How Does Detoxification Work? Understanding Phase I, Phase II, and Phase III Detoxification

A woman rests her hands on her stomach.

“Detoxing” is a trendy word for the biological process by which the body eliminates harmful toxins — and it’s happening all the time!

“Detoxing” is a trendy word for the biological process by which the body eliminates harmful toxins — and it’s happening all the time! Detoxification involves three critical phases: Phase I, Phase II, and Phase III (1). Each phase represents a part of the process for converting toxic substances into less harmful compounds and preparing them for excretion. While the body is detoxing all the time, sometimes this process can become a little sluggish or overloaded. The fact is we are surrounded by toxins and they can be a lot for our bodies to handle. That being said, it is definitely possible to support our bodily systems in functioning at their best, including our systems of detoxification!

Understanding each phase of detoxification allows us to provide our bodies with targeted support. This article explains each phase of detoxification, details how to support detoxification phase by phase, and provides some tips on safely supporting the body's innate ability to detoxify for all ages and stages of life.

Phase I Detoxification: The Activation Phase

Phase I detoxification primarily takes place in the liver, utilizing enzymes — mainly from the cytochrome P450 family — to process toxins (1). These enzymes transform pollutants, drugs, and other toxic compounds by adding a reactive group to their chemical structures. This modification often results in intermediates that are more reactive and potentially more toxic than their precursors (1. In essence, during phase I toxins become “activated.” But the body is wise, and this preparation is crucial as it sets the stage for the next phase of detoxification.

Factors such as genetics, diet, and environmental toxin exposure — as well as deficiencies in essential nutrients such as the B vitamins and antioxidants — can impair these enzymes (1), potentially leading to the accumulation of toxins.

If we are exposed to more toxins than our body can handle, our “toxin bucket" can start to overflow. This is not what we want, and managing our toxic load is a good reason to consciously seek out non-toxic alternatives whenever possible.

Phase II Detoxification: The Conjugation Phase

Following Phase I, the now reactive intermediates undergo Phase II detoxification where they are neutralized and made water-soluble for easier elimination (1). This phase involves several pathways, with conjugation reactions being key. These reactions attach small chemical groups to the intermediates, dramatically reducing their reactivity. There are several pathways that work on different kinds of toxins, with the main pathways including glutathione conjugation, sulfation, glucuronidation, acetylation, and amino acid conjugation (1).

The rate of Phase II reactions can vary among individuals due to genetic differences and dietary influences. Nutrients required for these reactions include glutathione, sulfur compounds from cruciferous vegetables, and amino acids from protein sources (1).

If Phase II detoxification is underfunctioning in comparison to Phase I detoxification, that can cause a buildup of toxic intermediates. Remember that Phase I can make toxins more active than their initial state, so if Phase I is working well, but Phase II is sluggish, the body can end up with a lot of active toxins that it cannot deal with effectively. 

Phase III Detoxification: The Elimination Phase

Phase III is the final step in the detoxification process, where the conjugated toxins are transported from the cells into the bile or urine for excretion (1). This phase relies on transport proteins and involves organs like the liver, kidneys, and intestines.

Key Processes in Phase III

  • Bowel Movements: Toxins are secreted into bile (2), carried to the intestines, and either reabsorbed or excreted in the feces. Constipation* can lead to the bile sitting in the intestines and colon for longer, and the toxins can be reabsorbed into the body. This is why it is crucial to ensure that you are pooping well before undergoing any kind of detoxification program!

  • Urination: Some toxins are excreted in the urine (3). Make sure you are well hydrated to support this process.

  • Sweating: Some toxins are excreted in the sweat (4,5). This is why it is important to sweat daily.

To learn more about detoxification, see: What Is Detoxification?

*For more information on constipation, see: Treating Constipation In Kids & Babies With Integrative Medicine 

Sweat dripping off of a woman

Detoxification of Acetaminophen: An Example of the Phases of Elimination in Action

Acetaminophen (Tylenol) is a common over-the-counter pain reliever that illustrates the detoxification process well. Here is how the body goes through the three phases of detoxification when tylenol is ingested:

  • Phase I: Acetaminophen is metabolized by enzymes such as CYP2E1 in the liver, which convert some of the drug into a toxic metabolite called N-acetyl-p-benzoquinone imine (NAPQI) (6).

  • Phase II: Glutathione in the liver quickly conjugates with NAPQI, neutralizing it into a non-toxic, water-soluble form that is safe for excretion (6).

  • Phase III: The conjugated metabolites are then transported out of the liver cells, into the bile and urine, and excreted from the body (6).

Learn more: Taking Tylenol? The Glutathione Connection 

How Do I Support My Body In Detoxifying Efficiently?

Supporting the detoxification pathways in the body is a way to give our body a little bit of extra love and care as it detoxifies. As we live in a world where our bodies are constantly bombarded with toxins, support is helpful to manage the buildup of toxins in our bodies effectively. While it may seem counter intuitive, I recommend going about supporting detoxification by working backwards, starting with Phase III and working backwards to Phase I.

The rationale behind working backwards in supporting detoxification phases is akin to ensuring a factory’s waste management system is fully operational before increasing production. If the waste disposal routes are compromised, ramping up waste production only exacerbates the buildup of waste. Here’s how to support each phase, starting with phase III: 

Phase III Detoxification Support

When we are supporting phase III detoxification, the focus is on elimination: sweating, peeing and defecating (pooping). We should be sweating each day, and defecating at least once a day, ideally 2-3 times per day.

Herbal Support for Phase III Detoxification:

  • Stinging Nettle: Known for its diuretic properties, Stinging Nettle may increase urine output, aiding in the elimination of toxins through the kidneys. It is also known for its blood purifying effect (7)

  • Milk Thistle: Milk Thistle supports bile production (8) which is essential for excreting waste products via the feces.

  • Marshmallow Root: Marshmallow root can gently stimulate the bowels (9) to help move waste out of the body.

Vitamin and Mineral Support for Phase III Detoxification:

  • Magnesium: Magnesium aids in the relaxation of the digestive tract and helps support regular bowel movements (10).

  • Vitamin C: Vitamin C can be supportive of kidney function (11).

Lifestyle Factors for Phase III Detoxification:

  • Hydration: Drinking adequate amounts of water is essential for renal function and helps facilitate the urinary excretion of toxins (12).

  • Regular Exercise: Exercising encourages sweating and helps move bowels.

  • Fiber Intake: Consuming high-fiber foods helps bind toxins (13) and promotes regular bowel movements (14), preventing reabsorption of toxins.

  • Castor Oil Packs: Castor oil packs may support regular bowel movements (15).

Phase II Detoxification Support

Phase II Detoxification is about neutralizing the reactive intermediates that have been created during phase I.

Herbal Support for Phase II Detoxification:

  • Milk Thistle: Milk Thistle supports Phase II by supporting liver function and glutathione production (16).

  • Turmeric: Turmeric has been shown in research to enhance endogenous glutathione synthesis (17), necessary for Phase II glutathione conjugation.

Vitamin and Mineral Support for Phase II Detoxification:

  • B-Vitamins: B vitamins are required for optimal liver function (18).

  • Selenium: Selenium can help protect the liver from oxidative damage (19) that can be caused by the reactive intermediates created during phase I.

  • Zinc: Zinc may be able to upregulate metallothionein, a protein that is associated with the Phase II detoxification of heavy metals (1).

Lifestyle Factors for Phase II Detoxification:

  • Adequate Protein Intake: Adequate protein intake provides the amino acids necessary for conjugation reactions in Phase II (1).

  • Sleep: Adequate and quality sleep each night allows the liver to perform detoxification processes more efficiently (20).

  • Castor Oil Packs: Castor oil packs are a great way to gently support the liver in working at its best.

Phase I Detoxification Support

Phase I detoxification is when the body takes the toxins it has been exposed to and “activates” them, preparing them to be neutralized during phase II.

Herbal Support for Phase I Detoxification:

  • Milk Thistle: Milk Thistle is known for its liver-protective properties (16).

  • Burdock Root: Burdock root is considered to be supportive of liver function (21).

  • Dandelion Root: Dandelion root nourishes the liver (22) and may help maintain the optimal operation of Phase I detoxification enzymes.

Vitamin and Mineral Support for Phase I Detoxification:

  • Vitamin C: Vitamin C is an antioxidant that helps protect cells from oxidative stress (23) and supports the activation of enzymes necessary for Phase I detoxification (1).

  • Vitamins A & E: Fat soluble vitamins A and E help protect the liver from the oxidative stress that can occur during Phase I detoxification (24,25).

Lifestyle Factors for Phase I Detoxification:

  • Minimize Toxin Exposure: Reducing exposure to environmental and dietary toxins decreases the load on Phase I detoxification pathways.

  • Nutrient-Rich Diet: Focus on a diet high in antioxidants to protect the body during the detoxification process.

How Do Binders Help Detoxification?

Binders, like activated charcoal, work primarily through a process called adsorption (26) — not to be confused with absorption. Adsorption is a surface-based process where substances stick to the outside of the charcoal particles. Activated charcoal has a porous texture, which increases its surface area, allowing it to bind with various toxins, chemicals, and gasses effectively. Once these toxins are bound, they are trapped and unable to be reabsorbed by the body, traveling through the gastrointestinal tract until they are excreted in the feces.

While binders do not directly participate in the biochemical detoxification phases (Phase I and Phase II), they are instrumental in Phase III. After the liver processes toxins, they are excreted into the bile and released into the intestines. Without binders, these toxins can potentially be reabsorbed into the bloodstream. Binders help capture these toxins in the gut (27) and assist in their final excretion, which reduces the recirculation and potential toxicity.

Detoxification During Childhood & Pregnancy and While Breastfeeding

The body is always detoxifying. However, when we speak of following specific detoxification plans that include herbs or pharmaceuticals, it is important to note that such plans are not always suitable for children, pregnant women, or nursing mothers. When supporting children in their detoxification processes, after vaccination for example, it is important to make sure their bodies are eliminating well first and foremost before looking for a gentle formula that is safe for children

Always do your due diligence and be cautious of anyone on the internet that advises you to put your child on a harsh detox regime. Regular exercise, adequate hydration, sound elimination (defecating, urinating and sweating), and a nutritious diet encourage detoxification in the body. When in doubt, seek the advice of a medical professional.

For more on detoxification for kids, see: 10 Ways To Support Detoxification In Kids 

A girl sits in a yoga pose outdoors.

Considerations for Detoxification While Taking Pharmaceutical Medications

If you are currently taking pharmaceutical medications, it is important to consult your healthcare provider before starting any kind of detox plan. Increased detoxification may increase the rate at which your medications are expelled from your body and make them less effective. This is an important consideration for all types of medications, but it may be especially important for those medications which require consistent levels in the system, such as medications for mental health, birth control pills, blood thinners, heart medications, etc.


Detoxification is an ongoing biological process that helps the body manage and eliminate toxins. It involves three critical phases: Phase I (activation), Phase II (conjugation), and Phase III (elimination), each playing a role in transforming toxic substances into safer compounds that can be excreted from the body. I recommend supporting these phases of detoxification by working backwards from Phase III to Phase I. This backwards approach helps ensure that the body's elimination systems are well-prepared before increasing its detoxification load.

Beneficial herbs include milk thistle, dandelion root, and burdock root. The adequate intake of vitamins and minerals (such as B-vitamins, vitamin C, and zinc), healthy lifestyle habits, and a nutrient dense diet are important ways to help our bodies detox effectively.

By understanding and supporting each phase of detoxification, you can support your body's natural ability to detoxify and thrive in a toxic environment.


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