Functional Medicine Detox Phases 1, 2, and 3

In Functional Medicine, “detox” encompasses biotransformation, transportation, and elimination. In these processes, harmful compounds are converted into waste products. These waste products are then eliminated from the body.

Your liver, gallbladder, and intestines are the critical players in this process. The liver manages the transformation stages (phases 1 and 2), processing all substances you ingest, touch, or inhale. Many people are familiar with supporting the liver to enhance detoxification.


Phase 3 is equally important and often overlooked. This phase relies on your gallbladder and intestines for transportation and elimination of the waste products created by the liver. Your liver packages waste products into bile which is then stored in your gallbladder. When you eat fat, bile is released from the gallbladder into your intestines, and eventually carried out through your stool.

Effective detoxification involves the coordinated efforts of the liver, gallbladder, and intestines. Supporting all three organs is essential for optimal detoxification and overall health. To a lesser extent, waste is also removed through your lungs (exhalation), skin (sweat), and kidneys (urine). Here, we focus on the primary detox phases involving the liver, gallbladder, intestines, and stool.

Functional medicine, liver cleanse, phase 1, phase 2, phase 3

Evolutionary Safeguards: Phase 1 Detox Enzymes and Their Crucial Role

Phase 1 primarily focuses on transformation, employing a set of enzymes called the cytochrome P450 family. These enzymes, which originated over three billion years ago, safeguard cells by:

  • Transforming volatile toxins into more minor compounds for further detoxification.
  • Converting fat-soluble (lipophilic) toxins into water-soluble (hydrophilic) forms for Phase 2 processing.

Phase 1 utilizes oxidation, reduction, and hydrolysis reactions to break down compounds into smaller molecules. But this process can produce less stable and potentially harmful byproducts like free radicals. These unstable molecules will not cause harm if phase 2 properly receives and handles these metabolites.

Fueling Phase 2 Detox: Essential Nutrients for Optimal Cleansing

Phase 2 builds on phase 1’s transformation process by conjugating unstable phase 1 metabolites with safer water-soluble components for elimination. It employs six conjugation pathways: glucuronidation, acetylation, methylation, amino acid conjugation, sulfation, and glutathione conjugation.

Phase 2 demands significant energy and nutrient resources. Energy is derived from ATP produced by mitochondria, while nutrients are obtained from food. Each conjugation pathway has specific nutrient requirements. For instance:

  • Glucuronidation utilizes carotenoids, magnesium, omega-3 and omega-6 fatty acids, probiotics, and flavonoids like quercetin.
  • Glutathione conjugation relies on amino acids like glycine, cysteine, and methionine and minerals like selenium and zinc.
  • Sulfation utilizes sulfur-rich foods and amino acids in eggs and garlic.
  • Methylation requires magnesium, B vitamins, saline, and methionine.

An effective detox diet emphasizes adequate protein intake to supply essential amino acids. It includes sulfur-rich foods and various fruits and vegetables representing all colors. It also includes high-quality omega-3 and omega-6 fatty acids. These nutrients are crucial to fulfill phase 2 detox requirements.

When the Phase 1-Phase 2 Balance is Disrupted: Understanding Detox Imbalances

Various positive and negative lifestyle factors activate Phase 1 detoxification enzymes throughout the day. These include:

  • Environmental toxins like dioxin, paint fumes, and pesticides.
  • Medications like steroids, sleeping pills, and birth control pills.
  • Consumables like caffeine, alcohol, and char-broiled meats.
  • Foods like tangerines, oranges, cruciferous vegetables, and garlic.
  • Many B vitamins, including inositol.

Conversely, phase 2 metabolism relies on an array of nutrients often deficient in our modern diets. This results in a sluggish phase 2 response that can’t keep up with phase 1 activation. A carefully crafted functional detox program helps restore balance. It enhances your body’s natural detox mechanisms by providing targeted support for both phases.

Phase 3 Detox: Transport and Elimination

This phase involves transporting phase 2 conjugates in the bile through the intestines for elimination through stool. Phase 3 requires a well-functioning digestive tract and healthy bowel movements to work effectively. As per the Bristol stool chart, this means having one or more Type #4 stools daily. If this isn’t the case, it’s crucial to tackle any underlying gut issues before embarking on a detox program.

bristol, poop, detox, functional medicine, detoxification, constipation, enema, laura paris

The Bathtub Analogy and Why We Prioritize Phase 3

Imagine phase 1 as a constant water drip from a leaky faucet into a bathtub. Phase 2 is the drain with small openings that can quickly become blocked. Phase 3 signifies the sewer line; you have a real problem if it becomes congested! When approaching a focused detox program, follow this sequence:

  1. Start with phase 3 to guarantee clear sewer pipes.
  2. Support phase 2 with food and supplements.
  3. Gradually stimulate phase 1 with food while minimizing exposure to chemicals and toxins.

While phases 1 and 2 focus on transformation, phase 3 is equally crucial for transportation and elimination. Neglecting one of these phases can lead to imbalances and hinder the body’s natural detox mechanisms. Hence, supporting all three phases through a targeted functional detox program is essential for restoring balance and enhancing detoxification processes.

Are you ready to focus on your health and start a personalized detox journey? Contact us today to create a customized plan for your unique needs and goals. Take the first step towards vitality and longevity by giving your body the proper support and nutrients for effective detoxification. Or plan to join our annual January 1-2-3 Functional Detox Program!

Liver detox, Phase 1, 2, 3 detoxification

Dr. Laura Paris is an IFM-certified functional medicine practitioner and doctor of acupuncture and Chinese medicine. She helps women regulate hormones and cycles, reclaim metabolic health, reverse autoimmunity and inflammation, and restore gut health.

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45 Comments

  1. Thank you Laura for this very informative and important post. It really is important to make sure your body has the nutritional support it needs while detoxing. I have a close friend that put herself in the hospital because she was doing ‘The Master Cleanse’ for 2 and a half weeks. At that point her body just started shutting down because she was malnourished.

    That was 30 months ago and she is still not recovered.

    I wrote an article about toxicity and detoxing and linked to this article to help explain the phases of detoxing.

    Thank you!

  2. Hi Laura,

    Can you tell me please why grapefruit isn’t a suitable food to eat in Phase 1? Other websites seem to approve of it.

    1. Sure! If you want to activate phase 1, then grapefruit will not help. Grapefruit inhibits phase 1. That’s why it can increase the level of prescription medications in your bloodstream, because it prevents your liver from metabolizing them. However, if phase 2 or 3 is sluggish (common), then it may be beneficial to slow down phase 1 with grapefruit, instead of ramping it up with coffee or alcohol. Ideally, with a well functioning phase 2 and 3, grapefruit is not a problem and the bioflavonoids are beneficial. However, of the 3 phases, it’s much more common that 2 and 3 are sluggish rather than 1. If you’re going to drink alcohol, perhaps a vodka with fresh grapefruit juice (greyhound) would be a good choice as alcohol revs up phase 1 and grapefruit slows it down. Not that I am encouraging that!

  3. How do you remedy chronic body odor? It isn’t a hygiene issue it’s an internal issue. How would one go about healing that? Need help asap please.

  4. Hi there, this was very informative. I have done several stool tests all which have shown very high levels of b-glucuronidase around 5300U/g just wondering what I can do for this, I suffer from insomnia. I eat super clean and haven been taking a b12 spray and calcium d-gluconate. Quite concerned by this but none has been able to assist me. Any input would be greatly appreciated. Thanks

    1. Glenn,

      I can’t give personal medical advice here. Please discuss with your medical provider.

      Best,

      Laura

  5. Thank you so much for such an amazing informative content. how long should I do phase 1 only before I start phase 2. or they should be done all at the same time?

    1. Maryam I cannot advise you personally without knowing you. I am planning a guided detox for March though, if you’re interested.

  6. Thank you so much for writing this! I have CBS which makes tolerating sulfur very difficult for me. I have dealt with many symptoms because of this issue… But I also have MTHFR and MTRR. It gets so confusing! Anyway, I am curious to know if There is ever a reason to slow down phase 2 and speed up phase 1? So many of my sulfur-based metabolites are through the roof high, like taurine. I wonder if slowing down phase 2 and somehow speeding up phase one will give me better results? Or maybe my thinking is totally backwards! But having excess ammonia due to CBS and all of the issues that present with MTHFR… Does one speed up methylation or slow it down? Of course, I would appreciate any theoretical answer… Not expecting medical advice by any means!

    1. I never recommend trying to speed up or slow down methylation. It’s too complicated and we don’t know long term effects. I do recommend supporting methylation to self regulate with diet primarily. Kara Fitzgerald has an excellent ebook for this.

  7. “However, if you take large supplemental doses of these antioxidants every single day, you run the risk of shutting down the production of your own master antioxidant, and hands down THE most important one: glutathione.”

    Which antioxidants, in what amounts, how and why do they shut down glutathione production? I have tried searching the internet but can find no reference to this. What do you base this argument on?

    1. Hello, thank you for your question. This is based on clinical data. When people take large amounts of any antioxidants, if all reactive oxygen species (ROS) are brought down to a very low level, then your body is not signalled to make as much glutathione. However, the glutathione that you make works far better than antioxidants taken in high doses. I don’t have information about specific antioxidants and their levels. Think of this as a situation when high doses of a supplement over a long period of time can put your own physiology out of balance.

  8. Please tell me how to help mold toxicity and chemicalsensitivity..I’m very toxic and skin burns and metal taste and eyes burn andbrain

    1. This isn’t something that can be answered on a website. You need to work with a practitioner who is skilled with these issues.

  9. Hi Laura,

    Would you recommend speeding up phase 1 or phase 2 to help with caffeine elimination? The caffeine in my one morning coffee lingers for a very long time in my body, and has a detrimental effect on my sleep. Do you think milk thistle is helpful for this issue?

    Thanks.

  10. Is it possible to do this intentionally by say giving a lipotropic injection followed by glutathione and exercise followed by infrared sauna and binders? And if so what is the timing between phases? There is the old niacin flush, but I’d like skip the flushing part.

  11. Thank you Laura. I’m a Functional Diagnostic Nutrition Practitioner, specifically helping people ditch gut pain and auto-immune flare ups, so I’m somewhat familiar with these detox process, but I’m curious about alcohol detox pathways. Specifically, I seem to have zero tolerance for any alcohol whatsoever .. one margarita, one glass of wine and I’m either in pain, fall asleep, heart palpitations and likely hungover. So .. I am wondering if there is a specific phase 2 or 3 pathway that might be malfunctioning and where I might be able to find more info on this and dig into it deeper.

    I appreciate any insight you have.

  12. What about someone who is COMT++ ?

    How do we know the difference between:

    Slow phase 1 vs fast phase 1? Aren’t some of us fast in Phase 1? Do we really want to speed up phase 1? (And if we got slow phase 2 we got a double whammy?!)

    Slow cytochrome p450 and Glutathione S-Transferase Genes?
    https://www.psychologytoday.com/us/blog/click-here-happiness/202001/are-your-genes-responsible-your-unhappiness

    I’m trying to understand where i really sit with these. I have some good clues (do horrible on coffee, can eliminate anesthesia very fast, have 4 genes that are worse for detoxing mold, have COMT++ and VDR Tak, some CBS defects and others.

    I don’t want to speed up phase 1 when i should not.

  13. There is inaccurate information in this article. Milk Thistle does not activate Phase 1. It inhibits Phase 1 and induces Phase 2.

    1. Thanks for this Martin. This was written 5 years ago and I can see that the information about how milk thistle can help support phase 1 was written inaccurately as it can inhibit phase 1 enzymes in vivo. I removed that part and put on on my list to update this post soon, and milk thistle deserves its own article. Thanks again,
      Laura

  14. Hey there Laura! I’d love to pick your brain on something to see if you have come up with anything surrounding phase 2 issues and sulfur intolerance. I am a practitioner also, and I am stumbling upon this, finding very little information that discusses these two as a whole! Phase 2 needs Sulfur. It is one of the biggest parts of that process. I am finding it really difficult to get that back in check after going through a few traumatic things that sent my body into a few chemical sensitivities. I’ve been able to rebuild it quite a bit and get back to a fairly good space with minimal sulfur intake, however if I over do it in the smallest way, it sends me into symptoms that are not pretty. It has caused estrogen dominance and a few other symptoms because of not having that Phase 2 working optimally. Again, I’ve been able to get a few things back in check but not in the ways I know I can. It’s funny that so many practitioners I talk with are stumped by this too, so I figured I’d ask since I came across your article. Hope you are well and thanks in advance! 😁

    1. I am happy to work with you on this, but this is a 1:1 project not suitable for website comments. Hope you understand!

  15. Thank you for this simple and informative description of the phases, a great tool! I am very curious about how menstruation relates to these phases of detox – does it trigger more of phase 1, therefore focus on phase 2 and 3 more in this time? Or is it more of a phase 2 where I could stimulate phase 1 prior to maximize the detox potential? Not finding any information about this, what do you think?

    1. Helena, that’s an interesting question! To my knowledge menstruation does not up-regulate or down-regulate phase 1 or 2, although it can speed up phase 3 (elimination) for some.

  16. Hi Laura,
    Excellent article on Phase 1, 2 and 3.
    As a practitioner, I learned about this years ago and struggled to come up with a meaningful game plan for myself back then as the indications were that I had problems with both 1 and 2, which were later confirmed by an Epigenetic DNA test.
    I have found that MSM works well for me and my clients, those of us not inclined to a high sulfur food diet. Also discovered at one point that periodically consuming half a bottle of Kyolic liquid odorless garlic over two days left me feeling awesome. Now I understand why😊

  17. I was diagnosed with alcoholic fatty liver disease 4 years ago and it absolutely terrified me. The doctors made it sound like a death sentence and it hit me hard. My life changed dramatically and I suffered terribly.

    Thanks to a website I lost weight and my liver function improved beyond belief. I feel more energized, happier and the transformation in my health has been nothing short of a miracle. I not only feel 100 times better, but I barely need to take any insulin at all anymore.

  18. Hi Laura, I am struggling and can’t get back on track and here I find no one to work with on opening the detox L pathways … I have oxalates, histamine and I believe salicylate intolerance… so I can’t use plants or row vegetables…I have to do rapid something because the toxins are recirculating in bloodstream and I’m brain foggy, dizzy and nauseous plus inflammation especially on the back of my neck towards small cerebellum …
    It is possible to work one on one?
    Thanks
    Adina

  19. Hi Laura,
    I have been reading a lot of your articles on your website, I came across this article I believe trying to find out more about the 3 detox pathways of the liver. I have been doing a pathogen / parasite cleanse for several months but my skin rashes have been getting worse. I don’t know if I am detoxing too much or my liver is having problems – ie, they are not all in sync and timing. I eat a lot of the foods you suggest in these and some other articles. I have had some lymph drainage issues as well so I don’t know if that is the problem. I guess my question is should there be a process or cleanse to focus on each phase for awhile or eating the foods and supplements you suggest would help? Do you have any guess on why I am having these rashes?

    With this program I am on for the parasites, they are starting a liver / gallbladder class but it is focused more on gallbladder stones and liver flukes, etc, I’m not sure how much detail they will go into the pathways, so I thought I would ask you.
    Thanks

    1. Hi Isabella, thank you for your comment and questions. I’m glad you are benefiting from the articles. Unfortunately I can’t troubleshoot your symptoms here, without digging into your case as a patient. I hope you understand. Best on your healing journey. Warmly, Laura

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