Medical Research Council Epidemiology Unit (NW), University of Cambridge, Cambridge, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wareham
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001205:Ascorbic Acid / Q000097:blood; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality*; D005260:Female; D050723:Fractures, Bone / Q000097:blood / Q000401:mortality*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012140:Respiratory Tract Diseases / Q000097:blood / Q000401:mortality*; D012959:Socioeconomic Factors; D006113:United Kingdom / Q000453:epidemiology; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000401:mortality*
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D; D001205:Ascorbic Acid