Rats, like humans, love sugar. Feed them a little, and they will want more. Let them at it, and they will increase their intake, drinking loads of sugar water just to maintain their fix. Columbia neuroscientist Nicole Avena showed that within just twenty-one days, their NA looks whipped, as would happen with any other drug of abuse.14 And even more so when given binge access.15
Until recently, scientists were locked in a vehement debate as to whether it was sugar or fat that caused your reward pathway to fire. Eric Stice in Oregon conducted a neuroimaging study that looked at fat and sugar separately, and together, in milk shakes that were calorically equivalent.16 Using four different combinations of high- and low-fat and high- and low-sugar milk shakes, he found that the high-fat variety caused greater activation in oral somatosensory regions (i.e., where you experience mouthfeel), while high-sugar more effectively recruited reward-related and gustatory (taste) regions. Increasing sugar caused greater activity in the reward pathway, while increasing fat did not. In other words, it’s the sugar that drives the dopamine, which drives the motivation for reward.
Dietary sugar is composed of two molecules: glucose and fructose. Glucose is the energy of life. Glucose is so important that if you don’t consume it, your liver makes it (gluconeogenesis). Conversely, fructose, while an energy source, is otherwise vestigial; there is no biochemical reaction that requires it. Yet, when consumed chronically and at high dose, fructose is similarly toxic and abused.17 Not everyone who is exposed gets addicted, but enough do to warrant a similar discussion.
These two molecules, glucose and fructose, activate different parts of the brain. On functional MRI (fMRI) scanning, the glucose molecule lights up areas associated with consciousness and movement, while the fructose molecule lights up the reward pathway and several sites in the stress-fear-memory pathway as well.18 These studies suggest that sugar is uniquely capable of driving the reward pathway and altering emotional responses.
Denying the Obvious
Not everyone subscribes to this expanded view of addictive substances. Drugs are a luxury. Food is a necessity. How can a food—like sugar—that is necessary for survival also be addicting? Because certain “foods” are not necessary for survival. We need essential nutrients that our body can’t make out of other nutrients, or we get sick and die. But there are only four classes of essential nutrients: (1) essential amino acids (nine out of the possible twenty found in dietary protein), (2) essential fatty acids (such as omega-3 and linolenic acid), (3) vitamins, and (4) other micronutrients, such as minerals. Just add water and stir. None of the foods that contain these essential nutrients are even remotely addictive. Of those substances that also contain calories, only alcohol and sugar have been shown to be addictive. The other addictive consumable found in food is caffeine.
Wait, I can hear it—you’re saying, sugar? A drug? How is that possible? It’s part of other foods. It’s in fruit. It provides calories. It’s an energy source. Moreover, it’s a commodity! We subsidize it! OK, let’s try an analogy. Can you name a substance that: (1) has calories, (2) is an energy source, (3) is not required by any biochemical reaction in the body, and (4) is not nutrition by anybody’s estimation, (5) when consumed in excess causes damage to cells, organs, and humans, (6) we love anyway, and (7) is addictive? Answer: alcohol. Alcohol’s got calories and is an energy source, but alcohol is not a food. Alcohol is not nutrition. There’s no biochemical reaction that requires it (40 percent of Americans don’t consume alcohol, and they’re not sick).19 Alcohol does not hurt you because it has calories or because it can cause weight gain. Alcohol is dangerous because it’s alcohol. It can fry your brain and your liver. It’s a drug and it’s addictive in a percentage of the population.
Same with sugar: it meets each one of these same criteria. Fructose, the sweet molecule in sugar, contains calories that you can burn for energy, but it’s not nutrition because there’s no biochemical reaction in any eukaryotic (animal) cell on the planet that requires it. It’s a vestige from when we split off the evolutionary tree from plants. And when consumed in excess, sugar fries your liver, just like alcohol.20 And this makes sense, because where do you get alcohol from? Fermentation of sugar: it’s called wine. Sugar causes diabetes, heart disease, fatty liver disease, and tooth decay. Sugar’s not dangerous because of its calories, or because it makes you fat. Sugar is dangerous because it’s sugar.21 It’s not nutrition. When consumed in excess, it’s a toxin. And it’s addictive. Fructose directly increases consumption independent of energy need.22 Sucrose establishes hardwired pathways for craving in these areas that can be identified by fMRI.23 Indeed, sweetness surpasses cocaine as a reward in rats.24 Animal models of intermittent sugar administration induces behavioral alterations consistent with dependence, i.e., bingeing, withdrawal, craving, and cross-sensitization to other drugs of abuse.25
The naysayers will still say, “But sugar is natural. Sugar’s been with us for thousands of years. Sugar is FOOD! How can food be toxic? How can food be addictive? This begs the question: What is food? Is sugar food? Webster’s Dictionary defines “food” as “material consisting essentially of protein, carbohydrate, and fat used in the body of an organism to sustain growth, repair, and vital processes and to furnish energy.” Well, sugar furnishes energy, so of course that makes it a food! For instance, a group of European academic researchers have joined forces into a political action group called NeuroFAST, which maintains that humans can succumb to “eating addiction” (it’s the person’s fault) but argue vehemently against the concept of “food addiction” (it’s the food’s fault).26 This is not a semantic difference. If it’s “eating addiction,” the food industry bears no responsibility. If it’s “food addiction,” they bear at least some corporate responsibility for our current medical and behavioral health debacle. NeuroFAST categorically insists that even though specific foods can generate a reward signal, they can’t be addicting, as they are necessary for survival. In their own words:
In humans, there is no evidence that a specific food, food ingredient or food additive causes a substance based type of addiction (the only currently known exception is caffeine which via specific mechanisms can potentially be addictive) . . . Within this context we specifically point out that we do not consider alcoholic beverages as food, despite the fact that one gram of ethanol has an energy density of 7 kcal.27
Interesting. NeuroFAST recognizes caffeine as addictive, yet they give it a pass. Caffeine is present in many foods (e.g., coffee), yet it is classified by the FDA as a food additive. It is also a drug; we give it to premature newborns with underdeveloped nervous systems to prevent apnea (stoppage of breathing). NeuroFAST then goes on to give alcohol a pass as well. Natural yeasts constantly ferment fruit while still on the vine or tree, causing it to ripen,28 yet NeuroFAST recognizes that purified alcohol is not a food. Alcohol is also a drug; we used to give it to women to stop premature labor. It is also addictive.
So what is the difference with refined sugar? The sucrose in your sugar bowl is the same compound as what is in fruit, but the fiber has been removed, and it’s been crystallized for purity. It’s this process that turned fructose from food into drug. And it’s the purification that made it addictive. Just like alcohol. So in a convoluted sort of way, NeuroFAST got it half-right. They state that food can’t be addictive, but they recognize that food additives can. But that means when these additives are added to our food, they can make our food addictive. Like sugar.
The sine qua non of this argument is soda. Is soda a food? Is there anything in soda that you need that could make it a food? Sugar—that’s an additive. Caffeine—another additive. Both addictive. Phosphoric acid, caramel coloring? No. Sodium? We’re all consuming triple what we need as it is.29 Water? Water’s necessary, but it’s not a food—it’s water.
In the Middle Ages, sugar was a spice. Up through the mid-1900s it was a condiment. Only in the last fifty years has it become a diet staple. And it’s addictive
for exactly the same reasons and via the same mechanism as alcohol. Sugar is not a food; it’s a food additive, just like alcohol. That’s why the FDA proposed changing the Nutrition Facts label to include “added sugar” (although the current administration may revoke this change). And that’s why children are getting the diseases of alcohol—type 2 diabetes and fatty liver disease—without alcohol. And that’s just what it does to your body and your reward pathway. Hold on, the party’s just getting started: Wait till you see what it does to the rest of your brain (in Chapter 9). Yum.
When “Want” Becomes “Need”
The DSM-V says all you need for addiction is tolerance and dependence (engaging despite conscious knowledge and recognition of their detriment), with resultant misery. Behaviors and substances that used to be excluded from the definition now qualify under this rubric. Can you honestly look yourself in the mirror and tell yourself that you have no addictions? Ben & Jerry’s, eBay, Facebook, porn, video games, coffee? How long did the rush from the new iPhone last? Or the new car? Or the new wife? As a society we’ve become tolerant by obtaining new stuff at a moment’s notice. We don’t just want, we need the newest, fastest, shiniest, classiest, coolest. You might call dopamine the dark underbelly of our consumer culture. It’s the driver of desire, the purveyor of pleasure, the neurotransmitter of novelty, the lever that business pushes to keep our economy going, but at a clear, perceptible, and increasing cost. We’ve purified our substances to concentrate their effects, and we are perpetually in need of the next shiny object.
Apparently that goes for presidents too. The Coolidge effect takes its name from an apocryphal story of an experimental government farm visited by President and Mrs. Coolidge. When Mrs. Coolidge came to the chicken yard she noted a randy rooster. She asked how often the rooster mated and was told, “Dozens of times each day,” to which she replied, “Tell that to the president when he comes by.” The president asked, “Same hen every time?” “Oh, no, Mr. President, a different hen every time.” The president said, “Tell that to Mrs. Coolidge.”
PART III
Contentment—The Bluebird of Happiness
7.
Contentment and Serotonin
Question: Over the course of history, what prescription medication has evidenced the greatest societal impact? Well, you could argue that cholesterol-lowering drugs (statins) are the most prescribed for the treatment and prevention of heart disease, and have made the most money. You could make the case that anti-malarials have saved millions of lives, especially in third-world countries. Protease inhibitors turned AIDS from a ruthless killer into a public nuisance. Non-steroidal anti-inflammatories such as ibuprofen and naproxen have alleviated pain in a majority of people. How about narcotics and anesthetics? Having surgery two hundred years ago without them was extremely unpleasant; although the recent scourge of opiate addiction might be starting to negate its positive impacts. Maybe Viagra? That has certainly increased the happiness of a portion of the population. Pick any of the above. You would be wrong.
Answer: fluoxetine (Prozac). Psychiatric hospitals once were the saddest places on earth (think One Flew Over the Cuckoo’s Nest [1962]: I still have nightmares about Nurse Ratched), chock-full of patients with schizophrenia (e.g., patients who thought people were out to kill them and/or plotted to kill others, due to dopamine dysfunction) and patients with clinical depression (e.g., people who would have welcomed being killed, due to serotonin dysfunction). But, at its worst, schizophrenia affected only about 1 percent of the population. Consider the fact that major depressive disorder (MDD) affects 16 to 18 percent of the U.S. population at some time in their lives, and that at any given moment 6 to 8 percent of the people you know are affected.1 This is a very big deal and takes a huge toll on the individual, on his or her family, and on society.
Psychiatric drugs are truly a miracle of Western civilization. For many years, scientists and doctors had been trying to understand what made some people suffer from severe depression while others seemed preternaturally happy and stars of their own Disney movie. In 1952 a serendipitous finding launched the field of modern psychopharmacology. As is the case with the first generation of many mood-stabilizing treatments, we used it to treat a different malady altogether. Patients with tuberculosis (TB) treated with a drug known as isoniazid (INH, still the drug of choice when you are exposed to someone with TB) out of the blue experienced a lifting of their depression. INH worked on the neurotransmitter serotonin (as well as other areas of the brain), and with more trials and focus, scientists were able to pinpoint that it was the effect of serotonin that caused depressed TB patients to reemerge into the world of the living. Thus, scientists learned that serotonin was responsible, in part, for the feelings of happiness and contentment. And, when out of whack, could cause severe irritability and depression.
Plumbing the Depths
There are two kinds of depression. People with “retarded” depression can’t get out of bed, and would kill themselves if they had the energy to do so. They often need to be hospitalized to be kept away from themselves. But they pale in numbers compared to the people with “agitated” depression, who are anxious, irritable, sleepless, and just plain miserable. Both types are associated with individuals eating and sleeping either far too much or far too little, both of which are activities that involve serotonin (see Chapters 9 and 18).
When Prozac, the first in the class of selective serotonin reuptake inhibitors (SSRIs), hit the market in 1986, prescriptions for antidepressants shot up a record 400 percent over the next fifteen years.2 The genius of Prozac was that it didn’t matter which form of depression you had. Whether you were climbing the walls or plumbing the depths of your psyche, Prozac could bring you to ground. Figure 7-1 demonstrates how both retarded and agitated depression can be helped by improving serotonin status.
Due to both Reagan’s funding cutbacks and Prozac’s successes, over the next two decades, in-patient psychiatric facilities closed faster than Blockbuster Video. I watched this phenomenon occur during my medical fellowship: there weren’t enough depressed people in the hospitals to keep them open, and nobody cared about the schizophrenics, so they got dumped onto the street, where they remain today.
Fig. 7-1: The highs and lows of depression. Depression comes in two varieties—retarded depression (slow thinking and behavior: I can’t get out of bed); and agitated depression (flight of ideas and inability to concentrate: I can’t get into bed). SSRIs are antidepressants that, by increasing the amount of serotonin in the synapse, can restore normal levels of mood in either type of depression.
Prozac or one of its many cousins—sertraline (Zoloft), citalopram (Celexa), and paroxetine (Paxil), to name but a few—are now prescribed to alleviate or mitigate a great many mental disorders. Today, SSRIs are the number three most prescribed class of drugs; more people under age sixty-five take antidepressants than any other medication,3 and as many prescriptions were filled for antidepressants as for cholesterol-lowering drugs.4 Currently 11 percent of all adolescents are taking an antidepressant5, 6 not just for depression but for anxiety, anger management, premenstrual syndrome, and obsessive-compulsive disorder as well. The frequency of diagnosis of depression is still on the rise. However, we don’t know if this is due to an increased awareness among the medical community (ascertainment bias), if insurance coverage has provided the impetus for overdiagnosing (pills are lucrative to drug companies, and cheaper than psychotherapy), if more adolescents are depressed because of bullying and school pressures, or if people and doctors want to provide a quick fix. But is it a fix? Not for everyone. And how does it work?
Before we start talking about serotonin and contentment, let’s go back to dopamine and motivation. Dopamine is the reward initiator, and firing of dopamine neurons changes behavior. Remember, the dopamine neurons in the VTA have two primary targets: (1) the nucleus accumbens (NA), where the dopamine signal is translated into desire and reward (I’m stressed, give me
a Krispy Kreme), and (2) the prefrontal cortex (PFC), where the dopamine signal is tempered by cognitive control (your personal Jiminy Cricket).
Happy Feet?
But serotonin differs from dopamine in many ways, which makes it difficult to understand and to study. First, serotonin is utilized by different parts of the body. The overwhelming majority (90 percent) is produced and used in the gut, where serotonin is involved in neural and hormonal responses to feeding and how full you are. Another 9 percent can be found in the platelets of our bloodstream, where serotonin helps our blood to clot. That leaves a total of 1 percent of all of your body’s serotonin in the brain itself.7 This is why we can’t just measure the amount of serotonin in blood or urine to diagnose depression—because the amount is more a reflection of what’s going on in the gut or the bloodstream than in the brain. As an example, carcinoid, which is a tumor of the intestine that overproduces serotonin, causes severe diarrhea, flushing, and abdominal pain and cramping, but it doesn’t have very much in the way of central nervous system actions, and it certainly doesn’t make its victims happy. But your urine and blood will definitely show high levels of serotonin and its breakdown products (Fig. 7-2). There’s no biomarker for depression, no blood test that your doctor can administer. To diagnose clinical depression, doctors use a questionnaire known as the Beck Depression Inventory (BDI), which scores different subjective symptoms of depression. This validated instrument is equivalent to your brain’s serotonin meter.
The Hacking of the American Mind Page 9