Weight loss engages a “starvation response” that acts to regain the lost weight, and this is a key reason why weight loss is difficult and often temporary. This starvation response includes an increase in the drive to eat and a decrease in calorie expenditure. Using a clever study design, Kevin Hall and colleagues recently quantified the contribution of eating drive to this starvation response. The results suggest that increased eating drive is the primary way in which the starvation response opposes weight loss.
Countless controlled trials have shown that weight loss is difficult, regardless of the approach. Not only is it unlikely that a person with obesity will lose all of his excess fat, but in most cases even moderate losses are regained over time. A key reason for this is that weight loss decreases the circulating concentration of the hormone leptin, activating a negative feedback process that I call the “starvation response”, which I explain in greater detail in my book. This response attempts to bring more calories into the body, and curtail the flow of calories out of the body, thereby refilling fat stores. The starvation response includes an increase in the drive to eat (hunger, food seductiveness) and a decrease in calorie expenditure (slowed metabolic rate and physical activity calorie expenditure).
The “calories out” side of this equation has been fairly well characterized, yet we don’t know nearly as much about the “calories in” side due to the challenges inherent in measuring it. A new paper from Kevin Hall’s research group asks the important question, how strongly does the increased drive to eat counter weight loss? To do this, they used a clever study design in which weight loss was covertly induced.
Hall’s team used data from a one year randomized, placebo-controlled trial of a drug called canagliflozin in 242 people with type 2 diabetes and obesity. Canagliflozin causes substantial loss of glucose via the urine and is used to improve blood glucose control in diabetes. This loss of glucose is roughly 90g per day, amounting to about 360 Calories.
Importantly, since this was a double-blind trial, neither the investigators nor the subjects had direct knowledge of who was receiving the drug. The study involved a long-term, covert perturbation of energy balance that “largely bypasses the volition of the subjects”, which makes it an unusually pure test of the brain’s response to changes in body weight.
Using previously validated mathematical models, and measured body weight changes, Hall’s team estimated the calorie intake of the canagliflozin and placebo groups over the course of the one-year trial. They then used the resulting output to estimate how calorie intake, calorie expenditure, and the drive to eat change with typical weight loss, using two years of data from a commercial weight loss program (Weight Watchers).
The canagliflozin group gradually lost weight over the course of the trial, eventually plateauing about 8 pounds (3.5 kg) lighter than at the beginning. In contrast, the placebo group lost about two pounds (just under 1 kg).
Hall’s model estimates that as the canagliflozin group lost weight and the starvation response kicked in, their calorie intake gradually increased by about 350 Calories per day, eventually halting their weight loss. The model estimates that for each 2.2 pounds (1 kg) of body weight lost, the brain ramps up the drive to eat by about 100 Calories per day in an attempt to regain the weight!
With this information in hand, the researchers were able to gain insight into what happens during typical weight loss due to diet and lifestyle change. Data from a two-year commercial weight loss trial showed that participants experienced their maximum weight loss at 6 months, then gradually regained over the following year and a half.
Plugging these numbers into Hall’s model, they estimate that the initial calorie deficit was about 700 Calories per day, but that this rapidly rebounded, and had almost returned to baseline by 9 months. This might suggest that the participants just stopped trying, but in fact this is unlikely to be the case, because they were still weight reduced at that point and therefore their brains were still experiencing a heightened drive to eat (see the line below labeled “homeostatic drive to eat”).
The researchers were actually able to quantify the effort the participants were putting into their diets by calculating the difference between actual calorie intake and the estimated drive to eat. The results suggest that even though people were already almost back to their baseline calorie intake by 9 months, and already beginning to regain weight, they were nevertheless expending considerable effort to stop themselves from eating substantially more than their baseline intake (to the tune of about 600 Calories per day).
Gradually, as their body weights rebounded over the last year and a half of the trial, their effort level declined toward baseline.
This study has a notable strength, which is that energy balance and body weight were perturbed without the participants’ knowledge. We can be confident that the effects the researchers observed had nothing to do with the participants’ conscious feelings or behaviors around dieting and weight loss. They were the result of nonconscious biological processes.
The study also had at least two notable weaknesses. The first is that the participants in the first trial had type 2 diabetes, which means that we can’t know how well the results would apply to people without diabetes. I’m not aware of any reason why they wouldn’t apply, and the results are consistent with what we know about weight regulation in people without diabetes, but we still have to be cautious. The second weakness is that the trial perturbed calorie balance via a specific mechanism– the excretion of blood glucose in the urine. It’s theoretically possible that the results would have been different if the drug had caused the participants to excrete fat. I don’t think this is very likely, but this question might be tractable by studying randomized trials of Olestra, the fat substitute that gets excreted in feces. Or perhaps by studying liposuction patients.
There are several interesting implications of this study. The first is that the data support our current understanding of how body weight is regulated. Even when energy balance was perturbed without the participants’ knowledge, a powerful starvation response occurred that favored the regain of lost weight. The data support the concept that a sort of body weight “set point” is defended against changes, particularly changes in the downward direction.
A second implication is that between the two arms of the starvation response– the increased drive to eat and the decreased calorie expenditure– the former is by far the most influential. In other words, the primary way in which the brain opposes weight loss is by increasing the biological drive to eat. The data also give us a quantitative estimate of this drive: for each 2.2 lbs (1 kg) of weight lost, the drive to eat increases by about 100 Calories per day*. This is even stronger than I would have predicted.
A third implication– which I think is the most novel of the study– relates to the dynamics of the heightened drive to eat that people experience when they diet, and how this undermines weight loss efforts. After a person loses weight, the biological drive to eat can be so high that they have to exert considerable effort just to prevent themselves from overeating substantially. Even though it seems like they’re no longer adhering to their reduced calorie regimen, they may still be trying hard to eat fewer calories– and succeeding, relative to the amount their brain “wants” them to eat.
The amount of effort that people put into a diet does slowly decline over time however, and as this effort recedes, the biological drive to eat takes over and weight comes back. It’s hard to fight the starvation response forever.
This study strengthens my conviction that the brain’s starvation response has to be managed for long-term weight loss success– and particularly its impact on the drive to eat. Rather than pretending like the starvation response doesn’t exist, as most weight loss approaches do, a better method may be to try to dampen appetite and/or passive calorie intake sufficiently to counterbalance the heightened drive to eat. In other words, find ways to keep the brain happy at a lower calorie intake rather than using willpower to continually struggle against the biological drive to eat.
* I don’t think these results can tell us whether or not the relationship is linear, e.g. if 1 kg of weight loss causes an increase in the drive to eat by 100 Calories, would a 5 kg loss cause an increase of 500 Calories, 10 kg, 1000 Calories, etc.? It’s possible that there is a plateau at some point where the response reaches its maximum strength. Another way of saying this is that this simple rule of thumb may not necessarily apply over the entire range of weight changes. We would need more research to explore this possibility.