The Obesity Code: Unlocking the Secrets of Weight Loss (Why Intermittent Fasting Is the Key to Controlling Your Weight)

by Jason Fung

LET’S CONSIDER A last analogy here. Suppose we manage a coal-fired power plant. Every day to generate energy, we receive and burn 2000 tons of coal. We also keep some coal stored in a shed, just in case we run low. Now, all of a sudden, we receive only 1500 tons of coal a day. Should we continue to burn 2000 tons of coal daily? We would quickly burn through our stores of coal, and then our power plant would be shut down. Massive blackouts develop over the entire city. Anarchy and looting commence. Our boss tells us how utterly stupid we are and yells, “Your ass is FIRED!” Unfortunately for us, he’s entirely right. In reality, we’d handle this situation another way. As soon as we realize that we’ve received only 1500 tons of coal, we’d immediately reduce our power generation to burn only 1500 tons. In fact, we might burn only 1400 tons, just in case there were further reductions in shipments. In the city, a few lights go dim, but there are no widespread blackouts. Anarchy and looting are avoided. Boss says, “Great job. You’re not as stupid as you look. Raises all around.” We maintain the lower output of 1500 tons as long as necessary. The key assumption of the theory that reducing caloric intake leads to weight loss is false, since decreased caloric intake inevitably leads to decreased caloric expenditure. This sequence has been proven time and again. We just keep hoping that this strategy will somehow, this time, work. It won’t. Face it. In our heart of hearts, we already ...

This has nothing whatsoever to do with a lack of willpower or any kind of moral failure. It’s a normal hormonal fact of life. We feel hungry, cold, tired and depressed. These are all real, measurable physical effects of calorie restriction. Reduced metabolism and the increased hunger are not the cause of obesity—they are the result. Losing weight causes the reduced metabolism and increased hunger, not the other way around. We do not simply make a personal choice to eat more. One of the great pillars of the caloric-reduction theory of obesity—that we eat too much because we choose to—is simply not true. We do not eat too much because we choose to, or because food is too delicious, or because of salt, sugar and fat. We eat too much because our own brain compels us to.

AND SO WE have the vicious cycle of under-eating. We start by eating less and lose some weight. As a result, our metabolism slows and hunger increases. We start to regain weight. We double our efforts by eating even less. A bit more weight comes off, but again, total energy expenditure decreases and hunger increases. We start regaining weight. So we redouble our efforts by eating even less. This cycle continues until it is intolerable. We are cold, tired, hungry and obsessing about calories. Worst of all, the weight always comes back on. At some point, we go back to our old way of eating. Since metabolism has slowed so much, even resuming the old way of eating causes quick weight gain, up to and even a little past the original point. We are doing exactly what our hormones are influencing us to do. But friends, family and medical professionals silently blame the victim, thinking that it is “our fault.” And we ourselves feel that we are a failure. Sound familiar?

DR. 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.

CERTAINLY, EXERCISE HAS great health benefits. The early Greek physician Hippocrates, considered the father of medicine, said, “If we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health.” In the 1950s, along with increasing concern about heart disease, interest in physical activity and exercise began to grow. In 1955, President Eisenhower established the President’s Council on Youth Fitness. By 1966, the U.S. Public Health Service began to advocate that increasing physical activity was one of the best ways to lose weight. Aerobics studios began to sprout like mushrooms after a rainstorm.

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.

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.

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.”

Certain foods, such as dietary fat, are easily absorbed and take very little energy to metabolize. Proteins are harder to process and use more energy.

the benefit of exercise has a natural upper limit. You cannot make up for dietary indiscretions by increasing exercise. You can’t outrun a poor diet. Furthermore, more exercise is not always better. Exercise represents a stress on the body. Small amounts are beneficial, but excessive amounts are detrimental.17 Exercise is simply not all that effective in the treatment of obesity—and the implications are enormous. Vast sums of money are spent to promote physical education in school—the Let’s Move initiative, improved access to sports facilities and improved playgrounds for children—all based on the flawed notion that exercise is instrumental in the fight against obesity.

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.

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.

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 incre...

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...

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 calori...

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.

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 obes...

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 i...

What causes weight gain? Contending theories abound: •Calories •Sugar •Refined carbohydrates •Wheat •All carbohydrates •Dietary fat •Red meat •All meat •Dairy products •Snacking •Food reward •Food addiction •Sleep deprivation •Stress •Low fiber intake •Genetics •Poverty •Wealth •Gut microbiome •Childhood obesity The various theories fight among themselves, as if they are all mutually exclusive and there is only one true cause of obesity.

Obesity is a hormonal dysregulation of fat mass. The body maintains a body set weight, much like a thermostat in a house. When the body set weight is set too high, obesity results. If our current weight is below our body set weight, our body, by stimulating hunger and/or decreasing metabolism, will try to gain weight to reach that body set weight. Thus, excessive eating and slowed metabolism are the result rather than the cause of obesity.

OBESITY IS NOT caused by an excess of calories, but instead by a body set weight that is too high because of a hormonal imbalance in the body.

Hormones are chemical messengers that regulate many body systems and processes such as appetite, fat storage and blood sugar levels. But which hormones are responsible for obesity? Leptin, a key regulator of body fat, did not turn out to be the main hormone involved in setting the body weight. Ghrelin (the hormone that regulates hunger) and hormones such as peptide YY and cholecystokinin that regulate satiety (feeling full or satisfied), all play a role in making you start and stop eating, but they do not appear to affect the body set weight. How do we know? A hormone suspected of causing weight gain must pass the causality test. If we inject this hormone into people, they must gain weight. These hunger and satiety hormones do not pass the causality test, but there are two hormones that do: insulin and cortisol.

This hormonal theory of obesity avoids making these false assumptions. Consider the following: Assumption 1: Calories In and Calories Out are independent of each other. The hormonal theory explains why Calories In and Calories Out are tightly synchronized with each other. Assumption 2: Basal metabolic rate is stable. The hormonal theory explains how hormonal signals adjust basal metabolic rate to either gain or lose weight. Assumption 3: We exert conscious control over Calories In. The hormonal theory explains that hunger and satiety hormones play a key role in determining whether we eat. Assumption 4: Fat stores are essentially unregulated. The hormonal theory explains that fat stores, like all body systems, are tightly regulated and respond to changes in food intake and activity levels. Assumption 5: A calorie is a calorie. The hormonal theory explains why different calories cause different metabolic responses. Sometimes calories are used to heat the body. At other times, they will be deposited as fat.

Hormones are molecules that deliver messages to a target cell. For example, thyroid hormone delivers a message to cells in the thyroid gland to increase its activity. Insulin delivers the message to most human cells to take glucose out of the blood to use for energy. To deliver this message, hormones must attach to the target cell by binding to receptors on the cell surface, much like a lock and key. Insulin acts on the insulin receptor to bring glucose into the cell. Insulin is the key and fits snugly into the lock (the receptor). The door opens and glucose enters. All hormones work in roughly the same fashion.

When we eat, foods are broken down in the stomach and small intestine. Proteins are broken into amino acids. Fats are broken into fatty acids. Carbohydrates, which are chains of sugars, are broken into smaller sugars. Dietary fiber is not broken down; it moves through us without being absorbed. All cells in the body can use blood sugar (glucose). Certain foods, particularly refined carbohydrates, raise blood sugar more than other foods. The rise in blood sugar stimulates insulin release.

Protein raises insulin levels as well, although its effect on blood sugars is minimal. Dietary fats, on the other hand, tend to raise both blood sugars and insulin levels minimally. Insulin is then broken down and rapidly cleared...

Insulin is a key regulator of energy metabolism, and it is one of the fundamental hormones that promote fat accumulation and storage. Insulin facilitates the uptake of glucose into cells for energy. Without sufficient insulin, glucose builds up in the bloodstream. Type 1 diabetes results from the autoimmune destruction of the insulin-producing cells in the pancreas, which results in extremely low levels of insulin. The discovery of insulin (for which Frederick Banting ...

At mealtimes, ingested carbohydrate leads to more glucose being available than needed. Insulin helps move this flood of glucose out of the bloodstream into storage for later use. We store this glucose by turning it into glycogen in the liver—a process called glycogenesis. (Genesis means “the creation of,” so this term means the creation of glycogen.) Glucose molecules are strung together in long chains to form glycogen....

But the liver has only limited storage space for glycogen. Once full, excess carbohydrates will be turned into fat—a process called de novo lipogenesis. (De novo means “from new.” Lipogenesis means “making...

Several hours after a meal, blood sugars and insulin levels start to drop. Less glucose is available for use by the muscles, the brain and other organs. The liver starts to break down glycogen into glucose to release it into general circulation for energy—the glycogen-storage proc...

Glycogen is easily available, but in limited supply. During a short-term fast (“fast” meaning that you do not eat), your body has enough glycogen available to function. During a prolonged fast, your body can make new glucose from its fat stores—a process called gluconeogenesis (the “making of new sugar”). Fat is burned to r...

Insulin is a storage hormone. Ample intake of food leads to insulin release. Insulin then turns on storage of sugar and fat. When there is no intake of food, insulin levels fall, and burning of sugar...

Normally, this well-designed, balanced system keeps itself in check. We eat, insulin goes up, and we store energy as glycogen and fat. We fast, insulin goes down and we use our stored energy. As long as our feeding and fasting periods are balanced, this system also remains balanced. If we eat breakfast at 7 a.m. and finish eati...

Glycogen is like your wallet. Money goes in and out constantly. The wallet is easily accessible, but can only hold a limited amount of money. Fat, however, is like the money in your bank account. It is harder to access that money, but there is an unlimited storage space for energy there in your account. Like the wallet, glycogen is quickly able to provide glucose to the body. However, the supply of glycogen is lim...

This situation, of course, partially explains the difficulty in losing accumulated fat. Before getting money from the bank, you spend what’s in your wallet first. But you don’t like having an empty wallet. In the same manner, before getting energy from the Fat Bank, you spend the energy in the Glycogen Wallet. But you also don’t like an empty Glycogen Wallet. So you keep the Glycogen Wallet filled, which prevents you from accessing the Fat Bank. In other words, before you can even begin to burn fat, you start feeling hungry and anxious b...

What happens to the excess fat that is produced through de novo lipogenesis? This newly synthesized fat can be stored as visceral fat (around organs), as subcutaneous fat (underneath the skin) or in the liver. Under normal conditions, high insulin levels encourage sugar and fat storage. Low insulin levels encourage glycogen and fat burning. Sustained levels of excessive insulin will tend to increase fat storage. An imbalance...

OBESITY DEVELOPS WHEN the hypothalamus orders the body to increase fat mass to reach the desired body set weight. Available calories are diverted to increase fat, leaving the body short of energy (calories). The body’s rational response is to try to get more calories. It increases the hormonal signals of hunger and decreases hormonal signals of satiety. We can resist the urge to eat and restrict our calorie consumption. Doing so will thwart the hypothalamus for a while, but it has other means of persuasion. The body conserves calories needed for fat growth by shutting down other functions, and metabolism slows. Increased Calories In and decreased Calories Out (eating more and moving less) does not cause obesity, but is instead the result of obesity.

Body set weight is tightly regulated. Most people’s weight remains relatively stable. Even people who gain weight tend to do so extremely gradually—1 to 2 pounds per year. This does not mean, however, that body set weight is unchanging. Over time, there is a gradual upward resetting of the body’s weight thermostat. The key to understanding obesity is to understand what regulates body set weight, why body set weight is set so high, and how to reset it lower.

As a key regulator of energy storage and energy balance, insulin is an obvious suspect as the body set weight regulator. If insulin causes obesity, it must do so predominantly through its effect in the brain. Obesity is controlled in the central nervous system through the body set weight, not in the ...

Certainly, the insulin response differs greatly between lean and obese patients. Obese patients1 tend to have a higher fasting insulin level, as well as an exaggerated insulin response to food. (See Figure 6.1. 2) It is...

ACTUALLY, I CAN make anybody fat. How? By prescribing insulin. It won’t matter that you have willpower, or that you exercise. It won’t matter what you choose to eat. You will get fat. It’s simply a matter of enough insulin and enough time.

High insulin secretion has long been associated with obesity:1 obese people secrete much higher levels of insulin than do those of normal weight. Also, in lean subjects, insulin levels quickly return to baseline after a meal, but in the obese, these levels remain elevated.

Insulin levels are almost 20 percent higher in obese subjects,2 and these elevated levels are strongly correlated to important indices such as waist circumference and waist/hip ratio. The close association between insulin levels and obesity certainly ...