Does coffee consumption impact on heaviness of smoking?

Background and AimsCoffee consumption and cigarette smoking are strongly associated, but whether this association is causal remains unclear. We sought to: (1) determine whether coffee consumption influences cigarette smoking causally, (2) estimate the magnitude of any association and (3) explore potential mechanisms. DesignWe used Mendelian randomization (MR) analyses of observational data, using publicly available summarized data from the Tobacco and Genetics (TAG) consortium, individual-level data from the UK Biobank and in-vitro experiments of candidate compounds. SettingThe TAG consortium includes data from studies in several countries. The UK Biobank includes data from men and women recruited across England, Wales and Scotland. ParticipantsThe TAG consortium provided data on n38181 participants. The UK Biobank provided data on 8072 participants. MeasurementsIn MR analyses, the exposure was coffee consumption (cups/day) and the outcome was heaviness of smoking (cigarettes/day). In our in-vitro experiments we assessed the effect of caffeic acid, quercetin and p-coumaric acid on the rate of nicotine metabolism in human liver microsomes and cDNA-expressed human CYP2A6. FindingsTwo-sample MR analyses of TAG consortium data indicated that heavier coffee consumption might lead to reduced heaviness of smoking [beta=-1.49, 95% confidence interval (CI)=-2.88 to -0.09]. However, in-vitro experiments found that the compounds investigated are unlikely to inhibit significantly the rate of nicotine metabolism following coffee consumption. Further MR analyses in UK Biobank found no evidence of a causal relationship between coffee consumption and heaviness of smoking (beta=0.20, 95% CI=-1.72 to 2.12). ConclusionsAmount of coffee consumption is unlikely to have a major causal impact upon amount of cigarette smoking. If it does influence smoking, this is not likely to operate via effects of caffeic acid, quercetin or p-coumaric acid on nicotine metabolism. The observational association between coffee consumption and cigarette smoking may be due to smoking impacting on coffee consumption or confounding.