Why Is Long-Term Weight Loss So Difficult? It's Biology, Not Willpower!

Donna Ryan, MD


May 25, 2022

It's an all-too-common story. A patient loses weight after changing his or her diet and physical activity.

Donna Ryan

Comprehensive lifestyle intervention (behavior changes around diet and physical activity) is foundational to weight loss efforts, including perhaps the addition of drugs, devices, or surgery. These interventions have been shown to produce weight loss associated with many health benefits, and medical cost savings.

The patient is delighted, feels better, and now "knows what to do" to avoid regaining weight. But in the reduced-weight state, the patient experiences biologic and physiologic changes that can't be perceived by them, but which drive weight regain.

Thus, we usually watch the patient slowly and inexorably regain all of the lost weight. This is demoralizing to patients, who frequently blame their "resolve." Understanding the biologic defense of body fat mass is essential to understanding the weight regain phenomenon and to helping patients succeed with long-term maintenance of weight loss.

When patients are at a reduced weight, we can measure changes in hormones of the gut-brain axis that regulate food intake, and we can measure changes in subjective reports of hunger around a meal. These changes drive increased food intake in the weight reduced state. We can also measure changes in resting metabolic rate and muscle efficiency caused by weight reduction, and this reduced energy expenditure also drives weight gain.

Biology of Weight Regain

What is going on here?

Even the very best lifestyle interventions are associated with weight regain, usually beginning after 1 year. Adding physical activity produces more weight loss than diet alone, but both diet only and diet plus exercise strategies are challenged by weight regain. In fact, across 29 long-term weight loss studies, regain of more than half of the lost weight occurred by 2 years, and 80% of lost weight was regained by 5 years.

A seminal study by Sumithran and colleagues provides insight into the biology of weight regain, describing the effect of weight loss on gut hormone responses (which drive hunger and satiety). In this study, 50 patients who were overweight or obese entered a metabolic unit and received a very-low-energy diet for 10 weeks. The mean weight loss was 14%. Then, the participants were allowed to be free-living but continued counseling was provided to support weight loss maintenance. At week 62 (1 year out of the unit), weight regain was 5% on average, with the mean weight loss down to 8% from baseline.

The investigators assessed hormonal and appetite changes in response to the reduced weight state, first at 10 weeks and then at 62 weeks.

Researchers found that levels of leptin, the hormone produced by body fat that signals satiety, changed with weight loss. The 13% weight loss at 10 weeks led to a 64% reduction in leptin levels. And even with some weight regain, when weight loss was down to 8% at 62 weeks, the leptin level was still reduced by 35%.

When leptin levels fall, energy is conserved via a reduction in resting energy expenditure — the body acts as if it is in starvation mode.

For other relevant hormones, weight loss at both 13% and 8% led to significant reductions in levels of peptide YY, cholecystokinin, insulin (P <.001 for all comparisons), and amylin (P =.002). These hormones also all promote satiety. Conversely, there was an increase in levels of ghrelin (P <.001) at both points, the hormone that promotes hunger. This would drive increased food intake.

Perhaps not unexpectedly, the study found an increase in subjective appetite that increased with weight loss.

Thus, patients with weight loss have a "double whammy": They have changes both in appetite regulation and energy expenditure that favor weight regain.

There is also no doubt that the modern environment is obesogenic. Changes in food and physical activity continue to drive increased intake, decreased activity, and ultimately weight gain. Behavioral factors may also play a role, and it is safe to say that we do not understand all of the factors that drive weight regain.

How Do Successful Losers Do it?

There are, however, some individuals who have been successful in maintaining large weight losses (> 30 lb) over 10 years. These individuals are part of the National Weight Control Registry (NWCR), which was founded in 1993 to identify successful weight-loss maintainers and describe strategies they use to achieve and maintain weight loss.

Although some weight regain occurred over time, these individuals were able to maintain 74% of their initial weight loss at 10 years, and 88% of them had maintained a 10% weight loss at year 10.

Noteworthy is that the individuals who had larger initial weight losses at entry into the NWCR maintained larger weight losses throughout the entire follow-up period. The participants reported high levels of physical activity (approximately 2000 kcal expended per week), low calorie and fat intake, high levels of dietary restraint, and low levels of disinhibition. In addition, most participants reported weighing themselves several times a week (Klem et al; McGuire et al; Thomas et al).

Understanding the physiologic, psychosocial, and environmental determinants of individual variability is an active area of obesity research.

Promoting Weight Loss Maintenance

The best and most important strategy is to continue patient contact after weight loss.

Medications approved for chronic weight management (orlistat, phentermine-topiramate, naltrexone-bupropion, liraglutide, and semaglutide) promote weight loss maintenance if they are taken long-term. For all of the medications, studies of 3 years' duration document weight loss maintenance, as well as weight regain if the medications are discontinued.

Other important strategies include approaching maintenance differently from active weight loss. Dietary approaches and promoting physical activity, such as in the NWCR, would be useful. Other behavioral techniques such as cognitive restructuring (small weight gain is not failure and re-initiation of lifestyle measures is possible) and relapse prevention (maintaining contact with patients and not waiting until large regain has occurred to intervene) are also key.

Patients need to understand the challenges facing them, so do discuss the biological challenges that losing weight brings.

Don't let patients blame themselves. It is biology, not willpower! If you understand the biology of weight regain, you will expect patients to be challenged by regain and you can intervene early.

So first and foremost, keep the patients coming back.

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