Citrulline: ↑Circulation, ↓ INOS In Endotoxinemia

[Mossy]

I would argue that its a good way to help attenuate sepsis. I just have a paranoia regarding sepsis so I supplement this daily.

Citrulline: just a biomarker or a conditionally essential amino acid and a pharmaconutrient in critically ill patients?
"In the previous issue of Critical Care, Ware and colleagues [1] showed that citrulline (CIT) plasma levels are extremely low in critically ill patients with sepsis and significantly lower in patients complicated with acute respiratory distress syndrome (ARDS). Thus, this study brings the new and important information that CIT depletion may be related to morbid events. In addition, these data form a strong rationale for CIT supplementation in intensive care unit (ICU) patients with sepsis."

"For a long time, CIT was considered just a 'garbage' amino acid because it is not included in proteins and is known only as an intermediary in the urea cycle. However, some early classic studies suggested that CIT had a unique metabolism and that its deficiency might be harmful (reviewed recently in [2]). The fact that CIT is almost absent from food (with the notable exception of watermelon) and is synthesized solely by the gut at the whole body level led Crenn and colleagues [3] to hypothesize, and then prove, that CIT plasma level is a reliable marker of intestinal functional mass. "

"I do not know of any data that establish, at the cellular level, that ARG is a better precursor of nitric oxide (NO) than CIT or vice versa. In addition, in vitro data suggest that the ability of ARG or CIT to generate NO in macrophages (which play a key role in sepsis and ARDS) is co-regulated by glutamine [13], whose availability is decreased in sepsis. In the case of sepsis, we cannot safely speculate, because, on the one hand, it is true that **** + ASL and NOS channel CIT, but on the other hand, the ARG transporter CAT2 (cationic amino acid transporter 2) is also connected to inducible NOS, and both are overexpressed in sepsis [14]. The absence of any difference in ARG levels between patients with ARDS and those without it apparently supports the authors' view that the key is CIT, not ARG. However, the absence of any correlation between amino acids and NO end-products (that is, nitrate + nitrate) supports the idea that the answer is in the lung, not in the plasma, and that - in the absence of measurements with stable isotopes, arterio-venous difference, and measurements in the bronchoalveolar fluid - all these considerations are just a matter of speculation.

This is specifically my point of interest in it, now, verses for working out.

I’ve been having what I would define as breathing/respiratory issues, as well as a sensitive/weak heart. So, your post, and @Vinero’s, caught my interest. The thought that really hit me is maybe a pro-Peat diet might be so anti-N.O., that for those in poor health, or with susceptibilities (as in your case g), there could be some exceptions to the rules. It’s at least worth consideration and investigation.

 

[Vinero]

This is specifically my point of interest in it, now, verses for working out.

I’ve been having what I would define as breathing/respiratory issues, as well as a sensitive/weak heart. So, your post, and @Vinero’s, caught my interest. The thought that really hit me is maybe a pro-Peat diet might be so anti-N.O., that for those in poor health, or with susceptibilities (as in your case g), there could be some exceptions to the rules. It’s at least worth consideration and investigation.

Indeed, almost everything Ray Peat recommends lowers NO. Caffeine, aspirin, niacinamide, Magnesium, Zinc, Vitamin E, Progesterone, Methylene blue, etc. all lower nitric oxide. Imagine a person taking all of these supplements, and on top of that supplementing lysine which blocks arginine absorption. The body will become unable to make any NO.

 

[Mossy]

Indeed, almost everything Ray Peat recommends lowers NO. Caffeine, aspirin, niacinamide, Magnesium, Zinc, Vitamin E, Progesterone, Methylene blue, etc. all lower nitric oxide. Imagine a person taking all of these supplements, and on top of that supplementing lysine which blocks arginine absorption. The body will become unable to make any NO.

Vinero, besides your pneumonia symptoms, which were blatant and obvious, do you watch for any other symptoms, prior to the severity of pneumonia, that help you to gauge your NO levels? I'll search the forum as well, but thought I'd ask in case you had a good approach.

As I had noted, I'm dealing with some persistent chest and respiratory issues, which are consistent with allergic reactions that I get frequently; but, they've been as severe and concerning as they've ever been, so I'm attempting to self-treat while I wait for my doctor, who can't see me for three more weeks. I'm trying to distinguish between an NO issue, an allergy issue, or maybe a new-found asthma issue. I am considering going to the ER, but am attempting to do my home-work first. If it persists any longer, or gets any worse, I'll just have to stop playing doctor and go.

 

[Mossy]

Vinero, besides your pneumonia symptoms, which were blatant and obvious, do you watch for any other symptoms, prior to the severity of pneumonia, that help you to gauge your NO levels? I'll search the forum as well, but thought I'd ask in case you had a good approach.

As I had noted, I'm dealing with some persistent chest and respiratory issues, which are consistent with allergic reactions that I get frequently; but, they've been as severe and concerning as they've ever been, so I'm attempting to self-treat, while I wait for my doctor who can't see me for three more weeks. I'm trying to distinguish between an NO issue, an allergy issue, or maybe a new-found asthma issue. I am considering going to the ER, but am attempting to do my home-work first. If it persists any longer, or gets any worse, I'll just have to stop playing doctor and go.

I just read @Koveras response to your post on this thread, with Ray's comments--they're very convincing to not do anything pro-NO. It does seem your stoppage of Lysine was the remedy to your NO issue, not taking a pro-NO supplement, which is what I'm considering.

I realize there are so many variables, and each situation is so different, but I'm just thinking out loud, as well as attempting to add something to the conversation.

 

[Vinero]

I just read @Koveras response to your post on this thread, with Ray's comments--they're very convincing to not do anything pro-NO. It does seem your stoppage of Lysine was the remedy to your NO issue, not taking a pro-NO supplement, which is what I'm considering.

I realize there are so many variables, and each situation is so different, but I'm just thinking out loud, as well as attempting to add something to the conversation.

I didn't take any supplemental l-arginine, but I did eat a lot of dark chocolate, which has a lot of arginine naturally.
And of course not taking Lysine.

 

[Vinero]

I just read @Koveras response to your post on this thread, with Ray's comments--they're very convincing to not do anything pro-NO. It does seem your stoppage of Lysine was the remedy to your NO issue, not taking a pro-NO supplement, which is what I'm considering.

I realize there are so many variables, and each situation is so different, but I'm just thinking out loud, as well as attempting to add something to the conversation.

Could you perhaps tell me what supplements you take?

 

[Mossy]

I didn't take any supplemental l-arginine, but I did eat a lot of dark chocolate, which has a lot of arginine naturally.
And of course not taking Lysine.

Ok, interesting--so, to some degree, your arginine intake was increased.

 

[Mossy]

Could you perhaps tell me what supplements you take?

I can't really take anything constantly--I am highly sensitive and allergic. When I first started Peating, I did try to to take daily all of the Peat staples: D, K2, E, aspirin (white willow bark), B3 niacinamide), and Caffeine (coffee).

The supplement I take the most consistently is Thorne D/K2, about 2000mg/600mcg a day. My blood test show I'm very low.

I will add additional Thorne K some days, as well as B vitamins, making my own make-shift Energin, and sometimes my own make-shift Estroban, but without the vitamin A. I get my A from liver. Also, I don't take vitamin E every day, but I have been increasing it because I remember reading a thread by Haidut that it is good for asthma; and while I can't say I have asthma, the symptoms are similar. I would have to say I have yet another bad allergic reaction; or, something else.

I am constantly trying to add supplements, but I very rarely can tolerate them. For instance, I've tried sweet wormwood recently, which gave me one of my worst allergic reactions yet. I also tried horse chestnut, in an attempt to help with blood flow to my feet (always cold). So, maybe I'm dealing with lingering effects from that.

My most recent successful supplement was Selenomethionine. But, to really see if it works long-term, I'll have to dedicate some time to just taking that.

I also take very low dose amino acids on an as needed basis: theanine, taurine, and sometimes lysine.

 

[Mossy]

P.S. with regard to my symptoms, I should add that I have a strange cough, which I've never had before. Like I get the sensation that I have to cough, to help my breathing--it's a hard dry cough, that is not too satisfying, like it doesn't clear out the chest or remedy the situation too much.

 

[Mossy]

I can't really take anything constantly--I am highly sensitive and allergic. When I first started Peating, I did try to to take daily all of the Peat staples: D, K2, E, aspirin (white willow bark), B3 niacinamide), and Caffeine (coffee).

The supplement I take the most consistently is Thorne D/K2, about 2000mg/600mcg a day. My blood test show I'm very low.

I will add additional Thorne K some days, as well as B vitamins, making my own make-shift Energin, and sometimes my own make-shift Estroban, but without the vitamin A. I get my A from liver. Also, I don't take vitamin E every day, but I have been increasing it because I remember reading a thread by Haidut that it is good for asthma; and while I can't say I have asthma, the symptoms are similar. I would have to say I have yet another bad allergic reaction; or, something else.

I am constantly trying to add supplements, but I very rarely can tolerate them. For instance, I've tried sweet wormwood recently, which gave me one of my worst allergic reactions yet. I also tried horse chestnut, in an attempt to help with blood flow to my feet (always cold). So, maybe I'm dealing with lingering effects from that.

My most recent successful supplement was Selenomethionine. But, to really see if it works long-term, I'll have to dedicate some time to just taking that.

I also take very low dose amino acids on an as needed basis: theanine, taurine, and sometimes lysine.

To clarify, I still do take all the Peat staples, just not daily. The most recent I've taken have been vitamin E (tocovit), aspirin (white willow bark), and B3 (niacinamide).

 

[Vinero]

P.S. with regard to my symptoms, I should add that I have a strange cough, which I've never had before. Like I get the sensation that I have to cough, to help my breathing--it's a hard dry cough, that is not too satisfying, like it doesn't clear out the chest or remedy the situation too much.

I did have some asthma-like symptoms in the weeks and months before getting the pneumonia. And also a cough.
I did read on nathan hatch his site that he also developed a cough after supplementing lysine, which went away after a few weeks when quiting the lysine.

 

[Mossy]

I did have some asthma-like symptoms in the weeks and months before getting the pneumonia. And also a cough.
I did read on nathan hatch his site that he also developed a cough after supplementing lysine, which went away after a few weeks when quiting the lysine.

OK, interesting. Though, my lysine intake is so small. Maybe I'll try something natural for arginine, like chocolate, to see if that remedies anything.

Thanks for your input.

 

[ddjd]

Contrastingly, l-lysine has no effects in the absence of endotoxin and thus appears to act as a selective modulator of iNOS activity.

Does this mean it lowers iNOS?

 

[managing]

How about a new twist to all this.

Citrulline is produced in the intestines by some bacteria. JCI - Arginine, citrulline, and nitric oxide metabolism in end-stage renal disease patients

Citrulline supplementation improves kidney disease. Not clear how, perhaps through arginine synthase inhibition?

l-Citrulline Protects from Kidney Damage in Type 1 Diabetic Mice

Thus, citrulline supplementation may be appropriate in some gut dysbiosis? And perhaps at low enough doses so as not to enhance NO production much? Or perhaps NO deficiency could be associated with gut dysbiosis and kidney dysfunction?

Also, citrulline is protective against altitude sickness. Not clear to me if it is competitive with CO2 or complimentar? Response of nitric oxide pathway to L-arginine infusion at the altitude of 4,350 m. - PubMed - NCBI

 

[Mossy]

How about a new twist to all this.

Citrulline is produced in the intestines by some bacteria. JCI - Arginine, citrulline, and nitric oxide metabolism in end-stage renal disease patients

Citrulline supplementation improves kidney disease. Not clear how, perhaps through arginine synthase inhibition?

l-Citrulline Protects from Kidney Damage in Type 1 Diabetic Mice

Thus, citrulline supplementation may be appropriate in some gut dysbiosis? And perhaps at low enough doses so as not to enhance NO production much? Or perhaps NO deficiency could be associated with gut dysbiosis and kidney dysfunction?

Also, citrulline is protective against altitude sickness. Not clear to me if it is competitive with CO2 or complimentar? Response of nitric oxide pathway to L-arginine infusion at the altitude of 4,350 m. - PubMed - NCBI

I'm open to this perspective. I checked my records, and the dose of citrulline malate that caused me low pulse, was 830mg. Maybe I can try a lower dose, or watermelon rinds juiced, or beet juice, which I have been taking. Ultimately, I am open to the idea of adding in a bit of N.O., short-term, to see if a better balance is created. I can say, based on my past citrulline experience, and some experience with arginine, I definitely don't do well will larger doses--so, it's no mystery that it was easy for me stay away from anything N.O. once I heard Peat's perspective on it.

 

[ddjd]

To clarify, I still do take all the Peat staples, just not daily. The most recent I've taken have been vitamin E (tocovit), aspirin (white willow bark), and B3 (niacinamide).

Mossy I'd be interested to know if regular Aspirin makes your sleep quality better or worse. I find it sends me off to sleep but I wake up feeling terrible like I've barely slept. Have you taken it before bed? Also does it cause you to get stomach soreness?

 

[managing]

I'm open to this perspective. I checked my records, and the dose of citrulline malate that caused me low pulse, was 830mg. Maybe I can try a lower dose, or watermelon rinds juiced, or beet juice, which I have been taking. Ultimately, I am open to the idea of adding in a bit of N.O., short-term, to see if a better balance is created. I can say, based on my past citrulline experience, and some experience with arginine, I definitely don't do well will larger doses--so, it's no mystery that it was easy for me stay away from anything N.O. once I heard Peat's perspective on it.

I thought this would be a good one to ask the man himself. If I get a response (usually do), I'll share.

 

[Mossy]

Mossy I'd be interested to know if regular Aspirin makes your sleep quality better or worse. I find it sends me off to sleep but I wake up feeling terrible like I've barely slept. Have you taken it before bed? Also does it cause you to get stomach soreness?

Hey Joeyd, it's exactly as you stated! It does send me off to sleep, but I do wake up feeling like something is off. I've reduced the dose to quite a small amount (40mg white willow bark), so the effect doesn't always leave me feeling terrible, but something is still off. For reference, that lower dose is still within the realm of benefits, per the study Haidut posted: "Basically, the two doses that they found effective were equivalent to a human dose of 41mg/kg and 82mg/kg of the willow bark extract".

For reference, I am highly sensitive to supplements and food, and am in a hair-trigger allergic state; so, I don't take aspirin every day--maybe a few times a week.

 

[Mossy]

I thought this would be a good one to ask the man himself. If I get a response (usually do), I'll share.

Great--thank you.

 

[ddjd]

Hey Joeyd, it's exactly as you stated! It does send me off to sleep, but I do wake up feeling like something is off. I've reduced the dose to quite a small amount (40mg white willow bark), so the effect doesn't always leave me feeling terrible, but something is still off. For reference, that lower dose is still within the realm of benefits, per the study Haidut posted: "Basically, the two doses that they found effective were equivalent to a human dose of 41mg/kg and 82mg/kg of the willow bark extract".

For reference, I am highly sensitive to supplements and food, and am in a hair-trigger allergic state; so, I don't take aspirin every day--maybe a few times a week.

out of interest, did you ever get your 23andme genetic testing done?