Looking at some current ME/CFS theories

I have been active reading research and hypothesis dealing with Myalgic encephalomyelitis/chronic fatigue syndrome for 20 years. I am also well trained in mathematics, statistics and modeling with some Ph.D. courses. Every time a new hypothesis comes out I review it to see if it is objectively better than the hypothesis that I am using.

What makes a hypothesis better?

  • How many observations in the literature does it give a simple direct explanation for?
  • Can it be used to make testable predictions?
  • And last, for illnesses, how long before it is actionable for treatment?
    • Do the actions work for a significant subset or the entire population?

For the microbiome hypothesis, the values of all of these is very high, especially the last one — you can take action today.

In this post I will review some recent posts by my long time friend, Cort Johnson.

Emerging Insights #II: “The Cellular Equivalent of Chronic Fatigue” Found in ME/CFS

Ten years ago, Fisher’s intuition was correct.  ME/CFS patients’ mitochondria are having problems producing energy. Something that’s gone wrong in one mitochondrial complex is throwing off the rest of the complex. The good news is that the problem is not subtle: Fisher appears to be seeing major problems across the mitochondrial pathways.

Microbiome dysfunction alters the metabolites that feed the body and the mitochrondria.

The bad news is how complex the mitochondria are. Fisher doesn’t think he’s going to find a single cause that responds to a single, simple fix. He also left open the possibility that the Complex V problems could be a consequence of another as yet unknown problem.

So no testable predictions nor actionable.

The Relevance of Research on Critical Illnesses for Chronic Fatigue Syndrome ME/CFS: A vicious cycle between cytokines, oxidative stress and thyroid hormones

We have predictions in this hypothesis

Given the reduced thyroid hormone activity in NTIS, clinicians began, as early as the 1980s, to suggest thyroid hormone supplementation in their critical NTIS patients in an attempt to increase their survival rates (Carter et al., 1977; Brent et al., 1986 and DeGroot, 1999). This approach continues to be debated today (Davis, 2008; Kaptein et al., 2010; De Groot, 2015; De Neto et al., 2016; Breitzig et al., 2018)… Given the impaired conversion of T4 to T3 in NTIS, some researchers also propose T3 supplementation (as opposed to T4 supplementation) (Biondi, 2014).

Positive results for some subsets of patients. I have the words “positive results” because that is often wordsmithing to keep funding grants coming.

Results with thyroid supplementation have been mixed (Farwell, 2008), but have most often been beneficial (see review in Fliers et al., 2015). Interestingly, positive results have reportedly been achieved by supplementing thyroid hormones in NTIS patients who had become ill after mold exposure (Somppi, 2017)…..  supplementation doses have to be very high to achieve results (Debavaye, 2008).  These suggestions regarding the type and quantity of thyroid hormone supplementation in NTIS echo the arguments made by some practitioners on T3 supplementation for ME/CFS (see my previous blog post).

Currently actionable: I read it as saying no.

Epstein-Barr Virus May Be Turning On Pathogenic Genes in ME/CFS

EBV related hypothesis has been around a long time and appears to apply to a subset. For other patients it is Q-Fever, Rickettsia, Giardiasis and Lyme. For all of these we hear terms like re-activation or occult form of the infection. While antibodies are found, those infections appear to be controlled. We now hit two paths: these turn on genes (an epigenetic change) or these cause a microbiome shift (with the change of metabolites produced perhaps triggering epigenetic changes).

We have no predictions here. Nor do we have any know actions to turn off pathogenic genes (assuming we can identify them).

Bottom Line

People often ask me what I think of this or that hypothesis. I evaluate them with the rule above. 95% of the time I quickly see that it is a speculative hypothesis “perhaps this may explain…” without sitting down and looking at the historic facts reports in decades of research. Often, I hate to say, the research is a specialist in area A and trying to see if his area of research may work for CFS — and perhaps get a grant to research.

When a new theory come across your groups, try applying the above criteria.