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Triple Antioxidant Combo Improves Outcomes in Patients Who Have Hepatitis C

Philadelphia • A triple antioxidant protocol combining alpha-lipoic acid, selenium, silymarin can improve outcomes in patients with hepatitis C, in some cases averting the need for conventional interferon/ribavirin treatment or liver transplant, said Burt Berkson, MD, at the annual meeting of the American Holistic Medical Association.
' I’ve never seen someone with frank hepatitis cured on conventional therapy”, said Dr. Berkson, who practices in Las Cruces, New Mexico. “Viral loads may drop, but they quickly bounce back when treatment is stopped.

Standard therapy with pegylated interferon and ribavirin give clinically meaningful reductions in viral load in less than 50% of all patients. And that’s foe the more susceptible HCV types 2 and 3. The numbers are under 20% for HCV type 1. These drugs also carry a significant side effects burden of severe flu-like symptoms, anemia, depression, thrombocytopenia, autoimmune reaction, renal problems, hair loss, and neuropsychiatric symptoms.“This is definitely a situation in which the treatment is often worse than the disease. We need something else. We need to try non-toxic protocols first”, said Dr. Berkson.

For the past decade, Dr. Berkson has utilized an antioxidant protocol consisting of alpha-lipoic acid (ALA), 300mg, twice a day; oral selenium, 200 mcg, twice a day; and oral silymarin (Milk Thistle), 300 mg per day. “I put all people infected with HCV on this combination, even if they are asymptomatic. I think you can prevent progression to frank liver damage.”

The antioxidant combination increases platelet count, increases albumin production, reduces ALT and slows prothrombin times to near normal. In some cases, abdominal ascites are resorbed. In addition to the ALA, silymarin and selenium, Dr. Berkson also recommends a good B vitamin complex because high dose ALA will deplete thiamine, niacin and riboflavin.
This combination of nutrients forms the nucleus of a comprehensive nutrition and lifestyle approach that emphasizes a vegetable and grain-rich diet, stress reduction, avoidable of highly processed foods, iron-rich foods (iron promotes hepatic damage), and elimination of tobacco, alcohol and other substances of abuse. He often advises patients to take coenzyme Q10, omega-3 fatty acids, psyllium fiber, and beta-carotene, while avoiding over-the-counter medicines like Tylenol that can be very damaging to the liver.

A study by US Army researchers looking at hepatitis C in Korean War era veterans showed that lifestyle factors were a major predictor of poor outcomes. Poor diet, high stress and frequent alcohol use were strong predictors of disease progression and death (Seeff LB et al. Ann Int Med 2000; 132(2): 105-11).

Dr. Berkson initially published his triple-antioxidant protocol in 1999, in the content of a pilot study involving three patients with cirrhosis, portal hypertension, and esophageal varies related to HCV. All three were candidates for liver transplant. After a year on ALA, selenium and silymarin, all were healthy, showed improved hepatic function, were able to return to work, and most importantly, avoided transplant (Branson BM. Med Kiln (Munch) 1999; 94 suppl.; 83-9).

Assessment and Evaluation
There are many different lab tests that can be used to assess the hepatic and overall health status of a patient with HCV. Unfortunately the numbers often lead to more confusion than clarity. Dr. Berkson relies on four key measures: platelet count, albumin levels, alanine aminotransferase (ALT), and viral load.

Platelet Counts: Progression of hepatitis-related liver damage leads to hepatic congestion and portal vein hypertension. This, in turn, leads to splenomegaly. As this occurs, platelets sequester, leading to measurable thrombocytopenia.

Albumin Levels: As virally induced apoptosis continues in the liver, albumin production tends to drop, making this a good marker for overall liver damage.

Alanine Aminotransferase (ALT): Elevated ALT may or may not be predicted of severity or poor outcome in hepatitis C. However, an abnormally low level of this enzyme is a clear indicator of end-stage cirrhosis. “They just don’t have enough liver cells left to produce the ALT enzyme,” said Dr. Berkson. Consequently, it is an important value to keep an eye on.

Viral Load: While it is important to track viral load, it is essential to remember two things: First, there is no clear correlation between serum HCV levels and the degree of liver damage. Second, viral testing methodologies, especially those based on polymerase chain reaction (PCR) technology, give highly variable and often exaggerated results. Particle estimates based on PCR are, “an artificial amplification of the actual amount of virus present in the blood, often by many millions,” said Dr. Berkson. Any single measurement of viral count is essentially meaningless; only by tracking viral load over time, using a consistent method, can one assess viral activity.
Lab tests should be part of a comprehensive assessment that includes careful history, and diet and lifestyle assessment.
Careful physical evaluation is also important. In particular, clinicians should be on the lookout for ascites. The portal hypertension secondary to cirrhosis often causes a ballooning of the small vessels of the digestive tract.

Alpha Lipoic Acid
Dr. Berkson’s interest in ALA extends back to the 1970’s. In 1979, he published an article describing use of ALA, then called thioctic acid, as a rescue therapy for acute hepatotoxicity caused by ingestion of Phalloides mushrooms (Berkson BM. N Engl J Med 1979; 300(7); 371). ALA is one of nature’s strongest antioxidants, particularly in neutralizing superoxide, free radicals. “I figured that if it could be used in acute liver disease, it might be useful for chronic liver disease as well.

ALA, a veritable sponge for free radicals, is produced naturally by the body in large quantities when we are young, but tends to drop off with age. In inflammatory disease, especially with a lot of macrophage activity, there are a lot of superoxide free radicals to sop up (Sigalou AB. Antioxid Redox Signal 2002 Jun; 4(3): 553-7.). “ In Russia, they use ALA for people with myocardial infarctions, to limit ischemic damage.”

ALA is also a key co-factor in the enzymatic process by which pyruvate is converted to acetyl co-A (Roche TE, Cate Rl. Biochem Res Commun 1976; 72(4): 1375-83.). “Without it, we get no energy from our cells.”
Organ meats are a rich dietary source of ALA, though it would be difficult to get therapeutic levels from diet alone. The majority of ALA supplements are derived from either tissue culture or they contain synthetic ALA.

For most HCV patients, oral supplementation with 300 mg ALA, twice daily, is sufficient to control free radical damage in the liver, said Dr. Berkson. He stressed the importance of selecting products carefully. “Use a good one. Make sure it is from European source materials,” to rule out contamination or sub-therapeutic dose levels. He recommended ALA products by Metabolic Maintenance ( and Bio Tech Pharmacal (, though he has no financial ties with either company and acknowledged there are other high-quality products on the market as well.

Some patients with advanced disease, especially those with severe cirrhosis, require intravenous ALA. Dr. Berkson, gives this as 100 mg IV, twice daily for five days. The main difficulty with IV ALA is that the product, Thioctacid 600T, is not available in the US. It is made by a German company called AstaMedica. “Aventis was going to come out with it in 2006, but it looks like that’s not going to happen. You have to write prescriptions for each patients, and have them order from pharmacies in the US can make it, but you need to ask about the source. It must be IV prescription grade.”

This trace element is, “almost like a birth control pill for retroviral replication,” said Dr. Berkson. When selenium is low, viral replication increases. As you raise the selenium level, you reach a point at which viral replication just stops. The mechanism behind this effect is not entirely clear.

In treating patients with HCV, he recommends 200 mcg oral selenium as selenium methionine, twice daily. There is also an intravenous form, called Selinase, which is available in Germany, But he seldom uses it. “We’ve had such wonderful results with the oral selenium that there’s really no need to go IV.”
It is very important to keep the daily dose around 400 mcg. Higher levels will add nothing to improve antiviral efficacy, and a daily intake of 800 mcg can be toxic. “You don’t want to go too high or people will start feeling sick, develop skin problems and in some cases lose their hair.”

Silmarin is an aggregation of flavonolignans derived from the Milk Thistle plant (silybum marianum), and it is the most commonly used botanical medicine for liver disease.
According to a summary from the Agency for Healthcare Research and Quality (AHRQ), Silymarin has anti-oxodant and antifibrotic effects in the liver. It also appears to block the entry of toxins also liver cells, and down-regulates inflammation (Agency for Healthcare Research and Quality 2000. US DHHS, Publication 01-E024).

There are three well-designed clinical trials of silymarin in hepatitis patients in the medical literature; all shows measurable benefit, through in one of the three, the finding were not statistically significant. (For a review of silymarin and other natural therapies for Hepatitis, join and download our article, “Nutritional Therapies, Botanicals Can Improve Outcomes in Chronic Hepatitis” in our July 2003 edition).

As part of his triple antioxidant protocol, Dr. Berkson recommends a total of 1,800 mg of a standardized silymarin product, to be taken in divided doses. Typically, this involves taking three 300-mg capsules with breakfast or lunch, and another three capsules at dinner.

The triple antioxidant regimen is a long-term treatment strategy, through many patients reported rapid improvements. According to Dr. Berkson, “People say they feel better after one week, and after one month they fell great. Even those who continue to drink alcohol seem to do pretty well on this protocol.”

Holistic Primary Care
Fall 2005


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