Do ME symptoms fit with the faulty energy metabolism hypothesis?

My PEM seems totally neurological: primarily lethargy and malaise. I don't suffer from physical problems. I'm sure my muscles could manage a 6-hr bike ride while I was suffering from PEM; it would just feel like horrible torture, and I might need someone with a whip to keep me from giving up. Thus I disagree with theories about energy metabolism, unless it's limited to brain cells involved in motivation and muscle signalling. I haven't suffered physically-induced PEM for quite a while (I use an effective PEM blocker), but IIRC, the severity and duration of my PEM didn't vary much with the strength of the trigger; a minute of washing windows caused similar severity and duration that a 40 km bike ride did.

I think PEM is a change in brain cell function. There's a trigger, and then some ratios of molecules changes, or there's a change in micropores in cell walls or whatever, which changes our perceptions and nerve signalling. That gradually returns to our ME baseline (rather than 'normal').

 

What is the PEM blocker? I don't think I've heard of this.

 

From a previous post by @Creekside

It does nothing for me, but.......

...and I'm not sure it's internally consistent with @Creekside's own hypothesis - but whatever works

 

Thanks, @Wonko.

I have curry most days and it contains cumin. Previously I used proper spices including cumin when cooking. No noticeable effect...or was there?

How much do you use, @Creekside?

 

Hmm, I like cumin too, but have found no effect on any symptoms.

 

Cumin works wonderfully for me. A level tsp of ground cumin blocks my physically-induced PEM completely for 3 days. I'm pretty sure I posted it on this forum long ago, and on PR and HR as well, but no one has reported that it works for them. It seems something unique to me. I keep hoping that it will work for someone else, so that researchers might follow up. It makes a huge difference in my quality of life (able to do physical activities again). Once in a while I start feeling unusually lousy, and realize that I'd forgotten to take my dose, so it's not placebo effect. FWIW, taking more cumin only increases the duration slightly: 3 full tsps lasted 6 days. I prefer the minimal dose every 3 days. I discovered cumin's effect by accident, when PEM expected after some physical exertion failed to show up.

I did some experimenting with other herbs and spices to try to identify the active chemical. I'm pretty sure that it's cuminaldehyde, but I don't have an alternate source to verify that with. Cuminaldehyde content varies with where it's grown. IIRC, the Turkish variety is high in cuminaldehyde, but cumin from some other countries (Egypt? India?) are low. The bulk bin seeds and non-name ground cumin have all worked for me, but some brands might not.

If it does work for someone else, please let me know.

 

@Creekside are you referring to black seeds aka black cumin? As in Nigella Sativa? Dr. Moreau mentioned thymoquinone, an active ingredient found in Nigella.

I took the Turkish formula oil for over a year but didn't notice anything helpful.

 

@Creekside referred to Cuminum cyminum earlier.

 

I've gotten into the habit of including the (Cuminum cyminum) whenever I mention cumin, because there is confusion. The black cumin is frequently mentioned as a health product, while regular cumin isn't. My guess is that it's the 'rare ingredient' marketing approach: sellers of fake treatments used rare ingredients because everyone already knew that the easily available ones didn't work. Rare ingredients have the 'I don't know for sure that it doesn't work' aspect.

As I said, I'm pretty sure that the active chemical is cuminaldehyde. I found one source saying that perilla had cuminaldehyde, but other sources say that it has perillaaldehyde. I didn't have a convenient source of that, so I didn't try it. I don't see a point in trying pure cuminaldehyde unless a researcher is going to follow up on why/how cumin is blocking my PEM.

 

Maybe there is some medium-term cumulative effect going on. Supposing the failure (or partial failure) of one subsystem leads to overloading of another subsystem, the latter then being forced to undertake an abnormal role, and thereby itself maybe hitting its own secondary failure mode. This is a common failure scenario for many things. e.g. Laptop lid hinge goes stiff which then stresses the case over time. Or some injury leading to an abnormal gait, then putting abnormal stresses on other parts of the body.

And though biology is mostly a mystery to me, from what I read here in S4ME it is has a lot in common with some pretty amazing and highly complex process control, which I do have some understanding of. Many of the transfer functions likely having time constants of some kind, meaning delays between cause and effect, some short and some not so short. These time delays often being due to an integral build-up effect, cumulative.

 

I have often thought of it this way. Some systems in the body can tolerate up to maybe an eighty percent failure. Like the heart circulation. Once that threshold is reached though you are in deep trouble, though minor symptoms occur earlier. With ME there is a small failure in many subsystems, with a few having larger failure. Each failure is within a compensatable range, but as you point out the compensation puts stress on other systems. ME is about partial failure in a great many interlocking systems, so that the overall failure is very high. For example, if you have a 10% failure in ten systems, the final result is an over 70% failure. Degradation in each subsystem has an impact on overall performance, and with enough sybsystems failing the total performance is bad.

With a computer analogy this might be partial CPU degradation, memory degradation, hard drive degradation, frayed wiring, a failing power supply, all at a low level of failure until you put them all together.

Whether or not this is some kind of cascading failure is not known. It is however possible that its not some kind of cascading failure effect, but many partial failures having a cumulative failure effect. Some knock on is still likely though even in this scenario.

 

The priority comes the other way down, given that there are:

• sudden onsets after physiological impacts
• outbreaks
• some genetical predisposition as suggested by twin studies

It might be a big mistake to assume that there must be something which is by no any means linked to any any mental thing, just to rule out to get mistreated.

It is an unbelievable event that the PACE trial managed to sidestep these first (and strong) hints.

 

I like the concept of linked subsystems failing and affecting other subsystems. It could explain the gradual changes in my ME symptoms over the years. One subsystem weakens, and another gradually strengthens to 'take up the load'.

 

I dont see how their should be a problem explaining PEM as related to metabolic problems if the metabolic problems are downstream of the ultimate cause of the disease, and thus different from inherited metabolic disorders (although I think some inherited metabolic disorders can present like me/cfs, if we are to believe the NIH has ruled people out based on finding those disorders in thorough workup, and ron tompkins says something similar)

When naviaux compares the hypo metabolism in me/cfs to sauer, it makes me think of taking the analogy further. Dauer is caused by prolonged exposure to periods of starvation, so the hypo metabolism is protective. But clearly me/cfs patients aren't suffering from a lack of calories. So what else could make hypometabolism protective?

Well, the term "oxidative stress" may be overused and too broad, because oxidative reactions and free radicals are sometimes good and protective... but if there is some sort of xeno biotic situation in me/cfs that causes oxidative stress from various sources... either the immune reaction to the organism or directly from the organism, or toxicity...? Then it makes sense for energy production to down regulate in response. Even though cellular oxidative metabolism isn't the sole source of oxidative radicals it is a source, and so if the body has too much damage from these going on it may shut down energy production to compensate. Also I believe there are enzymes involved in reducing oxidative radicals as a step in cellular metabolism, if those enzymes are impaired in any way this may be more important than hypometabolism in general.

The delayed symptoms in exertion, unlike primary mitochondrial diseases, could be explained by all I'm saying... if the hypometabolism is secondary rather than primary ... increasing oxidative stress through a number of things that are known to do so, like exercise , or stimulant usage , could cause a crash and down regulation of metabolism later.

One really really interesting clue in me/cfs for me was that prior to developing me/cfs I had ADHD and stimulant medications for it were well tolerated and sometimes even made me relaxed. After the infection that triggered my slow decline into total me/cfs , I started experiencing only negative side effects of stimulants , with none of the beneficial effects like focus. Before me/cfs ritalin would make me feel somewhat calm and focused at the same time. After me/cfs, I would feel extremely uncomfortable, wired, brain on fire., etc. From stimulants. There are other drugs in which my reaction changed so starkly before and after me/cfs that I have to imagine they hold clues to the pathophysiology. Stimulants increase oxidative stress which may not be a problem in otherwise healthy people