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Having Caffeine Jitters? The CYP1A2 Gene Could be to Blame

morning coffee

To say coffee is popular is quite the understatement. Ninety percent of Americans drink some form of caffeinated beverage every morning.

And while, the coffee culture in the United States is ubiquitous no matter what hamlet you call home, people respond differently to caffeine based in part on genetics.

When we drink caffeine, enzymes in the body break the drug down and get it out of our system. But here’s the deal: not everyone is born with the same enzyme activity for metabolizing caffeine. Some of us get rid of it fast, others, who have less enzyme activity, much slower.

Variants in a gene called CYP1A2 determine how fast your liver metabolizes caffeine. 1 Your CYP1A2 status determines how fast your body will clear the caffeine you drink. Slow metabolizers are more likely to have caffeine induced anxiety, sleep problems, and even high blood pressure as a result of having that morning cup of coffee.

By contrast, some of us are fast metabolizers of caffeine. The speed with which we break down caffeine determines the half life of the drug in our system. The half life of a drug like caffeine is the amount of time the drug is active before it is fully metabolized by the body. For those who carry the CYP1A2 gene associated with slower caffeine clearance, caffeine has a much bigger impact than it might on someone who carries a different variant of the gene.

In the standard western diet, coffee, which is chock full of polyphenols, is actually one of the primary sources of antioxidants for many Americans. And drinking coffee in moderation can be very healthy if you have the right genes.

Caffeine genetics and heart health

Genetic studies looking at how caffeine consumption can impact heart health are mixed, with some showing no increased risk for slow caffeine metabolizers, and others flashing warning signs.

One of the latest studies to look at the issue of caffeine consumption and genetics, which was published in the American Journal of Clinical Nutrition, found no increased risk for CYP1A2 genotypes when consuming moderate amounts of coffee.

In fact, the authors found that drinking moderate amounts of coffee was probably good for your heart. But be warned, they do say that drinking more than 5-6 cups of coffee per day is probably a bad idea and might play a role in increasing your risk for heart disease by as much as 22 percent.

One thing I find funny about the study is setting the upper limit of 5-6 cups as “healthy.” That’s a ton of caffeine! Depending on strength of the coffee, 5 cups in a day is close to, or above, 1 gram of caffeine, which has been described in the medical literature as the threshold when very severe side effects can develop.

To quote this old paper published by the military:

Extreme side effects were observed in humans at caffeine intakes of 1 g (15 mg/kg) (Gilman et al., 1990), including restlessness, nervousness, and irritability, and progressing to delirium, emesis, neuromuscular tremors, and convulsions. Other symptoms included tachycardia and increased respiration.

This study from the American Journal of Clinical Nutrition represents a departure from some others which found that high caffeine consumption and CYP1A2 do not mix. These studies found an increased risk of myocardial infarction (heart attack) and high blood pressure in slow metabolizers of caffeine. 2 3

This study from the Journal Hypertension, which looked at 553 individuals over a period of 8.5 years. The study authors found that caffeine drinkers with slow CYP1A2 metabolism were much more likely to develop hypertension than fast metabolizers.

This study from the Journal Genes and Nutrition found that slow caffeine metabolizers were more likely to have heart attacks as a result of drinking caffeine. In slow metabolizers drinking 3-4 cups a day of coffee caused a significant increased risk of heart attack that wasn’t seen in rapid metabolizers. Notably, this study was conducted in subjects under the age of 50.

Want to find out your caffeine metabolism status? We report on caffeine metabolism in our custom nutrition plan product.

Coffee half life and sleep duration

Think of this: we know caffeine has a half life, usually of about 5-6 hours, but this number varies a great deal based on genetics.

Let’s say I have a patient who I know is a slow metabolizer. It’s likely their morning cup of coffee has a half life of 7-9 hours. So, if they have 2 cups in the morning, then a decaf or two later in the day, how will that impact their sleep? When they want to get sleep later that night, the caffeine is still very active in their system.


Because it’s not just the half life, caffeine has a quarter life, meaning it’s still has its hooks in my patient long after that morning sip. According to sleep scientist Matthew Walker, author of Why We Sleep, caffeine’s quarter life is about double its half life. This means that slow metabolizers like my patient may still be feeling the effects of their morning coffee well into the night. No wonder caffeine has been shown to be so disruptive of sleep. 4 After all, it binds to and blocks our adenosine receptors, the signaling pathways the body uses to fall asleep each night.

Granted, one morning coffee may not be packing enough of a punch to keep most (some?) people awake all night, but that’s not what we are talking about, we are talking about disrupted sleep patterns. The biggest issue for many of us when it comes to caffeine consumption is sleep.

So, in a nutshell, caffeine can be a bad idea for slow metabolizers, not only because it has the potential to increase the risk for a cardiovascular event, but because it can badly disrupt sleep.

Caffeine genetics overview

While the CYP1A2 gene gets most of the attention, it is not the only genetic variant that factors in to personalizing coffee and caffeine consumption. As the chart below summarizes, other markers, such as ADA and ADORA2A play a role in how caffeine affects us.

Various genes in caffeine

The bottom line

The bottom line is that we know with 100% certainty that people metabolize caffeine at different rates based on genetics. If you are a slow metabolizer, it is likely best to keep a closer eye on how drinking coffee affects your blood pressure and sleep.

See also: Is Coffee Good or Bad for the Gut?

Dr. Aaron Gardner, BSc, MRes, PhD

Dr. Aaron Gardner, BSc, MRes, PhD is a life-scientist with a strong background in genetics and medical research, and the developing fields of personalized medicine and nutrition. Read his full bio here.

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