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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  • Amber Nerd

    I am really sensitive to caffeine and it is growing worse. I used to be able to handle a small cup of coffee once a week, but now I get jitters if I drink a 12oz cup of iced tea. About an hour ago, I ate some chocolate and it is keeping me awake. I am kind of neurotic and panic easily, so that may have something to do with it, but I want to be able to at least drink tea. Does anyone have any advice or suggestions?

  • Justina Siracusa

    Just stay away from all of it… I had no other choice. It can be done. For 3 years I have not touched any of it. And I had zero problems sine then !!! I Carry a pill in my car, in case I was exposed to something. So far it has not happened no mistakes. So over 3 years now I have been good. No chocolate, no caffeine or anything. Check all food and drink labels.

  • jehad

    I have some problem some time when I exposed to stress my stomach heart me and when I drink coffee I start to feel symptom of palpation and burning sensation in my stomach and nausea and vomiting and my abdomen start distended with gases , and if I don’t have stress I feel some symptoms but mild is this caffeine sensitivity

  • Mike

    Have you ever taken a fluoroquinolone (cipro, levaquin, avelox) within the last 5 years?

  • Sensitive to bacteria

    May be you need to clean the coffee pot. Bacteria growth you might be reacting to it.

  • Beth Ace Lord

    I can drink soda’s, tea etc, but when I drink coffee I seem to get bloated & heartburn etc. This wouldn’t be a caffeine sensitivity would it?? I mean I can drink some but not others. That doesn’t make sense to me

  • Ted

    No, it sounds like you are sensitive to the coffee itself, not the caffeine if other sources of caffeine don’t cause the same reaction.

  • Beth Ace Lord

    How would you think I could test to see what is causing this?

  • Beth Ace Lord

    Would it be the coffee bean & what are the side effects of coffee sensitivity? Also is there a way to fix it?

  • Ted

    I think you’ve already tested this, no? When you drink coffee you have stomach issues, when you drink something else you don’t. It’s like other food sensitivities, you should avoid the food in question. You could try a lighter roast and see if that helps but other than that there’s not much you can do.

  • Pete Dixon

    My coffee habit gave a mood disorder for over 25 years before I made the association. I had been diagnosed as Bipolar II and treated with Lithium and the usual antidepressants to no effect. Eventually I cut coffee cold turkey for unrelated health reasons and the mood disorder disappeared almost completely.

  • April Ramsey

    Oh man, that sounds like me. I use to drink so much of any and everything with almost not effect. However, when I stopped I there wasn’t the same buzzed affect that you had. Yet, now that I’ve started drinking more soda again I feel like it’s starting to have some affect on me for once, but if it has it’s been than it’s been pretty subtle.

  • Karlo

    Thank you for this. Suspect I might be similar. How long were you off coffee before you noticed an improvement in your mental state?

  • Nicholas Furr Koceja

    Its interesting in my case. I have never ever been fully awake as far
    as i know, in my entire life. maybe a few times, but the feeling is so
    rare, I’ve stopped trying to get a good night’s sleep. Of course, with my love of being a night-owl, and still having to get up early, I’ve rather recently started to have 5 hour energy if I need a pick-me up, usually if I’m driving and can’t seem to focus.

    However, in my case, it simply doesn’t work that way. 5 Hour Energy simply doesn’t work in the slightest (or didn’t used to) if your body is truly exhausted. It only works if my body still has that bit of energy, I.E only when waking up, or mid-day, never night. If its time to sleep, I could have a 5 hour energy and sleep 5 minutes later.

    The interesting part is I think my body has finally gotten slightly more sensitive to the stuff over time (a matter of 6 months-ish), so I can have less and less to get the full effect. I still specifically choose to not have caffeine unless I need it (with the exception of Surge, because i still love the taste), so I think I’m good on that front.

    I guess the moral of the story is Energy drinks don’t replenish any energy or focus you have, they simply make any energy you do have stronger. I to this day cannot understand people that have to have coffee every day, or even tea, and I’m a huge consumer of fresh sweet black tea. My body probably leans toward hyposensitive, which is A-OK with me! basically if I can function without it, then I go without it. Which, now, is maybe once a week, on average. Good stuff 🙂

  • Angela D Bradford

    I’m the same way! Coffee makes me have a bad reaction these days, but that’s just happened within the last year! I used to could drink as much as I could handle with no issue, then suddenly one day, bam, it started giving me the bad reaction! Every once in a while I’ll try to have some again and it will go fine and I’ll think oh it’s cool now, and I’ll go to have a cup the next day and there’s the trouble again! I wish I knew what the deal was, I can drink soda, like you, and be fine, so its gotta be the coffee. Could some medicine cause this? I recently started Methadone and it seems that’s when it all started..,…

  • jessica_uhl

    Yes, I do. I have Generalized Anxiety Disorder but I’m doing really well these days, not on any medication and very even keel. However, if I even drink a green tea, 9 times out of 10 later in the evening I’ll start crying or worrying about something that I think is ridiculous the next day 🙁

  • Stephanie

    Are there any alternatives to caffeine that work on people that are caffeine insensitive?

    I have never had any effect from caffeine. I don’t drink coffee, because I don’t like the taste. But I drink energy drinks or soda every once in a while and they never have the slightest effect on me. I also had coffee a couple of times to try if it would help me stay up when I am tired, but it didn’t. I once drank energy drinks within 5 hours that totaled up to 1000mg of caffeine and went right to bed after that and slept like a baby. The problem with that is that nothing helps me to stay awake when I need an energy push. Are there any alternatives?

  • Ted

    There are other stimulants on the market and some energy drinks and workout supplements contain them in addition to caffeine. Check out the drink called Red Line, Rhinorush energy shot, or the drink Spike Shooter.

  • Ali

    I am super sensitive to caffeine. I had some over seven hours ago and it still feels like the original burst. I get the jitters and my head feels like its spinning in circles. I become quite outgoing. This is a phenomena that only seems to occur with caffeine. Typing is actually extremely difficult at the moment. I know I probably shouldn’t drink it, so I only do every so often.

  • anon

    Thanks for this… Had half an iced coffee with about 1 expresso shot in it at 10am, felt like I was dying all day with diarrhea and anxiety, couldn’t sleep till about 5am. This has happened to me several times, it’s so annoying because I love the taste of coffee. Occasionally I won’t have such severe diuretic effects, that part is a bit random.

    I find it funny that it’s so socially acceptable while it has effects has significant as illegal drugs, to me at least. Had worse ‘bad trips’ on caffeine than other things :P. Reminds me of this video which may be nice to those who see the strange perceptions of drugs our society has https://www.youtube.com/watch?v=uow__z3Qo8c

Last Modified: May 30, 2017

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