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

by Jason Fung

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. Insulin is the main stimulus of glycogenesis. We can convert glucose to glycogen and back again quite easily. But the liver has only limited storage space for glycogen. Once full, excess carbohydrates will be ...

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 process in reverse. This happens most nights, assuming you don’t eat at night. Glycogen is easily available, but in limited supply. During ...

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 release energy, which is then sent...

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 ...

This process happens every day. 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,...

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 limited. Like the bank account, fat stores contain an unlimited amount of energy, but they are harder to access.

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 because your glycogen is becoming depleted. If you continually refill your glycogen stores, you never need to use your fat stores for energy.

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 subcutaneo...

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 between the feeding and fasting will lead...

Could insulin be the hormonal regulator of body weight? INSULIN, BODY SET WEIGHT AND OBESITY 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...

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, t...

The key to understanding obesity is to understand what regulates body set weight, why body set weight is set so ...

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 periphery. In this hypothesis, high insulin levels increase the body set weight. Certainly, the insulin response differs greatly between lean and obese pati...

Does insulin cause obesity? That question—the key to a hormonal theory of obesity—is explored in detail in the next chapter.

INSULIN I CAN MAKE YOU FAT 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 suggests—but does not prove—the causal nature of this relationship. Insulin levels can be difficult to measure since levels fluctuate widely throughout the day in response to food. It is possible to measure an “average” level, but doing so requires multiple measurements throughout the day. Fasting insulin levels (measured after an overnight fast) are a simpler, one-step measurement. Sure enough, research reveals a close association between high fasting insulin levels and obesity, and this relationship becomes even stronger when we consider only a person’s fat mass rather than his or her total weight. In the San Antonio Heart Study,3 high fasting insulin was tightly correlated to weight gain over ...

If you take insulin, will you get fat? The short answer is an emphatic “Yes!” Patients who use insulin regularly and physicians who prescribe it already know the awful truth:4 the more insulin you give, the more obese you get. Insulin causes obesity.

The only difference between the groups was the amount of insulin administered. Were these patients suddenly lacking in willpower? Were they lazier than they had been before the study? Were they more gluttonous? No, no and no. Insulin levels were increased. Patients gained weight.

Newer types of long-acting insulin produce weight gain, too.7 A 2007 study compared three different insulin protocols. What happened to the participants’ weight? The study noted, “Patients generally gained weight on all regimens.”

And reducing caloric intake proved useless. In a fascinating 1993 study,8 high-dose insulin allowed virtual normalization of blood sugars in a group of type 2 diabetic patients. Starting from zero, the dose was increased to an average of 100 units per day over a period of six months. At the same time, patients decreased their caloric intake by more than 300 calories per day. The patients’ blood sugar levels were great. But what happened to their weight? It increased by an average of 19 pounds (8.7 kilograms)! Despite eating less than ever, patients gained weight like crazy. It wasn’t calories that drove their weight gain. It was insulin.

Increased caloric intake did not account for the weight gain. Reduced caloric intake did not account for the weight loss. The defining element was insulin: its rise and fall corresponded to the rise and fall in weight.

I CAN MAKE YOU THIN IF INSULIN CAUSES weight gain, can lowering its levels have the opposite effect?

Type 1 diabetes is an autoimmune disease that destroys the insulin-producing beta cells of the pancreas. Insulin falls to extremely low levels. Blood sugar increases, but the hallmark of this condition is severe weight loss. Type 1 diabetes has been described since ancient times. Aretaeus of Cappadocia, a renowned ancient Greek physician, wrote the classic description: “Diabetes is . . . a melting down of flesh and limbs into urine.” No matter how many calories the patient ingests, he or she cannot gain any weight. Until the discovery of insulin, this disease was almost universally fatal. Insulin levels go waaayyy down. Patients lose a lot of weight. In the type 1 diabetic community, there is a disorder called “diabulimia.” Today, type 1 diabetic patients are treated by daily injections of insulin. There are some patients who wish to lose weight for cosmetic reasons. Diabulimia is the deliberate under-dosing of insulin for the purpose of immediate and substantial weight loss. It is extremely dangerous and certainly not advisable. However, the practice persists because it is an extremely effective form of weight loss. Insulin levels go down. Weight is lost.

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 ...

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 is set too high. Why? Because our ins...

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 ...

Obesity is a hormonal, not a calor...

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. Both fasting insulin and fasting leptin levels are higher in obese people, indicating a state of both insulin and leptin resistance. The leptin response to a meal was also different. In lean people, leptin levels rose—which makes sense, as leptin is a satiety hormone. However, in obese subjects, leptin levels fell. Despite the meal, their brains were not getting the message to stop eating. The leptin levels resistance seen in obesity may also develop due to self-regulation.31, 32 Persistently high leptin levels lead to leptin resistance. It is also possible that high insulin levels may cause increased weight gain by mechanisms unrelated to leptin in pathways yet to be discovered.

The crucial point to understand, however, is not how insulin causes obesity, but that insulin does, in fact, cause obesity.

Once we understand that obesity is a hormonal imbalance, we can begin to treat it. If we believe that excess calories cause obesity, then the treatment is to reduce calorie...

However, if too much insulin causes obesity, then it becomes clear we need to lower insulin levels. The question is not how to balance calories; the question is how to balance our hormones. The most...

I CAN MAKE YOU fat. Actually, I can make anybody fat. How? I prescribe prednisone, a synthetic version of the human hormone cortisol.

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.

THE STRESS HORMONE CORTISOL IS THE so-called stress hormone, which mediates the flight-or-fight response, a set of physiological responses to perceived threats.

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.

In our modern-day lives, we have many chronic, nonphysical stressors that increase our cortisol levels. For example, marital issues, problems at work, arguments with children and sleep deprivation are all serious stressors, but they do not result in the vigorous physical exertion needed to burn off the blood glucose. Under conditions of chronic stress, glucose levels remain high and there is no resolution to the stressor. Our blood glucose can remain elevated for months, triggering the release of insulin. Chronically elevated cortisol leads to increased insulin levels—as demonstrated by several studies.

In a sense, insulin resistance should be expected, since cortisol generally opposes insulin. Cortisol raises blood sugar, while insulin lowers it. Insulin resistance (discussed in depth in chapter 10) is crucial to the development of obesity. Insulin resistance leads directly to higher insulin levels, and increased insulin levels are a major driver of obesity. Multiple studies confirm that increasing cortisol increases insulin resistance.9, 10, 11

CORTISOL AND OBESITY HERE’S THE REAL question we are interested in: Does excess cortisol lead to weight gain? The ultimate test is this: Can I make somebody fat with prednisone? If so, that can prove a causal relationship, rather than a mere association. So does prednisone cause obesity? Absolutely! Weight gain is one of prednisone’s most common, well-known and dreaded side effects. This relationship is causal.

But the hallmark of Cushing’s syndrome, even in people with mild forms, is weight gain. In one case series, 97 percent of patients show abdominal weight gain and 94 percent show increased body weight.13, 14

Patients gain weight no matter how little they eat and no matter how much they exercise. Any disease that causes excess cortisol secretion results in weight gain. Cortisol causes weight gain.

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

SLEEP SLEEP DEPRIVATION IS a major cause of chronic stress today. Sleep duration has been steadily declining.21 In 1910, people slept nine hours on average. However, recently, more than 30 percent of adults between thirty and sixty-four years of age report getting fewer than six hours of sleep per night.

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.

A single night of sleep deprivation increases cortisol levels by more than 100 percent.27 By the next evening, cortisol is still 37 percent to 45 percent higher.28 Restriction of sleep to four hours in healthy volunteers resulted in a 40 percent decrease in insulin sensitivity,29 even after a single sleep-deprived night.30 After five days of sleep restriction, insulin secretion increased 20 percent and insulin sensitivity decreased by 25 percent. Cortisol increased by 20 percent.31 In another study, shortened sleep duration increased the risk of type 2 diabetes.32 Both leptin and ghrelin, key hormones in the control of body fatness and appetite, show a daily rhythm and are disrupted by sleep disturbance. Both the Wisconsin Sleep Cohort Study and the Quebec Family study demonstrated that short sleep duration33 is associated with higher body weight, decreased leptin and increased ghrelin. Sleep deprivation clearly will undermine weight loss efforts.34 Interestingly, sleep deprivation under low-stress conditions does not decrease leptin or increase hunger,35 which suggests that it is not the sleep loss per se that is harmful, but the activation of the stress hormones and hunger mechanisms. Getting enough good sleep is essential to any weight loss plan.

Highly refined carbohydrates are the most notorious foods for raising blood sugars. High blood sugars lead to high insulin levels. High insulin levels lead to weight gain and obesity. This chain of causes and effects has become known as the carbohydrate-insulin hypothesis. The man who found himself at the center of the controversy was the infamous Dr. Robert Atkins. In 1963, Dr. Robert Atkins was a fat man. Like William Banting 100 years before, he needed to do something. Weighing in at 224 pounds (100 kilograms), he had recently begun his cardiology practice in New York City. He had tried the conventional ways to lose weight, but had met with no success. Recalling the medical literature published by Drs. Pennington and Gordon on low-carbohydrate diets, he decided to try the low-carbohydrate approach himself. To his amazement, it worked as advertised. Without counting calories, he shed his bothersome extra weight. He started prescribing the low-carbohydrate diet to patients and had some notable success. In 1965, he appeared on the Tonight Show, and in 1970, was featured in Vogue. In 1972, he published his original book, Dr. Atkins’ Diet Revolution. It was an immediate bestseller and one of the fastest-selling diet books in history.

Dr. Atkins argued in his 1972 bestseller that severely restricting carbohydrates would keep insulin levels low, thus reducing hunger and eventually leading to weight loss.

During the forty years that the AHA advised a low-fat diet, the obesity crisis grew to gargantuan proportions. Yet at no time did the AHA question whether their completely ineffectual advice was actually helping people. Instead, doctors played their favorite game: blame the patient. It is not our fault the diet doesn’t work. It is their fault for not following the diet.

Four different popular weight plans were compared in a head-to-head trial. One clear winner emerged—the Atkins diet. The other three diets (Ornish, which has very low fat; the Zone, which balances protein, carbohydrates and fat in a 30:40:30 ratio; and a standard low-fat diet) were fairly similar with regard to weight loss. However, in comparing the Atkins to the Ornish, it became clear that not only was weight loss better, but so was the entire metabolic profile. Blood pressure, cholesterol and blood sugars all improved to a greater extent on Dr. Atkins’s diet.