You’ve finally made it to the last part of the three-part blog series! Last, but not least, we have the detoxification system, which focuses on the body’s main built-in detox organ, the liver. In case you missed it, in part 1 and part 2 of the three-part blog series, we covered the neuroendocrine and digestive systems. All 3 systems work together to create your foundational wellness. If one system is affected, you will most likely have symptoms in the other since they are all interrelated. 

Healing starts with addressing neuroendocrine and hormone health to ensure you are feeling balanced and are not causing more issues. Unbalanced cortisol, unregulated nervous system, thyroid issues, and female cyclic hormones affect everything, so it’s important to address this first when starting the healing protocol. 

Next, in the healing protocol we address the gastrointestinal (GI) system. An inflamed and leaky gut needs to be corrected before we detox since some toxins are eliminated through the GI tract. Furthermore, an inflamed gut causes endogenous toxins that add stress to the liver. If we do not eliminate these endogenous toxins, the liver is still going to be overwhelmed and unable to properly detox. Sometimes, reducing the toxin load from an inflamed gut is all the liver needs to heal and properly detox, leading to a reduction of symptoms even without doing a full detox protocol! As you can see, this systematic approach allows you to heal in a way that sets you up for long-term healing, starting upstream and working your way down. 

As we focus on the third and final major body system in this blog series, keep in mind that they all work together for your overall foundational health. 

Let’s Dive into the Third Stage of Healing! What is Detoxification?

The term detoxification, or appropriately termed biotransformation, refers to the body’s natural process of eliminating harmful toxins from the body. Today’s world is creating a toxin overload, whether that be heavy metals or chemicals in the air, water, and ingredients in everyday household and personal hygiene items. Also, the body creates harmful cells, and byproducts of body functions can also be considered toxins. Either way, it is vital for health and longevity to be to efficiently remove toxins from the body. Keep reading to find out just how you can eliminate unwanted toxins in your body.  

The liver is the main organ where detoxification takes place. It is responsible for filtering out toxic material from the blood as it passes through. Every toxin must be neutralized and excreted from the body. When the liver is overworked or overloaded, it can easily become “clogged”. This leads to toxin buildup, causing the harmful particles to be recirculated into the bloodstream. This recirculation of toxic material causes oxidative stress on the body as well as an overactive immune response, such as rashes, inflammation, etc. 

Examples of Toxins:

• Dietary toxins: ultra-processed diets, alcohol, caffeine, refined sugar, harmful artificial sweeteners
• Poor quality herbs and supplements
• Medications 
• Tobacco and other drugs
• Hormones and antibiotics found in animal meat
• Preservatives, pesticides, and dyes 
• Heavy metals: dental fillings, water pipes, cookware, cigarettes
• Everyday products: lotions, soap, shampoo, makeup
• Internal toxins: carbon dioxide, ammonia, bilirubin
• Free radicals 
• Bacterial overload from gut dysbiosis

Long story short, toxins are all around us! Since it is inevitable to avoid toxins, it is crucial that detox pathways are at prime functioning status to strengthen our ability to safely remove toxins. Detoxification is a complex process so bear with me as we break it down. Let’s dive into the 3 phases of detoxification!

Phase 1 Liver Detox: Cytochrome P450

The goal of detoxification is to take fat-soluble toxins and turn them into water-soluble molecules that can be excreted through urine, feces, or sweat. The products from phase 1 liver detox move into phase 2 to be inactivated and prepared for excretion.

Cytochrome P450 Pathway

In the first phase of phase detoxification, toxins in the blood push enzymes in the liver into action. These enzymes work together to create the Cytochrome P450 (or CYP 450) system. CYP 450 reacts with harmful substances to generate free radicals, such as superoxide, that are carried into phase two and eliminated from the body.

First, superoxide is created through a series of reactions such as oxidation, reduction, hydrolysis, hydration, and dehalogenation. Then, even more free radicals are created in the next enzymatic step utilizing B vitamins, glutathione, branched-chain amino acids, flavonoids, and phospholipids in the process. Thus, an optimal diet rich in these nutrients plays a huge role in the function of the CYP 450 enzyme within. 

Studies have found that a balanced detoxification system is improved by a diet rich in cruciferous vegetables, berries, spices, and high-quality protein such as organic meat,  fish, eggs, and plant-based foods that provide essential amino acids. Especially for those consuming plant-based diets, it is important to work with a functional medicine dietitian to ensure you are eating high-quality products as a lot of plant-based alternatives are highly processed and can contain ingredients that are processed as toxins.

Some people have genetic polymorphisms that alter the CYP 450 pathway, causing detox pathways to be blocked. Functional nutrition lab testing will help identify these genetic differences, which usually require temporary high doses of certain nutrients to help the body detox properly.

Managing Free Radical Intermediates After Liver Detox Phase 1

The cytochrome P450 pathway creates toxic free radicals that are moved onto phase two to be eliminated. Antioxidants help detoxification by neutralizing these free radicals. Free radicals are unstable, reactive molecules that cause oxidative stress and damage tissues.  

Antioxidants include vitamin A, vitamin E, vitamin C, glutathione, coenzyme Q10, thiols, flavonoids, silymarin, pycnogenol, polyphenols, zinc, copper, manganese, selenium, beta-carotene, zeaxanthin, and lutein. Consuming plenty of antioxidants through whole foods and high-quality supplements recommended by a functional medicine dietitian can help reduce toxin load and prevent oxidative stress.

I know seeing this long list of nutrients can feel overwhelming and daunting. It is important to emphasize the goal is always to get as many nutrients and vitamins through whole foods in the diet. Supplements are exactly that: to supplement any deficiencies in your diet or any deficiencies you may have. Eating a well-rounded diet with whole foods paired with the right labs will show us what needs you may have in the form of supplementation. 

Liver Detox Phase 2: Excreting Toxins from the Body

As we discussed earlier, the active metabolites created in the first phase undergo additional reactions in the second phase to become inactive and more water-soluble. Becoming water soluble allows for molecules to be mixed in with urine, feces, and sweat so that they can be excreted from the body. 

Phase II includes complex reaction cycles, such as glucuronidation, transsulfuration, glutathione conjugation, acetylation, amino acid conjugation, and methylation. These reactions rely on each other and require amino acids such as glycine, glutamine, cystine, taurine, N-Acetylcysteine, and methionine to create fully water-soluble molecules that are ready to be excreted. I know this all sounds overwhelming, so let’s break it down!

Methylation: 

Methylation is the process of transferring a methyl group (one carbon atom and 3 hydrogen atoms) from one molecule to another, changing its shape and polarity. This is important in detoxification because it turns neutralized toxins into water-soluble molecules so that they can be excreted from the body. Without proper methylation, toxins can continue to build up. 

Methylation metabolizes heavy metals, phenols, catecholamines (such as dopamine and epinephrine), estrogen, and carcinogens such as cigarette smoke, pesticides, diesel exhaust, and grilled meat/fish. Functional lab markers that may indicate impaired methylation include high homocysteine, formiminoglutamate (folate levels), methylmalonic acid (B12 level), xanthurenate (B6 levels), choline, amino acids (such as methionine, glycine, cysteine, serine) and genetic SNPs that some of require these nutrients as cofactors.

Products from methylation feed into the transsulfuration cycle to create glutathione, the master antioxidant. 

Transsulfuration Cycle 

Transsulfuration is tightly connected with methylation since the products of methylation often enter the transsulfuration cycle. Transsulfuration is the process of creating glutathione by combining amino acids, glycine, and cysteine. Glutathione, the master antioxidant, can then be used in other conjugation reactions to make toxins water soluble. Functional lab markers that may indicate impaired transsulfuration include serum glutathione, xanthurenate (B6 levels), and amino acids such as glycine, serine, cysteine, taurine, methionine, pyroglutamate, cystathionine. 

Glutathione Conjugation: The Master Antioxidant Comes into Play

Glutathione conjugation involves glutathione reacting with toxic molecules to become glutathione conjugates and easily excreted through the urine. Glutathione conjugation is the most important reaction for eliminating many environmental toxins and common carcinogens. 

Functional lab markers that address glutathione conjugation include serum glutathione, benzoate, hippurate, pyroglutamate, glycine, taurine, and specific genetic SNPs (mutations/alterations) that may interfere with this reaction. Nutrients needed to support glutathione conjugation include cysteine, glycine, and glutamate and sulfur-containing foods such as cruciferous vegetables, beef, fish, and poultry.

Glucuronidation: 

Glucuronidation involves making active toxins metabolites water soluble by reacting with glucuronic acid. Endogenous metabolites, meaning things that are produced inside the body on its own, such as used red blood cells, estrogens, and mineralocorticoids, as well as carcinogens and drugs interact with UGT enzymes, which are a class of drug-metabolizing enzymes that catalyze this whole reaction, to become glucuronidated molecules that can be excreted usually through bile or urine. 

It is said that 40-70% of all medications, such as Tylenol, NSAIDs, Lexapro, and codeine, are metabolized by glucuronidation. Beta-glucuronidase in GI Effects Stool Profiles are often used to determine glucuronidation status. Beta-glucuronidase is a vital enzyme to look at as it can be high either from lipopolysaccharides from a leaky gut or from decreased estrogen clearance also known as “dirty estrogen” which can point to other estrogen clearance issues, so it is important to address the root cause. Nutrients that help glucuronidation include alpha and beta carotene, quercetin, curcumin, and magnesium.

Acetylation:

Acetylation is a common reaction in the body that involves adding an acetyl CoA molecule to make something more water-soluble. This reaction is done by the enzyme N-alpha-acetyltransferase (NAT), an important enzyme in the detoxification process. Caffeine, histamines, and benzodiazepines are all metabolized using acetylation. Nutrients that are important for acetylation are B vitamins and vitamin C, such as citrus. 

Amino Acid Conjugation:

There are many different types of amino acid conjugations that work in detoxification to make toxic material water soluble. Amino acid conjugation generally metabolizes medications (such as aspirin and Alka Seltzer), salicylates such as food dyes, naturally occurring compounds in fresh food, and salicylic acid in cosmetic products. Adequate intake of amino acids such as glycine, taurine, and glutamine is required for this process. Collagen protein, turkey, soy, seaweed, eggs, beef, sunflower seeds, lentils, fish, and amaranth are all examples of foods high in these amino acids.

Urea Cycle:

Another important detox reaction is the urea cycle. Urea production eliminates ammonia and excess nitrogen from unused protein. A buildup of ammonia due to a clogged liver is extremely toxic to the brain leading to cognitive function decline initially with brain fog and downstream can even lead to psychosis and coma. Functional lab testing to see marker levels like organic acid orotate and amino acid arginine can help your functional medicine dietitian see if your urea cycle is functioning optimally. 

Phase 3: Elimination

Two down, one to go. Now that we’ve talked about how the body converts and processes toxins, let’s talk about how the body gets rid of them.

The neutralized, water-soluble non-toxic products are excreted from the body through urine, stool, bile, or sweat. Since the gastrointestinal system comes into play in this phase, it is important to ensure optimal GI health. This is why we start with work on gut health before detoxification. Furthermore, an inflamed and leaky gut creates endogenous toxins that need to be detoxified, adding stress to the liver. If we do not eliminate those endogenous toxins, the liver is still going to be overwhelmed and unable to properly detox. 

As you can also see, certain nutrients, such as sulfur-containing foods, are crucial for proper detox and liver health. These foods are often excluded from gut-healing diets, such as low FODMAP and low histamine diets. If you cannot handle foods like cruciferous veggies or have a bile acid deficiency, you may also see detox issues. Our goal is to have a strong enough GI system so that you can tolerate and include liver-loving foods such as broccoli, cabbage, and onion!

Addressing Your Own Detoxification

 

Signs You Have Poor Detoxification

• Weight gain
• Fatigue
• Sleep disturbances
• Hormone imbalances
• Anxiety
• Depression
• Insomnia
• Irritable Bowel Syndrome
• Allergies
• Headaches (including migraines)
• Muscle pain
• Addictions

Functional Diagnostic Nutrition Lab Testing

The first step to optimize your health is working with a functional medicine dietitian to assess your body’s detoxification status. First, we will focus on your neuroendocrine and gastrointestinal system function as we discussed in parts 1 and 2, but ultimately we will assess all 3 at the same time as they function together. Functional diagnostic nutrition lab testing and interpreted by a functional medicine dietitan to determine your liver health, essential nutrient levels, toxin load, and gastrointestinal health. These tests include the ION Profile with Amino Acids test, Organic acids test, GI Effects Stool Test, Nutritional gene testing, etc.

Pairing a functional gut clinic breath test and a comprehensive stool test with your detox markers from an ION Profile Amino Acids test will investigate areas of gut functioning such as small intestinal bacterial overgrowth and motility issues, as well as identify a need for bile acid support, enzymes, dysbiosis, parasite infections, fungal overgrowth, and other opportunistic bacterial overgrowth. The ION panel will also help us look for damaged mitochondria due to damaged phospholipid cell membrane integrity allowing toxins to enter the cell. Toxins inside the cell can damage mitochondria leading to stress and eventually cell death. This process of oxidative stress on the cell where the mitochondria sense cell stress is called the “cell danger response”, but more on that in a future blog.

Toxins Tested For in the ION Test

Heavy Metals: 

• Arsenic (cigarettes, cosmetics)
• Cadmium (shellfish, leafy veggies, cigarette smoke)
• Lead (soil, gasoline, fossil fuels)
• Mercury (fluorescent light bulbs, combustion)

Additional specialty lab testing for heavy metals may include:

• Aluminum (food additives, water, air, soil)
• Antimony (environment, air, soil, water)
• Barium (paint, bricks, glass, and rubber)
• Bismuth (electronics, batteries, crystal ware)
• Chromium (tobacco smoke, dyes and pigments)
• Tin (found in food packaging)

Strategies to Reduce Your Toxin Load

Now that we know what detoxification is and how to improve your detoxification pathways, the next step is to reduce your toxin load. In combination with strengthening your detox pathways, avoiding toxins is the best way to keep your liver healthy. But how do we reduce our toxin load in a toxin-filled world? 

Lifestyle Changes to Reduce Toxin Exposure

• Choose organic foods without pesticides, dyes, added sugar, inflammatory ingredients, antibiotics, or hormones
• Choose nontoxic cookware and dishware
• Use an air and water filter
• Mold and biotoxins
• Use organic and nontoxic beauty products, lotions, soap, hygiene/feminine products, etc.
• Reduce excess stress
• Be aware of radiation through wifi, X-rays, CT scans, 5G towers, etc
• Unplug the Wi-Fi box when not in use
• Ensure metal pipes in your home are nontoxic 
• Optimize health to reduce unnecessary medications
• Reduce smoking and drinking

I want to make a very important note here, you are NOT expected to make these changes overnight so don’t set that expectation or beat yourself up if you feel “behind”. This is a lifestyle change that takes many years. A lot of these things may even be out of your control right now. It is not about changing your entire life overnight but rather, taking small steps when and where you can gradually. 

Summary of Nutrients for Detoxification

As we have discussed before, there are also nutrients and foods that play a role in strengthening our body’s natural detoxification pathways. Different phases of detoxification are strengthened by different nutrients. Let’s go over what nutrients are most important and in which phases of detoxification.

Phase 1 Detox Foods: B vitamins, glutathione, branched-chain amino acids, flavonoids, and phospholipids

• B vitamins: peas, bananas, oranges, nuts, whole grains, liver
• Glutathione: dietary protein, broccoli, Brussels sprouts, cauliflower, kale, garlic, onions
• BCAA: beef, poultry, fish, eggs, dairy, nuts/seeds, quinoa
• Flavonoids: berries, cabbage, onions, kale, parsley, dark chocolate, oranges
• Phospholipids: eggs, liver, soybeans, peanuts
• Antioxidants: broccoli, spinach, carrots, potatoes, artichokes, cabbage, asparagus, avocados, radish, sweet potatoes, berries

Phase II Detox Foods: 

Glucuronidation:

-Alpha/beta-carotene: pumpkin, carrots, squash, sweet potato, red pepper, spinach

-Quercetin: apples, onions, kale, cherries, EVOO

-Chrysin/luteolin: broccoli, chili peppers, celery

-D-glucarate: apples, grapefruit, alfalfa, broccoli, Brussels sprouts, tomatoes 

-Citrus: grapefruit, oranges, tangerines

-Magnesium: halibut, almonds, cashews, soybeans, spinach, oatmeal, potatoes

Sulfation:

-Sulfur: chicken, haddock, sardine, cod, beef, dried peaches, egg, turkey, almonds, spinach, onion, cabbage

Methylation:

-Folic acid: liver, chicken, giblets, egg yolk, dried beans, lentils, split peas, soybeans, almonds, potatoes/sweet potatoes, spinach

-B12: liver, beef, chicken, fish, eggs, salmon

-B6: tuna, turkey, beef, chicken, salmon, sweet potatoes, potatoes, spinach, banana

-Methionine: egg whites, sesame seeds, soy, chicken, tuna, beef, chickpeas

Glutathione Support:

-Cysteine: duck, egg yolk, whey protein, red pepper, garlic, onion, broccoli, brussels sprouts

Phase III Detox Foods: 

-Fiber: raspberries, pear, apple, banana, peas, broccoli, Brussels sprouts, potatoes, cauliflower, whole grains, oatmeal, brown rice, lentils

-Sulfur: chicken, haddock, sardine, cod, beef, dried peaches, egg, turkey, almonds, spinach, onion, cabbage

You may have seen different trends online for different juice cleanses and liver cleanses. As we can see now, those are ineffective and typically hoaxes that use laxative properties to mimic a cleanse. We don’t need to cleanse our bodies because our livers are our natural detoxification organ.  More importantly, it is crucial to support our bodies’ natural detoxification pathways by identifying any areas for improvement or where we may be lacking and developing a plan to optimize our detoxification systems.

So, Where Do I Go From Here? 

While this all may seem overwhelming on your own, working with a registered dietitian is the best place to start to find the root of your symptoms! Schedule a free 15-minute nutrition strategy call, and we can discuss the best approach for you! This is the very first step before beginning the initial “Comprehensive Root Cause Analysis” appointment. Working with a skilled Kalish Method Practitioner, detoxification specialist, and functional medicine dietitian is essential in developing an individualized plan for long-lasting success!