HERBResearch Germany Dr. Mathias Schmidt Wartbergweg 15 D-86874 Tussenhausen-Mattsies Telefon: +49 (0) 82 68.90 81 74 Telefax: +49 (0) 82 68.90 81 75 e-mail: schmidt@herbresearch.de www.herbresearch.de Expert Report (Sulfad) Germany, 20.11.2008 Sulfad finished products contains milk thistle extract, liquorice extract, artichoke extract and curcuma extract. All these plants are used in liver protective preparations. 1-Milk thisle: In an increasingly toxic world, we place growing burdens on the body's detoxification system, the hub of which is the liver. Millions of compounds are detoxified within each liver cell, or hepatocyte. Inevitably, this wear and tear compromises liver cells and surrounding connective tissue. Hepatotoxicity is fast becoming a major health issue. In fact, many practitioners believe poor liver function caused by toxin accumulation or by liver-function decline may contribute to other seemingly unrelated illnesses, such as rheumatoid arthritis, eczema, migraine headaches and premenstrual syndrome, and may manifest symptoms of its own. As a result, milk thistle (Silybum marianum) is widely prescribed by herbalists throughout Europe and the Americas for liver protection. Milk thistle, also known as St. Mary's thistle and lady's thistle, is native to Asia Minor, North Africa, southern Europe and southern Russia. It has been naturalized to central Europe, North and South America, and South Australia. The herb has dark-green prickly leaves mottled or streaked with white veins, blooms from June to September and can grow to six feet tall. Its medicinal properties are found in the small, hard fruits, sometimes called seeds but known technically as achenes, that appear after the plant flowers.
Milk thistle fruits contain a mixture of flavonolignans a unique group of carbohydrates that share a common chemical structure. These flavonolignans, the plant's active constituents, are known collectively as silymarin. Silymarin usually comprises about 1.5 to 3 percent of the fruit and contains silybinin, the major constituent, along with isosilybin, dihydrosilybin, silydianin, silychristin, and probably a few flavonoids. The fruits also contain 20 to 30 percent fixed oil (a combination of fatty acids that are solid at room temperature), mucilage, protein and taxifolin (a chemical with unknown significance). Although milk thistle's mechanism of action has not been fully explained, the herb has a long history of use as a liver protectant and liver decongestant. (A liver decongestant stimulates bile flow through the liver and gallbladder, thus reducing stagnation and preventing gallstone formation and bile-induced liver damage.) Pharmacological investigations have centered on silymarin, which is most notable for its antihepatotoxic activity. This effect has been demonstrated against a variety of potent liver toxins including those from the death cap mushroom (Amanita phalloides). S. marianum extract works as both a preventive and antidote for death cap mushroom poisoning. Intravenous administration up to 48 hours after ingestion is effective. Finnish researchers conducted a double-blind, controlled study to look at the effect of milk thistle fruit extract on liver inflammation. They measured levels of serum transaminase, an enzyme released from inflamed liver cells, in 97 patients. All subjects reportedly abstained from alcohol during the four-week study during which they received either a 420 mg daily dose of standardized S. marianum extract (Legalon, manufactured by Madaus AG of Germany) or placebo. Subjects who received the extract showed a statistically significant decrease in liver enzymes compared with those taking placebo. In a larger clinical trial, researchers assessed the benefits of milk thistle extract on 170 patients, 91 of them alcoholics with liver cirrhosis. Subjects received 140 mg silymarin three times daily for 41 months. The four-year survival rate was 58 percent in the silymarin group and 39 percent in the placebo group a difference of 19 percent. The reduced death rate among those taking silymarin was most pronounced in the alcoholic cirrhosis subgroup. There were no side effects from silymarin. 5 This study is significant for several reasons. The results support the idea that long-term treatment with milk thistle extract is beneficial and not likely to be harmful. These results also suggest milk thistle extract may be particularly effective for patients with alcohol-induced liver damage.
In all, studies suggest S. marianum protects the liver. It is prescribed for any condition of threatened or obvious hepatotoxicity including chronic daily exposure to environmental pollutants, toxic effects of viral hepatitis, toxic side effects of certain medications, toxicity from chronic alcohol use, cirrhosis and fatty degeneration of the liver. Milk thistle extract should help improve liver function, protect hepatocytes and increase bile flow for anyone with these conditions. The antihepatotoxic effects are quite pronounced while the liver-decongesting and bile-stimulating effects are mild and gentle. This herb is extremely well tolerated. Milk thistle is effective in a variety of preparations, though the traditional one is a medicinal tea or decoction. Silymarin is poorly soluble in water but historical use indicates its bioavailability increases if the crushed fruits are soaked overnight before being boiled for 15 minutes. A therapeutic tea contains 1 to 3 tablespoons of crushed fruits per 8 to 10 ounces of water. Another preparation is alcohol and water extraction, commonly known as a tincture. Encapsulated standardized milk thistle extract is the preparation studied in clinical trials. Extracts are typically standardized to 70 percent of the silymarin complex. The typical dose is 200 to 420 mg daily taken in three divided doses with meals for eight weeks, then 280 mg/day in three divided doses. There are no known side effects or contraindications, and this herb is safe for use during pregnancy and lactation. Milk thistle can be taken as a preventive measure, particularly if a person eats chemically processed foods, is exposed regularly to foreign compounds that require detoxification, has a known liver disease or family history of liver disease, or drinks alcohol regularly. Long-term continued use has no known side effects or contraindications. Recommend that customers discontinue use for two to seven days every eight weeks to maintain effectiveness, as they should with any herbal medicine. Pollutants, toxic medications and exposure to infectious organisms underscore the need for liver protection. Milk thistle offers a reliable and safe solution. 2-Licorice (Glycyrrhizae radix) is one of the oldest and most frequently used botanical treatments in East Asia. Licorice has been recommended for its life-enhancing properties, detoxification and as a cure for digestive disorders and swelling. Herbal medicines containing licorice have shown stimulatory effects in immune systems. Licorice has also been reported to attenuate free radical-induced oxidative damage in the kidney and prevent
carcinogenesis induced by toxicants or hormones. Licorice contains flavonoids and pentacyclic triterpene saponins including liquiritigenin, liquiritin, isoliquiritigenin, liquiritin apioside and glycyrrhizin. Among these components, glycyrrhizin, which is the major constituent, comprises 4% to 13% of the dried root weight. Glycyrrhizin has antiviral. anticarcinogenic and hepatoprotective effects. Liquiritigenin, an aglycone of liquiritin, shows cytoprotective effects against heavy metals induced toxicity in a rat-derived hepatocyte cell line and hepatoprotective effects against acute injuries induced by acetaminophen. There are approximately 35 heavy metals in our environment. Heavy metals become toxic when they are not metabolized, which allows them to accumulate in many organs. 3-Artichoke has been shown to be a natural remedy which improve various digestive health disorders, shown to significantly lowered blood ldl cholesterol levels, prevent heart disease and atherosclerosis - plaque problems, enhance detoxification reactions, as well as protect the liver from damage. This combination of benefits is very important to healthy liver function. During detoxification of the liver, the toxic substance is often initially converted to an even more toxic form. Without adequate protection, every time the liver neutralizes a toxin, it is damaged in this process. Artichoke extract has been shown to provide these valuable preventitative health benefits and protection. The naturally occuring curcuminoids found in the curcuma rhizomes extract along with the flavonoid found in the milk thistle extract, those from the silymarin group found in the Milk Thistle, combined with the bioflavonoids and cynarine in the artichoke extract, all work synergistically with the procaine complexes to feed and protect damaged cells from free radical damage. The concept of hepato-protection basically reflects an appreciation of the liver's critical role in many aspects of metabolism and the importance of improving the liver's function by protecting it from damage. Antioxidants are among the many compounds that can offer significant protection of the liver. Artichoke extract has demonstrated a strong antioxidant potential and hepato-protective effect in recent research on animals. It protects the liver and the animal from the damaging effects of toxins, such as carbon tetrachloride and other environmental chemicals in a manner similar to that of silymarin from the milk thistle. Like milk thistle, artichoke extract stimulates the regeneration of damaged liver tissue. The usefulness of
artichoke for preventing or reducing build-up of fat in the liver from chronic alcohol consumption is noteworthy. The regenerative effect of artichoke leaf extract was studied on rats after removal of part of the liver. Clear signs of regeneration were observed, such as increase in liver tissue and liver cell content of RNA, stimulation of cell division and increase of blood circulation in the liver. Studies of hepato-protective action have only been done in animals, as the common procedure involves exposure to toxins. The basic research method for this type of investigation is to give the test substance, in this case artichoke leaf extract, to the animal prior to or simultaneously with administration of a toxic substance and observe the results 4-Curcuma longa (Zingiberaceae family, commonly known as temu lawak or turmeric in Indonesia and India), which is found both wild and cultivated in Indonesia, has been traditionally used for medicinal purposes. Turmeric is also used as a tonic in Indonesia. Many pharmacological and clinical studies are done on the efficacy of tumeric for the treatment of acute liver damage induced by acetaminophen and carbon tetrachloride in mice. The results clearly indicated that extract of turmeric could reduce significantly the acute elevation of serum transaminases levels induced by the two kinds of hepatotoxins, and alleviated the degree of liver damage at 24 hours after the intraperitoneal administration of two hepatotoxins. It may be concluded that turmeric can protect the liver from various hepatotoxins, hence turmeric could be useful in the treatment of liver injuries and has promise as a kind of broad spectrum hepatoprotective agent (4). Finally, I highly recommend the use of the combination of the four food plant extracts, because of the possible synergic effect of these plants in the liver protective effect and in the curative effect. Additionally, the mixture shows to have no toxic effect in the chronic toxicity study which was done on the finish product (sulfad). DR. Mathias Schmidt Member of the German FDA for the registration of herbal medicinal products