Science - June 9, 2011

Fat and healthy - on aspirin

The pharmaceutical industry thinks it can tackle overweight with a slimming pill. Two Wageningen professors argue for a different approach. An aspirin and careful supervision will go a long way.

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For a brief period, you could get a slimming pill that worked. The hope was that it would rid the west of public health risk number one: obesity. After a fortune had been spent on its development, the pill came onto the European market in 2006. It contained rimonabant, a substance that suppresses the appetite by blocking reward receptors in the brain. The pill worked: people really did lose weight. Nevertheless, it soon disappeared again. It turned out to suppress not just the appetite but also many pleasurable feelings, and people became depressed and even suicidal. So within two years the wonder drug had been taken off the market, and the pharmaceutical industry could wave goodbye to at least three billion dollars in development costs.
But the pharmaceutical firms have not given up their efforts to develop the ultimate slimming pill, and nor have we in the west stopped eating much too much. There seems to be an unstoppable rise in the numbers of overweight people, which have grown to epidemic proportions since 1980.
Renger Witkamp, professor of Nutrition and Pharmacology, is researching the relationship between food and medicines. He does not see much future in the drug companies' magic bullet, in view of the risks and side effects. He thinks a lot can be achieved by curbing the ill effects of overweight. For example, you can give overweight people a humble aspirin to keep them healthy. 'If you look at it at the population level, this seems to work, but adoption by individuals is still far off', says Witkamp. His colleague, Edith Feskens, personal professor of Nutrition, would prefer an approach that aims at preventing obesity. It should be made more difficult for people to make 'unhealthy' choices, she says.

Sweet dishes
Almost half the Dutch population are overweight, and this figure is still on the increase. The cause seems to be an inexplicable urge to eat too much, with a strong preference for highly calorific fatty and sweet dishes. With a fast food chain or snack bar on every street corner, temptation lies all around you. What is more, the Dutch get far too little exercise, on average. Intellectually, we all know we should eat less and exercise more, but knowing it is not enough. 'Eating is a primal urge which is difficult to control', says Witkamp. 'The body stimulates and rewards eating, by making molecules that create pleasurable feelings. In the brain, these molecules bind to the same receptors as cannabis and create the satiated feeling we have after a good meal.' The basis for this addiction and gluttony seems to be genetic. Prehistoric humans never knew where the next meal was coming from, so whenever they got hold of food, they made the most of it and ate all they could. The excess food was converted to fat in the body, and stored to help bridge times of scarcity.
Metabolic disaster
The same genes are catastrophic for modern western society where food is abundant. Because overweight brings many problems with it. Basically, the fatter a person is, the higher their risks of all sorts of diseases. 'Obesity is not a problem in itself, but the metabolic disaster it brings with it is a problem', says Edith Feskens. 'For example, obese people run ten times the risk of going down with diabetes. And overweight often goes together with low levels of healthy cholesterol, HDL, high blood pressure and, the new kid on the block, inflamed fat tissue.' Nutritionists suspect that these inflammations are largely responsible for a range of ailments, from cardio-vascular disease to cancers.
According to calculations by national public health institute the RIVM, life expectancy for obese people, like that of smokers, is six to seven times lower than that of people with a normal weight. Overweight people have 5 to 15 fewer healthy and productive years ahead of them. This means that overweight affects not only health but also the national budget. The costs for health care and lost working days amount to up to 1.2 billion euros per year, 2 percent of the total health expenditure in the Netherlands, according to RIVM calculations. In the US, these costs are up to about 150 billion dollars (100 billion euros).
Fries with mayonnaise
Solving the obesity problem with a simple pill poses massive challenges, as the pharmaceutical industry is finding out to its cost. 'If you press a button chemically, to suppress appetite or prevent fat storage for example, the body finds a way of bypassing this', explains Witkamp. 'Interfering with the brain chemically works best, but that is risky too, because of the side effects.' Undaunted by the fiasco of the first slimming pill that worked, the industry is going full steam ahead with developing its successor. A slimming pill by the name of Alli has recently become available on prescription at pharmacies and on the internet. It is selling well. This pill contains a substance called orlistat, which prevents fats from being broken down in the intestines, so they cannot be absorbed. The disadvantage is that the fat consumed in a portion of fries with mayonnaise leaks out of the anus, so that users of this medicine often use a pad in their underwear.
The industry is in hot pursuit of a pill that does not have such unpleasant side effects. One of the most extreme treatments currently being tested comes from cancer therapies. It involves what are known as angiogenesis inhibitors, which slow down the formation of blood vessels in a tumour, reducing circulation and with it the growth of the tumour. The idea is that the same trick could be done with fat tissue.
Fat tax
Witkamp think that the vast majority of overweight people should not take these sorts of heavy drugs. 'I look at developments in the pharmaceutical industry with astonishment', he says. 'Scientifically, it is interesting, but I wonder what you gain by it, in view of the risks and side effects.' Operations still work best: stomach stapling or surgical stomach reduction is highly effective.
The best remedy for obesity, of course, is changing behaviour. Exercising more and eating less is the obvious route to a slimmed-down society. But how do you get the overweight to do this? According to Professor Feskens, you have to make it harder for people to make 'unhealthy' choices. You could do that by slapping an extra 'fat tax' on unhealthy foods, by passing legislation to limit the number of snack bars and fast food restaurants, and by banning the sale of junk food in school canteens. 'I am amazed by the food that is sold in school canteens: fatty snacks and soft drinks', explains Feskens. 'There is a lot to be gained here.'
And diets? Feskens does not believe in them. What is needed, she says, is a healthy lifestyle. It is a thorn in the professor's side that diet gurus earn fortunes from dubious crash diets. 'I am something of a frustrated prevention expert with too little budget, pitched against the industry and the inventors of diets', she says. 'I think that people should be obliged to invest some of the money made from that sort of thing in nutrition research.'
Guzzling machines
Witkamp is not optimistic about the prospects of a solution to the obesity problem. 'We are still just incredibly efficient guzzling machines', he says. He thinks it would therefore be a big step in the right direction if we could soften the impact of overweight on health. Low-grade inflammations in fatty tissue are the heart of the problem. So these inflammations must be tackled. 'As early as the 19 th century, aspirin, the anti-inflammatory that had just been discovered, cured an enormous woman of her diabetes in what seemed a miraculous way', says Witkamp. 'Only the patient went from the frying pan into the fire, because the aspirin then gave her serious stomach complaints.' You do not get this problem with some of the anti-inflammatory foods discovered in modern times, such as unsaturated fats and red wine. Resveratrol, a substance naturally found in red wine, seems to increase the lifespans of fat mice dramatically. 'The fat mice were just as healthy as the thin ones, possibly because of the anti-inflammatory effect of resveratrol', explains Witkamp.

Chronic inflammations
For undisciplined eaters who do not drink red wine, a daily dose of aspirin may be the solution for keeping their fat healthy. According to Witkamp, this miracle cure works against chronic inflammation, even at low dosages. And yet it is by no means certain that people will be prepared to take a pill every day. 'People do not like medicines; compliance is low. I don't think it will work.'
Professor Feskens thinks that with good information campaigns and guidance, it should be perfectly possible to help people get thinner and healthier without the use of potions and powders. 'I think you can win the battle, but then we should go for a mix of measures that make for a healthier lifestyle: sport in groups, the guidance of a dietician, and eating less.' And that approach has already met with modest success. Among overweight people who opted for this mix of measures, under the guidance of a dietician and an exercise therapist, the number of new diabetes patients was halved. An overdose of supervision? 'Yes, but people who need supervision should get it. There was a good plan for including the approach in the basic health insurance package, but Minister Schippers has vetoed that. Worse still, the budget for lifestyle has been drastically cut. The high risk groups certainly won't be helped by that.'
Overweight in figures
The proportion of Dutch adults who are overweight is 52 percent for men and 42 percent for women. More than 10 percent of the population are categorized as seriously overweight, a proportion which has doubled in 30 years. Yet the Netherlands is not doing too badly compared to the rest of Europe. With the exception of the Swiss, the French and the Italians, people in other European countries are fatter. The British and the Germans are the fattest Europeans, with twice the number of seriously overweight people. Outside Europe, the US is way ahead of the field when it comes to overweight. It is estimated that nearly three quarters of Americans are overweight, and one third seriously so. Here too, the numbers have shot up in the last 30 years.
An increasing number of children are overweight too. Thirty years ago, about 6 percent of children between the ages of 2 and 18 years suffered from overweight, a figure which has more than doubled, to around 14 percent. In the US an estimated quarter of all children and teenagers are overweight, a figure which has tripled in 30 years.

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