L-Citrulline Supports Vascular and Muscular Benefits of Exercise Training in Older Adults

madman

Member
Age-associated reduction in endothelial nitric oxide (NO) synthesis contributes to the development of cardiovascular diseases and sarcopenia. L-Citrulline is a precursor of NO with the ability to improve vascular function and muscle protein synthesis. We hypothesize that vascular and muscular benefits associated with oral L-citrulline supplementation might be augmented by concomitant supplementation with exercise training in older adults.







Key Points

Aging is associated with hypertension and reduced muscle mass and strength (quality) that may be mediated by impaired nitric oxide bioavailability.

Oral L-citrulline increases plasma L-arginine and nitric oxide production.

L-Citrulline supplementation improves muscle protein synthesis, muscle mass, and oxygen delivery that may benefit exercise performance.

Combined with exercise training, L-citrulline may benefit vascular and muscular function via improvements in nitric oxide bioavailability and muscle protein synthesis in older adults.







SUMMARY

Evidence continues to emerge on the positive impact of chronic L-CIT on vascular and skeletal muscle function in older adults. L-CIT may improve exercise capacity by upregulating muscular perfusion and subsequent oxygen utilization. Evidence suggests that increased L-ARG and NO availability in skeletal muscle may be a crucial factor in promoting muscle function via PGC-1α stimulation of mitochondrial respiratory capacity. In addition, the action of L-CIT on muscle function also is related to its ability to promote muscle protein synthesis. Indeed, there are many studies that establish a continuum between experimental and clinical research that confirms its action. Although animal research is revealing the mechanistic insight upon how L-CIT positively alters the regulation of these physiological systems, human research is highlighting the effect of L-CIT on exercise performance and adaptations with exercise training. Future research is still needed to decipher the contribution of endothelial versus neuronal NO production to the vascular and muscular benefits observed after L-CIT supplementation to fully understand the ergogenic and therapeutic potential of this amino acid. More studies will be needed to investigate the additive clinical benefits of L-CIT supplementation and exercise training on arterial and muscle functions in older adults.
 

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madman

Member
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Figure 1. Potential mechanisms by which aging impairs vascular function
(A) and oral L-CIT may improve age-related vascular dysfunction (B). L-ARG is catabolized by the enzyme arginase into urea and L-ornithine (1). Age-related increased NADPH oxidase (NOx) activity increases superoxide anion (O2 −) production (2) and contributes to decrease BH4, leading to eNOS uncoupling (3). Uncoupled eNOS produces O2 −, which reacts with NO to produce peroxynitrite (ONOO−) (3), a substance that causes oxidative cell damage. The resultant low NO fails to properly activate the guanylate cyclase (GC)–GTP–cGMP signal transduction pathway, leading to impaired vasodilation (4). L-Ornithine produced by arginase increases the production of polyamine and proline, resulting in collagen synthesis and cell proliferation contributing to arterial stiffness (5). Oral L-CIT supplementation increases L-ARG bioavailability for eNOS by greater de novo synthesis (6) and inhibition of arginase activity (7), resulting in improved NO-mediated vasodilation (8) and decreased arterial stiffness (9). The precise mechanism by which L-CIT may decrease arterial stiffness is yet unknown.
 

madman

Member
Screenshot (1533).png

Figure 2. Purported mechanisms by which L-CIT improves exercise performance alone and combined with exercise training. De novo synthesis of L-ARG (1) from circulating L-CIT increases nNOS (nNOSμ) activity in the skeletal muscle (2). NO produced by nNOSμ stimulates expression of PGC-1α (3), a regulator of mitochondrial respiration. Improved peripheral NO-mediated vasodilation and subsequent muscle oxygen utilization in active skeletal muscles contribute to enhance exercise performance (4). An enhanced mitochondrial respiratory capacity from the combined effect of PGC-1α expression and O2 availability from vasodilation contributes to improve exercise performance (5). Moreover, L-CIT directly promotes muscle protein synthesis by stimulation of the mTORC1 pathway, which involves increased phosphorylation of S6K1 and 4E-BP1 (6). This effect of L-CIT on protein synthesis may improve muscle mass or strength when combined with exercise training in obese older adults (7 and 8). Enhanced mitochondrial metabolism and skeletal muscle function may contribute to improve exercise performance. *NO produced by nNOS may contribute to vasodilation after L-CIT supplementation.
 

DFW Guy

New Member
i have been taking one capsule of this combination. i have NOT noticed any positive changes whether it be sexually or athletically (pumps at gym, jogging). i may scrap the capsules and switch to citrulline bulk powder and evaluate it.

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madman

Member
i have been taking one capsule of this combination. i have NOT noticed any positive changes whether it be sexually or athletically (pumps at gym, jogging). i may scrap the capsules and switch to citrulline bulk powder and evaluate it.

View attachment 9938
That is a horribly low dose.

Aim for at least 2-3 grams of citrulline split twice daily.

Most are using 6 grams of citrulline daily (3 grams twice/day).
 

madman

Member



Table 1. Plasma l-arginine area under the curve (AUC) after 1 week of different l-citrulline and l-arginine dosing regiment.
Screenshot (1535).png

 
Last edited:

madman

Member
i have been taking one capsule of this combination. i have NOT noticed any positive changes whether it be sexually or athletically (pumps at gym, jogging). i may scrap the capsules and switch to citrulline bulk powder and evaluate it.

View attachment 9938

Forget capsules, the bulk powder is dirt cheap 1KG

Screenshot (1536).png





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Jungle Cruiser

New Member
FWIW - I use about 6 to 9 grams Citrulline Malate and a like amount of AAKG per day.

That would not be economically feasible absent bulk powder. HR Supplements (they used to be called "Hard Rhino") is another legitimate source, and they can provide COAs. I have no affiliation with them - other than having ordered from them for several years.
 

BuzzSaw

Member
I'm on a low dose of viagra (25mg daily), will this affect taking Citrulline? Also, is there a Citrulline that is more bio available, or are they all the same? thanks.
 
Citrulline and Arginine are complementary to most PDE-5 inhibitors. They stimulate Nitric Oxide (NO) which can make those medicines work more efficiently. (Simplistic explanation, I am sure someone on here can give the scientific version)
 

BuzzSaw

Member
Madman do I have to worry about TMAO?
I just read this article not sure if it related or not to citrulline can you take a look at it plz
Just googles foods high in TMAO:

Trimethylamine is present in high levels in milk obtained from wheat-fed cows. Choline is present in high amounts in: eggs, liver, kidney, peas, beans, peanuts, soy products, brussels sprouts, broccoli, cabbage, and cauliflower. Trimethylamine N-oxide is present in seafood.
 

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