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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  • Matthew Bryant

    I wonder if there’s any correlation between ADHD and Caffeine tolerance? Many people I know with ADHD will chug a 160 mg energy drink (Or in my case 16 oz of brewed black coffee) and suddenly their all their motion just ceases, meaning their functioning pretty normally, enhanced even in comparison. Most of these people, myself included are not regular caffeine drinkers either.

  • Manda

    That’s very interesting as I am the opposite. When I drink too much caffeine from pop or coffee, I get massive panic attacks (have since I was in 4th grade!) I discovered about two years ago that I can quite comfortably drink black tea, even have multiple cups without much issue. After three I start to get a little bouncy, but nowhere near the extent that two cans of mt dew causes. It’s amazing how each body reacts completely different from one to the next.

  • Andrew D

    Coffee chelates magnesium out of our already deficient bodies. When someone goes to the ER for a heart attack one of the first things the doctors do is to put the patient on an IV of magnesium. The best source of magnesium at home is to spray or rub magnesium chloride onto your skin. I also recommend adding sodium bicarbonate (baking soda) to your drinking water- it raises the alkalinity in our bodies and coffee is very acidic.

  • Nomad

    That is NOT the case. If you can’t metabolize caffeine and continue drinking it everyday it builds up until you get sick. If I have even one cup of coffee every morning I will not sleep until 4 or 5 the next morning and soon will barely sleep at all. I won’t go into all the the effects, there are too many. I become totally wired like I’m on drugs. Iv’e been hospitalized because I drank 1 16 oz. soda a day for a couple weeks. The doctor said I don’t metabolize caffeine and not to drink it. Before I knew this, I took 2 of those caffeine pills and was extremely ill for 3 days. It sucks. If I occasionally have some it’s not so bad, but absolutely CANNOT drink everyday.

    My husband is the complete opposite. He can drink a cup of coffee and take a nap 20 minutes later. We often joke that it would be great if he could borrow some of my sensitivity.

  • Max

    This is not to be sensitive to caffeine! Sensitive I mean big effects for small dose. Is the opposite of tolerence. You’re not sensitive, you can’t use caffeine, it’s different.

  • KW

    You’re an idiot. First of all, everyone can metabolize caffeine to an extent. Building a tolerance is a good idea for those who are hypersensitive but they want to consume caffeine anyway. Second, caffeine can’t “build up”. I don’t know where you got this information, but it is completely and utterly wrong. Your drinking of soda everyday combined with your hypersensitivity probably lead to a mild form of stimulant psychosis. Third, your statement “I become totally wired like I’m on drugs” because you are on drugs! Caffeine is a drug, I don’t know who told you it wasn’t or why you assume it wouldn’t be. Last, you butchered your doctor’s words because everybody can metabolize caffeine. The enzyme that “metabolizes” caffeine is produced by everyone. The amount may differ, so you may be hypersensitive, but you aren’t unable to metabolize caffeine.

    Before you go spilling your ignorance all over the internet and potentially misleading readers, do some research instead of proclaiming “This is NOT the case” because you don’t know what the hell the case is.


  • Nomad

    And you are a smart alec know-it-all. It CAN build up if your body isn’t processing it out. Within 3 days of having 1 cup of coffee a day my symptoms become worse and worse. It appears to take that long for my body to purge it completely. I have tried to build up a tolerance and just end up sick. I wasn’t in the hospital for psychosis, it was because my kidneys were shutting down. I can only repeat what the doctor said. He said not to drink caffeine and definitely not every day. Maybe I metabolize it very slowly, maybe I am a rare case, but if I end up in the hospital does it matter? If someone else is like me and I warned them it was worth it. Btw, I know its a drug. I was being sarcastic. Something your IQ is apparently unable to handle.

    You are just another pathetic p.o.s. that tries to bully other people on the internet because you are so sad in real life…that think they know everything about everything cause their mommy told them so special and perfect. Grow up.

    And no, I’m not going to start an internet war with you so you can feel like your junk is a little big bigger. This is my final answer? So rave away you nut job…show everyone what you truly are.

  • Nomad

    The article was clearly sing the term sensitivity as how much of the enzyme your body makes to break caffeine down. That is what I was referring to. Maybe you didnt read the article. Thats ok, I was just assuming that because you commented you had. Im sorry if my reply bothered you. I just dont want anyone else to get sick like I have.If you drink a bunch of caffeine it isnt going to cause your body to suddenly make more enzyme.

  • Ted

    While we encourage discussion, we don’t allow name calling and personal attacks. Your comments have been edited to remove these. Please comment respectfully.

  • susie

    Ted I have a question for you I have been drinking this amino energy orange drink for about 4 months now well just recently I got hives tongue swelling tight on the chest I had no clue it was the drink still don’t know been to the er 5 times this month n no one seems to know my question is how long does this stay in your body

  • susie

    Thank you

  • Ted

    Caffeine can stay in your system more than 24 hours depending on the amount you consumed. Also I’m not sure what else is in the drink, so those ingredients could be the culprit as well. I would quit it and see how your body responds. This does sound similar to symptoms described here.

  • Stephen

    Is it possible to find an enzyme supplement in order to be able to metabolise caffeine? I am not able to metabolise caffeine myself but I love the taste of black tea too much and don’t want to miss out on it. I want to enjoy it without suffering the consequences. I tried decaf teas but they are never fully decaffeinated and I am still sensitive to the very small levels. Other “teas” like roiboos or herbal teas are not teas and they don’t do the same for me like black tea does. I even like the idea of enjoying the odd coffee if an enzyme supplement works for me because I also love the smell and aroma of coffee. If CYP1A2 is the enzyme our bodies use to metabolise caffeine, then is this ever sold anywhere as a supplement?

  • Ted
  • SM


  • Rich

    Have you factored in sugar content as well?

  • Larry Harrison

    i dont know , it was after a concussion that i cant have even one cup of coffee. it makes me shake so bad i cant walk.before this i drank a pot a day along with energy drinks with no ill effects

  • Hyper-sensitive to caffeine here. It almost always makes me jittery. I don’t like the sensation, so I rarely consume caffeine. It’s usually as a rare thing, and often in the form of dark (85% or greater) chocolate, or decaf coffee (for the health benefits of coffee without addiction/withdraw nonsense).

  • lucas

    Just recently I discovered a much greater sensitivity to caffeine. I break out on my arms, and the level of anxiety is such that I find it very difficult to drive. Crazy!

  • lucas

    I’ve experienced the panic attacks, too. Driving was a nightmare, especially driving a stick shift! Much better now with no caffeine…btw, I LOVED coffee!

Last Modified: May 30, 2017