Biologisch Medisch Centrum Epe oxymatrine
Paul van Meerendonk

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Oxymatrine in the treatment of post viral fatigue

From DoctorMyhill


May 26th 2010 – Invest in ME International – 5th Conference A summary of the day and implications for treatment

Speakers: Professor Leonard Jason, Professor Norah Chapman, Dr John Chia, Dr Paul Cheney, Dr Jonathan Kerr, Dr Nancy Klimas, Professor Brigitte Huber

The role of viruses in CFS/ME

The emphasis of this conference was very much on viral causes of chronic fatigue syndrome / ME and the immune responses that go with that. Much discussion went into the classification of types of ME by various sub-groups particularly by Professor Jason and Dr Kerr, but my view is that at present this has little implication for treatment. Norah Chapman concentrated on cocksackie B infections, Dr John Chia on enteroviral infections, Brigitte Huber on retrovirus HERV K-18 (which we all have in our genome). All these viruses are implicated in cases of CFS/ME but what makes the difference between a short illness and recovery and illness and prolonged CFS is the response of the immune system to those viral insults. Studies show the virus continues to be present albeit at very low levels and because the virus is at such low levels this explains why many tests do not pick it up – it is simply below the level of the radar.

However this low level viral persistence may result in chronic inflammation in susceptible individuals wherever that virus happens to be and this would explain many of the symptoms of CFS/ME. So for example Dr John Chia found that in 165 patients with CFS 82% had high levels of entrovirus in the gastric antrum of the stomach. Norah Chapman found low level infection by defective cocksackie B viruses in non-dividing cells in particular muscle cells (including the heart muscle) and by implication brain cells (because these enteroviruses persist in non-dividing cells). Brigitte Huber showed that HERV K-18 MRNA levels are higher in CFS patients.

What this tells us is that patients with CFS/ME are not good at dealing with viral infections, they do not eradicate them efficiently and this viral DNA gets in the way of cell metabolism causing a low grade chronic inflammation which means cells malfunction.

The most important point about all this wonderful work is that it clearly establishes CFS/ME as a physical disorder with physical lesions and physical treatments.

The clinical picture

John Chia made the point that enteroviruses are the commonest cause of ‘flu-like symptoms. Enteroviruses may be picked up as a result of travel, water sports, gut infections or from local epidemics. He specifically mentioned vaccinations and allergies as risk factors. The way to diagnose an enteroviral infection is first of all to have an high index of suspicion! ‘Flu-like symptoms that persist for more than two weeks are highly suspect, but blood testing for antibodies can be misleading. There are often few physical signs, perhaps some ulcers on the tongue, possibly lymphadenopathy and tenderness of the abdomen particularly in the epigastrium, left iliac fossa and right iliac fossa. Sometimes there is sinusitis, colonic inertia and pelvic pain.

How well one deals with the virus depends on whether the immune system is in a state of Th1 or Th2 activation. If one is in a state of Th2 activation one will struggle to get rid of the infection and this state is characterised by allergy, female sex hormones (pregnancy, Pill, between menarche and menopause – ergo women are much more susceptible than men), excessive exercise, vaccinations or another recently acquired infection.

So for example Professor Huber pointed out that we all have HERV K-18 (indeed 8% of the human genome is made up of retrovirus) but the expression of this is induced by Epstein Barr and herpes virus, this activates virus in a way to produce a super-antigen which results in massive T-cell activation, i.e. inflammation. Epstein Barr virus is particularly good at doing this.

An awful lot of the discussion of the day revolved round immune responses to virus. My interest of course is in getting patients well and I have to say I dozed off during some of these discussions – partly because I’d had a 4am start and partly because I don’t see the relevance of esoteric immune discussions when it comes the business of getting patients well! I see the immune system as the army of the body and all the various players have army equivalents. So natural killer cells are our soldiers with machine guns, B-lymphocytes and T-lymphocytes are the messengers rushing around telling everybody what to do as well as lobbing cytokines and antibodies - our bombs and grenades. In chronic fatigue syndrome much of this activity is self destructive – it’s as if the army can’t stop fighting foreigners and has embarked on a civil war.

What is clear is that the total load of virus during the early phases is critical. Indeed this is well established in HIV infections. The above issues do of course have implications for treatment and this is how I see it all fits together.

During the acute stage

Treatment of the initial viral infection Keeping viral numbers down helps a lot. Viruses are killed by fever, one should rest up in bed to allow the immune system to be active, take high dose vitamin C which effectively kills everything in the gut – indeed in high doses this will cause diarrhoea and strip out virus yeasts and bacteria generally in the gut. An acid stomach will be protected against enteroviral infection because acid will kill virus. Do not take symptom suppression medication which reduces fever and pain because these are useful symptoms which kill virus - see Viral infections - avoid them and treat them aggressively.

Interventions to reduce inflammation

Inflammation is highly desirable in the early stages of viral infection but after two weeks probably counter-productive. Nutritional interventions to reduce inflammation will be very helpful. The problem with Western lifestyles is that with their high levels of sugar and refined carbohydrate, lack of sleep, lack of sunshine, chemical, physical and mental stress etc. they tend to be pro-inflammatory. This predisposes us to states associated with chronic inflammation – see Inflammation. All this will tend to be made worse by having poor antioxidant status – this is a disease-amplifying process – poor antioxidants means more free radicals means more inflammation. See

During the chronic stage


John Chia looked for Chinese herbs which had anti-viral activity - the idea here is to try to get rid of those last few viral particles that were causing so much havoc in terms of chronic inflammation. He came up with oxymatrine which he has now trialled in 500 ME/CFS patients and seen beneficial effects in 52%. In the short term this can increase symptoms, but in the medium term beneficial effects were seen in 52%. In a few of the responders and non-responders in which he measured cytokines gene expression there was an increase in the IL12/IL10 ratio in 7/7 and no increase in any of the 10 non-responders. Again those that responded showed low levels of enteroviral protein in stomach biopsies. This suggests that oxymatrine is useful in half of patients with chronic and low grade viral infections. Dr Chia has made up his own product Equilibrant which contains the active principle oxymatrine and recommends starting at one daily, gradually increasing to 3 twice daily according to clinical response. Expect to get worse initially, hence the need to start with low doses and build up slowly. My guess is Equilibrant will be more effective if the basic work up to treating CFS is followed (as in summary approach above!).


Treating Chronic Fatigue Syndrome (ME/CFS): Oxymatrine

Oxymatrine and CFSOxymatrine is an alkaloid derived from the roots and above ground portions of the Sophora plants. Many plant alkaloids are used in medicine; the best known alkaloids are the opiates but others include quinine (malaria), atropine, vincristine (an anti-leukemia drug) and hallucinogenic plants such as datura and mandrake.

First isolated over 50 years ago the matrine alkaloids - matrines and oxymatrine - have been a focal point of Chinese medical research into the treatment of cancer, viral hepatitis, viral myocarditis and skin diseases such as psoriasis and excema over the past 15 years. Oxymatrine first appeared in the West in tablet form in the U.S. in 1998.

Oxymatrine has antiviral effects in cell cultures and some Chinese studies suggest it can reduce the viral load and liver damage in humans with hepatitis B. Some Chinese researchers suggest oxymatrine injections in combination with Chinese herbs may be as effective as interferon in treating hepatitis but without the side effects. A review of Chinese studies suggested oxymatrine may be able to increase blood flow, increase heart muscle contractility and reduce coxsackie virus activity in patients with viral myocarditis. Oxymatrine is also considered an anti-cancer drug in China.

Oxymatrine is receiving increasing interest in the West with studies focusing on cancer, ischemia-reperfusion and hepatitis B in laboratory animals, culture studies, etc.

Oxymatrine May Be Beneficial in Chronic Fatigue Syndrome (ME/CFS) Because it may inhibit the activity of viruses that may be present in some patients.

Oxymatrine Studies in Chronic Fatigue Syndrome (ME/CFS) – no studies have examined oxymatrine’s effectiveness in ME/CFS.

Chronic Fatigue Syndrome (ME/CFS) Doctors Report

Dr. Chia, an infectious disease specialist focusing on chronic fatigue syndrome (ME/CFS), has finished the production of a pure form of Oxymatrine, an alkaloid derived from the Sophora plant in China. Oxymatrine is used to treat many diseases including hepatitis and cancer there. Oxymatrine has been an important part of Dr. Chia’s protocol for several years and it played an integral role in returning his son, Andrew Chia, to health.

The concern over the purity of products coming from China prompted Dr. Chia to produce a more stable and effective preparation of Oxymatrine called Equilibrant. He took the opportunity to add other immune factors to the mix. He stated that

"Equilibrant, containing oxymatrine and a number of immune modulators. This herbal preparation, a dietary supplement, is made from the highest quality extracts under FDA certified Good Manufacturing Practices (cGMP) in the United States. It is also laboratory tested in FDA registered analytical laboratories."

A Main Focus of Treatment - For many years Dr. Chia used interferons and Oxymatrine to treat his patients but he has dropped interferon use for all but one subset of patient. When I asked him about the efficacy of Oxymatrine a as a stand-alone treatment he stated:

"I have treated 70 patients with the combination of alpha and gamma interferon, and the efficacy is about 47% overall. I reserve the interferon treatment for patients with severe fibromyalgia without debilitating fatigue. The cost is prohibitive ($5000/month) and the side effect does not allow patient to continue the treatment for more than 1-3 months. Few patients had remission of symptoms for as long as 2-3 years. The chance of improvement is minimal, If the myalgia is not dramatically better by 2-4 weeks on interferon treatment."

"Since the herbal preparation is much cheaper, has better efficacy and less side-effects, I have not used interferon treatment for over a year. I learned to titrate the dose of the herbal preparation for patients with different symptomatology."

Dosing - Chronic fatigue syndrome (ME/CFS) - "The dose of Equilibrant should be increased slowly. I routinely start with one tablet with a glass of water before or with meal everyday for one to two weeks. If there is no increase of pre-existing symptoms, such as fatigue, myalgia, headache, the dose could be increased to one tablet 2 times a day for one to two weeks, then slowly work up to 2 to 3 tablets 2 times a day. No further escalation of dose should be done if there is significant increase in symptoms. Further titration can be done later as needed, depending on the patient’s response and tolerance."

Fibromyalgia - "Patients with significant fibromyalgia rarely need more than 1 tablet once or twice a day, but few can take up to 4-6 tablets/day. Pain can decrease as soon as 2 weeks, often afer an initial increase of myalgia. If the increase in pain persists for few weeks without improvement while taking one or two tablets/day, the patient will not likely respond and certainly should not take higher doses. "

Patients on heavy doses of narcotic pain medication are not good candiates for this herbal product since a further increase of myalgia may not be tolerated. Everyone has “bad” pain but the patients not needing much pain medications are better candidates for this herbal supplement. Again, the dose needs to be titrated.

Side effects, though usually temporary are not uncommon. They can be ameliorated by slowly increasing the dose.

"Side Effects Increase in symptoms, such as headache, myalgia, arthralgia, stomach complaints or bladder discomfort, can be seen in over 50% of the patients, lasting from a few days to few weeks, but could be relatively mild if the dose is increased slowly."

You’ll generally know if the preparation works in from one to three months. Longer courses may be necessary if the patient is tolerating the drug well. Expect to be taking the drug for a year (at least) if it works.

Prognosis - "On the average, the patient should have some signs of improvement by 4-6 weeks, but few may take more than 3 month, especially if the dose is escalated over 4- 6 weeks period. Since the symptoms are often cyclical, a longer course may be needed to fully evaluate the benefit of the herb, as long as the patients are tolerating it well. With significant responses, patients should not perform vigorous exercise in the first few months to avoid major relapse of symptoms. Most of the patients will need to take the herbs for more than one year, if there is significant response."

Patients with symptom flares can be on it long-term without side effects. Maintenance doses are possible.

"Patients with periodic exacerbations of symptoms while taking the herbs will not likely tolerate reduction of the dose after one year. If there is no response, equilibrant should be taper off in about two weeks instead of abrupt discontinuation. We have at least 30 patients taking the herbs beyond 2/12 years and are still doing well without any side-effects. Andrew (his son) is doing well on a maintainence dose of equillibrant, and will be starting pharmacy school in two days."

Fifty percent of patients have experienced improvement - some dramatic. Relatively long-term use of the herbs is required to prevent relapse in many patients.

Results. "We have given the herb to more than 350 patients over the last 2 1/2 years, and the overall improvement is about 52%. Some patients who lied down most the time went back to work in a few months (great responders), others would have at least enough improvement to do more in a day (parital responders). Relapses are common if patient stopped the herb in 3-6 months after significant improvement (2 out of 3 people). Few patients went in complete remission after taking the herbs for only 3 months, but none of these patients were females."

Patients with autoimmune manifestations or seizures should not take these herbs.

Warning: "This type of immune modulators should not be used in patients with autoimmune tendency or known seizure disorders."

"It is best that a physician supervises the patient on any herbal product and blood tests can be done in 2-3 months after starting the herbal product."

Price: Each Equilibrant box contains 90 tablets. The price is $ 49.95 USD per box. It is professionally packaged in blister cards, which protect the stability of each tablet. You can find the product here for more information.

Dr. Chia stated that the response to oxymatrine in his patients with enteroviral infections was ‘variable’. He will be reporting more on oxymatrines effectiveness at the IACFS/ME conference in March, 2008. A patient of Dr. Chia’s reported Dr. Chia uses a source from Kowloon Bay, HK as he is concerned about the purity of other sources.