Functional Medicine Detox Phases 1, 2, and 3

This post is an easy-to-understand explanation of the three phases of detoxification (detox). The next post is specifically about how to detox so read on after this one.

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Let’s get right to liver and gut

Most of your body’s toxic waste goes through three phases in your liver-gut and liver-kidney detox systems.

Phase 1

This is your first line of defense against toxins and uses a group of enzymes known as the cytochrome P450 family. These enzymes protect your cells from damage by:

  • Converting volatile toxins into smaller substances meant for further detox
  • Making toxins water-soluble in order to enter Phase 2

Phase 1 is activated by many external toxins. Examples include caffeine, alcohol, dioxin, paint fumes, steroids, pesticides, sleeping pills, contraceptive pills, and cortisone. It’s also activated in a favorable way by:

  • Citrus: tangerines and oranges (grapefruit shuts down Phase 1)
  • Vitamin C rich foods like strawberries and bell peppers
  • Crucifer veggies (also called Brassica): Brussel sprouts, broccoli, cabbage, cauliflower, collard greens, kale, and turnips
  • Vitamins: C and most of the Bs
  • Lipotrophics: compounds that break down fat in metabolism (cysteine, methionine, choline, and inositol)
  • Minerals: magnesium and iron
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Phase 1 causes oxidation and free radicals

Phase 1 is all about the oxidation of harmful toxins in order to break them down into less harmful metabolites. This is necessary, and it does result in free radicals which can do lots of harm (even to your DNA) if you don’t keep them moving through your detox pathways and OUT of your body!

It’s a good idea to increase antioxidants as protection. Some of the Phase 1 activators ARE antioxidants (like vitamin C and silymarin in milk thistle). However, it’s good to add more, especially polyphenols and flavonoids. If you eat 5-7 servings per day of a wide variety of fruits and vegetables every day you are probably covered.

Supplemental additions include things like resveratrol, coQ10, vitamins A, C, and E, minerals selenium, copper, zinc, and manganese. 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.

Phase 2

Phase 2 is all about conjugation, which uses 6 different pathways to take water-soluble Phase 1 metabolites OUT of your body through your bile, urine, and stool.

For the science types, these are glucuronidation, acetylation, esterification, amino acid conjugation, sulfation, and glutathione conjugation

Phase 2 absolutely requires:

  • Sulfur! (from crucifer veggies, garlic, onions, meat, and egg yolks)
  • Amino acids: glycine, cysteine (or n-acetyl cysteine), taurine, and methionine (meat)
  • Molybdenum, a trace mineral (leafy vegetables, liver)
  • Vitamin B12 (meat)
  • Glutathione, which is made from the above amino acids, or you can take it in a liposomal form.

Other nutrients and foods that help Phase 2 are flavonoids (found in fruits, vegetables, and many herbs), ellagic acid in red grape skin, garlic, rosemary, soy, and cabbage.

When Phase 2 goes awry

The catch is that Phase 2 liver detox is often sluggish, probably because of the lack of intake of the above nutrients in sufficient quantities. You really do not want this, because the metabolites of Phase 1 are quite dangerous and need to be moved out!

So, you may activate Phase 1 simply by your morning coffee and your evening glass of wine, yet if you have a sluggish Phase 2, you could suffer the results of these “toxins” hours later. This may explain your insomnia, brain fog, or hot flashes, for example.

There is growing scientific evidence suggesting that certain diseases are the direct result of damage to the body from poor Phase 2 detoxification. This includes cancer, Parkinson’s, fibromyalgia, chronic fatigue, lupus and immune dysfunction.

Phase 3

This is about transportation. It mainly refers to the transport of Phase 2 conjugates either: to your kidneys for further filtration and then out of your body via your bladder and urine OR out with your bile into your small intestine, and down through your GI tract for elimination via stool.

Phase 3 requires:

  • Adequate hydration for the kidney-urine elimination
  • Proper function of your GI system so that you can poop well! This means pooping daily, without constipation, sluggishness, loose stools, or diarrhea. You want your poop to score a #4 or 5 on this Bristol chart:
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What if your Bristol score is NOT ideal?

If you do not produce one or more #4-5 poops daily, something is causing this. You could have a myriad of underlying causes. Likely culprits include:

  • Dysbiosis –– an overgrowth of pathogenic microbes in your GI tract, or not enough core beneficial bacteria –– dysbiosis can cause loose OR sluggish stools.
  • Lack of fiber –– fiber feeds beneficial bacteria, their byproducts form stool –– lack of fiber can cause loose OR sluggish stool.
  • Magnesium deficiency –– so common! Often THE culprit of sluggish stools.
  • Food intolerance –– can cause loose OR sluggish stools.

Do get elimination in order before doing a focused detox or “cleanse.” Otherwise, it is not worth the collateral damage. You don’t want to push Phases 1 and 2 if Phase 3 is not working!


Please read on about how to do a smart and safe Functional Medicine Cleanse.

Do you want my help designing a custom detox plan for you? Please reach out!

paris healing arts, doctor laura paris, dr. laura paris, dr laura paris

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42 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😊

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