Coffee & Your Genetics | Are You Caffeine Sensitive? | Caffeine Metabolism- Thomas DeLauer

Coffee & Your Genetics | Are You Caffeine Sensitive? | Caffeine Metabolism- Thomas DeLauer

Coffee & Your Genetics | Are You Caffeine Sensitive? | Caffeine Metabolism- Thomas DeLauer

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you like your coffee I like my coffee we all like our caffeine but have you noticed that some people can tolerate more caffeine or some people are more sensitive to caffeine some people have a cup of coffee and it amps them up some people need like six cups to get the same way well believe it or not it’s not all about tolerance we actually have genotypes we actually have gene mutations and many many people that make us more sensitive to caffeine so what I’m talking about in today’s video is not your tolerance to caffeine not how much you’ve built up a tolerance but legitimately your sensitivity to caffeine like how much do you really need to get the desired effect and a lot of times it does come down to these genetic variations so we’re gonna get down the DNA path a little bit which is a little bit out of the realm of the stuff I normally talk about but what it has to do with coffee it has to do with caffeine I’m all over it so let’s get into it hey you are tuned into the Internet’s leading performance nutrition and fat loss channel with new videos coming out every single Tuesday Friday and Sunday at 7 a.m. Pacific time as well as a bunch of other videos peppered out in between just so you have amazing content also make sure you head on over to Haile calm to check out the premium performance apparel that I’m always decked out in in my videos alright so for once genetics play a role yeah we actually have to talk some stuff up to genetics I know in the world of fat loss we’re always trying to be like not it’s not genetics it’s all about what we apply here and there and the jury is still out on a lot of things when it comes down to fat loss but when it comes down to how we receive nutrients and different compounds and how they react within our bodies scientists and researchers are finding some pretty intriguing stuff so let’s take a look real quick at what happens with caffeine when you ingest it so when you consume some coffee or you consume some caffeine the first thing that it does is it goes to your liver okay and the liver breaks it down and the liver breaks it down with specific enzymes okay these are called cytochrome p450 enzymes and the one that we’re focusing on in particular today is cyp one A two okay the cyp one A two enzyme breaks down caffeine okay so 95 percent of the caffeine that you consume ends up getting broken down by the cyp one A two in the theobromine theophylline and para xanthine okay so it takes caffeine and it takes 95 percent of it and converts it into theobromine and theophylline and these other things okay so you’re left with a small percentage of caffeine that actually does its job on your brain yeah believe it or not most of the caffeine you consume ends up getting metabolized into other metabolites okay plain is simple so what we’re looking at here is when we look at the genetics there’s some interesting stuff that happens with the cytochrome p450 enzymes particularly with the c YP one A two so what they found is that there’s gene mutations that regulate the activity of C YP one a two so let me put this in perspective someone that has a gene mutation that allows the C Y P 1 a 2 to be super effective and super active is going to metabolize caffeine a lot more efficiently so they’re going to be someone that isn’t super sensitive to caffeine because that enzyme is so good that it breaks down more caffeine than normal so if you were to say hypothetically on average break down 95% of caffeine in a perfectly normal person okay do you have 5% of caffeine that’s readily available net right well if you’re someone that has this gene mutation or gene variation that affects the C by P 1 a 2 then you’re gonna have a more active enzyme so which means that when you consume caffeine you might only be left with 1 or 2% that’s actually gonna affect your brain you can soon the same amount of caffeine but the net percentage it’s actually going to affect you ends up less and all has to do with what this gene says now people that end up having a less active variation of this gene that controls the cyp 1 a to end up being those that are sensitive to caffeine you see it’s actually kind of funny it’s actually an inefficiency to metabolize caffeine that allows you to get more of an effect from it so because you’re not able to break the caffeine down you might be left with 10% which means if you put person a and person B right next to each other and they consume the same amount of caffeine person a might have 5% more caffeine hitting their brain than person B so it’s not necessarily always a fair assessment which makes some of the studies that we’ve looked at a little bit convoluted and a little bit confusing even at that but it doesn’t stop there there’s another thing there’s another variation that can actually apply and here’s where it gets kind of fun because I need to explain how caffeine actually works in the brain you see I’ve explained this in other videos but you have adenosine receptors in your brain and what happens is when you consume caffeine and after the metabolites are stripped away and you’re left with straight-up caffeine it binds to the adenosine receptors now normally adenosine tells your body to get tired tell your brain to get tired tells you it’s time to go to sleep so what’s happening is those adenosine molecules hit the adenosine receptors and tell you to get tired just so happens that caffeine is very similar to adenosine so it occupies the receptor so when it blocks the receptor it means that adenosine can’t hit it so it blocks the sleepiness basically the adenosine makes you sleepy and it’s temporarily being blocked by a caffeine molecule but it doesn’t stop there it’s not quite that easy and that’s where I get to explain some more genetic variations you see we have different kinds of adenosine receptors mainly just a 1 and a 2 a we’ll just call it a 2 for short so they both work with caffeine but we’re gonna focus mainly on a 2 because it’s the one that can have the variation you see you can actually have what’s called a polymorphism of the a 2 receptor this polymorphism makes you a lot more sensitive to caffeine basically it allows more caffeine to come in maybe perhaps than it should now what’s interesting is that they found that those that consume a lot of caffeine don’t have this polymorphism they don’t have this mutated gene this this morph thing they don’t have it now which came first the chicken or the egg is it because they consumed a lot of caffeine that they’ve actually changed their receptor to basically not be that affected by caffeine or are they born that way you see it’s kind of interesting because if you’re born that way you might naturally consume more caffeine because you don’t get as much of an effect from it so the world might never know unless we were to test someone literally from the time they were born and chronicled them throughout their entire life so we don’t really know the answer there but what we do know is that caffeine works upon a1 and a2 receptors in different ways and they actually have kind of opposing effects which makes it pretty cool you see that a 1 receptors actually become more dense when more caffeine comes in so look at it this way a 1 adenosine receptors are affected by tolerance okay those are affected by how much caffeine you consume so I want you to just envision this for a second this isn’t you know biologically right in terms of a diagram but I’m gonna explain it with my hands let’s say you have an adenosine molecule okay and it’s had a pretty thin membrane that caffeine can usually slide on in and just occupy that molecule right ok now I want you to envision that you’ve been consuming caffeine for a long time that adenosine receptor that a1 receptor has gotten a thicker membrane it’s become a little bit more closed off so it doesn’t absorb as much caffeine sometimes the caffeine just kind of bounces off and it just doesn’t do as much which means that you’re getting less of an effect from the caffeine because it’s not occupying the receptor the a to receptors on the other hand operate differently the a2 receptors receive more caffeine based on your genotype based on genes based on your DNA so that’s where things get wild is you can actually develop a tolerance to caffeine but still be sensitive to caffeine that’s what’s really wild is we have to look at it two different ways we have the tolerance side of things how tolerant you’re getting of caffeine but also how sensitive you are to it now it doesn’t necessarily mean that if you’re more sensitive to caffeine that you’re going to become more tolerant easier because they’re different receptors that are having a different effect the a2 receptor is the one that you’re affecting by drinking a lot of coffee the a one receptor is not really controlled at least not right now so some people end up with a double whammy for example some people end up with the gene variation that makes it so they have a more active cyp one A two so they don’t absorb much caffeine anyway plus they end up being not very sensitive to caffeine in the brain so they end up needing a lot of caffeine to give them desired effect then you have the opposite you might have people that have the less active cyp 1a2 enzyme it end up allowing a lot of caffeine in plus they have the a2 variation in their brain and their adenosine receptors that absorbs a lot more caffeine so this is where it gets really wild so those are the kind of people that could be super hyper sensitive to it have a small amount and just get a bunch of jitters and get cap kits like things ID and everything like that so it’s really really wild and how we look at this some of the things that you can do you can really test how sensitive you are just have a little bit of caffeine and honestly measure how fast it hits you how fast it hits you is less of a result of your tolerance and more a result of your overall sensitivity if you’re someone that can go and get a cold brew coffee and feel it in like 30 seconds you’re probably caffeine sensitive it doesn’t mean that you’re tolerant or not but that’s a good way to know that you might be someone that is going to get by with a little bit less caffeine and if you can control this then you can get the desired effect you see a man or woman shouldn’t be measured by how much caffeine they can ultimately consume that’s the thing I know guys all the time that are like oh I consume this much caffeine I’m such a badass I can do this I can do that that’s not how it works really so because again person a can consume half the amount of caffeine but absorb 50% more than the person that consumed twice as much and still actually get the same effect so you shouldn’t necessarily measure your Worth based on how much coffee or caffeine you consume you should base it on the desired effect that you’re trying to get how amped up do you get from it how much desired effect are you really getting from it so hopefully this kind of polarize things and gave you a different perspective in terms of caffeine because sometimes we do just have to let genetics be genetics and let caffeine just kind of do its thing we can’t always control it anyway I hope this gave you some information and I will see you in the next video

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Coffee & Your Genetics | Are You Caffeine Sensitive? | Caffeine Metabolism- Thomas DeLauer

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Coffee & Your Genetics | Are You Caffeine Sensitive? | Caffeine Metabolism- Thomas DeLauer…
Genetics & Caffeine-

Caffeine is metabolized by the liver using the enzyme CYP1A2, and 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. Some people genetically produce very little of this enzyme while others produce a large amount. The other genetic link to caffeine sensitivity involves the type of adenosine receptors a person has in his or 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.
Caffeine does not accumulate in our body, but is broken down in the liver – the liver enzymes responsible for metabolizing caffeine are called cytochrome P450 enzymes. One of them is a key enzyme called CYP1A2, which is responsible for inactivating 95% of all ingested caffeine – the ability to produce this enzyme is coded for by the CYP1A2-gene. Different people have different versions of the CYP1A2-gene, and these genetic variations determine how active the CYP1A2-enzyme is in each person

Adenosine Genetics-

Adenosine receptors exist in different forms, and adenosine A2 receptors are key to the stimulating effect of caffeine. A polymorphism of the adenosine receptor (ADORA2A polymorphism) is more likely to be found in those who self-report as caffeine sensitive. People with high habitual caffeine consumption typically do not carry this ADORA2A genotype. So, caffeine functions through adenosine A1 and A2A receptors on the cell surface; these two receptors have partially opposing effects. Chronic intake of caffeine increases the density of A1 receptors, which are believed to be responsible for caffeine tolerance. In contrast, a variation in the gene ADORA2A, encoding for A2a, is associated with sensitivity to caffeine. Specifically, individuals carrying two copies of the C allele at rs5751876 of this gene are more sensitive to caffeine than those carrying two copies of the T allele. Those with the T allele are more likely to experience anxiety after consuming caffeine.

Caffeine Sensitivity Groups-

Hypersensitive to Caffeine: These individuals have very low CYP1A2 activity – they will have a strong response to even small amounts of caffeine, and will commonly experience jitters and insomnia. Slow-metabolism in the liver and high binding in the central nervous system.

Normal Sensitivity to Caffeine-

This is the vast majority of individuals – they can consume up to 400 mg of caffeine per day without adverse side effects. The balance between caffeine inactivation in the liver and binding in the central nervous system means that the individual can typically drink 2–5 cups of coffee during the day but without adverse reactions or sleep disturbances.

Low Sensitivity to Caffeine-

These people have very high CYP1A2 activity, and often experience no effect at all from consuming caffeine – smokers often have increased CYP1A2 activity. Fast-metabolizers of caffeine. Higher intakes can be consumed, and coffee drinking before bedtime may not typically disturb sleep. Note: CYP1A2 declines with age, so you begin to become more sensitive to caffeine the older you become


For those hypersensitive to caffeine, should avoid highly caffeinated beverages like coffee and energy drinks – black tea or green tea is likely more ideal. Those with normal sensitivity should just be aware of how much they consume per day. Hyposensitive people should evaluate the necessity of caffeine – if large amounts of caffeine do not create the desired effects they should consider the benefits of consuming it.

1) Caffeine Sensitivity. (n.d.). Retrieved from

2) Coffee: how many cups are safe to drink? – Genes and Nutrition. (n.d.). Retrieved from


4) Rétey JV , et al. (n.d.). A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep. – PubMed – NCBI. Retrieved from

5) Sachse C , et al. (n.d.). Functional significance of a C–A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. – PubMed – NCBI. Retrieved from 1

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