The Caffeine Gene: Are You a CYP1A2 Ultrarapid Metabolizer?

Is caffeine bad for you? The answer depends on whether you're a CYP1A2 ultrarapid metabolizer or a slow metabolizer.

Maybe you're one of those people who can have an after-dinner cappuccino and still fall asleep at bedtime. Or maybe you're the opposite. Any caffeine after noon keeps you wide awake.

The difference lies in your genes. The CYP1A2 gene determines how your body metabolizes the caffeine found your favorite beverages—like tea, coffee, and soda—and how it makes you feel.

What is caffeine—and how does it affect the body?

Caffeine is a bitter substance that’s found naturally in more than 60 different plants, including coffee beans, tea leaves, and kola nuts. Kola nuts are used to make soda.

Caffeine acts as a natural stimulant, and for this reason, the FDA lists it as both a food and a drug.

Caffeine targets the central nervous system and makes you feel more awake, energized, and alert. It’s often described as a cognitive and physical performance enhancer. 

But everyone seems to react differently to caffeine. Some people get jittery and anxious from a few sips of coffee, while others can drink cup after cup without blinking an eye.

Recently, researchers discovered these variations in caffeine tolerance can be traced back to genetic differences, which brings us to the CYP1A2 gene.

What is CYP1A2, aka the caffeine gene?

The caffeine you ingest passes through the stomach and small intestine, entering the bloodstream in a little as 15 minutes. Your caffeine levels peak about 30 to 60 minutes after consumption and then start to decrease gradually.

The speed of this decline depends on your CYP1A2 gene, which controls an enzyme (also called CYP1A2) that is in charge of breaking down caffeine.

You have two copies of the CYP1A2 gene—one inherited from each of your biological parents. And each copy can be either a “fast” or “slow” version of the gene.

If you have two fast versions, you’re considered a fast caffeine metabolizer. “These are the people that can have an espresso and go right to sleep," says Tiffany Lester, MD, formerly with Parsley Health San Francisco.

In contrast, if you have one or two versions of the slow version of CYP1A2, you’re labeled a slow caffeine metabolizer. This means you clear caffeine from your system about four times slower than your quick-metabolizing counterparts, says Dr. Lester.

Other genes related to caffeine sensitivity

While CYP1A2 is the primary gene involved in caffeine metabolism, research suggests that other genes may also play a role.

ADORA2A is associated with caffeine sensitivity and its effects on anxiety and sleep disturbance. So even if you are a fast metabolizer, looking at ADORA2A can also help identify a problem with caffeine metabolism.

How to test for the CYP1A2 gene

Based on your reaction to caffeinated beverages, you probably already have a hunch as to whether you’re a fast or slow caffeine metabolizer.

But how do you know for sure? You can test for the caffeine gene through a simple saliva or blood test that analyzes your DNA.

“I don’t typically test for CYP1A2 in isolation,” explained Dr. Lester. In other words, this gene doesn’t influence health in a significant enough way that she would go out of her way to order the test for every patient.

“It usually comes up if a patient has done a 23andMe or other direct-to-consumer genetic test,” she continued.

If you’re a slow metabolizer, should you avoid caffeine?

The CYP1A2 gene made headlines in the mid-2000s when a study, published in the Journal of the American Medical Association, showed that slow metabolizers who drink more than four cups of coffee per day have an increased risk for nonfatal heart attack.

If you’re a slow caffeine metabolizer, should you be cutting out caffeine from your routine entirely? “No way!” said Dr. Lester. In fact, Dr. Lester is a slow caffeine metabolizer herself and still enjoys her daily dose.

That said, knowing that she has this genetic variant has helped her consume caffeine more strategically. “For someone like me who does have that genetic variant, I do not have caffeine after 8 a.m. Otherwise it will be difficult for me to fall asleep at night,” she said.

You can evaluate your relationship with caffeine and figure out what’s best for your lifestyle and genetics. Parsley Health’s doctors and providers are experts in helping members determine what works best for them—and how to still enjoy caffeine if they choose.

Are there other reasons to reduce your caffeine intake?

If you’re dependent on caffeine to function and get through the day—and you’re still tired even after getting plenty of sleep—you might have underlying condition.

“In that case, cutting out caffeine entirely for a period may be the best option to discuss with your doctor,” she explained. Plus, you'll want to get to the root cause of your fatigue.

Even if you’re a fast caffeine metabolizer, you can still experience side effects of too much caffeine, including the following.

Migraine

Insomnia

Restlessness

Frequent urination or inability to control urination

Stomach upset

Nervousness

Irritability

Fast heartbeat

Muscle tremors

Research suggests that, for healthy adults, a healthy caffeine intake can include up to 400 milligrams (mg) a day. If you’re consuming more than that, you may wish to cut your caffeine intake, especially if you’re a slow caffeine metabolizer or are experiencing unpleasant side effects.

You may also be a fast caffeine metabolizer and still have negative reactions to moderate or even low amounts of caffeine. This could indicate an underlying health concern, such as estrogen dominance.

Estrogen and caffeine are both broken down in the liver by the CYP1A2 enzyme. “Women that have estrogen dominance often do not have an abundance of this enzyme and therefore should not consume caffeine as they will also have a hard time detoxing it,” explained Dr. Lester.

The good news is that once you balance your hormones with the help of a doctor, you’ll likely be able to tolerate caffeine again.

Additionally some people should not drink caffeine or should limit their intake because of underlying conditions or because of medication interactions. Check with your doctor if you're unsure.

How to reduce caffeine intake and avoid caffeine withdrawal symptoms

If you’ve decided to pull back on your caffeine intake for any reason, the first step is to figure out how much caffeine you’re actually consuming.

Not every beverage contains the same amount of caffeine. Here are a few examples.

8 ounces of coffee: 95 to 200 milligrams

8 ounces of green tea: 14 to 60 milligrams

12 ounces of cola: 35 to 45 milligrams

8 ounces of an energy drink: 60 to 250 milligrams

“Each of these beverages has different amounts of caffeine with tea being the lowest. So, for example, someone with anxiety may not be able to tolerate an espresso but can happily drink a matcha latte,” Dr. Lester says.

Caffeine can also be hiding in places you might not expect. Kombucha and chocolate are two hidden sources of caffeine that you might not be taking into account.

When you’re cutting back on caffeine, Dr. Lester recommends going slowly, or you might experience caffeine withdrawal symptoms like headaches, irritability, and fatigue.

“A general rule is to go by halves. Cut down gradually by halving your intake every three days until you’re completely off any caffeine source,” she said.

What are the best healthy caffeine alternatives?

Cutting back on caffeine isn’t always easy. Caffeine is the most common “drug” in the world. About 1.6 billion cups of coffee are consumed per day globally. Caffeine is deeply ingrained in our culture and our daily routine. But turning to caffeine-free drinks can help you ease the transition.

1. Decaffeinated coffee, tea, and soda

The most obvious choice is the caffeine-free version of your favorite coffee- or tea-based beverage. But proceed with some caution. Many companies use harsh chemicals to remove caffeine. Opt for organic options or buy from companies that are transparent about their processes.

2. Caffeine-free herbal tea

Naturally caffeine-free options include herbal teas like chamomile, peppermint, rooibos, and hibiscus. You can also find herbal chai—made from rooibos or herbal tea instead of black tea—that tastes like your favorite chai without the stimulating effects.

3. Golden milk

An ancient Ayurvedic tradition, golden milk is a creamy, lightly sweet beverage that contains turmeric powder and steamed milk—and oftentimes honey, cinnamon, vanilla, and other spices. You can find golden milk or turmeric lattes in many coffee shops and cafes. It is naturally caffeine-free.

4. Mushroom drinks

Mushroom drinks, including mushroom coffee, have gained popularity as a functional beverage with potential health benefits. These include the following.

Mushroom coffee is a blend of coffee and functional mushroom extracts.

Mushroom teas are herbal teas infused with mushroom extracts.

Mushroom lattes are non-coffee beverages made with mushroom powders and milk alternatives.

Mushroom hot cocoa is cocoa mixed with mushroom extracts.

Takeaway

In the end, there’s no cut-and-dried equation for how much caffeine you should consume. Even if you’re a slow caffeine metabolizer, you can enjoy your morning coffee as long as you’re wise about your consumption.

Simply be mindful and know how much caffeine is too much for your health and sleep quality.