Published online 7 March 2006 | Nature | doi:10.1038/news060306-9

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Caffeine boosts risk of heart attacks in the genetically susceptible.

How many cups of coffee should you have? It may depend on your genes. © Getty

People carrying a common variation in a certain gene could be worsening their risk of a heart attack simply by drinking several cups of coffee per day.

A possible link between coffee and heart disease has been tested before, but the results have been controversial. One reason is that coffee addicts are more likely to smoke and indulge in other unhealthy behaviours; another is that coffee contains a mix of caffeine and other chemicals, so it is unclear what provokes the body.

In the new study, researchers specifically tested whether caffeine in coffee could promote heart problems by examining a gene called CYP1A2. The gene, which codes for an enzyme that helps to break down caffeine, comes in two flavours: one version, known as CYP1A2 *1F, metabolizes caffeine more slowly than the other.

People who carry one or two copies of the 'slow' gene are slow metabolizers and take longer to rid the body of caffeine than those who carry two copies of the 'fast' gene.

Ahmed El-Sohemy of the University of Toronto, Canada, and his team examined more than 2,000 people in Costa Rica who had suffered, but survived, a heart attack, and an equivalent group of healthy individuals. A questionnaire revealed that quaffing coffee boosted the risk of a heart attack in those who had genes making them slow metabolizers.

Slow metabolizers who drank two to three 250-millilitre cups of coffee each day were 36% more likely to have suffered a heart attack than single-cup drinkers. And those who drank four or more cups were 64% more likely to have been struck. The risk was greatest in those below the age of 60.

By contrast, one to three cups seemed to protect those individuals whose genes made them fast metabolizers. "The results are clear and quite striking," says El-Sohemy. Researchers do not know exactly how caffeine could be affecting the heart, but one idea is that it could affect the ability of blood vessels to expand and contract.

Drop the pick-me-up?

The study suggests that a simple genetic test could identify those who are slow caffeine metabolizers, and that these people could be advised to cut down on their morning pick-me-up.

But both El-Sohemy and other experts say they are not ready to make that recommendation yet. "Other conditions needs to be fulfilled before we can sound the alarm of 'Abandon Starbucks! Young CYP1A2 *1F carriers first!'" says Jose Ordovas, an expert in nutrition and genetics at Tufts University, Boston, Massachusetts.

People who consume a lot of coffee could also be more stressed and sleep less, and this could explain their heart problems, Ordovas says.

Coffee culture

To confirm the recent study, experts say that it needs to be repeated in other ethnically and genetically different populations, in which other genes and lifestyle factors could influence how caffeine affects the heart.

Researchers would then need to carry out clinical trials in which they randomly assign a group of individuals to take caffeine or a placebo, and examine whether the caffeine can cut cholesterol or other indicators of heart health.

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El-Sohemy notes that people cannot assume that they are slow metabolizers just because they become jittery after one cup of coffee.

The eye-opening effect of caffeine is determined primarily by the way it acts in the nervous system, rather than by how long it lingers in the body. So it is hard to determine slow metabolizers from fast ones just from the way they react to coffee.

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