Nitric oxide is a compound in the body which is important in many biological processes. One of its functions is to relax the smooth muscles around the blood vessels to increase bloodflow and normalize blood pressure. Nitric oxide is the same compound that is increased by the drug Viagra to increase bloodflow to certain parts of the body. Actually when i went to a doctor named Jay Goldstein, he was experimenting with Viagra to treat CFS!
In Martin Pall’s theory of the cause of chronic fatigue, nitric oxide plays a central role. Nitric oxide is very beneficial, but it is also extremely reactive with the free radical superoxide, to form the damaging free radical peroxynitrite. If higher than normal levels of nitric oxide are produced, it may react to form high levels of free radicals within the body that can cause inflammation, cell damage, and lower energy production in the mitochondria.
From what i’m reading, I dont think that nitric oxide is the enemy in chronic fatigue, but free radicals like superoxide and peroxynitrite that form in it presence are (i think). Nitroglycerin is used in people with heart problems because it increases levels of nitric oxide at that leads to a dilation of blood vessels and a decease of blood pressure. So increasing nitric oxide levels, can provide benefits, without CFS like symptoms. Maybe this is only true, if the exposure to high levels isn’t chronic.
In my personal case with CFS, their are supplements that i responded well in the short term, but then crashed, that increased nitric oxide. L-arginine and relaxin made me feel great in the short term, but then i crashed and felt worse than before after being on them for a few days.(These 2 supplements stimulate nitric oxide). But right now i am doing well on Sublingual B12 and CoQ10, which are both nitric oxide scavengers. I was wondering if the problem might be that i need to take these supplements at the same time. I feel like i need to stimulate nitric oxide, but at the same time take high doses of antioxidants to stop the increase in peroxynitrite and superoxide from getting out of control.
There also may be ways we can increase our sensitivity to nitric oxide. Drugs like ACE inhibitors might do this, while decreasing the formation of free radicals. SO it might not be a deficiency, it could be a sensitivity issue.
- Here is a youtube video about nitric oxide by Dr. Louis Ignarro. Go to 4:23 on the video to see, the man who won the noble prize for discovering nitric oxide, talk about optimizing nitric oxide levels in the body using supplements.
My hope is that there will be more research into Nitric Oxide as it relates to CFS. This is the first compound that i can see has a big effect on my symptoms. This might not be the answer to all types of CFS, but i do think it is a great direction to head in.
** Note – I’m not a doctor and am just trying to work this stuff out myself. If you have opinions or ideas to the contrary, feel free to write a comment.
Wow, hows it going?
Al
Very interesting and I am impressed with this. I particularly like the info on Ace Inhibitors and that they promote the formation of peroxynitrite. Thanks for the info. Danette
I completely agree that not enough NO is the cause of CFS.
I disagree with the Pall hypothesis that too much NO causes the production of peroxynitrite. That is incorrect. Peroxynitrite is only caused by near stoichiometric fluxes of NO and superoxide. The presence of peroxynitrite damage is a sign of not enough NO, not of too much.
NO/NOx physiology is under intense regulation. It is extremely difficult to perturb artificially. Essentially every non-physiological mechanism causes rebound. That is what supplemental L-arginine does.
Viagra does that too. I am pretty sure that Viagra will make CFS worse. It inhibits the phosphodiesterase that reduces cGMP, causing high cGMP levels, that turns off nitric oxide synthase earlier, and reduces the effects of NO that are not mediated through cGMP. There are a lot of NO effects not mediated through cGMP, breathing for example. Viagra makes obstructive sleep apnea worse via that mechanism (my hypothesis).
My blog is about NO physiology and at some point I will post about CFS. Right now I am working on a post about peripheral vascular damage.
Some of the symptoms of CFS and what is called Morgellons are the same. I think that Morgellons is low NO in the skin, CFS is low NO in the skeletal muscle. There are systemic effect too, and they are mostly the same. I have a blog about Morgellons.
Hello,
Interesting thoughts, in particular why dont people who use Nitro’s get CFS side-effects when elevated NO. I myself have CFS, have fully recovered for 8 yrs then are 2 yrs into relapse. I think the disease is more than NO depletion or elevation, but it does play a role. Im sure the underlying physiology of the disease sits on the axis between normal and coma, the brain gets an insult – Infection etc and goes into an autoprotection mode , which is where infected tissue is reprogrammed to function in a lower O2 environment which upgraded genetically the NO gene. However when the brain is confronted with having to produce extra energy , the NO gene is stimulated, producing excess NO. With more o2 being consumed during activity – this stimulate the L-Arginine NO pathway, producing those nasty by products. This is vicious cycle b/c the by procducts cause NS damage. Recently it have been mentioned 02 toxicity and ME. I only have theories like yourself, but this disease resembles Hashimoto Encephalopathy, Lymphatic Hypophositis, Atypical Addison,s, however it is a seperate entity b/c no disease has delayed 24-72 post-exertional fatigue, although one phenonemon that is strikingly similar is drug withdrawal – whereby pts get rebound excitatory neurotoxicity once the inhibitory substance is removed. I think when the brain goes into lock down mode – evidence SPECT Scans perfusion anolomies, slowed signalling on QEEG, HPA deficiencies – low temperature, slowed cortisol response, ( all markers of the shut down – inhibitory effect ), then once the NO pathway is induced the brain swings to NMDA neurotoxicity as seen in o2 toxicity. Depending on the level of activity ( o2 consumption ) and the shut down will determine how much post – exertional NS poisoning will occur. Finally yes, I have a medical background – Reg Nurse and was the Southern Regional Manager for a large drug company for 8 yrs.If thsi disease is a virus it is unique, i think that this disease is like cancer is that cells are reprogrammed, not producing tumours but major malfunction.
Good luck – Ash G.
Hi -
I do not come from a medical background but I am desperately trying to find answers—
Is it possible to overdose on l- arginine?
What would the effects be?
a) effects if one had Adrenal Fatigue
b) kidney malfunction
c) underactive thyroid?
I am a CFS patient of 35 years. My experience as a Nutritional Consultant has helped with some sucess in taking every possible herb/vitamin in an attempt to function. Taking nitro for approx 3 years has helped somewhat , but I am up to 7 tabs (.4) per day.
I am quite concerned with the affects this is having . However, after extensive research, and trying everything possible, I still feel half alive.
Your article was very good. I thank you for your input.
Thanks for the discussion. The conflicting theories about NO were driving me crazy!
What an interesting discussion. I have had CFS for 40 years and am almost completly bedridden, and I am happy to read these posts as I don’t have the mental energy that many people here do. I have never really understood the relationship of Nitric Oxide and CFS, but it’s going to be my next focus. I have severe problems with low phase II liver detox ablity. There are so many beneficial supplements I can’t take because the herx reaction causes me not to be able to function, just lie in bed feeling like I am dying, even with small amounts of many supplements. I am going to look into the NO thing. What does anyone think about taking arginine if you have high blood levels of HHV6, a herpes virus which everyone test positive for in terms of having antibodies. No one is even sure if these tests are accurate, or just mean you had an infection in the past, but arginine in the lab causes HHV6 to grow faster, yet it is so beneficial to the immune system. It’s inspiring that some people with CFS have the stamina and detachment needed to be their own experiments. I have been my own guinea pig and tried many things, but I don’t have a science background or a grasp of basic biochemistry . THANKS.
Whilst writing an essay on CFS at university (and suffering from CFS myself) i found that many CFS patients have higher than average NO levels, and high levels of NOS (which creates this in the body). Since working in a sleep department of a pharma company, i’ve seen that amongst NO’s many affects on the body it is capable of causing excessive sleepiness. Obviously this is key part of CFS symptomology. Interesting eh?