Hormones conspire to undo weight loss

As if Americans needed any reminder that weight loss is hard and maintaining weight loss even harder, a study has found that for at least a year, subjects who shed weight on a low-calorie diet were hungrier than when they started and had higher levels of hormones that tell the body to eat more, conserve energy and store away fuel as fat.

The report, published Wednesday in the New England Journal of Medicine, helps explain why roughly 4 in 5 dieters wind up gaining back lost pounds within a year or two of losing them -- and, sometimes, pack on a few extra pounds for good measure.

It is a close look at the disheartening pattern: In the wake of weight loss, “multiple compensatory mechanisms” spring to life, the study illustrates, and work together to ensure that weight loss is reversed quickly and efficiently.

The researchers, led by Joseph Proietto of the University of Melbourne’s Department of Medicine, write that more than one solution to the crisis of obesity will likely be necessary: “a combination of medications” that will have to be safe for long-term use.

The study comes as the quest to develop effective medications to fight obesity has hit a long rough patch. Over the last four years, the Food and Drug Administration has rejected or sent back for further research applications for the approval of four different weight-loss drugs. And it has ordered the withdrawal of one of only two over-the-counter medications already on the market, Meridia.


In almost all cases, regulators cited the drugs’ marginal effectiveness and concerns about their safety if used by a broad swath of the population over long periods.

Meanwhile, two-thirds of Americans and a growing proportion of the developing world’s population are overweight or obese, and though obesity rates in the U.S. have begun to stabilize, there’s been no real decline. Public health officials already fear that an entire generation of Americans will suffer poorer health and earlier deaths due to the extra pounds they carry.

The Australian study paints a “very comprehensive” and “really discouraging” picture of the breadth of the body’s response to weight loss, said Dr. Daniel Bessesen, an endocrinologist and obesity researcher at University of Colorado’s Denver Health Medical Center. It captures just how many resources the body musters to ensure that pounds are put back on -- a long list of hormones that regulate appetite, feelings of fullness after eating and how calories are used.

The study enrolled 50 obese men and women without major health problems, and put them on a strict low-calorie diet for eight weeks. Within two weeks after that diet, and again a year later, researchers measured subjects’ blood levels of nine distinct hormones that affect appetite and metabolism, and asked subjects about feelings of hunger after meals, between meals and as mealtime approached.

The challenges of weight control quickly became evident. Thirty-four of 50 enrolled subjects made it to the one-year mark. Four withdrew during the eight-week period of dieting -- a rigorous 550-calorie per day regimen. Seven failed to lose 10% of their body mass, which had been set as a condition of continued participation.

And five withdrew during the yearlong “weight maintenance” phase, when subjects got regular counseling on a diet-and-exercise plan to help them hold steady at the new weight.

Of those who remained, the average weight loss at 10 weeks, when hormone levels were first measured, was just short of 30 pounds.

One year out, those subjects had gained back an average of just over 12 pounds. But after and between meals, their appetites -- and the hormones that influence hunger -- rebounded even more robustly.

With names such as leptin, ghrelin, amylin, cholescystokinin and insulin, the hormones vary widely. Some are secreted from the gut, others by the pancreas or fat cells themselves. Some dial appetite up, others send word to the brain that plenty has been consumed, and still others help regulate how calories are used.

But 52 weeks after subjects had completed their crash diets and were struggling to maintain their loss, that cacophony of hormones was sending a single message, loudly, clearly and after every meal: Eat more.

And subjects were getting that message. When asked, they said they were just as hungry as they had been upon completion of their crash diets and significantly hungrier than they had been before their diets had begun.

“The high rate of relapse after dieting is not surprising,” the authors concluded.

Barbara E. Corkey, an obesity researcher at Boston University, said that although the subjects’ rapid regain of weight was no shock, the authors had turned up important evidence on how distinct hormones work individually and collectively to fight weight loss.

The result, she said, could help in devising new drugs and strategies to support dieters who just want to hang on to their losses.