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Phase 1 and 2 Liver Detox Pathways & How to Open Phase 3 Detox

September 17, 2020 by Amber

liver detoxification pathways

Unclogging phase 1 and 2 liver detox pathways by supporting the liver with nutrients required for liver detox is essential for optimal liver function. Supporting phase 3 liver detoxification is the first step to effectively detox toxic substances from the liver.

The liver detoxifies harmful substances, drugs, environmental toxins, and endotoxins via 3 phases of liver detoxification:

Phase 1 liver detox

Phase 2 liver detox

Phase 3 liver detox

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For optimal liver detoxification, it is essential that all three phases are open and working in harmony. Problems in liver detoxification occur if phase 1 is too fast, yet phase 2 detoxification pathways are too slow or if phase 3 detox is clogged.

Dr. Kelly Halderman coined the term phase 2.5 detox, where toxins from the liver enter the bile. Excess inflammation can cause the 2.5 detox door to close.

Many people will feel worse if they do a liver detox program yet have inflammation or a sluggish gallbladder involved in phase 3 detoxification. Toxins get reabsorbed into the bloodstream instead of exiting out of the liver and gallbladder.

To effectively detox the liver and eliminate toxic chemicals, all the detoxification pathways need to be open to safely detox. Inflammation needs to be reduced, and the gallbladder needs to be functioning optimally. Antioxidants are crucial for protecting the liver from oxidative damage

The liver also requires an ample supply of nutrients for the liver’s detoxification enzymes to detox.

There is a lot to know about liver detoxification. Your body will thank you when you support your liver with the proper nutrients and detox the right way. A healthy liver is necessary for a healthy body! The body’s ability to detox on a daily basis is dependant upon the liver being supplied with various nutrients and antioxidants to prevent liver damage.

Why you need to balance phase 1,2 and 3 liver deotx

For optimal liver detox, phase 1 and phase 2 detox need to balance each other. The products coming out of phase 1 detox are often more toxic than the original substance.

Phase 2 detox needs to keep up with phase 1 detox to conjugate the toxins coming out of phase 1. Often phase 1 detoxification is efficient, yet phase 2 detoxification pathways are slow. In this case, it is helpful to slow down phase 1 detox with foods such as grapefruit juice and curcumin for turmeric root.

It is also crucial that conjugated toxins get through the 2.5 detox door and out of the gallbladder. Reducing inflammation and supporting a sluggish gallbladder are essential first steps in opening up the liver’s detoxification pathways.

When implementing a liver detox protocol, work backward by starting with:

• Phase 3 detoxification – gallbladder support

• Phase 2.5 – reduce inflammation so toxins can get out of the liver and into the bile

• Phase 2 liver detox– support sluggish phase 2 detoxification pathways

• Phase 1 liver detox – ensure the liver has nutrient to support phase 1 detox

The best liver detoxification program has all three liver detox phases working together at the correct speed. Not too fast and not too slow. Just right.

Phase 1 Liver Detox

In phase 1 detox, substances go through the cytochrome p 450 enzyme system, where a group of enzymes breakdown harmful toxins into intermediate forms. Some toxins are ready for elimination at this stage, but most toxins are conjugated through one of the phase 2 detoxification pathways.

• Phase 1 liver detox uses oxygen to form a reactive site on a toxin

• Phase 2 liver detox adds a water-soluble group to the reactive site on a toxin

This two-step process is known as reduction/oxidation and conjugation, enabling a toxin or substance to be ready for escort out of the liver.

Phase 3 liver detox eliminates the water-soluble toxins through the bile and out of the gallbladder. Alkalinity promotes phase 3 detox, so alkaline-forming fruits and vegetables are fantastic foods for liver detox.

The nutrients required for phase 1 liver detox include B1, B2, B3, B6, choline, vitamin C, vitamin E, and magnesium and selenium.

Foods, herbs, drugs, nutrients, and environmental toxins can speed up or slow down phase 1 detox.

Depending on if your phase 1 liver detox is too fast or too slow, you can use foods to speed up or slow down phase 1 detox.

If you are taking any medication or drugs, you will want to consult with your doctor before making any changes to speed up or slow down phase 1 detox. Many medications are metabolized through the P450 enzyme system.

Phase 1 liver detox foods

Foods that speed up phase 1 liver detox include cabbage, broccoli, Brussel sprouts, charcoal-broiled meats, high protein diets, oranges, and tangerines.

Foods that slow down phase 1 detox include naringenin from grapefruit juice, curcumin from turmeric root, red chili pepper, clove oil, and quercetin.

These foods can be helpful to consume if phase 1 liver detox is too fast and phase 2 detox is too slow.

The first phase of detoxification will often produce highly toxic metabolites that can damage DNA and liver cells and wreak havoc if not conjugated through phase 2 liver detox in a timely matter. For this reason, all liver detoxification processes need to function optimally.

Phase 2 liver detox

Phase 2 liver detox has six major detoxification pathways to further conjugate toxins.

• Glutathione conjugation

• Sulfation

• Amino acid conjugation

• Glucuronidation

• Acetylation

• Methylation

Liver detoxification pathways and support nutrients

Glutathione conjugation:

Glutathione is the body’s most important antioxidant to protect the body against free radicals produced through phase 1 detox and oxidative stress.

Glutathione is used to detox environmental toxins and carcinogens and is very versatile in conjugating and binding many different types of toxins.

Optimal liposomal glutathione plus is a superior supplement to support phase 2 glutathione conjugation. Liposomal Glutathione Plus by Seeking Health is easily absorbed and utilized by the body and contains nutrients to support the recycling of oxidized glutathione.

Glucuronidation:

Glucuronidation is one of the most important detoxification pathways. This pathway is responsible for metabolizing drugs, estrogens and also conjugates bilirubin.

Calcium D-glucarate supports the glucuronidation pathways and metabolism of estrogen. Hormones are cleared through the glucuronidation pathway, such as estrogens. When this pathway is slow, the risk of hormone-related cancers can increase.

If someone is estrogen dominant and has a sluggish glucuronidation pathway, calcium D-glucarate helps support estrogen’s liver detox.

The supplement calcium D-glucarate also helps to ensure toxins stay conjugated and get eliminated from the body.

Acetylation

The acetylation pathway works on amines and endogenous substances such as histamine, caffeine, choline, and tyramine.

Vitamin B5 is an essential nutrient for the acetylation detoxification pathway. Slow acetylators can have an increased risk of bladder cancer.

Amino Acid Conjugation:

Amino acid conjugation uses amino acids to combine with toxins to neutralize them. Glycine and taurine are amino acids used for this pathway, along with glutamine, arginine, and ornithine.

Obtaining enough glycine and taurine protein-containing foods is essential for the amino acid conjugation pathway. Taurine and glycine are also crucial for the formation of bile acids. These amino acids are found in gallbladder nutrients to support a healthy gallbladder and liver.

Sulfation

The sulfation detox pathway is needed to detoxify food additives, toxins from intestinal bacteria, and the environment.

Sulfation is the main pathway for the elimination of steroid and thyroid hormones. Neurotransmitters and estrogens are also eliminated through the sulfation detox pathway.

Sulfite is a common food additive added to dried fruits and wine. Molybdenum is the co-factor for the sulfite oxidase enzyme, which converts sulfites into sulfates. Sulfates are much safer.

If you notice that wine gives you a wicked hangover, then molybdenum is your best friend to help detox sulfites found in wine.

Sulfur-containing foods such as radishes, onion, celery, kale, watercress, broccoli, cauliflower, eggs, fish, and meat are excellent sources of sulfur for the sulfation detoxification pathway.

Methylation:

The methylation pathway is responsible for methylating histamine. Slow methylation or SNPs in the MTHFR gene can cause symptoms of histamine intolerance. Methylation is also needed to process neurotransmitters such as dopamine, epinephrine, and norepinephrine.

SAMe is the primary methyl donor used in the body. Nutrients such as methionine, B2, folate, B12, B6, and magnesium are required for optimal methylation and production of SAMe.

Vitamin B2 and B12 are highest in animal protein. Folate and magnesium are abundant in leafy green vegetables.

A whole-food nutrient-dense diet is essential to provide the liver with all the nutrients required for optimal function of the liver’s detoxification pathways.

When you know where your weakness lies, you can then support specific detoxification pathways with nutrients and foods to improve phase 2 liver detox. 

Why it is crucial to support phase 3 liver detoxification

Before optimizing phase 1 or phase 2 liver detox, it is essential to ensure phase 3 detoxification of the toxin out of the gallbladder via the bile. Toxins will be reabsorbed into the bloodstream if they can’t get out via the bile and eliminated through the feces.

Gallbladder nutrients help support both bile production and flow so toxins can be escorted out of the body.

Liposomal curcumin helps to reduce inflammation to ensure that the 2.5 detox door is open so that toxins can get out of the liver and into the bile.

Phosphatidylcholine is a critical nutrient to prevent bile from getting thick and sludgy. Bile flow is crucial for eliminating toxins out of the gallbladder, also known as phase 3 liver detoxification.

Optimal detox contains vitamins, minerals, and herbs to support overall detoxification, including phase 1 and phase 2 liver detox.

An effective detoxification program ensures all the liver’s detoxification pathways are open. The detoxification pathways need to be working together in a timely matter. Food that cleanse the liver should be eaten daily to provide the liver with the nutrients it needs to detox.

The detoxification of toxins relies upon a healthy liver that has all phases of detoxification working together to remove harmful compounds from the body. in today’s modern world the toxic load on the liver is increasing due to environmental toxins, pesticides and the contamination of products and water with heavy metals.

Personal care products are another source of toxic compounds that can negatively affect the liver. More than ever, people must maintain a healthy diet and lifestyle to deal with all the external toxins we are exposed to just by living our normal lives.

Thankfully there are liver-supporting herbs such as milk thistle that helps the liver to deal with the excess toxic burden. It is one of the most well-researched herbs for the liver and has been used to treat alcoholic liver disease, acute and chronic viral hepatitis, and toxin-induced liver diseases. Milk thistle is also high in liver protective antioxidants that reduce oxidative stress which damages the liver.

Leading a healthy lifestyle and making sure that phase 1 and 2 liver detox are working together in harmony is crucial for overall health. You also must ensure that you have opened up all the different pathways, including the phase 3 liver detox that many people skip or miss.

References:

The 7 Day Detox Miracle

The Liver Gallbladder Master Class

Filed Under: Liver Detox

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Reader Interactions

Comments

  1. curtis Richart

    August 25, 2021 at 3:43 am

    Thank you Amber for all the info 😀
    Is it good to take oxbile to help with phase 3? And or to assist with any stage of liver detox etc. ? What else would be good to take for the gallbladder?

    Again thank you for your expertise!

    Curtis

    Reply
    • Amber

      October 9, 2021 at 10:46 am

      Your welcome, so many good things for the gallbladder such as beets, artichoke, dandelion tea, lemon, apples. Gallbladder nutrients by seeking health contain nutrients required for both bile production and flow. Two crucial aspects for phase 3 detox. Ox bile does further help with fat digestion but not so much with opening up the phase 3 detox of promoting bile flow. Ox bile can be beneficial for someone who has had their gallbladder removed. I have also used it to help reduce SIBO. Hope that helps 🙂

      Reply
  2. John Navarro

    February 24, 2023 at 2:22 am

    Thank you for this information. It is presented in an easy to understand manner and is to-the-point. Greatly appreciated!

    Reply
    • Amber

      February 27, 2023 at 6:02 am

      Thanks John, I’m so glad you found the information helpful and easy to understand!

      Reply
  3. Donna

    March 17, 2023 at 12:39 am

    Hi Amber. i have Gilbert’s syndrome which considerably slows down the phase 2 detoxification pathway. Do you know if there’s a supplement available that has most of those ingredients that you mention under the phase 2 detox?

    Reply
    • Amber

      March 28, 2023 at 5:36 am

      Hi Donna, I am not familiar with which pathway is clogged in Gilberts syndrome and the cause for it, but Im sure there must be something that can help with it 🙂

      Reply

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Hey! I’m Amber, a nutritional therapy consultant helping people to improve digestion, beat the bloat and lose weight. Sharing weight loss tips, gut health tips and whole food recipes that are gluten-free.

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