Serum 25-hydroxyvitamin D, mortality, and incident cardiovascular disease, respiratory disease, cancers, and fractures: a 13-y prospective population study

Am J Clin Nutr. 2014 Nov;100(5):1361-70. doi: 10.3945/ajcn.114.086413. Epub 2014 Sep 17.

Abstract

Background: Vitamin D is associated with many health conditions, but optimal blood concentrations are still uncertain.

Objectives: 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.

Design: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Ascorbic Acid / blood
  • Body Mass Index
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / mortality*
  • Female
  • Fractures, Bone / blood
  • Fractures, Bone / mortality*
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Motor Activity
  • Multivariate Analysis
  • Proportional Hazards Models
  • Prospective Studies
  • Respiratory Tract Diseases / blood
  • Respiratory Tract Diseases / mortality*
  • Socioeconomic Factors
  • United Kingdom / epidemiology
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / mortality*

Substances

  • Vitamin D
  • 25-hydroxyvitamin D
  • Ascorbic Acid