Evaluation of the impact of CYP1A2 induction by charbroiled meal on metabolic phenotype

Clin Nutr ESPEN. 2018 Oct:27:96-99. doi: 10.1016/j.clnesp.2018.06.002. Epub 2018 Jun 28.

Abstract

Background & aims: The process of grilling food items often generates polycyclic aromatic hydrocarbons which are established inducers of CYP1A2, a human drug metabolising enzyme, known to activate some procarcinogens. The impact of such induction on CYP1A2 metabolic phenotype has been the subject of some discordant findings. This study, while considering some limitations in previous study designs, evaluated the effect of CYP1A2 induction by the consumption of charbroiled meal on its metabolic phenotype.

Methods: Caffeine was administered to 17 healthy subjects before, and after, four consecutive days of charbroiled beef ingestion. Blood and spot urine samples were subsequently collected at the 4th and 6th hour post caffeine-administration, respectively, for the assessment of CYP1A2 activity. An additional caffeine administration and sample collection was repeated 48 h after the cessation of charbroiled-beef intake. CYP1A2 activity, derived as the log-transformed molar ratios of caffeine and its metabolites, was statistically analysed for changes in metabolic phenotype.

Results: Urinary and plasma metrics of CYP1A2 activity had mean reference values of 1.53 and 0.38, respectively, in the study subjects. CYP1A2 metabolic phenotype before and after the ingestion of charbroiled meal was not significantly different. However, urinary and plasma metrics of CYP1A2 activity decreased by about 19% (1.53 vs 1.24) and 65% (0.38 vs 0.14), respectively, 48 h after the cessation of charbroiled meal ingestion.

Conclusions: The induction of CYP1A2 by the consumption of charbroiled meals may not portend increased rate of CYP1A2-activation of procarcinogens in humans. However, a potentially significant CYP1A2 inhibition which might result in increased-exposure for drugs predominantly metabolised by this enzyme is likely.

Keywords: CYP1A2; Caffeine; Charbroiled meal; Induction; Inhibition; Metabolic phenotype.

MeSH terms

  • Adult
  • Animals
  • Caffeine / administration & dosage
  • Caffeine / pharmacology
  • Carcinogens / metabolism
  • Cattle
  • Cooking / methods*
  • Cytochrome P-450 CYP1A2 / metabolism*
  • Cytochrome P-450 CYP1A2 Inducers / adverse effects*
  • Cytochrome P-450 CYP1A2 Inducers / analysis*
  • Eating
  • Female
  • Health Surveys
  • Healthy Volunteers
  • Humans
  • Male
  • Meals
  • Phenotype
  • Polycyclic Aromatic Hydrocarbons / metabolism*
  • Red Meat / adverse effects*
  • Red Meat / analysis*
  • Young Adult

Substances

  • Carcinogens
  • Cytochrome P-450 CYP1A2 Inducers
  • Polycyclic Aromatic Hydrocarbons
  • Caffeine
  • CYP1A2 protein, human
  • Cytochrome P-450 CYP1A2