Dr. Myhill’s notes on fatigue, the immune system’s energy demands, and Rituximab
By Dr. Sarah Myhill, MD* •
February 17, 2012
Dr. Sarah Myhill is a UK-based physician with a special interest in nutrition and fatigue. Her pioneering research (“Chronic Fatigue Syndrome and Mitochondrial Dysfunction”) suggests the cells’ energy generating mitochondria are dysfunctional in chronic fatigue syndrome (ME/CFS) and other 'neuro-immune' illnesses. This article is excerpted with kind permission from Dr. Myhill’s educational website (DrMyhill.co.uk).*
Energy Expenditure in ME/CFS: Immune Wastage of Energy and Rituximab
We all have a pot of energy which is available to us to spend over the day. What prevents us spending too much is the symptom of fatigue.
We have to spend that pot of energy just to stay alive in "house keeping" duties - but in addition mentally, physically, emotionally or immunologically.
In ME/CFS either that pot of energy can be small (because of poor mitochondrial function, poor fuel supply, poor adrenal function, poor thyroid function and so on), or we can be spending energy wastefully.
Of course, the business of pacing is all about spending mental and physical energy judiciously. Many have experienced how energy sapping it is to expend emotional energy.
However, I suspect a greatly overlooked cause of wasting of energy is immunological.
Energy must be expended on daily "house keeping" duties. I was intrigued to see the following energy expenditure breakdown in Wikipedia:
- Liver 27%,
- Brain 19%,
- Heart 7%,
- Kidneys 10%,
- Skeletal muscle 18%,
- Other organs 19%.
It astonished me that the liver consumes more energy than the heart and brain combined! Much of this has to do with assimilating and detoxing food from the gut!
I see the immune system to be like the brain, i.e. it is enormously demanding of energy. We all know this - if a healthy person develops influenza, then he becomes bed-bound for two weeks (she becomes bed-bound for a week….!).
Work done by Caroline Pond has demonstrated that when wild animals put on weight, the first place they dump their fat resources is around lymph nodes; i.e., the immune system.
Bone marrow, of course, is very fatty, so this suggests the immune system is not just demanding of energy, but energy in an intensive form; i.e., fats and oils.
The immune system spends energy fighting infection, which is, of course, highly desirable. However, if it gets its wires crossed, it may end up fighting the body itself (autoimmunity), or fighting substances which do not cause harm, and this is allergy.
However, in ME I suspect there is another immunological waste of energy which has to do with microbes, possibly “allergy” to microbes.
A great many cases of ME follow viral infection and/or vaccination. In these conditions the immune system is switched on to fight the offending microbe.
In the short term this is highly desirable. To be effective, all vaccinations contain immune adjuvants which are there specifically to fire up the immune system. When this works in our favor, we call it immunity.
However, when it works against us, we call it allergy. Clinically, we know that vaccinations can trigger allergies.
There is no doubt that there are some ME patients who do not recover until they start taking antivirals (see work by Dr. Martin Lerner in my page "Valacyclovir in the treatment of post viral fatigue syndrome,” Sep 2010), antibiotics or antifungals.
In these cases, there is often no overt evidence of infection.
I suspect what is going on here is that these microbes are present in low levels which would not normally cause harm to the body, but the immune system continues to fight.
It is a sort of inappropriate immune activation against microbes or “allergy” to microbes. This is hugely wasteful of energy. Such patients will have a large immunological hole draining their daily energy bucket.
What we perceive going on in the body is not what is really going on in the body, but it is what the brain tells us is going on in the body!
The brain has a complete map of the body, which includes sensory and motor functions. Ref “Phantom Limb Syndrome” by Dr. VS Ramachandran (University of California, San Diego).
It is possible that this could explain the mechanism by which healing and touch therapies such as Bowen therapy, Reiki, Kinesiology, etc. work. These techniques are literally re-mapping the brain to perceive things quickly, or direct motor actions correctly.
It is possible that the immune system has a similar mapping process.
I think of the immune system as having a “map” of what should and should not be present in the body. I imagine it “sniffing” about the place looking for foreigners.
There are many good doctors who have experimented with many different types of immunotherapy, such as neutralization, enzyme potentiated desensitization (EPD) and, of course, homeopathy; and it may well be that they are having their beneficial effects because of this re-mapping of the immune system.
All these mechanisms are characterized by extremely low levels of molecules or antigens being applied with profound effects that cannot be explained by conventional pharmacology.
Treatment of Badly Educated B Lymphocytes
Immune mapping probably takes place in B lymphocytes. They start life in the bone marrow, move into the blood stream, and are educated by the thymus gland and lymph nodes. This takes a few months. The mature B lymphocytes become the decision makers for immune attack or immune tolerance (war or peace!).
Post infectious ME patients may have B lymphocytes constantly at war. These white cells have been badly educated, their wires are crossed.
This therefore gives us a model for treatment.
Either we can re-educate these B lymphocytes or we can kill them, or we can try to reduce the things they are inappropriately reacting against, which may be foods (diet) or microbes (with antimicrobials which could be drug or herbal, change the gut flora with probiotics).
Re-educate B Lymphocytes with Immunotherapy
Perhaps desensitization with neutralization, EPD or homeopathy are techniques directed at re-educating these B lymphocytes to respond appropriately by remapping the immune system?
In the case of neutralization the result may be immediate. With EPD (and I know much more about this because I have been using EPD for 25 years!) the result is often delayed by a few months, it lasts weeks to months, and then patients may need a top up of the treatment.
Although these desensitizations are largely directed at foods, inhalants and chemicals, some microbial antigens are also included. See “Enzyme Potentiated Desensitisation (EPD) - how it works".
Kill B Lymphocytes with Rituximab
This drug is a monoclonal antibody specifically effective against the CD20 receptor on B lymphocytes. It specifically depletes B lymphocytes; i.e., it kills off the standing army – if this army is involved in civil war, then its depletion is a very desirable action!
Rituximab is primarily used in cancer chemotherapy. By pure chance a patient who had severe ME received this drug as part of a treatment for her lymphoma and her ME symptoms disappeared. She was delighted! Her daily energy bucket was no longer being immunologically drained!
This prompted a study by her Norwegian oncologists, Prof Olag Mella and Dr. Oystein Fluge at Haukeland University Hospital, Bergen, to conduct a placebo controlled double blind trial into the effectiveness of Rituximab in ME.
This was done with 15 patients receiving the active preparation and 15 the placebo… [See “Benefit from B-Lymphocyte Depletion Using the Anti-CD20 Antibody Rituximab in Chronic Fatigue Syndrome: A Double-Blind and Placebo-Controlled Study.”] Rituximab had a highly significant beneficial effect.
What was so interesting about this effect is that it took 2 to 4 months to start, it lasted for 2 to 6 months, then some patients relapsed but some were cured!
This fits very nicely with the time scales I see in my EPD patients – again there is a delayed start, improvement, then top ups required according to the clinical response.
Another way to tackle this problem of inappropriate activation against microbes would be to use therapeutic agents which may be herbal, or prescription medication, to try to reduce the level of microbes so much that the immune system stops reacting.
It may be that this approach explains the success of Dr. Martin Lerner’s work with antivirals, treatments with antibiotics for Lyme disease, and with antifungals for chronic yeast problems.
It is the old story - we have a lot more good questions than good answers, but at least we are asking the right questions!
* This article is reproduced with kind permission from Dr. Sarah Myhill’s educational website (DrMyhill.co.uk)® Sarah Myhill Limited, Registered in England and Wales: Reg. No. 4545198.
Note: These statements have not been reviewed by the FDA. They are general information, based on the research and opinions of Dr. Myhill unless otherwise noted, and are not intended to diagnose, prevent, treat or cure any illness, condition or disease. This material is not intended to replace a one-on-one relationship with a qualified healthcare professional and is not intended as medical advice. It is always very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.
||Discuss This Article
Mit, dysfunction and PPAR interference by Pthalates
|Posted by: IanH
Feb 18, 2012
There is quite a significant amount of evidence that many common pthalates are synthetic ligands of the PPARs (Peroxisome proliferation activator receptors). Some studies have been looking at the link between pthalates, PPAR function and obesity as well as more general endocrine dysfunction. We need to look at the role of pthalates, PPAR function and ME. Research by Myhill and by Bell have shown evidence that mitochondrial dysfunction is at the heart of ME but not a simple phosphorylation problem. Others have suggested a methylation problem. Pthalate interference of PPAR function in susceptible individuals would lead to the many varied symptoms of ME.
|Posted by: IanH
Feb 22, 2012
Does anyone know of more research following up on the work done by Brad Chazotte after his article?
Mitochondrial dysfunction in CFS, in "Mitochondria in Pathogenesis" ed: Lemasters, J.J. and Nieminen, A-L., kluwer Academic/Plenum Publishers, NY. 2001.
(He did no more work on CFS.)
In this article Prof Chazotte demonstrates changes/differences in the membrane potential of mitochondria in mononuclear leukocytes. (Using a confocal microscopy technique)
People with CFS (ME) have at least a 12mV lower membrane potential than normals and often have MPs of less than 100mV indicating dysfunctional mitochondria and energy production. He found no difference in sex of patients. (we all know there is no difference, only a difference in diagnosis).
He also found that IFNalpha reduced the Mp - virtually switching the mitochondria off, making them indistinguishable from the surrounding cytoplasm.
I believe there are two possibilities for mitochondrial dysfunction in ME. Virus inducing high cytokine levels, such as IFNalpha or IL-2 and these in turn interfering with mitochondrial function. &/OR toxin induced metabolic-endocrine dysfunction in genetically susceptible individuals, toxins such as phthalates, which have been shown to induce mitochondrial dysfunction via PPAR interference in hepatocytes. We have seen recently how PPAR "dysfunction" is implicated in MS.