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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
Beyond, PNR2008, justy and 6 others like this.
alex3619

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. triffid113
    Heaps, my genetic makeup is a taurine-generator and I am drowning in taurine and I can tell you that w/o DHEA I am still EXTREMELY sensitive to msg (it could kill me).

    Alex, your protocol disturbs me because you are picking and choosing B vitamins when they are synergistic and should be taken together at least in a low dose. I am wondering why you are attacking only phosphidoesterases [sic!] and skipping basics like supplying B2 and B3 for the Krebs cycle? And I am wondering if you are taking the active form of CoQ10 (ubiquinol).

    I never got on the reservatrol bandwagon because I take sooooo many supplements and that one was merely touted to the rafters for longevity (when I am more interested in making the time I've got have quality). I have tried it several times with no discernible results, but maybe I'll give it a try again.

    I started taking melatonin at 6mg)since Life Extension said it is the MOST IMPORTANT ANTIOXIDANT TO THE BRAIN NEXT TO DOPAMINE! (I lead my life by the principle that antioxidants are numero uno in importance in a supplementation strategy).

    If I fail to take 400-600mg magnesium citrate/day I cannot sleep. I think this is actually a good thing because with low magnesium you die of heart trouble so I'd rather be notified by wakefulness and be forced to take care of it every day than let the problem build up. How much mg do you take? what form?
  2. alex3619
    Hi Unim, I was using 98% resveratrol. Dosage seems to be variable. I am currently taking 600mg about once or twice a week. I don't need to take it every day. However I have higher body weight than most ME patients, so 300mg would be a more equivalent dose for many. There are signs that resveratrol sometimes fails to control my breathing issues, but only occasionally, and not very severely.
  3. Unim
    Hi Alex,

    Very interesting! Were you using any particular form of resveratrol when you noticed this? It seems to come in two forms, the high purity 98% pharma grade or a lower 50% purity in typical supplements. Also was there any particular dosage you found necessary?

    Thanks
  4. alex3619
    There are so many pathways involved in excitotoxicity that I am mostly taking a wait and see what the research turns up attitude. Sure there are lots of possibilities, but which one do *I* have? Or most of us? We need both more science and more testing.
  5. Lotus97
    Ginger makes me overstimulated. I'm not sure if that has anything to do with triggering a crash or not.

    And do you disagree with Rich about some of the symptoms from methylation due to excitotoxicity? He thought it was from a drop in glutathione in the astrocytes which then causes a glutamate buildup:
    http://forums.phoenixrising.me/index.php?threads/l-cystine-may-help-to-lower-excitotoxicity-on-methylation-protocol.18721/#post-284509

    It seems that eicosanoids are involved with astrocytes or microglia which also leads to glutamate. Also quinolic acid (QUIN) or inflammatory cytokines.
    http://www.tuberose.com/MicroglialActivationAndNeurodegeneration.html
  6. alex3619
    I am not sure why ginger causes a crash, but I have an idea - this is hypothetical though. Ginger suppresses excessive utilization of arachidonic acid, which blocks series 2 eicosanoid hormones, which is a good thing. However this means arachidonic acid levels rise ... and rise ... and rise. This then overwhelms the ginger and the benefits go away. However if you then stop taking the ginger, the increased arachidonic acid leads to increased eicosanoid synthesis. This magnifies symptoms, and induces a crash. Most supplements and herbs are tinkering with peripheral mechanisms of ME, they do not seem to be correcting the underlying cause ... and thats part of why they have problems. Until we really understand the cause its going to be hard to get treatment right, which is why we are all searching.
    Lotus97 likes this.
  7. Lotus97
    Why could ginger cause a crash? There were two periods where I was drinking ginger tea and lost some weight and each time I experienced a relapse afterwards. I thought maybe ginger played a part, but I wasn't sure why or if it was just a coincidence (since there were several other factors involved). It seems like for every good thing about a supplement I learn there's also a certain contraindication.
  8. alex3619
    Be very very careful with ginger. It may help at first, but I predict a big crash if you use it too much. Lots of things help a bit with eicosanoids, but most of those fail at some point.
  9. Lotus97
    Ginger and rosemary are supposed to help with eicosanoids. I don't know the details and it seems there are good and bad eicosanoids (?) New Chapter is selling an extract of ginger and rosemary:
    http://www.iherb.com/New-Chapter-Ginger-Force-60-Softgels/95
    (actually, it's mostly ginger)
  10. PNR2008
    I am happy you are here on PR. Just to tell you what happened to me today. I have a thinning membrane in my right eye that probably will detach in the future, the dr thought it was ready to blow 4yrs ago but here I am. My sister had two detached retinas and my brother one so I'm at risk. Anyway I'm concerned but know what to look for when it will happen so not obsessive about it. The thing is this, after two hrs of tests now at home I can barely walk and it was all brain stuff. One test my brain zoned out for a few seconds just to regroup. It's the tests that are killing me, eye tests, tilt table, MRI, spect and BEAM scans even spread out I'm losing it. DON"T TOUCH ME YOU CREEPS. Sorry had to vent a little, still glad for your input.