Since my ‘Canary’ article on how mast cell activation could be behind the disease Myalgic Encephalomyelitis, I’ve had lots of questions from fellow M.E. sufferers, which I’ll aim to answer with this post. Bear in mind I’m not a doctor, so am guessing the answers on what I’ve learned about mast cell activation over the past year or so.
Q. Is there one virus implicated in ME?
This is where I think the mast cell theory really comes into its own. About 70% of ME cases begin with a virus, though there are other cases where it is triggered by vaccination, a traumatic physical event such as a car accident, and yet others have a slow, insidious onset of unknown cause. Researchers have searched for over 20 years for a single viral cause and found precisely nothing. This is because I think that any virus can cause mast cell activation in susceptible people. The virus is then dealt with by the immune system, which means there is no virus to find, but for some unknown reason the mast cells stay permanently activated and make us feel like the virus is still there due to the mediators they are releasing.
Even if researchers found a common virus, it wouldn’t explain those cases of ME which started by other means. Viral infections can trigger mast cell activation. But so can vaccinations, stress, environmental toxins, infection by parasites and bacteria, allergic reactions, and several other things. This is why, to me, mast cell activation is a better explanation for ME than a single virus.
Q. Why do some people have mild ME and others very severe?
When mast cells activate they can release 30 mediators, which affect more than 200 proteins within the body. With my hypothesis that ME is down to leaking mast cells, it could be that in one individual the mast cells are only leaking, for example, 5 mediators, whereas in others they are leaking 25 mediators. This would explain why some people are the ‘walking wounded’ whereas others are bedridden. Genetics, I feel, will also play a large part in why one person gets very ill whereas another doesn’t – for more on genes see the next Question.
Q. What about M.E. Sub-Groups?
Not all people with ME have the same illness experience. One of my friends sleeps all the time. I have severe insomnia. Another friend has thyroid problems. I do not. Another friend has horrendous stomach symptoms. Until 2 years ago I could eat whatever I liked. We all have ‘core’ common symptoms, such as post-exertional fatigue, muscle weakness, flu-like symptoms, dysautonomia, problems with temperature regulation, cognitive dysfunction/brain fog. But then we also have other symptoms which are often unique to us.
Here is the technical explanation for these differences in symptoms:
Different stimuli, including mediators secreted or presented by nearby cells, may affect the amount and type of mediators released from mast cells or the expression of early response genes, with individual factors, alone or in combination, exerting a different spectrum of stimulatory, co-stimulatory, or regulatory effects on mast cell functions.
In addition, dozens of mutations have been found on the KIT gene in people with mast cell disease. Each mutation leads KIT to behave in a different way, driving the cells to produce different aberrant mediator expression patterns leading to different clinical presentations.
No, it doesn’t mean much to me either! Here is the non-technical explanation:
Our mast cells may be leaking common mediators, such as histamine, heparin and prostaglandins, which are causing the common problems, but may also be leaking individual mediators unique to us depending on how our illness started, and what other issues we currently have, eg. genetic predisposition, lifestyle, exposure to environmental toxins etc.
Even if our mast cells are all leaking the same mediators, people with mast cell diseases have been found to have dozens of genetic mutations which affect mast cell expression, which would mean that each mediator would produce a unique set of symptoms depending on the genetic mutation each person has.
Q. Why do some people with ME recover and others don’t?
For a start I don’t think everyone who is diagnosed with ‘Chronic Fatigue Syndrome’ has ME. So those people who say they had ME but recovered using an anti-candida diet, or by cutting out gluten, didn’t have ME in the first place.
However, I know for a fact I have ME yet I have made a degree of recovery and am not as ill now as I was in the first 10 years. I think mast cell activation perpetuates mast cell activation. There is a feed-back loop whereby mast cells leak mediators, which in turn stimulate mast cells, which produce further mediators, which further stimulate mast cells…….and so on. I think I inadvertently broke the cycle slightly by changing the drug I was taking to help my insomnia, and by eating bioflavanoid rich foods. I switched to Zispin (mirtazapine) to help me sleep, not knowing that mirtazapine is an antihistamine used to treat mast cell activation disorder. I also started juicing daily, including loads of mast cell stabilizing foods such as berries, red grapes, apples, carrots and ate a largely raw food diet which contained huge amounts of vitamin C (another potent mast cell stabilizer). By doing this I think I broke the feedback loop of some of the mediators, though obviously not all as I’m still ill. Other people, with different mediators or differently expressed mediators to me, might find others ways to break the cycle, such as particular supplements, meditation (anything which helps stress is brilliant, as stress causes mast cell de-granulation as explained in the Canary article) or certain drugs like Naltrexone (see end question).
Q. Why don’t anti-histamines ‘cure’ ME?
Histamine is only 1 out of dozens of mediators produced when mast cells are activated. Anti-histamines do nothing to stop mediators other than histamine affecting our symptoms.
As it is, we only have drugs which target H1 and H2 histamine receptors. We have nothing to stop histamine binding to H3 or H4 receptors.
And even those drugs which target H1 and H2 only stop histamine from binding to the receptors. The histamine itself is still left to float around the body binding to other receptors, like H3 or H4.
So, anti-histamines will help specific individual symptoms, like excess stomach acid, or itchy eyes, but not much else. There is no cure for mast cell diseases like Mastocytosis or MCAD. Mast cell stabilizers can help the mast cells to not release their mediators quite so readily, but nothing we currently have at our disposal stops the mast cells from de-granulating full stop.
Q. What about Rituximab and other drugs used to treat ME?
As I outlined in my Canary article, there have been exciting research developments in treating ME using the anti-cancer drug Rituximab. Funnily enough, anti-cancer drugs are also used to treat Mast Cell Disease, particularly Imatinib as discussed by Dr Afrin in his 2011 lecture on MCAS.
I have a friend who was bedridden from 1994 until she started taking a low dose of Naltrexone in 2011. Although still very much suffering with ME, she has made a good degree of recovery and is now thinking of living independently for the first time in her life. Naltrexone is also used to treat mast cell disease (see Dr Afrin’s lecture).
I don’t think ME is Mast Cell Activation Disorder – they are 2 distinct illnesses. What I am proposing is that mast cell activation may be responsible for the symptoms of ME, and that this area really does need to be explored by researchers working in the ME field. The pieces fit so neatly together that, to me, the correlation between mast cell activation and ME is striking. In 20 years of researching ME nothing else has ever come closer to explaining how ME starts, is perpetuated, the kinds of symptoms it produces, why test results are always negative, or why a diagnostic test is so illusive (there is no test for mast cell activation, not yet at any rate).
If it looks like a duck, and quacks like a duck…………you all know the ending 😉