'Coffee is harmless' - scientists disagree

Emerging findings from genetics suggest a very different take on one of our favorite drinks. Photo / Getty Images

When an expert panel concluded earlier this year that drinking five cups of coffee a day can be part of a "healthy lifestyle", even hinting that coffee is good for you, the announcement prompted a glut of headlines extolling the habit.

"Do you love coffee? You should probably be drinking even more," one news outlet crowed.

This burst of coffee enthusiasm was set off by the conclusions of the federal advisory committee that helps write the US government's Dietary Guidelines for Americans.

"Strong and consistent evidence shows that consumption of coffee within the moderate range (three to five cups per day...) is not associated with increased risk of major chronic diseases," the panel's report said. "Moderate coffee consumption can be incorporated into a healthy lifestyle."

Yet at least for some scientists, it's far from clear that coffee is harmless. In fact, emerging findings from genetics suggest a very different take on one of our favorite drinks: while coffee might possibly be beneficial for some people, it very well may be harmful for others.

In research not cited by the advisory committee, scientists have identified at least one specific location in the genome - a single nucleotide out of roughly three billion - that determines whether a person processes caffeine quickly or slowly. And in those with the gene variant for handling caffeine slowly - roughly 50 per cent of people - more coffee has been linked in separate studies to a higher risk of hypertension (high blood pressure) and heart attacks.

Unfortunately, because genetic testing is expensive and rarely done, most people have little idea which gene variant they carry.

Regardless, the genetics research leads some experts to question whether a general rule about the effects of coffee - good or ill - is possible.

In fact, the coffee argument reflects a deeper uncertainty about the nutrition advice routinely dispensed to the general public: How useful are dietary rules that apply to everyone, when genetic differences mean that foods affect us differently?

"There are spectacular metabolic differences in people and to expect that coffee will have the same health effects on everyone is absurd," said Sander Greenland, an emeritus epidemiology professor at UCLA, an expert in research methodology who has studied coffee. "They want to come out with the generalized recommendations? It's laughable."

The finding of the advisory panel is supported by dozens of studies showing that, on average, people who drink coffee are no worse off than those who don't.

In fact, several suggest that coffee drinkers may be more resistant to heart disease and other health troubles. Those studies, however, do not examine whether the test subjects process caffeine differently, or how genetics affects how people handle the stimulant.

Asked about those issues, some members of the federal advisory panel cast doubt on the science supporting the idea that genetics dramatically affects coffee's effects on humans.

"Right now, there is limited evidence to recommend different diets or foods based on genotypes," said Frank Hu, a Harvard epidemiologist on the panel who has studied coffee's impacts.

Given its popularity, the debate over coffee may be particularly important for public health. According to survey data from an industry association, on any given day more people report drinking coffee than even tap water, bottled water, or soft drinks.

In a survey of 2,000 adults, nearly 60 per cent said they'd had coffee the day before.
The ubiquity of coffee has inspired dozens of studies of its health effects and collectively, at least, these efforts show little cause for worry.

One of the most notable was a study, conducted by National Institutes of Health scientists and published in the New England Journal of Medicine in 2012. The results suggested that coffee has far-reaching benefits - almost a miracle drug.

The researchers examined the health and coffee habits of more than 400,000 people over 13 years. They found that the people drinking larger amounts of coffee seemed to be healthier, though researchers said the benefits appeared to plateau after about three cups.

Those who drank coffee were less likely to die of almost anything - heart disease, stroke, diabetes, even accidents - than non-drinkers. For example, people who had six cups of coffee a day were 10 per cent less likely to die from any cause and 12 percent less likely to die of heart disease.

Indeed, there have been so many studies on coffee that in compiling their recommendation, the panel relied on so-called "meta-analyses", which are used to combine the data from multiple studies.

One of the most important meta-analyses, which was published by Hu and colleagues two years ago, included the records for more than 1.2 million people.

What they found is that, when it comes to coffee, moderate consumption is associated with better health: people who drank some coffee - about one to four cups - had a lower risk of heart disease.

Studies do not examine whether the test subjects process caffeine differently, or how genetics affects how people handle the stimulant. / Getty Images

Those who had no coffee, or had lots of coffee - five cups per day or more, showed neither elevated nor lowered risks of heart disease.

The researchers speculated that coffee, which is a complex chemical stew, may have both good and bad effects, and that in moderate amounts, the good effects outweigh the bad ones.

"Moderate coffee consumption was associated with lower [heart disease] risk, with the lowest...risk at three to five cups per day of coffee consumption," the researchers wrote.

Scientists, however, are careful to note that the data in these studies are not generated from true experiments - that is, the people were not randomly assigned to drink coffee or not.

Instead, the scientists merely followed people and recorded their health and coffee habit. While that might seem like a minor distinction, it means that some other difference between coffee drinkers and non-drinkers - not just their coffee intake - might have caused the health differences that were observed.

Another concern about the evidence favoring coffee is that the studies don't always agree with one another.

For example, two years ago, a group of researchers from various universities looked at records for 43,000 people over more than 30 years and came to different conclusions: Among people less than 55 years old, people who drank more than four cups per day had a 50 per cent higher risk of death.

"Based on our findings, it seems appropriate to suggest that younger people avoid heavy coffee consumption," the researchers wrote in Mayo Clinic Proceedings.

Other scientists have suggested that such inconsistencies between studies might reflect a deeper problem - that the speed with which people process caffeine is influenced by heredity.

The most striking experiment in this regard involved 83 sets of same-sex twins, some identical, some fraternal.

Each of the twins were given 200 milligrams of caffeine; six hours later, a urine sample was taken to see how much of the caffeine had been broken down, or metabolized.

The identical twins, who match each other genetically, processed caffeine very similarly - if one identical twin was a "slow metabolizer", so was the other.

By contrast, the fraternal twins, who are less alike genetically, were much less likely to process caffeine in the same way. In fact, the rates of caffeine metabolism in identical twins were twice as correlated as those between fraternal twins.

At the same time, researchers know that most caffeine in the body is broken down by an enzyme known as CYP1A2, which is produced in the liver. The enzyme is produced, or more specifically, encoded, by virtue of a gene of the same name.

Repeated studies - in Mexico, Germany and China - have shown that a single genetic building block on that gene helps determine whether people process caffeine quickly or slowly. The portion of people with the "slow" gene varies by country, but appears to be roughly 50 per cent of people.

That discovery led other scientists to theorize that people who process caffeine more slowly may be more susceptible to coffee's potential dangers. In two more recent studies, one in 2006 and another in 2009, scientists found that indeed genetics might have significant implications for coffee drinkers.

Among those with the gene for "fast" caffeine metabolism, coffee drinking was associated with a lower risk of high blood pressure and heart attack; among those with "slow" caffeine metabolism, by contrast, coffee drinking was associated with higher risk of high blood pressure and heart attack.

"There seems to be a Jekyll and Hyde aspect to coffee," said Paolo Palatini, a medical professor at the University of Padua, in Italy, who led the 2009 study on coffee and high blood pressure.

For anyone looking for usable advice, the state of the science may be too ambiguous to offer much help.

Many people have little idea of their coffee genetics - that is, whether they process coffee quickly or slowly. In the United States, even the genetic testing firm 23andme currently does not offer results for this portion of CYP1A2.

The idea that coffee's effects may depend on genetics matches the widespread idea that coffee has different effects on people. Some people can sleep after a cup of coffee; others are up all night long.

"The only hint may come from symptoms after drinking coffee," Palatini said. "There are people who feel nervous, suffer insomnia and even have tremor after one cup, attesting to a direct effect of caffeine on the brain."