Liver Detox Genes: Phase I and Phase II Metabolism

Liver DetoxGenesEveryone interested in health these days seems to be doing a ‘detox’ or a ‘cleanse’.  There is a lot of general talk about eating clean and cleansing the liver, but there doesn’t seem to be much out there that gets down to the science of how our body’s detoxification systems work.

Like most things, not everyone’s detoxification genes work at the same rate due to genetic variations.  This plays a big role in how well medications and herbal supplements work.

Why is this important?

So why should you care that you have a genetic variant that slows down or speeds up the metabolism of different substances?  The rate that a medication or supplement is metabolized affects how well your body will react to that drug — too fast and you may not get the effect needed; too slow and you may build up too much in your body when you take the next dose.  For each polymorphism that speeds up or slows down drug metabolism, you should read up on any pharmaceutical medications that are broken down by that gene/enzyme. Wikipedia usually has a good list of the ‘substrates’ that are metabolized by that enzyme.  I suggest writing the information down so that you can talk to your doctor about it if needed.  Also, look at any herbs that can inhibit or induce that gene as well as the endogenous substances metabolized by the gene.

New!  I’ve consolidated most of the links below into a ‘report’ format.  You can link to 23andMe and pull in your data to see where you have polymorphisms in your detoxification genes. Click here for free detox genes report  No catch or anything to sign up for.  I just think it is important for everyone to know this information – especially if you take prescription medications!

Phase I detoxification

350px-Xenobiotic_metabolismA lot of toxins – whether eaten, breathed, or created in our bodies – are broken down by the Cytochrome P450 enzymes in what is known as phase I of detoxification. Most of this takes place in the liver, which is the body’s main organ for detoxification.

Let me try to give a simple explanation….    CYP450 is a group term for the enzymes that take a drug (or xenobiotic substance) and break it into metabolites, or smaller substances.  CYP450 enzymes have iron and oxygen in them, and through a redox reaction, it can make a drug more polar.  Polar molecules are more hydrophilic (likes water) and are able to be eliminated through the kidneys.  Here is a better explanation on YouTube:

Phase I Liver Detox Genes:

  • CYP1A1 – metabolism of estrogen, polyaromatic hydrocarbons, and more
  • CYP1A2 – metabolism of caffeine, Cymbalta, Welbutrin, aflatoxin B, and more
  • CYP2A6 – metabolism of nicotine, coumarin, and more
  • CYP2C9 – metabolism of warfarin, Crestor, celecoxib, and more
  • CYP2C19
  • CYP2D6
  • CYP3A
  • CYP2E1

Phase II detoxification

Phase II  detoxification involves taking the metabolites of phase I and changing them so that they can be excreted.  Sometimes the metabolites of phase I are carcinogenic or reactive, so having phase II detox in sync is very important.

After a toxin passes through Phase II, it needs to be excreted from the body (Phase III).  Some are processed through the kidneys and out through urine, others go through the intestines and out.  Bile acids are important in the process, as is proper kidney function.

More reading about detoxification pathways:

Updated: Feb. 2017

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