Does coffee consumption impact on heaviness of smoking?

Background and Aims: Coffee 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. Design: We 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. Setting: The TAG consortium includes data from studies in several countries. The UK Biobank includes data from men and women recruited across England, Wales and Scotland. Participants: The TAG consortium provided data on n ≤ 38 181 participants. The UK Biobank provided data on 8072 participants. Measurements: In 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. Findings: Two-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). Conclusions: Amount 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.