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

[Adlyfrost]

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.

Before I had even heard of CFS I was convinced for a time that I had porphyria. I tried citrulline maleate as a result and it seemed a magic bullet at first- mega energy like I had never experienced. Then I would get these random panic attacks/ highly caffeinated feelings and were extremely scary- I found myself out of breath and dizzy. Almost exactly what happens when I take too much greens. I am convinced it is too much NO.

My naturopath has been trying for months to combat NO that leads to superoxide and peroxinitrite with sophisticated antioxidant nutraceuticals. I have also tried eating a high anti-oxidant raw-ish vegan-ish diet lately which really seems to help with inflammation. (I have a lot more inflammation since starting my micro-doses of folate-which is a lifesaver but also can cause more NO than my body can handle right now).

Unfortunately , the folate is not nearly high enough to turn on all my mutated genes and get them working- (if it was high enough, like Fredd's theory- I believe I could handle the extra NO. But I am just not there yet. )

The only things so far that has worked for my seemingly high NO symptoms are:
1. hydroxocobalamin- until it turns to methylated then I need a little niacin also to calm down.
2. fruit. I had gone off it before for candida and lack of fruit did help with parasites and candida but also left me feeling hormone-less and more prone to inflammation and panic attacks from greens. I think fruit feeds flora that are potent scavengers of NO. Anyway, a regimen of Candex and other colon hygiene and supplements will hopefully keep the creatures from getting out of control again while eating fruit.

If I needed more NO however, I would just eat low oxalate raw greens. But this is what gets me in trouble- at first greens make me feel amazing and like citrulline, later I get the attacks and inflammation. I don't know how many people with CFS are like this- when NO is a catch 22- can't live without it or with it. Hopefully my new regimen will help me live in balance with NO without it turning into stuff that will make me sick.

Regarding citrulline, I've heard amazing things about it! I wish it had been the answer to my prayers I thought it was going to be. My reaction is rare from what I have heard but if one tries it, I myself would proceed very cautiously.

 

[Crux]

When I have a negative reaction to nitrate containing foods, I believe it's because I'm producing too much nitric oxide to battle an infection.

Nitric oxide only becomes toxic in excess. The body produces it (iNOS) to fight infections. Sometimes NO production becomes excessive - even neurotoxic. ( Some bacteria produce it too, as it's antimicrobial. Bacteria produce antibiotics to inhibit other bacteria.)

Excessive NO production has been detected in CFS : http://www.ncbi.nlm.nih.gov/pubmed/20469961

I'm taking Berberine to decrease a possible cause of my own excessive NO production.
http://www.ncbi.nlm.nih.gov/pubmed/26027164
http://www.ncbi.nlm.nih.gov/pubmed/26398393

I hope to eventually benefit from nitrates, because, they can really increase energy.

 

[Adlyfrost]

"When I have a negative reaction to nitrate containing foods, I believe it's because I'm producing too much nitric oxide to battle an infection."

Yeah which would make sense why some PWME have excess NO- constantly fighting viruses, mold, SIBO etc. And as I posted earlier, these microbes have Nitric Oxide defense mechanisms to neutralize it.

"I hope to eventually benefit from nitrates, because, they can really increase energy."

I agree @Crux that NO is a key piece of the puzzle for our energy.

My experience is though, that once I have infections in check, I still have problems with NO overproduction. Possible causes:
1. EMF's- gated voltage calcium channels being disrupted, too much calcium in the cell leading to too much production
2. methyfolate introduction after years of not having it and / or, as Fredd said, not enough methylation
3. diet- leafy greens- high nitrate foods
4. Body's over-response to healing and keeping infections from coming back
5. genetics
6. combination

Having balanced NO is where I want to go- keep eating the leafy greens and other NO rich foods for energy but sop up excess NO with scavengers.

If I had an infection though, I dont think scavenging for NO would be advantageous. When I was really sick with viral and candida and parasite symptoms, I could barely stay coherent throughout the day. I was also so cold. Chocolate for example, was an excellent medicine- high NO! But it did not get me better long term.

To kill the candida I needed enzymes and a candida diet and lots of enemas. The viral symptoms needed glutathione, folate, B12 and other nutraceuticals for my genes. But raising NO- either with greens, citrulline, chocolate, etc. never cured me- though it may have been part of my bodies ability to fight infection.

But NO is also part of my problems with inflammation. NO, in my experience has been a double-edged sword! But everyone is different.

 

[Crux]

@Adlyfrost ,

Even with tests and symptoms, sometimes it's hard to tell if we've truly tamped down infections. I've noticed that the ranges for normal commensal bacteria may be too high. Some people are feeling poorly when stool tests report normal, but high normal bacteria, especially those in the Enterobacteriaceae family.

Also, perhaps the body remains in high alert after infection, overproducing NO. Another difficult gas to measure, but nitrite can be measured. The normal range could be questioned, though.

I do feel much better taking berberine for now, but the symptoms, (especially migraine), come back when I stop...may have to take it longer. Since berberine is antimicrobial, I'm not worried about its iNOS ihibiting properties.

 

[Adlyfrost]

I did not know about berberine NO inhibitive properties. I will definitely check it out!

 

[Crux]

http://www.ncbi.nlm.nih.gov/pubmed/26027164

 

[Deltrus]

Hello everyone, I have a question. BH4 is a calatylst / co-factor in NO production.

I thought that catalysts don't get "used up". Don't they get recycled since they aren't used in the reaction?

Or does the body only produce a small amount of BH4, and all this BH4 is constantly being used for NO production?

 

[Biarritz13]

Before I had even heard of CFS I was convinced for a time that I had porphyria. I tried citrulline maleate as a result and it seemed a magic bullet at first- mega energy like I had never experienced. Then I would get these random panic attacks/ highly caffeinated feelings and were extremely scary- I found myself out of breath and dizzy. Almost exactly what happens when I take too much greens. I am convinced it is too much NO.

My naturopath has been trying for months to combat NO that leads to superoxide and peroxinitrite with sophisticated antioxidant nutraceuticals. I have also tried eating a high anti-oxidant raw-ish vegan-ish diet lately which really seems to help with inflammation. (I have a lot more inflammation since starting my micro-doses of folate-which is a lifesaver but also can cause more NO than my body can handle right now).

Do you remember how long this magic bullet last?

 

[Biarritz13]

A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by Abeta(25-35).

 

[Gingergrrl]

Valerian and gotu kola herbs both stimuate the GAD enzyme which converts glutamate into GABA

I know this is a very long thread that spans five years but I am very interested in the supplement "Gotu Kola" which I highlighted in the above quote. I am not sure if @aprilk1869 still posts on PR but am curious if anyone else has ever tried this supplement?

My interest in it is that it is supposed to assist the process of converting glutamate to GABA which is messed up for me b/c of having the GAD65 autoantibody. I continue to have an insane startle reflex (it was really bad tonight) and am considering trying this herb/supplement to see if it can increase GABA.

I apologize that I did not read this entire thread and found it in a Google site search. Was curious @Hip if you have tried this supplement and what are your thoughts on it converting glutamate to GABA in someone like me who has a defect in this process b/c of the autoantibody.

Thanks in advance for any responses.

 

[Violeta]

@Gingergrrl , I just started taking bacopa, the herb that has almost identical action as gotu kola, and I had almost overnight improvement in symptoms such as anxiety and fatigue. For neurological action, it's recommended to take them with ghee, as the fat will help it get to the brain. I haven't yet been able to make myself do that, so I take it with raw milk.

I didn't realize gotu kola (or bacopa) is good for startle reflex. I also have that to the extreme. Do you have the reflex just to sound or is it also visual for you?

 

[Gingergrrl]

@Violeta, I have not heard of Bacopa but I just ordered Gotu Kola this morning and it should arrive in a few days. Am excited to try it (starting with micro dose to make sure I am not allergic). It can help with the startle reflex and my messed up GAD65 antibody and produce more GABA. That was my non-scientific explanation but it has helped with the startle reflex in rats and humans, and from what I read, can also help with blood pooling in the legs and leaky blood vessels so hoping it will get more blood up to my lungs and heart for breathing.

I have a good feeling about this one and if not, it was very inexpensive to try. To answer your question, my #1 startle trigger is an unexpected noise (like my dog barking, knock at the door, or last night a TV tray table fell over and hit the wall making a loud crashing sound). Visual things can startle me if someone enters the room very quietly and I am not wearing glasses/contacts and just see a shadow but majority of the time, it is a noise trigger. Will reports back on the Gotu Kola once it arrives and I get to try it.

 

[Hip]

Was curious @Hip if you have tried this supplement and what are your thoughts on it converting glutamate to GABA in someone like me who has a defect in this process b/c of the autoantibody.

I feel worse on gotu kola (Centella asiatica), and I seem to remember that this is one of those supplements that ME/CFS patients tend to report feeling worse on.

Note that Centella asiatica should not be confused with Bacopa monnieri (the confusion arises because both are sometimes called Brahmi).

 

[Gingergrrl]

I feel worse on gotu kola (Centella asiatica), and I seem to remember that this is one of those supplements that ME/CFS patients tend to report feeling worse on.

@Hip, In what way did you feel worse on Gotu Kola, if you remember? I apologize that I have not read this entire thread. I am still not 100% certain if I have ME/CFS although I do often get very unpredictable side effects to meds and supplements. My hope with Gotu Kola is that it will increase GABA and reduce my startle reflex which is causing me great distress at present.

Note that Centella asiatica should not be confused with Bacopa monnieri (the confusion arises because both are sometimes called Brahmi).

The one I ordered is 100% "Centella Asiatica" or "Gotu Kola" and is not Bacopa Monnieri which I had not heard of prior to this post.

 

[Hip]

@Hip, In what way did you feel worse on Gotu Kola, if you remember?

I can't actually remember, unfortunately; I seem to remember it was only a mild negative effect though, nothing of concern.

If you want to increase GABA activation, the herb kava kava root 300 gm daily is good. This is one of the very few herbs/drugs that act on the GABAergic system without causing a tolerance and loss of effect over time. In fact, kava apparently increases GABA receptors over time, so possibly increases the effect over time.

The other approach, instead of boosting GABA activation, is to inhibit NMDA activation. GABA and NMDA are the two sides of the seesaw: GABA calms the neuron, whereas NMDA excites the neuron. So to calm neurons, you can either boost GABA activation, or inhibit NMDA activation (or both). The numerous ways you can inhibit NMDA activation are detailed in this post, this post and this post.

 

[Gingergrrl]

I can't actually remember, unfortunately; I seem to remember it was only a mild negative effect though, nothing of concern.

No problem and am glad it was so mild that you don't remember what it was LOL. Will definitely check out the other posts that you have linked me to as well. Thanks again.

 

[Violeta]

@Violeta, I have not heard of Bacopa but I just ordered Gotu Kola this morning and it should arrive in a few days. Am excited to try it (starting with micro dose to make sure I am not allergic). It can help with the startle reflex and my messed up GAD65 antibody and produce more GABA. That was my non-scientific explanation but it has helped with the startle reflex in rats and humans, and from what I read, can also help with blood pooling in the legs and leaky blood vessels so hoping it will get more blood up to my lungs and heart for breathing.

I have a good feeling about this one and if not, it was very inexpensive to try. To answer your question, my #1 startle trigger is an unexpected noise (like my dog barking, knock at the door, or last night a TV tray table fell over and hit the wall making a loud crashing sound). Visual things can startle me if someone enters the room very quietly and I am not wearing glasses/contacts and just see a shadow but majority of the time, it is a noise trigger. Will reports back on the Gotu Kola once it arrives and I get to try it.

Yes, I read such good things about gotu kola, too. I was going to order some for my husband when I ordered my bacopa because my husband needs help with getting the blood moving upward out of his legs, too. I am going to just give him some of my bacopa for now and then order the gotu kola next time.

Did you see while reading about it that if you take it with different mediums it will affect different areas of your body. To get it to the neurons, it's recommended to take it with fat.


Yes, I have a very bad startle reflex, my reflex will often startle others in the room with me when the actual noise didn't! My visual startle reflex is something that happens when I'm in the passenger seat of a car and I see some movement off in the periphery. My reaction can really startle the driver, not good.

I didn't want to confuse the matter by bringing up the bacopa, but they are so similar that I thought I would share how it's going for me.

Yes, keep us posted on how it goes for you.

PS: After reading this study, I wish I would have ordered the gotu kola, too.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116297/

 

[Gingergrrl]

Yes, I read such good things about gotu kola, too. I was going to order some for my husband when I ordered my bacopa because my husband needs help with getting the blood moving upward out of his legs, too. I am going to just give him some of my bacopa for now and then order the gotu kola next time.

@Violeta Does your husband have POTS or another autonomic disorder that causes blood pooling in his legs? Please let me know if he tries the Gotu Kola and it helps him with this issue. Several docs think the blood pools in my feet/legs or even splanchic pooling and not enough blood getting to my heart and lungs when I stand and that this is part of why I cannot adequately breathe when I stand up.

Did you see while reading about it that if you take it with different mediums it will affect different areas of your body. To get it to the neurons, it's recommended to take it with fat.

No, I think I missed this part. My GK has not arrived yet from Amazon and I think a friend mentioned to me that I should take it with food and I am going to re-check this. So, the ideal scenario is to eat it with fat? Would almond butter or peanut butter be adequate?

Yes, I have a very bad startle reflex, my reflex will often startle others in the room with me when the actual noise didn't!

Yes, me too!!!

My visual startle reflex is something that happens when I'm in the passenger seat of a car and I see some movement off in the periphery. My reaction can really startle the driver, not good.

For some reason, I don't really have this issue in the car as passenger although I am surprised that I don't. Although if we are driving and the radio suddenly turned on to full volume without me expecting it or there was a loud noise outside, this would startle me.

I didn't want to confuse the matter by bringing up the bacopa, but they are so similar that I thought I would share how it's going for me.

Am glad you brought it up, thank you.

Yes, keep us posted on how it goes for you.

I will and it should arrive in the next few days.

PS: After reading this study, I wish I would have ordered the gotu kola, too.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116297/

I will definitely read the study and if you do want to order it on Amazon, mine was only $13 (in the US).

 

[Violeta]

@Violeta Does your husband have POTS or another autonomic disorder that causes blood pooling in his legs? Please let me know if he tries the Gotu Kola and it helps him with this issue. Several docs think the blood pools in my feet/legs or even splanchic pooling and not enough blood getting to my heart and lungs when I stand and that this is part of why I cannot adequately breathe when I stand up.



No, I think I missed this part. My GK has not arrived yet from Amazon and I think a friend mentioned to me that I should take it with food and I am going to re-check this. So, the ideal scenario is to eat it with fat? Would almond butter or peanut butter be adequate?



Yes, me too!!!



For some reason, I don't really have this issue in the car as passenger although I am surprised that I don't. Although if we are driving and the radio suddenly turned on to full volume without me expecting it or there was a loud noise outside, this would startle me.



Am glad you brought it up, thank you.



I will and it should arrive in the next few days.



I will definitely read the study and if you do want to order it on Amazon, mine was only $13 (in the US).

For couple of years my husband had been complaining of feeling light headed, but he doesn't complain about it anymore. I don't know if it was when he would get up or not, though, and it could have been from not eating right or his deep vein thrombosis, which he didn't realize he had.

His body does need help with getting the blood moving upwards, his ankles very often are swollen.

How did you find gotu kola, it does sound like it is what you need.

I think that probably almond butter or peanut butter would be okay. Since I was reading about it in ayurvedic articles, they recommended ghee, but just taking it with food that has fat is going to have to do for me.

Where did you get yours, what brand?

 

[Violeta]

@Gingergrrl , how are you doing with the gotu kola?