Food on the Brain
Daniel Fisher, 01/10/05
Are the high-fat, sugar-laden things we crave addictive? Here’s what the latest scientific research is telling us.
In a lab at Brookhaven National Laboratory on Long Island, Gene-Jack Wang is injecting overeaters with a radioactive sugar solution and putting them into a positron-emissions tomography machine to see how their brains react to food. If Dr. Wang’s previous studies are any indication, he will see that a test subject’s striatum, a sort of communications hub inside the brain, has fewer dopamine receptors than the striatum of someone with normal eating habits. Wang has already demonstrated that the mere sight and smell of food can cause a release of dopamine, a neurotransmitter associated with motivation and pleasure. He’s also shown that drug addicts have a similar shortage of dopamine receptors.
A PET scan of a methamphetamine user shows a diminished area of dopamine receptors requiring more drugs to give pleasure.
The PET scan of a morbidly obese patient shows a similar lack of dopamine receptors. Could food play a role similar to narcotics?
Add it up and a theory emerges: Overeaters consume more food than is good for them to get the kick that dopamine delivers–the same reason that cokeheads snort cocaine. “They use eating as a means to compensate,” says Wang, a Johns Hopkins-trained physician who has studied addiction for more than a decade. Wang’s theory could mean nothing more than that drugs hijack the same brain circuits that evolved over millions of years to motivate people to find and eat food. That doesn’t mean food is a drug. Nobody ever went through withdrawal after going cold turkey on Big Macs, after all.
And yet his research has ominous implications for food companies as they brace for a wave of tobacco-style litigation over the nation’s obesity problem. If lawyers can show that food has addictive properties, they can argue that overeating isn’t a choice but a compulsion. If they can trace the compulsion to specific ingredients such as fat or high-fructose corn syrup, they might have the evidentiary equivalent of nicotine–a substance manufacturers may have manipulated to hook their customers on food.
“You could make things more addictive,” says Dr. William Jacobs, an obesity researcher at the University of Florida. “Just like the Colombia cartel invented crack cocaine.”
So far scientists are a long way from uncovering a smoking French fry. No one has found credible evidence that manufacturers are taking advantage of a mystery ingredient that overrides conscious choice, although some people think they’re close to establishing just that. Dr. Neal Barnard of the Physicians Committee for Responsible Medicine, author of Breaking the Food Seduction St. Martin’s Press, 2003), maintains that chocolate acts on the brain like heroin. And cheese, he says, breaks down into potentially addictive casomorphins in the digestive tract. “There are people who crave cheese,” says Barnard, a vegetarian who is also active in the animal-rights movement. “It acts just like an addicting substance.”
But there is no proof that casomorphins enter the bloodstreams of adults, turning them into Brie-gobbling junkies. Researchers have uncovered some evidence that certain foods stimulate more dopamine release in mammals than others–critical to the legal argument that those foods are unreasonably addictive and dangerous–but their findings are tentative or difficult to replicate in humans.
Ann Kelley of the University of Wisconsin, for example, has shown that giving calorie-packed chocolate Ensure, a diet supplement, to rats rapidly reduces pleasure-inducing endorphins, an effect also seen in rats that have been given narcotics. Normal diet has no such effect. “The implication is that long-term overingestion of foods that are highly preferred could have a druglike effect on the brain,” says Kelley, whose work is funded in part by an institute that gets money from PepsiCo, Procter & Gamble and other food manufacturers.
Researchers have seen signs of a similar brain preference for sweet and fatty foods in humans. Still, the evidence isn’t clear-cut. Kelley determined brain-endorphin levels by killing and dissecting the rats; PET scans and other nonlethal methods aren’t as accurate.
One of the most cited studies, by University of Washington researcher Adam Drewnowski, found that women who were given a drug that blocks opioid receptors consumed less sweet, high-fat foods–but only if they were bulimic. He has no explanation for why the drug didn’t affect the diets of 12 control subjects of normal weight. The opioid blocker “works, we see it,” he says. “But only in a person whose system is disturbed.”
All this uncertainty is understandable, given the complex mechanisms behind eating and obesity. Pharmaceutical manufacturers have sought in vain to find a miracle drug that would make people lose weight; most, like fen-phen and methamphetamines, have side effects worse than the problem they’re trying to solve. Acomplia from Sanofi-Aventis blocks cannabinoid receptors, the same brain receptors that give pot smokers the munchies, but also causes depression in some patients (FORBES, “The Ultimate Pill?” Dec. 13, 2004, p. 96).
Obesity runs in families–genes alone can predict up to 40% of the chance of becoming severely overweight–and overeating seems linked to other family-related disorders such as alcoholism and drug addiction. They all appear to involve disruptions to the brain’s reward system, which dispenses pleasure-inducing dopamine in response to species-propagating behavior such as eating, drinking water or having sex. Cocaine addicts, for example, have fewer dopamine receptors either as a result of the constant stimulation by the drug–it blocks transporters that normally usher dopamine back into brain cells to be recycled–or because they were born that way.
From Aroma to Appetite
1. Empty stomach releases ghrelin, an appetite stimulant, to the hypo-thalamus, which controls the body’s metabolism.
2. The hypothalamus releases dopamine to the nucleus accumbens and striatum, motivating the conscious area of the brain to find food.
3. The smell of food stimulates the amygdala, also a center of emotion, and causes further dopamine release by the nucleus accumbens.
4. Sight, smell and taste of food stimulates release of endorphins (opioids) and dopamine by the orbitofrontal cortex, further stimulating the conscious part of the brain to eat.
5. Leptin released by fat cells eventually overpowers ghrelin and signals the hypothalamus to shut down the dopamine flow. As a result, appetite wanes.
Overeaters have a similar shortage of dopamine receptors, but researchers don’t know if that is an inherited difference, one developed by overeating or a combination of the two. Scientists also are far from unraveling the connections between the largely autonomous parts of the brain that regulate day-to-day energy consumption and expenditure, and the conscious brain that directs behavior such as walking across the street to get a bacon cheeseburger.
Body weight is controlled mostly by the hypothalamus, a structure at the center of the brain that fine-tunes metabolism to a level that no conscious calorie-counter could match. Rockefeller University researcher Jeffrey Friedman has calculated that an imbalance of as few as 1,700 calories a year would lead to weight gain or loss over time. The hypothalamus reacts to ghrelin, a hormone excreted by an empty stomach, by releasing appetite-stimulating neurotransmitters into other parts of the brain. It shuts off the neurotransmitters in response to leptin, a hormone released by fat cells.
Scientists still don’t know exactly how the hypothalamus communicates with the cerebral cortex, the site of conscious thought, although dopamine is believed to play a role. The ill-fated diet drug fenfluramine, for example, stimulated dopamine release within the hypothalamus and had the paradoxical effect of reducing appetite. The hypothalamus also has connections to the cortex via the striatum and the nucleus accumbens, a structure that secretes its own dopamine and opioids in response to food (see graphic).
The exact role of the nucleus accumbens is a mystery. It processes sensory information from the mouth and nose–wow, that pizza smells good!–and releases dopamine and opioids in response. Researchers have even seen a bias for fatty foods as opposed to carbohydrates, something they can’t explain. Stimulate the nucleus accumbens in rats and they gorge themselves on the stuff; administer an opioid blocker and they stop. Mice bred without dopamine receptors in the nucleus accumbens quickly starve themselves to death.
Ann Kelley has found an even more powerful layer of control in the amygdala, a center for emotions that also has rich nerve connections to the nose. When she neutralizes the amygdala in rats with a drug that halts its function, they no longer pig out even if their nucleus accumbens is stimulated. The implication, she says, is that the emotional response to food and its aromas–remember the popcorn you had on your first date?–might be more important than the weight-control system of the hypothalamus. One implication: Advertising campaigns that conjure up images of home and hearth might also stimulate the amygdala.
Fact is, the human brain has a multitude of ways to stimulate appetite and only a few to turn it off. That makes sense in evolutionary terms because until recently mankind existed in a state of constant food scarcity. “Think about it: Your brain is walking through these megastores and saying, ‘Aren’t I a great hunter? I can catch king salmon or Kobe beef without any chance of being attacked by a sabre-toothed tiger,'” says Mark Gold, distinguished professor of neuroscience at the McKnight Brain Institute at the University of Florida.
The multibillion-dollar question is whether certain easily manipulated food ingredients can trigger one of those pathways to say “eat,” even when other parts of the brain are saying “enough.” Lawyer Christopher Cole in the Washington office of Paul, Hastings Janofsky & Walker advises food companies on defense strategies should food litigation take off. So far he hasn’t seen anything in the research to worry about. But he’s keeping a close eye on the obesity journals: “Once you characterize [obesity] as an illness and you argue that companies are urging people to catch that illness, you can build a case.”