Functional Medicine Detox Phases 1, 2, and 3
This post is a breakdown of the 3 phases of detoxification (detox). In functional medicine, we call this “biotransformation and elimination.” It refers to the bodily processes of transforming harmful compounds into waste products and getting them out of the body. We do some of our detox through our skin, lungs, and kidneys (via sweat, breath, and urine), but it’s your liver, gallbladder, and intestines that do the heavy lifting. Think liver > gallbladder > intestines > poop.
You may have heard of the first two phases of detoxification, which take place primarily in your liver, and to a small extent in peripheral tissues. Your liver is an amazing engine that processes every single thing that you swallow, eat, drink, or breathe. It’s important to give it lots of love. Detox programs are typically all about supporting the liver, for good reasons.
Phase 3 is getting the rest of the junk out of your body through your gallbladder and intestines via bile and stool. Let’s dig in…
Phase 1: Fat-soluble to water-soluble
Phase 1 uses a group of enzymes known as the cytochrome P450 family. These enzymes originated 3.5 billion years ago to protect cells from damage by:
- Transforming volatile toxins into smaller substances meant for further detox
- Making fat-soluble (lipophilic) toxins water-soluble (hydrophilic) in order to enter Phase 2
Phase 1 uses the biochemical reactions of oxidation, reduction, and hydrolysis to transform compounds into smaller molecules. In the process, it creates less stable and potentially more harmful metabolites, such as free radicals. This is all well and good as long as Phase 1 metabolites keep moving through your detox pathways and out of your body. This means that the phase 2 and 3 pathways must be open and functional. If this is not the case, and they are shut down, then it’s actually dangerous to activate Phase 1. Never do a “cleanse” that activates Phase 1 if the next phases are blocked.
Phase 1 is activated by many many things in our daily life, both good and bad. Examples include:
- Things we consume like caffeine, alcohol, and char-broiled meats
- Toxicants in our environment like dioxin, paint fumes, and pesticides
- Medications like steroids, sleeping pills, and birth control pills
- Foods like tangerines and oranges, cruciferous vegetables, and garlic
- Most of the B vitamins, including inositol
If you don’t feel well on birth control, or when you take B vitamins, it could be because you are activating Phase 1 when the next phases are sluggish. Supporting Phase 2 detox pathways to move these intermediate compounds out of your body is super important. In addition, increasing antioxidants through food or supplements will help protect you from volatile Phase 1 metabolites.
Phase 2: Get it out of the liver via the bile
Phase 2 is all about conjugation, which links the unstable Phase 1 metabolites with a water-soluble component that’s ready for elimination. It uses six different conjugation pathways: glucuronidation, acetylation, esterification, amino acid conjugation, sulfation, and glutathione conjugation.
Phase 2 requires a lot of energy and nutrients.
The energy comes from ATP that your mitochondria make, and the nutrients come from nutrient-dense foods. Each conjugation pathway has a set of nutrient needs. For example:
- Glucuronidation needs carotenoids, magnesium, omega 3 and 6 fatty acids, probiotics, and flavonoids like quercetin
- Glutathione conjugation requires the amino acids glycine, cysteine, and methionine, and the minerals selenium and zinc
- Sulfation uses sulfur-rich foods and amino acids like eggs, garlic, and taurine
- Methylation requires magnesium, B vitamins, choline, and methionine
A good detox diet emphasizes adequate protein, sulfur-rich foods, fruits and veggies from all colors of the rainbow, and high-quality omega-3 and 6 fatty acids.
When the Phase 1-Phase 2 balance goes awry
As we mentioned above, Phase 1 is easily and frequently activated by things that you may consume every day, such as your morning coffee, daily B vitamin complex, birth control pill, or evening glass of wine. It’s also activated by the plethora of toxic chemicals in our environment. None of us are immune to these toxins in our water supply, in our soil, and in the air that we breathe. And, the number of different chemicals allowed and dumped into our environment increases yearly.
The catch is that Phase 2 detox is often sluggish and not able to keep up with Phase 1 activation. This is because it is far too easy to be deficient in the nutrients that the Phase 2 pathways need. Vegans may be deficient in amino acids from protein, minerals from meat and seafood, and vitamin B12 which is animal-derived. On the flip side, people on a keto diet may be low in the phytonutrients, antioxidants, and vitamins found in plant foods. In our modern world full of processed foods and fad diets, it takes knowledge and effort to eat a diet that supplies adequate Phase 2 nutrients.
So, you may activate Phase 1 simply with your morning coffee or your evening glass of wine, yet if you have a sluggish Phase 2, you could suffer the results later. This may explain your insomnia, brain fog, or fatigue. Over time, it can contribute to bigger problems like cancer, Parkinson’s, dementia, cardiovascular disease, and premature aging.
This is where well-designed and medically supervised detox programs come into play.
While your liver is capable of and should be running efficient Phase 1 and 2 detox all day long, it’s very common for Phase 2 to back up. Plus, our exposure to toxins just keeps climbing. A focused and safe medical detox program allows you to lighten toxic burdens while giving extra support to your detox pathways. Spring and fall are great times to do focused detoxes. A quarterly detox is even better.
Phase 3
This is about transportation. It mainly refers to the transport of Phase 2 conjugates out with your bile into your intestines for elimination via stool. Phase 3 also includes transport to your kidneys for further filtration and then out of your body via urine.
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:
What if your Bristol score is NOT ideal?
If you do not produce one or more #4-5 poops daily, something is causing this. This needs to be fixed, especially before doing a focused detox program. While loose stools aren’t ideal, sluggish stools or constipation are worse for detox. There are a myriad of potential causes, including:
- Dysbiosis –– An overgrowth of pathogenic microbes in your GI tract, or not enough core beneficial bacteria
- Lack of fiber –– Fiber feeds beneficial bacteria, binds with waste, and keeps you regular
- Magnesium deficiency –– Sluggish stools or constipation are signs of low magnesium, as well as anxiety, muscle cramps, and insomnia
- The wrong foods –– Food sensitivities can cause sluggish or sticky stools
- Medications ––Many medications slow motility, such as trendy weight loss drugs, benzodiazepines, and opiates
The bathtub analogy and why we start with Phase 3
Think of Phase 1 as a steady drip of water into the bathtub. You can’t turn it off. Phase 2 is the drain, and that can easily get clogged. Phase 3 is the sewer line, and if that’s clogged, you’ve got a real problem! With a focused detox program, approach it in this order:
- Start with Phase 3, and make sure the sewer pipes are clear
- Support Phase 2 with food and supplements
- Gently activate Phase 1 with food while lowering exposure to chemicals and toxins
Join our next Detox Program!
We offer medically-supervised group detox programs 2-4 times a year. Contact us to get on the list for the next program.
Dr. Laura Paris, DACM is an Institute for Functional Medicine certified practitioner and Doctor of Acupuncture & Chinese Medicine who specializes in the intersection of hormones, inflammation, and autoimmunity. She helps women balance their hormones, reverse chronic inflammation, and get into remission from autoimmunity.
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!
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.
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!
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.
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
Glenn,
I can’t give personal medical advice here. Please discuss with your medical provider.
Best,
Laura
Shouldn’t the “goal” stools be three and four, not four and five?
Really the goal is 4. 3 and 5 are both close, but 4 is the goal.
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?
Maryam I cannot advise you personally without knowing you. I am planning a guided detox for March though, if you’re interested.
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!
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.
“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?
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.
Please tell me how to help mold toxicity and chemicalsensitivity..I’m very toxic and skin burns and metal taste and eyes burn andbrain
This isn’t something that can be answered on a website. You need to work with a practitioner who is skilled with these issues.
Bristol Chart link not working :/
Fixed, thank you!
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.
Honestly for this I would cut out the caffeine.
Do you ever work with people i the UK?
Yes, I do Sarah.
Great information, thank you for putting this together! But, your link to part 2 seems to be broken.
Thank you! Hm, the link is working on our end. Try again?
Nope. Still getting a 404. When I try from either link (top or bottom). Not sure why.
This is a great explanation of what a liver detox is broken down into the phases, thank you. Just to let you know that the follow on post says the page is no longer found:
https://www.parishealingarts.com/functional-medicine-cleanse-detox/
Thank you!
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.
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.
Does schizandra take you through all 3 detox phases?
Thanks
Not that I know of, but if you research it and find otherwise please report back!
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.
There is inaccurate information in this article. Milk Thistle does not activate Phase 1. It inhibits Phase 1 and induces Phase 2.
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
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! 😁
I am happy to work with you on this, but this is a 1:1 project not suitable for website comments. Hope you understand!
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?
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.
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😊
Thanks for stopping by and for the tips!
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.
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
Yes we do work with patients one on one, in the U.S.