Supports for Liver Detoxification

The body's ability to detoxify uses several organs such as kidneys, the liver, the skin, bowels and lymphatic system.

 THE LIVER¹

The liver involves phase 1 and phase 2 enzymes. Phase 1 enzymes are  responsible for breaking down  fat-soluble toxins. Phase 2 enzymes break down these fat soluble compounds into water soluble compounds that are safer for the body to excrete via the kidneys. Phase 1 cytochrome P450 enzymes (CYP450) bio-transform harmful substances by adding a hydroxyl, carboxyl or amino group via either oxidation, reduction or a hydrolysis reactions. Examples of CYP450 enzymes are: CYP1A/1A2, CYP2A-E. Certain phytochemical compounds can either induce the more detoxing pathways such as phase 2 reactions, or inhibit the more harmful reactions like phase 1 enzymes. After a toxin has passed through the CYP450 enzymes it can then be conjugated with a water-soluble or hydrophilic substance in phase 2 detoxification. These enzymes include adding various groups such as sulfur, glutathione, glucoronic acid, amino acids, methyl or acetyl groups.

Phase 1 toxins:

• xenobiotics (antibiotic compounds from the environment)
• steroid hormones
• pharmaceuticals

CYP1A metabolizes pro-carcinogen hormones and pharmaceuticals. In particular it also metabolizes heterocyclic aromatic amines/amides (HCAs) which are present in animal fats exposed to heat (ex. BBQ meats)

CYP1 enzymes also form clinically relevant estrogen metabolites such as 2-hydroxy and 4-hydroxy estrogens, with 4-hydroxy having implications in estrogen-dominant cancers (ex. Breast cancer, endometrial cancer)². Although these enzymes are thought of as toxin-producing and promotion of them is possibly discouraged, they still play an important role in overall toxin elimination thus a balance of phase 1 to phase 2 enzymes is encouraged.

Nutritional Phase 1 Inducers¹

Nutrient Inducers of CYP450 enzymes:

• Green tea
• Caffeic acid in coffee
• Cruciferous vegetables (Broccoli, Brussel sprouts, Cauliflower, Cabbage)
• Grapefruit juice

A clinical study found that dietary indole-3 carbinole (I3C), induces CYP1A enzymes to metabolize estrogens, making I3C from broccoli or supplement form clinically relevant for potential prevention of estrogen-related cancers. Grapefruit juice is a well known inducer of this enzyme category and thus is discouraged to use alongside many pharmaceutical drugs that are known to increase this enzyme. Although carcinogenic compounds/reactive oxygen species are created via Phase 1, their function is still relevant in order to initiate the deactivation process. It is thought that the balance of phase 1 and phase 2 is more important, promoting compounds that   induce more phase 2 activity to balance out phase 1.

Nutritional Phase 1 Reducers¹

Nutrient Reducers of Phase 1:

• Berries
• Quercetin
• Apeiaceous vegetables (carrots, parsnips, celery and parsley)

Along the lines of phase 1 inducers are certain plant compounds that can reduce the activity of the CYP450 enzymes. This is important because modern society promotes higher CYP450 or phase 1 activity, making it a clinical focus to increase foods and plant compounds that encourage phase 2 and phase 1 reduction. Examples are: berries with ellagic acid inhibiting CYP1A1 overactivity, apiaecous vegetables and quercetin for CYP1A2 activity. Apeiaceous vegetables include carrots, parsnips, celery and parsley. Low dose turmeric appears to induce phase 1, whereas higher doses may actually inhibit it. This dual relationship is seen in many plant compounds.

Nutritional Phase 2 Inducers

Nutrient Inducers of Transferases:

• Cruciferous vegetables
• Soy foods (ex. Genestein)
• Resveratrol
• Citrus foods
• Teas (rooibos, dandelion)
• Spices (Rosemary, Curcumin)

UDP Glucoronyl transferases, Sulfotransferases, Glutathione S-Transferases are the main Phase 2 liver enzymes. UDP Glucoronyl tranferases  add glucuronic acid to make the compound more water-soluble and excretable via the kidneys. This occurs in the liver and small intestine through the hepatocytes. Glucoronidation reactions are important for 40-70% of medications. Cruciferous vegetables, soy foods, resveratrol  (in red wine) and citrus foods induce these enzymes, along with rooibos, dandelion teas and rosemary, curcumin, soy and astaxanthin.

Nutrient Inducers of Glutathione:

• Cruciferous vegetables
• Allium vegetables
• Resveratrol
• Spices such as Curcumin and Rosemary
• Fish oil
• Green tea
• Citrus fruits

Glutathione is an endogenous antioxidant (occurs naturally in the body).There are many substances and compounds that promote this enzyme activity, along with restoring it. Cruciferous vegetables, allium family vegetables(garlic) and resveratrol are examples . Other studies show curcumin, fish oil, green tea and citrus as well. Herbs such as rosemary have also been shown to promote GST activity. Sulfur-containing foods also promote glutathione production, along with the amino acids cysteine and methionine. Sulfur foods are: cruciferous family, kale, spinach , allium family along with a commonly known one of beans.

Supplement/Vitamin Inducers of Glutathione:

• Vitamin B6
• Magnesium
• Folic acid
• Alpha lipoic acid
• Selenium

From a supplement and mineral perspective vitamin B6, magnesium , folic acid, alpha-lipoic acid and selenium may encourage glutathione synthesis. Vitamin B6 is a cofactor in the conversion of homocysteine into endogenous glutathione. Examples of B6-containing foods are: animal products and seafood, chickpeas/legumes, sweet potatoes and bananas. A study feeding mice a B6 and biotin deficient diet led to fatty liver disease. The same cannot be directly translated to humans, but is suggestive of how important B vitamins are for proper liver functioning.

Important Amino Acids:

Certain essential amino acids are also required for conjugation of enzymes. These amino acids are: Glycine, Taurine, Glutamine, Ornithine and Arginine. Examples of glycine from food are: turkey, pork, chicken and eggs. Vegan sources are pumpkin seeds, beans, sunflower seeds and lentils. Taurine is found in meat and fish. Cystine can be synthesized in the body from cysteine  which requires niacin, B6 and homocysteine. Glutamine can be found in animal products, spinach, parsley and cabbage. Arginine is found largely in chicken, pumpkin seeds, soybeans, butternuts, eggs, peanuts and other seeds/lentils. Overall, it seems like a combination of many of the mentioned compounds is the best approach. It also seems best to recommend a  whole foods approach as oppose to higher doses of a single supplement.

OTHER ORGANS OF DETOXIFICATION (SKIN, BOWELS AND KIDNEY)

 SKIN³

We detoxify compounds through our skin via sweat glands, and the skin, covering the whole body, is the body's largest organ of elimination. The skin can degrade, inactivate, and eliminate various xenobiotics and toxic compounds through its reactive oxygen species scavenging system. Beneath the skin is the lymphatic system. Unlike the blood vascular system, the lymphatic system requires movement from respiratory and skeletal muscles for movement⁴. Certain herbs, known as lymphatics, can activate the lymphatic system by creating a pumping action. Lymphatics work as “blood purifiers” that move lymph and increase lymphatic flow moving fluid and protein away from areas of inflammation. These herbs also have laxative and cholagogue (stimulates bile duct contraction) effects which will further help with detoxification.  Rumex crispus (Yellow dock), Iris versicolor (Blue Flag) and Galium aparine (Cleavers) are all examples of herbal lymphatics⁵. Other lifestyle strategies such as movement/exercise, deep breathing, hydrotherapy, massage and dry brushing are also good supports which stimulate the muscles involved in lymphatic flow.

BOWELS

Another important organ of detoxification are the intestines, particularly the large intestine/colon. According to research, intestinal immunity, microbial  eradication and toxin eradication all occur in the colon⁶.Constipation from various reasons, such a lack of fiber, medication side-effects or improper microflora can allow this toxin reabsorption. Inflammation, whether from an inflammatory disorder/condition such as Inflammatory bowel disease (Crohn's, Celiac Disease, Ulcerative Colitis), food sensitivities, stress and poor diet can all impair the the body's ability to detoxify these intruders. Laxative herbs are important in this case. Examples are burdock, yellow dock and gentian, along with flax seed, fruits/vegetables and whole grains/oats⁷. Burdock is a gentle stimulating laxative, unlike Senna which can create dependance for regular bowel movements. Gentian is a type of bitter herb that stimulates stomach acid. This helps to promote bile and enzyme production, which absorbs fat-soluble toxins to be broken down in the liver. Exercise, adequate fluid intake and abdominal stretching are other gentle ways to stimulate bowel movements.

KIDNEY^8,9

Common botanical diuretic herbs are Solidago spp (Goldenrod), Petroselinum (Parsley), and Urtica doica (Nettle). Diuretic herbs can work either by being stimulating, osmotic or cardiac/peripheral circulatory stimulants. Stimulating diuretic herbs work by irritating the kidneys and improving blood flow to that area. Arctostaphylos uva-ursi (Bearberry), Juniperus communis (Juniper), Apium graveolens (Celery),  and Parsley are examples.  Osmotic diuretics on the other hand, lead to diuresis through the  mucilage and polysaccharides in them, creating an osmotic pull between larger sugars passing through the urine. Other diuretics work more on the cardiac or peripheral circulatory system. This is done via increasing renal blood flow. Examples are Achillea millefolium (Yarrow), Crataegus spp. (Hawthorne) and Convallaria majalis (Lilly of the Valley).

Conclusion

Poor detoxification systems can lead to fatigue, mood disorders, hormone imbalances, chronic infections and even chronic illness over time. Incorporating exercise, stress reduction, foods and herbs that promote healthy detoxification can lead to improved vitality in one's mind and body.