Detoxification and Weight Management
Liver detoxification is a three-phase process required to remove toxins from the body. Phases I and II of liver detoxification mobilize exogenous and endogenous toxicants, such as environmental toxins, xenobiotics, heavy metals, medications, and metabolic waste, to undergo biotransformation. Phase III, also known as the “elimination” phase, ensures the effective excretion of toxins to attenuate potential recirculation. Hence, regular bowel movements are crucial for successful detoxification; constipation hinders toxin removal, while diarrhea can cause dehydration and electrolyte imbalances. These three phases must function optimally and be balanced with healthy lifestyle habits and a myriad of supportive nutrients.
Research suggests that the exposure, accumulation, and removal of toxins may be associated with chronic diseases like cardiovascular disease and type 2 diabetes. Moreover, the accumulation of toxic trace elements in the body is associated with metabolic disorders linked to being overweight or obese. Anecdotal reports suggest that detoxification may support overall weight management by promoting toxin removal. Toxins stored in adipose (fat) cells are released during weight loss, emphasizing the need for healthy liver detox and elimination to help mitigate toxin recirculation.
While the liver works to detoxify the body every day, 'detox' plans are short-term and must be well-managed to promote metabolic detoxification or biotransformation and (equally as important) to avoid causing harm. A holistic detox plan should help ensure minimum daily energy requirements and nutritional adequacy. An inadequate diet (low-calorie, low-protein, low-fiber, low-vitamin, or low-mineral) may increase stress, elevate cortisol, and stimulate appetite, which may make losing weight challenging. Studies in animals and humans indicate that nutrient deficiencies can hinder enzymatic reactions in detoxification. Furthermore, short-term energy-restricted diets may lead to short-term weight loss, but their impact on long-term weight management is unclear.
A proper diet, adequate sleep, and appropriate amounts of physical activity are crucial for optimal detoxification function and weight management. Nutritional strategies should favor a high-quality, mixed, varied whole foods diet complemented with supplements to balance and support detoxification pathways.
Nutrients for Phase I Liver Detoxification
Various macronutrients and micronutrients are required for proper phase I detoxification performed by cytochrome P450 enzymes. Nutritional cofactors supporting phase I detoxification include riboflavin, niacin, vitamin B6, folate, vitamin B12, glutathione, flavonoids, phospholipids, and branched-chain amino acids.
Resveratrol, found in grapes, wine, peanuts, and soy, exhibits potential benefits for phase I detoxification. Apiaceous vegetables like carrots, celery, parsley, and parsnips, and quercetin in apples, blueberries, and yellow onions may also positively influence this phase. In vivo studies suggest that green tea, black tea, curcumin, garlic, fish oil, astaxanthin, rosemary, chamomile, peppermint, and dandelion may favorably impact phase I detoxification.
Certain foods may upregulate or inhibit P450 enzyme activity, working to balance phase I to phase II metabolic pathways favorably. For instance, grapefruit is a well-known P450 enzyme inhibitor. Depending on the serving size, many foods may both upregulate or inhibit phase I enzymes and are commonly referred to as bifunctional modulators. The most well-known foods that directly induce P450 enzymes with antioxidant properties and help with the successful removal of toxins through their fiber content are cruciferous vegetables, such as broccoli, kale, bok choy, watercress, and cauliflower.
Biotransformation in phase I creates reactive oxygen species (ROS) by-products. Optimal antioxidant status is crucial to quench ROS and attenuate oxidative stress. Examples of food sources or nutrients that demonstrate potent antioxidant properties are glutathione, carotenes, ascorbic acid, vitamin E, selenium, copper, zinc, manganese, bioflavonoids, milk thistle, N-acetyl-L-cysteine, green tea, and various polyphenols.
Nutrients for Phase II Liver Detoxification
After phase I detoxification, toxins are deemed an “intermediate metabolite” that must be further metabolized by phase II detoxification. Intermediate metabolites are often more toxic than their parent compound. If phase II detoxification pathways are inefficient, the intermediate metabolites may cause cellular damage by binding with various proteins, lipids, or nucleic acids in the cell. Phase II detoxification increases the water-solubility of the toxic metabolites, leading to enhanced and successful excretion in stool and urine.
Phase II pathways include glucuronidation, sulfation, glutathione conjugation, acetylation, amino acid conjugation, and methylation. Nutrients may support phase II detoxification in one or two ways. Firstly, the nutrient may beneficially induce or activate the phase II pathways. Secondly, they may be a dietary source of necessary phase II compounds to promote function and efficiency. For example, nutrients or food sources that induce the glucuronidation pathway are cruciferous vegetables, resveratrol (e.g., grapes, wine, peanuts, soy), citrus, dandelion, rooibos tea, rosemary, soy, ellagic acid (e.g., berries, pomegranate, walnuts), ferulic acid (e.g., whole grains, asparagus, olives), curcumin, and astaxanthin. Dietary sources of D-glucaric acid necessary for glucuronidation are legumes, fruits, and vegetables (e.g., oranges, spinach, apples, broccoli, cauliflower, cucumber, lettuce, celery, green pepper, and tomato).
High-quality, bioavailable protein is necessary for the phase II amino acid conjugation pathway, requiring the amino acids glycine, taurine, glutamine, ornithine, and arginine. The glutathione conjugation pathway requires glutathione precursors (cysteine, glutamic acid, and glycine) and the supportive nutrients of N-acetyl cysteine, vitamin B6, magnesium, selenium, folate, and alpha-lipoic acid. The sulfation pathway requires sulfur-rich foods, such as cruciferous vegetables, allium plants (e.g., onions, leeks), poultry, and seafood. The methylation pathway requires methionine, vitamin B12, vitamin B6, betaine, folate, and magnesium. Any of these nutrients may come from dietary sources or through supplementation.
Supporting Phase III “Elimination”
Phase I and II transform toxins into water-soluble products that can now be eliminated. The elimination of toxins requires the aid of the kidneys, gallbladder, and intestines through the proper regulation and frequency of urination and bowel movements.
Dietary fibers support the body’s main detoxification organs, the liver and kidneys, by promoting healthy bowel movements and intestinal motility. Fiber may also support detoxification through its systemic benefits in supporting healthy microbial environments, gut barrier function, healthy inflammatory and immune responses, and by potentially activating detoxifying enzymes in the liver, such as cytochrome P450 enzymes in phase I detoxification.
Activated charcoal and zeolite help promote toxin elimination through adsorption and ion exchange processes. Binders like clinoptilolite may promote the body’s response to certain toxins and heavy metals, supporting intestinal barrier integrity and liver function. Lastly, chlorella promotes cellular health and detoxification pathways by interfering with toxin absorption and helping to mitigate the absorption of harmful substances.
Supporting regular bowel movements to promote proper elimination and detoxification should be individualized based on a patient’s dietary and lifestyle needs and access. For instance, magnesium citrate may support those with occasional constipation. Detoxifying through sweating may be encouraged through sauna use or exercise. Some lifestyle hacks that may help to promote regular bowel movements are Epsom salt baths or dry brushing to stimulate the lymphatic system.
Every day, the human body is exposed to hundreds of toxic substances like heavy metals, drugs (pharmaceutical or recreational), household cleaners, pollutants, and endogenous toxicants such as reactive oxygen species. A holistic plan to support liver detox and weight management considers all three detoxification phases, antioxidant status, bowel movement regularity, nutrient density, and health-promoting lifestyle techniques.
By Danielle Moyer Male, MS, CNS, LDN