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LIVERIN Holistic detoxification of the liver ADIRONDACK (M) SDN. BHD. The liver is the main detoxifying organ in the body The liver utilizes a 2 phase system in detoxifying the body of harmful substances 2 Phases of detoxification • Phase 1 • It transform the fat soluble toxins into water soluble compounds (both body and within the liver) • Phase 2 • Sending the toxins back to the kidney for elimination or into the bile for elimination via the GI tract. LIVER DETOXIFICATION PROCESS TOXINS (non polar) Endotoxins Xenobiotics INTERMEDIATE METABOLITES May be toxic PHASE I Cytochrome P 450 enzymes Hydroxylation via redox reactions Critical cofactors : NADH, NADPH, B6, Mg EXCRETION (polar molecules) Kidney ---- Urine Bile ---------- Faeces PHASE II Conjugation reactions Glutathione conjugation Amino acid conjugation Glucuronidation Sulfation Methylation Acetylation Liver detoxification has to be holistic • Detoxification rates : If : Result : Phase 1 > Phase 2 Liver toxicity or damage due to excessive accumulation of activated intermediates (free radicals) Imbalanced Detoxification Phase 2 Conjugation Phase 1 Cytochrome P 450 enzymes Non polar (Fat loving) xenobiotics Free Radicals (Reactive intermediate) Damage to DNA, RNA and Proteins Inert water soluble metabolites Supportive Nutrients for Detoxification Pathways Lipid-soluble molecule Phase 1 (Cytochrome P450 Enzymes) Activated Intermediates Riboflavin (Vit B2) Niacin (Vit B3) Pyridoxine (Vit B6) Vitamin B12 Glutathione Branched-chain amino acids Flavonoids Phospholipids Phase II (Conjugation Pathways) Excretory derivatives ATP Glutathione Polar Glycine (water soluble) Taurine Glutamine Ornithine Arginine Serum Methyl donors N-acetylcysteine Cysteine Bile Kidney Methionine Faeces/stools Urine You need Liverin if you have any of these symptoms • Chronic constipation • Frequent gas and bloating • Excess weight • Frequent fatique • Impaired digestion • Irritable Bowel Syndrome (IBS) • Candida infection • • • • • • • • Parasite infestation Recurring headaches Bad breadth Hemorrhoids Irritability Frequent colds Protruding belly. Leaky gut syndrome. GI and Liver Health Dysregulating factors Medications Alcohol Food allergies Infectious agents Pollutants Stress Low stomach acid Low secretory IgA The Road to Immunity by Stephen Bock GI tract is overburdened imbalances result Poorer absorption of nutrients Higher levels of toxins and allergens are absorbed through gut mucosa Creates food allergies Additional burdens LIVER is overburdened Fewer nutrients are available for defense and repair Immune suppression Cellular damage Bioaccumulation of toxins that are not excreted Metabolic poisoning Chronic illness Alterations in organ functions Toxic chemicals Hormones Antigens/antibody complexes More detoxifying creates increased oxidant stress Free radical damage Mitochondrial problems Benefits of Liverin • • • • • • • Increased Energy and Vitality Weight Loss Better Gut Function Clearer Thinking Improved Skin Better Sleep Improved Mood Phase 1 (Cytochrome P450 enzymes) Vitamin B complex (Vitamin B2, B6, B9 and B12) Other vitamins (Vitamin C, vitamin D, vitamin K) Mineral : Magnesium Phospholipids (Lecithin) Phase 2 (Conjugation pathways) Free radicals Anti-oxidants Vitamin E Glutathione Alpha Lipoid Acid Selenium Flavanoids e.g. EGCG, Pine bark extract, Noni, Andrographis panuculata, Amino acids Branched chain amino acids L-lysine, L-arginine, L-cysteine, L-methionine, L-ornithine, L- glycine, L-glutamine), Betaine PHASE 1 INGREDIENTS No Name of ingredient Function 1. Vitamin E A natural antioxidant that may treat fatty liver disease. Vitamin E protects the liver from damage caused by free radicals, which harm liver cells, tissues and organ. 2. Zinc sulphate monohydrate Zinc deficiency is often linked to liver cirrhosis. In fact, zinc supplementation improves the neurological symptoms and malnutrition associated with liver diseases. Zinc supplementation also help to protect against acute and chronic liver diseases. Even alcoholic liver diseases may occur due to decreased levels of zinc in the body, and zinc supplementation may help manage alcoholic liver diseases by inhibiting the formation of free oxygen radicals and enhancing the activity of antioxidant pathways. 3. Choline or Lecithin(phospholipids) Choline is the precursor of many chemicals with similar structures that are known as phospholipids. Phospholipids play many important roles in the body, including formation of the cell membranes that surround and protect cells as well as transmission of nerve signals, explains the Linus No Name of ingredient Function Low levels of choline have been linked to fatty liver disease, according to the Northwestern University Feinberg School of Medicine. Heavy consumption of alcohol, which is one cause of fatty liver, tends to break down choline, which may lead to deficiencies in choline. Researchers do not know if the choline deficiency actually causes liver damage. 4 Riboflavin ( Vitamin B2) Vitamin B2 help the body cells to create energy from the metabolization of carbohydrates, protein, and fat.. Riboflavin is critical for normal growth and repair. It is needed to facilitate normal reproduction, cell growth and repair, and development of tissues. The body utilizes vitamin B2 to keep tissue health and to help accelerate healing of injuries. 5 Pyridoxine (Vitamin B6) When people suffer from a damaged liver or liver disease, they most likely have a deficiency of vitamins B6, D, C and K. When the liver lacks the ability to regenerate itself; a vitamin therapy regimen is required to help rebuild and regenerate the damaged liver. According to a study published by the Journal of Nutrition, the metabolism of vitamin B6 can regenerate the liver . 6. Folic Acid (Vitamin B9) Folic acid helps the body to form red blood cells and helps prevent neural tube defects. Folic acid also plays a role in protein metabolism and helps reduce blood homocysteine levels. Liver damage may reduce your ability to process this vitamin, possibly leading to a folic acid deficiency. 7. Niacin (Vitamin B3) Niacin, also known as vitamin B3 is used as a cholesterol and blood lipid (fat) lowering agent. Niacin blocks the release of lipids into the blood and is useful for treating a wide variety of blood lipid disorders. It lowers low-density-lipoprotein (LDL) cholesterol, triglycerides and lipoprotein A. It also increases "good" high-density-lipoprotein (HDL) cholesterol. 8. Ascorbic Acid (Vitamin C) Leucocyte ascorbic acid (LAA) levels were measured in 138 patients with liver disease. Significantly reduced levels were found in 37 patients with alcoholic liver disease (P less than 0-01) and 25 patients with primary biliary cirrhosis (P less than 0-05). Ascorbic acid deficiency occur in liver disease. 9 Vitamin D According to the Science Daily website, patients with chronic liver disease often develop a vitamin D deficiency. The liver produces 25-hydroxy (25-OH) vitamin D, also known as calcidiol, the immediate precursor to the metabolically active 1,25 dihydroxyvitamin D 1-25 vitamin D, also known as calcitriol. Liver disease could lead to impaired absorption of vitamin D, which is possibly connected to impaired bile acid production or gut edema associated with portal hypertension. In recent decades, researchers have discovered that a healthy liver is necessary to maintain adequate levels of vitamin D in the body. Many kinds of liver diseases that cause damage to the liver can result in low levels of vitamin D in the body. 10 Vitamin K The liver synthesizes bile acids, secreting them into the small intestine. From there, bile acids play a crucial role in absorption of lipids. Decreased bile salt synthesis results in an impaired absorption of vitamin K, causing liver disease. 11 Betaine Betaine is a natural chemical found in the stomach that carries and donates methyl molecules throughout the 12. Branched chain amino acid Branched-chain amino acid (BCAA) granules improved the outcome for patients with liver disease. Benefits of branched-chain amino acid enriched nutrients for patients with liver cirrhosis. The rationale for recommendation of branched-chain amino acids (BCAA; valine, leucine, and isoleucine) in treatment of liver failure is based on their unique pharmacologic properties, stimulatory effect on ammonia detoxification to glutamine (GLN), and decreased concentrations in liver cirrhosis 13. Flavonoids ( in this case EGCG from green tea extract and pycogenol from pine bark extract). Flavonoids, polyphenolic compounds found in plants, have antioxidant powers that may provide important health benefits. Flavanoids contain antioxidants that may protect the body’s cells from harmful free radicals from cigarette smoke and other environmental contaminants, according to the Cleveland Clinic. Free radical damage can increase LDL, or “bad” cholesterol, increasing the risk for heart disease. Researchers at Cornell University have found that extracts from flavonoid-rich onions provided strong anti-proliferation effects against liver and colon cancer cells. 11 Phospholipids (Lecithin) One of the most common conditions affecting the liver is fatty liver disease (steatosis). It is almost entirely influenced by lifestyle choices but is also reversible. Fatty liver disease can be caused by alcohol abuse (alcoholic steatosis) or by other lifestyle factors such as poor eating habits, sedentary lifestyle and smoking, the British Liver Trust explains. This is known as non-alcoholic fatty liver disease (NAFLD). Fatty liver can cause liver inflammation and progress to scarring. Advanced fatty liver disease can cause cirrhosis and liver failure. Phospholipids are capable of repairing damage to the liver caused by alcohol, poor diet and other factors. They are an important component of cell membranes and contribute the overall functioning of the cells. They help to form a semi-permeable bilayer that encloses the cytoplasm (cellular fluid) and allows for transportation of substances in and out of the cells. Magnesium stearate Magnesium stearate is a magnesium salt containing stearic acid. Stearic acid is an 18 carbon long saturated fat, common in our food supply. It is readily metabolised to oleic acid (the monounsaturated fat found in olive oil). Stearic acid is unique among all saturated fatty acids PHASE II 1 Soy protein Soy protein could significantly reduce fat accumulation and triglycerides in the livers of obese patients by partially restoring the function of a key signaling pathway in the organ. 2 Whey protein Whey protein decrease total cholesterol and LDL cholesterol. 3 L-lysine As a building block of proteins in the body, lysine is a vital nutrient for supporting proper growth and development. The nutrient can be used to control cholesterol levels, prevent osteoporosis and other age-related bone density conditions, support growth and reduce anxiety and stress. 4 L-Methionine L-methionine exerts many key functions in the liver, including serving as a precursor for cysteine, 1 of 3 amino acids of glutathione—the major physiologic defense mechanism against oxidative stress. Lmethionine is particularly important in opposing the toxicity of free oxygen radicals generated by various pathogens, including alcohol, which cause oxidative stress largely by the induction of cytochrome P4502E1 (CYP2E1) and by its metabolite acetaldehyde. L-methionine also acts as the main methylating agent in the liver. 5. L-cysteine L-cysteine counteracts the mild pain reliever and its effects on the liver. The body converts the dietary supplement into cysteine, and then into glutathione, an effective antioxidant that fights free radicals in your body, according to the University of Maryland Medical Center, or UMMC. 6. L-arginine L-arginine is an amino acid that’s made in the body and found in foods such as soybeans, nuts and grains. Its main functions are to convert toxic ammonia to the waste product urea and provide immune system support. L-arginine shows promise in improving fatty liver disease, or hepatic steatosis, by increasing blood flow to the organ. Scientists at the University College London in the United Kingdom observed that rats with hepatic steatosis taking L-arginine daily for 12 weeks experienced improvements in blood flow to the liver. Researchers stated that L-arginine increases the production of nitric oxide, a gas molecule that boosts blood flow. The findings were reported in the November 2005 issue of "Microvascular Research.” 7 L- ornithine Amino acid L-ornithine-L-aspartate reduces ammonia in the body, thus helping with liver cirrhosis. The L-ornithine-L-aspartate granules showed the level of ammonia was significantly decreased. And minimal hepatic encephalopathy was significantly improved. L-ornithine is crucial for removal of bodily wastes, and some research also suggests this amino acid may help boost your energy 8 Glutamine The most abundant amino acid in the body is glutamine, which is normally made by thebody but is also supplied from proteincontaining foods. It serves a variety of functions including the removal of excess ammonia waste product and regulating immune system functions, and is needed in digestive processes. As an amino acid, or protein building block, glutamine also serves as a precursor in the formation of glutathione, an antioxidant important for protecting your liver from free radical damage. In the event of liver injury and low production of glutathione, available glutamine compensates for this lack of glutathione and aids in generating stored glutathione to keep the liver protected, according to a 1992 review in the "Annals of Surgery." 9 Glycine Chronic cholestasic liver diseases lead to liver injury and ultimately progress to portal fibrosis, cirrhosis, and end-stage liver disease requiring liver transplantation. A research group in the US and Germany investigated the effects of (dietary) glycine against oxidant-induced injury caused by bile duct ligation in rats. The study demonstrate that hepatic injury due to BDL is significantly reduced by dietary glycine and glycine decreases liver injury thru a direct effect on hepatocytes. Glycine prevents hepatic damage caused by hypoxia-reoxygenation, diminishes mortality due to endotoxin and minimizes alcoholic liver injury by decreasing blood ethanol 10 Glutathione The levels of glutathione in the liver is critically linked to the livers capacity to detoxify. This means that the higher the glutathione content, the greater the livers capacity to detoxify harmful chemicals and toxins. Typically, when we are exposed to chemicals like alcohol and pollution which can damage the liver, the concentration of glutathione in the liver is substantially reduced. This reduction makes the liver susceptible to damage. Glutathione is an antioxidant enzyme often referred to as the body's "master antioxidant" due to its central role in protecting the body's cells from free radical damage. Glutathione is composed of the amino acids cysteine, glutamine and glycine and is concentrated in the liver, although it carries out its work throughout the body. This important enzyme is involved in protecting cells from environmental toxins, drugs and alcohol as well as toxins produced by the body itself as a result of normal metabolism. Depletion of glutathione lead to cell’s death. 11 Alpha Lipoid Acid More recently, in 1999 Berkson published three case reports using a triple-antioxidant supplement regimen in patients with liver disease, including chronic hepatitis C infection. After several months of treatment with a combination of alpha lipoic acid, selenium and silymarin, all three patients recovered most or all of their liver function, avoided liver transplantation and went on to live healthy, productive lives free of the symptoms of liver disease.From 2006 to 2008, studies in humans and animals have shown that alpha lipoic acid can provide important improvements in the following: recovery following liver surgery; protection from chemotherapy side effects and chemical poisoning; liver regeneration; and protection against liver and kidney damage . ALA is also an excellent antioxidant and recycles other nutrients such as co-enzyme Q-10, vitamin C, and vitamin E. In addition, ALA chelates heavy metals such as mercury, lead, and arsenic, and it stabilizes NF kappa B transcription factor so that it helps to inactivate deleterious genes. It can also help people with diabetes mellitus by increasing the sensitivity of their cells to insulin, and it helps reverse diabetic neuropathies. 12 Selenium Selenium boosts liver protection .Required in small amounts to maintain good health, selenium is essential for many body processes and is especially abundant in the kidneys, liver, spleen, testes and pancreas. Of particular interest to those with chronic liver disease, selenium boasts several functions that make it a valuable component to any liver wellness program. Selenium is a liver ally for several reasons: 1. Antioxidant – Trace amounts of selenium are necessary to form two enzymes – glutathione peroxidase and thioredoxin reductase – both of which indirectly reduce certain oxidized molecules. Since oxidation is a known manner in which liver damage occurs, antioxidants like selenium help preserve liver tissue. 2. Immune Strength – A variety of sources indicate that selenium and Vitamin E act synergistically to strengthen immunity by aiding in the production of disease-fighting antibodies. 3. Cancer Prevention – Believed to mobilize cancer-fighting cells, selenium may be helpful in preventing cancer. Since those with advanced liver disease are at risk of developing liver cancer, any efforts that could stop cells from going awry is generally welcomed. 4. Tissue Elasticity – This trace element is needed for tissue elasticity, an important characteristic for those with chronic liver disease. Because rigidity in liver tissue and local blood vessels are consequences of several types of liver disease, efforts to preserve elasticity also helps support healthful hepatic circulation. The following studies corroborate the belief that selenium is valuable 13 Flavanoids Flavonoid-rich foods has high antioxidant effects. Antioxidants may protect the body’s cells from harmful free radicals from cigarette smoke and other environmental contaminants, according to the Cleveland Clinic. Free radical damage can increase LDL, or “bad” cholesterol, increasing the risk for heart disease. Green Tea (EGCG) Green Tea is a good source of antioxidants. It is loaded with catechins, a substance that is known to improve liver function. They are even more powerful than Vitamins C and E when it comes to preventing damage to cells according to Harvard Women's Health Watch. Studies from the American Journal of Clinical Nutrition (AJCN) also showed that green tea had the ability to suppress liver injuries . Phyllanthus Phyllanthus niruri has been found to exhibit inhibitory effect on hepatitis B virus evident by its exhaustive utility in cases of chronic jaundice. An aqueous extract of the plant Phyllanthus niruri inhibits endogenous DNA polymerase of hepatitis B virus and binds to the surface antigen of hepatitis B virus in vitro. Effect of Phyllanthus niruri extracts on woodchuck hepatitis virus surface antigen was also observed in a study of rats. However, till date, research studies are very limited for this claim. [2, 3] Phyllanthus niruri extracts may have benefits of liver protection. Its protein fractions protected liver tissues against oxidative stress by improving anti-oxidative defense in mice. It may also benefit hepatitis B. Researchers injected partially purified protein fraction of Phyllanthus niruri intraperitoneally in mice either prior to (preventive) or after the induction of liver toxicity (curative). Researchers observed a reduction of elevated glutamate pyruvate THANK YOU FOR YOUR KIND ATTENTION