Association of coffee drinking with mortality by genetic variation in caffeine metabolism: Findings From the UK Biobank

JAMA Internal Medicine Jul 11, 2018

Loftfield E, et al. - In this large prospective cohort study, researchers assessed links between coffee drinking and mortality by genetic caffeine metabolism score. Data reported that coffee drinking was inversely linked with mortality, including among those drinking 8 or more cups per day and those with genetic polymorphisms showing slower or faster caffeine metabolism. The study findings suggested that coffee drinking can be part of a healthy diet and offers reassurance to coffee drinkers.


  • The UK Biobank is a population-based study that welcomed approximately 9.2 million people from across the United Kingdom to take part.
  • Researchers utilized baseline demographic, lifestyle, and genetic data from the UK Biobank cohort, with follow-up starting in 2006 and ending in 2016 to assess hazard ratios (HRs) for coffee intake and mortality, utilizing multivariable-adjusted Cox proportional hazards models.
  • Potential effect modification was investigated by caffeine metabolism, characterized by a genetic score of previously identified polymorphisms in AHR, CYP1A2, CYP2A6, and POR that influence caffeine metabolism.
  • Of the 502,641 members who consented with baseline data, those who were not pregnant and had complete data on coffee intake and smoking status (n = 498,134) were included.
  • Total, ground, instant, and decaffeinated coffee intake were the analyzed exposures.
  • All-cause and cause-specific mortality were the main outcomes and measures.


  • The study results showed that the mean age of the participants was 57 years (range, 38-73 years); 271,019 (54%) were female, and 387,494 (78%) were coffee drinkers.
  • It was observed that 14,225 deaths occurred over 10 years of follow-up.
  • Findings revealed that coffee drinking was inversely associated with all-cause mortality.
  • HRs for drinking less than 1, 1, 2 to 3, 4 to 5, 6 to 7, and 8 or more cups per day were 0.94 (95% CI, 0.88-1.01), 0.92 (95% CI, 0.87-0.97), 0.88 (95% CI, 0.84-0.93), 0.88 (95% CI, 0.83-0.93), 0.84 (95% CI, 0.77-0.92), and 0.86 (95% CI, 0.77-0.95), respectively using non–coffee drinkers as the reference group.
  • Data reported that similar associations were noted for instant, ground, and decaffeinated coffee, across common causes of death, and regardless of genetic caffeine metabolism score.
  • According to the findings, the HRs for six or more cups per day ranged from 0.70 (95% CI, 0.53-0.94) to 0.92 (95% CI, 0.78-1.10), with no evidence of effect modification across strata of caffeine metabolism score (P=.17 for heterogeneity).
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