The liver, the body's second largest organ after the skin, plays a key role in detoxification, being designed to protect humans from poisoning (Kalra & Tuma, 2018; Weaver, 2023). This busy organ, regulates blood sugar levels, uses bile to digest fats, creates blood clotting factors and carrier proteins, and serves as storage for B12, iron, copper, and fat-soluble vitamins A, D, E, and K). It neatly turns triglycerides into cholesterol and breaks them down when needed for energy (Axe, 2023; Lauren, 2017).
Metabolism and detoxification of xenobiotics (foreign substances) are critical liver functions. The liver uses lipid busting enzymes (lysosomes) to breakdown substances, but metabolism and detoxification primarily occur through biotransformation (Kalra & Tuma, 2018).
The liver’s process of detoxifying is complex, but it changes lipid soluble materials into water soluble ones to be eliminated (Weaver, 2023). The transformation of toxic ingredients fulfills the liver’s primary function: to maintain overall health through 2 detoxification phases. By changing threatening substances into less toxic water-soluble forms, they aren’t assimilated into fatty tissues and are readily excreted. Occasionally, the end products of phase 2 are more toxic and must be reprocessed to be broken down further for elimination through the urine, feces, or sweat (Dm, 1991; Weaver, 2023).
The liver’s protective abilities transform functional groups stuck to molecules and medications (xenobiotics), using enzymes through catalysis, oxidation, reduction, and hydrolysis and/or conjugation (Dm, 1991; Hodges & Minich, 2015). The process of elimination is phase 3, which uses six different pathways.
Phase I liver detoxification is the first line of defense against toxins, consisting of the cytochrome P450 family enzyme group. They specifically neutralize substances like caffeine and alcohol. Byproducts of Phase I detoxification may still pose a threat to the body. Phase II’s detoxification role ensures toxins do not accumulate (Jambhulkar, 2019). Phase 1 will briefly create free radicals; but the liver’s antioxidant supply can generally handle them. However, if dietary antioxidants are low or if toxic exposure is sustained, toxins become hazardous (Lauren, 2017).
Minimal physical activity, aging, or heavy metal toxicity causes Phase 1 to become sluggish. Vitamin and mineral deficiency also cause sluggishness if cofactors (vitamins B2, B3, magnesium, and iron) are depleted as they assist with enzymatic function. If phase 1 is quicker than phase 2, antioxidants can't manage the excess free radicals, causing oxidative injury and chemical sensitivity (Lauren, 2017).
Known as conjugation, Phase II liver detoxification, neutralizes byproducts of Phase I by creating water-soluble toxins that can be excreted from the body. The key molecules assisting in this process include glutathione, sulphate, and glycine (Lauren, 2017; Liver Detoxification Pathways, n.d.). Important food constituents needed here include amino acids from protein rich foods and sulfuric compounds from broccoli, Brussel sprouts, cabbage, cauliflower, egg yolks, garlic, kale, onions, and shallots, (Weaver, 2023).
If the byproducts can't be neutralized, they will continue to accumulate within the system. If the liver is functioning poorly, those substances will be challenging to excrete and end up accumulating in the liver and fatty tissues damaging DNA and proteins (Jambhulkar, 2019).
The final phase of physiologic detoxification is phase III, involving the movement of toxins out of liver, kidney, and intestinal cells and into the urine and feces for elimination. Bowel movements and filtration of toxins is the most critical phase of detoxification overall (Shade, 2022).
When a person experiences nutrient depletion the rate at which their liver enzymes can be created and available to neutralize toxic substances is affected (Lauren, 2017). If the individual has built up adequate nutrient levels in the tissues and blood, the liver capably produces enzymes in phase two, and at a simultaneous rate breaking down these substances into less toxic water-soluble products. These phases take nutrients that support detoxification and assist the excretion of these once toxic substances from the body (Jambhulkar, 2019).
Our diet is important in providing essential nutrients to the liver for efficient breakdown of toxic materials during phase 1 and phase 2 of detoxification. Vitamin C, iron, and Glutathione are key nutrients required in phase 1 detoxification (Axe, 2023; Lauren, 2017). Although many foods contain glutathione, they are often neutralized by digestive enzymes before being utilized. However, eating foods that contain glutathione precursors are known to assist with glutathione production and availability within the body (Liver Detoxification Pathways, n.d.).
Hodges & Minich (2015) elaborate that specific foods can positively balance or upregulate metabolic pathways that assist with toxin biotransformation and resulting elimination. Key nutrients for Phase 1 include B vitamins and iron. Optimal antioxidant foods and supplements are needed in this phase as they limit the harm of this partially altered product (Lauren, 2017; Weaver, 2023). Berries, cruciferous vegetables, garlic, soy, and turmeric have been suggested as supportive whole foods for liver detoxification and are commonly prescribed functional medicine and naturopathic based treatments.
Clinical studies report exposure to toxic buildup contributes to heart disease, obesity, and type 2 diabetes. Hodges & Minich (2015) report a person’s environment and diet are key determinants of developing chronic disease. These influences also significantly affect future generations related to transgenerational epigenetic inheritance. Research recommends therapeutic approaches occur with an experienced licensed medical prescriber/provider as many nutrients exert biphasic, dose-dependent effects. Everyone may be influenced by their unique genetic polymorphisms that can alter or limit treatment results (Hodges & Minich, 2015).
Food-based nutrients can strongly affect detoxification pathways; everyone needs to try consuming a mixed complex whole-foods diet. This is essential as foods serve as “bifunctional modulators,” being able to prevent or induce dose specific responses within detoxification enzyme activities (Hodges & Minich, 2015; Lauren, 2017). Because some substances are transformed into more toxic byproducts via specific enzymes, the varied diet synergistically can decrease toxicity (Dm, 1991; Weaver, 2023).
Consuming unprocessed foods rich in amino acids and sulfur assists with detoxification within phase 2. When a person ingests low amounts of these constituents, liver enzymes can’t keep up and become sluggish. This leads to inefficient breakdown of the water-soluble substance which is expected to be excreted through the urine, feces, or sweat (Lauren, 2017).
High stress, inadequate rest, low physical activity, and a highly processed diet causes a poorly functioning liver, leading to gastrointestinal microbiome imbalance. Unhealthy bacteria proliferate decreasing healthy functioning bacteria. This results in frequent illness and inflammation related to toxic accumulation. Inadequately reduced byproducts and poor excretion, causes metabolic derangement. Symptoms include brain fog, difficulty losing weight, elevated triglycerides and LDL, frequent illness, higher fasting blood glucose, hormone imbalance, low energy, obesity, and poor sleep (Lauren, 2017).
Taking glutathione as a food source or nutrient may not be helpful as it is poorly absorbed and neutralized by digestive enzymes. However, consuming a diet comprised of key building blocks greatly contributes to naturally building glutathione within the body. Glutathione precursors are found in cruciferous vegetables, alpha-lipoic acid, cysteine, milk thistle, selenium, and vitamin E. Vitamin C aids liver detoxification pathways by protecting detoxification enzymes created in phase I and phase II pathways from oxidative damage (Liver Detoxification Pathways, n.d.).
Phase 2: Six Detoxification Pathways
Sulfation | Adds a sulfate group (SO2-4) including endotoxic bacteria, Tylenol, Bisphenol A, and xenoestrogens. Primary Pathway for eliminating adrenal, sex, and thyroid hormones along with neurotransmitters. Sulfur derived from sulfur containing Amino acids (Methionine & Cysteine) Requires Molybdenum, B12, folate, magnesium, B6, SAMe, and taurine) Caution in individuals w/sulfur sensitivity. |
Glucuronidation | Comes from glucose. This is added to meds like Aspirin, benzoate food additives, preservatives, and is added onto steroid hormones. Requires magnesium, B vitamins, and calcium D-glucarate (assists in estrogen elimination). |
Glutathione Transferase | Is the major antioxidant in managing free radicals in phase 1. Is also a side group added to phase 2. Overcomes heavy metals, solvents, pesticides, and PAHs. Needs these key building blocks: cysteine, glutamic acid, and glycine. Can be regenerated using antioxidants like Vitamin C and Alpha lipoic acid (ALA). |
Acetylation | In glycolysis, is an omnipresent biochemical body process. Produces the end product pyruvate which changes to Acetyl CoA. Above is accomplished via pyruvate oxidation in mitochondria. Becomes a phase 2 side group. Acetyl CoA adheres to histamine, serotonin, salicylic acid, tobacco, and car exhaust. Needs Molybdenum, iron, vitamins B1, B2, B3, B5, and Vitamin C. |
Amino Acid Conjugation | Involved Amino Acids include glycine, taurine, glutamine, arginine, and ornithine. Eliminates the solvent toluene, the food preservative benzoate, and other environmental chemicals. Requires the body to be alkaline, not acidic. Requires Amino acids derived from eating plenty of protein. Needs cofactors folic acid, manganese, and vitamins B2 and B6. |
Methylation | Involves adding a methyl group (-CH3) to several types of hormones, neurotransmitters, and toxins to make them water soluble. The amines (serotonin, melatonin, histamine, tyramine, and catecholamines) go through this pathway. Catecholamines include dopamine, norepinephrine, and epinephrine). Phenols use this path (salicylic acid (aspirin), cannabinoids, estradiol, and BPA) . Genetic mutations within the methylation cycle contribute to mental/emotional imbalance, migraines, hormone imbalance (especially estrogen dominance), and toxicity. Main methyl donor group is derived from the amino acid methionine. Methionine is converted into SAMe. SAMe donates a methyl and if not recycled back into methionine, gets broken down into cysteine where it converts to a sulfate, or changed into glutathione, or an antioxidant for use in phase 1. Requires B12, folic acid, magnesium, choline, methionine, betaine, and molybdenum. |
Lauren, D. (2017, September 30). How the Liver Detoxifies | Dr. Lauren Deville, Naturopathic Doctor - Tucson, AZ. Dr. Lauren Deville. https://www.drlaurendeville.com/liver-detoxifies/ |
Liver Detox in a Nutshell
References
Axe, J. (2023). Detox Your Liver: Try My 6-Step Liver Cleanse. Dr. Axe. https://draxe.com/nutrition/liver-cleanse/
Dm, G. (1991). Detoxification Pathways in the Liver. Journal of Inherited Metabolic Disease. https://pubmed.ncbi.nlm.nih.gov/1749210/
Hodges, R. E., and Minich, D. M. (2015). Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: a Scientific Review with Clinical Application. Journal of Nutrition and Metabolism, 2015(760689), 1–23.
Kalra, A., & Tuma, F. (2018, December 18). Physiology, Liver. National Library of Medicine; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK535438/
Kawaduji Jambhulkar, R. (2019, May 18.). Biotransformation, Detoxification, Metabolism of XenobioticsWww.youtube.com. Retrieved February 11, 2024, from https://www.youtube.com/watch?v=Y8dguLjPXaY
Lauren, D. (2017, September 30). How the Liver Detoxifies | Dr. Lauren Deville, Naturopathic Doctor - Tucson, AZ. Dr. Lauren Deville. https://www.drlaurendeville.com/liver-detoxifies/
Liver Detoxification Pathways. (n.d.). Ask the Scientists. https://askthescientists.com/qa/liver-detoxification-pathways/
Shade, S (2022, November 28). WHAT EXACTLY IS PHASE III OF DETOXIFICATION? – DR. CHRIS SHADE. Www.drchrisshade.com. Retrieved March 3, 2024, from https://www.drchrisshade.com/blog/what-exactly-is-phase-iii-of-detoxification/
Weaver, L (2023, March 27,). Understanding detoxification: how the liver works. Dr Libby. https://www.drlibby.com/health-wellbeing/understanding-detoxification-how-the-liver-works/