Why does weight loss increase mortality risk?

POSSIBLE EXPLANATIONS FOR INCREASED HEALTH RISKS ASSOCIATED WITH WEIGHT LOSS — 

As weight loss has been associated not only with health benefits, but also with health hazards (Table 1), it is important to find some putative explanations for these paradoxical effects. 

One explanation is simple; the associations could be the result of residual confounding and therefore be spurious and classified as artifacts. It is well known that chronic devastating disease will lead to weight loss in many patients, for example, cardiac cachexia or advanced chronic obstructive pulmonary disease, and thus associate observational weight loss with increased mortality risk. 

In the studies from the Nordic countries (7–10), researchers have however tried to avoid this fallacy by excluding unhealthy subjects at baseline for follow-up analyses, as well as excluding the first few years of follow-up regarding mortal events to avoid confounding by subclinical disease. 

Another explanation is that psychiatric conditions such as depression, eventually leading to suicide, could influence the association between weight loss due to poor appetite in depressed subjects with later mortality risk. This could well be true for some select subjects, but cannot be accepted as a more general explanation for larger groups of people experiencing weight loss. 

A third explanation is based on the fact that biological involution (e.g., reduced weight and height) in healthy subjects is part of a normal aging process. This is supposed to take a more rapid course in subjects showing signs of early ageing, thereby increasing the risk of early-onset mortality. For CVD, this can be called the early vascular aging syndrome. 

Finally, it is difficult to rule out the possibility that weight loss per se could be hazardous to health, at least in some susceptible individuals. One piece of evidence supporting this hypothesis is the well-known risk of cholelithiasis attacks in obese patients after rapid intentional weight loss (13). If correct, this hypothesis based on observation could be extrapolated to other unwanted health risks and eventually an increased mortality risk in a subset of people, even after intentional weight loss. 

To settle this research dilemma based on observations, it takes well-designed, randomized, controlled intervention studies in large groups of overweight/obese subjects who are losing weight, either after drug treatment or surgery, or a combination of these modes of interventions

Read more