Читать книгу The Obesity Code - Jason Fung - Страница 13
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THE OVERFEEDING PARADOX
SAM FELTHAM, A qualified master personal trainer, has worked in the U.K. health-and-fitness industry for more than a decade. Not accepting the caloric-reduction theory, he set out to prove it false, following the grand scientific tradition of self-experimentation. In a modern twist to the classic overeating experiments, Feltham decided that he would eat 5794 calories per day and document his weight gain. But the diet he chose was not a random 5794 calories. He followed a low-carbohydrate, high-fat diet of natural foods for twenty-one days. Feltham believed, based on clinical experience, that refined carbohydrates, not total calories, caused weight gain. The macronutrient breakdown of his diet was 10 percent carbohydrate, 53 percent fat and 37 percent protein. Standard calorie calculations predicted a weight gain of about 16 pounds (7.3 kilograms). Actual weight gain, however, was only about 2.8 pounds (1.3 kilograms). Even more interesting, he dropped more than 1 inch (2.5 centimeters) from his waist measurement. He gained weight, but it was lean mass.
Perhaps Feltham was simply one of those genetic-lottery people who are able to eat anything and not gain weight. So, in the next experiment, Feltham abandoned the low-carb, high-fat diet. Instead, for twenty-one days, he ate 5793 calories per day of a standard American diet with lots of highly processed “fake” foods. The macronutrient breakdown of his new diet was 64 percent carbs, 22 percent fat and 14 percent protein—remarkably similar to the U.S. Dietary Guidelines. This time, the weight gain almost exactly mirrors that predicted by the calorie formula—15.6 pounds (7.1 kilograms). His waist size positively ballooned by 3.6 inches (9.14 centimeters). After only three weeks, Feltham was developing love handles.
In the same person and with an almost identical caloric intake, the two different diets produced strikingly different results. Clearly, something more than calories is at work here since diet composition apparently plays a large role. The overfeeding paradox is that excess calories alone are not sufficient for weight gain—in contradiction to the caloric-reduction theory.
OVERFEEDING EXPERIMENTS: UNEXPECTED RESULTS
THE HYPOTHESIS THAT eating too much causes obesity is easily testable. You simply take a group of volunteers, deliberately overfeed them and watch what happens. If the hypothesis is true, the result should be obesity.
Luckily for us, such experiments have already been done. Dr. Ethan Sims performed the most famous of these studies in the late 1960s.1, 2 He tried to force mice to gain weight. Despite ample food, the mice ate only enough to be full. After that, no inducement could get them to eat. They would not become obese. Force-feeding the mice caused an increase in their metabolism, so once again, no weight was gained. Sims then asked a devastatingly brilliant question: Could he make humans deliberately gain weight? This question, so deceptively simple, had never before been experimentally answered. After all, we already thought we knew the answer. Of course overfeeding would lead to obesity.
But does it really? Sims recruited lean college students at the nearby University of Vermont and encouraged them to eat whatever they wanted to gain weight. But despite what both he and the students had expected, the students could not become obese. To his utter amazement, it wasn’t easy to make people gain weight after all.
While this news may sound strange, think about the last time you ate at the all-you-can-eat buffet. You were stuffed to the gills. Now can you imagine downing another two pork chops? Yeah, not so easy. Furthermore, have you ever tried to feed a baby who is absolutely refusing to eat? They scream bloody murder. It is just about impossible to make them overeat. Convincing people to overeat is not the simple task it first seems.
Dr. Sims changed course. Perhaps the difficulty here was that the students were increasing their exercise and therefore burning off the weight, which might explain their failure to gain weight. So the next step was to overfeed, but limit physical activity so that it remained constant. For this experiment, he recruited convicts at the Vermont State Prison. Attendants were present at every meal to verify that the calories—4000 per day—were eaten. Physical activity was strictly controlled.
A funny thing happened. The prisoners’ weight initially rose, but then stabilized. Though at first they’d been happy to increase their caloric intake,3 as their weight started to increase, they found it more and more difficult to overeat, and some dropped out of the study.
But some prisoners were persuaded to eat upwards of 10,000 calories per day! Over the next four to six months, the remaining prisoners did eventually gain 20 percent to 25 percent of their original body weight—actually much less than caloric theory predicted. Weight gain varied greatly person to person. Something was contributing to the vast differences in weight gained, but it was not caloric intake or exercise.
The key was metabolism. Total energy expenditure in the subjects increased by 50 percent. Starting from an average of 1800 calories per day, total energy expenditure increased to 2700 calories per day. Their bodies tried to burn off the excess calories in order to return to their original weight. Total energy expenditure, comprising mostly basal metabolic rate, is not constant, but varies considerably in response to caloric intake. After the experiment ended, body weight quickly and effortlessly returned to normal. Most of the participants did not retain any of the weight they gained. Overeating did not, in fact, lead to lasting weight gain. In the same way, undereating does not lead to lasting weight loss.
In another study, Dr. Sims compared two groups of patients. He overfed a group of thin patients until they became obese. The second group was made up of very obese patients who dieted until they were only obese—but the same weight as the first group.4 This resulted in two groups of patients who were equally heavy, but one group had originally been thin and one group originally very obese. What was the difference in total energy expenditure between the two groups? Those originally very obese subjects were burning only half as many calories as the originally thin subjects. The bodies of the originally very obese subjects were trying to return to their original higher weights by reducing metabolism. In contrast, the bodies of the originally thin subjects were trying to return to their original lower weights by increasing metabolism.
Let’s return to our power plant analogy. Suppose that we receive 2000 tons of coal daily and burn 2000 tons. Now all of a sudden, we start receiving 4000 tons daily. What should we do? Say we continue to burn 2000 tons daily. The coal will pile up until all available room is used. Our boss yells, “Why are you storing your dirty coal in my office? Your ass is FIRED!” Instead, though, we’d do the smart thing: increase coal burning to 4000 tons daily. More power is generated and no coal piles up. The boss says, “You’re doing a great job. We just broke the record for power generation. Raises all around.”
Our body also responds in a similarly smart manner. Increased caloric intake is met with increased caloric expenditure. With the increase in total energy expenditure, we have more energy, more body heat and we feel great. After the period of forced overeating, the increased metabolism quickly sheds the excess pounds of fat. The increase in nonexercise activity thermogenesis may account for up to 70 percent of the increased energy expenditure.5
The results described above are by no means isolated findings. Virtually all overeating studies have produced the same result.6 In a 1992 study, subjects were overfed calories by 50 percent over six weeks. Body weight and fat mass did transiently increase. Average total energy expenditure increased by more than 10 percent in an effort to burn off the excess calories. After the forced overfeeding period, body weight returned to normal and total energy expenditure decreased back to its baseline.
The paper concluded “that there was evidence that a physiological sensor was sensitive to the fact that body weight had been perturbed and was attempting to reset it.”
More recently, Dr. Fredrik Nystrom experimentally overfed subjects double their usual daily calories on a fast-food diet.7 On average, weight and body mass index increased 9 percent, and body fat increased 18 percent—by itself, no surprise. But what happened to total energy expenditure? Calories expended per day increased by 12 percent. Even when ingesting some of the most fattening foods in the world, the body still responds to the increased caloric load by trying to burn it off.
The theory of obesity that’s been dominant for the last half century—that excess calories inevitably lead to obesity—the theory that’s assumed to be unassailably true, was simply not true. None of it was true.
And if excess calories don’t cause weight gain, then reducing calories won’t cause weight loss.
THE BODY SET WEIGHT
YOU CAN TEMPORARILY force your body weight higher than your body wants it to be by consuming excess calories. Over time, the resulting higher metabolism will reduce your weight back to normal. Similarly, you can temporarily force your body weight lower than your body wants it to be by reducing calories. Over time, the resulting lowered metabolism will raise your weight back to normal.
Since losing weight reduces total energy expenditure, many obese people assume that they have a slow metabolism, but the opposite has proved to be true.8 Lean subjects had a mean total energy expenditure of 2404 calories, while the obese had a mean total energy expenditure of 3244 calories, despite spending less time exercising. The obese body was not trying to gain weight. It was trying to lose it by burning off the excess energy. So then, why are the obese . . . obese?
The fundamental biological principle at work here is homeostasis. There appears to be a “set point” for body weight and fatness, as first proposed in 1984 by Keesey and Corbett.9 Homeostatic mechanisms defend this body set weight against changes, both up and down. If weight drops below body set weight, compensatory mechanisms activate to raise it. If weight goes above body set weight, compensatory mechanisms activate to lower it.
The problem in obesity is that the set point is too high.
Let’s take an example. Suppose our body set weight is 200 pounds (approximately 90 kilograms). By restricting calories, we will briefly lose weight—say down to 180 pounds (approximately 81 kilograms). If the body set weight stays at 200 pounds, the body will try to regain the lost weight by stimulating appetite. Ghrelin is increased, and the satiety hormones (amylin, peptide YY and cholecystokinin) are suppressed. At the same time, the body will decrease its total energy expenditure. Metabolism begins shutting down. Body temperature drops, heart rate drops, blood pressure drops and heart volume decreases, all in a desperate effort to conserve energy. We feel hungry, cold and tired—a scenario familiar to dieters.
Unfortunately, the result is the regain of weight back to the original body set weight of 200 pounds. This outcome, too, is familiar to dieters. Eating more is not the cause of weight gain but instead the consequence. Eating more does not make us fat. Getting fat makes us eat more. Overeating was not a personal choice. It is a hormonally driven behavior—a natural consequence of increased hunger hormones. The question, then, is what makes us fat in the first place. In other words, why is the body set weight so high?
The body set weight also works in the reverse. If we overeat, we will briefly gain weight—say to 220 pounds (approximately 100 kilograms). If the body set weight stays at 200 pounds, then the body activates mechanisms to lose weight. Appetite decreases. Metabolism increases, trying to burn off the excess calories. The result is weight loss.
Our body is not a simple scale balancing Calories In and Calories Out. Rather, our body is a thermostat. The set point for weight—the body set weight—is vigorously defended against both increase and decrease. Dr. Rudolph Leibel elegantly proved this concept in 1995.10 Subjects were deliberately overfed or underfed to reach the desired weight gain or loss. First, the group was overfed in order to gain 10 percent of their body weight. Then, their diet was adjusted to return them to their initial weight, and then a further 10 percent or 20 percent weight loss was achieved. Energy expenditure was measured under all of these conditions.
As subjects’ body weight increased by 10 percent, their daily energy expenditure increased by almost 500 calories. As expected, the body responded to the intake of excess calories by trying to burn them off. As weight returned to normal, the total energy expenditure also returned to baseline. As the group lost 10 percent and 20 percent of their weight, their bodies reduced their daily total energy expenditure by approximately 300 calories. Underfeeding did not result in the weight loss expected because the total energy expenditure decreased to counter it. Leibel’s study was revolutionary because it forced a paradigm shift in our understanding of obesity.
No wonder it is so hard to keep the weight off! Diets work well at the start, but as we lose weight, our metabolism slows. Compensatory mechanisms start almost immediately and persist almost indefinitely. We must then reduce our caloric intake further and further simply to maintain the weight loss. If we don’t, our weight plateaus and then starts to creep back up—just as every dieter already knows. (It’s also hard to gain weight, but we don’t usually concern ourselves with that problem, unless we are sumo wrestlers.) Virtually every dietary study of the last century has documented this finding. Now we know why.
Consider our thermostat analogy. Normal room temperature is 70°F (21°C). If the house thermostat were set instead to 32°F (0°C), we’d find it too cold. Using the First Law of Thermodynamics, we decide that the temperature of the house depends upon Heat In versus Heat Out. As fundamental law of physics, it is inviolable. Since we need more Heat In, we buy a portable heater and plug it in. But Heat In is only the proximate cause of the high temperature. The temperature at first goes up in response to the heater. But then, the thermostat, sensing the higher temperature, turns on the air conditioner. The air conditioner and the heater constantly fight against each other until the heater finally breaks. The temperature returns to 32°F.
The mistake here is to focus on the proximate and not the ultimate cause. The ultimate cause of the cold was the low setting of the thermostat. Our failure was that we did not recognize that the house contained a homeostatic mechanism (the thermostat) to return the temperature to 32°F. The smarter solution would have been for us to identify the thermostat’s control and simply set it to a more comfortable 70°F and so avoid the fight between the heater and the air conditioner.
The reason diets are so hard and often unsuccessful is that we are constantly fighting our own body. As we lose weight, our body tries to bring it back up. The smarter solution is to identify the body’s homeostatic mechanism and adjust it downward—and there lies our challenge. Since obesity results from a high body set weight, the treatment for obesity is to lower it. But how do we lower our thermostat? The search for answers would lead to the discovery of leptin.
LEPTIN: THE SEARCH FOR A HORMONAL REGULATOR
DR. ALFRED FROHLICH from the University of Vienna first began to unravel the neuro-hormonal basis of obesity in 1890; he described a young boy with the sudden onset of obesity who was eventually diagnosed with a lesion in the hypothalamus area of the brain. It would be later confirmed that hypothalamic damage resulted in intractable weight gain in humans.11 This established the hypothalamic region as a key regulator of energy balance, and was also a vital clue that obesity is a hormonal imbalance.
Neurons in these hypothalamic areas were somehow responsible for setting an ideal weight, the body set weight. Brain tumors, traumatic injuries and radiation in or to this critical area cause massive obesity that is often resistant to treatment, even with a 500-calorie-per-day diet.
The hypothalamus integrates incoming signals regarding energy intake and expenditure. However, the control mechanism was still unknown. Romaine Hervey proposed in 1959 that the fat cells produced a circulating “satiety factor.”12 As fat stores increased, the level of this factor would also increase. This factor circulated through the blood to the hypothalamus, causing the brain to send out signals to reduce appetite or increase metabolism, thereby reducing fat stores back to normal. In this way, the body protected itself from being overweight.
The race to find this satiety factor was on.
Discovered in 1994, this factor was leptin, a protein produced by the fat cells. The name leptin was derived from “lepto,” the Greek word for thin. The mechanism was very similar to that proposed decades earlier by Hervey. Higher levels of fat tissue produce higher levels of leptin. Traveling to the brain, it turns down hunger to prevent further fat storage.
Rare human cases of leptin deficiency were soon found. Treatment with exogenous leptin (that is, leptin manufactured outside the body) produced dramatic reversals of the associated massive obesity. The discovery of leptin provoked tremendous excitement within the pharmaceutical and scientific communities. There was a sense that the obesity gene had, at long last, been found. However, while it played a crucial role in these rare cases of massive obesity, it was still to be determined whether it played any role in common human obesity.
Exogenous leptin was administered to patients in escalating doses,13 and we watched with breathless anticipation as the patients . . . did not lose any weight. Study after study confirmed this crushing disappointment.
The vast majority of obese people are not deficient in leptin. Their leptin levels are high, not low. But these high levels did not produce the desired effect of lowering body fatness. Obesity is a state of leptin resistance.
Leptin is one of the primary hormones involved in weight regulation in the normal state. However, in obesity, it is a secondary hormone because it fails the causality test. Giving leptin doesn’t make people thin. Human obesity is a disease of leptin resistance, not leptin deficiency. This leaves us with much the same question that we began with. What causes leptin resistance? What causes obesity?
