Nitric Oxide, Peroxynitrite, and the Impairment of Mitochondrial Replication in CFS

[Crux]

Any one else have problems with raw greens / too much nitric oxide?

Yes, along with cocoa.

Here's some info about dietary nitrates, formation of NO,ammonia, etc. in the gut.
http://www.hindawi.com/journals/bmri/2009/284718/

This article is about excess NO formed in a dysbiotic gut :
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049941/

NO has been described as a 'janus molecule', I would agree. It's necessary for health, but if too much is produced from inflammation/infection, it can be neurotoxic.
http://annalsofneurosciences.org/journal/index.php/annal/article/viewArticle/173/427

 

[Adlyfrost]

Thank you for your reply @Freddd . I'm on 100 mcg's of methyfolate and any more and the above symptoms you listed do tend to appear. I had tried to shoot for 800mcg's + in the past but my muscles felt like rubber bands being twisted so tight they would break, including my heart. It was the scariest feeling in the world. I tried potassium and I felt my blood pressure drop, felt faint and broke out into cold sweats and the muscle tension still persisted- the second scariest feeling in the world. So I tried coconut water- started spending $20 a day to drink four liter cartons. That worked better for my muscles but the sugar brought back candida and I gained a ton of weight not to mention was in the poor house. Potassium bicarbonate sports drinks worked ok but muscle cramping developed and I found myself too mentally hyper and aggressive to function around people: I am studying to be a speech therapist and I couldn't control my impulses and provide the calm vibe needed for my clients- and I found myself with such nervous exhaustion that I had no time except to titrate doses of potassium throughout the day and experimentally titrate up the folate and minerals and lecithin and all the other baseline nutrients, etc. and even then I had horrible side effects. And it seemed there was no end in sight- no leveling off. And then stomach pain developed and I tried this for 2 months before seeking help with a naturopath who put me on methyl/hydroxy combo with folinic/methyfolate with a little SAME along with addressing other SNP's including glutathione which I desperately needed and at least now I have my sanity and I am not experiencing serious illnesses like viruses.

I will check out Carmen Wheatley. That sounds interesting.

The longterm side effects you describe above were starting to set in a few years ago: I was losing feeling in my legs and they were so weak I could hardly walk up stairs. I know that some day I will likely have to go methylfolate/methylcobalamin without the hydroxy, cold turkey. I have a family history of MS so I was scared, still am. After grad school though, when perhaps I can take some time off to experiment. But maybe not dibencozide - it makes me feel crazy- it likes to work while I am sleeping and give me panic attacks, tight muscles, etc. and then I get no sleep. I hate that stuff.

Until then I want to treat the NO / peroxynitrite problems a la carte. I am also looking to try other NO scavengers such as curcumin. I know it is not the best or most efficient method but at least I am keeping it together while I finish grad school. I am just relieved there is something I can take and still do my almost raw vegan diet that seems to be as important to my health as the supplements.

I know the "dead-lock quartet" has helped so many people and I have been following your posts for the past few years. I just, quite frankly, don't have the balls to do it right now. I am hoping to fix my deranged mineral transport in the mean time so that when I do try it again it goes more smoothly. Someday I will definitely give it another shot.

 

[Adlyfrost]

@Adlyfrost Apart from what Fred says about the difficulty some have with converting folinic acid (greens) to folate there's the difficulty some of us have with oxalates.

Beets and carrot juice are high in oxalates and spinach is extremely high. If your body can't get rid of oxalates, levels will build up if you're eating high oxalates foods and can cause joint pain - even gout - and cognitive problems. Maybe that's part of your situation?

Edit: just saw your other thread where you mention oxalates. Have you thought of trying a lower oxalate diet to see if you feel better?

Yes I eliminated all high oxalate foods- esp chard, beets and spinach which are like poison to me and it helped greatly! But didn't fix the problem. I am looking for a product called oxalobacter for the gut - a probiotic missing in people who have trouble with oxalates.

 

[Adlyfrost]

Yes, along with cocoa.

Here's some info about dietary nitrates, formation of NO,ammonia, etc. in the gut.
http://www.hindawi.com/journals/bmri/2009/284718/

This article is about excess NO formed in a dysbiotic gut :
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049941/

NO has been described as a 'janus molecule', I would agree. It's necessary for health, but if too much is produced from inflammation/infection, it can be neurotoxic.
http://annalsofneurosciences.org/journal/index.php/annal/article/viewArticle/173/427

Thanks @Crux. I do not get this problem myself from cooked processed cocoa. Raw cacao made me feel like this though. Perhaps the break down of high nitrate foods in the gut makes all the difference then. Interesting.

Also I got the same side effects from taking citrulline and citrulline maleate. But that is the urea cycle- not sure why cuz citruline is product of arginine / NO synthase but maybe it was a feedback loop-type reaction.

 

[Freddd]

Thank you for your reply @Freddd . I'm on 100 mcg's of methyfolate and any more and the above symptoms you listed do tend to appear. I had tried to shoot for 800mcg's + in the past but my muscles felt like rubber bands being twisted so tight they would break, including my heart. It was the scariest feeling in the world. I tried potassium and I felt my blood pressure drop, felt faint and broke out into cold sweats and the muscle tension still persisted- the second scariest feeling in the world. So I tried coconut water- started spending $20 a day to drink four liter cartons. That worked better for my muscles but the sugar brought back candida and I gained a ton of weight not to mention was in the poor house. Potassium bicarbonate sports drinks worked ok but muscle cramping developed and I found myself too mentally hyper and aggressive to function around people: I am studying to be a speech therapist and I couldn't control my impulses and provide the calm vibe needed for my clients- and I found myself with such nervous exhaustion that I had no time except to titrate doses of potassium throughout the day and experimentally titrate up the folate and minerals and lecithin and all the other baseline nutrients, etc. and even then I had horrible side effects. And it seemed there was no end in sight- no leveling off. And then stomach pain developed and I tried this for 2 months before seeking help with a naturopath who put me on methyl/hydroxy combo with folinic/methyfolate with a little SAME along with addressing other SNP's including glutathione which I desperately needed and at least now I have my sanity and I am not experiencing serious illnesses like viruses.

I will check out Carmen Wheatley. That sounds interesting.

The longterm side effects you describe above were starting to set in a few years ago: I was losing feeling in my legs and they were so weak I could hardly walk up stairs. I know that some day I will likely have to go methylfolate/methylcobalamin without the hydroxy, cold turkey. I have a family history of MS so I was scared, still am. After grad school though, when perhaps I can take some time off to experiment. But maybe not dibencozide - it makes me feel crazy- it likes to work while I am sleeping and give me panic attacks, tight muscles, etc. and then I get no sleep. I hate that stuff.

Until then I want to treat the NO / peroxynitrite problems a la carte. I am also looking to try other NO scavengers such as curcumin. I know it is not the best or most efficient method but at least I am keeping it together while I finish grad school. I am just relieved there is something I can take and still do my almost raw vegan diet that seems to be as important to my health as the supplements.

I know the "dead-lock quartet" has helped so many people and I have been following your posts for the past few years. I just, quite frankly, don't have the balls to do it right now. I am hoping to fix my deranged mineral transport in the mean time so that when I do try it again it goes more smoothly. Someday I will definitely give it another shot.

@Adlyfrost,

I found the muscle weakness came with the copper deficiency which also included gums that were dark cyanotic red and inflammed and not a healthy pink as well as spider veins and varicose veins. Also, dry and brittle hair and nails. Good luck.

 

[Crux]

Thanks @Crux. I do not get this problem myself from cooked processed cocoa. Raw cacao made me feel like this though. Perhaps the break down of high nitrate foods in the gut makes all the difference then. Interesting.

This goes against all the wonderful things about chocolate and flavanols in general.
Flavanols tend to release NO by stimulating niric oxide synthase. (NOS)

This is good for most people, healthy people.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678700/

 

[alicec]

I am looking for a product called oxalobacter for the gut - a probiotic missing in people who have trouble with oxalates.

There have been several posts about such a probiotic, see here and here. I am just waiting for results of a uBiome analysis (to see if the O. formigenes has colonised) before I report back on my experiences taking the probiotic.

 

[Adlyfrost]

@alicec That is so cool! Can't wait to hear your report!

Speaking of gut microbes, I noticed my problems with greens making me feel badly were not as bad when I had candida. They really started acting up when I eliminated fruit / all sugar and took Candex religiously. Could a little bit of Candida be actually good for me???

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC420131/

I NEVER thought I would want that again. But "good" yeast like saccromyces boulardii also do the same. Apparently peroxynitrite is candicidal and yeasts can defend themselves against it. So it's I guess even free radicals, or shall I say oxidants, are not all bad.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC174197/

Perhaps that is why people with prolonged stress to the immune system have problems with this oxidant. Below is about the most exhaustive explanation of theories about peroxynitrite and oxidant/anti-oxidant balance and their roles in immunity and metabolism I have ever seen online.

http://www.medicalinsider.com/cardiac3.html#sod

 

[Adlyfrost]

Two words: VGCC & EMF's.

This is scary for me because I got REALLY sick after moving from Florida to the northeast, to this awful neighborhood with HUGE power lines! After moving here, next to POWERLINES, I just didn't feel like ever moving or exercising- was just so tired- like nervous exhaustion. Then viral symptoms came and I became rapidly worse until I got some help in Fall 2014 and it has been a huge fight to get better. Until now, I always thought problems were due to the extreme cold here. But this would explain why I don't feel better in the summer either!

Before moving next to powerlines in the NE, my CFS in FL was somewhat manageable and rather stagnant from the time I was 28-39 yrs old. I always suspected the move here next to powerlines may have contributed to my rapid decline here but I have always had a huge phobia of power lines too, so I was hoping I was blowing my fears out proportion. They radiate only between 1 and 2 miliguass in the home. I figured the colder weather seemed like a more reasonable culprit.

Then I discover increasing NO a big part of why I feel awful after eating greens (since taking nitric oxide scavengers do make me feel so mo much better) and also the calcium in the cell connection to excess NO production (coupled with my genetics with variants that hamper ability to make SOD, glutathione, etc leading to peroynitritee and super oxide- leading to inflammation, sickness, etc). ALL this now seems to confirm my worst fears about EMF's. I am stuck where I live now for at least a year and a half.

Here is Martin Pall's explanation of how microwaves and LF EMF's cause excess calcium in cells leading to disease states caused by too much NO (to simplify it):

 

[alicec]

Can't wait to hear your report!

You will find it here.

 

[GreyOwl]

I have a question about oxalates relating to metabolism please: assuming a toxic injury to the liver, what would the presumed effect on metabolism have to be to produce a moderate number of Oxalate crystals in urine (and assuming that the presence of these in the urine is not a normal event, such as in the urine of a young child). We find Oxalate crystals in my daughter's urine during relapses (not sure why my iPad auto-capitalises Oxalate...). Thanks.

ETA: I found this thread, thanks http://forums.phoenixrising.me/index.php?threads/high-oxalates-b12-deficiency.36187/

 

[alicec]

assuming a toxic injury to the liver, what would the presumed effect on metabolism have to be to produce a moderate number of Oxalate crystals in urine

Oxalate is not processed via phase I and II pathways in liver. It is simply expelled from the cell and disposed of via faeces, urine, skin or lungs.

There is another oxalate thread you may find of interest here

 

[Biarritz13]

@ahmo
Martin Pall's theory and Dave Whitlock's theory (which is detailed in this thread) take opposing views: Whitlock proposes that ME/CFS is caused by a low basal level of NO, whereas Pall thinks there is too much NO (and peroxynitrite) in ME/CFS patients.

The ability of humming to raise NO only applies to the sinuses and nasal cavities, unfortunately. Still, it might be worth trying humming if you have chronic nasal congestion or sinusitis, as NO is a potent anti-microbial, and so should fight nasal and sinus infections.

Does it imply that if Citrulline Malate works well that Whitlock may be right? Or is that too simple?
Because I have seen a lot reporting great improvements on it, even if it doesn't last that much.

 

[ahmo]

@Theodore I don't know.my strategy has been to just decrease peroxynitrite, using antioxidants.

 

[Biarritz13]

@Theodore I don't know.my strategy has been to just decrease peroxynitrite, using antioxidants.

Interesting. Peroxynitrite is the ugly one, I wonder what would be the result if you add on top of your antioxidants, a supplement that will increase your NO.


"In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future."

 

[ahmo]

I haven't pursued that path. Seems like it's time for me to check it out. thx.

 

[Biarritz13]

A study suggests that when taking Pycnogenol, more NO is provided in response to neurotransmitters allowing for better expansion of arteries to carry more blood. This process serves to meet the enhanced oxygen demand of the performing muscle and avoid anaerobicmetabolism. This was reported by Dr. Yukihito Higashi. "These results also lead me to determine that Pycnogenol will be a useful natural alternative therapy in various diseases in which oxidative stress is involved in the pathogenesis."

After two weeks of supplementation with Pycnogenol, results revealed blood flow increased in response to acetylcholinestimulation by 42 percent. In contrast, the control group receiving the placebo did not show a pronounced blood flow increase in response to neurotransmitter stimulation.

"Acetylcholine stimulates the cells of arteries to produce NO from L-arginine faster," Dr. Higashi said. "In turn, the NO causes the muscle surrounding arteries to relax, which results in an increase of blood vessel diameters. When subjects had taken Pycnogenol the relaxation of arteries was increased by 42 percent as compared to the group taking placebotablets."

@ahmo. I would like to offer you a cocktail, Pycnogenol, Citrulline Malate + antioxydants

 

[ahmo]

Interesting possibility. I used pycnogenol for some time, then didn't feel it doing anything. I've been using MitoQ, but more than 5mg every other day created more need for antioxidants. I used citrulline until I no longer needed it or extra malic acid, following detox and adding FMN of B2.

Edit: wrong; I switched from pycnogenol to resveratrol and/or astaxanthine. Which my body later rejected in preference to acai. Lot's of antioxidants happening here, including food-based. Which seems to be a good approach, a cascade of different AO substances.

 

[Biarritz13]

Interesting possibility. I used pycnogenol for some time, then didn't feel it doing anything. I've been using MitoQ, but more than 5mg every other day created more need for antioxidants. I used citrulline until I no longer needed it or extra malic acid, following detox and adding FMN of B2.

Edit: wrong; I switched from pycnogenol to resveratrol and/or astaxanthine. Which my body later rejected in preference to acai. Lot's of antioxidants happening here, including food-based. Which seems to be a good approach, a cascade of different AO substances.

Why did you switch to resveratrol?
I think pycnogenol is much more potent...Which one did you use BTW? The french one or the chinese one?

 

[ahmo]

I'm not sure which pycnogenol, I'd used a couple different ones. I just go on what my body prefers. As I've sampled different forms of AO, some have been left behind and new ones taken their place. It took me some time to get that red wine resveratrol was giving me histamine problems, so I switched to knotweed only. Then acai replaced that.