Caffeine Metabolism and Your Genes

Caffeine molecule

Whether you start your morning with a cup of coffee or a cup of tea, caffeine remains the most popular ‘drug’ of choice for a large percentage of the population.

Caffeine wakes us up by blocking the adenosine receptor.  Caffeine also acts as a central nervous system stimulant, increasing reaction time.

Genetics determine how quickly your body processes and eliminates caffeine and whether it is likely to make you jittery or anxious.

Caffeine Sensitivity Genes:

CYP1A2 gene:

This gene codes for the enzyme that metabolizes, or breaks down, caffeine in the body.

If you are a slower metabolizer, you will feel the effects of caffeine for a longer time.

If you are a fast metabolizer, you will break down and get rid of caffeine more quickly from your system.

Check your genetic data for rs762551 (23andMe v.4, v.5; AncestryDNA):

  • C/C: Slower metabolizer of caffeine
  • A/C: Intermediate metabolizer of caffeine
  • A/A: Fast metabolizer of caffeine [ref]

ADORA2A Gene (Adenosine 2A receptor):

This gene codes for the adenosine receptor protein, which, among other things, plays a role in the brain in regulating dopamine and glutamine release.  Caffeine partially blocks the receptor. Both of the variants listed below are very common.

Check your genetic data for rs5751876 (23andMe v.4, v.5)

  • C/C: no increase in anxiety from caffeine
  • C/T: no increase in anxiety from caffeine
  • T/T:  high caffeine dose more likely to make you anxious[ref] [ref]

Check your genetic data for rs2298383 (23andme v.5 only):

  • T/T: no increase in anxiety from caffeine (avg. amount)
  • C/T: no increase in anxiety from caffeine
  • C/C:  high caffeine dose more likely to make you anxious[ref][ref]

Interesting studies on ADORA2A:

  • While the two variants above are tied to increased anxiety with caffeine, they are also found to correspond with increased anxiety in general (not linked to caffeine).
  • Have dry eyes? These two ADORA2 variants lead to slightly increased tear volume with caffeine consumption.
  • A study found that those who were more susceptible to anxiety from caffeine were, also likely to have a higher habitual caffeine intake. Those drinking more coffee tended to build up a tolerance to the anxiety-inducing effects regardless of genotype.


Diet and Lifestyle:
Looking for a way to pep up your morning coffee?  Here are a couple of options:

Include Bulletproof Brain Octane Oil in your coffee:
Add Lion’s Mane and Chaga mushroom extracts with cognitive benefits (my new favorite!): More of a tea person?  Black teas have the highest caffeine content, ranging from 25 – 50 mg per 8oz cup, while white tea has a much lower caffeine content.

Coffee consumption studies:
If your beverage of choice in the morning is coffee, here are some studies on the effects:

  • A meta-analysis study showed that coffee consumption (4 cups a day) decreased the risk of breast cancer in post-menopausal women by 10%.  Another study indicates that the reduction in risk (found to be closer to 30% for those drinking 5 cups a day) may be due to something else in coffee other than caffeine because other caffeinated drinks did not give the same result.
  • For those with the BRCA1 mutation, one study found that coffee consumption before age 35 for those with the C-allele reduced their risk of breast cancer by 64%.[ref]
  • Another meta-analysis found that high coffee consumption may lead to a decreased risk of pancreatic cancer.

More to read:


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3 Comments on “Caffeine Metabolism and Your Genes

  1. I found out the hard way that I was an intermediate metaboliser of caffeine well before 23andMe data! I heard somewhere about cycling off caffeine every 6 weeks or so for a full 7 days. I’ve been doing this for the last few years and I feel it does help reset caffeine’s stimulatory effect. Whether my adensoine recptors are squeaky-clean or not by the end of this wash out period, I have no idea. BTW C8 caprylic acid in the Brain Octane is strong stuff I find. If I have 1 tbsp in a Bulletproof style coffee in the morning I feel alert and little appetite until about 6pm. Which makes me wonder whether there’s a genetic component here?

    • Hi Chris,
      I’ve found that most people aren’t all that surprised on their genetics for caffeine metabolism. Those of us who are slow or intermediate metabolizers already knew that caffeine too late in the day isn’t a good idea :-)
      I’m sitting here this morning drinking my coffee with Brain Octane oil in it also. I’ve looked into the metabolism of C8 and C10 fatty acids just a bit, but I haven’t dug into the genetics of it very much. I do know that in a small study of Alzheimer’s patients the cognitive benefits of MCT oil were only apparent in those with the APOE E4 variant. Not sure if that has any application though for people without Alz.
      Thanks for commenting,

  2. I’m a fast metabolizer which I was very happy to learn, I love my coffee! I did have a bout with insomnia several years ago and stopped drinking coffee or anything caffeinated after noon which, along with whatever else I was trying helped, so who knows? As a teenager I used to go to sleep with a diet coke next to my bed without any problem (probably not so good for my teeth), so maybe other things play into how fast a fast metabolizer metabolizes? I gradually quit coffee when I found out I was pregnant for the rest of my pregnancy and survived ok, but wouldn’t want to make it a lifetime change! MCT Oil did nothing for me :-(

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