Is the Fatigue in ME an Eicosanoid Phenomena?

Blog entry posted by alex3619, Nov 27, 2012.

This is not one of my planned blogs, just something I thought I should report. I have been interested in eicosanoid impact on CFS and ME since 1993, based on the work of Dr. Andriya Martinovic. Eicosanoids are generally very short acting and short range hormones. They are used by a cell to communicate with itself, but also nearby cells.

I am experimenting with a new shotgun protocol. A simplified description is its a combination of methylation, antioxidant and one specific anti-inflammatory, with some minimal mineral support.

In particular:

Methylation: Methyl B12 and methyl folate.
Antioxidants: C, E, Q10, NAC, lipoic acid, resveratrol, grapeseed.
Antiinflammatory: Resveratrol.
Minerals: Magnesium, selenium.

I am still playing with doses, so have no idea what a proper dose is. I have selenium in there because it enhances tolerance to LPS which is something for another (planned) blog next year. I also wonder if molybdenum should be on the list.

Over the last two decades on various protocols I have completely restored my energy a number of times. In the most spectacular partial remission, on my first shotgun protocol leading up to my going to the 1999 Sydney CFS conference, I went from being too exhausted to want to walk across the room to walking five hours per day, every day, on the Sydney beachfront (Manly?). This in a matter of weeks. What is the issue though is that never, I mean absolutely never, has any of my protocols touched my deep down intractable fatigue.

Until today.

I am now having brief episodes of zero fatigue. This does not mean I have energy, I just have no fatigue. I can however feel that I have not had enough sleep, this is a different issue.

A huge downside of resveratrol is that it can wipe out my capacity to sleep if I take too much. No matter how tired I get, sleep is impossible. This is an eicosanoid phenomena I think, probably PGD2 (prostaglandin D2, an arachidonic acid derived eicosanoid) deficiency. On the other hand too much PGD2 can cause hypersomnia. This can be induced by antioxidants, excessive NO or excessive inflammation. The primary source of PGD2 affecting sleep is from the brain, though almost every tissue in the body makes it especially mast cells. PGD2, as well as other eicosanoids, appear to affect vasoregulation.

With respect to mast cells I think most of us do not have a mast cell problem. I do however think we have an eicosanoid regulation problem, and one of the sources of that could be mast cells. However I cannot rule out the existence of subgroups with mast cells disorders.

So the resveratrol, though a herbal antioxidant, makes tolerance of other antioxidants (and probably methylation) much greater, at least for me. However the reverse is also true. The antioxidant pentet makes resveratrol more tolerable.

With respect to methylation I find that the symptoms people are ascribing to low potassium disappear on resveratrol. This implies that these symptoms are eicosanoid induced, though this is not certain. So taking potassium may be a method of altering these symptoms in a drug-like not a deficiency-like way. However I am also aware that about half of us have low intracellular potassium, so there may be subgroups. This is because both potassium and eicosanoids are very important in maintaining blood vessel tone I think.

My respiratory hyper-responsiveness also seems to disappear on resveratrol. If I get an attack while on resveratrol I guess I will have disproved that, but it hasn't happened yet. It has happened when I forgot to take resveratrol and just took antioxidants.

To be clear though I am ignoring something here, at least for now. The source of resveratrol I am using also contains grape seed extract. I think thats a good antioxidant but I am not aware its anti-eicosanoid, though it can have an impact on nitric oxide (a biphasic impact depending on dose). It also might be important that my resveratrol is grape seed sourced.

My new Zombie Science blog is almost done.

Bye, Alex
picante, rosie26, Beyond and 8 others like this.

About the Author

I am a long term ME patient with many complications. While I have pushed research advocacy since 1993, I became political around 2009. My current project is a book called "Embracing Uncertainty". Uncertainty in medical science seems anathema to too many doctors. "I do not know" is something more doctors should be honest about.
  1. alex3619
    Latest: resveratrol can boost mitochondrial function.
    triffid113 likes this.
  2. alex3619
    Darn, via PDE4 I can now tie PGD2 to low HDL and to exaggerated LPS response. This is getting interesting. It is also linked to rheumatoid arthritis and abnormal adrenal response. Exploring the nature of those links is one of my goals for the next month or so. It can even drive a TH2 response perhaps ... still looking at this. It may even lower excessive folate usage, though this is still very unsure.

    In case people are wondering, PDE4 is phosphodiesterase-4.

    Other side effects of PDE4 inhibition include nausea or vomiting, but my sleep issues arrive at much lower doses than appear necessary for nausea or vomiting - I have not experienced either.
  3. alex3619
    Resveratrol appears to block a substance called PDE4, which might also make it an immune modulator.

    However based on my reaction its affect on reducing sleep appears to be prolonged, which means that sleep might continue to be compromised for some time after ceasing resveratrol.

    However there is some indication that some of the negative effects of lack of sleep will be alleviated with this approach, due to decreasing PDE4 activity, and this should improve memory.

    It isn't simple.
  4. alex3619
    My Zombie Science blog is done and I am now working on the sequel. I would like to post both together before Christmas, but if not I will post the Zombie Science blog alone. It discusses the impact of zombie science under the influence of churnalism and dogmatic verificationism. It leads into a discussion of the concept of balance of power.
  5. Xandoff
    Looking forward to Zombie Science Blog.
    PNR2008 likes this.
  6. heapsreal
    You may have looked into this but thought i would mention it anyway.
    The amino acid taurine which doesnt become apart of the protein supply but instead polices our cell membranes, keeps potassium and magnesium inside the cells and keeps excess sodium out, so works like a natural diuretic. This mechanism can also possibly reduce your need to supplement with potassium which can have its issues if one over supplements with it. Taurine also has some brain calming effects and is used in seizure disorders. it can also reduce the excitotoxic effects of msg and aspartame.

    I mainly mention this as it may be helpful for you in maintaining intracellular potassium levels.

    PNR2008, Lotus97 and WillowJ like this.