Nitric Oxide - Our Friend?

[Marco]

This is a fairly dated (2008) opinion piece (and may have been discussed before), but presents a very different slant on the involvement of nitric oxide in the pathogenesis of ME/CFS that appears to be completely at odds with the process proposed by Martin Pall etc. In essence, he proposes, a low NO state is characteristic of the fight or flight response to 'stress' that temporary halts the recycling and repair of mitochondria. The problem arises when this state becomes established and chronic.

What I find interesting is the suggestion that ME/CFS is an altered state of physiological homeostasis. It is well recognised that complex systems with feedback loops can under certain conditions shift to a different yet stable state as opposed to the common assumption that there is a single state of physiological homestasis and that deviation from this represents illness. Illness (or at least our illness) may be our physiology maintaining homeostatis around an inappropriate state of chronic activation.

This ties in with my own personal subjective feeling that my symptoms fluctuate around a constant state of illness rather than just feeling more of less 'well' if that makes any sense?

I also appreciate that this raises the whole issue of the stress response again, but no-one is suggesting that the 'stress' needs to be psychological.

Any thoughts?



The author of this blog contacted me to write a short piece on how I understand the role of NO in CFS and my suggestions on how to deal with it. I am not a clinician, I am a researcher in NO (nitric oxide) with a chemical engineering background, so I tend to see physiology as a complicated chemical plant with exquisitely complex, precise, distributed and redundant control systems. We are mostly ignorant of the details of that control system, but that there is a control system and that it (usually) functions exquisitely well is beyond doubt. In CFS, much of that disruption results from low basal nitric oxide (my hypothesis).

In summary, I see CFS as the consequence of low NO skewing the physiology into a permanent fight or flight state. The only way I know to get out of that state is to restore basal NO levels long enough for physiology to remodel itself into the low stress state.

http://www.zimbio.com/Chronic+Fatig.../69/Engineering+Perspective+CFS+Dave+Whitlock

 

[Jenny]

This is really interesting Marco. I entirely agree that our symptoms feel like our bodies' systems have been set to a new state, and that we have to take a systems approach to understand what's going on.

I've been puzzled by Pall's theory since there's other evidence that our problem is not enough NO, rather than too much. I have a genetic variation in eNOS (not uncommon) which shows that my vascular tone and blood flow is affected by a low capacity for the production of NO. I tried to discuss with Marty Pall how my results could be compatible with his theory, but he said he couldn't explain it.

It's disappointing that the researcher you've given the link to doesn't have many suggestions for increasing NO, but he does suggest lettuce, and I've heard elsewhere that this is worth trying. We'd need very large quantities though!

Jenny

 

[lucy]

Very interesting, I will try to read it. I as always thinking NO was foe, not friend. Especially the fact that it is generated in endothelium during exercise for me was an important relation with excercise intolerance. Morover, lack of NO guarantees that there will erection problems. Is there such a fact about ME/CFS male patients?

 

[Crappy]

This is an area of some speculation. You delve into the subject fairly deep. I find it fascinating the body uses so many control mechanisms i.e. hormones, electrical currents, a multitude of chemical reactions, peptides, minerals, gases, it is a stunningly complex machine. The processes are controlled so tightly too.

The NO idea has been examined in many circles relating to this condition; in fact my LLMD recommends supplementation. I was an amateur weight lifter in my youth, and I know the athletic community has toyed with NO increasing supplementation for years. I began to understand the importance of NO in this physiology when a very detailed stress test revealed very poor aortal dilation significantly impaired VO2 max response. Some speculate it is this impaired response that is the cause of post exertional fatigue.

I have tried supplementation for this condition with no noticeable improvement. One Dr., Dr. Shoemaker applies Cialis for this condition. The medical community is behind the curve in techniques to modify NO production. If I really wanted to influence NO production I would use a product like N.O.-XPLODE. http://www.bodybuilding.com/store/bsn/xplode.html Theoretically you could manipulate production to any level you want.

I would advise caution in manipulating NO, because +NO means +O2, and O2 has been found to cause significant harm in CFS/ME patients. Dr.Cheney http://www.dfwcfids.org/index.shtml seems to think NO is being down regulated because of the bodies basic need to limit free radical damage for basic survival. So +NO= +O2= +free radicals, which are out of control in CFS/ME people.

 

[Marco]

This is making me rethink my current regime of antioxidants. While I have noticed some possibly coincidental moderate improvements my inflammatory symptoms are as bad as ever :


"I think that self-selected diet choice may be a control parameter that physiology uses to modulate its state of oxidative stress. If the setpoint calls for oxidative stress, it is better to eat a diet devoid of antioxidants so that physiology doesnt need to destroy them by generating more superoxide (which physiology has an unlimited capacity to do). This makes sense, if an organism needs to enter the fight or flight state, it cant allow what it ate a few hours before impede that. If an organism is already in a state of oxidative stress, better to not eat anything that makes that state harder to maintain."


I agree that unfortunately he doesn't seem to be offering any easy solutions outside of his 'topical nitric oxide producing bacteria, pat pending) although one of the few supplements that I found beneficial is the green barley grass type powders that you make into a drink. Possibly another source of nitrate?

Following on from the above, I have always found that any intervention, however beneficial, loses its effect after two or three months at most. Again I see it as if the ME/CFS state is acting like a 'centre of gravity' (or basin of attraction of you like chaos theory) which tends to drag you back to the same disordered state. Although having an untreated chronic illness would have the same effect and is a more concise explanation!

Lucy - Re erectile dysfunction, you might like to check out the 'What's happening in 2011' topic on the home page:innocent1:

 

[Mark]

Thanks for posting this Marco. I came across this blog post a few months ago and also found it very interesting, but didn't have time to follow up on it.

One thing that stayed with me from reading this was the potential significance of 'mast cells'. I may have this wrong, but I came away with the sense that there are a very small number of such cells in the body that have a role in communication, so that fluctuating NO levels could send signals out all over the body.

The connection I found myself trying to make, was with my strange 'itching' reaction. When my hand, or foot, or any other part of my body, is touching something that I react to (could be the glossy cover of a magazine, for example), this reaction starts. It starts and stops all the time, all day every day, as I navigate through my environment and find oases of calm where I no longer itch. Anyway...when it starts up, it will often (but not always) begin with slight tickling sensations, or itches, or stabbing pains, at the site where I'm touching the thing that sets me off - but very rapidly I then get further such reactions all over my body, in sites that commonly itch when I'm reacting to something. In other words, within seconds or sometimes minutes of touching something with my hand, I feel the reaction in my leg, or in my back...and over the next few minutes that reaction grows, and grows, until my whole body is tingling.

So reading about the NO levels and the mast cells made me wonder whether something like this could explain how this itching spreads across my body. Maybe, when that provocative chemical gets through to my body, it causes some kind of signalling via cells like these. It could even be that the painful sensations I feel are the activity of cells like these.

Hope I've remembered the source of the mast cell connection correctly...anyway, the NO theory is all very interesting, and I do think there is something significant here, waiting to be fully understood...

 

[illsince1977]

Itching brings to mind histamines.

 

[Mark]

Itching brings to mind histamines.

Anti-histamines have no effect; there is no rash and allergy testing is all negative. The sensitivity has to be some kind of other response - a medically unexplained phenomenon, according to my doctors. I think it's fairly clear it isn't mediated by histamines like a conventional allergic response.

 

[Mark]

I should add that more sensitive allergy testing (or rather, sensitivity testing, perhaps) by Allergy UK successfully identified the pattern of sensitivities I had already determined through experience.

But those tests aren't considered valid in the UK - presumably because they work?

 

[August59]

This is a good subject to talk about anyway. I think I remember awhile back a discussion on NO and if I remember correctly NO is not look at the same depending on where it occurs. High is bad in blood vessels and low was bad during certain actions in the brain. I'm going to see if I can find that info.

 

[AFCFS]

I hve been using NEO40 for the past few days. Initially it made me feel a bit tired (described here - Nitric Oxide and Neo40(R)), but now it seems to have helped with cognition and cognitive clarity quite a bit.

From the Neogenis Labs website:

Do all Nitric Oxide-generating products contain L-arginine?
L-arginine is a semi-essential amino acid used for Nitric Oxide production. It is found in many bodybuilding supplements on the market today. However, clinical trials have shown that in patients with heart conditions, at risk for heart attack or over 40 years old, L-arginine can actually do more harm than good. Neo40® Daily does not contain L-arginine and employs a different mechanism for generating Nitric Oxide in the body that is not contingent on health level or age.

 

[PointsNorth]

I tried an NO supplement a while back as I thought it might work for me as a vasodilator. I got mixed results and decided to discontinue.