Noo much NO (nitric oxide toxicity)

[nothuman]

Anyone know much about this and how common it is? And what symptoms it could cause? I realize I consume an outrageous amount.

 

[Elvia1023]

Your post made me think of a certain study. Whilst it's not directly related I think it's very interesting nonetheless. It was done on rats so that's something that needs to be taken into consideration but I do think there would be a cross over effect in humans and that's been shown in other studies. The equivalent dose for humans would be 160mg per kg so for a 100kg (220lbs) guy that is 16g per day.

Citrulline Supplementation Induces Changes in Body Composition and Limits Age-Related Metabolic Changes in Healthy Male Rats.

Moinard C1, Le Plenier S2, Noirez P2, Morio B3, Bonnefont-Rousselot D4, Kharchi C5, Ferry A6, Neveux N7, Cynober L7, Raynaud-Simon A8.

BACKGROUND:

Aging is associated with profound metabolic disturbances, and citrulline may be of use to limit them.

OBJECTIVE:

The aim of this work was to evaluate the long-term effect of citrulline supplementation on metabolism in healthy aged rats.

METHODS:

Twenty-month-old male rats were randomly assigned to be fed (ad libitum) for 12 wk with either a citrulline-enriched diet (1 g ⋅ kg(-1) ⋅  d(-1)) or a standard diet [rendered isonitrogenous by addition of nonessential amino acids (NEAAs)]. Motor activity and muscle strength were measured, body composition was assessed, and muscle metabolism (protein structure, mitochondrial exploration, and transductional factors) and lipid metabolism (lipoprotein composition and sensitivity to oxidative stress) were explored.

RESULTS:

Compared with the NEAA-treated group, citrulline supplementation was associated with lower mortality (0% vs. 20%; P = 0.05), 9% higher lean body mass (P < 0.05), and 13% lower fat mass (P < 0.05). Compared with the NEAA-treated group, citrulline-treated rats had greater muscle mass (+14-48% depending on type of muscle; P < 0.05 for tibialis, gastrocnemius, and plantaris). Susceptibility to oxidation of lipoproteins, as measured by the maximal concentration of 7-ketocholesterol after copper-induced VLDL and LDL oxidation, was lower in citrulline-treated rats than in NEAA-treated rats (187 ± 8 μmol/L vs. 243 ± 7 μmol/L; P = 0.0005).

CONCLUSIONS:

Citrulline treatment in male aged rats favorably modulates body composition and protects against lipid oxidation and, thus, emerges as an interesting candidate to help prevent the aging process.

 

[Elvia1023]

Here is a new and very detailed write up on l-citrulline...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073798/

Including...

A major limitation of l-citrulline research to date is the short-term nature of most of the intervention periods of study. Long-term studies (>6 months) investigating the effects of l-arginine supplementation have demonstrated a concerning lack of safety and efficacy with respect to improvements in blood pressure regulation [171,172]. Basic mechanistic studies in human umbilical endothelial cells have shown that repeated exposure to l-arginine promotes oxidative stress by increased superoxide formation and reduced eNOS protein expression [173]. It is thus plausible that prolonged exposure to l-arginine promotes cellular tolerance and maladaptation. The safety and efficacy of long-term l-citrulline supplementation therefore requires further investigation. Finally, except for pharmacokinetic studies, most l-citrulline supplementation studies fail to report the plasma/serum concentrations that were achieved.

In conclusion, l-citrulline is a unique amino acid that exerts its effects on cardiometabolic health via direct and indirect pathways. The variety of applications for which l-citrulline has been utilized underscores the importance of l-citrulline in vascular health, protein metabolism, and lipid metabolism. However, the direct role of l-citrulline, outside of its function as a precursor of l-arginine, is still not well characterized. The interaction of l-citrulline with other pharmaceutical drugs for the treatment of hypertension, atherosclerosis, insulin resistance, T2D, and cardiovascular disease should also be investigated, as some of these drugs have been shown to affect citrulline metabolism [13,174,175].

 

[Kaladryn]

You know there is also a whole debate on whether increased vasodilation is a good thing. In sports like rock climbing, the "pump" is a bad thing. In bodybuilding, the pump is a good indicator, perhaps, that the whole muscle has been stimulated, it's a good way to improve mind-muscle connections, and maybe pre-exhaust the muscle but ultimately I think it makes me weaker when the muscle gets pumped. Does the pump promote or cause anything? Or is it just an effect?

 

[chopsuey]

I always wondered if it's bad to jack up/sustain NO too much too( like by taking citruline multiple times per day with cialis etc)

Interesting article here:

https://redlightman.com/blog/red-light-therapy-treats-erectile-dysfunction

They have references but its a bit over my head, not sure what to make of it. From my understanding, I suggest reading the whole thing after the Nitric Oxide bullet but here's an excerpt:

"Mentioned above as a metabolic inhibitor, NO actually has various other effects on the body, including vasodilation[3,7]. NO is produced from arginine (an amino acid) in our diet by an enzyme called NOS. The problem with too much sustained NO (from stress/inflammation, environmental pollutants, high-arginine diets, supplements) is it can bind to respiratory enzymes in our mitochondria, preventing them from using oxygen. This poison-like effect prevents our cells from producing energy and carrying out basic functions. The main theory explaining light therapy is that red/infrared light might be able to photodissociate NO from this position, potentially allowing mitochondria to function normally again (see Fig 4.)."

So from my understanding too much NO binds to michondria causing problems/can't be used for regular function since tied up?

 

[Elvia1023]

You know there is also a whole debate on whether increased vasodilation is a good thing. In sports like rock climbing, the "pump" is a bad thing. In bodybuilding, the pump is a good indicator, perhaps, that the whole muscle has been stimulated, it's a good way to improve mind-muscle connections, and maybe pre-exhaust the muscle but ultimately I think it makes me weaker when the muscle gets pumped. Does the pump promote or cause anything? Or is it just an effect?

So many factors but I think for bodybuilding getting a great pump is only a positive thing (when most of the time). In many ways it goes back to the training thread and if you can build muscle using lighter weights. Although I get an amazing pump with heavy or light weights. I like to use a combination of the two and usually in the same workout. Generally a big lift then finish with something to swell the muscle as much as possible and get as much blood in there. It is true though that sometimes if you overdo nitric oxide (pump) products it may go against you and negatively effect your training. That's why there needs to be balance in my eyes. Although sometimes I will dose cialis, pump product (citrulline, glycerol, arginine etc), electrolytes, carbs and plenty of water and just go for it

I always wondered if it's bad to jack up/sustain NO too much too( like by taking citruline multiple times per day with cialis etc)

Interesting article here:

https://redlightman.com/blog/red-light-therapy-treats-erectile-dysfunction

They have references but its a bit over my head, not sure what to make of it. From my understanding, I suggest reading the whole thing after the Nitric Oxide bullet but here's an excerpt:

"Mentioned above as a metabolic inhibitor, NO actually has various other effects on the body, including vasodilation[3,7]. NO is produced from arginine (an amino acid) in our diet by an enzyme called NOS. The problem with too much sustained NO (from stress/inflammation, environmental pollutants, high-arginine diets, supplements) is it can bind to respiratory enzymes in our mitochondria, preventing them from using oxygen. This poison-like effect prevents our cells from producing energy and carrying out basic functions. The main theory explaining light therapy is that red/infrared light might be able to photodissociate NO from this position, potentially allowing mitochondria to function normally again (see Fig 4.)."

So from my understanding too much NO binds to michondria causing problems/can't be used for regular function since tied up?

I don't know but that's why I take breaks from everything especially the likes of cialis and citrulline. I like to run most things in cycles including many of my supplements.