Addressing Energy Problems in ME/CFS

In this video, I research ways to address energy problems in ME/CFS and try a couple of new approaches. One worked, albeit incompletely. The script, with links to sources and products, is below.

In a couple of other videos (here and here), I’ve discussed recent findings regarding energy problems in the cells of people with ME/CFS. (That’s myalgic encephalomyelitis, or chronic fatigue syndrome.) In this video, I try to figure out what I — a person with this disease — might do about it. And then I do it, with some success. As usual, I’ve simplified the biological details.

First some background: Two Norwegian researchers, Fluge and Mella, found a problem with the conversion of glucose into fuel in the cells of people with ME/CFS. Glucose is a sugar, so this is a problem converting sugar into ATP, the main fuel in cells.

In a chain of steps, glucose gets turned into pyruvate. Most of the time, a molecule named pyruvate dehydrogenase, or PDH, then helps to convert pyruvate into acetyl-CoA. Acetyl-CoA eventually gets turned into fuel in the form of ATP. Otherwise, pyruvate turns into lactate, and we feel bad.

So, to restate it briefly, either:

  • PDH helps convert pyruvate into fuel, or
  • the pyruvate becomes lactate, which causes pain and weakness, and we rely on less efficient methods to make ATP.

What Fluge and Mella found in ME/CFS patients is higher amounts of several molecules that hinder PDH, leading to less fuel and more lactate. Here are the molecules that Fluge and Mella found were higher in people with ME/CFS:

  • PDH kinases 1, 2, and 4, known as PDK1, PDK2, and PDK4.
  • Sirtuin 4, and
  • PPARδ (P-PAR-delta)

Fluge and Mella mention that a pattern like this can happen as a response to starvation. I don’t really know what to do with that knowledge.

But there’s a similar, inborn genetic problem called pyruvate dehydrogenase complex deficiency, or PDCD. People with ME/CFS don’t have PDCD. Our energy problems aren’t due to a genetic mutation that directly affects PDH from before birth. Instead, we’ve developed a similar problem for different reasons.

But, because of the overlap, some of the treatments for PDCD might help people with ME/CFS. I did some research online, and the brief version of what I found is to maximize energy production via three supplements: lipoic acid, carnitine (I use acetyl-L-carnitine), and thiamine (I use benfotiamine). Flooding our cells with these three substances makes it more likely that they’ll be able to convert pyruvate into energy.

Wait, you might say – isn’t all the pyruvate turned into lactate in ME/CFS? In fact, this is an incomplete process in a couple of ways. The kinases don’t turn off PDH like a switch; instead, they hinder it, making its success less likely but not impossible – kind of like making a basketball rim a little smaller. Plus, the kinases don’t necessarily affect all of the many sites in a cell that produce ATP.

In addition, these three supplements should help to maximize the other, less efficient types of energy production — that is, from fat and amino acids.

More than a month ago, I started taking them all together, and … it worked for me! My stamina improved noticeably, my recovery after over-exertion was faster, and my heart rate was noticeably lower (by about 10 beats per minute). My pulse feels stronger, and my fitness tracker has an easier time finding it, so I think that my heart has more energy. Moreover, a key symptom has decreased, presumably because I started these supplements: this is a debilitating ache radiating from my torso that accompanies post-exertional malaise.

Nonetheless, these gains, while welcome and real, are limited, and I’ve still spent quite a bit of the past few weeks laid out in bed. My many autonomic problems remain, although some are weaker. And my irritable bowel syndrome, disease-related lactose intolerance, need for sleep, and sleep problems didn’t change noticeably.

These supplements are a work-around, making the best of a sorry situation. I also read up on each of the various molecules that Fluge and Mella found at elevated levels in ME/CFS, looking for ways to counteract them. The table summarizes what I found:

  • Sirtuin 4
    • none identified
  • PPARδ
    • none available
  • PDH kinases 1, 2, and 4 are inhibited by:
    • ADP
      • I think that this already should be around.
    • NAD+
      • But this aids sirtuins, so …
    • CoA-SH
      • Supplements named like this actually contain only ‘precursors’ because it has to be synthesized in the body.
    • Pyruvate
      • This obviously is too plentiful already.
    • Dichloroacetic acid (DCA)
      • This drug is dangerous, requires special care, and isn’t completely effective.
    • Coumarins, possibly

From my perspective, only the last item, coumarins, seemed promising. I found an article in which researchers used a computer model to identify substances that might inhibit the PDH kinases. In the two inhibitors that they found, the key parts were coumarins, which are high in various foods, including ordinary (not “true”) cinnamon. This finding was based only on a computer simulation, so who knows?

I wanted to know, so I bought cinnamon supplements to see what might happen. And .. the major result was negative: a tremendous increase in my Periodic Limb Movement Disorder, or restless legs, while trying to sleep. In no way did I improve. So I stopped taking them and felt better.

By the way, our cells produce another molecule, pyruvate dehydrogenase phosphatase, which counteracts PDH kinases. But I couldn’t find any sufficiently specialized substance to take that would stimulate it.

So, to summarize, here are four approaches I considered:

  • Eradicating the signal in the blood that causes cells to reduce the conversion of pyruvate into ATP.
    • That’s the reason to take rituximab, antivirals, and/or antibiotics and to avoid triggers.
  • Stopping the signal inside the cell to make more PDH kinases.
    • As far as I can tell, this is not currently possible. Perhaps the drug suramin would do this by getting cells to ignore the signal in the blood.
  • Stopping the kinases from attaching to PDH.
    • This is what I hoped the coumarins in cinnamon would do.
    • Researchers – not specialists in ME/CFS – are trying to develop other drugs that will reduce the power of the PDH kinases, so maybe we’ll have other options eventually.
  • Optimizing everything that already works.
    • This is the hope for most of the various supplements I take, including the lipoic acid, carnitine, and thiamine that are recommended for the similar disease, PDCD. And they have helped in a welcome but limited fashion.

I wish I had even better news. But this exploration has helped me to improve my health noticeably, if incompletely. I hope you get some benefit from it it, too.

Some sources:

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2 responses to “Addressing Energy Problems in ME/CFS

  1. Great summary/explanation, Tracy. Thank you for sharing your experiences.

    Liked by 1 person

  2. I appreciate your science-based approach to managing your illness
    and am glad that it seems to be helping.

    Liked by 1 person

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