The CYP450 family of enzymes is responsible for breaking down and getting rid of all the various toxins that we come in contact with daily. CYP1A2, a part of the CYP450 family, is of interest to many due to its impact on caffeine. (Learn more about other detoxification genes.)
If you’ve ever wondered why you can’t drink coffee after 3pm and your friends can drink it at dinner, this gene likely holds the answer.
What is CYP1A2?
The CYP1A2 gene codes for an enzyme involved in the metabolism of several different xenobiotics, including:
- aflatoxin B1 (toxic mold found on grain)
In addition to these xenobiotics, CYP1A2 also breaks down endogenous substances such as melatonin, bilirubin, and estrogens.
Substrates, Inducers, and Inhibitors: When it comes to the CYP 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.
In addition to caffeine, CYP1A2 breaks down several prescription medications (substrates). Among these medications, more common medications include clozapine, olanzapine, theophylline, and tizanidine. You should pay attention to genetic variant interactions with medications along with other substances (e.g. caffeine) that are also metabolized using 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. For example, smokers who take duloxetine (Cymbalta) may have lower levels of the drug in their system.[ref]
CYP1A2 is also induced (activated) by cruciferous veggies such as cabbage, cauliflower, and broccoli.
Which supplements inhibit CYP1A2?
- St. John’s wort.
There is a list of drugs, inducers, and inhibitors of CYP1A2 on Wikipedia. Popular drugs metabolized, at least partially, by CYP1A2 include Wellbutrin, Zyprexa, and Cymbalta — as well as caffeine.
Genetics and CYP1A2
In looking at CYP1A2, there are several genetic variants 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.
What are the consequences of inhibited or increased activity?
Well, it depends on what substance you are breaking down. CYP1A2 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.
Thus, the rate at which toxins metabolize, in conjunction with how well Phase II detoxification moves out the metabolites, affects the risk of certain cancers.
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.
CYP1A2 Genetic Variants:
One of the fun things to find out from your CYP1A2 genes is whether you are a fast or slow metabolizer of caffeine. This first variant is very well studied for the speed of caffeine metabolism.
Check your genetic data for rs762551 (23andMe v4, v5; AncestryDNA):
- A/A: Fast metabolizer of caffeine – increased CYP1A2 activity
- A/C: medium caffeine metabolizer[ref]
- C/C: slower caffeine metabolizer, lower CYP1A2 activity
Members: Your genotype for rs762551 is —.
Studies on this variant show:
- increased risk of esophageal cancer for those with A/A, especially with salt tea consumption (Asian population).[ref]
- lower blood pressure for those carrying the variant (A/A, A/C), but only in non-smokers[ref]
- people carrying the variant (A/A, A/C) tend to drink more coffee[ref]
- Asians carrying the variant are at a slightly lower risk of colon cancer[ref]
Other CYP1A2 variants have also been shown to decrease the activity of this gene as well:
Check your genetic data for rs12720461 (23andMe v4, v5; AncestryDNA):
- C/C: typical
- C/T: decreased activity (carrier of one CYP1A2*1K allele)
- T/T: decreased activity (CYP1A2*1K )[ref]
Members: Your genotype for rs12720461 is —.
Check your genetic data for rs72547517 (23andMe v4, v5; AncestryDNA):
- A/A: decreased activity or inactive (CYP1A2*8)[ref]
- A/G: decreased activity (carrier of one CYP1A2*8 allele)
- G/G: typical
Members: Your genotype for rs72547517 is —.
Check your genetic data for rs72547515 (23andMe v4,v5; AncestryDNA):
- A/A: decreased activity or inactive (CYP1A2*16)[ref]
- A/G: decreased activity (carrier of one CYP1A2*16 allele)
- G/G: typical
Members: Your genotype for rs72547515 is —.
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?
- Clozapine (Clozaril)
- Melatonin (endogenous)
- Olanzapine (Zyprexa)
- Ramelteon (Rozerem)
- Zolmitriptan (Zomig)
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]
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 (cimetidine), curcumin, or ciprofloxacin.
Additionally, infections can decrease CYP1A2 activity (more in the Member’s Blueprint).
This members-only section includes additional supplement information and a recap of your genotypes. Consider joining today to see the rest of this article.
Related Articles and Genes:
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.
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 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.