1. The best evidence that there is no safe amount of alcohol consumption is the Mendelian randomization (MR) by Holmes et al from 2014 [1]. I believe that the more recent paper making such claims is no better than the usual observational studies. But the MR paper is convincing to me. The risks for mild drinking appear to be low enough that I don't abstain, and I am happy to tell my patients about my thought process.
2. While we like to claim that a study randomizing people to alcohol wouldn't be ethical, pre-2014 I don't think that would have been true. I think there was enough equipoise. Post-2014, I would need to see some strong counter-evidence to make me think there is equipoise once again.
3. The environment changes. A trial came out last week showing that ASA may be harmful for older healthy people [2]. This probably reflects that our bloodstream is no longer nicotine-filled, etc., so the heart attack risk is low enough that the bleeding risk may outweigh it. There may be something about alcohol that was helpful in the 1950s that is no longer so today, due to these environmental changes.
2. While we like to claim that a study randomizing people to alcohol wouldn't be ethical, pre-2014 I don't think that would have been true. I think there was enough equipoise. Post-2014, I would need to see some strong counter-evidence to make me think there is equipoise once again.
3. The environment changes. A trial came out last week showing that ASA may be harmful for older healthy people [2]. This probably reflects that our bloodstream is no longer nicotine-filled, etc., so the heart attack risk is low enough that the bleeding risk may outweigh it. There may be something about alcohol that was helpful in the 1950s that is no longer so today, due to these environmental changes.
1 = (Free full link): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091648/
2 = https://www.nejm.org/doi/full/10.1056/NEJMoa1800722?query=fe...