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!

Get Help Quitting Caffeine

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  • G Kay

    I used to drink A LOT of coffee a day – about 4 to 5 cups. All of a sudden it started to bother me. I’d feel nauseous and shaky and overly chatty. I stopped drinking it immediately and the side effects I experienced were a feeling of fogginess and poor memory. It’s over a year later and I still feel foggy and forgetful. Could it be that the lack of caffeine is affecting me in this way, so long after? Could the large amounts of it that I was consuming changed my brain chemistry? It’s strange that these cognitive issues began as soon as I quit drinking caffeine.

  • Ted

    It could be. Some people who have consumed caffeine for years and years feel that it permanently alters the chemistry of their brain and they could be right. I don’t think there are any studies regarding this, but it certainly is plausible.

  • Marcus Yates

    I used to drink very large amountd of coffee. now, I can’t metabolise it. even one can of coke takes about 2 to 3 weeks for me to metabolise. during that time I am very mentally sick. can’t think, feel mental. if I had heaps of coffee I would have hallucinations everything. I have zero history of any mental illness and with zero coffee am completely normal. I am sooo sensitive to caffeine I can’t even have the smell around me, or I actually feel really foggy and terrible for hours after. I avoid coffee and it’s smell like the plague. it’s evil. I can’t believe more studies haven’t been done.

    one lady lost most of her life to caffeine allergy. she was put on anti psychotics until later in life a good doctor told her to stop drinking coffee. that’s all it was. but even if she didn’t have coffee for a week it was still in her system making her mental…how would you know.

  • Gary Shaw

    I ,apparently, fall in to the hyposensitive category. I would even say I’m on the far end of that spectrum. I used to drink around two pots of coffee a day with little to no effect. I finally became curious after a discussion today as to why. I thought it was just a developed tolerance, but after a little research it seems that hypothesis would be incorrect.

  • Anon

    Sadly, I’m on the very far side of the hypersensitive category. I can’t drink a low-dose instant coffee without heart palpitations, anxiety, trembling, facial flushing and irritability occurring within 30 minutes! :/ Even the smell can, psychosomatically, cause very similar symptoms.

  • Mary Crossland

    I’d love that too! I really like the buzz and mental clarity and focus that caffeine gives me. But hate that I can’t sleep that night. An enzyme would be awesome!

  • Mary Crossland

    I know other people that it makes sleepy too. Do you still drink it?

  • Mary Crossland

    Me too, hypersensitive. I mix instant and decaf instant in 1:3 proportions and can drink a cup a day made with one tsp. of that. That is about 12 mg. of caffeine. If I skip the coffee, I can have a little chocolate that day, but never either after noon, or I won’t be able to sleep.

  • Ted

    There is! Well it’s an herb that helps your body metabolize caffeine faster. See our page here.

  • Mary Crossland

    I checked that out. Very cool. Can’t see how many tablets in the package though, is it 30?

  • Mira Smint

    Same effect on me! High five! Though people find me weird that I don’t drink coffee at all..
    Do you also get a depressing feeling at the end of the day because of the irritability?

  • Ted

    yes, 30 capsules per bottle.

  • Lristi

    I had 200mg at 12:30 PM yesterday and I am up now, 9 am can’t sleep. I got 2 hrs of sleep last night. Maybe I’m hypersensitive.

  • KingDingleBarryObummer

    So if I am hypersensitive to caffeine could the diuretic effect be that much more pronounced and long lasting? For example if I drink one cup of coffee in the morning and drink the appropriate amount of water during that day, could my caffeine hypersensitivity be impairing my capability to get hydrated i.e. making me urinate out all my water instead of using it for biological functions.

  • Ted

    If you have the coffee do you use the bathroom more all day than you do when you don’t have coffee and drink the same amount of water?

  • KingDingleBarryObummer

    Thanks for responding.
    I’m not sure. I have been drinking half/caff coffee everyday for years. This morning was the first day I haven’t had a cup in years. I haven’t really been paying attention to urine volume but I will try to – I do tend to urinate frequently on the regular though. I had a cup of regular yesterday for a change and didn’t sleep all night so I decided I should quit. After reading your article I noticed I do get the shakes but just ignore it because I like the taste and mood lift from caffeine. If I ever drink even decaf in the evening I don’t sleep all night so I think I am one of the hypersensitive people.
    I read people with Chronic Fatigue Syndrome and other things have problems absorbing the water they drink because they urinate most of it out. I am not educated but I just had a little pet theory that maybe they are super slow caffeine metabolizers and even if they just have small amounts of caffeine per day it could keep them in constant “diuresis mode.” I don’t think it’s common knowledge that certain people can be affected for days from caffeine. I saw in your other article that low blood volume and heart palpitations can occur. Wouldn’t it raise blood volume since you would be getting less dehydrated? My hands are pretty cold today, so maybe I am experiencing that effect.

  • Nyx

    I took some natural energy over pills two weeks ago (bought them in the grocery store) and had a bad reaction (I essentially got high) and experienced extreme vertigo episodes for about a week. It tapered off but now I can’t seem to have any caffeine beyond a small coffee or tea in the morning without having a vertigo attack or feeling high again. If I have another coffee or tea mid afternoon it completely messes me up. I was totally fine before. Problem is I’m sure I have chronic fatigue and by mid afternoon I’m ready to fall asleep. My vitamin levels and everything are all normal.

  • JTT

    I am super hypersensitive to Caffeine. I heard blood types can be more or less sensitive. (I am O Neg). I DO drink decaf coffee every morning but that’s all I can do. I took 3 sips of a coke the other night before bed and i Couldn’t fall asleep until morning! If I drink caffeine I get very jittery under my skin and heart goes crazy. I HATE the feeling. I can’t do too much dark chocolate either due to the caffeine. I’ve always been this way.

  • Delwin Smith

    Hypersensitive over here 🙁 . .Its my drug. When I need it, I have a double Americano. Always helps me concentrate and with my performance, I like this feeling. Unfortunately, this always leads to really bad withdrawal symptoms the next day, the fatigue and head aches are the worst. It sucks because I love coffee, after realizing that I was actually addicted to caffeine, I decided to quite. WOW, that sucked! Head aches, body aches, fogginess, depression. This lasted for 1 week, this is when I switched over to decaf, because I cannot live without the taste of freshly ground coffee in this life. . . Is there no way someone’s caffeine sensitivity can be altered from say Hyper to Normal? I’d love that.

  • Meagan Haoui

    I feel like I swing between “normal” and hypersensitive. I used to drink a coffee or latte just about every day, and if I had them 10 days in two weeks, I might experience hypersensitivity (jittery and elevated heart rate) one or two days out of the ten. One of these days unfortunately fell on a day I was going to the doctor for a follow up on high blood pressure issues and my BP was crazy high. The doctor suggested I cut coffee out entirely, which I did. I switched to black tea and was fine for a few months, but now I’m having the same problem, an issue maybe 10-20% of the time. Not sure why my sensitivity would vary so much. No other changes, for the most part (similar diet and activity level). Back in high school and college I could drink coffee all day and night, with no real effects.

Last Modified: May 30, 2017