THE ART OF medicine is quite peculiar. Once in a while, medical treatments become established that don’t really work. Through sheer inertia, these treatments get handed down from one generation of doctors to the next and survive for a surprisingly long time, despite their lack of effectiveness. Consider the medicinal use of leeches (bleeding) or, say, routine tonsillectomy. Unfortunately, the treatment of obesity is also one such example.
Obesity is defined in terms of a person’s body mass index, calculated as a person’s weight in kilograms divided by the square of their height in meters. A body mass index greater than 30 is defined as obese. For more than thirty years, doctors have recommended a low-fat, calorie-reduced diet as the treatment of choice for obesity. Yet the obesity epidemic accelerates. From 1985 to 2017, the prevalence of obesity in Canada tripled, from 6 percent to 18 percent.1 This phenomenon is not unique to North America, but involves most of the nations of the world.
The Calorie Deception
The Calorie-Reduction Error
TRADITIONALLY, OBESITY HAS been seen as a result of how people process calories, that is, that a person’s weight could be predicted by a simple equation: Calories In – Calories Out = Body Fat This key equation perpetrates what I call the calorie deception. It is dangerous precisely because it appears so simple and intuitive. But what you need to understand is that many false assumptions are built in.
Assumption 1: Calories In and Calories Out are independent of each other
THIS ASSUMPTION IS a crucial mistake. As we’ll see later on in this chapter, experiments and experience have proven this assumption false. Caloric intake and expenditure are intimately dependent variables. Decreasing Calories In triggers a decrease in Calories Out. A 30 percent reduction in caloric intake results in a 30 percent decrease in caloric expenditure. The end result is minimal weight loss.
Assumption 2: Basal metabolic rate is stable
WE OBSESS ABOUT caloric intake with barely a thought for caloric expenditure, except for exercise. Measuring caloric intake is simple, but measuring the body’s total energy expenditure is complicated. Therefore, the simple but completely erroneous assumption is made that energy expenditure remains constant except for exercise. Total energy expenditure is the sum of basal metabolic rate, thermogenic effect of food, nonexercise activity thermogenesis, excess post-exercise oxygen consumption and exercise. The total energy expenditure can go up or down by as much as 50 percent depending upon the caloric intake as well as other factors.
Assumption 3: We exert conscious control over Calories In
EATING IS A deliberate act, so we assume that eating is a conscious decision and that hunger plays only a minor role in it. But numerous overlapping hormonal systems influence the decision of when to eat and when to stop. We consciously decide to eat in response to hunger signals that are largely hormonally mediated. We consciously stop eating when the body sends signals of satiety(fullness) that are largely hormonally mediated.
For example, the smell of frying food makes you hungry at lunchtime. However, if you have just finished a large buffet, those same smells may make you slightly queasy. The smells are the same. The decision to eat or not is principally hormonal. Our bodies possess an intricate system guiding us to eat or not. Body-fat regulation is under automatic control, like breathing. We do not consciously remind ourselves to breathe, nor do we remind our hearts to beat. The only way to achieve such control is to have homeostatic mechanisms. Since hormones control both Calories In and Calories Out, obesity is a hormonal, not a caloric, disorder.
Assumption 4: Fat stores are essentially unregulated
EVERY SINGLE SYSTEM in the body is regulated. Growth in height is regulated by growth hormone. Blood sugars are regulated by the hormones insulin and glucagon, among others. Sexual maturation is regulated by testosterone and estrogen. Body temperature is regulated by a thyroid-stimulating hormone and free thyroxine. The list is endless.
We are asked to believe, however, that growth of fat cells is essentially unregulated. The simple act of eating, without any interference from any hormones, will result in fat growth. Extra calories are dumped into fat cells like doorknobs into a sack. This assumption has already been proven false. New hormonal pathways in the regulation of fat growth are being discovered all the time.
Leptin is the best-known hormone regulating fat growth, but adiponectin, hormonesensitive lipase, lipoprotein lipase and adipose triglyceride lipase may all play important roles. If hormones regulate fat growth, then obesity is a hormonal, not a caloric disorder.
The Exercise MythDR. PETER ATTIA is the cofounder of Nutrition Science Initiative (NuSi), an organization dedicated to improving the quality of science in nutrition and obesity research. A few years ago, he was an elite long-distance swimmer, one of only a dozen or so people to have swum from Los Angeles to Catalina Island. A physician himself, he followed the standard prescribed diet high in carbohydrates and trained religiously for three to four hours daily. He was also, by his own estimation, about forty pounds (18 kilograms) overweight with a body mass index of 29 and 25 percent body fat.
But isn’t increasing exercise the key to weight loss? Caloric imbalance—increased caloric intake combined with decreased caloric expenditure—is considered the recipe for obesity. Up until now, we’ve assumed that exercise was vitally important to weight loss—that by increasing exercise, we can burn off the excess calories that we eat.
THE LIMITS OF EXERCISE: A HARSH REALITY
The Complete Book of Running by Jim Fixx became a runaway bestseller in 1977. The fact that he died at age fifty-two of a massive heart attack was only a minor setback to the cause. Dr. Kenneth Cooper’s book The New Aerobics was required reading in the 1980s where I went to high school. More and more people began incorporating physical activity into their leisure time. It seemed reasonable to expect obesity rates to fall as exercise rates increased.
After all, governments around the world have poured millions of dollars into promoting exercise for weight loss, and they succeeded in getting their citizens moving. In the United Kingdom from 1997 to 2008, regular exercise increased from 32 percent to 39 percent in men and 21 percent to 29 percent in women.1 There’s a problem, though. All this activity had no effect on obesity at all. Obesity increased relentlessly, even as we sweated to the oldies.
The phenomenon is global. A recent eight-country survey revealed that Americans exercised the most—135 days per year compared to a global average of 112 days. The Dutch came in last at 93 days.3 Weight loss was the main motivation for exercise in all countries. Did all this activity translate into
lower rates of obesity? Glad you asked. The Dutch and Italians, with their low exercise rates, experienced less than one-third the obesity of those iron-pumping Americans.
The problem was apparent in the American NHANES data as well. From 2001 to 2011, there was a general increase in physical activity.4 Certain areas (Kentucky, Virginia, Florida and the Carolinas) increased exercise at Herculean rates. But here’s the dismal truth: whether physical activity increases or decreases, it has virtually no relationship to the prevalence of obesity. Increasing exercise did not reduce obesity. It was irrelevant. Certain states exercised more. Other states exercised less. Obesity increased by the same amount regardless.
Is exercise important in reducing childhood obesity? The short answer is no. A 2013 paper5 compared the physical activity (measured using accelerometry) of children aged three to five years to their weight. The authors concluded there is no association between activity and obesity. What went wrong? Inherent to the Calories In, Calories Out theory is the idea that reduced
physical activity plays a key role in the obesity epidemic. This idea is that we used to walk everywhere, but now we drive. With the increase in laborsaving devices such as cars, our exercise has decreased, leading to obesity. The proliferation of video games, television and computers is also believed to contribute to a sedentary lifestyle. Like any good deception, this one sounds pretty reasonable at first. There is a small problem, though. It is just not true. Researcher Dr. Herman Pontzer studied a hunter-gatherer society living a primitive lifestyle in the modern day.
The Hadza in Tanzania often travel 15 to 20 miles per day to gather food. You might assume that their daily energy expenditure is much higher than a typical office worker. Pontzer discusses the surprising results in a New York Times article: “We found that despite all this physical activity, the number of calories that the Hadza burned per day was indistinguishable from that of typical adults in Europe and the United States.”6 Even if we compare relatively recent activity rates to those of the 1980s, before the obesity epidemic came into full swing, rates have not decreased appreciably.7 In a Northern European population, physical-activity energy expenditure was calculated from the 1980s to the mid 2000s. The surprising finding was that if anything, physical activity has actually increased since the 1980s. But this study’s authors went one step further.
They calculated the predicted energy expenditure for a wild mammal, which is predominantly determined by body mass and ambient temperature. Compared to its wildmammal cousins such as the seemingly vigorous cougar, fox and caribou, Homo obesus 2015 is not less physically active. Exercise has not decreased since hunter-gatherer times, or even since the 1980s, while obesity has galloped ahead full steam. It is highly improbable that decreased exercise played any role in causing obesity in the first place. If lack of exercise was not the cause of obesity epidemic, exercise is probably not going to reverse it.
THE AMOUNT OF calories used in a day (Calories Out) is more accurately termed total energy expenditure. Total energy expenditure is the sum of basal metabolic rate (defined below), thermogenic effect of food, non-exercise activity thermogenesis, excess post-exercise oxygen consumption and, of course, exercise.
Total energy expenditure = Basal metabolic rate + Thermogenic effect of food + Nonexercise activity thermogenesis + Excess post-exercise oxygen consumption + Exercise.
The key point here is that total energy expenditure is not the same as exercise. The overwhelming majority of total energy expenditure is not exercise but the basal metabolic rate: metabolic housekeeping tasks such as breathing, maintaining body temperature, keeping the heart pumping, maintaining the vital organs, brain function, liver function, kidney function, etc.
Let’s take an example. Basal metabolic rate for a lightly active average male is roughly 2500 calories per day. Walking at a moderate pace (2 miles per hour) for forty-five minutes every day, would burn roughly 104 calories. In other words, that will not even consume 5 percent of the total energy expenditure. The vast majority (95 percent) of calories are used for basal metabolism.
Basal metabolic rate depends on many factors, including
- gender (basal metabolic rate is generally higher in men),
- age (basal metabolic rate generally drops with age),
- weight (basal metabolic rate generally increases with muscle mass),
- height (basal metabolic rate generally increases with height),
- diet (overfeeding or underfeeding),
- body temperature,
- external temperature (heating or cooling the body) and
- organ function
Nonexercise activity thermogenesis is the energy used in activity other than sleeping, eating or exercise; for instance, in walking, gardening, cooking, cleaning and shopping. The thermogenic effect of food is the energy used in digestion and absorption of food energy. Certain foods, such as dietary fat, are easily absorbed and take very little energy to metabolize. Proteins are harder toprocess and use more energy. Thermogenic effect of food varies according to meal size, meal frequency and macronutrient composition. Excess postexercise oxygen consumption (also called after-burn) is the energy used in cellular repair, replenishment of fuel stores and other recovery activities after exercise.
Because of the complexity of measuring basal metabolic rate, nonexercise activity thermogenesis, thermogenic effect of food and excess post-exercise oxygen consumption, we make a simple but erroneous assumption that these factors are all constant over time. This assumption leads to the crucially flawed conclusion that exercise is the only variable in total energy expenditure. Thus, increasing Calories Out becomes equated with Exercise More. One major problem is that the basal metabolic rate does not stay stable. Decreased caloric intake can decrease basal metabolic rate by up to 40 percent. We shall see that increased caloric intake can increase it by 50 p
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 caloricreduction 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.
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 calorioes, 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?
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?