A safe level of alcohol consumption: the right answer demands the right question.

Alcohol has been produced by humans for nearly ten millennia, but gold-standard evidence by which to judge the health effects of limited alcohol consumption remains elusive, introducing serious difficulty in considering the safety of alcohol consumption. To do so, physicians and policymakers must consider the population, dose and context of alcohol consumption and the end-point, preferably a holistic composite, of interest. The limitations of new research trends, such as mega-cohorts, genetic instrumental variable analysis and modelling studies, must also be viewed against the much larger backdrop of existing evidence. Some existing guidelines, such as the 2015-2020 Dietary Guidelines for Americans, succeed remarkably in this task. Nonetheless, large-scale randomized trials are urgently needed if future generations are to enjoy any greater insight into the health effects of population-wide alcohol consumption than the current one has.