Caffeine has been getting a bad rap recently. Whether it’s highly caffeinated energy drinks making it difficult for kids to concentrate in class, or too many teas and coffees during the day leaving us unable to sleep at night, caffeine, in many people’s eyes, is a cause for alarm.
As such, the general advice regarding caffeine consumption increasingly seems to be to cut back on it or cut it out altogether. But it’s not as if caffeine is entirely without merit. There’s no denying it’s a psychoactive substance. Or, to put it more bluntly, caffeine is a drug (the world’s most widely consumed drug, in fact – chances are, you’re under its influence right now).
But, like many drugs, in the right dose, it has benefits. It was the clarity and energy that doses of caffeine provided (distributed via the tea and coffee houses of Europe) that helped usher in the Enlightenment and make the switch from farms to factories during the Industrial Revolution.
But dosage is the key variable. And although coffee and tea have been providing us with a tasty pick-me-up for centuries, nowadays more of us are consuming caffeine in much higher concentrations due to the boom in energy drinks and tablets.
This has prompted a rise in research into caffeine, as scientists work to better understand its effects on us and the mechanisms by which it produces them. So what are we learning from all this research? For one thing, just how differently each of us processes and reacts to caffeine.
But perhaps more importantly, it’s providing evidence that as well as perking us up in the morning, a few cups of coffee or tea each day might also help us stave off illnesses, such as diabetes and certain forms of cancer. So does caffeine really deserve its bad reputation?
The dose makes the poison
Anyone who consumes caffeine every day knows the importance of dosage: how much to take and when to take it. Get the dose right, and caffeine can lift your mood and make you more alert; overdo it and you risk anxiety, tremors and disrupted sleep.
Both the US Food and Drug Administration and the European Food Safety Authority say that a daily caffeine intake of 400mg (about two to three mugs of filter coffee, depending on the size of the mug) won’t cause problems for healthy adults.
As for when to take caffeine – or rather, when to stop taking it in order to prevent it from affecting your sleep, that depends on how you administer it.
Researchers in Australia and the UK published a study in the journal Sleep Medicine Reviews earlier this year that tried to give clear guidance on when your last ‘dose’ of caffeine should be. According to their report, you should drink your last tea or coffee 8 hours and 48 minutes before you go to bed.
If, however, you use a pre-workout caffeine supplement, which typically has double the caffeine of a cup of coffee, that should be taken no later than 13 hours 12 minutes before bedtime.
The problem with giving definitive directions on how much caffeine is okay and when to stop consuming it, however, is that some of us are more sensitive to it than others.
How long it hangs around inside our bodies varies, too – caffeine has a half-life (the time required for a substance to lose half of its initial effectiveness) of 3-7 hours in adults. The reason for this is genetic. But to understand it, you first need to know what caffeine does inside your body.
Caffeine and your genes
During the day, a molecule called adenosine builds up in your brain. Adenosine binds with receptors on nerve cells, or neurons, slowing down their activity and making you feel drowsy.
But caffeine is also able to bind with these receptors, and by doing so it blocks adenosine’s effect, making your neurons fire more and keeping you alert. Caffeine also activates the pituitary gland at the base of your brain.
This releases hormones that tell the adrenal glands on your kidneys to produce adrenaline, causing your heart to beat faster and your blood pressure to rise. If, however, your daily caffeine intake is consistent, your brain will adapt to it.
“Your brain is like, ‘Okay, every morning I’m getting this caffeine that’s binding to these receptors and blocking adenosine from binding to them’. And so [your brain] creates extra receptors to give adenosine more of an opportunity to bind with them and have its usual effect,” says Prof Jennifer Temple, whose lab at University at Buffalo in New York, carries out research on the effects of caffeine.
“And more adenosine is also produced to counteract the caffeine. That’s why it takes more and more caffeine to have the same effect.”
These adaptations take place rapidly – within as little as a week. Part of the differences in how we respond to caffeine is down to the extent to which each of our bodies have adapted to it.
But then there’s also the effect of our genes. Caffeine is mainly broken down, or metabolised, by the CYP1A2 enzyme in the liver, and the gene that codes for that enzyme has been found to vary a lot between people.
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Research shows that, for the most part, it’s the version of the CYP1A2 gene you have that determines how quickly you can metabolise caffeine and therefore how long it hangs around in your body. Fast metabolisers are able to clear caffeine quickly, so the effect of an espresso wears off faster for them.
The adenosine receptors in the brain also vary a lot depending on a person’s genetic makeup. And there are also some variants of the ADORA2A gene, which encodes one type of adenosine receptor, that make people particularly sensitive to caffeine. It’s also our genes that influence how much caffeinated coffee and tea we drink each day.
“Coffee is naturally a bitter substance and so it’s interesting how such a bitter beverage has become so popular,” says Marilyn Cornelis, Associate Professor of Preventive Medicine at Northwestern University in Illinois who researches the links between genes and caffeine.
“Based on evolution, we should naturally avoid bitter foods – it’s a protective effect your body has to avoid poisonous things.” It’s therefore logical to assume that people who are less sensitive to bitter tastes will be the ones who drink more coffee. But that’s not the case.
A study led by Cornelis and published in Scientific Reports shows that the version of the CYP1A2 gene we have influences how much coffee we drink to a much greater extent than our sensitivity to bitter tastes.
People with the version of CYP1A2 that makes them fast metabolisers drink more coffee. And tests show fast caffeine metabolisers have lower caffeine levels in their blood.
“It suggests that they’re metabolising caffeine so quickly, [that] they’re consuming more coffee to get the stimulant effects we equate with caffeine,” says Cornelis.
But whether you’re a fast caffeine metaboliser or not, chances are you’re pretty good at moderating your caffeine intake.
“The data suggests that, whether they’re conscious of doing it or not, people do a really good job of adjusting their caffeine intake to hit their sweet spot,” says Temple. “Because when they go over it, the effects are unpleasant and there’s a memory of that, so they go back to their sweet spot.”
That perfect balance of caffeine intake is potentially harder to gauge with caffeinated energy drinks, though. Studies show that the top-selling caffeinated energy drinks in the UK and US contain 75-160mg of caffeine.
But research published in Drug and Alcohol Dependence reported that some contain as much as 500mg of caffeine. By comparison, a 240ml mug of filter coffee contains about 190mg. The varied caffeine levels in different energy drinks can make judging your caffeine intake tricky.
But the complicating factors don’t end there. “Energy drinks contain other ingredients that interact with the caffeine in a way that we’re still trying to understand because we don’t know what they are,” explains Temple.
“All these blends are proprietary so we don’t know the exact formulation. But people respond differently. [So] we’re studying the effects of energy drinks in the same way we’ve been studying coffee and caffeine systematically,” she says.
Read more:
- Why do I feel wiped out after too much caffeine?
- In praise of caffeine, the world’s most widely consumed psychoactive drug
The benefits of caffeine
While the formulations of caffeinated energy drinks, and the effects they have on us has prompted a lot of recent research, there’s also a growing interest in caffeine’s beneficial effects. For example, caffeine is increasingly being used as a legal performance-enhancing drug in competitive sports. A review of research into caffeine and athletic performance by the International Society of Sports Nutrition in 2022 said caffeine has a ‘small to moderate effect’ on muscular endurance and strength.
Its biggest effects on performance are seen in endurance sports, though. It’s thought that at least some of this performance boost is likely down to caffeine aiding muscle contraction by changing levels of calcium, sodium and potassium, as well as acting as a painkiller.
There has also been a raft of studies attempting to determine how caffeine boosts our cognitive abilities. They’ve found that a moderate dose, up to 300mg, helps us stay focused for longer. Some research also shows that in the long term, caffeine can boost our memory, but here the evidence is somewhat mixed.
When it comes to determining the long-term health benefits of caffeine, things get complicated as most of the research has been carried out with coffee, which contains a cocktail of bioactive ingredients. Deciphering whether it’s caffeine or one of the many other components of coffee that brings about a health benefit, is difficult.
There’s good news for coffee drinkers, though. A review published in The New England Journal of Medicine in 2020 reports that your regular coffee fix reduces the risk of cardiovascular disease, type 2 diabetes, liver disease and certain forms of cancer, such as liver cancer.
For some conditions, such as type 2 diabetes, research shows it’s not the caffeine but some other component of coffee that helps to prevent them – as decaf coffee reduces the risk just like caffeinated coffee.
“But interestingly, if you look at other conditions, such as Parkinson’s disease, it seems to be completely the caffeine,” says Rob van Dam, Professor of Exercise, Nutrition Sciences and Epidemiology at The George Washington University in Washington DC, who led the review.
“Then there are some that sit in the middle, like liver cancer – it seems that caffeine may have some benefit, but there might be additional gain from some other components of coffee.”
In the future, scientists will discover more about how our genes determine the effects caffeine and coffee have on us. And the more we learn, the closer we’ll get to the prospect of personalised guidance for daily caffeine intake.
“Most of the guidelines for caffeine have really been just looking at the population level,” says Cornelis. “They don’t account for the individual variation and we’re at a stage in research where there are opportunities for personalised nutrition.”
It means that one day a genetic test could tell you precisely what the ‘sweet spot’ for your daily caffeine intake is. And that day might not be as far off as you think. “When I first started this genetic research during my PhD around 2001, I couldn’t imagine a day where every individual would be able to access their full genome. Well, it’s 2023 and we’re at that point where people are knowledgeable about their genetics and have paid these companies to get access to them. I’ve had people email me and say, ‘Hey, I just got my genotype back and I read your paper and it looks like I’m a rapid caffeine metaboliser.’”
About our experts
Prof Jennifer Temple is director of the Nutrition and Health Research Laboratory at the University of Buffalo. Here she studies how caffeine impacts humans – particularly adolescents. Her research has been published in journals including Physiology and Behavior, Nutrition Research, and Neuroscience and Biobehavioral Reviews.
Dr Marilyn Cornelis is Associate Professor of Preventive Medicine at Northwestern University, where she studies the link between caffeine and genes. Her work has been published in journals including Nature and Nutrients.
Prof Rob van Dam studies the role of diet in preventing disease at the Milken Institute School of Public Health. His work has been published in the Lancet, JAMA, BMJ, Annals of Intern Medicine, and Circulation.
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