Liver Diseases - Natural Therapies

Liver diseases include a number of different health conditions; in conventional medicine, they are bundled under the umbrella term “hepatology”, which typically includes the health conditions related to the liver, the gallbladder, and the pancreas. Over the last several years, there has been an increase in the use of complementary and alternative medicines, especially herbal therapies, among patients with liver disease.^[1] This trend does not seem to be occurring because physicians or specialists are recommending them to their patients; instead, patients are actively seeking out natural remedies to help improve their symptoms or in the hopes of reversing disease processes.

Recently, a survey showed that in chronic liver disease patients, almost one third reported using natural remedies, including vitamins and dietary supplements.^[2] Many characteristics were found to predict use of complementary and alternative medicine, including higher education and family income, certain diagnosed health conditions (like hepatitis C for example), and a history of prior hospitalization. Liver-disease patients are also seeking to use therapies that are safe and are often of the belief that natural or herbal remedies cannot cause any harm. For the most part, many of the natural remedies have excellent safety profiles. However, many specialists are not trained in the use of natural remedies and so will often recommend patients avoid any nonpharmaceutical approaches to err on the side of safety, in case there are drug-herb interactions. A prudent approach would be to discuss supplement use with patients and make recommendations based on the evidence available, something that naturopathic doctors do consistently. Some of the most common liver conditions include nonalcoholic fatty liver disease (NAFLD), hepatitis, cirrhosis, and liver failure. There are many natural supplements available with some evidence behind them, as well as numerous diet and lifestyle measures that have shown benefit. This article will review some of the most evidence-based treatments available for these conditions.

Nonalcoholic Fatty Liver Disease (NAFLD)

NAFLD ranges from mild to more severe and can include hepatic insulin resistance, as well as potentially fibrosis and cirrhosis. NAFLD is essentially how the liver will display metabolic syndrome. This means the underlying physiological issues are inflammation, lipid overload, and oxidative stress. From an evidence-based perspective, one therapeutic option is choline. Choline is a constituent of phosphatidylcholine, which is a component of cell walls and membranes. It is involved in fat and cholesterol metabolism and transport. Choline aids in fat metabolism and transport away from the liver.^[3] A few herbal options have also shown benefit for NAFLD. Based on a clinical study of patients with nonalcoholic fatty liver disease, Gynostemma pentaphyllum may decrease serum triglyceride levels. Based on a clinical study of patients with nonalcoholic fatty liver disease, Gynostemma pentaphyllum may also decrease ALT, ALP, or AST levels (liver enzymes). In the trial, the treatment group saw significant reductions in BMI, AST, ALP, insulin, and insulin resistance index.^[4] These are all positive outcomes. Rhubarb has also been studied. The effective rate of rhubarb (as Danning Pian) for the improvement of clinical symptoms, serum ALT levels, blood lipid, and fatty liver was 85.8%, 78.2%, 39.6%, and 34.0%, respectively, after therapy for three months. The general mild adverse events (15%) included diarrhea, skin rash, and for some possible mild to moderate elevation of serum ALT level.^[5] Green tea extract has also been studied; green tea extract inhibits intestinal lipid absorption and may regulate accumulation of fatty deposits in the liver.^[6]

Finally, omega-3 fatty acids may reduce the accumulation of fatty deposits in the liver, improve insulin sensitivity, and reduce markers of inflammation.^[7] Supplementation with omega-3 fatty acids appears to safely reduce nutritional hepatic steatosis in adults. Omega-3s can be used as DHA in kids and as EPA in adults. From a diet and lifestyle perspective, wine consumption is associated with reduced prevalence of suspected NAFLD. In terms of dieting, low carbohydrate intake appears beneficial. Results indicate that patients on a low-carbohydrate diet had increased fat burning throughout the entire body. Maintenance of normal body weight and avoidance of intake of excess lipogenic simple sugars would seem beneficial for the prevention of NAFLD and its metabolic consequences.^[8]

Hepatitis

Hepatitis is a condition that occurs when there is inflammation of the liver cells, usually from a viral infection (like hepatitis B or hepatitis C), but it can also occur due to alcohol intake. If alcohol is the cause, then probiotics may be a good treatment option. In one study, probiotic therapy was associated with a significant end-of-treatment reduction in ALT, AST, GGT, lactate dehydrogenase, and total bilirubin. Probiotics restored bowel flora and improve liver enzymes in human alcohol-induced liver injury.^[9] Two herbs are also helpful: Cordyceps sinensis and Silybum marianum. Results show that Cordyceps could modulate the cellular immune function, inhibit the humoral immune hyperfunction, and increase serum complement level in patients with posthepatitic cirrhosis, which were correlated to the improvement of hepatic function. A daily dose of 4.5 g has been shown to improve liver function in patients with hepatitis B and posthepatic cirrhosis.^[10] For Silybum, one study showed that one month of 420 mg silymarin daily improved transaminases v. placebo.^[11]

Dietary interventions are also useful. Carbohydrate intake was shown to have a protective effect on the risk of cirrhosis, whereas saturated lipid intake (> 40.4 g fatty acid per day) had a significant multiplicative effect on the risk associated with alcohol consumption.^[12] If hepatitis B is the cause, then the same herbs (Cordyceps and Silybum) may be helpful. A randomized controlled trial on patients suffering from hepatic fibrosis showed beneficial effects on T lymphocyte subsets (CD4, CD8), hyaluronic acid, and precollagen type III, following three months of treatment using Cordyceps sinensis.^[13] For Silybum, liver-related mortality was significantly reduced in all trials, and usage led to no increase risk of adverse events.^[14] Similary, probiotics (Bifidobacterium) levels in 16 patients with chronic hepatitis B, 16 patients with hepatitis B virus–related cirrhosis (HBV cirrhotics), and 15 healthy subjects showed that Bifidobacterium longum was less commonly detected in HBV cirrhotics.^[15] This means supplementation may be protective.

For hepatitis C, in vitro work has shown that the herb curcumin can inhibit the replication of hepatitis C virus.^[16] Antioxidants and polyunsaturated fatty acids may also be helpful. A recent Cochrane review found no evidence to support or refute antioxidant supplements; however, a recent observational study comparing responders and nonresponders (to standard treatment of interferon-α and ribavirin treatment) with chronic hepatitis C revealed that responders had similar antioxidant and polyunsaturated fatty acids (PUFAs) profiles as healthy subjects, plus higher antioxidant, eicosapentaenoic, and arachidonic acid levels, but lower stearic acid than nonresponders.^[17]

Cirrhosis and Liver Failure

Cirrhosis is the result of longstanding liver disease, and it means that scar tissue has replaced healthy tissue, leading to a loss of liver function. There are many potential causes; some of the above-mentioned conditions can cause cirrhosis. Historically, cirrhosis patients have been advised to consume a low-protein diet in order to minimize the production of ammonia and other toxic amino acid metabolites. More recent research has demonstrated that the negative effects of protein malnutrition outweigh the benefits of a low-protein diet. Correction of protein malnutrition in cirrhosis patients may improve overall liver function and reduce the incidence of complications such as encephalopathy, ascites, and diabetes.^[18] Estimated protein requirements for protein malnourished cirrhosis patients is 1.8 g/kg of body weight per day, and 1 g/kgbw for well-nourished cirrhosis patients.^[18] Vitamin D is a supplemental therapy that has supportive evidence. 61 patients with cirrhosis were assessed for vitamin D deficiency.^[19] 29.5% had severe vitamin D deficiency < 7 ng/ml [17.5 nmol/L] and 42.6% had moderate vitamin D deficiency 7–19 ng/ml [17.5–47.5 nmol/L], for a total 72.1% with moderate or severe vitamin D deficiency. Subnormal serum 25-hydroxyvitamin D [25(OH)D] levels in patients with cirrhosis may be due to impaired 25-hydroxalation of vitamin D in the liver. Vitamin D deficiency can contribute to bone loss in patients with cirrhosis.^[19]

Zinc is a mineral that can be supplemented in cirrhosis patients. 45 mg of zinc three times daily for two to three months in patients with advanced cirrhosis, with low to low– normal baseline serum zinc levels, was shown to significantly improve liver function (as per ALT, ALP, galactate elimination capacity, and antipyrine clearance), nutritional status [24-hour urinary creatinine excretion, serum albumin, prealbumin, retinol-binding protein, and insulin-like growth factors (ILGF)], as well as glucose disposal.^[20] Finally, l-carnitine is an evidence-based supplement for cirrhosis. In one study, 31 cirrhosis patients were randomly assigned to receive three grams of l-carnitine twice daily for four weeks or to serve as the control group. The l-carnitine patients had a 46% decrease in mean serum ammonia concentration after one week, and a 70% decrease after four weeks. Serum ammonia levels were completely normal after four weeks in 14 of the 16 patients receiving l-carnitine.^[21]

If liver failure occurs, there is often biochemical evidence of thiamine deficiency early in the course of the illness, probably as a result of inadequate intake of the vitamin. This means that supplements of the vitamin should be included in the routine management of patients with acute hepatic failure.^[22] Antioxidants may also be helpful, since liver transplant recipients are at increased risk of oxidative stress due to preexisting liver failure, ischemia-reperfusion injury, functional impairment of graft, rejections, and immunosuppression.^[23]

Conclusion

Overall, the message is that there are many herbal and nutritional supplements available to treat liver diseases. Many of them are evidence-based, but should be taken after ensuring they are safe. That means they should be prescribed by a licensed naturopathic doctor, who will ensure there are no dangerous interactions going on, and who can supervise case management. There are also several dietary and lifestyle approaches that can be helpful. The exact nature of each treatment depends on which condition is being treated and should be individualized for each patient.