Caffeine Sensitivity

genes and caffeine sensitivity

Caffeine sensitivity is determined by the efficiency of the human body to process and metabolize caffeine.

This shouldn’t be confused with caffeine tolerance, which describes how the body responds to caffeine over time.

Sensitivity has more to do with a person’s unique genetic makeup as this determines to what degree a given amount of caffeine will affect a person.

Genetic Link to Caffeine Sensitivity

Caffeine is metabolized by the liver using the enzyme CYP1A2. The ability to produce this enzyme is regulated by the CYP1A2 gene. Slight changes in the DNA sequence of this gene determine how efficiently a person can metabolize caffeine and thus eliminate it from the body.¹

Some people genetically produce very little of this enzyme while others produce a large amount. The majority of humans are somewhere in the middle.

The AHR gene also plays a role in caffeine sensitivity in that it regulates the turning on and off of the CYP1A2 gene. 10% of the population are rapid caffeine metabolizers and thus not very caffeine sensitive. ²

The third genetic link to caffeine sensitivity involves the type of adenosine receptors a person has in his/her brain. Those lacking the correct adenosine receptors in their brain are unresponsive to the awakening effects of caffeine because the caffeine molecule cannot properly bind to the receptors. ³

Determine your caffeine sensitivity by taking a DNA test (such as the 23andMe Health + Ancestry test).

6 More Genetic Links

The most recent research from The Harvard School of Public Health found 6 new genetic variants associated with the way people metabolize and form addiction to caffeine.4

The 120,000 person study revealed:

  • 2 genes related to how caffeine is metabolized.
  • 2 genes associated with how we feel rewarded from caffeine.
  • 2 genes that regulate fat and sugar in the bloodstream as a response to caffeine.

More research in Italy and the Netherlands has shown the gene PDSS2 may also be responsible for speed of metabolism. People with a specific variation drink less coffee than others. It is thought that the PDSS2 dictates sensitivity at lower levels of consumption, while CYP1A2 determines consumption at higher caffeine levels.

Three Levels of Caffeine Sensitivity

Based on the genetic data we have to date, we can identify people with 3 distinct levels of caffeine sensitivity, which in turn determines to what degree the effects of caffeine will be realized.

1. Hypersensitive to Caffeine

These people react to very small amounts of caffeine. Even at amounts less than 100 mg, people who are hypersensitive to caffeine can experience overdose symptoms such as insomnia, jitters, and an increased heartbeat.

For these people, it can take as much as twice as long for caffeine to metabolized. 

2. Normal Sensitivity to Caffeine

People who show normal sensitivity to caffeine can usually have 200-400 mg of caffeine daily without any adverse reactions. These people have no trouble sleeping as long as the caffeine is consumed early enough in the day.

The majority of humans fall under this category and this group is what the recommended daily safe dose of caffeine has been established for. 

3. Hyposensitive to Caffeine

About 10% of the human population are hyposensitive to caffeine. They process caffeine so efficiently that these people report taking large doses ( >500 mg) without much effect at all. Those hyposensitive can also consume caffeine shortly before bedtime and still get a good night’s sleep.

These people are more prone to consuming large doses of caffeine in order to get the desired effects. 

Determining Your Level

3 levels of sensitivity
In order to safely use caffeine, it’s important to understand your level of caffeine sensitivity.

Based on the three descriptions above, you should be able to identify your level of caffeine sensitivity and then follow our recommendations below.

  1. For those hypersensitive to caffeine, we recommend that they cautiously consume caffeine and avoid highly caffeinated beverages like coffee and energy drinks. Black tea or green tea is probably a wise choice for this group.  Quitting caffeine altogether may be an even better option.
  2. Those with normal sensitivity should be aware of how much caffeine they are consuming and keep this within the daily safe dose guidelines of between 300-400 mg. This equates to 2-3 cups of brewed coffee (not Starbucks), two 16 fl.oz. energy drinks, 7-8 cups of black tea.
  3. Hyposensitive people should evaluate the necessity of caffeine. If large amounts of caffeine do not create the desired effects such as wakefulness, alertness, and productivity, then we would question the benefits of consuming it. Since caffeine is toxic, large doses daily could be doing damage over time, which isn’t yet fully understood.

Caffeine Sensitivity Isn’t Exactly Black and White

While the above guidelines and caffeine sensitivity levels may apply to many, there are some that could fall somewhere in the middle.

Some people could be normal but lean toward the hypersensitive category or learn toward the hyposensitive category. Human genetics are complex and people are unique with many subtle genetic variations.

Also, some people can develop caffeine hypersensitivity over time instead of from having it from birth.

If you don’t align perfectly in one of the sensitivity categories above, it’s okay!

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  • Ted

    That’s not good, sorry to hear. Have you read our article on caffeine allergy? You may find it interesting.

  • Megan Ahearn

    Hypo-Sensitive here, my whole life I’ve never experience any increased energy levels or alertness from caffeine. I love tea and love coffee but again, never any real effects. I usually drink tea just for the calming effects of a warm drink, and a cup of coffee a day only because it helps keep my digestion regular. I could drink a whole pot or case of energy drinks and go straight to sleep, thanks for the interesting read!

  • raja777m

    Drinking Coca-Cola(starting from a 20Oz bottle), Frappe Mocha(any size, starbucks) makes my Bowels move within few mins. Usually I don’t drink coffee or tea at all.

    Maybe I need to use this negative effect as bed coffee for better results.

  • Dan

    Hi Nomad, I know this discussion is a little old but I wanted to add that I think I have had and am having a similar experience with caffeine. The first time I knew for sure it was caffeine was when I drank a teapots worth(4 cups) of strong tea, causing the worst heart palpitations and anxiety I’ve ever experienced.
    Over the last several days I haven’t haven’t been eating as healthy as usual, including large sodas and amounts of black tea more in larger quantities that usual. This cumulated yesterday and today with nausea, dehydration, insomnia, heart burn, queasiness, heart palpitations, anxiety attack and a second day of diarrhea. I found this site looking for confirmation and basically wanted to do like you and provide an additional testimonial.

  • Wow! This explains a lot — all those times people have told me that their son or daughter had one sip of caffeine and was bouncing off the walls, or those people who boast about how many energy drinks they can consume without feeling anything. This is definitely news I can use! This might have to go in the next edition of “Are You a Monster or a Rock Star: A Guide to Energy Drinks — How They Work, Why They Work, How to Use Them Safely”.

  • Becci Murtagh

    I can’t even handle white tea! I had a green tea just now in a cafe with a friend and I am rocking!!!! Hence why I’ve just googled to see what’s going on. I nearly broke down in tesco, I can’t handle!

  • Flo Toheaven

    If I have one cup of caffeinated black tea/green tea, my heart races and I get extremely anxious

  • Bharat

    When i was doing my PhD, i used to take over 10 espressos per day and still fall asleep at my regular time. No amount of caffeine had ever kept me up in the night. Never jitters or something like that. THe reason I was taking coffee was to unwind by a small walk to the pantry before starting to think in a different direction…! now, I understand why…

  • Darien Genova

    I’m 21, and when I was in high school I drank 2 monsters every day. They never affected me at all, I just liked the taste. When I was 19 I noticed that coffee made me sick, my heart rate would drop and I would get really shaky. Now I can’t drink coffee unless it’s decaf and I can’t drink energy drinks at all. I can drink pop and teas though with no problem. Though, I tend to shy away from carbonated drinks now because I also had a kidney stone at 19. Working at Taco Bell and drinking mountain dew 24/7 took it’s toll. My thing is, I suffer from migraines and caffeine helps them go away. But when ever I take an Excedrin migraine or drink some coffee or even an energy drink I have all those same symptoms again. Shaky to the point where it looks like I have Parkinson’s, my heart rate slows a lot, I get hot and cold flashes, I feel like throwing up, and mostly do, and I just want to sleep. So I have no idea what to do to help my migraines without all that happening. And I also don’t know where I fit with these categories. My dad can’t drink coffee or energy drinks either, but he just gets too jittery. My mom gets an extra shot of espresso in her coffee every day.
    Any suggestions?


    Maybe you have adrenal fatigue? just a suggestion .. you might want to Google this to check it out, but I bet all that caffeine from the Monsters and Mtn. Dew burned out your adrenals, big time …

  • Darien Genova

    I don’t think that’s it.

  • Ted

    It sounds like you are hypersensitive but also you may have developed an allergy-like response to caffeine. See here:

  • John Polak

    I’m very intolerant to Caffeine, when I was young, I used to like Iced Cappuccino, and used to drink tea a lot without any effects when I was young, when I was 19, i drank like 250ml of coffee that is high in Caffeine, then I was ok until, few days later, that I developed Stomach issues, and it damaged one of my nostrils that I can smell that wasn’t there. I had a panic attack, even anxiety attack that leads me to develop Hyperventilation and it leads me to drink in a lower caffeine doses, But it turns out I was still intolerant to them, but no stomach aches, but just weakness, and anxiety attacks, in which I ended up drinking 500ml of water to flush them out from my system and I’m now taking .5mg of Klonopin to relieve anxiety attacks 3 times a day. I am also Lactose Intolerant on White Milk, but not other milk products like cheese, yogurt, etc. my mother never had any intolerance to caffeine, but me, I am very intolerant to caffeine. It must been my hormones that had changed or something.

  • Sarah Smith

    Very interesting! I’m hypersensitive; even a can of soda will produce those effects. I just started drinking coffee this year since I started college; I like specialty coffees, but the amount of sugar added to them doesn’t help matters. I’m wondering if this might be due in part to the fact that, as a kid, I had my right adrenal gland removed because of cancer. Could a reduced amount of adrenaline in my body have anything to do with this?

  • Emily

    I don’t think so. I have an autoimmune disease that destroyed both of my adrenal glands, and now I have to take cortisol and aldosterone replacement steroids for the rest of my life (no doctor has ever mentioned adrenaline). I’m hyposensitive to caffeine and always have been, even though I don’t drink it very often. However, we have different conditions, so I can’t say for sure. Best of luck in college!

  • Lucifer

    Same thing has happened to me my heart feels funny when I drink caffeine, i get elated and then deflated very quickly… It’s like I get a 5 min boost and then tired as F… lol but hey guess I’m getting old

  • Josie Rylands

    My sensitivity to caffeine seems to have varied wildly just in the past year. I used to be able to drink coffee whenever I liked, and I still rarely feel the effects during the daytime. I would get a coffee largely for an excuse to leave the lab & have a change of scenery, which improved my alertness and concentration by themselves, but I seldom felt that the caffeine was affecting me. Since July, however, drinking coffee and sometimes tea past 4pm or so keeps me awake. I don’t notice the effect until I’m in bed and I can feel my pulse racing and my eyelids failing to become heavy. It’s a shame because I enjoy having a cup of something after lunch. Speaking of which, I’d better go and get the kettle on before my caffeine deadline passes!

  • Cayte Scarlett

    I seem to be in the middle range; but tend toward hypersensitivity. If I have more than two cups in a sitting, I can get the jitters and/or restless leg syndrome. This is especially true if I have coffee later in the day, or at night. RLS is extremely annoying and uncomfortable! It’s especially frustrating when it happens at bed time.

  • Bill Nye

    ayy lmao

  • Bill Nye

    Caffeine makes me sleepy and or drowsy in most cases.

Last Modified: May 30, 2017