Nicorandil.....A role in treating CFS

[Hip]

One intriguing method of increasing blood circulation is whole body periodic acceleration, which is just mechanical vibration applied to the body. This vibration apparently increases brain blood flow by 180%.

One company here sells a bed that will apply these vibrations to the body all night long: NINS Exer-Rest bed.

 

[kangaSue]

Now that's interesting being a phosphodiesterase inhibitor, the same class as cilostazol which has also been used successfully to treat bowel ischemia. This was my next option if taking nicorandil didn't work for me. It is already used for peripheral artery disease,particularly intermittent claudication.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3284045/

Just came across this piece of research http://jpet.aspetjournals.org/content/317/3/1238.abstract which shows that similarly to nicorandil, this drug cilostazol (Pletal) also has a k+ channel activator action. When the other modes of effect are taken into consideration, may be superior to using nicorandil.

 

[kangaSue]

I think the blood supply problems with many me/cfs are quite subtle, but body wide.

My next move will be to try the K channel activator. My digestive problems (also hiatus hernia and serious reflux) are not really disabling. I am confined to bed most of the time because of the brain hypoperfusion.

There's some more pertinent info here for you on cilostazol re hypoperfusion, mouse studies show it to reduce cerebral hypoperfusion; http://www.onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2009.00615.x/full For all intents and purposes, this looks as good as ibudilast that has been getting some positive press of late. You can only get cilostazol (Pletal) as a private script in Oz, not on the PBS. About $80 when I enquired 12 months ago.

 

[RustyJ]

There's some more pertinent info here for you on cilostazol re hypoperfusion, mouse studies show it to reduce cerebral hypoperfusion; http://www.onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2009.00615.x/full For all intents and purposes, this looks as good as ibudilast that has been getting some positive press of late. You can only get cilostazol (Pletal) as a private script in Oz, not on the PBS. About $80 when I enquired 12 months ago.

$80 for how much? How long will that last, can you recall? Maybe I can get it overseas cheaper. I've got a bit of time, as I have to finish course of antibiotics.

 

[kangaSue]

$80 for how much? How long will that last, can you recall? Maybe I can get it overseas cheaper. I've got a bit of time, as I have to finish course of antibiotics.

That was for a regular monthly prescription supply. Didn't look further into it but I assume that gets you the normal recommended dose of 100mg tablets, twice daily, so 60 tablets.

 

[kangaSue]

Just come across this bit of information. It refers to cardiac mitochondria specifically, which is this drugs target so don't know if this can be assumed of mitochondria influence elsewhere in the body.

http://www.scbt.com/datasheet-200995.nicorandil.html

"Nicorandil is also described to suppress mitochondrial permeability transition triggered by oxidative stress resulting from ischemia-reperfusion injury, preventing mitochondrial uptake/ overload and oxidative damage."

 

[dannybex]

Also, be aware that some supplements can thicken the blood, and so may reduce blood microcirculation:

Pro-coagulants Supplements ("blood thickeners"):
Coenzyme Q10
Ginseng
Green tea
Vitamin K

@Hip, I'm curious where you read that coQ10 is a 'blood thickener'? And any other info that might help clarify this?

Thanks in advance.

 

[Hip]

@Hip, I'm curious where you read that coQ10 is a 'blood thickener'? And any other info that might help clarify this?

I can't remember now, but a quick Google search reveals this:

Warfarin (Coumadin) is used to slow blood clotting while coenzyme Q-10 might increase blood clotting. By helping the blood clot, coenzyme Q-10 might decrease the effectiveness of warfarin (Coumadin) and increase the risk of dangerous clots.

Source: here.

 

[Jon_Tradicionali]

Nicorandil has just come up on my list of drugs to try.

@Hip
Did you manage to trial this drug?

@kangaSue
Are you still taking this drug?

 

[Hip]

@Hip
Did you manage to trial this drug?

Not yet, I sort of forgot about it.

But I am glad you brought up this question, because having recently discussed on this post and thread the unfortunate tolerance and loss-of-effect problems of the vasodilating drugs nitroglycerin and isosorbide dinitrate (which vasodilate by increasing nitric oxide, as nicorandil does), I just now tried to find out whether nicorandil might also lose its vasodilating effect after a while.


The good news is that it seems that nicorandil does not lose its effect: this study demonstrated that nicorandil does not produce tolerance, and does not lose its effect, whereas nitroglycerin and isosorbide dinitrate do.

@zzz actually obtained full remission from severe ME/CFS using isosorbide dinitrate, but this drug no longer works for him now, possibly due to this problem tolerance and loss-of-effect (this problem is called "nitrate tolerance").


If nicorandil maintains its ability to produce nitric oxide and vasodilation, this might make it a far superior drug for increasing nitric oxide and vasodilation.

 

[MeSci]

Have only just found this thread but it appears to be for people whose ME is associated with hypotension. Some of us - like me - have never had this, so I assume that the thread isn't relevant to us?

This poll shows about 25% of respondents having hypertension.

 

[kangaSue]

Nicorandil is often used as an anti-anginal in resistant hypertension but it works for both hypertension and hypotension. My G.P. was concerned to prescribe it for me initially because of my hypotension, his understanding was that it only lowered b.p., but I saw a study (which I can't find at the moment) that said it can raise the b.p. in hypotension but does not affect b.p. in healthy subjects with normotension.

I am still using this drug. I am not doing as well on nicorandil as when I first posted but I think that's more to do with a progression of my G.I.disorder and not a loss of effect as I tried cutting it out to try another vasodilator but I couldn't maintain the oral diet without it.

 

[Hip]

@kangaSue
I wonder if the supplement arachidonic acid (an omega 6 fatty acid) might also help increase bowel vasodilation. This study talks about arachidonic acid-induced vasodilation of small mesenteric arteries.

You can buy arachidonic acid here.



By the way, is the non-occlusive mesenteric ischemia that you have caused and underpinned by vasculitis? If so, since vasculitis is thought to be autoimmune driven, might some treatments for autoimmunity be helpful? Vasculitis is type III autoimmunity, according to this article: type III hypersensitivity (autoimmunity type and hypersensitivity type use the same classification system).

Systemic lupus erythematosus and rheumatoid arthritis are type III autoimmune conditions.

 

[MeSci]

@kangaSue
I wonder if the supplement arachidonic acid (an omega 6 fatty acid) might also help increase bowel vasodilation. This study talks about arachidonic acid-induced vasodilation of small mesenteric arteries.

You can buy arachidonic acid here.

Arachidonic acid is an area of interest for @alex3619 - he might have some views on supplementing it.

 

[kangaSue]

@kangaSue
I wonder if the supplement arachidonic acid (an omega 6 fatty acid) might also help increase bowel vasodilation. This study talks about arachidonic acid-induced vasodilation of small mesenteric arteries.

You can buy arachidonic acid here.



By the way, is the non-occlusive mesenteric ischemia that you have caused and underpinned by vasculitis? If so, since vasculitis is thought to be autoimmune driven, might some treatments for autoimmunity be helpful? Vasculitis is type III autoimmunity, according to this article: type III hypersensitivity (autoimmunity type and hypersensitivity type use the same classification system).

Systemic lupus erythematosus and rheumatoid arthritis are type III autoimmune conditions.

I looked at arachidonic acid a while back but couldn't fathom whether it would be pro or anti inflammatory for me. The other stumbling block is that a high percentage of us with gastroparesis (GP) are hypersensitive to fats and lipids taken orally, for that reason I don't cope with vitamins A,E,D or K either, even in the smallest amounts. Perhaps the answer to GP can be found in dysfunction of lipid signaling. This article http://www.nature.com/ajg/journal/v108/n5/full/ajg201376a.html also makes a connection to IBS.

The NOMI is still unexplained, vasculitis has been ruled out and nothing autoimmune has been found in the limited antibody testing that I've had done. The only thing I've found that comes close to explaining it is a small study on NOMI where all confirmed cases had significantly narrowed superior mesenteric artery and vein compared to controls (11 NOMI patients, 44 controls) http://europepmc.org/abstract/MED/24022230

This is not a measurement that is generally recorded as a matter of course in a CT Angiogram as far as I can tell, there is nothing indicated on my my scan reports so I'm in the dark as to what my artery diameters are. Anyway by-pass surgery would be the only fix for that but the complication rates are high and 3 year outcomes are not very encouraging so I haven't pursued it.

 

[Hip]

The only thing I've found that comes close to explaining it is a small study on NOMI where all confirmed cases had significantly narrowed superior mesenteric artery and vein compared to controls (11 NOMI patients, 44 controls) http://europepmc.org/abstract/MED/24022230

Might supplements or drugs that promote angiogenesis help I wonder? Angiogenesis is the formation of new blood vessels.

Fibroblast growth factors FGF-1 and FGF-2 promote angiogenesis (but I think more the smaller blood vessels). FGF-2 is available as a supplement called Laminine, which I have tried myself (unfortunately it is sold in under a mutli-level marketing system).

The growth factor VEGF is involved in angiogenesis too.


This Google search might help locate drugs, supplements and diets that increase angiogenesis.

Angelica, Astragalus, lactate and hydrogen peroxide appear to promote angiogenesis.

N-acetyl-cysteine and EGCG (from green tea) inhibit angiogenesis.

 

[alex3619]

Arachidonic acid is an area of interest for @alex3619 - he might have some views on supplementing it.

Arachidonic acid can help. It can also severely harm us. Take too much and you will collapse in pain. Take a bit more and you will die. Its very very dangerous, especially free arachidonic acid.

The use of arachidonic acid to treat CFS goes back to about 1988. It is, however, arachidonic acid restriction that is more useful than supplementation. See the research by Martinovic, though sadly a lot of that is hard to find (there is only one paper on PubMed).

Arachidonic acid can increase oxidative stress. Its an inflammatory molecule (though a few of the products are not inflammatory, the majority are) because it results in synthesis of series 2 eicosanoids. Ideally many of us could do with more in our cells, but we have trouble making it. The big issue though is this: it is very likely we overuse it. Even a low dose supplementation might result in bad effects, especially over time. Any inflammatory state, or an increase in NO or ONOO can increase its utilization.

One of the ways alcohol can damage us is it induces an increase in release of arachidonic acid. In my opinion this is how alcohol actually kills people, because if you block arachidonic acid metabolism there is a much better chance of surviving alcohol poisoning.

I have not investigated this topic in years though. I do not know what current science is saying.

 

[alex3619]

Just a comment on arachidonic acid defiiciency, this can also be dangerous. It can result in death or severe symptoms. Its one of those Goldilocks substances that has a narrow range for optimum health.

 

[kangaSue]

Might supplements or drugs that promote angiogenesis help I wonder? Angiogenesis is the formation of new blood vessels.

Fibroblast growth factors FGF-1 and FGF-2 promote angiogenesis (but I think more the smaller blood vessels). FGF-2 is available as a supplement called Laminine, which I have tried myself (unfortunately it is sold in under a mutli-level marketing system).

The growth factor VEGF is involved in angiogenesis too.


This Google search might help locate drugs, supplements and diets that increase angiogenesis.

Angelica, Astragalus, lactate and hydrogen peroxide appear to promote angiogenesis.

N-acetyl-cysteine and EGCG (from green tea) inhibit angiogenesis.

Nicorandil is demonstrated to promote angiogenesis through up-regulation of both VEGF and basic FGF.
http://hyper.ahajournals.org/content/46/4/647.full.pdf

It is said that ischemic preconditioning (inflating and deflating a blood pressure cuff for repeated short period, 5 minutes on, 5 minutes off for 3 repetitions) enhances the effect so I should give that a try when I can get hold of a manual b.p. machine.

 

[kangaSue]

Arachidonic acid can help. It can also severely harm us. Take too much and you will collapse in pain. Take a bit more and you will die. Its very very dangerous, especially free arachidonic acid.

The use of arachidonic acid to treat CFS goes back to about 1988. It is, however, arachidonic acid restriction that is more useful than supplementation. See the research by Martinovic, though sadly a lot of that is hard to find (there is only one paper on PubMed).

Arachidonic acid can increase oxidative stress. Its an inflammatory molecule (though a few of the products are not inflammatory, the majority are) because it results in synthesis of series 2 eicosanoids. Ideally many of us could do with more in our cells, but we have trouble making it. The big issue though is this: it is very likely we overuse it. Even a low dose supplementation might result in bad effects, especially over time. Any inflammatory state, or an increase in NO or ONOO can increase its utilization.

One of the ways alcohol can damage us is it induces an increase in release of arachidonic acid. In my opinion this is how alcohol actually kills people, because if you block arachidonic acid metabolism there is a much better chance of surviving alcohol poisoning.

I have not investigated this topic in years though. I do not know what current science is saying.

I think in my case (for intestinal ischemia) I need to be inhibiting arachidonic acid metabolism. When all else fails to ease my gut pain, I find red wine, about half a small glass, quickly quells the discomfort which I believe is being caused by an inflammatory source. Unlike other alcohol sources, polyphenols in red wine are known to strongly inhibit arachidonic acid metabolism. http://ncbi.nlm.nih.gov/pubmed/16487260