Jeremy Piper/Bloomberg

When an expert federal 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 national habit.

“Do you love coffee? You should probably be drinking even more.”
“Coffee’s Great, U.S. Panel Says in Official Diet Recommendations”
“Up to 5 Cups of Coffee a Day OK, Gov't Advisory Committee Says”

This burst of enthusiasm was set off by the conclusions of the federal advisory committee that helps write the influential Dietary Guidelines for Americans: “Strong and consistent evidence shows that consumption of coffee within the moderate range (3 to 5 cups per day...) is not associated with increased risk of major chronic diseases,” the panel 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 America’s favorite drink: 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 percent of people - more coffee has been linked in separate studies to a higher risk of hypertension 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.”

“There’s clearly some genetic variance that alters our ability to metabolize caffeine,” said Marilyn Cornelis, a Northwestern med school professor who has led some of the research connecting genetics, heart attacks, and coffee.  “A one-size fits all recommendation for coffee won’t work. Some people just can’t tolerate it.”

The finding of the federal 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. In their view, the evidence for an interaction between coffee and a person’s genetics, or “genotype,” is weak.

“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. “The observed gene-caffeine interactions have not been replicated in other studies and populations yet and thus these results need to be interpreted cautiously...[the] clinical implications of these results are not ready for prime time yet.”

Alice Lichtenstein, a Tufts University professor and another member of the federal advisory panel,  said that “the Dietary Guidelines are meant for the general population...when looking at the totality of the data in an unbiased way, moderate consumption of caffeine is not associated with increased long-term health risks and in some cases is associated with benefit.”

But she noted that the panel's report warns against taking up coffee drinking simply for its health benefits. She also allowed  that some people handle foods differently, and “for those individuals the guidance will need to be modified.”

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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 percent 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. During the study period, 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 percent less likely to die from any cause, 12 percent less likely to die of heart disease and 17 percent less likely to die of stroke than a person who abstains from coffee.

 “Our results provide reassurance with respect to the concern that coffee drinking might adversely affect health,” the NEJM article concluded.

Indeed, there have been so many studies on coffee that in compiling their recommendation, the federal advisory panel relied on so-called “meta-analyses,” which are used to combine the data from multiple studies. Of those, a meta-analysis published by Hu and colleagues two years ago in the journal Circulation may have been the most weighty of all. They reviewed 36 studies that examined the connection between heart disease and coffee; together those studies included the records for more than 1.2 million people.

What they found is that, when it comes to coffee, moderate coffee drinking is associated with better health: people who drank some coffee - about 1 to 4 cups - had a lower risk of heart disease. Those who had no coffee, or had lots of coffee - 5 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 3 to 5 cups per day of coffee consumption,” the researchers wrote.

One of the virtues of such studies as evidence is that they include so many people, from so many different populations.

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, and it's not exactly clear why that should be. 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 4 cups per day had a 50 percent 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.

Hu and his colleagues have suggested that those contrary findings might be explained by weaknesses in the study - maybe the group of 43,000 people was not large enough, or maybe the measures of coffee intake were off.

But other scientists have suggested that such inconsistencies between studies might reflect a deeper problem. As Greenland put it, the inconsistencies may be “signaling that some crucial information is missing from the analyses.”

One of the pieces of missing information could be the genetics of the person drinking coffee.

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Scientists have recognized for more than a decade 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.

What the scientists found is that the identical twins, who match each other genetically, process 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. More specifically, the rates of caffeine metabolism in identical twins were twice as correlated as those between fraternal twins.

The process of caffeine metabolism "is mainly governed by genetic factors," the researchers concluded.

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 percent 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.

Both research efforts showed this curious divergence: in some people, drinking coffee was associated with better health while in others, it was associated with worse. Scientists suggested that this could be because coffee contains some beneficial substances - and if you can tolerate the caffeine, those aspects of coffee could improve your health.

“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, which was published in the Journal of Hypertension.

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

For starters, many people have little idea of their coffee genetics - that is, whether they process coffee quickly or slowly. In the U.S., the genetic testing firm 23andme currently does not offer results for this portion of CYP1A2, though some people may have a hint of how caffeine affects them.

“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.”

The broader issue is that the science, as some scientists argue, remains too unsettled to deliver clear answers.

The case in favor of coffee offers large numbers - lots of studies involving lots of people - but they are not completely consistent. By contrast, the case raising questions about coffee and genetics is based on a relative handful of studies - involving only several thousand people. But 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.

Even those scientists most involved in the genetics investigations were reluctant to say their case is proven - they all favor more research. Beyond saying that people with high blood pressure ought to limit themselves to no more than three cups per day, Palatini was loath to lay down any more general rules about coffee drinking.

But he and others suggested that the genetic evidence turned up so far is strong enough, that it is premature for the Dietary Guidelines for Americans to say that three to five cups of coffee a day does no harm.

Echoing others, Palatini said the advice from the advisory committee  is probably “too optimistic.”