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

by Jason Fung

If you take insulin, will you get fat? The short answer is an emphatic “Yes!”

THE RESULTS ARE very consistent. Drugs that raise insulin levels cause weight gain. Drugs that have no effect on insulin levels are weight neutral. Drugs that lower insulin levels cause weight loss. The effect on weight is independent of the effect on blood sugar. A recent study29 suggests that 75 percent of the weight-loss response in obesity is predicted by insulin levels. Not willpower. Not caloric intake. Not peer support or peer pressure. Not exercise. Just insulin.

Insulin causes obesity—which means that insulin must be one of the major controllers of the body set weight. As insulin goes up, the body set weight goes up. The hypothalamus sends out hormonal signals to the body to gain weight. We become hungry and eat. If we deliberately restrict caloric intake, then our total energy expenditure will decrease. The result is still the same—weight gain.

As the insightful Gary Taubes wrote in his book Why We Get Fat: And What to Do about It, “We do not get fat because we overeat. We overeat because we get fat.” And why do we get fat? We get fat because our body set weight thermostat ...

Hormones are central to understanding obesity. Everything about human metabolism, including the body set weight, is hormonally regulated. A critical physiological variable such as body fatness is not left up to the vagaries of daily caloric intake and exercise. Instead, hormones precisely and tightly regulate body fat. We don’t consciously control our body weight any more than we control our heart rates, our basal metabolic rates, our body temperatures or our breathing. These are all automatically regulated, and so is our weight. Hormones tell us we are hungry (ghrelin). Hormones tell us we are full (peptide YY, cholecystokinin). Hormones increase energy expenditure (adrenalin). Hormones shut down energy expenditure ...

Dr. Robert Lustig, a pediatric obesity specialist, believes that high insulin levels act as an inhibitor of leptin, the hormone that signals satiety. Leptin levels increase with body fat. This response acts on the hypothalamus in a negative feedback loop to decrease food intake and return the body to its ideal weight. However, because the brain becomes leptin resistant due to constant exposure, it does not reduce its signal to gain fat.30

In many ways, insulin and leptin are opposites. Insulin promotes fat storage. Leptin reduces fat storage. High levels of insulin should naturally act as an antagonist to leptin. However, the precise mechanisms by which insulin inhibits leptin are yet unknown.

The question is not how to balance calories; the question is how to balance our hormones. The most crucial question in obesity is how to reduce insulin.

I CAN MAKE YOU fat. Actually, I can make anybody fat. How? I prescribe prednisone, a synthetic version of the human hormone cortisol. Prednisone is used to treat many diseases, including asthma, rheumatoid arthritis, lupus, psoriasis, inflammatory bowel disease, cancer, glomerulonephritis and myasthenia gravis. And what is one of the most consistent effects of prednisone? Like insulin, it makes you fat. Not coincidentally, both insulin and cortisol play a key role in carbohydrate metabolism. Prolonged cortisol stimulation will raise glucose levels and, subsequently, insulin. This increase in insulin plays a substantial role in the resulting weight gain.

CORTISOL IS THE so-called stress hormone, which mediates the flight-or-fight response, a set of physiological responses to perceived threats. Cortisol, part of a class of steroid hormones called glucocorticoids (glucose + cortex + steroid), is produced in the adrenal cortex. In Paleolithic times, the stress that led to a release of cortisol was often physical: for instance, being chased by a predator. Cortisol is essential in preparing our bodies for action—to fight or flee. Once released, cortisol substantially enhances glucose availability,1 which provides energy for muscles—very necessary in helping us to run and avoid being eaten. All available energy is directed toward surviving the stressful event. Growth, digestion and other long-term metabolic activities are temporarily restricted. Proteins are broken down and converted to glucose (gluconeogenesis). Vigorous physical exertion (fight or flight) soon often followed, burning up these newly available stores of glucose. Shortly thereafter, we were either dead, or the danger was past and our cortisol decreased back to its normal low levels. And that’s the point: the body is well adapted to a short-term increase in cortisol and glucose levels. Over the long term, however, a problem arises.

stress causes weight gain—something that many people have intuitively understood, despite the lack of rigorous evidence. Stress contains neither calories nor carbohydrates, but can still lead to obesity. Long-term stress leads to long-term elevated cortisol levels, which leads to extra pounds.

Reducing stress is difficult, but vitally important. Contrary to popular belief, sitting in front of the television or computer is a poor way to relieve stress. Instead, stress relief is an active process. There are many time-tested methods of stress relief, including mindfulness meditation, yoga, massage therapy and exercise. Studies on mindfulness intervention found that participants were able to use yoga, guided meditations and group discussion to successfully reduce cortisol and abdominal fat.20

Population studies consistently link short sleep duration and excess weight,24, 25 generally with seven hours being the point where weight gain starts. Sleeping five to six hours was associated with a more than 50 percent increased risk of weight gain.26 The more sleep deprivation, the more weight gained.

Getting enough good sleep is essential to any weight loss plan.

Conventional caloric theories of obesity assume that losing 10 pounds (4.5 kilograms) is the same experience whether you’ve been overweight for one week or one decade. If you reduce the calories, the weight will be lost. But this is simply not true. Likewise, the carbohydrate-insulin hypothesis makes no allowance for duration of obesity: reducing carbohydrates should cause weight loss, regardless of how long you’ve been overweight. But that’s not true either. But the time frame matters a lot. We may try to downplay its effects, but the idea that long-standing obesity is much more difficult to treat has the stench of truth. So we must acknowledge the phenomenon of time dependence. Obesity at age seventeen has consequences that reach decades into the future.1 Any comprehensive theory of obesity must be able to explain why its duration matters so much.

High insulin levels cause weight gain. Food choices play a role in raising insulin levels. But we are missing yet another pathway that increases insulin, one that is both time dependent and independent of diet: insulin resistance.

Insulin resistance is Lex Luthor. It is the hidden force behind most of modern medicine’s archenemies, including obesity, diabetes, fatty liver, Alzheimer’s disease, heart disease, cancer, high blood pressure and high cholesterol. But while Lex Luthor is fictional, the ...

THE HUMAN BODY is characterized by the fundamental biological principle of homeostasis. If things change in one direction, the body reacts by changing in the opposite direction to return closer to its original state. For instance, if we become very cold, the body adapts by increasing body-heat generation. If we become very hot, the body sweats to try to cool itself. Adaptability is a prerequisite for survival and generally holds true for all biological systems. In other words, the body develops resistance. The body resists change out of its comfort range by adapting to it. What happens in the case of insulin resistance? As discussed before, a hormone acts on a cell as a key that fits into a lock. When insulin (the key) no longer fits into the receptor (the lock), the cell is called insulin resistant. Because the fit is poor, the door does not open fully. As a result, less glucose enters. The cell senses that there is too little glucose inside. Instead, glucose is piling up outside the door. Starved for glucose, the cell demands more. To compensate, the body produces extra keys (insulin). The fit is still poor, but more doors are opened, allowing a normal amount of glucose to enter. Suppose that in the normal situation we produce ten keys (insulin). Each key opens a locked door that lets two glucose molecules inside. With ten keys, twenty glucose molecules enter the cell. Under conditions of resistance, the key does not fully open the locked door. Only one glucose molecule ...

Antibiotic resistance is not new. Alexander Fleming discovered penicillin in 1928. Mass production of it was perfected by 1942, with funds from the U.S. and British governments for use in World War II. In his 1945 Nobel lecture, “Penicillin,” Dr. Fleming correctly predicted the emergence of resistance. He said, There is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non lethal quantities of the drug make them resistant. Here is a hypothetical illustration. Mr. X. has a sore throat. He buys some penicillin and gives himself, not enough to kill the streptococci but enough to educate them to resist penicillin.2

WHAT ABOUT VIRAL resistance? How do we become resistant to viruses like measles or polio, for instance? Before the development of vaccines, it was viral infection itself that caused resistance to further infection. If you became infected with measles virus as a child, you’d be protected from reinfection with measles for the rest of your life. Most (though not all) viruses work this way. Exposure causes resistance.

viruses cause viral resistance. Higher doses, usually in the form of repeated vaccinations, cause more resistance.

WHEN COCAINE IS taken for the first time, there is an intense reaction—the “high.” With each subsequent use of the drug, the high becomes less intense. Sometimes users start to take larger and larger doses to achieve the same high. Through exposure to the drug, the body develops resistance to its effects—a condition called tolerance. People can build up tolerance to narcotics, marijuana, nicotine, caffeine, alcohol, benzodiazepines and nitroglycerin.

drugs cause drug resistance.

So let’s recap what we know: •Antibiotics cause antibiotic resistance. High doses cause more resistance. •Viruses cause viral resistance. High doses cause more resistance. •Drugs cause drug resistance (tolerance). High doses cause more resistance.

IF INSULIN RESISTANCE is similar to other forms of resistance, the first thing to look at is high, persistent levels of insulin itself.

A 1993 study measured this effect.8 Patients were started on intensive insulin treatment. In six months, they went from no insulin to 100 units a day on average. Their blood sugars were very, very well controlled. But the more insulin they took, the more insulin resistance they got—a direct causal relationship, as inseparable as a shadow is from a body. Even as their sugars got better, their diabetes was getting worse! These patients also gained an average of approximately 19 pounds (8.7 kilograms), despite reducing their calorie intake by 300 calories per day. It didn’t matter. Not only does insulin cause insulin resistance, it also causes weight gain.

SO WE KNOW that insulin causes insulin resistance. But insulin resistance also causes high insulin—a classic vicious or self-reinforcing, cycle. The higher the insulin levels, the greater the insulin resistance. The greater the resistance, the higher the levels. The cycle keeps going around and around, one element reinforcing the other, until insulin is driven up to extremes. The longer the cycle continues, the worse it becomes—that’s why obesity is so time dependent. People who are stuck in this vicious cycle for decades develop significant insulin resistance. That resistance leads to high insulin levels that are independent of that person’s diet. Even if you were to change your diet, the resistance would still keep your insulin levels high. If your insulin levels stay high, then your body set weight stays high. The thermostat is set high, and your weight will be drawn irresistibly upward. The fat get fatter. The longer you are obese, the harder it is to eradicate. But you already knew that. Oprah knew it. Everybody already knew it. Most current theories of obesity cannot explain this effect, so they instead ignore it. But obesity is time-dependent. Like rust, it takes time to develop.

A diet high in foods that provoke an insulin response may initiate obesity, but over time, insulin resistance becomes a larger and larger part of the problem and can become, in fact, a major driver of high insulin levels. Obesity drives itself. A long-standing obesity cycle is extremely difficult to break, and dietary changes alone may not be sufficient.

What about insulin resistance? At the very beginning of obesity, a person will manifest little insulin resistance, but it develops over time. The longer you are obese, the more insulin resistance you have. Gradually, that insulin resistance will cause even your fasting insulin levels to rise. The high insulin levels are the primary insult. Persistent high insulin levels lead gradually and eventually to insulin resistance. Insulin resistance in turn leads to higher insulin levels. But the crucial starting point of the vicious cycle is high insulin levels. Everything else follows and develops with time—and the fat get fatter.

HOW DOES INSULIN resistance produce obesity? We know that the hypothalamic area of the brain controls the body set weight and that insulin plays a key role in resetting the body set weight up or down. As insulin resistance develops, does it develop in all the cells in the body, including the brain? If all cells are insulin resistant, then high levels of it should not increase the body set weight. However, all the cells in the body are not equally resistant. Insulin resistance is compartmentalized.

The main compartments are the brain, liver and muscle.

Changing the resistance of one does not change resista...

For example, hepatic (liver) insulin resistance does not affect insulin resistance in the brain or muscle. When we ingest excess carbohydrates, we develop hepatic insulin resistance. Significant dietary intervention will reverse the hepatic insulin resistance, but will have no effect on insulin resistance in the muscles or the brain. Lack of exercise may lead to insulin resistance in the muscles. Exercise ...

In response to hepatic or muscle insulin resistance, overall insulin levels increase. However, at the appetite centers in the hypothalamus, insulin’s effect is unchanged. The brain is not resistant to insulin. When high insulin levels reach the br...

HIGH HORMONAL LEVELS by themselves cannot cause resistance. Otherwise, all of us would quickly develop crippling resistance. We are naturally defended against resistance because we secrete our hormones—cortisol, insulin, growth hormone, parathyroid hormone or any other hormone—in bursts. High levels of hormones are released at specific times to produce a specific effect. Afterward, the levels quickly drop and stay very low.

Consider the body’s daily rhythm. The hormone melatonin, produced by the pineal gland, is virtually undetectable during the day. As night falls, it begins to increase, and its levels peak in the early morning hours. Cortisol levels also rise in the early morning hours and spike just before we awaken. Growth hormone is secreted mostly in deep sleep and is usually undetectable during the day. Thyroid-stimulating hormone peaks in early morning. The periodic release of all these hormones is essential in preventing resistance.

Whenever the body is exposed to a constant stimulus, it acclimates to it (once again, homeostasis at work). Have you ever watched a baby sleep in a crowded, noisy airport? The ambient noise is very loud, but constant. The baby adapts by developing resistance to the noise. It basically just ignores it. Now imagine the same baby sleeping in a quiet house. A slight creak of the floorboards may be enough to wake him up. Even though i...

What our body does, in effect, is to continually keep us in a quiet room. Every once in a while, we are momentarily exposed to a sound. Each time this happens, we experience the full effect. We are never given a chance to get accustomed to it—to develop resistance. High levels alone do not lead to resistance. There are two requirements for resistance—high hormonal levels and constant stimulus. We’ve known this for quite some time. In fact, we use this to our advantage in drug therapy for angina (chest pain). Patients prescribed a nitroglycerin patch are often given the instructions to put the patch on in the morning and take it off in the evening. By alternating periods of high drug effect and low drug effect, there is no chance for the body to develop resistance to the nitroglycerin. If the drug patch is worn constantly, it quickly becomes useless. Our body simply develops drug resistance.

In the case of insulin resistance, it comes down to both meal composition and meal timing—the two critical components of insulin resistance. The types of food eaten influence the insulin levels. Should we eat candy or olive oil? This is the question of macronutrient composition, or “what to eat.” However, the persistence of insulin plays a key role in the development of insulin resistance, so there is also the question of meal timing, or “when to eat.” Both components are equally important. Unfortunately, we spend obsessive amounts of time and energy trying to understand what we should be eating and devote virtually no time to when we should be eating. We are only seeing half the picture.

Pulses of insulin (mealtimes) are followed by a long fasting period (sleep), as illustrated in Figure 10.1. However, the situation changes entirely when we are constantly exposed to insulin. What would happen if daily eating opportunities are increased from three to six—which is exactly what’s happened since the 1970s. Moms everywhere knew that eating snacks all the time was a bad idea: “It’ll make you fat”; “You’ll ruin your dinner.” But nutritional authorities have now decided that snacking is actually good for us. That eating more often will make us thinner, as ridiculous as that sounds. Many obesity specialists and physicians suggest eating even more frequently, every 2.5 hours. An American survey of more than 60,000 adults and children10 revealed that, in 1977, most people ate three times a day. By 2003, most people were eating five to six times a day. That is, three meals a day plus two to three snacks in between. The average time between meals has dropped 30 percent, from 271 minutes to 208 minutes. The balance between the fed state (insulin dominant) and the fasted state (insulin deficient) has been completely destroyed. (See Figure 10.2.) We now spend most of our time in the fed state. Is it any great mystery that we’re gaining weight?

But the story gets worse. Insulin resistance, in turn, leads to higher fasting insulin levels. Fasting insulin levels are normally low. Now, instead of starting the day with low insulin after the nightly fast, we are starting with high insulin. The persistence of high insulin levels leads to even more resistance. In other words, insulin resistance itself leads to more resistance—a vicious cycle.

Several myths are often perpetuated to convince people that snacking is beneficial. The first myth is that eating frequently will increase your metabolic rate. Your metabolic rate does increase slightly after meals to digest your food—the thermogenic effect of food. However, the overall difference is extremely small.12 Eating six small meals per day causes the metabolic rate to go up six times a day, but only a little. Eating three larger meals per day causes metabolic rate to go up three times a day, but a lot each time. In the end, it’s a wash. The total thermogenic effect of food over twenty-four hours for both the grazing and gorging strategies is the same: neither yields a metabolic advantage. Eating more frequent meals does not aid in weight loss.13

The second myth is that eating frequently controls hunger, but evidence is impossible to find. Once people decided that grazing was better, I suppose all sorts of reasons were invented to justify it. Recent studies14 don’t support this notion.

The third myth is that eating frequently keeps blood glucose from becoming too low. But unless you have diabetes, your blood sugars are stable whether you eat six times a day or six times a month. People have fasted for prolonged periods without low blood sugar, the world record being 382 days.15 The human body has evolved mechanisms to deal with prolonged periods without food. The body instead burns fat for energ...

Crazier still—we have been brainwashed to believe that constant eating is somehow good for us! Not just acceptable, but healthy.

FUELING THE INCREASE in eating opportunities was the desire of big food companies to make more money. They created an entirely new category of food, called “snack food,” and promoted it relentlessly. They advertised on TV, print, radio and Internet.

But there is an even more insidious form of advertising called sponsorship and research. Big Food sponsors many large nutritional organizations. And then there are the medical associations. In 1988, the American Heart Association decided that it would be a good idea to start accepting cash to put its Heart Check symbol on foods of otherwise dubious nutritional quality. The Center for Science in the Public Interest1 estimates that in 2002, the AHA received over $2 million from this program alone. Food companies paid $7500 for one to nine products, but there was a volume discount for more than twenty-five products! Exclusive deals were, of course, more expensive. In 2009, nutritional standouts such as Cocoa Puffs and Frosted Mini Wheats were still on the Heart Check list. The 2013 Dallas Heart Walk organized by the AHA featured Frito-Lay as a prominent sponsor. The Heart and Stroke Foundation in Canada was no better. As noted on Dr. Yoni Freedhoff’s blog,2 a bottle of grape juice proudly bearing the Health Check contained ten teaspoons of sugar. The fact that these foods were pure sugar seemed not to bother anybody.

Researchers and academic physicians, as key opinion leaders, were not to be ignored either. Many health professionals endorse the use of artificial meal-replacement shakes or bars, drugs and surgery as evidence-based diet aids. Forget about eating a whole, unrefined natural-foods diet. Forget about reducing added sugars and refined starches such as white bread. Consider the ingredient list of a popular meal-replacement shake. The first five ingredients are water, corn maltodextrin, sugar, milk protein concentrate and canola oil. This nauseating blend of water, sugar and canola oil does not really meet my definition of healthy. In addition, impartiality—or the lack thereof—can be a serious issue when it comes to publishing medical and health information. The financial-disclosures section of some papers published in journals and on the web can run for more than half a page. Funding sources have enormous influence on study results.3 In a 2007 study that looked specifically at soft drinks, Dr. David Ludwig from Harvard University found that accepting funds from companies whose products are reviewed increased the likelihood of a favorable result by approximately 700 percent! This fin...

But the obesity epidemic couldn’t very well be ignored, and a culprit had to be found. “Calories” was the perfect scapegoat. Eat fewer calories, they said. But eat more of everything else. There is no company that sells “Calories,” nor is there a brand called “Calories.” There is no food called “Calories.” Nameless and faceless, calories were the ideal stooge. “Calories” could now take all the blame. They say candy doesn’t make you fat. Calories make you fat. They say that 100 calories of cola is just as likely as 100 calories of broccoli to make you fat. They say ...

One of the worst myths is that eating more frequently causes weight loss. Eat snacks to lose weight? It sounds pretty stupid. And it is.