Fat Chance: The bitter truth about sugar. Dr. Lustig Robert

And food and drugs cross over. With time we can become sensitized to a substance and need more of it to get the same effect. Once sensitized, animals and humans may become hyperresponsive to a new substance; this is known as cross-sensitization. In other words, if the brain has been wired for addiction, it’s easy to switch from one substance to another. Ask recovering alcoholics about their incessant need for coffee, tobacco, and/or sugar. A reinforcer is a stimulus that increases the probability that an animal or human will respond to the addictive drug. Food is a form of positive reinforcement. Dopamine stimulation in the NA reinforces the intake of drugs or alcohol and also of food.

      The reinforcing effect of dopamine is attributed to D₂ receptor stimulation. As stated before, food intake increases as a result of morphine and marijuana use. The film Harold and Kumar Go to White Castle details the odyssey of two very stoned guys who seek to overcome seemingly insurmountable obstacles in their quest for a hamburger. We can measure this by dopamine release and D₂ receptor signaling. Why does dopamine matter so much? In a normal person, dopamine will be cleared from the D₂ receptors after he is satiated. If you have a decreased dopamine binding capacity, there is a perceived need for compulsive food intake to provide excess stimulation of these depressed circuits, thereby driving continued weight gain.

       The Usual Suspects: Leptin and Insulin

      Yup, them again. Not only are they central in the starvation response, but they are also key players in this hedonic pathway, modulating reward in response to meals. In normal circumstances, after you’ve eaten a sufficient amount, leptin sends a signal to the VTA to suppress the release of dopamine, thereby reducing the reward of food.³

      So leptin extinguishes reward. But what if you are leptin resistant? That’s what obesity is: leptin resistance. If leptin can’t act, then the dopamine isn’t cleared from the NA, and the impetus for further consumption persists. If you’re leptin resistant, do you really think you have the willpower to ignore both the starvation signal and the reward signal, when every food outlet you pass by provides you with sight or smell cues to chow down? Starvation and reward conspire to thwart every obese person.

      What about insulin, leptin’s accomplice? Normally, people are sufficiently sensitive to insulin. Insulin’s job is to clear dopamine from the synapses (that pathway between the cells) in the NA.⁴ Thus, the rise in insulin that occurs during a meal blunts the reward of further food intake (I’ve eaten enough—I really don’t need a second helping). This acts as a servomechanism built into the hedonic pathway to prevent overfeeding. But what happens when you are insulin resistant? Insulin resistance leads to leptin resistance in the VTA, contributing to increased caloric intake by preventing dopamine clearance from the NA. Increased pleasure is then derived from food when energy stores are full.⁵ Insulin and leptin resistance lead not only to increased food intake but to increased palatable food intake or anything that is high in both fat and sugar: the muffins, the Cinnabons, the cookies, the cheesecake. Is it any wonder Mrs. Fields is in every shopping mall?

       Defining Food Addiction: Liking, Wanting, and Needing

      Look, we all like fast food. And why wouldn’t we? It’s designed to contain the greatest concentration of fat, sugar, salt, and caffeine, and is placed into as small a package as possible. Yummmm. It provides food cheaply, quickly, and without table service. The pretty packaging and restaurant environment increase its salience (the properties that make you like it more). Ten years ago, fast food locations in the United States generated more than $125 billion, which accounts for 15 percent of sales of the entire U.S. food industry. But liking it isn’t the same as wanting it. And wanting it isn’t the same as needing it.⁶

      Liking is an aesthetic state. You can turn it on and turn it off. As dopamine is released into the NA, our consumption of a Big Mac heightens our sense of reward. Then comes the insulin rush, and that should be the end of it. But when you’re insulin resistant, wanting is a psychological state and needing becomes a physiologic state. You can’t turn it on and off anymore. This is the nature of addiction to any substance of abuse. It’s what happens with nicotine, morphine, cocaine, and alcohol—and it happens with food. It can happen to anyone. It can happen to you.

      Substance dependence, in this case synonymous with addiction, is defined by the American Psychiatric Association (APA) as “a maladaptive pattern of substance abuse leading to clinically significant impairment or distress.” There is currently no standardized definition for food addiction despite many hypotheses in the medical literature. There are seven criteria for substance dependence according to the APA Diagnostic and Statistical Manual, the DSM-IV-TR. The first two are considered physiologic, whereas criteria 3–7 are considered psychological dependence. All these are seen in the obese, especially those who frequent fast food restaurants. To be considered addicted to any substance of abuse, one must meet at least three of the seven.

      1. Tolerance. This is defined as the need for more substance to get the same effect, or when the same amount of substance produces less effect with continued use. That Big Mac still generates the dopamine rush, but the reward isn’t maintained, as your insulin won’t clear the dopamine from the NA. Since insulin resistance generates leptin resistance, you can’t stop the dopamine neurons in the VTA from firing in the first place. So your NA is awash in dopamine, and the insulin rush from the meal can’t turn it off. Since your hypothalamus and your NA won’t respond to the leptin signal, the drive to eat just keeps coming. And here’s the kicker: the more and the longer your NA is exposed to dopamine, the more those D₂ receptors are going to be down-regulated. After chronic dopamine exposure, the D₂ receptors themselves start to disappear. The locks vanish, much to the chagrin of the keys, which have nowhere to go. Now it takes more dopamine to ensure that the few receptors that don’t disappear are occupied. You need to eat more Big Macs just to get the same level of reward.

      2. Withdrawal. This is characterized by physical signs (such as tremors) and psychological ones (anxiety, depression). This occurs due to lack of dopamine D₂ receptor occupancy. In animals, anxiety and depression are indicated by unwillingness to spend time in a risky environment. In humans, withdrawal is expressed as symptoms of depression and anxiety. If you try to stop eating those Big Macs, your dopamine drops and you are consumed by feelings of anxiety and depression (just like those patients treated with rimonabant—the “anti-munchie” medicine). The only choice is to increase the dopamine, reoccupy those diminished D₂ receptors, and maintain the vicious cycle of Big Mac consumption.

      If you need proof, I suggest you rent the 2004 documentary Super Size Me. The film’s author and star, Morgan Spurlock, began as a reasonably healthy specimen at 6 feet 2 inches and 185 pounds (for a BMI of 23.8, within the normal range). He was eating a reasonably healthy diet (his girlfriend was a vegan chef) before beginning a thirty-day ordeal of eating every meal at McDonald’s. By day eighteen, he relates to the camera, “You know, I was feeling awful. I was feeling like s--t. I was feeling sick, and unhappy…. Started eating; now I feel great. I feel so great, it’s crazy.” Mr. Spurlock just described withdrawal. In eighteen days, he went from being a person with healthy eating habits to a fast food addict.

      3. Bingeing. This is defined as an escalation of intake, using a greater amount of the substance or using for a longer duration than intended. In animals, this can be measured by an increase in the number of times the animal presses a lever to self-administer a drug—or, in the case of a human, continuing to eat after satiety has been achieved. One can easily conceptualize binge drinking (think of the movie Animal House or your stereotypical chug-a-lug frat guy), but binge eating is harder to define. It is highly subjective, since what is a large amount to some may not be perceived as unusual by others. Binge eating disorder includes eating until uncomfortable; eating when not hungry; eating alone due to shame; feeling disgusted, depressed, or guilty after overeating; and marked distress over the bingeing. Many afflicted people will consume massive amounts of food, such as an entire sheet cake, alone and in the dark of their kitchen, with massive shame.

      4. Desire or attempts to cut down or quit. As mentioned previously, diets and miracle