CYP1A2 Gene: Fast or Slow Caffeine Metabolizer?

CYP1A2 is a phase I detoxification enzyme that breaks down caffeine — as well as several other important toxins such as aflatoxin B1 from mold. If you’ve ever wondered why you can’t drink coffee after 3 pm and your friends can drink it at dinner, this gene likely holds the answer. 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.  

What does CYP1A2 do?

The CYP family of genes encodes enzymes that are used by the body to break down and get rid of things like toxins, pollutants, drugs, and even things we eat every day. 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 CYP1A2 gene codes for an enzyme involved in the metabolism (breakdown) of several different substances, including:

• 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

Medications:
CYP1A2 also breaks down several prescription medications (substrates). Among these medications, more common medications include clozapine, olanzapine, theophylline, and tizanidine.

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.
• Other substances, called inducers, cause the body to produce more of the enzyme.
• Plus, there are substances that inhibit the enzyme.

You should be aware of genetic variant interactions with medications as well as other substances (such as caffeine) that are metabolized by the same enzyme.[ref]

What speeds up CYP1A2?

The polycyclic aromatic hydrocarbons (PAHs) found in cigarette smoke upregulate 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.

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.

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.

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 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, or cancer causing substances. 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 and CYP1A2:

Related Articles and Topics:

Detoxification: Phase I and Phase II Metabolism
Learn how the different genetic variants in phase I and phase II detoxification genes impact the way that you react to medications and break down different toxins.

CYP2D6: Variants that cause reactions to common medications
CYP2D6 is responsible for the breakdown and elimination of about 25% of prescription medications. Genetic variants in CYP2D6 can significantly impact the way that you react to certain drugs.

ABCC11 gene: Ear wax and no body odor
The ABCC11 gene determines both the type of earwax a person has and whether they have no armpit or body odor.