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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  • Never Wired

    I too must be Hypo-Sensitive. I started drinking coffee in high school to complete papers that were due the next day (I’m such a procrastinator!) As time went on, I acquired a taste for coffee, but didn’t notice any effects, so I started drinking more and more. After a while, I grew tired of filling an entire Double Big Gulp + coffee mug up with an entire 12 pot of brewed coffee. I switched to espresso. I figured this would allow me to get more caffeine with less fluid, less trips to the bathroom and Maybe would actually give me energy. Alas! No, that didn’t work either! I only found myself making daily latte runs getting 6 shots at a time, sometimes 8, Sometimes 2x a day and STILL NOTHING!!! I even drank 4 and 6 shots a couple of hours before bed and had no trouble sleeping. Finally, I decided to just quit cold turkey. I was mildly disappointed. No headaches, no grouchiness, no withdrawal symptoms that I’d heard other people mention. What I DID notice though was this. After about 7 days of no caffeine, I WAS BUZZED. I Couldn’t sleep more than about 6 hours, I had more energy than I knew what to do with and I had a hard time focusing on one task at a time. I stayed caffeine free for about 6 months and then decided that I actually functioned better, stayed focused better with caffeine, than without.
    I have used your “caffeine calculator” for Wired X344 and my weight. Though it says the safe limit is 1.6 cans, this is based on those who fall within the “normal sensitivity” limit. I can tell you that one can has NO noticeable effect on me. 2 cans however, clears my mind and gives me an increase in stamina and energy. I do use my hands all day and have not noticed any shakiness or tachycardia.

  • Lucy

    I became same like you. I like coffee or other soft drinks. but cant drink. Have u found any ways to treat?.

  • Justina Siracusa

    Has ANYONE ever tried carob powder?? Its said to contains no caffeine or theobromine. I have become soo extremely sensitive to all stimulants. I can’t have coco either. I have such a afoul reaction to caffeine, its scary.

  • Justina Siracusa

    Have you ever tried carob? its a coco substitute. Said to contains no caffeine or theobromine. Not sure — but that is what the internet said. I got some, yet have not had it yet. I can not have any stimulants. All of a sudden a few years back, I had this problem happen. Its so bad. There is a stimulant called theobromine in coco.

  • Justina Siracusa

    I tried swiss water coffee that is 99.9 percent caffeine free and I still felt problems..

  • Justina Siracusa

    Has anyone ever tried Swiss water coffee? I still had a problem with it.
    I did not get it grown in a way that it could have been contaminated… YET I still had a reaction to it. Its said to be 99.9 percent caffeine free!!

    I felt ok at first. Then I went to the store. I had some unpleasant racing feelings. I only had a half a cup, and it was not a strong dose. I miss having coffee but My body has changed and I can not have any stimulants. Not even coco. I cant handle the theobromine.

  • Justina Siracusa

    Best way Is to avoid all stimulants like the plague. Coco has theobromine also. Get caffeine free soda. Coke makes it and its not diet. Swiss water coffee is 99.9% caffeine free. (yet I still felt it) Don’t get it grown in the store because it will get some regular coffee grinds mixed in with the process.

  • ScandinavianJake

    I never tried carob powder or Swiss water coffee, but I have the same problem as you.

    It is possible to get some pretty good replacement coffee (Like something which is made of vegetables, usually barley, and gives a similar taste; you can find this in any vegetarian store)
    But the taste and kick is never quite the same.

  • Justina Siracusa

    Were you always this way with caffeine or anything else? It happened to me 3 years ago. I ended up in the ER once because of it. I do think I caused it to myself. I was over-drinking energy drinks and all types of stimulants, all the time.. I just cant metabolize a drop any more. I get panic attacks that are psychical, I can in no way talk myself out of the effects. I have had severe carpal spasms. I now Stay far far far away form the nonsense. I do miss coffee and chocolate. I will try the carob stuff soon. Swiss coffee was my last hope. And even that did not work.

  • ScandinavianJake

    I had a little bit the same as you.
    I used to have no problem at all drinking coffee or tea. Then around 3 years ago also I became more and more sensitive to the effects of it.

    These days I can’t drink one cup of coffee either.
    I try decaffeinated coffee and tea, but even that is starting to have an effect on me.

    Thought I think my effect is a little bit different than yours. For me it seems to be more a problem digesting the caffeine than panic attacks.

    Right now I’m trying something new called peppermint oil, which apparently has worked for a lot of people.

  • ScandinavianJake

    I heard about something called peppermint oil, apparently it works for some people, thought not guaranteed.

  • Justina Siracusa

    Well I just tried the carob chips. I read that there are zero stimulants in them. But I also read that the it could have things added to it, so depending on the company I guess. I had about 5 chips lol .( I had gotten the chips in a bag/like for baking). The tiny amount did not upset me, yet I kind of fell posibally something. I need to experiment more.
    Also. Stay far away from Guarana- Its in drinks a lot of the time and it has caffeine!! If you try Acai itself does not contain caffeine. However, many acai supplements contain added caffeine or Guarana

  • Justina Siracusa

    And this is my results from my dna.

    gs159CYP1A2 fast metabolizer Your CYP1A2 fast metabolizer status means that you are less stimulated by caffeine.

    I do not get it.

  • Justina Siracusa

    I take a few sips of caffeine and I am having a psychical reaction. Even chocolate. I tried to go back to it in tiny amounts a few times, and had bad scary reactions. I was not always like this. Now I avoid stimulants and I am ok. What the heck happened..?

  • Justina Siracusa

    It can contain very small amounts of theobromine because of how its processed. Just google the words _ Carob and stimulants to get some other findings. YET STILL HAS NO CAFFEINE.

  • EffinBiatch

    You have burned out your adrenals especially those of us that drank coffee without food (sweet foods are even worse than no food)
    It can take years to replenish but you will likely drink coffee again

  • mia

    Is it possible to have developed a caffeine intolerance over time? As someone who used to consume about 8-10 oz of caffeinated coffee every day with no problems, I am now so hypersensitive that just 25 mg sends me off the wall with crippling anxiety, shakiness, nausea, and other symptoms. Does anyone know why this may be? I do separately suffer from an anxiety disorder, so I suspect this may have something to do with it.

  • Ted

    Yes, genes can turn on or switch off as we age.

  • Brandos12

    Excuse my avatar, I added that years ago when I was younger haha. I am now 21 and I used to be able to drink coffee everyday without any bad side affects. Last summer I sometimes drank quad shot espressos with no big issue, and my body was so used to caffeine that sometimes I would hardly notice any positive effects either. The past year I have been under a lot of stress in college and that really affected my stomach. Throughout the year, there have been times where I couldn’t eat food or coffee without feeling nausous, and there were other times where I felt fine and I could drink coffee again just fine. Early this summer I started drinking coffee again and I enjoyed the positive effects of being more alert and productive in the morning. However, now I can’t drink coffee without feeling nauseous. Even if I drink just one cup along with plenty of food and water. I was also feeling nauseous after eating again. I haven’t been that stressed out this summer either. I got tested for H. Pilori and that came back negative. I’m not sure what it is, but I’m starting to feel a little better after eating (not feeling as nausous). I just had a cup of coffee because I needed the energy to finish something at work, and I supplemented it with lots of ginger tea and bread to absorb the acid. Right now It’s been about 4 hours after drinking coffee and I feel okay, if not a little nauseous/dizzy. We’ll see how I’ll feel later, but I think I’ll avoid caffeine for the next 6 weeks and hope I can drink coffee again when school starts!

  • Karen

    I had one cup of BLACK iced tea yesterday afternoon and did not sleep the whole night (as I am writing this at 4:30am), am nauseous and have been to the bathroom 3 times since I’ve gotten home from work.

    My family makes fun of me as they are all heavy coffee drinkers. I’ve always claimed to be completely caffeine intolerant. I guess it’s true.

    I feel so sick.

Last Modified: May 30, 2017

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