Detoxification: Phase I and Phase II Metabolism

Your body has an amazing capacity to rid itself of harmful substances through detoxification pathways. We are all exposed to toxicants (man-made toxins) through pesticide residue, air pollution, skin care products, and medications. Plus, our bodies all break down and eliminate substances made and used within ourselves as well as natural plant compounds.

Many people have genetic variants that impact the different ways of breaking down and eliminating toxins. The key here is understanding where you have a genetic susceptibility — and then optimize your diet or avoid certain toxicants or medications.

First, let me explain how phase I and phase II detoxification works. Then I’ll link to important genetic variants in these pathways. These articles can help you to understand how your body eliminates specific substances — from breaking down prescription medications to eliminating pesticide residue.

What are the detoxification pathways?

Your body metabolizes (breaks down) the foreign substances that come into it.

This is usually a two or three stage process. In a nutshell, substances need to be water soluble to be eliminated via feces and urine, and the goal of ‘detox’ is to get rid of substances that your body doesn’t want.

Phase I breaks apart big toxins and makes them into polar molecules. This breaking apart is called metabolism, and the substance that is formed is called a metabolite.

Phase II binds something to the metabolite from Phase I and makes it water soluble so it can be excreted.

Some researchers include a third phase to the process – the elimination of the Phase II products (urine, feces, sweat — all of these means that you need you to drink sufficient water).

How does phase I and phase II metabolism apply to medications?

The rate that a medication is metabolized affects how 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.

Some medications are designed so that the metabolite – the substance created after phase I metabolism – is actually the active drug. These types of medications are called pro-drugs.

Doctors often say “try this medication and see how it works for you”.  Knowing how your genes work, you can know what is more likely to work.


Phase I detoxification genes

A lot of toxins – whether eaten, breathed, or created in our bodies – are broken down by the Cytochrome P450 (CYP450) family of enzymes in phase I of detoxification. Most of this takes place in the liver, which is the body’s main organ for detoxification.

Quick science explanation: The  CYP450 enzymes have iron and oxygen in them, and through a redox reaction can make a drug or toxicant more polar. These metabolite molecules then pass through phase II detoxification to become even more hydrophilic (water loving) so that they can easily be eliminated.

The following articles list the genetic variants related to phase I detoxification of toxicants, medications, and substances produced within the body.  Read through the article and click the link to see your data on 23andMe.  (Members will see their genotype right in the articles.)

  • 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 – metabolism of Plavix, some proton pump inhibitors, more
  • CYP2D6 – metabolism of some antidepressants, antipsychotics, more
  • CYP3A4 – metabolism of half of all prescription drugs
  • CYP2E1 – metabolism of fatty acids, alcohol, and some aesthetics

If you are a Genetic Lifehack’s member, the place to start is the Detoxification Topic Report. This report shows you which CYP variants you carry so that you can read just the more relevant articles.


Phase II detoxification genes:

Phase II  detoxification involves taking the metabolites of phase I and modifying them so that they can be easily excreted.

Sometimes the metabolites of phase I are carcinogenic or reactive, so having phase II detox in sync is very important. You want to have fast and efficient phase II detoxification.

The following articles explain your genetic susceptibility variants related to phase II detoxification as well as what you can do to avoid problems here.


Elimination:

After a toxin passes through Phase II, it needs to be excreted from the body  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.

You can promote elimination by staying hydrated (peeing it out) and by normal bowel movements (pooping regularly).

Additionally, some substances can be eliminated through sweat, so a sauna can be beneficial for elimination.


Originally published 5/2015. Updated 1/2020.