Citrulline increases mTOR

In case this isn’t commonly known. I was surprised to read that citrulline increases mTOR. “On the other hand, it has been shown that CIT can stimulate the mammalian Target of Rapamycin (mTOR) pathway, independent of insulin, the growth hormone (GH) or type 1 insulin-like growth factor (IGF1), improving muscle protein synthesis (MPS) [[15]”(Combined Effects of Citrulline Plus Nitrate-Rich Beetroot Extract Co-Supplementation on Maximal and Endurance-Strength and Aerobic Power in Trained Male Triathletes: A Randomized Double-Blind, Placebo-Controlled Trial - PMC)]


Yes, The nutrient sensing system activates mTOR when you take citrulline. In the same way that other nutrients activate mTOR. But Citrulline might also have mTOR independent pathways for preserving or building muscle.

A poster from the Gordon Lynch lab:

“Both citrulline and arginine increase mTOR phosphorylation and protein synthetic rate in an in vitro model of starvation. Importantly, mTOR phosphorylation is critical for the protective effects of arginine, but not citrulline, on skeletal muscle. Therefore, citrulline may attenuate muscle wasting in vitro by directly activating proteins downstream of mTOR, such as 4EBP1.”

Citrulline supports healthy muscles in other ways than through mTOR activation. Through increased whole body blood perfusion. Most people know that hypoperfusion is damaging to the brain, but the same goes for the rest of our organs. And aging comes with decreased blood circulation throughout the entire body. Especially when it comes to people with tendencies toward metabolic dysfunction. I think an optimized vascular system is a somewhat overlooked perspective. Therefore, I am glad to see the relatively new interest in the off-target effects of Viagra/Cialis.

“Furthermore, L-citrulline prevented inflammation (LPS) and oxidative stress (H2O2) induced muscle cell wasting. In conclusion, we demonstrate a novel direct protective effect of L-citrulline on skeletal muscle cell size independent of L-arginine that is mediated through induction of the inducible NOS (iNOS) isoform. This discovery of a nutritional modulator of iNOS mRNA expression in skeletal muscle cells could have substantial implications for the treatment of muscle wasting conditions.”

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

" 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"


Thanks for the info. Citrulline seems like a worthy add despite my desire to reduce supplementation. I won’t take it on rapa day, though.

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Beet root :face_vomiting: citrulline malate :nauseated_face: though not as bad as beet root (it’s sort of okay with sodium bicarbonate though). I was thinking of getting isosorbide dinitrate or just plain nitroglycerine instead though (they beneficial effect is due to that all these are all nitrate donors)

(oh and they do not work in combination with caffeine!)

Yes, I have seen it mentioned that caffeine and beet juice do not interact well, and that they might cancel out each other’s effect on performance.

  1. I’d be grateful If you have human studies to share on the subject?

  2. I have read anecdotal reports that some can mix caffeine and beet juice and do well, and others say that they (when mixing) do worse, when it comes to aerobic performance. But I have not read that people do worse (performance-wise) when combining citrulline and caffeine.

  3. I know that in my case, too much citrulline before aerobic exercise, decrease my endurance. I get too much blood in my quadriceps, and my legs feel heavy. Some kind of pump that makes running more difficult

Take L-Citrulline instead of Citrulline Malate to avoid the sour taste

  1. I have found a few studies on how caffeine and beet juice might interact. None can be said to be convincing. Some showed no effect from combining them, and one showed a positive effect.
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@John_Hemming so taking Citrulline with meals as mTOR was activated anyhow at that time?