CYP1A2 Gene: Fast or Slow Caffeine Metabolizer?

Key Takeaways:
~ CYP1A2 is a phase I detoxification enzyme that breaks down caffeine as well as several other important toxins such as aflatoxin B1 from mold.
~CYP1A2 also plays a role in estrogen metabolism.
~ Common genetic variants in CYP1A2 influence whether you are a fast or slow metabolizer of caffeine.

This article dives into the background science behind how CYP1A2 works, as well as how your genetic variants affect caffeine metabolism. I’ll explain how to know if you are a fast or slow metabolizer of caffeine, and how this can also impact other medications.

Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today.  

CYP1A2 Function: Caffeine Metabolism and More

The CYP family of genes codes for enzymes that are used by the body to break down and get rid of things like toxins, pollutants, drugs, and substances our body naturally makes. Genetic variants in the CYP genes impact how quickly we break down various drugs and other toxins, and understanding your genetic polymorphisms (variants) can shed light on how your body reacts to things.

The function of the CYP1A2 enzyme is to break down certain substances to make them more easily excreted from the body.  Specifically, the CYP1A2 enzyme is involved in the metabolism (breakdown) of:[ref]

• caffeine
• aflatoxin B1 (toxic mold found on grain)
• acetaminophen

In addition to the above, CYP1A2 also breaks down endogenous substances in the body such as:

• melatonin
• bilirubin
• estrogens

Related article: Estrogen metabolism (including role of CYP1A2)

Medications:
CYP1A2 also breaks down several prescription medications (substrates). Among these medications, more common medications include clozapine, olanzapine, theophylline, and tizanidine.[ref][ref] However, many medications are metabolized by multiple CYP enzymes, so genetic variants in CYP1A2 alone may not accurately predict your response to a medication.

Substrates, Inducers, and Inhibitors:

• When it comes to the CYP450 enzymes, there are substances that the enzyme acts on to break it down, called substrates. Caffeine would be an example of a substrate of CYP1A2.
• Other substances, called inducers, cause the body to produce more of the enzyme.
• Inhibitors are substances that inhibit the enzyme from being produced or from working normally.

Genetic variants interact with medications as well as other substances (such as caffeine) that are metabolized by the same enzyme.[ref] For example, someone with a slow CYP1A2 genotype may find that taking an inhibitor of CYP1A2 at the same time as drinking a caffeinated beverage causes the caffeine to remain in their system longer.

There is a list of drugs, inducers, and inhibitors of CYP1A2 on Wikipedia. Popular drugs metabolized, at least partially, by CYP1A2 include bupropion, olanzapine, and duloxetine.

What speeds up CYP1A2 (inducers)?

The polycyclic aromatic hydrocarbons (PAHs) found in cigarette smoke upregulate or increase the expression of CYP1A2. Thus, cigarette smoking may cause a faster clearance of some drugs that are metabolized through CYP1A2. Smoking may also make you clear out caffeine faster.

For example, smokers who take duloxetine may end up with lower levels of the drug in their system because cigarette smoke speeds up CYP1A2.[ref]

CYP1A2 is also induced (activated) by cruciferous vegetables such as cabbage, cauliflower, and broccoli.[ref]

Which supplements inhibit CYP1A2?

CYP1A2 is inhibited, at least partially, by the following natural supplements:[ref][ref][ref]

• curcumin
• turmeric
• peppermint
• chamomile
• dandelion
• St. John’s wort

If you take an inhibitor supplement along with drinking a caffeinated drink, you may find that the effects of caffeine last longer.

Fluvoxamine is an SSRI that is also a strong CYP1A2 inhibitor.[ref]

CYP1A2 Gene: ultrarapid metabolizers vs. decreased activity

In looking at CYP1A2, there are several polymorphisms, or SNPs, that either increase the activity or decrease the activity of this enzyme.

People who have the CYP1A2 A/A genotype for rs762551 are rapid or ultrarapid metabolizers. This means that they will break down or metabolize substances such as caffeine more rapidly. Caffeine will be cleared out more quickly and not affect an ultrarapid metabolizer for as long. Unsurprisingly, ultrarapid metabolizers also tend to drink more coffee, on average.

The rs762551 C/C genotype is linked to decreased CYP1A2 enzyme activity. People with this genotype will break down caffeine more slowly and may find that it bothers their sleep at night.

What are the symptoms of slow or fast CYP1A2?

Well, it depends on what substance you are breaking down. For example, CYP 1A2 metabolizes some pro-carcinogens from tobacco smoke into carcinogens. It also helps to turn aflatoxins (molds found in grains) into active compounds involved in liver cancer. Once CYP1A2 metabolizes these carcinogens, the body must eliminate them. Genetic variants can also impact how quickly the second phase of detoxification works.

Thus, the rate at which CYP1A2 metabolizes certain toxins affects the risk of certain cancers in conjunction with how well Phase II detoxification moves out the metabolites.

A slow or reduced function isn’t always bad. For example, slow or inactive CYP1A2 is thought to decrease the risk of liver toxicity from aflatoxin B. This is because CYP1A2 turns the pro-carcinogenic molecules into carcinogens, which then have to be removed from the body.

Lifehacks for CYP1A2

Your genetic variants are estimated to determine about 75% of your CYP1A2 enzyme activity, with food, supplements, and smoking impacting about 25% of the enzyme activity level.[ref]

If you are taking a drug, such as clozapine, that is metabolized by CYP1A2, you should look at both your genes and interactions with smoking.

What drugs are metabolized by CYP1A2?

Drugs that are metabolized by CYP1A2 include: [ref][ref]

• caffeine
• clozapine
• fluvoxamine
• melatonin (endogenous)
• olanzapine
• ramelteon
• tacrine
• theophylline
• zolmitriptan

CYP1A2 inhibitors:

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 is 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.[ref]

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 pair caffeine with a CYP1A2 inhibitor like cimetidine, curcumin, or ciprofloxacin.

COVID or viral infections and CYP1A2:

Related Articles and Topics:

Detoxification: Phase I and Phase II Metabolism
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