CYP2A6: Breaking down nicotine and other medications

The CYP450 family of enzymes is tasked with breaking down and eliminating substances in the body. These enzymes metabolize both substances produced within the body, such as estrogen, and the toxicants that we are exposed to, such as medications and pollutants.


CYP2A6 is part of the CYP450 family of genes that code for the detoxification enzymes. The CYP2A6 enzyme is involved in the metabolism, or breaking down, of:

  • nicotine
  • several cancer drugs
  • valproic acid
  • coumarin

The estrogen hormone, estradiol, causes higher CYP2A6 activity, and women usually have a somewhat higher activity of this enzyme.[ref]

Quitting Smoking:

When it comes to smoking, the CYP2A6 genetic variants impact the speed at which nicotine is metabolized. Interestingly, researchers link the genetic variants of CYP2A6 that cause decreased enzyme activity with a lower level of dependence in smokers, making it easier for them to quit. Basically, the slower CYP2A6 variants make the effects of nicotine last longer, thus reducing the number of cigarettes smoked.

On the other hand, people with increased CYP2A6 enzyme activity have an enhanced metabolism of nicotine and are likely to smoke more cigarettes per day.[ref]

Genetic Variants – CYP2A6:

There are quite a few variations of CYP2A6.  Below are just a few that are available in common genetic sequencing.

In general, research shows that people with reduced (or slow) CYP2A6 activity are more likely to quit smoking. Amongst smokers, slow CYP2A6 activity is linked with smoking fewer cigarettes per day.[ref][ref]

Check your genetic data for rs1801272 (23andMe v4; AncestryDNA):

  • T/T: CYP2A6*2 – reduced activity [ref][ref]
  • A/T:  One CYP2A6*2 allele, reduced activity
  • A/A: typical*

*note: listed in the plus orientation to match 23andMe, AncestryDNA data

Check your genetic data for rs5031017 (23andMe v4 only):

  • A/A: CYP2A6*5 – non-functioning variant [ref]
  • A/C:  One CYP2A6*5 allele, reduced activity
  • C/C: typical

Check your genetic data for rs5031016 (23andMe  v4, v5; AncestryDNA):

  • G/G: CYP2A6*7 – non-functioning variant [study]
  • A/G:  One CYP2A6*7 allele, reduced activity
  • A/A: typical

Check your genetic data for rs28399444 (23andMe v4 only):

  •  -/- : CYP2A6*20 – non-functioning variant [study]
  • -/TT:  One CYP2A6*20 allele, reduced activity
  • TT / TT: typical


Another gene, POR (P450 cytochrome oxidoreductase), codes for an enzyme that can also alter the activity of other CYP450 enzymes.

Check your genetic data for rs1057868 (23andMe v4, v5; AncestryDNA):

  • C/C: normal enzyme activity
  • C/T: normal enzyme activity
  • T/T: may increase CYP2A6 enzyme activity in people with normal CYP2A6 variants[ref]


Grapefruit juice:
Grapefruit juice contains a substance that inhibits CYP2A6 enzyme activity.  So be careful – especially if you have a slow variant of the gene – with combining grapefruit juice with any drug that is metabolized by CYP2A6.[ref]

Higher doses of cinnamon, such as you might take for regulating blood sugar levels, has been shown to inhibit CYP2A6 enzyme activity.[ref]  If you are a slower CYP2A6 metabolizer, you may want to be careful about too much cinnamon if you also take one of the medications listed below.

Drugs that are metabolized by CYP2A6 include: [ref – read for more info]

  • nicotine
  • tegafur
  • Letrozole
  • Efavirenz
  • Artemisinin
  • valproic acid
  • Pilocarpine

Check out the substrates column the CYP2A6 article on Wikipedia for more drugs and substances metabolized by CYP2A6.


More to read:

This is part of an ongoing series on the genes involved in Phase I detoxification.

Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.