~Caffeine is metabolized using the CYP1A2 enzyme.
~Genetic differences in CYP1A2 impact how quickly you will metabolize caffeine.
~The Adenosine receptor (ADORA2A) is blocked by caffeine.
~Some people with ADORA2A variants get jittery or anxious with caffeine.
Caffeine Metabolism and Adenosine Receptors:
Whether you start your morning with a cup of coffee or 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.
Changes to the adenosine A2A receptor gene (ADORA2A) also give rise to variations in how we respond to caffeine. Changes in the way the adenosine receptor functions, due to genetic variants, can alter a person’s response to caffeine.[ref]
Caffeine also acts as a central nervous system stimulant, increasing reaction time.
Genes determine 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 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 Genotype Report
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This gene codes for the enzyme that metabolizes or breaks down the 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 v4, v5; 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, helps regulate dopamine and glutamine release in the brain. Caffeine partially blocks the receptor. Both of the variants listed below are very common.
Check your genetic data for rs5751876 (23andMe v4, v5)
- 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 v5 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).[ref]
- Have dry eyes? These two ADORA2 variants lead to slightly increased tear volume with caffeine consumption.[ref]
- 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.[ref]
CYP1A2 inhibitors: Slowing Down Caffeine Metabolism
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Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.