A Review of Plants Used in
in the Treatment of Liver Disease: Part 1

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:    Frankp@chiro.org

FROM:   Alternative Medicine Review 1998 (Dec); 3 (6): 410–421 ~ FULL TEXT

Scott Luper, N.D.

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Introduction

Treatment options for common liver diseases such as cirrhosis, fatty liver, and chronic hepatitis are problematic. The effectiveness of treatments such as interferon, colchicine, penicillamine, and corticosteroids are inconsistent at best and the incidence of side-effects profound. All too often the treatment is worse than the disease. Conservative physicians often counsel watchful waiting for many of their patients, waiting in fact for the time when the disease has progressed to the point that warrants the use of heroic measures. Physicians and patients are in need of effective therapeutic agents with a low incidence of side-effects. Plants potentially constitute such a group.

In recent years many researchers have examined the effects of plants used traditionally by indigenous healers and herbalists to support liver function and treat diseases of the liver. In most cases, research has confirmed traditional experience and wisdom by discovering the mechanisms and modes of action of these plants as well as reaffirming the therapeutic effectiveness of certain plants or plant extracts in clinical studies.

Several hundred plants have been examined for use in a wide variety of liver disorders. Just a handful have been fairly well researched. The latter category of plants include: Silybum marianum (milk thistle), Picrorhiza kurroa (kutkin), Curcuma longa (turmeric), Camellia sinensis (green tea), Chelidonium majus (greater celandine), Glycyrrhiza glabra (licorice), and Allium sativa (garlic). This review will be divided into two parts. Silybum marianum and Picrorhiza kurroa, will be reviewed in Part One. Curcuma longa, Camellia sinensis, Chelidonium majus, Glycyrrhiza glabra, and Allium sativa will be reviewed in Part Two.

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Silybum marianum (milk thistle)

Silybum marianum is currently the most well researched plant in the treatment of liver disease (with over 450 published peer review papers). The genus Silybum is a member of the daisy family (Compositae). The plant itself is a stout thistle, growing one to three meters tall in rocky soils, with large purple flowering heads (Figure 1) The leaves are characterized by distinct white "milky" veins that give the plant its common name.

History, Early Authors

Silybum is cited as one of the oldest known herbal medicines. Dioscores first described the plant. In Roman times, Pliny the Elder (A.D. 77), a noted naturalist, described the medicinal uses of milk thistle, indicating it was "excellent for carrying off bile." [1] Culpeper (1650) wrote of its effectiveness in removing obstructions of the liver and spleen. [2] But it has been relatively recent clinical research, especially in Germany, which has brought the use of Silybum to prominence in the treatment of chronic or acute liver disease, as well as protecting the liver against toxicity.

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Active Constituents

The active constituents of milk thistle are flavonolignans including silybin, silydianin, and silychristine, collectively known as silymarin. Silybin (Figure 2) is the component with the greatest degree of biological activity, and milk thistle extracts are usually standardized to contain 70–80 percent silybin. Silymarin is found in the entire plant but is concentrated in the fruit and seeds. Silybum seeds also contain betaine (a proven hepatoprotector) and essential fatty acids, which may contribute to silymarin's anti-inflammatory effect.

Pharmacokinetics

Silymarin is not water soluble and so cannot be taken as a tea. It is typically administered as an encapsulated standardized extract. The absorption with oral administration is rather low with only two to three percent of the silybin recovered in 24 hours from rat bile. [3,4] The peak plasma levels after an oral dose are achieved in four to six hours in both animals and humans. [3–5] Silymarin is cleared from the body predominantly via the bile and to a lesser extent the kidney. The clearance half-life is six to eight hours. [5]

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Clinical Indications

Mushroom Poisoning: The most remarkable use of silymarin is in the treatment of Amanita mushroom poisoning. The Amanita genus is widespread in Europe and North America, and several species are considered choice by mushroom collectors. Unfortunately, the genus also contains several of the most toxic mushrooms in existence. Amanita mushrooms possess two extremely powerful hepatotoxins, amanitin and phalloidin (the LD50 of amanitin is 0.1 mg/kg body weight). Historically, the accidental ingestion of mushrooms containing these toxins results in about 60 cases of poisoning per year in the United States and Europe, with a mortality rate of about 30 percent. [6]

In mice, silymarin was 100 percent effective in preventing liver toxicity if given before or up to ten minutes after Amanita toxin poisoning. Severe liver damage (and death) was avoided if silymarin was administered within 24 hours. [7] In a study with dogs (who model human Amanita poisoning quite well), none of the dogs died when given silymarin 5–24 hours after ingesting an LD50 dose of Amanita phalloides (85 mg/kg). In comparison, untreated dogs experienced a mortality rate of 33 percent. Liver enzyme studies and liver biopsies in the controls and treated dogs demonstrated a significant hepatoprotective effect for the silymarin. [6]

The hepatoprotective effects of silymarin in humans after ingestion of Amanita toxins have been repeatedly demonstrated. In one series of 18 patients treated with silymarin, all patients survived except one particularly high-dose suicide. The authors concluded, "Administration of silymarin even up to 48 hours after mushroom ingestion appears to be an effective measure to prevent severe liver damage in Amanita phalloides poisoning." [8] In a 1995 study of 41 mushroom poisoning victims, none died in the group which included silymarin in the treatment regimen. [9]

A 1996 report made the case that silymarin may be useful even three days post toxification. A family of four poisoned by Amanita mushrooms was admitted to the hospital with severe liver damage. Although all were treated with standard therapy, there was a worsening of the clinical picture until the third day, when it was decided to add silybin dihemisuccinate by intravenous route to the therapy. After the beginning of silybin administration the patients showed a favorable course with a rapid resolution of the clinical picture, although the prognosis appeared severe on the basis of hepatochemical examination results. [10]

A particularly dramatic case of a very severe accidental poisoning in a seven-year-old girl resulted in her entering a hepatic coma. The authors reported the girl's survival was due in large part to treatment with silymarin in combination with high doses of G-penicillin. [11]

General Hepatoprotective: Many studies have demonstrated the beneficial hepatoprotective effects of treatment with silymarin. In a Finnish military hospital study on consecutive patients with elevated serum liver enzymes (mostly due to ethanol ingestion), 420 mg/day silymarin was found to significantly lower liver enzymes ? aspartate aminotransferase (AST), alanine amino-transferase (ALT) ? after four weeks. Histologic examination of liver biopsies also demonstrated a statistically significant improvement. [12]

In an Italian study of 20 patients with chronic active hepatitis, 240 mg/day of silybin-phosphatidylcholine complex for only seven days was found to significantly lower serum liver enzymes ? AST, ALT, gamma-glutamyl transferase (GGT), alkaline phosphatase, and total bilirubin. [13]

In a Hungarian study of 36 patients with chronic alcoholic liver disease, 420 mg/day of silymarin resulted in a normalization in serum liver enzymes (AST, ALT, GGT), total bilirubin, and an improvement in the histological examination of liver biopsies after six months of treatment. In addition, procollagen III peptides (a marker of active fibrosis) were found to be significantly decreased in the treatment group. [14]

In an Austrian study involving 170 patients with liver cirrhosis, 420 mg/day of silymarin for an average of 41 months resulted in a significant improvement in survival (58% in silymarin-treated patients and 39% in the placebo group (P = 0.036)). No side-effects of silymarin were noted in this study [15] or in others cited above.

Not every study found a beneficial effect of silymarin administration. In a French study on 116 patients with histologically proven alcoholic hepatitis, 420 mg/day of silymarin for three months was not found to significantly alter the course of the disease. Both the treated and the placebo groups had similar rates of abstinence (46%), and significant improvement in the score of alcoholic hepatitis and serum amino transferase activity, irrespective of treatment with silymarin or placebo. Four patients died of hepatic failure during the trial, one in the treatment group and three in the placebo group (not statistically significant). As usual, no side-effects were noted. [16]

It is interesting to note that while silymarin has been shown to have a profound hepatoprotective effect on chronic exposure to ethanol, it has no direct effect on ethanol metabolism. When studied, silybin had no effect on reducing blood ethanol levels or the rate at which ethanol is removed from the body. [17]

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