From the January 1999 Issue of Nutrition Science News
By Marilyn Sterling, R.D.
Intelligent lifestyle and nutrition choices may thwart the liver disease long considered unstoppable
The liver truly is remarkabledirectly affected by nearly everything a person eats, drinks and breathes, it is still durable and capable of regeneration. Tucked away on the right side of the abdomen, the liver is the human body's largest internal organ, serving as command central for a variety of vital metabolic processes. Because of its essential role, protecting the liver from the numerous lifestyle, environmental and viral insults that can accumulate and destroy its ability to function is paramount. Several types of liver disease can result from the onslaught of life, including cancer, alcohol-related liver disorders, viral hepatitis and cirrhosis.
Cirrhosis of the liver is the fourth most common cause of death among people between the ages of 30 and 50, and the eighth most common killer overall. A liver affected with this chronic degenerative disease becomes hardened and scarred and eventually so damaged it can't function because normal blood flow through it is blocked. The degeneration process dramatically affects the organ's metabolic processes and detoxification abilities.
The liver is the body's recycling center, where thousands of compounds are taken apart and put together again as useful and essential body chemicals. Its several detoxification techniques include filtering large toxins from the blood, synthesizing and secreting bile to carry many impurities out of the body, and neutralizing unwanted chemical compounds in a two-step enzymatic process generally referred to as Phase I and Phase II detoxification. Toxins such as alcohol, urea from amino acid breakdown and environmental invaders are turned into benign by-products that are either used or excreted. Small wonder that when the liver fails, the only effective treatment is a transplant.
With all that at stake, it is important to understand and avoid the risk factors that contribute to cirrhosis. Whether a person is trying to prevent cirrhosis or manage the condition, understanding the roles of alcohol consumption, hepatitis and toxic exposure is critical.
Alcohol and cirrhosis are a roulette gamenot all serious alcoholics develop cirrhosis, though some social drinkers do. Women do not process alcohol as efficiently as men and are thus more likely to develop cirrhosis from drinking. Alcohol is a toxin that damages the liver directly, and the two pathways for breaking down alcohol in the liver also generate dangerous oxygen derivatives, or oxidants, that lead to collagen scar-tissue formation.
Chronic hepatitis, a viral liver disease, is gaining on alcohol as the leading cause of cirrhosis. Although hepatitis A, spread through contaminated water and food and excreted in stools, does not cause cirrhosis, other forms are not so benign. If a hepatitis B or C infection is not completely eradicated through treatment, the chronic hepatitis that remains can eventually lead to cirrhosis.
Hepatitis B, transferred through body fluids such as saliva and blood, progresses to cirrhosis about 5 percent of the time. One in every 250 people is a carrier of hepatitis B, and 30 to 40 percent of them have no symptoms. It is estimated that one in every 20 people will contract hepatitis Bone-third of them without symptoms. In fact, A simple test can determine whether a person has hepatitis, which is a good idea for those in doubt, because future problems are just as likely even if no symptoms are present. The hepatitis B vaccine is recommended for those at risk, including adolescents and health care workers.
Hepatitis C is harder to contract. It is usually transmitted via contaminated needles or transfusions of infected blood, and in some cases it has been transmitted sexually. Hepatitis C becomes chronic in 80 to 85 percent of patients, and up to 30 percent of them develop cirrhosis. It is estimated that 4 million people have hepatitis C, many of them silent carriers, and the number is growing rapidly. The usual treatment is a course of interferon alpha, which enables invaded cells to be more readily recognized and killed by T lymphocytes and inhibits virus production within infected cells. This treatment is often unsuccessful, however, and has unpleasant side effects including flulike symptoms. Even those patients whose liver enzymes normalize completely after the interferon treatment, indicating they are cured, often relapse, meaning the disease was quiescent for a time. Other antiviral drugs, when combined with interferon, offer hope for more successful eradication of hepatitis C.
Toxic chemical exposure is yet another cause of cirrhosis. Many commonly used chemicals and solvents are liver toxins. A seemingly benign medication, if it triggers an allergic reaction, can also cause cirrhosis. Although the liver is the primary site of detoxification, the very process can poison it. Chemicals that cause cirrhosis often do so by forming oxidants, which are by-products of metabolic activity.
Toxins, which include environmental and normal body chemicals, are detoxified in the liver by chemical neutralization. Briefly, Phase I enzymes directly neutralize many of the chemicals or convert them to substances that are then processed by Phase II enzymes. Sometimes these intermediate substances are more toxic or more chemically active than they were before, further underscoring the importance of a fully functional liver. Phase I detoxification involves a group of enzymes called the cytochrome P450 system. These myriad enzymes metabolize many of the same chemicals to ensure all are neutralized.
Nourishing the Liver
Is there any way to prevent cirrhosis? Could nutrition help? With hundreds of thousands of people at risk, these should be urgent public health questions. The only "cure" for cirrhosis is a $400,000 liver transplant, so finding a way to prevent cirrhosis could save many lives, not to mention billions of dollars. Unfortunately, society invests most of its health care dollars in treatment rather than research on prevention. On the bright side, there are some intriguing clues about the development of cirrhosis. People who already have liver damage, however, have complicated metabolic issues and need personalized diet therapy from a registered dietitian. Here are some avenues that may help heavy alcohol drinkers or people with chronic hepatitis avert cirrhosis development:
Limit iron because hepatitis viruses thrive in iron-rich environments. An iron surfeit impairs many aspects of immune function including T lymphocyte proliferation and maturation. Also, iron catalyzes damage by oxidants. While iron deficiency is common among women who menstruate, older women and men often have an excess because they don't excrete as much. Limiting iron intake weakens hepatitis and increases the chance of successful interferon therapy.  Patients with hepatitis C might want to avoid iron-enriched cereals, food cooked in iron pots, multivitamins containing iron, molasses, and liver and limit their intake of meatall of which contribute excess iron. Vitamin C increases iron absorption, so supplements or foods high in vitamin C should not be taken with meals.
Supplement with choline, an amino acid that is part of the phospholipid lecithin. Alcoholism causes a relative choline deficiency in the liver by decreasing the enzyme methionine synthetase, which is necessary for choline production. A choline deficiency, which promotes liver damage, can be corrected with lecithin supplements. Choline increases the activity of the enzyme hepatic collagenase, which breaks down collagen, preventing cirrhosis. In an experiment on primates, baboons were fed high-alcohol diets for eight years. Most developed cirrhosis. However, no members of a group provided with lecithin supplementation during the experiment developed cirrhosis. Large-scale trials are now under way to see if lecithin has the same protective effect in humans. [2-5]
Reduce fat intake because evidence from one study showed this helped hepatitis C patients who drank alcohol. Those patients who ate high-fat, low-protein and low-carbohydrate diets were more apt to progress to cirrhosis.  One reason could be that unsaturated fatty acids are prone to oxidation, which is dangerous to a damaged liver. This might also explain why one animal experiment found cirrhosis was reversed in animals consuming saturated rather than unsaturated fats (i.e., butter rather than sunflower oil). While intriguing because cirrhosis is often considered irreversible, no research has been conducted in humans in regard to cirrhosis and fat-type consumption.
Limiting fat shouldn't be taken to extremes, however. People do need to meet their intake requirement for essential fatty acids.  In fact, another experiment on monkeys showed that those with diets low in essential fatty acids and low in antioxidants were more apt to develop alcoholic cirrhosis. 
Vitamin E helps maintain high levels of glutathione in people with hepatitis or with other liver problems. [9,10] Glutathione (GSH), an antioxidant present in the liver, is the body's key protector against the oxidizing compounds that lead to cirrhosis. By maintaining GSH levels, vitamin E supplementation may help protect against cirrhosis. In one study, almost 50 percent of people with hepatitis C who did not respond to interferon therapy improved dramatically with 800 IU of vitamin E daily. 
Just because vitamin E helps protect the liver, however, does not mean all antioxidants are equally helpful in liver-related problems. Vitamin A, for example, can build to toxic levels in damaged livers. 
S-adenosyl-L-methionine and N-acetyl cysteine (NAC) also help maintain glutathione. Scientists are interested in these amino acids because they may counter the altered biochemistry found in patients with liver disease, such as the glutathione decrease caused by alcohol and hepatitis. S-adenosyl-L-methionine prevented alcohol-induced glutathione depletion in a baboon study.  It is now being tested on humans but is quite expensive.
In a study of people with hepatitis C, 600 mg daily of NAC enhanced the effectiveness of interferon therapy.  However, another study did not confirm this finding.  Regardless, NAC protects against damaging oxidant-producing immune factors called cytokines and chemokines released in the liver in response to heavy-metal exposure.  Some researchers predict that future treatment of hepatitis C will depend upon antioxidant therapies such as NAC. 
Eating cruciferous vegetables can enhance the liver's ability to detoxify. Substances that harm the liver act synergistically. Alcoholics, for example, are more susceptible than nonalcoholics to other liver toxins, and people with hepatitis cannot tolerate alcohol. Therefore, it is important for people who are at risk of cirrhosis to avoid toxic chemicals and ensure their bodies' capacity for detoxification is maximized.
Here is where the cabbage family shines. The cruciferous vegetables activate the liver's cytochrome P450 detoxification chain. Even more exciting, researchers have recently found that brussels sprouts stimulate the liver's Phase II enzymesthe first dietary component shown to affect this important detoxification system. The cruciferous vegetable family includes broccoli, cauliflower, kale, mustard greens, radish, bok choy and brussels sprouts.
In addition to dietary modifications and nutritional supplements, there are a variety of herbs with scientific evidence of liver-supportive actions.
Milk thistle (Silybum marianum), also called St. Mary's thistle or mariana thistle, is the best-known liver tonic, having been described in herbals since the late 1600s. Its most active constituent, silymarin, is a powerful antioxidant that inhibits harmful oxidants and prevents formation of leukotrienes, one type of dangerous oxidant produced by the immune system.
Silymarin not only prevents glutathione depletion but actually increases quantities of it. As well, it has the ability to stimulate protein synthesis in the liver. [18-20] In recent experiments, silymarin protected animals from radiation damage. A 100-mg/kg/day dose protected rat livers from gamma radiation damage. Using 70 mg/kg twice daily for two weeks or more repaired radiation damage. [21 ] Another study found that animals supplemented with silymarin did not show damage from carbon tetrachloride, a substance commonly used to induce liver destruction. [22 ]
However, a recent double-blind, controlled study of 200 alcoholic and hepatitis C cirrhotics did not show a benefit from silymarin supplementation. The subjects were given either 450 mg silymarin or placebo daily for two years. Both groups had comparable numbers of deaths during this time period14 of those taking silymarin and 15 of those taking placebo diedso it was determined that silymarin supplementation did not influence survival. [23 ] The study patients were very ill to begin with, so perhaps silymarin would be more effective in preventing than treating cirrhosis in those with existing liver damage and in hepatitis patients who are not alcoholics. 
Artichoke (Cynara scolymus) leaves are another liver remedy. Recent animal tests show supplementation with artichoke prevented a liver toxin from causing oxidation, thus preventing glutathione destruction.  The active compound, cynarin, is found in highest concentrations in the leaves. Chlorogenic acid and other antioxidants are also present.
Licorice root (Glycyrrhiza glabra), in the form of the injectable active principle glycyrrhizin, a saponin glycoside, has been used for liver problems in Japan for 20 years. Controlled trials have shown that glycyrrhizin use in chronic hepatitis is associated with improvement in liver enzymes. Liver biopsies confirmed that the liver cells of those taking the compound vs. a placebo were healthier. [25,26]
Long-term supplementation with the Japanese glycyrrhizin medicine Stronger Neo-Minophagen C [TM] (SNMC) has been found to prevent liver cancer in people with hepatitis C. During a period of 10 years, the control group had 2.5 times the liver-cancer rate as those treated with the herb. [27 ] Several mechanisms make glycyrrhizen efficacious including stimulation of the cytochrome P450 system and disruption of the hepatitis virus surface.  A similar compound called Potenlini [TM] , used in China, is effective for cirrhosis caused by either hepatitis or alcohol.  The licorice extract is usually provided in an injectable form, so it is not possible to compare these medicines with oral licorice root consumption. Large amounts of licorice can lead to hypertension and dangerous potassium depletion, so its use should be supervised.
For decades we have accepted that cirrhosis is not preventable, but by putting together what we now know about the liver, there is hope. One thing is certain: Relying on costly, unpleasant interferon and antiviral therapy followed by exorbitantly expensive, often unsuccessful liver transplants is not a rational way to approach the current and growing cirrhosis epidemic. Health care practitioners should encourage cost-effective nutrition therapies to slow or prevent cirrhosis in the first place.
Diet For A Healthy Liver
Marilyn Sterling, R.D., is a freelance writer, consultant and practicing nutritionist in northern California.
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