Burgers on the brain

Can you really get addicted to fast food? The evidence is piling up, and the

lawyers are rubbing their hands. Diane Martindale reports

MIDDLE-AGED janitors rarely make their mark on science. But Caesar Barber

looks like breaking the mould. Last July, Barber, a 56-year-old diabetic and

double heart-attack victim from Brooklyn, sued McDonald's, Burger King, KFC

and Wendy's, claiming that his illnesses were partly their fault. He had

eaten in their restaurants for years, he said, without ever being told that

the food was damaging his health.

Barber's class-action lawsuit was the first volley in a long-awaited legal

assault against the fast-food industry and its role in the obesity epidemic

that is swamping the US health-care system (see "Fat facts"). Inspired by

the success of Big Tobacco, the lawyers behind it believe they can force

fast-food chains to meet their fair share of the enormous cost of caring for

obesity. Pulling the strings is John Banzhaf, of George Washington

University Law School in Washington DC, who masterminded the Big Tobacco

crusade.

That campaign won him plaudits all over the world. But "Big Fat" is a

different matter. To many - including a federal judge who last month

dismissed a similar lawsuit against McDonald's - it seems blatantly absurd.

Surely people who become fat and ill because they have eaten too much fast

food only have themselves to blame?

Perhaps not. New and potentially explosive findings on the biological

effects of fast food suggest that eating yourself into obesity isn't simply

down to a lack of self-control. Some scientists are starting to believe that

bingeing on foods that are excessively high in fat and sugar can cause

changes to your brain and body that make it hard to say no. A few even

believe that the foods can trigger changes that are similar to full-blown

addiction. The research is still at a very early stage, but thanks to Caesar

Barber it is about to be thrust firmly into the limelight.

Taking on the fast-food industry was always going to be a much tougher

assignment than beating the cigarette barons. Tobacco is obviously

addictive. Nobody needs to smoke. And the tobacco companies knew their

products were addictive yet covered it up. None of these accusations can be

levelled at food.

Banzhaf maintains that he can win regardless. He points out that he doesn't

have to prove that the fast-food chains are entirely responsible for

obesity. All he has to do is convince a jury that his clients' health

problems were not entirely their own fault - that the fast-food companies

share the blame. Perhaps, for example, they should have labelled the food to

inform customers of its high calorific value.

Any hint that the food is addictive, though, would make Banzhaf's job a

great deal easier. And he knows it. Banzhaf already says he believes that

fast food has "addictive-like" properties. "We might even discover that it's

possible to become addicted to the all-American meal of burgers and fries,"

he says.

But how can something you need for survival be addictive? The answer could

be in the food itself. The difference between a fast-food meal and a

home-cooked one is the sheer quantity of calories and fat it delivers in one

go. The US Department of Agriculture's recommended daily intake for a normal

adult male is 2800 kilocalories (11,723 kilojoules) and a maximum of 93

grams of fat. A meal at a fast-food outlet - burger, fries, drink and

dessert - can deliver almost all of that in a single sitting (see Diagram).

Biologists are now starting to realise that a binge of these proportions can

trigger physiological changes which mute the hormonal signals that normally

tell you to put down the fork.

In the past decade, researchers have discovered myriad hormones that play a

role in regulating appetite. Under normal conditions these hormones control

eating and help maintain a stable body weight. Leptin, for example, is

continuously secreted by fat cells and its level in the bloodstream

indicates the status of the body's fat reserves. This signal is read by the

hypothalamus, the brain region that coordinates eating behaviour, and taken

as a guideline for keeping reserves stable.

The problem is, people who gain weight develop resistance to leptin's power,

explains Michael Schwartz, an endocrinologist at the University of

Washington in Seattle. "Their brain loses its ability to respond to these

hormones as body fat increases," he says. The fatter they get, and the more

leptin they make, the more insensitive the hypothalamus becomes. Eventually

the hypothalamus interprets the elevated level as normal - and forever after

misreads the drops in leptin caused by weight loss as a starvation warning.

But you don't need to become overweight to perturb your leptin system. The

latest research suggests that it only takes a few fatty meals. In a study

published in December, physiologist Luciano Rossetti of the Albert Einstein

College of Medicine in New York City fed rats a high-fat diet and found that

after just 72 hours the animals had already lost almost all of their ability

to respond to leptin (Diabetes, vol 50, p 2786). The good news, says

Rossetti, is that these changes are reversible. "But the fatter a person

becomes the more resistant they will be to the effects of leptin and the

harder it is to reverse those effects."

Sarah Leibowitz, a neurobiologist at Rockefeller University in New York

City, has more evidence that eating fast food is self-reinforcing. Her

experiments show that exposure to fatty foods may quickly reconfigure the

body's hormonal system to want yet more fat. She has shown that levels of

galanin, a brain peptide that stimulates eating and slows down energy

expenditure, increase in rats when they eat a high-fat diet.

In fact, Leibowitz has found that it only takes one high-fat meal to

stimulate galanin expression in the hypothalamus. When the effects of

galanin are blocked, the animals eat much less fat. "The peptide is itself

responsive to the consumption of fat, which then creates the basis for a

vicious cycle," she says.

What's more, early exposure to fatty food could reconfigure children's

bodies so that they always choose fatty foods. Leibowitz found that when she

fed young rats a high-fat diet, they invariably became obese later in life.

She is still investigating what's going on, but her theory is that an

elevated level of fats called triglycerides in the bloodstream turns on

genes for neuropeptides such as galanin that promote overeating. This

suggests that children fed kids' meals at fast-food restaurants are more

likely to grow up to be burger-scoffing adults.

Rossetti's most recent studies have also found a connection between

triglycerides and food intake. Using a catheter implanted in the brain,

Rossetti delivered lipids directly into the arcuate nucleus - a region of

the hypothalamus - to either normally fed rats or overfed rats, and then

measured their food intake for three days. In the normally fed group the

excess fats curbed food intake by up to 60 per cent. But the overfed rats

just carried on scoffing. What's more, Rossetti discovered that this effect

is not dependent on the composition of the diet, whether high-fat or

high-sugar, but instead depends on the total amount of calories.

Hormonal changes may remove some element of free will, but on its own that

hardly means that fast food is addictive. However, there is another strand

of research that suggests gorging on fat and sugar causes brain changes

normally associated with addictive drugs such as heroin.

It is already well established that food and addiction are closely linked.

Many addiction researchers believe that addictive drugs such as cocaine and

nicotine exert their irresistible pull by hijacking "reward" circuits in the

brain. These circuits evolved to motivate humans to seek healthy rewards

such as food and sex. Eating energy-dense food, for example, triggers the

release of endorphins and enkephalins, the brain's natural opioids, which

stimulate a squirt of dopamine into a structure called the nucleus

accumbens, a tiny cluster of cells in the midbrain. Exactly how this

generates a feeling of reward isn't understood, but it is clear that

addictive substances provide a short cut to it - they all seem to increase

levels of dopamine in the nucleus accumbens. Repeated use of addictive

substances is thought to alter the circuitry in as yet unknown ways.

Sugar junkies

Most of this research has been done with the aim of understanding drug

addiction. But a few researchers are now asking whether the brain's reward

circuits can also be hot-wired by mega-doses of fat and sugar. John Hoebel,

a psychologist at Princeton University in New Jersey, is interested in

whether it is possible to become dependent on the natural opioids released

when you eat a large amount of sugar. Along with a team of physiologists

from the University of the Andes in Mrida, Venezuela, Hoebel recently

showed that rats fed a diet containing 25 per cent sugar are thrown into a

state of anxiety when the sugar is removed. Their symptoms included

chattering teeth and the shakes - similar, he says, to those seen in people

withdrawing from nicotine or morphine. What's more, when Hoebel gave the

rats naloxone, a drug that blocks opioid receptors, he saw a drop in

dopamine levels in the nucleus accumbens, plus an increase in acetylcholine

release. This is the same neurochemical pattern shown by heroin addicts as

they go into opioid withdrawal (Obesity Research, vol 10, p 478). "The

implication is that some animals - and by extension some people - can become

overly dependent on sweet food," says Hoebel. "The brain is getting addicted

to its own opioids as it would morphine or heroin. Drugs give a bigger

effect, but it's essentially the same process."

As yet no one knows how a big hit of fat and sugar compares with a dose of,

say, heroin. But Hoebel says: "Highly palatable foods and highly potent

sexual stimuli are the only stimuli capable of activating the dopamine

system with anywhere near the potency of addictive drugs."

Ann Kelley, a neuroscientist at the University of Wisconsin Medical School

in Madison, has uncovered more evidence that the release of opioids in the

nucleus accumbens tells your brain to keep eating. She found that if rats'

opioid receptors are overstimulated with a synthetic enkephalin, the rats

eat up to six times the amount of fat they normally consume. They also raise

their intake of sweet, salty and alcohol-containing solutions, even when

they are not hungry.

Kelley has also discovered that rats that overindulge in tasty foods show

marked, long-lasting changes in their brain chemistry similar to those

caused by extended use of morphine or heroin. When she looked at the brains

of rats that received highly palatable food for two weeks, she saw a

decrease in gene expression for enkephalin in the nucleus accumbens. "This

says that mere exposure to pleasurable, tasty foods is enough to change gene

expression, and that suggests that you could be addicted to food," says

Kelley.

However, the idea that food is addictive is far from mainstream. And while

many nutritionists think it is a plausible idea that deserves more research,

others are sceptical. Michael Jacobson, executive director of the Center for

Science in the Public Interest, a Washington DC lobby group that focuses on

nutrition, doesn't think the argument will fly. So far, the CSPI has not

seen any evidence that fast food is addictive."Considering the paucity of

evidence, I think the burden is on advocates of the addiction argument to

provide evidence of addictiveness," Jacobson says.

Some practitioners also dispute the idea. There is no reliable evidence that

addiction can account for bingeing and obesity, says Jeanne Randolph, a

psychiatrist at the University of Toronto who specialises exclusively in

treating obese patients. Randolph admits that the behaviour of many of her

patients is remarkably similar to drug cravings: at predictable times of

day, in predictable circumstances, they describe an increasingly intense

drive to obtain their preferred sugary snack or junk food, and afterwards

feel immediate relief and calm. But, she says, you can explain this without

invoking addiction. Fast food, sweets and snacks in which simple sugars

predominate can set up a cycle of instant satiation followed by a plunge in

blood sugar, which leads to a natural desire for another snack."It's a

set-up for a late-afternoon binge rather than an addiction."

The argument has a long way to go. But chances are it won't get the chance

to mature naturally. Some time soon the allegation that fast food is

addictive will be made in court, and once that happens the terms of the

debate are out of the scientists' hands. It won't make for a scholarly

discussion. But it is still a debate worth having.

What constitutes an addiction?

Addictiveness has proved surprisingly hard to define, and there are several

different ways of judging whether a substance is addictive. One of the most

widely used is known as the DSM-IV criteria, devised by the American

Psychiatric Association. To be addictive, a substance has to meet at least

three of the following criteria:

* Taken in larger amounts or over a longer period than intended

* Persistent desire or unsuccessful efforts to cut down or control use

* A great deal of time spent seeking the substance out, using it or

recovering from its effects

* Important social, occupational or recreational activities given up or

reduced because of substance use

* Continued use despite knowledge of harmful consequences

* Increased tolerance with use

* Withdrawal symptoms

Fat facts

* More than 60 per cent of American adults and 13 per cent of children

and adolescents are classified as overweight or obese. The adult figure has

doubled since 1980; for children and adolescents it has trebled

* In 2000, the US healthcare system spent $61 billion on the diagnosis,

care and prevention of obesity

* Last year, Americans spent about $115 billion on fast food, more than

on higher education or personal computers or new cars

* Americans spend about half of their food budget on meals and drinks

consumed outside the home, and consume about a third of their daily energy

this way