ABSTRACT:

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 causally influences cigarette smoking, 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 summarised 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 N = 8,072 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% CI -2.88 to -0.09). However, in vitro experiments found the compounds investigated are unlikely to significantly inhibit 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 on 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.