At first glance, the report by Sinha and colleagues1 from the National Institutes of Health–AARP (formerly known as the American Association of Retired Persons) Diet and Health Study seems to clearly show a higher risk of cancer and cardiovascular mortality with greater consumption of total red meat or total processed meat. The research question is timely and important owing to plausible biological mechanisms for such adverse effects, especially for processed meats, and because these associations are not as well established as popularly believed, particularly for cardiovascular outcomes. A closer review, however, raises important questions about what the findings really show. In such a large community-based population with broad socioeconomic, geographic, ethnic/cultural, and lifestyle diversity, control for confounding factors is particularly important. Paradoxically, the large numbers of events in this cohort make attention to confounding most critical because very small observed risk differences (eg, relative risks of 1.1-1.3) are rendered statistically significant, but are also precisely those most susceptible to being due to bias.
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