Why caffeine hits some people hard and leaves others unfazed

Emily is twenty years old, standing outside a London café at six in the evening, and she has just finished her second cup of coffee. She drinks two cups most days, sometimes adds an energy drink, and can consume cola late into the night without consequence. She sleeps fine. We all know someone like Emily—the person who seems immune to caffeine, who can drink espresso at dinner and drift off an hour later while the rest of us lie awake, mind racing, heart thumping against our ribs.

The difference between Emily and everyone else comes down to three things: how often you drink coffee, what you do with your body, and a single gene you inherited from your parents. Caffeine is the most widely used psychoactive substance on Earth. More than two billion cups of coffee are consumed daily, and that count doesn't include energy drinks, cola, chocolate, chewing gum, or sports supplements—all of which contain the chemical. It sharpens focus, staves off drowsiness, and makes us feel alert. The catch is that too much causes headaches, jitters, a racing heart, and sleepless nights. But here's what many people misunderstand: caffeine doesn't actually give you energy. It works by blocking adenosine, a chemical that accumulates in your brain throughout the day and signals that you're tired. Caffeine masks that signal. It doesn't fuel you; it lies to your brain.

The real mystery is why the same cup affects people so differently. The answer begins in your liver. When you drink coffee, caffeine enters your bloodstream and reaches your brain within minutes. At the same time, an enzyme in your liver begins breaking it down—a process called metabolism—and your kidneys flush it out through urine. That cleanup can take anywhere from six to twenty hours, depending entirely on who you are. Dr. Marilyn Cornelis, an associate professor of nutrition at Northwestern University in Chicago, explains that you might drink one cup and feel nothing. But two or three hours later, that caffeine is still circulating. Add a second cup, and suddenly you're anxious. The difference between calm and wired is timing and accumulation.

The speed at which your liver processes caffeine is controlled by a single gene called CYP1A2. Ancestry appears to play a role: a study published this year found that Europeans and South Americans tend to metabolize caffeine faster on average than other populations. But genetics is only part of the story. Smoking accelerates the breakdown by as much as sixty-five percent, which may explain why smokers drink more coffee and why people who quit smoking often find their usual cup suddenly feels too strong. Certain antibiotics, contraceptive pills, and other prescription medications slow the process, trapping caffeine in your system longer. Pregnancy does the same thing—hormonal changes suppress the liver enzyme that breaks down caffeine, which is why the NHS advises pregnant women to keep intake below two hundred milligrams a day, roughly two mugs of filter coffee, as higher amounts have been linked to low birth weight and other complications.

Then there is tolerance. If you drink coffee every day, your brain adapts. The chemical becomes less noticeable. Stop drinking it for a few weeks, and those adaptations reverse. Your first cup back might leave you feeling unusually wired or jittery—your body has forgotten how to handle it. Sleep researcher Dr. Lindsay Browning, a psychologist, says the evidence suggests caffeine doesn't just prevent sleep; it degrades sleep quality. She recommends avoiding it after about two in the afternoon if you plan to be in bed by ten. But she's careful to note that no single rule works for everyone. "A blanket hard-and-fast rule isn't helpful," she says, "because it doesn't really allow for the intricacies and the individualisation of what's really going on."

For most adults, the advice is straightforward: moderation. Sensitivity varies so much from person to person that what matters is knowing yourself. Peter Rogers, an emeritus professor of nutrition at the University of Bristol, points out that caffeine is relatively safe. Drink too much and you'll feel jittery and unpleasant, and you'll naturally stop. Overdoses are rare; severe poisonings almost always involve concentrated caffeine products where several grams are swallowed in minutes. For regular coffee drinkers, there's good news: decades of research suggest that moderate consumption is linked to better health outcomes. People who drink coffee tend to have lower risks of several major diseases and may even live slightly longer than those who don't. Emily's two cups a day, and her evening cola, probably aren't hurting her. But for someone else, that same routine might mean staring at the ceiling until midnight.