Citrulline increases muscle mass and reduces fat mass by blocking the aging process

If you are heading towards old age, a daily dose of the alpha amino acid L-citrulline may help reduce the amount of fat and increase the amount of muscle you have. Researchers at the Sorbonne in France suggest this in an animal study they published in the Journal of Nutrition. Citrulline has a positive effect on body composition because it blocks aging processes at a fundamental level.

The researchers did an experiment with rats aged 20 weeks, ‘young elderly’. They gave the animals 1 g citrulline per kg bodyweight [structural formula on the right] every day for 12 weeks, or 1 g of a mixture of other non-essential amino acids. The human equivalent of the dose used would be 0.16 g per kg bodyweight.

At the end of the supplementation period the rats in both groups weighed the same, but their body composition was different. The animals that had been given citrulline had 13 percent less fat and 9 percent more lean body mass than the animals that had been given the mix of non-essential amino acids.



The figure above shows that the rats in the citrulline group had 14-48 percent more muscle mass after the supplementation than the animals in the other group.

The citrulline supplementation had no relevant effect on the anabolic signal molecule mTOR, but cells did manufacture more proteins such as TFAM as a result of the supplementation. These proteins enable cells to build up and repair more mitochondria. Mitochondria convert nutrients into energy.

NEAA = rats that were given non-essential amino acid mix in their food; CIT = rats that were given citrulline.


This suggests that citrulline delays aging. During the process of aging the number of mitochondria in all cells decreases and their quality declines too. The result is that tissue dies off as the energy supply decreases and the mitochondria start to produce more and more aggressive oxygenated radicals.

Citrulline seems to reduce this last aspect of aging. At least, the researchers found less oxidised LDL in the rats’ blood. Oxidised cholesterol is bad news for the blood vessels, so this effect of citrulline is also positive.

“Citrulline treatment in male aged rats favourably modulates body composition and protects against lipid oxidation and, thus, emerges as an interesting candidate to help prevent the aging process”, the researchers concluded. “Our results provide a strong rationale for promoting trials with citrulline in humans.”

The study was financed by the French Association Against Myopathies. The first author and two other co-authors of the study work for the French company Citrage [citrage.com]. Citrage sells citrulline supplements designed to maintain muscle strength.

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


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

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

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.

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 ?mol/L vs. 243 ± 7 ?mol/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. PMID: 26019250 [PubMed - indexed for MEDLINE] Source: http://www.ncbi.nlm.nih.gov/pubmed/26019250

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