How Detoxification Works

The Liver

Before your eyes start to gloss over in preparation of an anatomy lesson, I promise this will be short and sweet and really solidify why liver detoxification is important.

In the liver, we do something that’s called ‘hepatic detoxification’ which involves two steps. Phase I is the breakdown of endogenous and exogenous chemicals (the chemicals we make from inside our body and the ones we pick up from outside our bodies). The water-soluble toxins get broken down and eliminated by the bladder and bowels straight away. The water-insoluble toxins, however, must first be dissolved in water, or oxidized before they can be excreted from the body. This poses a problem because these toxic intermediates actually become more toxic as they have now become reactive oxygen species (ROS). If the liver is unable to keep up with detoxification, these ROS then pose an inflammatory threat to other tissues of the body if not excreted.

However, if the liver is working at an optimal rate, these toxic intermediates are shuttled straight into Phase II, or the conjugation and binding of these toxic intermediates into safer, water-soluble compounds that we can readily get rid of through the bladder and bowels.

These process combined are called bio-transformation. In order to have optimal bio-transformation, you have to have balanced Phase I and Phase II. For example, if your Phase I was fast and your phase II was sluggish, you’d have a build up of those toxic intermediates in the body, as we explained above.

This is why it is so important to facilitate optimal detoxification by removing environmental toxin exposure while also incorporating necessary nutrients in our diets.



Phase I detoxification is activated by many external toxins. Examples include caffeine, alcohol, dioxin, paint fumes, steroids, pesticides, sleeping pills, contraceptive pills, and cortisone.

It is also activated in a favorable way by herbs (milk thistle, caraway, dill), citrus, vitamin C, lipotrophics (compounds that break down fat in metabolism like cysteine, methionine, choline, and inositol), minerals (magnesium and iron).

Phase I detox involves the cytochrome P450 enzyme pathway.

An enzyme is a compound that lowers the activation energy of a reaction and ‘makes it go faster’.

Cytochromes are a series of enzymes in a metabolic pathway; they will have different numbers associated with them which represents their ability to refract light at a frequency certain frequency. For example cytochrome p450 refracts light at a frequency of 450.

Why is this important? Because each toxicant to the body (alcohol, tobacco, pharmaceuticals, pesticides, herbicides, hormones, etc.) require a different cytochrome to metabolize it through oxidation, reduction, hydrolysis, etc.

Phase I causes oxidation and free radicals that can do lots of harm to our tissues and DNA if you don't keep them moving through the detox pathway (mentioned above). It's a good idea to increase anti-oxidant consumption (polyphenols and flavenoids) for this reason.


Phase II detoxification is where this metabolized intermediate reactant is conjugated (or bound to a sulfur-containing compound, glutathione, acetylates, amino acids, and methyls), to take those water-soluble Phase I metabolites OUT of our body through bile, urine, and stool.

There are 6 reactions that occur in this phase, all requiring different nutrients.

  1. Methylation - detoxes estrogen, dopamine, histamine (produced during an allergic reaction), and heavy metals. Uses methyltransferases (found in liver, brain, placenta, breast, red blood cells, and lungs) that transfer a methyl group from a donor to an acceptor. Need magnesium, B vitamins, choline (avocados, eggs, liver, non-GMO soy lecithin), and SMAe in order to do their job
  2. Sulfation - detoxes neurotransmitters, steroid hormones, thyroid hormones, acetaminophen, phenols from wine, and any excess bile acids. Biggest inhibitor is NSAIDs, synthetic estrogen, testosterone. Best food to support sulfation are high sulfur foods (egg yolks, brassica and cruciferous vegetables families, MSM supplement, Vitamin A, niacin, Vitamin C.
  3. Glucuronidation - detoxes bilirubin, salicylates, morphine. Foods that helps support this pathway include fish oil, limonene, SAMe. Inhibitors include aspirin and fluoride
  4. Glutathione - detoxes heavy metals and bacterial toxins. Promote this pathway with brassica family veggies, limonene, Vit C, NAC, possible chelation. Deficiencies that impair this pathway are zinc, selenium, B vitamins
  5. Amino acid conjugation
  6. Acetylation

The catch is the phase II detox is often sluggish, probably due to lack of intake of nutritious foods. This is why it is important to make sure every leg of the system is working before ramping up detoxification through supplements.

Phase III or Elimination is the third step for these conjugated compounds to be excreted to the kidneys and out as urine or to the bile in the gallbladder and eventually out through the intestines as stool.

Next we will talk about what impairs our detoxification processes.

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