Regular readers are well aware that losing weight is never a ‘cure’ for obesity – in fact, we know that any weight loss (by whatever means – perhaps with the exception of surgery) leads to hormonal changes that will facilitate weight regain. This is why conventional (diet and exercise) weight-loss strategies sooner or later tend to result in relapse or weight regain.
Just how pervasive and multi-faceted these long-term hormonal responses to weight loss are, is demonstrated by Priya Sumithran and colleagues from the University of Melbourne, in a paper published in the New England Journal of Medicine.
In order to examine whether or not changes in the circulating levels of several hormones involved in the homeostatic regulation of body weight persist over time, the researchers studied 50 overweight or obese individuals, who participated in a 10-week very-low-calorie-diet weight-loss program.
The 36 subjects, who completed the intervention lost about 14% of initial weight and were still well below initial weight (about 8%) 62 weeks after the start of the study.
This weight loss was associated with significant reductions in levels of leptin, peptide YY, cholecystokinin, insulin, and amylin, whereas levels of ghrelin, gastric inhibitory polypeptide, and pancreatic polypeptide increased – most of these changes were still clearly evident at 62 weeks.
In addition, subjective levels of hunger increased and remained significantly elevated at 62 weeks.
Thus, the authors note that:
“One year after initial weight reduction, levels of the circulating mediators of appetite that encourage weight regain after diet-induced weight loss do not revert to the levels recorded before weight loss.”
Given these profound and persistent hormonal changes that affect hunger, appetite, and metabolism, it should come as no surprise that maintaining weight loss is so difficult. It certainly seems like the homeostatic system is happy to wait for the weight to come back – even if this takes several months or even years.
As I have noted before, the challenge in obesity treatment is never how to lose weight – it is all about how to keep it off. This is why, I am never too enthusiastic about new diets or medications that promise to help lose weight – unless these diets or medications also counteract or effectively block the counter-regulatory responses seen in this study, chances are that they will be ineffective in the long term.
Or, as the authors put it:
“..successful management of obesity will require the development of safe, effective, long-term treatments to counteract these compensatory mechanisms and reduce appetite. Given the number of alterations in appetite-regulating mechanisms that have been described so far, a combination of medications will probably be required.”
We do not really need new treatments for weight loss – we do, however, need treatments for weight-loss maintenance or for keeping patients in ‘remission’.
Unfortunately, the regulators still do not appear to have a pathway for approving drugs that will help with the latter.
Hat tip to Bill Colmers for pointing me to this article.
Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, & Proietto J (2011). Long-term persistence of hormonal adaptations to weight loss. The New England journal of medicine, 365 (17), 1597-604 PMID: 22029981