There are three types of review articles referenced here: 1) In a general review a broad picture of the scientific studies and evidence available on a particular topic is presented, 2) In a systematic review, data from a set of studies on a particular question or topic are collected, analyzed, and critically reviewed, and 3) A meta-analysis uses statistical techniques to analyze results from a collection of individual studies.

Milk Thistle

Milk thistle (scientific name Silybum marianum) is a plant from the aster family. The active extract of milk thistle believed to be responsible for the herb's medicinal qualities is silymarin, found in the fruit. Milk thistle has been used in Europe as a treatment for liver disease and jaundice since the 16th century.

Summary of the research findings

The results of scientific studies to date do not definitively find that milk thistle is beneficial in treating hepatitis C in humans.

Studies in laboratory animals suggest that silymarin may have various benefits to the liver, such as promoting the growth of certain types of liver cells, having a protective effect upon liver cells, fighting a chemical process called oxidation that can damage cells, and inhibiting inflammation. However, in some cases, a consistent pattern of benefit was not seen, and these studies did not specifically examine the effects of silymarin on
hepatitis C.

There have been some studies on silymarin or milk thistle in humans. These studies have generally been small and on liver diseases rather than on hepatitis C infection specifically, and the results have been contradictory (with some positive and some negative). A review and a meta-analysis published in 2001 on silymarin in the treatment of liver diseases found it to be generally safe, but contained no firm conclusions with regard to its use to treat viral hepatitis. A 2002 systematic review on milk thistle for liver disease found "no reduction in mortality (frequency of death as an outcome), in improvements in histology (tissue studies) observed through liver biopsy, or in biochemical markers of liver function" and that the data was too limited to support recommending milk thistle for treatment of liver disease.

To obtain more extensive and reliable data, NCCAM is sponsoring a clinical trial on the use of milk thistle for hepatitis C.

Side effects and other risks

Milk thistle is generally well-tolerated and has shown few side effects in clinical trials. It can cause a laxative effect; less common effects include nausea, diarrhea, abdominal bloating, fullness, and pain. Milk thistle can produce allergic reactions, which tend to be more common among people who are allergic to plants in the same family (e.g., ragweed, chrysanthemum, marigold, and daisy).

Licorice Root

Licorice root is the peeled or unpeeled dried root of the licorice plant (Glycyrrhiza glabra). The primary active component of licorice root is a substance called glycyrrhizin. Licorice root has been in use in China since the second and third century B.C. and in the West since Egyptian, Greek, and Roman times.

Summary of the research findings

Laboratory studies of glycyrrhizin in cell cultures suggest that it may have antiviral properties.

In a review of several randomized controlled trials, researchers reported that glycyrrhizin has potential for reducing long-term complications in chronic hepatitis C in those patients who may not respond to interferon. Several of the trials reviewed indicated improvements in liver tissue damaged by hepatitis. Some also showed improvements in how well the liver did its job after treatment.

A 1997 study and a 2002 review suggest that long-term administration of glycyrrhizin might prevent liver cancer in patients with chronic hepatitis C.

The use of glycyrrhizin as a complementary therapy (i.e., used in addition to conventional interferon therapy) has been studied, but no significant benefit has been found. Recent clinical trials have shown that taking glycyrrhizin lowers the levels of liver enzymes (increased levels of certain liver enzymes indicate liver damage or inflammation). However, taking the herb did not reduce the amount of HCV in patients' blood, a critical indicator of the long-term progress of the infection.

Side effects and possible risks

Taking licorice over a prolonged period of time can lead to potentially serious side effects, including high blood pressure, salt and water retention, swelling, depletion of potassium, headache, and/or sluggishness. Glycyrrhizin can worsen ascites, the accumulation of fluid in the abdominal cavity, a condition that can be caused by cirrhosis. The herb also can interact with certain drugs, such as diuretics, digitalis, antiarrhythmic agents, and corticosteroids.

Ginseng

The herb ginseng comes in two types: American ginseng (Panax quinquefolius) and Asian ginseng (Panax ginseng). Among the Asian forms of ginseng are Chinese, Japanese, and Korean ginseng. (So-called "Siberian ginseng" is not a true ginseng.) Ginseng has been used for thousands of years in Asia. It is usually used with the belief that it will boost the immune system and increase stamina; such properties are thought to be more useful for the elderly and those recovering from illness.

Summary of the research findings

The research on ginseng that has been done to date has been primarily in animal models and human tissue in the laboratory. Some beneficial effects of ginseng on the liver were seen in these studies. Researchers concluded that ginseng may also help strengthen glandular systems and the ability to resist disease.

One study found that ginseng may be helpful for elderly people with liver conditions similar to hepatitis.

No conclusions can be drawn about the possible usefulness and safety of ginseng as a treatment in people who have hepatitis C, because it has not yet been studied formally in people.

Side effects and possible risks

General adverse (negative) effects of ginseng can include insomnia, headache, nosebleed, nervousness, and vomiting. Prolonged use of caffeine and a high dose of ginseng may be associated with hypertension, which is of particular concern for people with cardiovascular disease or diabetes. In addition, people with diabetes who use insulin should be aware that ginseng has demonstrated hypoglycemic effects (lowering of the blood sugar). Ginseng has been shown in laboratory studies to inhibit grouping of platelets in the blood, increasing bleeding risk. Because of this, using ginseng along with NSAIDs (non-steroidal anti-inflammatory drugs), such as aspirin or ibuprofen, should be discussed with your health care provider.

Thymus Extract

The thymus is a gland that is involved in the regulation of the body's immune response. Thymus extract products consist of peptides taken from the thymus glands of cows or calves and are sold as dietary supplements. Often, these products carry claims of boosting immune system functioning to combat diseases, such as hepatitis C. These over-the-counter supplements should not be confused with the prescription drug thymosin alpha-1.

Summary of the research findings

There has been little testing of bovine thymus extract for treatment of hepatitis C. A small clinical trial of a product called Complete Thymic Formula, which contains bovine thymus extracts along with vitamins, herbs, minerals, and enzymes, did not find the product beneficial for hepatitis C patients who had not responded previously to interferon therapy. However, this small study does not provide sufficient evidence to draw firm conclusions about either Complete Thymic Formula or thymus extracts in general.

Side effects and possible risks

In the study of Complete Thymic Formula, one adverse event was reported: a patient developed thrombocytopenia, a drop in the number of platelet cells in the blood; the patient recovered after treatment was stopped. In general, no adverse effects from thymus extracts have been reported. However, since thymus extracts are derived from animals, there can be concern related to possible contamination from diseased animal parts. Accordingly, people on immunosuppressive drugs or who have suppressed immune systems, such as transplant recipients or persons with HIV/AIDS, should use caution about thymus extracts and consult with their health care provider.

Schisandra

Schisandra is a plant that has been used (through extracts from its fruit) in traditional Chinese medicine and in Kampo, traditional Japanese medicine. There are several species, including Schisandra chinensis, native to northeastern China and Korea, and Schisandra sphenanthera, native to China.

Summary of the research findings

Research has primarily focused on the various lignans (a class of plant nutrients) and essential oils in the dried fruit of schisandra. Major constituents include the lignans gomisin A, schizandrins and schizandrol, vitamins C and E, and others.

Studies of the effects of schisandra in the liver have mostly been in animal models. These studies have suggested that extracts of the fruit have a liver-protective effect, a helpful effect on some liver enzymes, and an antioxidant effect.

Schisandra is also used in herbal formulas. For example, an herbal medicine called TJ-108 (Ninjin-yomei-to is one of its Japanese names) used in Kampo has schisandra fruit among its herbal components. In one very small study, TJ-108 was compared with two other Kampo herbal formulas for effects in 37 patients who had chronic hepatitis C and had been treated before with interferon. The findings were that TJ-108 may have antiviral properties, which the authors attributed to schisandra fruit and its lignan gomisin A. These findings need to be interpreted with caution because of the study's small size and because use of an herbal formula, not schisandra alone, was evaluated; herbal formulas contain many ingredients that could cause a variety of effects.

There are no reports on the safety and effectiveness of using schisandra alone for treatment of hepatitis C in humans in the sources reviewed for this report.

Side effects and other risks

Schisandra is considered generally safe. In some people, however, it may cause heartburn, acid indigestion, decreased appetite, stomach pain, or allergic skin rashes. Antioxidants are substances (such as vitamin E) that help prevent oxygen from reacting with other chemicals in cells (oxidation), a process that can have negative effects.

Colloidal Silver

Silver is a metallic element that is mined as a precious metal. People are exposed to silver, usually in tiny amounts, through their environment, drinking water, food, and possibly work or hobbies. Colloidal silver supplements consist of tiny silver particles suspended in a liquid base. They are often marketed with a variety of unproven health claims, including for immunity, diabetes, cancer, and AIDS.

Summary of the research findings

Silver has had some medicinal uses going back for centuries. However, more modern and less toxic drugs have eliminated the vast majority of these uses. Reviews in the scientific literature on colloidal silver have concluded that:

Silver has no known function in the body.
Silver is not an essential mineral supplement or a cure-all and should not be promoted as such.
Claims that there can be a "deficiency" of silver in the body and that such a deficiency can lead to disease are unfounded.
Claims made about the effectiveness of colloidal silver products for numerous diseases are unsupported scientifically.
Colloidal silver products can have serious side effects (discussed below).
Laboratory analysis has shown that the amounts of silver in these supplements vary greatly, which can pose risks to the consumer.

Side effects and other risks

Animal studies have shown that silver builds up in the tissues of the body. In humans, this accumulation can have a serious side effect called argyria, a bluish-gray discoloration of the body, especially of the skin, other organs, deep tissues, nails, and gums. How this happens is not fully known, but silver-protein complexes are thought to deposit in the skin and then be processed by sunlight (similar to traditional photography). Argyria is not treatable or reversible. Other possible problems include neurologic problems (such as seizures), kidney damage, stomach distress, headaches, fatigue, and skin irritation.

Colloidal silver may interfere with the body's absorption of the following drugs: penacillamine, quinolones, tetracyclines, and thyroxine.