How citrulline keeps muscles strong during physiological stress
According to previously published studies, supplementation with citrulline may be an interesting option if you want to retain or build muscle mass if you consume few calories or if there are few proteins in your diet. Researchers at Inserm in France studied the effect of citrulline on muscle cells – and discovered why.
Few amino acids
The researchers put muscle cells in test tubes, and mimicked the conditions that you find under normal conditions [Ctrl], in people with a low protein diet [AA/serum-] and in people with a low protein diet who supplement with supplement with L-citrulline [AA/serum + Cit].
The researchers then looked at the amount of energy [actually: ATP] that the muscle cells invested in a number of processes, one of which was the production of muscle protein. They discovered that as the supply of amino acids diminishes, the muscle cell primarily reduces the synthesis of muscle protein. Citrulline supplementation, however, put an end to this cellular austerity measure.
The researchers also simulated the effects of an muscular energy deficit in their test tubes. In organisms these effects occur for example as a result of a low-calorie diet or extreme exertion – and as a consequence of the use of the downright dangerous killer drug DNP.
DNP sabotages the conversion of energy from nutrients into energy phosphate in the cells, and forces cells to release that energy as heat instead. As a result, cells must continuously convert nutrients into energy, and the energy consumption of the body increases drastically.
Under standard conditions, the amino acid leucine was the best booster of muscle protein synthesis, the researchers found. But under energy stress caused by DNP, citrulline provided the most powerful anabolic or anti-catabolic stimulus.
“The consensus view that amino acid availability is the major limiting step in protein synthesis has prompted the idea that citrulline may stimulate protein synthesis after protein/energy deficiency by acting as a nitrogen source”, write the researchers. “However, this hypothesis can be ruled out, because ARG (arginine) did not stimulate protein synthesis in the relevant incubation condition.”
“This work adds decisive evidence to the earlier ideas of a hierarchical arrangement of ATP-consuming processes [Biochem J. 1995 Nov 15;312(Pt1):163-7.] with protein synthesis being very sensitive to a decrease in ATP/ADP ratio. While many of these bioenergetic effects can be explained today by signalling pathways like those linked to AMPK, the effects of citrulline that we observed were not accompanied by any change in ATP/ADP ratio, respiration, or AMPK activation.”
“We propose that it is the hierarchy of ATP allocation to different ATP-consuming processes that is altered, for example, by a decrease in the activation energy of one or several enzymatic step(s) involved in or controlling protein synthesis.”