Cirrhosis and Liver Disease

Nutritional and Supplemental Support

The same rule that applies to conventional pharmaceuticals applies to nutritional supplements: they should be used with caution by people with liver diseases because they are often metabolized in the liver. It is important that people with liver disease work in close cooperation with a knowledgeable and qualified physician to design a program of nutritional support.

Nevertheless, there are numerous nutritional approaches that have been studied in liver disease that can help slow the inflammation associated with advancing liver disease and support healthy liver function. For more detailed information on Vitamin Depot Online.com ’s anti-inflammatory recommendations, please see the Inflammation chapter. It is also critical that alcohol be strictly avoided.

The following nutrients have been shown to enhance liver function and reduce inflammation:

Fish oil. Omega-3 fatty acids and sesame lignans have been shown to reduce inflammation, which is a distinctive feature of liver disease and cirrhosis (Barham JB et al 2000; Dias VC et al 1995; Gronn M et al 1992; Shimizu S et al 1991; Chavali SR et al 1999; Utsunomiya T et al 2000).

Studies have shown that reducing the ratio of omega-6 to omega-3 fatty acids prevents liver damage induced by total parenteral (intravenous) nutrition in newborn piglets, rats, and humans (Van Aerde JE et al 1999; Yeh SL et al 1997; Chen WJ et al 2003; Alwayn IP et al 2005). Thus, it may be prudent for patients with cirrhosis to take fish oil supplements and lower their consumption of omega-6 fats, such as those found in corn oil.

It is important that any increase in fatty acids be accompanied by an increase in vitamin E. Without supplemental vitamin E, even fish oil can be detrimental. Diets containing 35 percent of calories from fish oil are likely to exacerbate liver damage due to alcohol and other toxins because fish oil’s polyunsaturated bonds are so readily oxidized by free radicals (Nanji AA et al 1989a,1989b,1994).

Monounsaturated oils, such as olive oil, should be the major source of fat calories for those with cirrhotic liver disease. Monounsaturated oils are preferable since saturated fats from animal sources usually contain considerable amounts of arachidonic acid, the precursor to inflammatory prostaglandins. For those whose main source of fat calories is animal fat, supplementation with eicosapentaenoic acid (EPA) may help to reduce the buildup of pro-inflammatory arachidonic acid and reduce levels of inflammatory mediators (Barham JB et al 2000).

In addition to using olive oil in preference to corn oil or animal fats, people with liver disease would most likely benefit from supplementation with a dose of fish oil high enough to inhibit inflammatory prostaglandin synthesis without providing a significant target for reactive oxygen species. While more work is needed to determine how much fish oil is too much, the nutrition studies cited above suggest that supplementation with fish oil should be limited to about 10 percent of total calories (Nanji AA et al 2001). Also, maintaining high levels of antioxidant nutrients such as vitamin E will help limit oxidant damage from polyunsaturated fats.

SAMe. By increasing oxidative stress, many liver toxins, such as alcohol and acetaminophen, deplete glutathione and other important antioxidant molecules. As a result, SAMe, a glutathione precursor, is also decreased (Lieber CS 2002). In both rodents and nonhuman primates, depletion of antioxidants occurs at early stages of liver disease. Supplementation with SAMe restores levels of glutathione and decreases liver damage in animals and it has been recommended as an area of study for humans with early liver disease or with chronic exposure to liver toxins, including alcohol (Lieber CS 2002; Vendemiale G et al 1989).

In one clinical trial, 123 patients with alcoholic liver cirrhosis were given either a placebo or 1200 mg daily of oral SAMe. At the end of the two-year trial, 30 percent of the placebo-treated patients had died, compared with 16 percent of people in the SAMe group. When the patients with the most severe disease were excluded from the calculation, these numbers became 29 percent in the placebo group and only 12 percent in the SAMe-supplemented group (Mato JM 1999). The livers in the patients with the most advanced cirrhosis may have been too damaged to respond to the SAMe.

PPC. Phosphatidylcholines are produced in the liver through a process involving SAMe. Supplementing alcohol-treated rats or baboons with polyenylphosphatidylcholine (PPC) during alcohol feeding prevents the depletion of SAMe (Aleynik SI et al 2003).

In rats, PPC treatment accelerated regression of preexisting fibrosis (Ma X et al 1996). In a baboon study, none of the animals fed 2.8 g PPC per 1000 calories (about 2 g daily per 20 kg body weight) developed fibrosis or cirrhosis, even after 6.5 years of alcohol feeding, whereas 10 out of 12 untreated baboons developed fibrosis or cirrhosis (Lieber CS et al 1994). In addition to preventing alcohol-induced oxidative stress, PPC stimulates the enzyme responsible for the breakdown of liver collagen (Lieber CS et al 1994).

Among humans, two years of treatment of alcoholic cirrhosis patients with 4.5 g daily of PPC resulted in favorable changes in two blood parameters of liver damage, bilirubin and liver transaminases, among certain subgroups. Fibrosis, however, continued to progress, leading the authors to conclude that while PPC is effective in preventing liver damage among animals, it is less effective among humans with long histories of drinking (Lieber CS et al 2003a).

Silymarin. A standardized plant extract from milk thistle, silymarin contains about 60 percent silibinin (Boigk G et al 1997). Silymarin appears to inhibit the formation of mediators of inflammation, such as leukotrienes (Dehmlow C et al 1996). In animal studies, silymarin protected the liver from carbon tetrachloride damage and slowed the accumulation of scar tissue in the biliary tract (Kravchenko LV et al 2000; Batakov EA 2001; Boigk G et al 1997). In baboons, silymarin slowed the progression of alcohol-induced liver fibrosis (Lieber CS et al 2003b).

Some placebo-controlled human trials have shown promising results. For example, in one study of patients with alcoholic cirrhosis, mortality was 39 percent among the patients treated with Legalon, a proprietary standardized product containing 70 percent to 80 percent silymarin, after 24 to 41 months of treatment. Mortality in placebo-treated patients was significantly higher, 58 percent (Ferenci P et al 1989). In another clinical study, this same silymarin preparation normalized blood levels of bilirubin and other markers of liver disease after six months (Feher J et al 1989). Favorable changes in blood chemistry were noticed in as little as four weeks (Salmi HA et al 1982).

Improvements were also observed with a silymarin-phospholipid complex in patients with chronic active hepatitis (Buzzelli G et al 1993). Recently, an Italian firm has developed a proprietary preparation of silibinin complexed with both vitamin E and phospholipids. The complex successfully protected rat livers against necrosis and inhibited collagen formation in rats after bile duct obstruction (Di Sario A et al 2005).

Antioxidants. Since cirrhosis is the result of chronic injury to the liver from free radicals, antioxidant therapy may slow the progression of the disease. Studies have found that people with cirrhosis have low levels of vitamin C and vitamin E (Prakash S et al 2004).

In one remarkable study, patients with hepatitis C were given seven oral antioxidants, glycyrrhizin (500 mg twice daily), schisandra (500 mg three times daily), silymarin (250 mg three times daily), ascorbate (2 g three times daily), lipoic acid (150 mg twice daily), L-glutathione (150 mg twice daily), and alpha-tocopherol (800 IU daily) for 20 weeks. Four different intravenous antioxidant preparations, including glycyrrhizin (120 mg), ascorbic acid (10 g), L-glutathione (750 mg), and B-complex (1 mL; composition not specified), were also administered twice weekly for the first 10 weeks. No significant side effects were observed. Normalization of liver enzymes, which indicated reduced liver injury, occurred in 44 percent of patients. One-fourth of the patients showed viral load decreases of 90 percent or more. Histologic improvement was noted in 36 percent of patients (Melhem A et al 2005).

Consistent with these findings, an Italian study demonstrated that eating foods high in antioxidants (fruits and vegetables) decreased the progression of cirrhosis, while a high level of fatty animal products and sugar from nonfruit sources increased it (Corrao G et al 2004).

Animal products are high in arachidonic acid, a precursor to inflammatory mediators such as prostaglandins and leukotrienes, and sugars from nonfruit sources are more likely to increase insulin levels because fiber is not present to slow the absorption of sugar. High insulin levels stimulate the conversion of arachidonic acid into inflammatory prostaglandins. The resulting inflammation generates high levels of reactive oxygen species. Thus, cirrhotic patients should avoid nonfruit sources of sugar or consume additional fiber when nonfruit sugars are consumed.

Selenium, a potent antioxidant, appears to protect against hepatic cancers. In a four-year trial, selenium-enhanced table salt reduced primary liver cancer 35 percent in study participants compared with controls. In a study involving hepatitis B patients, one 200-mcg tablet of selenium daily reduced the incidence of primary liver cancer to zero. When selenium supplementation ceased, primary liver cancer incidence began to rise, indicating that hepatic carcinoma risk may be minimized with selenium supplementation (Yu SY et al 1997).

Branched-chain amino acids. The branched-chain amino acids (BCAAs) include leucine, isoleucine, and valine. They must be obtained in the diet because the human body cannot make them. Cirrhotic patients have an increased energy requirement that BCAAs seem to fill better than glucose or amino acids (Kato M et al 1998). Supplementing the diet with these amino acids lowers hospital admission rates and improves nutritional parameters, liver function tests, and overall quality of life in patients with liver disease (Marchesini G et al 2003). In addition, supplementing with BCAAs after surgery for hepatic carcinoma shortens hospital stays and improves the return of liver function (Meng WC et al 1999). Encephalopathy is also alleviated after treatment with BCAAs (Marchesini G et al 1990).