Kathy E. Acquistapace, DC, NHP, CNC
Maintaining liver health is integral to healthy living. The liver is responsible for metabolizing nutrients, hormones and by-products—it’s exposed to everything we eat, drink and breathe. Consequently, it’s just as important to be proactive—supporting the health of a non-diseased liver to ensure it stays healthy—as it is to be reactive—finding ways to strengthen a diseased liver.
The largest organ inside the body, the liver is located below the diaphragm in the right upper quadrant of the abdominal cavity; it is sheltered by the rib cage. In an adult, the liver normally weighs about 3 pounds and extends approximately from the right fifth rib to the lower border of the rib cage (along an imaginary line extending down from the middle of the collar bone).
Because the liver detoxifies every toxin our body is exposed to, it’s important to keep it functioning optimally by taking proactive steps. Even individuals who have hepatitis, cirrhosis, primary sclerosing cholangitis and other liver disorders can significantly improve the quality of their lives by finding ways to nourish the health of this important organ.
Before discussing ways to improve liver health, it’s important to understand how the liver works and the various diseases that can affect its function.
Liver Regeneration
One of the most interesting properties of the liver is its ability to regenerate. It accomplishes this feat with the help of hepatocytes, the most abundant and metabolically active cells in the liver. They lie together in cords, or sheets, in close association with bile ducts and sinusoids. The sinusoids are lined by a single layer of endothelial cells, where oxygen, nutrients, and poisons are removed from the blood, and products made by hepatocytes for use elsewhere in the body are secreted into the blood. Kupffer cells, found in the sinusoids, are specialized "scavengers" that can engulf foreign particulate matter, worn-out blood cells, and bacteria.
Because all hepatocytes can perform the necessary hepatic functions and all have an equal ability to replicate, the liver can undergo compensatory growth and restore its size. Liver regeneration plays an important role after surgical removal of a portion of liver (partial hepatectomy) and after injuries that destroy portions of the liver, such as viral, toxic, or ischemic damage. However, excessive damage can reach a "point of no return," and normal tissue will be replaced with scar tissue. The liver's ability to regenerate is also compromised by pre-existing or repeated liver damage or disease.1
Liver Function
The body depends on the liver to perform a number of vital functions, and although there is substantial overlap, they can be divided into three basic categories:
1. Regulations, Synthesis, and Secretion.
Hepatocytes take up glucose, minerals, and vitamins from portal and systemic blood and store them. In addition, they can produce many important substances needed by the body, such as blood clotting factors, transporter proteins, cholesterol, and bile components. By regulating blood levels of substances such as cholesterol and glucose, the liver helps maintain body homeostasis.
2. Storage.
The liver is designed to store important substances such as glucose (in the form of glycogen). The liver also stores fat-soluble vitamins (vitamins A, D, E and K), folate, vitamin B12, and minerals such as copper and iron. However, excessive accumulation of certain substances can be harmful. For example, people with an inherited condition known as Wilson's disease cannot secrete copper into bile normally and usually have a low blood level of the copper-binding protein ceruloplasmin. Retained copper accumulates in the liver leading to cirrhosis, and in the central nervous system resulting in neuropsychiatric symptoms.
3. Purification, Transformation, and Clearance.
The liver removes harmful substances such as ammonia and toxins from the blood and then breaks them down or transforms them into less harmful compounds. In addition, the liver metabolizes most hormones and ingested drugs to either more or less active products.
a. Ammonia. The liver converts ammonia to urea, which is excreted into the urine by the kidneys. In the presence of severe liver disease, ammonia accumulates in the blood because of both decreased blood clearance and decreased ability to form urea. Elevated ammonia levels can be toxic, especially to the brain, and may play a role in the development of hepatic encephalopathy.
b. Bilirubin. Bilirubin is a yellow pigment formed as a breakdown product of red blood cell hemoglobin. The spleen, which destroys old red cells, releases "unconjugated" bilirubin into the blood, where it circulates in the blood bound to albumin. The liver efficiently takes up bilirubin and chemically modifies it to "conjugated," or water-soluble, bilirubin that can be excreted into bile.
c. Hormones. Since the liver plays important roles in hormonal modification and inactivation, chronic liver disease may cause hormonal imbalances. For example, the masculinizing hormone testosterone and the feminizing hormone estrogen are metabolized and inactivated by the liver. Men with cirrhosis, especially those who abuse alcohol, have increased circulating estrogens relative to testosterone derivatives, which may lead to body feminization.
d. Drugs and Alcohol. Nearly all drugs are modified or degraded in the liver. In particular, oral drugs are absorbed by the gut and transported via the portal circulation to the liver. In the liver, drugs may undergo first-pass metabolism, a process in which they are modified, activated, or inactivated before they enter the systemic circulation, or they may be left unchanged. Alcohol is primarily metabolized by the liver, and accumulation of its products can lead to cell injury and death.
e. Toxins. The liver is generally responsible for detoxifying chemical agents and poisons, whether ingested or inhaled. Pre-existing liver disease may inhibit or alter detoxification processes and thus increase the toxic effects of these agents. Additionally, exposure to chemicals or toxins may directly affect the liver, ranging from mild dysfunction to severe and life-threatening damage.1
Hepatitis and Cirrhosis
Liver disease has numerous causes, ranging from microbial infections and neoplasms to metabolic and circulatory problems.
Hepatitis involves inflammation and damage to the hepatocytes. This type of insult may result from infectious agents, toxins, or immunologic attack. In addition, other disorders such as Wilson's disease can cause hepatitis, and some diseases such as alpha 1 -antitrypsin deficiency can imitate hepatitis. Hepatitis can also result as a secondary complication of primary sclerosing cholangitis, a disease in which the bile ducts inside and outside the liver become narrowed due to inflammation and scarring. This causes bile to accumulate in the liver and can result in damage to liver cells and hepatitis. However, the most common cause of hepatitis is viral infection.
Three major viruses cause hepatitis in the United States: hepatitis viruses A, B, and C. Together, they infect nearly 500,000 people in the United States every year.
In addition, bacteria, fungi, and protozoa can infect the liver, and the liver is almost inevitably involved to some extent in all blood-borne infections.
Toxins such as alcohol, drugs, or poisons also can cause hepatitis directly by damaging liver tissue or indirectly by reducing defenses or stimulating an autoimmune response. The exact mechanism of how this happens is not always clear. Alcohol is primarily metabolized by the liver, and these metabolites can cause liver damage. The risk of hepatic toxicity increases if more than 40 grams, or about four drinks, are consumed per day.
Numerous medications can damage the liver, ranging from mild, asymptomatic alteration in liver chemistries to hepatic failure and death. Liver toxicity may or may not be dose-related.
Both environmental and industrial toxins can cause a variety of changes in the liver. Hepatic damage is not necessarily dose-dependent and can range from mild, asymptomatic inflammation to fulminate failure or progressive fibrosis and cirrhosis.
Immune System Involvement
The immune system functions primarily to recognize "foreign" or "non-self" antigens, for example, invading viruses, bacteria, and their proteins. These antigens may be recognized by antibodies, but occasionally, autoimmunity develops, whereby the immune system incorrectly reacts against "self" antigens, (one's own cells). This occurs in autoimmune hepatitis and primary biliary cirrhosis, two diseases in which the immune system attacks and destroys portions of the liver. If unchecked, persistent inflammation can eventually lead to cirrhosis. Cirrhosis is characterized anatomically by widespread nodules in the liver combined with fibrosis. The fibrosis and nodule formation causes distortion of the normal liver architecture, which interferes with blood flow through the liver. Cirrhosis can also lead to an inability of the liver to perform its biochemical functions.2
Neoplastic Disorders
The liver is the most frequent site for blood-borne malignant tumor metastases, including colorectal, breast, lung, stomach, pancreas, and ovarian cancers, and malignant melanoma among others. Primary malignant liver cancer—hepatocellular carcinoma (HCC)—most commonly occurs in patients with cirrhosis from viral infection, alcoholism, hemochromatosis, or alpha 1 - antitrypsin deficiency. Men are affected more frequently than women, and the prognosis is dismal, with an average survival of about six months after symptoms begin.
Pesticide Protection
While no one knows for certain what triggers liver cancer development, the medical literature has established a link between exposure to some pesticides and a higher risk of developing this disease. In addition, animals exposed to certain pesticides also appear to have an increased risk of liver cancer.
In one study, researchers investigated whether DDE, the major and most persistent derivative of the pesticide DDT, could have a role to play in the development of liver cancer and other malignancies. They examined the association of the adipose DDE levels of population samples from 22 U.S. states with age-adjusted mortality rates between 1975 and 1994 for liver cancer as well as multiple myeloma, non-Hodgkin lymphoma, and cancers of the breast, corpus uteri, and pancreas. The researchers found that liver cancer mortality increased significantly with adipose DDE levels in both sexes among whites, but not among African Americans. Breast cancer mortality was inversely correlated with adipose DDE levels among both white and African American women. No association was observed for pancreatic cancer and multiple myeloma.3
Other researchers have established a link between liver cancer and pesticide exposure. The rate of hepatocellular carcinoma is increasing in Egypt where the major risk factors are chronic infections with hepatitis B and C viruses. A major segment of the population is employed in agriculture, raising the possibility that exposure to pesticides is an additional liver cancer risk factor. Therefore, Egyptian researchers investigated pesticides as environmental risk factors for liver cancer while taking into account viral risk factors. They conducted a study of 236 subjects with confirmed liver cancer and 236 healthy controls. Patients who agreed to participate answered a questionnaire and gave a blood sample for hepatitis virus testing. The researchers used the questionnaire data to determine the specific pesticides to which each subject came in contact. Subjects also reported duration of pesticide exposure.
Among rural males, who received a greater exposure to pesticides, there was a statistically significant association between pesticide exposure and development of liver cancer. In urban subjects, who received less exposure to pesticides, this association between liver cancer and pesticides was not observed.4
According to the researchers, “This study therefore suggests that exposures to organophophorus and carbamate pesticides are additive risk factors to current hepatitis C virus and hepatitis B virus infection among rural males.”
Liver’s Involvement in Extrahepatic Disorders
The liver may be affected by numerous conditions, particularly autoimmune disorders, in which the immune system attacks the body's own normal tissues. Some examples include rheumatic diseases (such as systemic lupus erythematosus and rheumatoid arthritis) and inflammatory bowel diseases (such as ulcerative colitis and Crohn's disease).
Systemic infections, such as tuberculosis, candidiasis, and toxoplasmosis, may spread to the liver. In addition, heart failure can lead to liver congestion, scarring, and ascites, because blood cannot drain from the liver properly when the heart is not pumping effectively.1
Maintaining a Healthy Liver
A number of nutritional supplements have been found to contain significant liver protective substances and actions.
N-acetyl cysteine (NAC) protects the liver from damage from advanced glycation end products (AGEs) and the effects of a high-fat diet. N-acetyl cysteine increases production of the antioxidant glutathione in the liver.5 The liver uses glutathione to help break down toxins. Several scientific articles have found a direct link between glutathione levels and hepatitis B and C viral activity. When viral load increases, glutathione decreases. Researchers have reported that adding NAC to hepatitis-B producing cell lines can reduce hepatitis viral load 50 fold.6 Studies have also shown that NAC can protect against neurobehavioral deficits in animals exposed to pesticides as well as increase the survival time and reduce the cardiovascular toxicity of rats exposed to the pesticide aluminium phosphide.7-8
Silymarin, or milk thistle, is hepatoprotective against many forms of liver injury and is widely used in human liver diseases, such as hepatitis C and alcoholic cirrhosis, with an excellent safety profile. Silibinin, the main component of silymarin, has a strong affinity for the cytochrome P450 enzymes. These enzymes are produced by the liver and are the main constituents the liver uses to break down and eliminate toxins.9 In vitro, Silymarin also has strongly inhibited the growth of both hepatitis B virus positive and hepatitis B virus negative liver cancer cells.10
Curcumin, a yellow ingredient isolated from turmeric (curcumin longa), has exhibited a variety of biological activities (including antioxidative actions) in the liver. Curcumin can effectively inhibit the free radical induced lipid peroxidation and protein oxidative damage of liver mitochondria. In liver cancer cells, curcumin also has been shown to inhibit cell growth and to trigger apoptosis (programmed cell death).11
Dandelion is another nutrient commonly used to maintain liver health. In research using rat models, dandelion increases phase I and phase II detoxification enzymes in the liver. It also has a positive effect on antioxidant enzymes and lipid profiles.12
Green tea polyphenols also possess liver-supporting activities. A powerful antioxidant, green tea contains a group of polyphenols known as catechins. One catechin in particular—epigallocatechin-3-gallate (EGCG)—has been shown to possess anti-tumor properties. Researchers have found that EGCG can trick cancer cells into fragmenting their DNA, leading to apoptosis (programmed cell death). EGCG inhibits the promotion stage of chemical carcinogenesis in the liver, and reduces levels of enzymes required for cancer cell growth.13
Green tea’s other actions include protecting the liver against pesticide exposure. In one study, mice were exposed to the pesticides pentachlorophenol (PCP) and diethylnitrosamine (DEN). In the first experiment, groups of 15 male mice were initially treated with DEN at a dose of 20 p.p.m. in the drinking water for the first 8 weeks followed by PCP at concentrations of either 0 (basal diet), 300 or 600 p.p.m. in the diet for 23 weeks. None of these animals received green tea. Further groups of animals, however, were treated with DEN and PCP in the same manner but also received 2 percent green tea infusion from week 10 until death.
PCP exposure at the high dose promoted liver cancer, and also caused progression of cystic hyperplasias of the intrahepatic bile ducts to full-fledged tumors. Co-administration of green tea, however, was able to prevent the increases and multiplicities of liver tumors and also arrest the progression of bile-duct tumors.
In a second experiment, researchers administered the green tea before giving the animals the pesticides and continued green tea administration past the point of exposing the animals to the chemicals. Green tea prevented the damage to liver cells and intrahepatic biliary epithelial cells caused by PCP.14
The study authors wrote, “These findings suggest that regular intake of green tea may reduce the carcinogenic risk posed by an environmental pollutant, PCP, presumably due to effects on oxidative stress.”
A recent study published in the Journal of the American Medical Association indicates vitamin K2 (a natural form of the vitamin) may also play a role in supporting liver health. Researchers studied 40 women diagnosed with viral liver cirrhosis who were admitted to a university hospital between 1996 and 1998. The 21 treated subjects received 45 mg per day of vitamin K2. Liver cancer was detected in only 2 of the 21 women given vitamin K2 compared to 9 of the 19 women in the control group. The cumulative proportion of patients with liver cancer was smaller in the vitamin-K-treated group. According to the study authors, there is a possible role for vitamin K2 in the prevention of hepatocellular carcinoma in women with viral cirrhosis.15
Conclusion
In today’s industrialized world, our livers are bombarded with toxins. Consequently, this vital organ needs extensive support in order to remain strong and healthy. Nutrients such as NAC, silymarin, turmeric, green tea, dandelion and vitamin K2 can help ensure that even the most sluggish of livers can function at an optimal level.
References
1. Worman, Howard J. The Liver Disorders Source Book. 1: 1-5; 3: 11-12; 4: 43-48, 67, 82, 93, 97, 215, 227, 238.
2. American Liver Foundation, Hepatitis and Liver Disease in the United States. 2005 Jan;06.
3. Environ Health Perspect. 2000 Jan;108(1):1-4. Cancer mortality and environmental exposure to DDE in the United States. Cocco P, Kazerouni N, Zahm SH.
4. Int J Hyg Environ Health. 2005;208(5):329-39. Associations of pesticides, HCV, HBV, and hepatocellular carcinoma in Egypt. Ezzat S, Abdel-Hamid M, Eissa SA, Mokhtar N, Labib NA, El-Ghorory L, Mikhail NN, Abdel-Hamid A, Hifnawy T, Strickland GT, Loffredo CA.
5. Li SY, Liu Y, Sigmon VK, McCort A, Ren J. High-fat diet enhances visceral advanced glycation end products, nuclear O-Glc-Nac modification, p38 mitogen-activated protein kinase activation and apoptosis.
Diabetes Obes Metab. 2005 Jul;7(4):448-54.
6. [No authors listed] Hepatitis viral load correlates to glutathione levels. Posit Health News. 1998 Fall;(No 17):14-5.
7. Kamboj A, Kiran R, Sandhir R. Carbofuran-induced neurochemical and neurobehavioral alterations in rats: attenuation by N-acetylcysteine. Exp Brain Res. 2006 Apr;170(4):567-75. Epub 2005 Nov 24.
8. Azad A, Lall SB, Mittra S. Effect of N-acetylcysteine and L-NAME on aluminium phosphide induced cardiovascular toxicity in rats. Acta Pharmacol Sin. 2001 Apr;22(4):298-304.
9. Dryden GW, Song M, McClain C. Polyphenols and gastrointestinal diseases. Curr Opin Gastroenterol. 2006 Mar;22(2):165-70.
10. Varghese L, Agarwal C, Tvagi A, Singh RP, Agarwal R. Silibinin efficacy against human hepatocellular carcinoma. Clin Cancer Res. 2005 Dec 1;11(23):8441-8.
11. Notarbartolo M, Poma P, Perri D, Dusonchet L, Cervello M, D’Alessandro N. Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relationship to changes in NF-kB activation levels and in IAP gene expression. Cancer Lett. 2005 Jun 16;224(1):53-65.
12. Maliakal PP, Wanwimolruk S. Effect of herbal teas on hepatic drug metabolizing enzymes in rats. J Pharm Pharmacol. 2001 Oct;53(10):1323-9.
13. Klaunig J. Chemopreventive effects of green tea components on hepatic carcinogenesis. Prevention Medicine. 1992; 21:510-519.
14. Umemura T, Kai S, Hasegawa R, Kanki K, Kitamura Y, Nishikawa A, Hirose M. Prevention of dual promoting effects of pentachlorophenol, an environmental pollutant, on diethylnitrosamine-induced hepato- and cholangiocarcinogenesis in mice by green tea infusion. Carcinogenesis. 2003 Jun;24(6):1105-9. Epub 2003 Apr 24.
15. Habu D, Shiomi S, Tamori A, Takeda T, Tanaka T, Kubo S, Nishiguchi S. Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. JAMA. 2004 Jul 21;292(3):358-61.
