The Unfinished Debate on Wine and Other Alcoholic Beverages: Conflicting Evidence, Public Health Messages and the Missing Trial.

The overall health impact of alcohol remains controversial. The Global Burden of Disease (GBD) study made headlines in 2018 by stating that zero alcohol was the safest option. However, its 2022 update introduced age-specific adaptations, asserting that moderate drinking may offer net benefits in some populations. The 2025 U.S. Surgeon General report also discouraged any alcohol intake because of associated cancer risks, but a simultaneous report by the National Academies emphasized tailoring recommendations to individual risks. Mendelian randomization (MR) studies found no health benefits and highlighted increased risks-even at low alcohol doses-challenging dozens of conventional epidemiologic findings in large observational cohorts, some of them of high methodological quality. Given these contradictions, there is a pressing need for large randomized controlled trials in drinkers promoting cessation versus moderation. While small trials have shown some metabolic and cardiovascular benefits of moderate red wine consumption, no large-scale randomized trial has yet assessed hard clinical outcomes comprehensively. Without such evidence, debates will persist. Current guidelines appropriately discourage alcohol in certain populations, but generalizations such as "no safe level of alcohol" might lack sufficient empirical support and perhaps they need a tailored and practical strategy in the context of precision medicine. A balanced, evidence-based approach-free from bias, independent of the industry and grounded in rigorous research-is essential for informed public health policy decisions.