Pros and cons of L-arginine supplementation in disease

Vissers, Yvonne L. J.; Debats, I.B.J.G.; Luiking, Yvette C.; Jalan, Rajiv; Hulst, René R. W. J. van der; Dejong, Cornelis H. C.; Deutz, N.E.P.

doi:10.1079/nrr200490

Cited by 12 publications

(5 citation statements)

References 244 publications

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“…Polyamines are important mediators of cell growth, and proline is a precursor of collagen synthesis and the production of extracellular matrix molecules by fibroblasts (18,29). These processes normally involve an increased demand and use of arginine, but these factors were not observed in our nonunion patients.…”

Section: Discussionmentioning

confidence: 68%

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Impaired fracture healing associated with amino acid disturbances

Wijnands¹,

Brink²,

Weijers³

et al. 2012

The American Journal of Clinical Nutrition

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Section: Discussionmentioning

confidence: 68%

“…In conditions of stress, such as wound healing and inflammation, arginine metabolism changes, and arginine availability is probably limited (15)(16)(17)(18). These effects are partly due to the increased activity of arginase, which converts arginine into ornithine and urea and results in decreased plasma arginine concentrations.…”

Section: Introductionmentioning

confidence: 99%

Impaired fracture healing associated with amino acid disturbances

Wijnands¹,

Brink²,

Weijers³

et al. 2012

The American Journal of Clinical Nutrition

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“…This positive enhancement of the plasma arginine concentration was also present in the arginase-treated group, which strengthens our hypothesis that citrulline may be the preferred substrate to increase the arginine availability in arginine-deficient conditions. In addition, gastrointestinal complaints after the intake of large l -arginine amounts are not observed in studies with large oral l -citrulline amounts [ 43 , 53 , 54 , 55 ]. Furthermore, in humans, l -citrulline supplementation is a good therapeutic strategy to combat splanchnic hypoperfusion-induced intestinal compromise in strenuous exercise, as this resulted in an increased number of perfused small sublingual vessels and prevention of splanchnic hypoperfusion and gastrointestinal damage [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity

et al. 2015

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Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with l-arginine supplementation exhibited less consistent results; however, l-citrulline, the precursor of l-arginine, may be a promising alternative. In this study, we determined the effects of l-citrulline compared to l-arginine supplementation on arginine-nitric oxide (NO) metabolism, arginine availability and microcirculation in a murine model with acutely-enhanced arginase activity. The effects were measured in six groups of mice (n = 8 each) injected intraperitoneally with sterile saline or arginase (1000 IE/mouse) with or without being separately injected with l-citrulline or l-arginine 1 h prior to assessment of the microcirculation with side stream dark-field (SDF)-imaging or in vivo NO-production with electron spin resonance (ESR) spectroscopy. Arginase injection caused a decrease in plasma and tissue arginine concentrations. l-arginine and l-citrulline supplementation both enhanced plasma and tissue arginine concentrations in arginase-injected mice. However, only the citrulline supplementation increased NO production and improved microcirculatory flow in arginase-injected mice. In conclusion, the present study provides for the first time in vivo experimental evidence that l-citrulline, and not l-arginine supplementation, improves the end organ microcirculation during conditions with acute arginase-induced arginine deficiency by increasing the NO concentration in tissues.

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“…Previous meta-analysis and systematic reviews evaluated the value of enhanced nutrition as a possible additional treatment in surgical patients and critically ill patients. Most studies using arginine as supplement [ 271 , 272 ] investigated a combination of different nutrition compounds [ 134 , 273 ], such as omega-3-fatty-acids, glutamine [ 31 , 274 , 275 ], or nucleotides [ 275 ], unfortunately all with different results. A prospective, randomized, double-blind, placebo-controlled study in ICU patients, used oral arginine supplementation added to the enteral nutrition which resulted in enhanced arginine and ornithine concentrations, possibly by an increased arginase activity in this patient population without an enhancement of the NO production [ 276 ].…”

Section: Enhancement Of Arginine and Citrulline Availability In Sementioning

confidence: 99%

Arginine and Citrulline and the Immune Response in Sepsis

et al. 2015

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Arginine, a semi-essential amino acid is an important initiator of the immune response. Arginine serves as a precursor in several metabolic pathways in different organs. In the immune response, arginine metabolism and availability is determined by the nitric oxide synthases and the arginase enzymes, which convert arginine into nitric oxide (NO) and ornithine, respectively. Limitations in arginine availability during inflammatory conditions regulate macrophages and T-lymfocyte activation. Furthermore, over the past years more evidence has been gathered which showed that arginine and citrulline deficiencies may underlie the detrimental outcome of inflammatory conditions, such as sepsis and endotoxemia. Not only does the immune response contribute to the arginine deficiency, also the impaired arginine de novo synthesis in the kidney has a key role in the eventual observed arginine deficiency. The complex interplay between the immune response and the arginine-NO metabolism is further underscored by recent data of our group. In this review we give an overview of physiological arginine and citrulline metabolism and we address the experimental and clinical studies in which the arginine-citrulline NO pathway plays an essential role in the immune response, as initiator and therapeutic target.

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Pros and cons of L-arginine supplementation in disease

Cited by 12 publications

References 244 publications

Impaired fracture healing associated with amino acid disturbances

Impaired fracture healing associated with amino acid disturbances

Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity

Arginine and Citrulline and the Immune Response in Sepsis

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