Understanding Long-term Effects of Weight Loss

Abstract

The majority of Americans enter midlife overweight or obese. With this excess weight come other cardiometabolic risk factors, and an inc easing propor ion of adults are living with chronic disease. For the growing segment of the middle-aged and older population who are overweight or mildly obese, the question might reasonably be asked, Does losing weight improve longevity? Conversely, Is it harmful for persons who are already overweight to continue gaining weight into old age? In this issue of Epidemiology, Myrskyla and Chang1 report that large weight loss was related to elevated mortality, with a much stronger association in persons with low body mass index (BMI) at baseline. Large weight gain was associated with mortality, but only in persons who were initially obese. No data were available to indicate whether subjects intended to lose weight. Although the authors do not state explicitly that they were evaluating the effects of purposeful or intentional weight loss, their extensive efforts to exclude the influence of disease-related weight loss in their analyses suggest that this was their aim. They concluded that they found no benefits to mortality from weight loss, whereas weight gain seemed to be harmless except in very obese persons. Can observational studies, using only observed body weight change and limited behavioral and health data, answer questions about the long-term benefits and harms of weight loss? Many previous studies have reported elevated risk of death in persons who have lost weight. Problems with interpreting these studies have been well described.2-7 The fundamental issue is that unintentional weight loss is common in older people8'9 and often caused by underlying disease or psychosocial problems that are themselves associ ated with increased mortality. If these conditions are undetected (or if necessary data are not available to the researcher), it is difficult to account for their effects. More recent studies have asked subjects whether they intended to lose weight. This strategy represents an advance, but it only partially disentangles intentional from unintentional weight loss7: among persons expressing the intent to lose weight, a substantial proportion of actual weight loss is likely the result of other causes such as stress or disease.7'10 To move the field forward, it will be necessary to collect much richer, denser, and more biologically relevant data. Others have already described the data and design elements needed to advance our understanding of the long-term harms and benefits of weight change.3'6'7'11 I will highlight 3 of these elements. In a commentary in Epidemiology 10 years ago, Tim Byers stated that epidemiol ogists had reached the limits of what could be learned in observational studies that simply estimate associations between undifferentiated weight loss and mortality.11 Byers called on epidemiologists to engage a major effort to uncover the specific reasons for weight change. Similar comments have been made by others.3 Byers noted that episodes of substantial weight loss, including unintentional weight loss, are common but poorly understood. He suggested the possibility of unintentional weight loss syndromes that could be precursors to chronic disease. Researchers now recognize and are beginning to understand several weight loss syndromes in older persons and in those with disease.12-14