CYP1A2 – Breaking down caffeine and more

The CYP450 family of enzymes is responsible for breaking down and getting rid of all the various toxins that we come in contact with on a daily basis.  CYP1A2, a part of the CYP450 family, is of interest to many due to its impact on caffeine.

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 is involved in the metabolism of several different xenobiotics, including:

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

When it comes to the CYP enzymes, there are substances that the enzyme acts on to break it down, called substrates. Additionally, there are substances that cause more of the enzyme to be produced by the body (called inducers), as well as substances that inhibit the enzyme.

In addition to caffeine, CYP1A2 breaks down several prescription medications (substrates). Among these, clozapine, olanzapine, thoephylline, and tizandine are important. People should watch out for interactions with genetic variants and with other substances (e.g. caffeine) that are also metabolized using the same enzyme. [ref]

The polycyclic aromatic hydrocarbons (PAH's) that are 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.

It is inhibited, at least partially, by[ref][ref][ref]:

  • cumin
  • turmeric
  • peppermint
  • chamomile
  • dandelion
  • St. John's wort.

There is a list of drugs, inducers, and inhibitors of CYP1A2 on Wikipedia.  Popular drugs that are 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.

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 is involved in turning aflatoxins (mold found on grain) into active compounds involved in liver cancer.  Once these carcinogens are metabolized by CYP1A2, they also have to be eliminated by the body.

Thus, the rate at which the toxins are metabolized, in conjunction with how well Phase II detoxification is doing at moving out the metabolites, all affect the risk of certain cancers.

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.


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