Why do some people need 10 cups of coffee just to make it through the day, while others feel wired from just one cup?
Part of the answer may be in your genes.
Researchers from UNC-Chapel Hill, the Harvard School of Public Health, and five other institutions have pinpointed two genetic variants that may help explain why some people crave more caffeine than others.
Study coauthor Marilyn Cornelis of the Harvard School of Public Health knows one caffeine addict firsthand.
"My father drinks 10 to 15 cups of coffee a day," she said.
Whether they prefer to slurp coffee, sip tea, or guzzle soda, many people can't get by without their daily dose.
Caffeine is the most widely used mood-altering drug in the world, ahead of nicotine and alcohol.
Nearly 9 out of 10 American adults use caffeine every day in some form or another, consuming an average of 210 to 240 milligrams per person a day - roughly equal to two to three cups of coffee, or five or six cans of soda.
Caffeine isn't just an adult vice - thanks largely to skyrocketing soda trends, more than 75 percent of Americans age 2-11 consume caffeine on a daily basis, and caffeinated energy drinks with names like Red Bull or Rockstar are increasingly popular with teenagers.
Caffeine. Some people can't live with it, and others can't live without it.
"We all know people who can drink a pot of coffee and go straight to bed, and others who have a Coke at lunch and say it keeps them up all night," said Duke University caffeine researcher James Lane, who wasn't an author on the study.
Studies of identical twins have long led scientists to suspect that genes played a role, accounting for about 43 percent to 58 percent of the differences in caffeine consumption between people.
But no one knew what specific genetic variants were involved.
So colleagues from UNC-CH, Harvard and elsewhere scanned the genomes of nearly 50,000 Americans of European descent, looking for tiny variations in DNA, called single-nucleotide polymorphisms, or SNPs (pronounced "snips") that show up repeatedly in people with higher caffeine intake.
The data were collected from U.S. nutritional surveys conducted between 1984 and 2001, with participants reporting how often, and how much, they consumed coffee, tea, soda and chocolate, among other foods and drinks.
Pooling all the data, the researchers identified two variable snippets of DNA - out of the more than 2.5 million they examined - that differed consistently with caffeine consumption.
One of the variants was located near a gene called CYP1A2, which plays a role in caffeine metabolism, and the second was near a gene dubbed AHR, which regulates CYP1A2.
While everyone has two copies of each of these genes - one inherited from each parent - the copies vary subtly from one person to the next.
People with the most caffeine-craving version of either gene drank an average of 38 to 44 mg more caffeine per day than people with the least caffeine-craving version - roughly equal to a can of soda or half a cup of coffee.
But there are probably more genetic links than the two found here.
"The effects are small; I don't think it's worth paying a lot of money to get tested" to see if you are genetically predisposed, said UNC-CH researcher and study co-author David Couper.
But the findings, published in the journal PLoS Genetics, are an important step towards understanding why caffeine has different health effects for different people, the researchers say.
How it works
Caffeine works by blocking the action of adenosine, a brain chemical that promotes our natural urge to sleep.
So if you feel a boost of energy after sipping a cappuccino or throwing back a Red Bull, you're not imagining that caffeine buzz.
Ask a marathon runner, a college crammer, or anyone who works late nights: People love caffeine because it counters fatigue, improves concentration and alertness, quickens reaction time and enhances mood.
Caffeine is listed as "Generally Recognized As Safe" by the U.S. Food and Drug Administration.
Indeed, research suggests that caffeine can actually be beneficial to your health.
Studies show that it helps alleviate pain, and reduces your risk of developing Parkinson's, Alzheimer's, and certain types of cancer.
But for people with certain medical conditions, the down sides of that daily espresso go beyond insomnia or coffee breath, says Duke medical psychologist Lane, who has studied the health effects of caffeine for more than 20 years.
In particular, people with heart disease, high blood pressure, anxiety or Type II diabetes may want to quit or curb their caffeine intake, Lane says.
"Consuming caffeine on a regular basis raises your blood pressure higher than it otherwise would be, and that could increase your risk of heart disease over the long term," he said.
Caffeine also raises levels of stress hormones like adrenaline and cortisol, and makes it harder to control glucose levels, which could be bad news for stress management or diabetes control.
Studies suggest that some people are more sensitive to caffeine than others, or are slower to eliminate it from their bodies, which means that a small dose can have large effects.
"Even after having one cup in the morning they might still be feeling its effects at the end of the day," Lane said.
In contrast, people who are less sensitive to caffeine or whose bodies get rid of it faster can drink more of it, "but they also might want to drink more because it doesn't persist as long in their system," Lane added. "Differences in how people respond to caffeine might explain why people choose to drink more or less."
The study, which was largely funded by the National Institutes of Health, isn't the first to find genetic links to caffeine consumption.
To find out if additional genes might play a role, they're conducting a much larger study focused on coffee drinkers that includes more than 90,000 people and a wider range of ethnic groups, including African-Americans.
Researchers say the results will help us understand why the effects of caffeine vary from person to person, and help flag patients who are more likely to suffer negative side effects.
Harvard's Marilyn Cornelis: "It's called personalized medicine."