Low plasma lycopene concentration is associated with increased mortality in a cohort of patients with prior oral, pharynx or larynx cancers

J Am Coll Nutr. 2004 Feb;23(1):34-42. doi: 10.1080/07315724.2004.10719340.


Objective: This analysis was conducted to evaluate the association between plasma beta-carotene, alpha-carotene, lycopene, lutein/zeaxanthin, total carotenoids, retinol, alpha-tocopherol and subsequent mortality.

Methods: Blood samples collected longitudinally from 259 participants in a chemoprevention trial aimed at the prevention of second cancers of the oral cavity, pharynx, or larynx were analyzed by high performance liquid chromatography for selected micronutrients. All-cause mortality (primary outcome) and cause-specific mortality (secondary outcomes) were evaluated in relation to plasma micronutrient concentrations at baseline and longitudinally.

Results: A total of 61 deaths occurred over a follow-up time of up to 90 months. Cox proportional hazards models with time-dependent covariates were used for data analyses. In models adjusted for age, plasma cholesterol, time-dependent smoking, treatment arm, study site and gender, only plasma lycopene was significantly inversely associated with total mortality [hazard ratio (HR) above versus below median = 0.53, 95% confidence interval (CI) 0.30-0.93]. Plasma alpha-carotene was inversely associated (HR 0.24, 95% CI 0.08-0.75) while plasma retinol was positively associated (HR 5.12, 95% CI 1.54-17.05) with cardiovascular death. Smoking status modified plasma nutrient associations with total mortality. Lycopene (HR 0.08, 95% CI 0.02-0.36), alpha-carotene (HR 0.25, 95% CI 0.09-0.73) and total carotenoids (HR 0.22, 95% CI 0.07-0.70) were inversely associated with mortality in non-smokers, while plasma retinol (HR = 3.56, 95% CI 1.40-9.09) and alpha-tocopherol (HR = 2.47, 95% CI 1.02-5.98) were positively associated with mortality in smokers.

Conclusions: Only plasma lycopene was significantly associated (inversely) with total mortality in the full study population. Smoking modifies associations between nutrients and mortality.

Publication types

  • Multicenter Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antioxidants / metabolism*
  • Carcinoma, Squamous Cell / blood*
  • Carcinoma, Squamous Cell / mortality
  • Carotenoids / blood*
  • Chromatography, High Pressure Liquid
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Laryngeal Neoplasms / blood*
  • Laryngeal Neoplasms / mortality
  • Lycopene
  • Male
  • Middle Aged
  • Mouth Neoplasms / blood*
  • Mouth Neoplasms / mortality
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / mortality
  • Pharyngeal Neoplasms / blood*
  • Pharyngeal Neoplasms / mortality
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Seroepidemiologic Studies
  • Smoking / blood
  • Smoking / mortality
  • Survival Rate


  • Antioxidants
  • Carotenoids
  • Lycopene