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Nicorandil.....A role in treating CFS

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
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

I would not attach any significance to a non-human study. They are on average equally likely to be relevant or irrelevant to humans.

I found these human studies on red wine and blood pressure from a Highwire search:

http://ajcn.nutrition.org/content/95/6/1323.full

http://hyper.ahajournals.org/content/45/5/874.full

http://eurheartj.oxfordjournals.org/content/28/14/1683 (a review which includes human and animal info, plus a good reference list with crosslinks)

http://circres.ahajournals.org/content/111/8/1065.full
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK

I would advise taking note of this from the paper:
Hypotension in Volume- or Salt-Depleted Patients

In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients (eg, those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with BENICAR. Treatment should start under close medical supervision. If hypotension does occur, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline.

Impaired Renal Function

In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen (BUN) have been reported. There has been no long-term use of olmesartan medoxomil in patients with unilateral or bilateral renal artery stenosis, but similar results may be expected.

The prescribing information for BENICAR HCT also includes the following warnings regarding its hydrochlorothiazide component:

BENICAR HCT is not recommended in patients with severe renal impairment and is contraindicated in patients with anuria or hypersensitivity to other sulfonamide derived drugs.

Hepatic Impairment

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Hypersensitivity Reaction

Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history.

Systemic Lupus Erythematosus

Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.

and this thread.
 

Hip

Senior Member
Messages
17,824

Very good to know, MeSci, especially this excerpt from your thread:
In brief, it says you should temporarily stop taking ACE inhibitors, Angiotensin receptor blockers, NSAIDS, diuretics or metformin if you have an incidental illness involving fever, sweating, tremor, vomiting and/or diarrhoea, as there is a danger of kidney damage from the drugs when you have such illnesses.


I just starting looking through my Benicar notes while writing this post today, on my experiments with Benicar and the Marshall Protocol.
 
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kangaSue

Senior Member
Messages
1,851
Location
Brisbane, Australia

Hip

Senior Member
Messages
17,824
@kangaSue
Have you looked at a prebiotic called resistant starch?

According to this study, RS is fermented by bacteria in the colon to create short-chain fatty acids (SCFA), mainly acetate, propionate, and butyrate. SCFAs then stimulate colonic blood flow.

There is a massive thread on resistant starch, rivaling War and Peace in its length. Quite a few ME/CFS patients seem to have benefited from RS.

Also on that thread, some very good good results were obtained with an unusual probiotic called Clostridium butyricum, which produces butyrate (I understand it converts lactate to butyrate in the gut). This new thread was started on Clostridium butyricum.
 

kangaSue

Senior Member
Messages
1,851
Location
Brisbane, Australia
@kangaSue
Have you looked at a prebiotic called resistant starch?

According to this study, RS is fermented by bacteria in the colon to create short-chain fatty acids (SCFA), mainly acetate, propionate, and butyrate. SCFAs then stimulate colonic blood flow.

There is a massive thread on resistant starch, rivaling War and Peace in its length. Quite a few ME/CFS patients seem to have benefited from RS.

Also on that thread, some very good good results were obtained with an unusual probiotic called Clostridium butyricum, which produces butyrate (I understand it converts lactate to butyrate in the gut). This new thread was started on Clostridium butyricum.

Thanks Hip.

I have followed the resistant starch thread and gave it a shot with cold rice pudding but it is just as much a challenge for me as regular fiber after a couple of days. Tried both long grain and short grain rice as there is a difference in fiber content, also tried it as re-fried rice kept below 35 deg C, to no avail. Potato is particularly indigestible for me so wasn't game to try potato starch.

I have tried a few different probiotics along the way, they have always produced a rapid disagreeable reaction but I will look into Clostridium butyricum
 

Hip

Senior Member
Messages
17,824
ThaI have tried a few different probiotics along the way, they have always produced a rapid disagreeable reaction but I will look into Clostridium butyricum

The butyrate produced by Clostridium butyricum I am assuming has a vasodilating effect in the bowels, as it is a SCFA. This probiotic is available as Miyarisan® on eBay and Amazon, which has a history of use in Japan. Clostridium butyricum is a spore forming bacterium, though, so it is considered a soil-based organism (SBO) probiotic.

I have just started taking Miyarisan myself, after reading the very good results some ME/CFS patients were getting from it on the resistant starch thread.

You can also buy butyrate as a supplement.
 
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Hip

Senior Member
Messages
17,824
Actually acetate, the acid in vinegar, which is also classified as a SCFA (see a list of SCFAs here), seems to have a vasodilating effect (see this study).

I sometimes take a tablespoon of vinegar with my meals, as my stomach acid levels I think are low.
 

kangaSue

Senior Member
Messages
1,851
Location
Brisbane, Australia
Actually acetate, the acid in vinegar, which is also classified as a SCFA (see a list of SCFAs here), seems to have a vasodilating effect (see this study).

I sometimes take a tablespoon of vinegar with my meals, as my stomach acid levels I think are low.

Not game to try plain vinegar, I have done this with both apple cider vinegar and red wine vinegar. Both resulted in the fastest rejection of anything I have tried before, just a teaspoon of either resulted in them being vomited back within two minutes.
 

Hip

Senior Member
Messages
17,824
Not game to try plain vinegar, I have done this with both apple cider vinegar and red wine vinegar. Both resulted in the fastest rejection of anything I have tried before, just a teaspoon of either resulted in them being vomited back within two minutes.

Wow, that's some strong reaction.
 

tdog333

Senior Member
Messages
171
Any updates? I have been clear of CFS for about a year now, my energy is great, however I have horrible gastroparesis and nausea, any time I eat anything, water included I get bad bad bad nausea and headaches, it gets worse the bigger the meal I eat. I've had all the work ups done and nothing major can be found, I've tried quite a few herbs, nothing really works. They only thing that gives me any relief is peppermint oil, I take a ton of peppermint oil which takes the edge off the nausea, but I have to dose it every 20 minutes or it wears off. I'm thinking about giving Nicorandil a try. My doctor said he thinks it might be worth a shot.

PS: I stick to a very strict diet, only meat really, and some fat, carbs really mess me up for some reason and give me bad colon pain.

Edit: Also has anyone who has taken this med experienced any side effects? I read that severe mouth ulcers and GI ulcers occur sometimes
 
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leokitten

Senior Member
Messages
1,542
Location
U.S.
@deleder2k if you haven't seen this thread thought you would be interested. I definitely am glad to have seen this!

Nicorandil is a dual mode of action vasodilator that stimulates sGC like the newer drug Adempas that Fluge/Mella have been using on patients with success, but nicorandil has been around a long time and is far cheaper.
 

deleder2k

Senior Member
Messages
1,129
Interesting. Wiki says:
There are multiple mechanisms causing the increased smooth muscle contraction involved in coronary vasospasm, including increased Rho-kinase activity. Increased levels of Rho-kinase inhibit myosin phosphatase activity, leading to increased calcium sensitivity and hypercontraction.[1] Rho-kinase also decreases nitric oxide synthase activity, which reduces nitric oxide concentrations.[2] Lower levels of nitric oxide are present in spastic coronary arteries.[3]L-type calcium channel expression increases in spastic vascular smooth muscle cells, which could result in excessive calcium influx, and hypercontraction.[4]

Do we want lower NOS activity?
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
Any updates? I have been clear of CFS for about a year now, my energy is great, however I have horrible gastroparesis and nausea, any time I eat anything, water included I get bad bad bad nausea and headaches, it gets worse the bigger the meal I eat. I've had all the work ups done and nothing major can be found, I've tried quite a few herbs, nothing really works. They only thing that gives me any relief is peppermint oil, I take a ton of peppermint oil which takes the edge off the nausea, but I have to dose it every 20 minutes or it wears off. I'm thinking about giving Nicorandil a try. My doctor said he thinks it might be worth a shot.

PS: I stick to a very strict diet, only meat really, and some fat, carbs really mess me up for some reason and give me bad colon pain.

Edit: Also has anyone who has taken this med experienced any side effects? I read that severe mouth ulcers and GI ulcers occur sometimes

I wonder whether the lack of carbs is causing or contributing to your gut problems. Do you know whether it is specific types of carb that cause you problems? Some of us are OK as long as we avoid gluten and reduce grains and sugar. Have you tried potatoes, veg, resistant starch? Without a good gut microbiome - which needs some carbs to feed it - all kinds of things go wrong, and yours must be starving (or dead or out of balance)!
 

leokitten

Senior Member
Messages
1,542
Location
U.S.
Interesting. Wiki says:

Do we want lower NOS activity?
I think you are misreading the Wikipedia text. Artery vasospasm, which causes angina, has been linked to higher rho-kinase activity which causes lower NOS activity and lower NO concentrations. That entire paragraph is discussing the physiology of the disease, not the drug nicorandil. Nicorandil counteracts these physiological changes.
 

deleder2k

Senior Member
Messages
1,129
Ah, okay. My bad. Thanks for clarifying. I wonder if testing the drug out has been a topic for Fluge and Mella.
 
Messages
15
Is it an approved drug in Norway? pilot trials could be more difficult if not?
 
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tdog333

Senior Member
Messages
171
I wonder whether the lack of carbs is causing or contributing to your gut problems. Do you know whether it is specific types of carb that cause you problems? Some of us are OK as long as we avoid gluten and reduce grains and sugar. Have you tried potatoes, veg, resistant starch? Without a good gut microbiome - which needs some carbs to feed it - all kinds of things go wrong, and yours must be starving (or dead or out of balance)!

I was eating carbs and having diarrhea every day, only white rice really, I've tried rotating all sorts of food and carbs and any time I add carbs in my gut gets painful and bloated, even gluten free grains seem to mess me up, although it's a slower process, I've had lots of stool tests and sibo/breath tests done and my beneficial bacteria is still very high somehow(probably from avocados). I tried resistant starch for a couple months, and saw small improvements, but it didn't do anything miraculous, potatoes give me really bad intestinal pain
 
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