Which is better arginine and citrulline

When we consume arginine, an enzyme called nitric oxide synthase NOS for short breaks it down into a gas called nitric oxide NO for short and citrulline. That citrulline then heads to the kidneys, which recycle it back into arginine so the cycle can continue. When we consume citrulline, it travels straight to the kidneys to transform into arginine and start the same cycle.

That nitric oxide gas both arginine and citrulline eventually produce holds the ticket to their health and fitness benefits. Because it increases blood flow throughout the body. Together, these factors help muscles function at their best and delay fatigue. What does that mean for your workouts? Improved endurance, performance, and recovery, says Antonio Castillo M. Science backs this up: According to a study of 22 male cyclists published in the Journal of the International Society of Sports Nutrition , athletes who supplemented with 2.

Meanwhile, study of 56 male soccer players published in the European Journal of Clinical Nutrition found that athletes who supplemented with two grams of arginine for 45 days saw significant improvements in their VO2 max a measure of how efficiently the body uses oxygen. The NO-producing amino acids offer similar benefits for strength-training athletes, too. When arginine is catabolized by arginase, the products are urea, ornithine, polyamines and proline, and when degraded by iNO, the products are a large amount of NO and citrulline In the innate immune system, the NO produced in macrophages and neutrophils is necessary to kill invasive microorganisms such as viruses, bacteria, and fungi and tumor cells With arginine deficiency, both the innate and adaptive immune responses are impaired and are associated with sepsis and inflammatory conditions such as bacteremia and endotoxemia 2 — 5.

When arginine is deficient, NO production is then limited, thereby increase host susceptibility to invading pathogens However, with all these studies currently, the majority of them focus on the adult population or the adult animals. Studies that focus on the pathophysiology mechanism and intervention with arginine or citrulline in the pediatric population remain scarce.

Recently we found that L-arginine could enhance neonatal Treg related IL production We then tried to mimic the pediatric population with our animal study design which not only explored the effects in which both L-arginine and L-citrulline therapy on innate and the adaptive immune, but also studied the regulatory mechanism of these immune responses. We demonstrated that supplementation of L-arginine and L-citrulline have distinct role in the immune modulation of T cells via cytokines production and regulation in infant rats.

These amounts are within the range of doses used in previous literatures 37 , Citrulline is an amino acid which is a precursor and a metabolite of arginine and its effects in the immune cells are thus partly related to arginine.

An impaired conversion of citrulline to arginine by argininosuccinate synthase ASS results in immune dysfunction, increased susceptibility to infections and decreased NO production 40 , A study by Breuillard et al.

Similar to the observed decreased arginine concentration in sepsis and endotoxemia, a reduced citrulline production and bioavailability is also noted in sepsis, endotoxemia and inflammatory conditions 20 , Several studies had tried to evaluate the supplementation of citrulline in models of sepsis and had found citrulline to be a more productive arginine precursor than arginine 44 , Early experimental studies have also suggested its therapeutic potential to restore arginine metabolism in critically ill patients with sepsis 3 , Asgeirsson et al.

These inconsistent results may due to different species of rats as well as a different age group of the study subjects. In cell culture study, we used an arginine-enriched medium, and this may also contribute to different consequence. Thus, L-arginine and L-citrulline supplementation have different modulatory effect for T-cells function of infants Figure 6. To our knowledge, this is the first experiment on the modulatory effect of L-citrulline on Treg response in the literature.

Figure 6. L-arginine and L-citrulline supplementation modulate the Treg function distinctly for infants. More than different effects, it seems that L-citrulline supplementation has a more potent effect than L-arginine supplementation in the modulation of the immune response for newborn.

Once L-arginine is orally administered, it is extensively catabolized by arginase in the gut and liver 45 , This may limit its bioavailability as a substrate for NOS Previous reports demonstrated that L-citrulline is an potent precursor of L-arginine, thus contributing to sustained L-arginine supply for nitrogen homeostasis L-citrulline supplementation was even observed to increase plasma L-arginine levels in healthy human volunteers more effectively than L-arginine itself in equivalent dose In contrast to L-arginine, previous researches have demonstrated that L-citrulline suppresses arginase activity, acting as a strong allosteric inhibitor Collaborate with more abundant arginase in neonatal leukocytes 18 , these could explain the more potent effect of L-citrulline than L-arginine in the modulation of the immune response for newborn.

SIRT-1 is a class III histone deacetylase and its immune regulatory role has become more prominent in recent years study. SIRT1 is well known to involve extensively in many physiological as well as pathological conditions such as aging, cancer, neurodegenerative diseases and metabolic processes The regulatory role of SIRT-1 in the immune system has been revealed recently.

NO plays an important role in many physio-pathological conditions in brain, either as a signaling molecule or as a cytotoxic host defense mechanism 60 , Adequate NO generation is dependent on proper supply of L-arginine. Under proin flammatory conditions, argininosuccinate synthetase expression is increased in glioma cells and astroglial cultures, a functional role in the recycling of L-citrulline to generate L-arginine for the production of NO has been demonstrated In neonatal hypoxia-ischemia model, excessive NO combine with superoxide radicals to produce oxidative stress and result in mitochondrial dysfunction and neuronal toxicity has been demonstrated Thus, the effects of both L-arginine and L-citrulline on neonatal brain and potential neuroinflammatory responses need to be further studied.

Our study has several limitations. First, we administrated the amino acids via intraperitoneal injection rather than oral supplementation. This is because we wanted to study the supplementary effects of indicated amino acids for infant rats while they are still un-weaned. Thus, we do not know whether the immune regulatory effect of indicated amino acid supplementation via a different route will be similar or not. Besides, we did not use arginine free culture medium for cell culture and thus might mask or influence the possible effects of the supplementation of arginine or citrulline on the immune response.

However, we have provided evidences showing the sustained immune regulatory effects of L-arginine and L-citrulline supplementations even when splenocytes are later culture in amino acid enriched medium.

While supplement with L-arginine and L-citrulline to infantile rats have distinct Treg immune modulatory effects. Exogenous supplementation of indicated amino acids has the potential to be a strategy for infants in immune dysregulated conditions.

All authors have read and approved the final manuscript and agreed to be accountable for all aspects of the work. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Arginine deficiency in preterm infants: biochemical mechanisms and nutritional implications.

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Prenatal dexamethasone and postnatal high-fat diet decrease interferon gamma production through an age-dependent histone modification in male sprague-dawley rats. J Mol Sci. Dwyer JM, Johnson C. The use of concanavalin A to study the immunoregulation of human T cells. Supporting Information. Figure S1. Figure S2. Figure S3. Figure S4. Figure S5. Table S1. Methods S1. Detailed information of material and methods used in this study. Video S1.

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