Detoxification: Phase I and Phase II Metabolism is Genetic

Our body has an amazing capacity to rid itself of harmful substances! We take in toxins daily through eating natural plant toxins. We are exposed to toxicants (man-made toxins) through eating foods with pesticides residue, breathing in air pollution, and slathering on skin care products.

What if you could know which toxins and toxicants are most important to avoid? or which medications will actually work well for you? Our detoxification genes work at different rates due to genetic variations. Understanding your own genes for detoxification can help you prioritize which toxicants are the most harmful to you and which drugs to avoid.

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.  Phase I breaks apart big toxins and makes them into polar molecules.  Phase II binds with the metabolites from Phase I and makes them water soluble so they can be excreted. Some researchers include a third phase to the process — elimination of the Phase II products.

How does the detox pathways influence your reaction to medications?

The rate that a medication or supplement is broken down, or 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.

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

Phase I detoxification genes

Phase I and Phase II metabolism. Image from Wikimedia Commons.

A lot of toxins – whether eaten, breathed, or created in our bodies – are broken down by the Cytochrome P450  family of 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.

A simplified explanation…. CYP450 is a group term for the enzymes that take a substance (xenobiotics or endogenous) and breaks it into metabolites, or smaller substances.  CYP450 enzymes have iron and oxygen in them, and through a redox reaction can make a drug more polar.  Polar molecules are more hydrophilic (likes water) and are able to be eliminated through the kidneys.

For each variant 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.

Phase I Liver Detox Genes- click to read more and check your 23andMe results:

  • 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
  • CYP3A – metabolism of half of all prescription drugs
  • CYP2E1 – metabolism of fatty acids, alcohol, and some aesthetics

Phase II detoxification genes:

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.

Phase II Liver Detox Genes- click to read more and check your 23andMe results:

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.

More to read:


Updated: Feb. 2018



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