Acetyl L- Glutathione, ATP, Baking Soda, Sam-e & Catalase = No PEM after exercise

[Hip]

Have you ever tried a nitroglycerin tablet just to see what happens? I got hold of one years ago, it was quite an experience but now I wonder if my experience was typical.

What was your experience with nitroglycerin? @zzz went into full ME/CFS remission for nearly 8 years after just one 10 mg dose of isosorbide dinitrate, which is very similar in action to nitroglycerin.

 

[Sherlock]

What was your experience with nitroglycerin? @zzz went into full ME/CFS remission for nearly 8 years after just one 10 mg dose of isosorbide dinitrate, which is very similar in action to nitroglycerin.

From the nitro: I had very profound temporary BP reduction from vasodilation, but zero lasting effects after 15 minutes, and no effects that I recall related to typical CFS symptoms.

If you're looking for increased blood flow, I'll mention that I also sometimes had very profound temporary BP reduction from vasodilation with niacin - probably with more than usual dietary arachidonic acid which amplifies the effect of the niacin.

Btw, I was under the casual impression that most PWCFS (but not me) had excess NO (as an antimicrobial) and therefore also suffered a lot of oxidative damage from excess peroxynitrite.

 

[Hip]

If you're looking for increased blood flow, I'll mention that I also sometimes had very profound temporary BP reduction from vasodilation with niacin - probably with more than usual dietary arachidonic acid which amplifies the effect of the niacin.

Yeah at one stage I'd take 200 mg of niacin every day to induce a full niacin flush, which I found helped a little bit with the anxiety symptoms I had.

Btw, I was under the casual impression that most PWCFS (but not me) had excess NO (as an antimicrobial) and therefore also suffered a lot of oxidative damage from excess peroxynitrite.

Dave Whitlock says ME/CFS has low NO, whereas Prof Martin Pall says the opposite, that ME/CFS has high NO (and high peroxynitrite).

I have an idea that they both might be right:

To fight an infection, the immune system may generate a hell of a lot of NO via the iNOS enzyme, which is secreted by the immune system. For antimicrobial purposes, iNOS pumps out NO at levels 1000 times higher than the NO generated by the other two NO enzymes, eNOS and nNOS.

So my idea is that when iNOS is at a high level on a long term basis (as a result of fighting the chronic infections found in ME/CFS), after some time the body might up-regulate the processes that break down iNOS, to ensure blood levels if iNOS-generated NO don't get too high. These processes that break down iNOS may then start breaking down eNOS (which makes NO for vasodilation) and nNOS (which makes NO for neurotransmission) as well. So what may happen is that high levels of iNOS may inadvertently cause a reduced levels of eNOS and nNOS.

Either that, or the chronic high levels of NO generated by iNOS may cause epigenetic changes that down-regulate the gene expression of eNOS and nNOS, so that you don't get sufficient NO made for vasodilation or neurotransmission.

So in summary, my idea is that the chronically high levels of iNOS might conceivably have a paradoxical effect of lowering eNOS and nNOS.


Anyway, this is how I speculate ME/CFS may involve both high NO in the areas of infection, and low NO everywhere else. Just an idea.


Note that asymmetric dimethylarginine (ADMA) and N(G)-monomethyl-l-arginine (l-NMMA) are the body's inhibitors of the NOS enzymes. ADMA levels are increased in patients with fibromyalgia. 1

 

[MeSci]

One of the things I have learned through much dietary experiment is that not all saturated fatty acids are the same. "Saturated Fat" can be any combination of four fatty acids: Lauric, Myristic, Palmitic, and Stearic. Coconut oil is mostly Lauric. Chocolate is mostly Stearic. Dairy fats are mostly Palmitic. I don't know if I was having a reaction to dairy proteins that somehow made me process the fats differently, or if it was the Palmitic acid. Whatever it was, the dairy fat sent my lipids into orbit, and removing dairy has resulted in their slowly coming down.

By chocolate, do you mean cocoa butter? The fat content of chocolate confectionery is commonly largely from milk (unless you have rich dark chocolate of course).

 

[MeSci]

Maybe this site will be of interest to some. It gives a lot of info about physiological pH balance and pH tests. There are some links to other pages at the top.

 

[Sherlock]

after some time the body might up-regulate the processes that break down NO

I remember from (Nobel Laureate co-discoverer) Ignarro's book that NO has a very short half life. Maybe <1 sec?

That said, I might very well fit in generally with your idea about reduced eNOS:

I started unusually with sudden onset hypertension and orthostatic hypotension. I'd always had a good NO response from exercise, so I thought I could get my BP back to normal that way but it just would not work anymore for about a year. I was terrified that my arteries didn't dilate anymore, so that's why I took the GTN. I was mostly diastolic, but labile, and sometimes up to 165/115 which was scary.

Arginine did nothing for me. [Neither did Mg.] I didn't try citrulline. Eventually, exercise shear forces eventually worked again and I was usually back to 120/80 - except when I was sick and inflamed with burning eyes etc then my BP would be up.

So that's my datapoint. Any observations?

(Except now I'm in a freakish new phase where I think that it's chymase which gives me intractable 140/90 all the time.)

Dave Whitlock says ME/CFS has low NO, whereas Prof Martin Pall says the opposite, that ME/CFS has high NO (and high peroxynitrite).

Thanks for elucidating. That did make me chuckle , too It's the kind of thing that makes me say that experts should by all means be listened to, but never blindly believed. Then again, I think it's downright difficult to measure NO directly so maybe they can't be blamed on this one point.

Oh, btw, if histamine depletion via niacin reduces anxiety for some (it doesn't for me) then maybe a mast cell stabilizer would do the same (tart cherry does so very remarkably and very unexpectedly for me). I can't get over it.

 

[Sherlock]

The fat content of chocolate confectionery is commonly largely from milk (unless you have rich dark chocolate of course).

and the milk proteins bind to the healthful plant compounds that make chocolate good for you. Also, Dutching (lye processing?) destroys the good molecules, too.

Stearic would be naturally in the cocoa, IIRC.

Speaking of palmitic, that's usually said to be the most atherogenic - yet that's the one that results from de novo lipogenesis.

 

[Gondwanaland]

tart cherry

Interestingly it is frequently recommended to gout sufferers (I think this has already been said here )

 

[Gondwanaland]

If the first statement were true about excess NADH being the problem, then how come a ketogenic diet made you (and many others with ME/CFS) dramatically sicker? By removing glucose and eating a high fat diet you sharply decreased NADH input to complex I and instead relied on FADH2 and complex II to get your energy which sounds like it went down to about zero using this approach.

When you have time, could you please expand a little on that?

 

[Sherlock]

Interestingly [tart cherry] is frequently recommended to gout sufferers (I think this has already been said here )

Yes, you've been making me wonder if I have hyperuricemia - also a possible cause of polyuria for me. I have an Fx of hyperuricemia and uric acid stones, but then I don't ever overeat and don't have organ meats etc. (except when I tried raw chicken livers for fun ) My big toes never hurt. Zero alcohol for many months.

Also, the benefit of tart cherry on my joints has plateaued. But it still powerfully prevents flushing so apparently it's still stabilizing Mast Cells.

 

[Gondwanaland]

@Sherlock I don't have gout (my father had it once) but my serum uric acid levels over the past 3-4 years ranged from 5.4 to 6.7 (2.4 - 5.7 mg/dL) dropping to 5 right after my alkalizing protocol and rising again to 5.8 one month later.

 

[Sidereal]

When you have time, could you please expand a little on that?

If you want to understand this stuff I would recommend reading Peter over at Hyperlipid blog. This summary post is probably the most accessible: http://high-fat-nutrition.blogspot.com/2013/08/protons-so-far-some-sort-of-summary.html but the whole Protons series of blogposts he's written is worth the time investment.

 

[pemone]

If the first statement were true about excess NADH being the problem, then how come a ketogenic diet made you (and many others with ME/CFS) dramatically sicker? By removing glucose and eating a high fat diet you sharply decreased NADH input to complex I and instead relied on FADH2 and complex II to get your energy which sounds like it went down to about zero using this approach.

My working hypothesis (based on blood, hair, urine and symptoms) is that I have a mercury toxicity, made significantly worse by my taking high doses of alpha lipoic acid starting in Nov 2013. ALA ends up being a very good heavy metal chelator that goes intracellular and across the blood brain barrier. It converts to a dihydroxy form that is a two thiol chelator. So I may have moved mercury, which was very high in blood, into the intracellular environment and into my brain, where it then impaired my electron transport chain and brought on the sudden fatigue and neurological symptoms.

Complex II of the electron transport chain contains a iron-sulfur complex. Mercury has high affinity for those metal binding sites. For example, mercury will bind to a single thiol enzyme or protein was one MILLION times greater affinity than a metal like zinc. So one possibility is that my Complex II was highly impaired and I simply was not able to utilize fats very efficiently. Many complexes in ETC contain the Iron-sulfur complexes. ATP Synthase contains other metals. They are all targets for mercury.

Can you show me a good diagram that illustrates the pathway you are referring to? Because all of the fatty acid metabolism charts I found did not show feeding to Complex II. What I am wondering is if aerobic metabolism is impaired, does the body resort to using fat in a different pathway that is far less efficient? Please see this diagram:
http://www.bmb.leeds.ac.uk/illingworth/bioc1110/pathways.gif

In that diagram, both fats and glucose produce Acetyl-CoA, which then becomes the input to the Krebs cycle.

The thing is, eating larger amounts of glucose did not fix what was broken. What it did do is send my blood glucose over 160 one hour after eating the glucose. And I still felt broken in terms of energy. And I still went into glycolysis and got horrific PEM symptoms after exercise. So I think the change of diet was simply coincidental to the ingestion of the high dose ALA, and I have problems blaming the result on a high fat diet.

 

[pemone]

A plaque is covered with a fibrous matrix cap. What's accepted is that most AMI occurs when inflammatory Matrix MettaloProteinases break down the cap enough so that it either ruptures or erodes. That exposes material to circulation that sets off the coagulation cascade, just like forming a scab on a skin cut. If this clot (thrombosis) blocks offf the entire artery flow, then that's an infarction. (Though most cell death actually occurs during reperfusion, when blood flow is eventually restored and large amounts of damage occur from free radicals. So taking antioxidants when in danger of thrombosis is probably a good idea. They actually tie off rat brain arteries, then after a few minutes untie and measure resulting damage in the antioxidant versus control groups. )

Keeping the clot from getting big enough to completely block off an artery is a good idea That's why aspirin, clopidigrel and other antiplatelet drugs work to prevent death. A small clot that blocks off only partially would be an episode of unstable angina.

What do you think of the use of fibrin dissolvers like nattokinase? My sedimentation rate showed very low inflammation but also suggested I have very thick blood. I have been using fibrin thinners hoping that this would increase oxygen flow to deep tissues.

Burt a piece of an atheroma breaking off and blocking a smaller diameter section downstream is probably also unstable angina, and a harbinger of worse to come.

Stable angina, OTOH, occurs during exercise when a heart artery is severely but partially blocked and can't allow enough blood to pass during need for increased blood flow to heart muscle. Eventually, the blockage can become 100% and cause an AMI / heart attack, but those are only ~15% of total heart attacks. Also since they take a lot of time to develop, there was also time to develop corollary arteries to supply blood flow around the blockage.

During another lower-body ultrasound procedure a few years ago the tech made a comment to me that "you have the cleanest arteries I have ever seen." I have a feeling that my low inflammation markers, together with those kinds of ultrasounds, suggest I do not have an immediate risk of LDL blockage. I'll get the carotid ultrasound done and if that is clean I think I have bigger problems to worry about in the short term.

P.S. If you were the one that got Steve Fowkes here, then bravo and thanks go to you.

You are welcome. Steve is definitely a gift to the world, and I would probably be lost in my understanding of things without him.

P.P.S. You sound as if you might be an atypical responder to diet. So yes, your experimentation is the best way to go, IMO. One example: the Pritikin group has study wherein some hi-carb lo-fatters don't get smaller LDL - so they are opposite of typical.

Fructose is the main source for the really nastiest VLDL. I get maybe a fistful of berries each day, definitely no commercial high fructose corn syrup in anything I eat.

Also IMO Paleo had a lot of cool hype and a lot of false preaching, but only some truths underneath.

I've decided that each of us has somewhat unique responses to diet. It's better to just use a glucometer, a ketone meter, and your general sense of well being and energy as guides to how your body works. I like many of the ideas in Paleo, but the main problem with this diet is that it does not define what it is very well. So on a Paleo forum you see a lot of people eating whatever they feel like eating and calling it Paleo. It becomes a popular religion more than a diet.

In general, I find diets to be a very shallow concept. What matters is what happens to your body's biochemical markers over time as you stay on that diet. The proof is in the pudding.

 

[Sherlock]

The thing is, eating larger amounts of glucose did not fix what was broken. What it did do is send my blood glucose over 160 one hour after eating the glucose. And I still felt broken in terms of energy. And I still went into glycolysis and got horrific PEM symptoms after exercise. So I think the change of diet was simply coincidental to the ingestion of the high dose ALA, and I have problems blaming the result on a high fat diet.

Do you mean that you regularly eat Very Low Carb, then experience high BG after eating carbs?

If so, that's a surprise that VLCers discovered a few years ago - they call it physiological insulin resistance.
https://duckduckgo.com/html/?q=physiological insulin resistance

For energy, I'd try sucrose instead of glucose. That's what VLC athletes do -- e.g., Crossditters or VLC UltraMarathoners like Tim Olson on competition day.

 

[pemone]

Yes, which is how I went to pH school so to speak It was really impressive to me how I could turn the strip to blue by taking enough bicarb. When alkaline, there also was no burning sensation - which was really a very valuable learning experience. So now I go by the presence or lack or burning.

I do exactly the same. I treat to the presence of the symptom, and I also treat to an acidic urine pH (which probably means I over-alkalize at times). I can get PEM in my brain simply by thinking hard for three hours. Exercise is not required. I guess that makes sense since the brain uses more glucose than anything else in the body and if you are stuck in glycolysis I guess those brain tissues could get acidic as well?

 

[pemone]

Have you ever tried a nitroglycerin tablet just to see what happens? I got hold of one years ago, it was quite an experience but now I wonder if my experience was typical.

I probably want to stay away from that stuff. It apparently does not give the same kind of nitrate / nitrite response that you get from food, and I think dependency on that would be dangerous. The body will eventually respond to nitroglycerin and compensate for it, requiring higher doses. The body will not compensate for food high in nitrates.

 

[pemone]

By chocolate, do you mean cocoa butter? The fat content of chocolate confectionery is commonly largely from milk (unless you have rich dark chocolate of course).

I was referring to 100% cacao, no sugar added.

 

[pemone]

I remember from (Nobel Laureate co-discoverer) Ignarro's book that NO has a very short half life. Maybe <1 sec?

That said, I might very well fit in generally with your idea about reduced eNOS:

I started unusually with sudden onset hypertension and orthostatic hypotension. I'd always had a good NO response from exercise, so I thought I could get my BP back to normal that way but it just would not work anymore for about a year. I was terrified that my arteries didn't dilate anymore, so that's why I took the GTN. I was mostly diastolic, but labile, and sometimes up to 165/115 which was scary.

Arginine did nothing for me. [Neither did Mg.] I didn't try citrulline. Eventually, exercise shear forces eventually worked again and I was usually back to 120/80 - except when I was sick and inflamed with burning eyes etc then my BP would be up.

Arginine did nothing for me, even at doses over 20 grams a day. Citrulline did nothing for me, even at similar doses. Neo40 - a beet based supplement - only moved me into very low levels of nitrites (on my test strips). The solution was to eat large quantities of nitrate rich foods. Here are some high nitrate foods:
http://www.berkeleytest.com/plant-based.html

I had a Youtube video posted here somewhere and now I cannot locate it. That showed the top 10 nitrate foods.

I find that - so far - celery and butter lettuce both reliably raise my nitrite levels. Celery unfortunately contains a lot of nonsoluble fiber and causes me digestion problems. I'm still trying to get it sorted out but you might want to experiment with those foods.

 

[pemone]

Do you mean that you regularly eat Very Low Carb, then experience high BG after eating carbs?

If so, that's a surprise that VLCers discovered a few years ago - they call it physiological insulin resistance.
https://duckduckgo.com/html/?q=physiological insulin resistance

No, and I am aware of that issue. I mean that after converting to a higher carb diet and staying on that diet for more than a month, that a single starchy meal with >50 grams of starchy carbs would send my blood glucose very high.

Going back to the mercury hypothesis, mercury binds to both the insulin receptor and to insulin itself. I might just have impaired glucose metabolism, and this might entirely resolve once I get my mercury levels in tissue and blood lower.