Why Triple Antioxidants Relieve the Symptoms of Chronic Hepatitis C

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Why Triple Antioxidants Relieve the Symptoms of Chronic Hepatitis C

A reader named wrote to me about some ideas he had on how the methylation cycle block theory could be applied to patients with chronic Hepatitis C.Here’s what he wrote to me:I came to the GSH-competitive hypothesis of CFS through a paper by Molson and Bounous, and I adapted it when I realised how many endogenous antioxidants had l-methionine as a rate-limiting factor in their synthesis. The best analogy I’ve thought of so far is a room full of smokers, and only methionine has a lighter. It’s a sad analogy and I’m searching for a better one!What is revealing is that l-methionine isn’t generally part of HCV protocols but, through chance (inability to access NAC in deepest New Zealand) I ended up using it, and, with selenium, it turned around the depression (as in, reluctance to do anything challenging, and desire to sleep) almost overnight.And now I find in your blog that people with CFS use l-methionine

perhaps more than those with Hep C. Certainly the applied science on yr blog is ahead of its application in Hep C: yours is very much like the approach we need.

Here is his paper:Why Triple Antioxidants Relieve the Symptoms of Chronic Hepatitis C,by D. , 5 - 10 - 2007

Just because you have a positive test for Hep C, a bad outcome is far from inevitable. Many people with Hepatitis C never develop symptoms. Even if you’re already sick with chronic Hepatitis C you can turn your life around, by making healthier diet, exercise and drug choices and by using the appropriate dietary supplements to replace the body’s depleted antioxidants and assist the recovering liver. This article describes how antioxidants are depleted in hepatitis C, the methods of antioxidant repletion, and the results of antioxidant protocols in hepatitis C. It’s important to realize that antioxidants are not an antiviral therapy; viral levels will only decline slowly. The benefit of antioxidants is that they can prevent lipid peroxidation (the mechanism of liver damage in cirrhosis) and reduce or prevent the disabling symptoms of hepatitis: fatigue, nausea, pain, depression, tiredness, irritability. They improve liver function by protecting

existing liver cells and protecting the DNA in new cells (formed to replace the liver cells destroyed by immune attack) from the damage that causes the decline in liver function seen in long-term cirrhosis.I know these methods work because I use them myself. In four years I have gone from being very sick, depressed and addicted to being healthy, happy and productive, with liver enzymes well inside the normal range.

Tests, studies and trials involving hepatitis C populations all over the world show the same results; compared to healthy populations, people with chronic hepatitis C (CHC) have depleted levels of antioxidants (both dietary, e.g. beta-carotene, vitamin E, lycopene, and endogenous, e.g. glutathione, alpha-lipoic acid), antioxidant enzymes, and most vitamins and minerals used in antioxidant synthesis (e.g. selenium, zinc, magnesium). The only minerals whose levels are regularly found to be normal or elevated in hepatitis C are iron and copper, transition elements which are a source of free radicals.This systemic antioxidant depletion is characteristic of CHC, and the depletion is more marked in patients with cirrhosis. The wide-ranging consequences of this antioxidant depletion syndrome account for most of the unpleasant, disabling and life-threatening symptoms of CHC, including muscle fatigue, depression, and liver damage. There are no longer

enough antioxidants being produced to quench the free radicals that are generated in the course of the liver cells performing their normal duties, let alone deal with the reactive peroxides that are generated by the immune system’s attack on the infected liver cells, and this shortfall is what allows the lipid peroxidation process that causes hepatocellular fibrosis and leads to cirrhosis.

Antioxidant precursors include the amino acid l-methionine, which is in demand for the production of immunoglobulins (antibodies) and the antioxidants l-cysteine, glutathione (GSH), alpha-lipoic acid (ALA), Co-enzyme Q10 (CoQ10), carnitine, taurine, and creatine. Given a limited supply of l-methionine the body will supply its essential systems first; the immune system has priority, then the liver, and the needs of the muscles come last. In order for the limited intake of l-methionine to supply l-cysteine for antibody production and GSH for immune cell function and liver cell protection (and the production of liver GSH in CHC is often inadequate to provide such protection), the muscles become starved of taurine, creatine, carnitine, GSH, and ALA. Antioxidants are needed by muscle cells both to produce energy and to recover after exertion, and this explains why fatigue and muscle pain (myalgia) so often result from a liver infection. Parallel

processes play a role in depression; l-methionine is also the precursor for the methyl-donor S-adenosylmethionine (SAMe) which plays a vital role in serotonin synthesis. The increasing demand for l-methionine’s many metabolites in chronic hepatitis C creates a bottleneck in the body’s antioxidant and methyl-donor supply lines.

There has been considerable research and experimentation done to learn which combination and dosage of antioxidants is most effective at reversing the depletion that occurs in hepatitis C and relieving the symptoms of CHC, including protecting against cirrhosis and liver cancer. A consensus has developed favouring a combination of Alpha-lipoic acid (lipoic acid), Selenium, Silymarin (milk thistle), and vitamins E and C, the so-called “triple antioxidant†method. Other antioxidants used include SAMe and glycyrrhizin from liquorice and a number of Japanese trials have successfully used an IV product called Stronger Neo-Minophagen C, which is a compound of glycyrrhizin, l-cysteine, l-glycine and dl-methionine, but the advantage of Triple Antioxidants is that they are safe enough, and convenient and effective enough, to be taken by people who are not lucky enough to have a doctor willing to study, diagnose and treat the antioxidant depletion caused

by CHC. Although this treatment was developed through the study and treatment of CHC by doctors and scientists working in world-renowned hospitals and universities, and cannot be called an “alternative therapyâ€, many doctors in this country are prejudiced against anything that does not arrive via the drug companies and the government drug purchasing agency Pharmac and are embarrassed to be found standing out from the herd.

Triple Antioxidants as developed by Burt Berkson MD, and the similar mixed antioxidants (not including selenium) recently trialed in Israel, provide benefits in the following parameters:

Liver Enzymes: are rapidly reduced, tending to become normal. In most cases where ALT is normalized it stays normal once treatment is stopped; however it is recommended that antioxidant therapy be maintained as long as the disease persists. ALT levels are an indication of ongoing liver damage, not of viral load, but the destruction of infected liver cells accelerates the spread of HCV. The normalization of liver enzymes is indicative of a low rate of hepatocellular necrosis.

Fatigue: Alpha-lipoic acid is able to replete GSH, taurine, carnitine and creatine in muscles, both by sparing their precursors and by re-activating used antioxidants. N-acetyl l-cysteine (NAC), l-methionine, whey protein and other precursors have also been used. Ascorbic acid plays an essential role in l-carnitine synthesis. In the Israeli trial 58% of patients had improved scores in the SF-36 quality of life questionnaire after treatment. The ability of triple antioxidants to restore normal, pre-disease energy levels is usually the first benefit to be appreciated by the patient.

Viral Load: A decrease in viral load (one log) was seen in 25% of the Israeli subjects (few of whom received all of the triple antioxidants) after 20-40 weeks and a significant decrease was seen in all three of Berkson’s patients over a longer period. A steady decrease in viral load can be expected throughout long-term treatment, but the decrease does not account for the beneficial effects of triple antioxidants, which can still occur when the viral load stays more or less constant. In no case so far has viral load increased during antioxidant treatment.

Histology: histological improvement was noted in 36.1% of the Israeli subjects. In a separate study, high dose Vitamin E (d-alpha tocopherol) 600 IU stopped the progress of fibrosis, preventing cirrhosis, for as long as treatment lasted. Antioxidants have the potential to prevent lipid peroxidation, the disease process that causes fibrosis. In a Chinese population study selenium supplementation (200mcg) reduced the rate of hepatocellular cancer (HCC) in subjects with cirrhosis due to chronic HBV to zero. HCC in cirrhosis occurs for much the same reasons regardless of the cause. Selenium elevates levels of the antioxidant enzyme glutathione reductase (GR) and excess selenium forms methyl selenium, which has been shown to have a pharmacological action against many cancers. That neither selenium nor any other mineral was included in the Israeli trial may account for the failure of some participants to respond to mixed antioxidants as selenium is needed

for the synthesis of GSH enzymes and for the formation of glutathione itself.

Summary: Antioxidants do not act as potent antivirals, but do tend to restrain HCV replication. Triple antioxidants are effective at preventing cirrhosis and cancer in CHC, and are also effective against fatigue, depression, pain and GI disturbance. Patients are most likely to respond when doses of ALA, ascorbic acid, and glutathione or its precursors can be increased on a PRN basis and when B vitamins and essential minerals, especially selenium but also magnesium, zinc and manganese, are supplemented.

Many people who have CHC do not develop serious symptoms and stay healthy without treatment. We can hypothesize that a combination of influences may be at play in these individuals: a healthy lifestyle low in oxidative stressors such as alcohol, cigarettes and drugs, a diet low in iron, calories, saturated fats and toxic chemical additives and high in antioxidants and easily assimilable protein, and a genetic predisposition to avoid accumulation of iron and copper, and to produce higher than normal levels of endogenous antioxidants (e.g. GSH, GR, ALA, CoQ10), as well as a genetic tendency against high levels of autoimmune and inflammatory activity. To such an individual life-long infection with hepatitis C might be largely benign, and such habits and genetic tendencies might account for the variable but significant percentage of persons with CHC who never become ill.

It seems it is not always essential to clear the virus to control or eliminate the symptoms of CHC, and in any case viral clearance by chemotherapeutic intervention is not always possible. In developed countries most people with CHC are IVDU, and in Australia, for example, 95% of IVDU will not access combination therapy (interferon plus Ribavirin). In most of these cases antivirals will be medically contraindicated for these individuals due to alcohol or intravenous drug use, mood disorders, autoimmune syndromes etc. It may be thought possible to manage these symptoms in some cases, but this means accepting an increased risk of unwanted outcomes. In any case, antivirals are only effective in approximately half of cases, they are often blamed for causing lasting health problems, and have unpleasant side effects that can seem counterproductive, leading to patients dropping out of treatment. Viral clearance, both spontaneous and chemotherapeutic, is

associated with a decreased rate of cirrhosis and hepatocellular cancer, but on long term follow up the other, extrahepatic symptoms of hepatitis C can persist: fatigue, depression, upper right quadrant pain, arthralgia (joint pain) and autoimmune disease have been seen at the same rates, for example nine years after spontaneous clearance, and the picture after chemotherapeutic clearance is often worse, due to the longer period of infection pre-clearance and the effects of the antivirals. Thus antioxidants may be of value to anyone who has ever had Hepatitis C and is in less than perfect health as a result.

There are many cases where antioxidants and antivirals have been combined and in none of these has the antiviral clearance rate suffered. The ability of antioxidants to improve viral clearance rates from combination therapy varies and seems to depend, naturally enough, on the combination and doses of antioxidants; iron levels and the availability of dietary methionine and selenium are other factors that could be critical. A reductionist approach to medicine is singularly unrewarding when dealing with nutrients. The action of any single nutrient depends on its context in the matrix of all nutrients; whether its co-factors are present in sufficient quantity, whether competitive nutrients are present, amongst other things, may be critical. Diet, exercise, water, sunlight are just some of the possible influences. Berkson’s approach, which can scarcely be bettered, was to supplement the action of the triple antioxidants (alpha lipoic acid 600 mg,

selenium 400 mcg, silymarin 900 mg daily in two doses) with moderately high doses of Vitamin E (400 iu d-alpha tocopherol) and vitamin C (4 g ascorbic acid in divided doses), as well as a high dose B complex pill (B100, 2x daily) and a multimineral supplement (including adequate magnesium, zinc, molybdenum, chromium and manganese). He also recommended his patients eat a diet with only moderate calories, eat 5+ fruit and veges, drink 8 glasses of water daily, and get exercise and sunlight.Because the extra-hepatic HCV syndromes tend to persist even after the desired SVR result of combination therapy, there is a need for antioxidants to be used by these patients, as well as in the conservative management of hepatitis C. For the patient the disease does not end when the virus dies, but when their health is restored to normal. There is no reason to accept continued disability or discomfort due to a past or current infection with HCV when this safe,

cheap and convenient treatment yields such a high rate of improvement. “If it’s so good why doesn’t everyone use it?†is the standard question at this juncture, to which the response is two-fold; one, they do: hundreds of thousands of HCV sufferers are already using antioxidants. And two: although antioxidant treatment of CHC is safe, convenient, effective, and relatively cheap it is not simple. It is not a one-pill, magic bullet fix. To apply it properly in a given case can take some understanding of antioxidant metabolism, which can be gained by reading, and some awareness of one’s own antioxidant status, which depends on the ability to analyze one’s diet, or on diagnostic tests that, apart from iron levels, are not part of everyday medical practice. Many people imagine that antioxidant treatment of Hep C requires the co-operation of a doctor, and if their doctor fobs them off they do nothing, or make a half-hearted attempt, for example

taking silymarin or selenium but nothing else.

My experience with Triple Antioxidants was typical; for years I told my doctors I wanted to try N-acetylcysteine, showing them papers etc. without generating any interest. At that time the only NAC I knew of in New Zealand was being used by hospitals. I went to study NAC in the medical library and discovered the importance of l-methionine and selenium to GSH synthesis. I now knew I could find all I needed in heath shops and pharmacies. I began with selenium, silymarin, vitamin E, vitamin C, and a gram a day of l-cysteine, later switching to NAC or l-methionine. The depression associated with CHC lifted immediately, the abdominal pain ceased, my digestion improved, and my energy levels increased rapidly. After two years I learned the importance of the iron connection and stopped using the foods (Milo, Marmite, most breakfast cereals) and multivitamins that are fortified with non-heme iron; after a few weeks my heath improved further. Four years after

beginning daily antioxidants my liver enzymes, which had reduced sharply at the start, became normal. However, switching to Berkson’s triple antioxidants (in the form of a product called Hep C Complete) was an improvement over my previous regime, and all residual fatigue disappeared. I now seem to have normal levels of physical and mental energy and I no longer tire easily. I might recommend in some cases using 600mg of NAC with the triple antioxidants (or using whey protein or spirulina as a source of readily assimilable protein), using omega-3 fish oil and vitamin D to lessen auto-immune activity, and I emphasize the importance of ensuring adequate magnesium, folate, B6, choline, and Vitamin D, from diet or supplements. Berkson treated each patient individually according to their symptoms, but his basic “Triple Antioxidants†regime is still the gold standard of treatment for preventing and alleviating the symptoms of hepatitis C and protecting

the liver, just as combination therapy, for all its faults, is still the gold standard of treatment for killing the hepatitis C virus.

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