Caffeine Metabolism and Your Genes

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.  Adenosine builds up in the brain over the course of a day, causing us to feel sleepy. By blocking the adenosine receptor with caffeine, you no longer feel sleepy. But when the caffeine wears off, the adenosine is still there – causing the rebound effect of feeling even sleepier.

Caffeine also acts as a central nervous system stimulant, increasing reaction time.

Caffeine molecule

 

Genes determines how quickly your body processes and eliminates the caffeine and whether it is likely to make you jittery or anxious.

The CYP1A2 gene encodes the enzyme that breaks down caffeine. Other drugs can also be broken down with the CYP1A2 gene (e.g. clozapine, olanzapine, theophylline), so be careful with drinking caffeine with certain medications. [ref]

People with genetic variants in the CYP1A2 gene can break down caffeine more slowly, causing them to feel the effects of caffeine longer.


Caffeine Sensitivity Genes:

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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]

Members: Your genotype for rs762551 is .


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]

Members: Your genotype for rs5751876 is .

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]

Members: Your genotype for rs2298383 is .

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.

Lifehacks:

CYP1A2 inhibitors: Slowing Down Caffeine Metabolism

Curcumin is an inhibitor of CYP1A2 in humans and in animals. A recent animal study found that curcumin prevented liver damage from aflatoxin B exposure. A potent carcinogen, aflatoxin B is a toxin produced by mold (Aspergillus) and sometimes found in peanuts, corn, and other grains. Curcumin can be taken as a supplement and is also found in the spice, turmeric.

Other inhibitors of CYP1A2 include ciprofloxacin (antibiotic) and cimetidine (aka Tagamet).[ref] So keep in mind that your caffeine metabolism may be altered when taking a CYP1A2 inhibitor.

In other words: If you are normally a fast metabolizer and drink coffee or tea with dinner, you may find yourself having problems sleeping if you couple that caffeine with a CYP1A2 inhibitor like Tagamet, curcumin, or ciprofloxacin.

Diet and Lifestyle:

Looking for a way to pep up your morning coffee without adding caffeine?  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.  If you are a slow caffeine metabolizer, try switching to white tea.

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.

Related Genes and Topics:

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Modafinil: Will it work for you?
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ABCC11 gene: Ear wax and no body odor
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Genetics of Double Eyelashes
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Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.