Serum 25-hydroxyvitamin D, vitamin A, and lung cancer mortality in the US population: a potential nutrient-nutrient interaction

Cancer Causes Control. 2012 Sep;23(9):1557-65. doi: 10.1007/s10552-012-0033-8. Epub 2012 Jul 25.


Objective: Excess vitamin A may interrupt vitamin D-mediated transcription of target genes. This study investigated whether serum 25-hydroxyvitamin D [25(OH)D] concentrations were associated with lung cancer mortality, and whether this association varied by excess circulating vitamin A and vitamin A/β-carotene supplement use.

Method: We analyzed 16,693 men and women in the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994. Lung cancer mortality (n = 258, 104 were former smokers and 23 were never smokers) were identified through National Death Index as of 2006. Serum 25(OH)D was measured by a radioimmunoassay. Vitamin A biomarkers including serum retinol, β-carotene, and retinyl esters were measured by HPLC. Supplement use for the past month was obtained by self-report. Multivariate-adjusted hazard ratios (HR) were estimated by Cox proportional hazard models.

Results: There was no association of serum 25(OH)D with overall lung cancer mortality. Among nonsmokers, ≥44 vs. <44 nmol/L of serum 25(OH)D was associated with a decreased risk (HR = 0.53, 95 % CI = 0.31-0.92, former/never smokers and HR = 0.31, 95 % CI = 0.13-0.77, distant-former [quit ≥20 years]/never smokers). The associations were not observed among participants with excess circulating vitamin A (serum retinyl esters ≥7.0 μg/dL or the ratio of retinyl esters to retinol ≥0.08) or vitamin A/β-carotene supplement users. However, statistical evidence to support effect modification of vitamin A was less clear.

Conclusions: Serum 25(OH)D concentrations were inversely associated with lung cancer mortality in nonsmokers. The beneficial association was diminished among those with excess circulating vitamin A or vitamin A/β-carotene supplement users.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dietary Supplements / adverse effects*
  • Female
  • Follow-Up Studies
  • Food-Drug Interactions
  • Humans
  • Lung Neoplasms / blood*
  • Lung Neoplasms / mortality*
  • Male
  • Middle Aged
  • Nutrition Surveys
  • Proportional Hazards Models
  • Risk Factors
  • United States / epidemiology
  • Vitamin A / blood*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • beta Carotene / blood


  • beta Carotene
  • Vitamin A
  • Vitamin D
  • 25-hydroxyvitamin D