When you are a weight loss doctor, your friends and colleagues cannot help but comment on your work. Many conversations contain the question, "Isn't it all just....(carbs, laziness, fast food, inactivity, genes, fructose - fill in speculation here). I began to avoid the subject of my job like it was my dirty secret, but it came up fairly regularly nonetheless. Of the many completely wrong-headed things that non-obese people wonder, the one that came up most often was, "how does a  person let themselves get that way?"

To really respond to that question would have required a discussion as long as this post I'm writing, but my quicker response was, "people don't let themselves get any particular way at all. You didn't let yourself get to be 6 feet tall or 200#, your body decided that for you. A person with a serious weight problem has always spent a tremendous amount of effort struggling to get skinnier. If weight loss was a matter of deciding to change, we would not have obesity at all. A heavy person, walking around in our judgmental, body-conscious society, is living proof that we cannot decide our weight."

What we know from trials that are published in medical journals is that we when we lose weight, the body will adapt. It does this through changes in our metabolic rate, as discussed in my previous post, and also by changing hormones that are involved in energy balance. The idea that hormones control our body composition is not new. Defects in growth hormone, estrogen, and insulin have been recognized for nearly 100 years. But interest by researchers is increasing as the number of hormones identified as playing a role in weight regulation has grown considerably in the last two decades, with the current count at least 25.

With regard to searching for a signal that might alter weight regulation, the hormone most studied is leptin, a chemical that is made primarily in adipose tissue. Leptin is generally considered to be a "stop eating" signal to the brain. The amount of leptin in the circulation is proportional to the size of the adipose tissue, so, in the simplest of worlds, leptin could be a very good candidate for the main regulator of our size over long periods of time. As we grow larger, the quantity of leptin grows with us, telling the brain areas responsible for feeding: "hey, we are big enough down here, it's okay to eat a little less today."

The possibility that leptin was the key regulator of weight was first suggested by the fact that replacing the hormone in people who were born with a defective gene (they were remarkably large, even as toddlers) permanently relieved them of their obesity. Initial excitement about giving other obese patients leptin for weight loss died down quickly in the late 1990s, when it was found to be of no help at all. Typical obese patients have a normal leptin gene and in fact make more leptin than their lean peers. Heavier people actually become less responsive to the signal leptin sends over time, so this does not seem to be something we can over-ride by giving more.

Counteracting leptin's signal to eat less are a host of hormonal signals, generally responding to low energy status between meals. Among the most important is ghrelin, which is secreted from the stomach when it's empty. Because they are located in stomach wall, one might think that the ghrelin secreting cells are somehow responsive to the stretch of the wall during a meal. However, the cells that secrete ghrelin are responsive to sugar, protein and fat in the food that we eat.

Ghrelin tells the brain when the nutrients in the stomach are running low and sends a signal to that effect to the hypothalamus, encouraging an "eat more" response. There are other important hormonal signals, such as amylin from the pancreas, as well as CCK and peptide YY from the intestine which all sense nutrients flowing through the gut and report back to the brain on the feeding status of the body. When we "go on a diet" we are purposely underfeeding nutrients to this regulatory system.

This does not go unnoticed. The signaling that ensures that humans survive through all manner of nutrient environments exists to adapt to these changes. It does so by altering the amounts of these gut and organ hormones.

In a study by Priya Sumathrin in 2011 entitled, Long-Term Persistence of Hormonal Adaptations to Weight Loss, researchers sought to quantify these hormonal changes by measuring blood levels of 50 volunteers while they lost weight. The dietary intervention lasted 10 weeks and the method was to use a very low calorie diet (~500 calories/day). They successfully reduced the participants to 10% less than their original weight, 25-30 pounds (11-13 kg) on average.  The hormones studied included leptin and ghrelin. They found that, as the study subjects became lighter, the hormones responded exactly as one might expect: the leptin (eat less) signal decreased and the ghrelin (eat more) signal increased, in an apparent effort to drive the body back to the baseline weight. Several of the hormones, including leptin, CCK and amylin, remained abnormal for at least a year, confirming that the hormones match the metabolic findings of Liebel and Hirsch. The authors concluded that these hormone changes support the view of a body weight set point and that the hormonal adaptations help to explain the generally abysmal rates of permanent weight loss produced by dieting.

We don't seem to have a set point, as much as a set trend upward. It makes sense that, when the normal trend is disrupted, the body would need to be better at putting a stop to weight loss, rather than gain. If we could lose weight just as easily as we gain it, people would drop dead with regularity, due to accidental starvation. That’s not a winning strategy for the species, so we are not programmed that way. On the other hand, increased weight kills slowly, if at all, so the body is right to "prefer" that slow upward trend as a safety policy.

With regard to the study above, during a severely limiting diet, rather than a body weight set point, it seems more likely to me that the body is focused on an energetic set point that it is in the habit of maintaining. The changes in hormone levels don't come from our body somehow weighing us, moment to moment. They come from signals related to nutrient availability. Glucose, amino acids and break down products of fatty acids are all sensed in the hypothalamus of the of the brain. In addition, insulin levels inform the brain of how recently we have eaten.

Leptin and adiponectin are secreted from the fat cells and give a clear message regarding the long term storage of energy. CCK and PYY from the intestine let the hypothalamus know what's coming in the next few hours. Since one of the main roles of these hormones and regulators is to let us know whether or not to eat, it seems logical that they would react and adapt to coordinate greater appetite when we systematically eat less on a low calorie diet.

So with all this regulation working against our efforts to lose weight, how does anyone succeed?

The fact is, very few people do succeed for any length of time. Apart from the very intense, semi-starvation diets designed to study the body's reaction to weight loss, the typical diet interventions reported in the medical literature show very modest one year results. One of the landmark studies in weight loss and its effect on diabetes risk highlights this well. The Diabetes Prevention Program was an extremely well funded interventional study that sought to compare metformin to an intensive lifestyle program focusing on weight loss, better eating and exercise for diabetes prevention.

The encouraging finding, reported in 2002, was that you could reduce the ten year risk of developing diabetes through a very intensive and prolonged effort with classes, group exercises, monitoring and frequent follow up. One of the reasons the study is so often cited is the fact that a very small overall weight loss, just 7% of body weight on average, reduced the risk of diabetes by 50%. From an obesity perspective however, the fact that the average weight loss was 11.3 pounds (5.6 kg) in this very well executed program is disheartening. I certainly wouldn't have had many patients return for their second visit if I had promised them those results.

This study is not an outlier. In fact, the DPP results are better than most. In an analysis comparing the recommendations from Atkins, Zone, Ornish and "LEARN" philosophies, published in JAMA in 2007, researchers found one year weight loss to range from 4.8 pounds (2.2 kg) to 10.3 pounds (4.7 kg). I suppose I could mention where the different diets fell in that range, but really, who cares? None of these results appear worth pursuing to me. A person with a 10 pound weight problem does not have a weight problem. 

Commercial diets, when actually studied, do about the same as the trials run by physicians and professors. In a review of major commercial weight loss programs in the U.S., Adam Tsai and Thomas Wadden looked at Weight Watchers, Jenny Craig, L.A. Weight Loss, eDiets and meal replacement plans such as Optifast and Medifast. They found that one year weight loss ranged from an increase of 3.2% body weight in one Weight Watchers group to a loss of 15% in a group counseling model with meal replacements at very low calories. While the percentages are encouraging, (overall, about 7% weight loss at one year across all groups), the actual weight loss was modest in these groups, as the participants tended to be fairly light compared to the physician led trials. The Optifast meal replacement studies, which produced the greatest change in body weight, by percent, averaged  just 14 pounds (6.5 kg) lost at one year. 

In my own clinic, I tracked results over three years for quality improvement purposes. I averaged the same percent as most programs report: about 7% of total body weight for patients who stuck with me for more than 12 weeks. If we included drop outs (55%), the results would be far worse (one must assume that the patients dropped out because my advice wasn't working for them). My patients were heavier than those in most studies, so that 7% equated to 27 pounds (12 kg) at an average of one year.

Since I had some patients who did remarkably well, I liked to look at my median weight loss, to get rid of the outlier effect (and really, we should insist on this for all weight loss studies). This was consistently running at 20 pounds (9 kg) through the years that I practiced weight loss medicine. Twenty pounds may sound like an acceptable result for a clinic median if you fail to consider that the average weight for the group was 305 pounds (137 kg) at first visit. So, a typical patient of mine could expect, through a tremendous amount of tracking, repeat visits, constant analyzing and continuing dietary change, to get from 305 to 285 pounds over the course of about a year. 

Clinicians argue that a 5-10 percent change in body weight significantly improves risk factors for disease, like blood sugar and triglycerides. This was the take home message of the DPP trial. But whether doctors think the lab improvements that accompany a 10 or 20 pound loss is worth the effort may be irrelevant when we are specifically targeting obesity in a clinic, non-research setting. What do patients think about these numbers? This was tested by GD Foster and Thomas Wadden in 1997. In the Journal of Consults in Clinical Psychology, they examined patient expectations by asking new clients to their program to propose hard numbers for weight loss goals. Sixty women with average weight of 220 pounds (99 kg) were asked to define a one year goal that they would consider a "dream weight," a "happy weight," an "acceptable weight" or a "disappointed weight."

After a year, 47% of patient participants failed to reach their "disappointed weight." This was despite the fact that the program was quite successful by medical standards, inducing, on average, a 35 pound (16 kg) weight loss.

In my weight loss practice, it was routine for new patients to express a desire to lose 100 pounds, or to reach a "normal" weight, despite the fact that this result almost never occurs. The reassurance that they would likely have improvements in their labs and reach a "not even disappointed" weight goal was something I discussed with hesitance. If obesity were a behavioral problem that could be solved by effort, it wouldn't be unrealistic to try for a "dream weight." If what we weigh was under our personal control, we would be right to simply make a resolution, head down to the weight loss doctor to get a safe program and get going. We could put the blame on ourselves for being heavy and rightfully take charge of this aspect of our health by resolving to live differently. The unfortunate truth is that neither our current nor our future weight is under our control. Our internal regulatory mechanisms, responding to our food environment, decide our size and shape.


Sumathrin, et. al. Long-Term Persistence of Hormonal Adaptations to Weight Loss. NEJM. Oct 27, 2011.

Tsai, AG, Wadden, TA. Systematic Review: An Evaluation of Major Commercial Weight Loss Programs in the United States. Ann Intern Med. 2005;142: 56-66.

Gardner, CD, et. al. Comparison of the Atkins, Zone, Ornish and LEARN Diets for Change in Weight and Related Risk Factors Among Overweight Premenopausal Women. JAMA, March 7, 2007.