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.
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.