Biologisch Medisch Centrum
Lezing UMC Utrecht
Arts Paul van Meerendonk
Cvs en fibromyalgien
Virus en DNA
Viruses and mitochondria
Virussen en immuunsysteem
CVS ME aantoonbaar
Oxymatrine in the treatment of post viral fatigue
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 http://drmyhill.co.uk/wiki/Antioxidants
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!).