I am still unclear if this proved it is autonomic/neuro based vs. micro-vascular angina, vs. virus in the heart, vs. histamine/MAST cell, vs. pure ME/CFS (cellular/mitochondrial issue) etc.
Yes, it can certainly get confusing with all these symptoms, many of which seem unrelated, and many of which would seem to require different treatments. So I think that this is a good time to bring in
Occam's Razor to slash away a lot of this complexity. From Wikipedia:
Occam's razor (also written as
Ockham's razor and in
Latin lex parsimoniae, which means 'law of parsimony') is a problem-solving principle devised by
William of Ockham (c. 1287–1347), who was an English
Franciscan friar and scholastic philosopher and theologian. The principle states that among competing hypotheses that predict equally well, the one with the fewest assumptions should be selected. Other, more complicated solutions may ultimately prove to provide better predictions, but—in the absence of differences in predictive ability—the fewer assumptions that are made, the better.
Or as Albert Einstein so concisely put it, "A good theory should be as simple as possible, but no simpler."
We know that ME/CFS typically starts with a single trigger, and then a whole panoply of symptoms tends to erupt. Over time, new symptoms or comorbid illnesses tend to pile on as well. In the worst cases, dysfunction and infection can spread to many different bodily systems.
One can treat these symptoms individually, but it can be very difficult to get good results by this method in cases where there are so many of them. And if the various comorbid illnesses are treated without an awareness of their interrelationship, it is very hard indeed to make significant progress.
Yet ME/CFS has certain fundamental qualities present in everyone; that's why we consider it a single disease (though a multi-faceted one, to be sure), and that's why it's even possible to make a case definition, even though the definitive one may not exist yet. These two factors imply that there is some underlying disease process common in all of us, even though it never manifests exactly the same in any two people. But it would seem to reason that if we could address this underlying process, we should be able to treat the entire illness. And getting to the root of this illness would seem to be more effective than chopping away at the branches.
To get at the root of the illness, we need a good theoretical underpinning. There are certainly no shortage of theories out there, but this is where Occam's Razor can guide us. Is there a theory that can explain
everything in one fell swoop? And if so, are there large-scale clinical results supporting it?
Those people who are familiar with my posts undoubtedly know what's coming next. Dr. Goldstein came up with what is in essence a very simple theory for what is going wrong in ME/CFS (although the details, like the disease itself, are quite complex). In his most recent article, published last year, he said, "I view CFS as a nitric oxide and glutamate disorder, affecting primarily the brain." This view is consistent with the theories of Dr. Paul Cheney, Dr. Rich van Konynenburg, and Dr. Martin Pall, among others. It is supported by Dr. Goldstein's experience with over 20,000 patients; in the later years of his career, he stated that he was able to get all but two or three percent of his patients asymptomatic, or nearly so, and and most of them in a matter of days. No one else has had similar success treating this illness, before or since.
Dr. Goldstein listed all the usual suspects as possible triggers for ME/CFS. But the exact mechanism by which glutamate and nitric oxide became imbalanced was unidentified. In recent years, strong evidence has emerged for a microglial inflammatory process in the brains of ME/CFS patients. And some of the results of this type of inflammation are toxic amounts of glutamate and nitric oxide.
But does this explain all the effects of ME/CFS? Well, let me ask the question: Without a brain, how well does the rest of the human body function? And although we have a brain (although sometimes it doesn't feel like it), its functionality is reduced, sometimes severely. Not surprisingly, more and more evidence is tying the operation of the brain together with the operation of the immune system; a PubMed search will provide plenty of examples. And without a healthy immune system, infectious diseases can flourish. So can autoimmune diseases. And the Th1 => Th2 shift that occurs in the immune systems of many (if not most) people with ME/CFS is well documented; one of the results of this is increased allergic reactions, such as you have been experiencing,
@Gingergrrl.
Now on one hand, when acute symptoms arise, such as increased allergic sensitivity, it's good to treat them directly, as the long term effects of more fundamental treatments may take a while to spread throughout the body.
@Gingergrrl, this is why the decision of your doctor to treat your histamine problems aggressively makes complete sense.
However, for a full resolution of symptoms, the use of an agent that works directly on microglial inflammation appears to be the most effective approach. Valcyte seems to be the most effective drug found so far here, although as other have noted, there are many other drugs that act in this area as well. Valcyte is also a powerful immunomodulator. From
Dr. Jose Montoya's conference call of 2/23/15 with Dr. Elizabeth Unger, who is the Branch Chief of the Chronic Viral Diseases Branch of the CDC:
Valgancyclovir – we discovered this drug has immunomodulatory abilities that were not known before our work at Stanford. These include a temporary but significant decrease in circulated monocytes and a shift towards a TH1 profile.
We believe that immunomodulation not only could partially explain the benefit of Valgancyclovir, but could easily turn out to be crucial in the treatment of ME/CFS. In fact, our cytokine data and that of others support this view.NK cell function: we’ll apply novel technology to the NK cell deficiency in ME/CFS shown by several groups
We believe suppressing herpes viruses may be an important component in what should be a holistic approach to treat ME/CFS patients
These immunomodulatory abilities are not merely theoretical, nor is the only basis for them observed differences in white cell counts. Back in 2001, I had figured out that this drug had immunomodulatory properties, and I used it to kick-start a nearly dead immune system. I later used it to get my immune system to get rid of non-herpes viral growths far more effectively that even a healthy immune system would. During this process, a large HPV wart I had had on my right index finger for over forty years disappeared completely, leaving healthy skin in its place. And Valcyte is known to have no effect on HPV viruses.
But Valcyte is not an immune activator - it didn't leave my immune system in a state of over-activation, and I didn't suffer any auto-immune effects. Instead, Valcyte is, as Dr. Montoya states, it is an immunomodulator, which in this case means that it just makes the immune system work properly. Or, in my case, better than properly.
Recently, some of us have found that low dose Valcyte can work far more effectively for far more people and with few or no negative side effects. This is a very new area and still being explored. Personally, I have found that a dose of 14 mg (1/32 of a tablet) per day works very well. I use it five days on and two days off; this is the same schedule used at the clinic where I initially got my ganciclovir infusions, and the pulsed dosing seems to maximize the immunomodulatory effects of Valcyte (avoiding the "temporary" aspect that Dr. Montoya mentions) while giving the body time off to help prevent any negative reactions.
For those who are interested, I'll be posting a detailed thread about the theory and use of low dose Valcyte in the near future. I'll also discuss new evidence I have found that Valcyte may be helping mitochondrial functionality.
Meanwhile, although Valcyte certainly is an effective monotherapy for many people, its effects can be enhanced by various other drugs. Foremost among these is magnesium, whose effects are very complementary to those of Valcyte. Magnesium does have some microglial inhibiting properties, though these are far weaker than Valcyte's. Its most helpful effects come from the fact that it is the single most powerful NMDA antagonist. So whereas Valcyte inhibits glutamate release, magnesium calms down the NMDA receptors, which have typically been put into a hyperactive state from the release of too much glutamate.
@Gingergrrl, I think that it was the combined effect of these two drugs that had such a strong effect on your autonomic symptoms when you were receiving relief from the Valcyte, and that as the inflammatory reactions from your latest traumas gradually subside with the help of these two drugs, you will be able to experience the same effect again, and be able to continue your recovery.
Within this framework, I think I can answer some other questions that were asked in a way that should make sense.
How does Isordil compare to a Nitroglycerin patch? The reason I ask is that my cardio said if the Nitro helps me, then he can prescribe me a patch (but wouldn't do this if I never tried the Nitro or if it didn't help me.)
The overall action is similar, but a nitroglycerin patch appears to be somewhat more effective than Isordil. Dr. Goldstein prescribed nitroglycerin patches for his patients who responded positively to the sublingual version of nitroglycerin.
I know beyond a shadow of a doubt that my cardio will say that this is proof of micro-vascular angina (even though it did not work the first time I tried it.)
It doesn't really matter. At the top of page 4 of
Betrayal by the Brain, you will find microvascular angina listed by Dr. Goldstein as one of the disorders that should be amenable to his neurosomatic treatments. In other words, you may very well have microvascular angina, but if so, it is of autonomic origin just like your POTS symptoms, and will respond to the same treatment. Early on in your nebulizer treatments, you commented on how they reduced your angina significantly. And early on in my own nebulizer treatments, I could feel my angina lessening during the treatment. This is far too fast a reaction to be anything other than neurological.
However, magnesium is also extremely useful in enhancing mitochondrial function (among many other things), and since the half heart muscle is composed of mitochondria, this is an excellent treatment for your heart in other ways.
What do you mean exactly re: the neuro effects of nitrates? Is there a page in the Goldstein book that I can read on this to try to understand it better? I always feel so dumb asking these basic questions.
The neurological effect of nitrates simply means that these drugs can help your brain work better, and relieve many if not sometimes all of your ME/CFS symptoms. Although Dr. Goldstein discusses nitroglycerin extensively in
Betrayal by the Brain (you can look in the index to see where), I don't think that reading this will help you understand the process any better. Much of the mechanism of action of nitroglycerin in ME/CFS, like much of the action of virtually all of Dr. Goldstein's drugs, is unknown.
There is the question of why nitroglycerin initially had no effect for you, and now it does. Like me, you appear to be one of the fortunate people who responds to this drug. But your recent traumas may have caused so much inflammation that the neural network switching that nitroglycerin causes in susceptible people simply could not happen. As you have been on a therapeutic dose of Valcyte for a number of days, the inflammation may have dropped to a level where the nitroglycerin could work. As you have seen, low dose Valcyte can often have positive effects in a matter of days, versus the months it often takes Valcyte to work at a standard dose. The reason for this appears to be that at a low dose, Valcyte's negative, inflammatory effects are negligible, while its beneficial effects seem to be undiminished. In other words, Valcyte's beneficial effects seem to top out around the dose you are taking. This has been observed in a number of people so far.
@zzz will know much more about this than me but I was under the impression that Goldstein used nitro on his patients for ME/CFS in general not just when they were having an attack of angina.
This is true. As Dr. Goldstein used nitroglycerin purely for its neurological effects, and as these could encompass all ME/CFS symptoms, whether or not someone was suffering from angina was not a criterion for his use of this drug.
@zzz do you know if oral timed-release capsules would work similarly to sublingual nitroglycerin for ME/CFS purposes?
It would certainly make sense that they would, but not having seen evidence of this, I can't say for sure. However, the effectiveness of nitroglycerin patches for this purpose certainly does seem to imply that timed-release capsules would work.
@Gingergrrl, it is certainly possible that you have an active Coxsackie B viral infection. But as you have noted, you cannot tolerate Dr. Chia's drugs. The best way for you to fight such an infection, if it exists, is with an enhanced immune system, and Valcyte will give you that over time on your current regimen. Without a reasonably functioning immune system, an antiviral can't completely eradicate viral activity anyway.
To summarize,
@Gingergrrl, I think that the two primary treatments that you are doing - Valcyte and magnesium - have the potential to address all your problems. I find it quite interesting that if you read the thread
Jennifer brea- does anyone know what treatments she is doing?, you find that two of her main treatments are Valcyte and magnesium. And now nitroglycerin appears to be helpful for you as well. I think that there are other treatments of Dr. Goldstein's that would also speed up your recovery process; we can talk about this privately if you like.
I should also add a disclaimer here. Although I think that this post has wide applicability, it is directed primarily to
@Gingergrrl and her particular circumstances. Low dose Valcyte and magnesium are not guaranteed to work for everyone. And even in those for whom these drugs work, optimal dosing may be different from what
@Gingergrrl is using. Much more research is needed in this whole area.