Ricerc@Sapienza

The obesity paradox refers to extant evidence showing that obesity in older subjects or in patients with several chronic diseases may be protective and associated with decreased mortality. A number of mechanisms have been postulated to support the existence of obesity paradox; however, marked heterogeneity was found across studies and this has cast doubt on the actual presence of this phenomenon. The aim of the present narrative review is to summarize evidence underlying the concept of obesity paradox, focusing on limitations and bias related to this phenomenon, with emphasis on the use of body mass index (BMI). A major cause of the discrepancy between studies may be related to the use of BMI in the definition of obesity, that should consider, instead, excess body fat as the main characteristic of this disease and as the unique determinant of its complications. In addition, the adjustment for potential confounders (e.g., stage and grade of diseases, smoking habit, inability to capture the presence of signs of undernutrition in the normal-weight comparative group, consideration of body composition) may significantly scale down the protective role of obesity in terms of mortality. However, it is still necessary to acknowledge few biases (e.g., reverse causation, attrition bias, selection bias of healthy obese subjects or resilient survivors) that would still apply to obesity even when defined according with body composition. Further research should be prompted in order to promote correct phenotyping of patients in order to capture properly the trajectories of mortality in a number of diseases.