For Your Health

[Past and present]

***Is Milk Thistle Useful for Viral Hepatitis***

..Written by Case Adams, Naturopath

...Milk thistle has been successfully used to treat liver inflammation for centuries. Over recent years, doctors have been applying it to hepatitis conditions with varying success. Now recent research is confirming that Milk thistle's primary constituent complex, Silymarin, may indeed be helpful for liver inflammation, but its ability to treat viral hepatitis is being questioned.

..Hepatitis C infection is quickly becoming an epidemic. According to Centers of Disease Control statistics, deaths from hepatitis C infections (HCV) doubled between 1999 and 2007. HCV-related deaths have now surpassed HIV-linked deaths according to the CDC. And baby boomers account for an estimated three out of four HCV infections within the U.S.

..Viral hepatitis C is a leading cause of liver disease outside of cirrhosis – often caused by alcohol and/or pharmaceutical use. Hepatitis C is an infection caused by a virus communicated through sexual contact, needle sharing, blood transfusion and between mother and child. The virus has infected some 170 million people around the world, and an estimated 3.2 million people in the U.S. are infected with HCV.

..Silymarin and HCV
The most convincing evidence for the treatment of hepatitis C with Silymarin was published last winter. The study comes from the Medical School of Iran's Isfahan University. The researchers treated 55 patients – 45 men and 10 women – with active and chronic cases of HCV infections with 630 milligrams a day of Silymarin for 24 weeks.

..Before and after the treatment, the researchers tested the patients for ALT and AST serum amino transferases (liver enzymes), liver fibrosis, and RNA to measure their liver inflammation levels. After 24 weeks of treatment, the ALT liver enzyme levels went down from an average of 108 U/L to an average of 70, and AST levels went from an average of 99 U/L to an average of 60.

..Fibrosis markers were also found to be significantly decreased among those HCV patients with liver fibrosis. Quality of life scores improved significantly, and of the 55 patients treated, nine had HCV-negative RNA levels after the treatment.
The researchers concluded that, "this study indicated that in patients with CHC performing Silymarin (650 mg/day) for 6 months, improved serum HCV-RNA titer, serum amino transferases (ALT, AST), hepatic fibrosis and patient's quality of life."

..While these results certainly seem promising, a more recent study, published in July's Journal of the American Medical Association (JAMA) found quite the opposite results.
This study, from the Liver Center at the University of North Carolina, Chapel Hill, conducted in four medical centers, included 154 adults with chronic hepatitis C viral infections.

..The study was randomized, double-blinded and placebo-controlled. It involved only those with serum alanine aminotransferase (ALT) levels above 65 U/L or more and had undergone interferon therapy without success. In other words, these were chronic, severe cases.
The patients were given either 420 milligrams of Silymarin, 700 milligrams of Silymarin, or a placebo three times per day for 24 weeks.

..The researchers' protocol measured success by how many of the patients reached the normal range of ALT levels as long as the decline went down by 50%. The normal range is 45 U/L – which is a significant drop from the 65+ U/L levels – with some much higher.
The results were disappointing. There were only two people within each of the Silymarin treated groups, and two people in the placebo-group that satisfied the research protocol for success. That meant less than 4% of the Silymarin-treated patients were considered clinically improved.

..However, when mean ALT levels among the treatment groups are compared, the placebo group's levels went down an average of 4.3 U/L, the 420 milligram Silymarin group's levels went down an average of 14.4 U/L, and the 700 milligram Silymarin group's levels went down by 11.3 U/L on average. This means that the liver inflammation reduction for the Silymarin groups were between two and three times that of the placebo group.

..Still, their inflammation reduction was fairly low by treatment standards. The researchers concluded that, "higher than customary doses of Silymarin did not significantly reduce serum ALT levels more than placebo in participants with chronic HCV infection unsuccessfully treated with interferon-based therapy." The operator here is "significantly." This did not mean that Silymarin did not reduce ALT levels. It also does not clarify that ALT levels were lower among the 420-milligram group.

..While this study certainly appraises the use of Silymarin as not very beneficial, quite contrary to the Iranian study, there are caveats to consider. It should also be noted that the Iranian study did not use a placebo, but rather simply measured enzyme levels before and after treatment, with the patients all knowing they were in the treatment group. This could have swung the results towards the positive.
Does this mean that Silymarin and thus Milk thistle is useless for hepatitis-C infections?

..This was the conclusion of researchers from the University of Calgary, who published a 2005 study that reviewed the research to date on Silymarin for chronic hepatitis C and B infections. They found that while Silymarin was effective in decreasing serum transaminases (ALT and AST) in most of the research, there was little evidence showing its effectiveness in reducing viral hepatitis C and B infections.

..The Big Caveats: Milk thistle constituents and their delivery
Last December a study from the University of North Carolina's Eshelman School of Pharmacy shed light on the relative differences in efficacy between liver inflammation and hepatitis-C. The researchers gave patients with either non-cirrhosis liver disease or hepatitis-C either doses of Silymarin or placebo every eight hours for a week. Every 48 hours they sampled the subjects' blood and measured circulating levels of Silymarin constituents (flavonolignans) and their conjugates.


..The researchers found that while the non-cirrhosis liver disease subjects readily processed the Silymarin constituents into conjugates, those with hepatitis-C did not or did to a far less degree. The research established that in order for the Silymarin to become effective, the liver must be readily able to process Silymarin's active constituents - which include silybin A, silybin B, silibinin, silychristin and others – into conjugates.

..Conjugating is a process that takes place in the liver as the liver attaches molecules to a substance in order to give it the ability to be either useful to the body or be excreted out of the body. An active liver will attach, for example, sulfur or cysteine to a toxic molecule in order to process the substance for excretion out of the body.

..In the case of Silymarin, the conjugation of Silymarin's flavonolignans in this study illustrated that a fatty liver is typically strong enough to process and utilize the active elements of Silymarin for inflammation reduction. Meanwhile, chronic hepatitis-C viral infections may well weaken the liver to the point that it cannot process the Silymarin constituents well.
Another aspect to this – the elephant in the room if you will – is whether the extraction of Silymarin from the whole herb Milk thistle has anything to do with its lack of effectiveness in hepatitis-C infections.

..We know pharmacologically that even the Silymarin extract contains a number of constituents: silibin, silibinin, silicristin, silidianin, isosilibinin and others.

..There are also several forms of Milk thistle, including forms taken from the fruit, seeds, leaves or the roots. Each of these parts of the plant contain different constituents.
In fact, some herbs or extracts labeled as Milk thistle are drawn from the leaves, which have little of the medicinal benefit contained in the fruits and the seeds.

..Other compounds found in the fruits and seeds besides its flavonolignans include betaine, trimethylglycine, fixed oils and various amines. Because the flavonolignans – 50% to 70% silybin – are not water soluble, they are not absorbed readily.
Furthermore, Silymarin's compounding and delivery system is critical to its ability to deliver its active constituents. And some clinical use has concluded that intravenous injection is a preferable way to deliver the antiviral effects of Silymarin, while infusion methods (such as tea) may well be useless.

..Another important constituent of Milk thistle is dihydroquercetin. While dihydroquercetin has been considered an impurity by pharmacologically oriented doctors trained with the premise that a medicine's success is based on a single active constituent, dismissing dihydroquercetin from Milk thistle's therapeutic effects would be a mistake.

..A recent review of research from the UK's Robert Gordon University School of Pharmacy and Life Sciences recently established that dihydroquercetin – also called taxifolin –is "a potent flavonoid" with significant therapeutic properties and several mechanisms of action.

..The research summarized dihydroquercetin's many therapeutic mechanisms
inhibiting P450 processes that can burden the liver
detoxifying enzymes that can slow down the liver
blocking fatty acid enzymes in cancer cells
moderating the effects of TNF-alpha – an important inflammatory component of HCV
effecting NF-kappa beta response – another important aspect of HCV infections
neutralizing oxidizing reactions (antioxidant)

..These effects of dihydroquercetin tell us two important things: Dihydroquercetin is an important constituent of Milk thistle. Without it, Milk thistle's effectiveness as a therapeutic agent may well be compromised.

..Indeed, it would not be surprising if the past clinical success of Milk thistle with hepatitis C infections (including the Iranian research) occurred prior to modern super-extraction methods that remove many important "impurities" of Milk thistle to extract Silymarin – such as dihydroquercetin.
While this assumption deserves additional research to confirm, dismissing the use of whole herb-extract Milk thistle for hepatitis C infections could well be like tossing the baby out with the bath water.


...Case Adams is a California Naturopath and holds a Ph.D. in Natural Health Sciences. His focus is upon science-based natural health solutions. He is the author of 20 books on natural health and numerous print and internet articles. His work can be found at http://www.caseadams.com.
References
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