Arginine Aspartate Research Articles

The Effects of Arginine-Based Supplements on Fatigue Levels following COVID-19 Infection: A Prospective Study in Romania.

The purpose of this study was to examine the effects of two arginine-based supplements on the fatigue level of patients following the COVID-19 infection. This is a prospective study of the SARS-CoV-2-infected patients divided into two groups (according to family physicians' prescriptions, Group 1 of patients were treated with Astenor Energy® containing arginine aspartate, B6 vitamin, biotin and magnesium, and Group 2 of patients were treated with Astenor Forte® containing L-arginine and malic acid). The patients visited their family physicians from October 2021 to January 2022, complaining of physical and/or mental fatigue following the COVID-19 infection. We recorded 505 patients (146 patients in Group 1 and 359 patients in Group 2) and analyzed the fatigue level using the Fatigue Assessment Scale (FAS) through its total (FAS-T), mental (FAS-M) and physical (FAS-P) scores, at baseline and after three months of treatment. There was no difference between the two groups in terms of age (p = 0.265), but more men were included in Group 1 than in Group 2 (p = 0.001). The patients from Group 2 were significantly more likely to be treated at home than those included in Group 1 (89.7% vs. 65.1%, p < 0.0001) because of the lower severity of the COVID-19 infection (asymptomatic or mild: 82.5% vs. 48.7%, p < 0.0001). After 3 months of treatment, patients indicated no fatigue in the higher percentage compared to than at the baseline (68.7% vs. 27.7%), and the fatigue level significantly decreased both in Group 1 (median baseline 33.0 vs. follow-up 17.00, p < 0.0001) and Group 2 (median baseline 25.0 vs. follow-up 17.00, p < 0.0001). These findings suggest that supplements with L-arginine may be proposed as a remedy to restore physical and mental performance affected by the fatigue burden in people with COVID-19 or following the COVID-19 infection.

RGD-incorporated biomimetic cryogels for hyaline cartilage regeneration

Maintaining the integrity of articular cartilage is paramount to joint health and function. Under constant mechanical stress, articular cartilage is prone to injury that often extends to the underlying subchondral bone. In this study, we incorporated arginine–aspartate–glycine (RGD) peptide into chondroitin sulfate-based cryogel for hyaline cartilage regeneration. Known to promote cell adhesion and proliferation, RGD peptide is a double-edged sword for cartilage regeneration. Depending on the peptide availability in the microenvironment, RGD may aid in redifferentiation of dedifferentiated chondrocytes by mimicking physiological cell-matrix interaction or inhibit chondrogenic phenotype via excessive cell spreading. Here, we observed an increase in chondrogenic phenotype with RGD concentration. The group containing the highest RGD concentration (3 mM; RGD group) experienced a 24-fold increase in COL2 expression in the 1st week of in vitro culture and formed native cartilage-resembling ectopic tissue in vivo. No sign of dedifferentiation (COL1) was observed in all groups. Within the concentration range tested (0–3 mM RGD), RGD promotes chondrocyte redifferentiation after monolayer expansion and thus, formation of hyaline cartilage tissue.

Sexual and reproductive health: the science behind supplementation in aging

Introduction Throughout lifespan people are increasingly committed to take control of their own health and well-being, including fertility and sexual enhancement. Food supplements (FS) industry specifically caters for this segment market. However, FS are not medicines and thus, are not subject to the same strict regulations. Misbranded, unsafe and unlawful products are on the market [1], claiming scientifically unsubstantiated benefits, without disclosing potential side effects [2] and/or interactions [3], thus representing a public health hazard. The purpose of this work was to give an overview of the main FS intended for male and female sexual performance and reproductive health, available in Portugal. Materials and methods Consumption data in pharmacies (2015–2018) was provided by ANF and inclusion criteria was FS which sold >1000 units/year. Formulas were analysed, to address the alleged bioactive substances, in a perspective of efficacy and safety. Results Overall consumption of the FS studied has risen 48% in the years analysed and target mainly the male population (≈70% of products), although there are brands specifically designed for women. Botanicals, isolated or combined, used for sexual performance problems, such as erectile dysfunction and low sexual desire, mostly claim to: (a) improve genital blood flow [vasodilators as Pausinystalia macroceras, Ferula asafoetida L., Pinus pinaster, Gingko biloba, Epimedium grandiflorum L.], (b) increase testosterone levels [Withania somnifera, Tribulus terrestris, Maca- Lepidium meyenii], or (c) act as tonics/stimulants [Eleutherococcus senticosus, Panax ginseng, Turnera diffusa, guarana]. Plant extracts are at times associated with vitamins (A,D,E,C, folic acid), minerals (Zn, Se, Fe, Mg) and amino acids (arginine aspartate, L-carnitine). For fertility/climacterium associated symptoms, DHA, EPA, lycopene and CoQ10 are also found. Discussion and conclusions Scientific evidence to support the claims of sexual enhancement is low/medium for all the plants, which however are not without harm. There is lack of studies in humans, no established daily doses and many of the side effects (e.g. severe hepatotoxicity of genus Pausinystalia; estrogen-like effect of Maca in gynaecological cancers) are not well documented. Associations of bioactives are common and increase the potential of side effects/toxicity and should be avoided. Relevant interactions with drugs [e.g. MAO inhibitors with Pausinystalia and P. ginseng; anticoagulants (e.g. warfarin) with P. maritima, P. ginseng, E. senticosus, G. biloba, F. asafoetida, E. grandiflorum; antihypertensive drugs with T. terrestris, F. asafoetida, E. grandiflorum, W. somnifera and Pausinystalia] are also possible, especially in case of polymedicated aging consumers. Moreover, since potentially harmful active pharmaceuticals, or its analogs, continue to be identified in FS, consumers should be aware of the risk in which they incur. Informed counselling by health-professionals is thus of the utmost importance and the subject should be taught to doctors, pharmacists, nutritionists and nurses.

Pyruvate dehydrogenase complex deficiency: updating the clinical, metabolic and mutational landscapes in a cohort of Portuguese patients

BackgroundThe pyruvate dehydrogenase complex (PDC) catalyzes the irreversible decarboxylation of pyruvate into acetyl-CoA. PDC deficiency can be caused by alterations in any of the genes encoding its several subunits. The resulting phenotype, though very heterogeneous, mainly affects the central nervous system. The aim of this study is to describe and discuss the clinical, biochemical and genotypic information from thirteen PDC deficient patients, thus seeking to establish possible genotype–phenotype correlations.ResultsThe mutational spectrum showed that seven patients carry mutations in the PDHA1 gene encoding the E1α subunit, five patients carry mutations in the PDHX gene encoding the E3 binding protein, and the remaining patient carries mutations in the DLD gene encoding the E3 subunit. These data corroborate earlier reports describing PDHA1 mutations as the predominant cause of PDC deficiency but also reveal a notable prevalence of PDHX mutations among Portuguese patients, most of them carrying what seems to be a private mutation (p.R284X). The biochemical analyses revealed high lactate and pyruvate plasma levels whereas the lactate/pyruvate ratio was below 16; enzymatic activities, when compared to control values, indicated to be independent from the genotype and ranged from 8.5% to 30%, the latter being considered a cut-off value for primary PDC deficiency. Concerning the clinical features, all patients displayed psychomotor retardation/developmental delay, the severity of which seems to correlate with the type and localization of the mutation carried by the patient. The therapeutic options essentially include the administration of a ketogenic diet and supplementation with thiamine, although arginine aspartate intake revealed to be beneficial in some patients. Moreover, in silico analysis of the missense mutations present in this PDC deficient population allowed to envisage the molecular mechanism underlying these pathogenic variants.ConclusionThe identification of the disease-causing mutations, together with the functional and structural characterization of the mutant protein variants, allow to obtain an insight on the severity of the clinical phenotype and the selection of the most appropriate therapy.

Genome-wide identification, characterization and expression analysis of non-RD receptor like kinase gene family under Colletotrichum truncatum stress conditions in hot pepper.

Receptor like kinases (RLKs) are preserved upstream signaling molecules which regulate several biological processes from plant development to various stress adaptation programs. Non arginine aspartate (non-RD) a prominent class of RLKs plays a significant role in disease resistance and apoptosis in plants. In present investigation, a comprehensive in silico analysis for non-RD Kinase gene family as well as identification of gene structures, sequence similarity, chromosomal localization, gene duplication analysis, promoter analysis, transcript expression profiles and phylogenic studies were done. In this study, twenty-six genes were observed on nine out of twelve chromosomes. All these genes were clustered into five subfamilies under large monophyletic group termed as Interleukin-1 Receptor-Associated Kinase (IRAK) family. Some of the important physiochemical properties of twenty-six proteins are determined and ranged in the following order: (a) Amino acids size ranged from (620 to 1781) (b) Molecular weight ranged as of (70.11 to 197.11 KDa) and (c) Theoretical PI ranged from (5.69 to 8.63) respectively. Structural diversity in genomic structure among non-RD kinase gene family was identified and presence of pathogen induced cis regulatory elements including STRE, MYC, MYB, and W box were found. Expression profiles revealed the potential ability of three genes CaRLK1 from LRRXII and CaRLK15,16 from stress antifung subfamily were pointedly upregulated beyond the severe stress time period (9 DAI) in anthracnose resistant genotype PBC-80 in response to Colletotrichum truncatum infection. Subsequently, in silico studies from the available genome sequencing data helped us to identify candidate genes tangled in inducing disease resistance.

Characterization of a Functionally Unknown Arginine-Aspartate-Aspartate Family Protein From Halobacillus andaensis and Functional Analysis of Its Conserved Arginine/Aspartate Residues.

Arginine–aspartate–aspartate (RDD) family, representing a category of transmembrane proteins containing one highly conserved arginine and two highly conserved aspartates, has been functionally uncharacterized as yet. Here we present the characterization of a member of this family designated RDD from the moderate halophile Halobacillus andaensis NEAU-ST10-40T and report for the first time that RDD should function as a novel Na+(Li+, K+)/H+ antiporter. It’s more interesting whether the highly conserved arginine/aspartate residues among the whole family or between RDD and its selected homologs are related to the protein function. Therefore, we analyzed their roles in the cation-transporting activity through site-directed mutagenesis and found that D154, R124, R129, and D158 are indispensable for Na+(Li+, K+)/H+ antiport activity whereas neither R35 nor D42 is involved in Na+(Li+, K+)/H+ antiport activity. As a dual representative of Na+(Li+, K+)/H+ antiporters and RDD family proteins, the characterization of RDD and the analysis of its important residues will positively contribute to the knowledge of the cation-transporting mechanisms of this novel antiporter and the roles of highly conserved arginine/aspartate residues in the functions of RDD family proteins.

On the mechanism of photoinduced dimer dissociation in the plant UVR8 photoreceptor

UV-B absorption by the photoreceptor UV resistance locus 8 (UVR8) consisting of two identical protein units triggers a signal chain used by plants in connection with protection and repair of UV-B induced damage. X-ray structural analysis of the purified protein [Christie JM, et al. (2012) Science 335(6075):1492-1496] [Wu D, et al. (2012) Nature 484(7393): 214-220] has revealed that the dimer is held together by arginine-aspartate salt bridges. In this paper we address the initial processes in the signal chain. On the basis of high-level quantum-chemical calculations, we propose a mechanism for the photodissociation of UVR8 that consists of three steps: (i) In each monomer, multiple tryptophans form an extended light-harvesting system in which the La excited state of Trp233 experiences strong electrostatic stabilization by the protein environment. The strong stabilization singles out this tryptophan to be an efficient exciton acceptor that accumulates the excitation energy from the entire protein subunit. (ii) A fast decay of the locally excited state by charge separation generates the radical ion pair Trp285(+)-Trp233(-) with a dipole moment of ∼18 D. (iii) Key to the proposed mechanism is that this large dipole moment drives the breaking of the salt bridges between the two monomer subunits. The suggested mechanism for the UV-B-driven dissociation of the dimer that rests on the prominent players Trp233 and Trp285 explains the experimental results obtained from mutagenesis of UVR8.

Free Energy of Solvated Salt Bridges: A Simulation and Experimental Study

Charged amino acids are the most common on surfaces of proteins and understanding the interactions between these charged amino acids, salt bridging, is crucial for understanding protein-protein interactions. Previous simulations have been limited to implicit solvent or fixed binding geometry due to the sampling required for converged free energies. Using well-tempered metadynamics, we have calculated salt bridge free energy surfaces in water and confirmed the results with NMR experiments. The simulations give binding free energies, quantitative ranking of salt bridging strength, and insights into the hydration of the salt bridges. The arginine-aspartate salt bridge was found to be the weakest and arginine-glutamate the strongest, showing that arginine can discriminate between aspartate and glutamate, whereas the salt bridges with lysine are indistinguishable in their free energy. The salt bridging hydration is found to be complementary to salt bridge orientation with arginine having specific orientations.

A randomized, double‐blind, crossover, placebo‐controlled comparative clinical trial of arginine aspartate plus adenosine monophosphate for the intermittent treatment of male erectile dysfunction

Efficacy and safety of l-arginine aspartate 8 g combined with 200 mg of adenosine monophosphate (AA) with placebo (PL) alone for intermittent treatment of mild-to-moderate erectile dysfunction (ED) were compared. The study design was a double-blind, PL-controlled, two-way crossover randomized clinical trial with 26 patients. Efficacy was assessed by International Index of Erectile Function (IIEF) and two additional validated questionnaires [the Erection Hardness Score (EHS) and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS). During each crossover period, separated by a 2-week wash-out period, drugs were administered orally, 1-2 h before sexual intercourse. Primary endpoint was a change in the IIEF. Secondary endpoints were patient and investigator assessments of treatment success. Investigators' and patients' assessment of efficacy was significantly improved by the combination vs. PL (p = 0.01 and p = 0.04 respectively]. EHS and EDITS questionnaires were both improved by the combination (p = 0.015 and p = 0.017 respectively). There was no significant difference in terms of tolerance between AA and PL or severe adverse events. ED patients demonstrated significant improvements in all IIEF domains with the exception of the Sexual Desire and Orgasmic Domains when treated with AA compared with PL. This pilot phase II study showed that the on-demand oral administration at a high dosage of l-arginine aspartate-adenosine monophosphate combination may be effective in patients with mild-to-moderate ED, is very well tolerated and could be tested as a safe first-line therapy in a larger size phase III study.

The chronic oral administration of arginine aspartate decreases secretion of IGF‐1 and IGFBP‐3 in healthy volunteers

To investigate the effect of chronic oral arginine aspartate on the growth hormone (GH), GH-releasing hormone (GHRH), insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) secretions in healthy volunteers. Twenty-three healthy non-athlete volunteer males were administered arginine aspartate (30 g) orally once daily at 21:00 h for 21 consecutive days. Subjects were hospitalized on days 0, 1, 3, 5, 7, 14 and 21 of treatment. At each hospitalization, concentrations of GHRH, GH, IGF-1 and IGFBP-3 were measured over 4 h after arginine aspartate intake. GH, IGF-1 and IGFBP-3 concentrations were also determined over 12 h at days 0, 1 and 21. Compared with day 1, 4 h GH levels dropped at day 5 and subsequently rose to levels not significantly different from initial ones. The latter was substantiated by 12 h GH levels that did not significantly change from days 1 to 21. GHRH levels were not statistically different, although there was a trend in median values that seemed to inversely mirror those of GH. This dynamic over the course of the study for GH and GHRH was accompanied by a general decrease in IGF-1 and IGFBP-3. In healthy volunteers, a chronic oral treatment with 30 g/day arginine aspartate is followed by a decrease in IGF-1 and IGFBP-3 secretions.

Pyruvate dehydrogenase deficiency: identification of a novel mutation in the PDHA1 gene which responds to amino acid supplementation

The pyruvate dehydrogenase complex (PDHc) is an intramitochondrial multienzyme system, which plays a key role in aerobic glucose metabolism by catalysing the oxidative decarboxylation of pyruvate to acetyl-CoA. Genetic defects in the PDHc lead to lactic acidemia and neurological abnormalities. In the majority of the cases, the defect appears to reside in the E(1)alpha subunit, the first catalytic component of the complex. The report is on a 6-year-old Portuguese boy with mild neurological involvement and low PDHc activity with absence of E1alpha on immunoblotting analysis. Molecular studies showed a novel and "de novo" mutation in the PDHA1 gene, R253G. Treatment with arginine aspartate showed complete clinical and biochemical recovery. We hypothesise that arginine aspartate acts as a chemical or pharmacological chaperone, and suggest amino acid supplementation as a possible therapy in PDHA1 mutations with mild phenotypes. our results encourage the use of amino acid supplementation to overcome the metabolic/biochemical changes induced by PDHA1 gene specific mutations associated with mild PDHc phenotypes.

The influence of arginine supplementation on performance and metabolism in athletes : review article

Objective: The aim of this review was to investigate the effects of supplementation with mainly in combination with aspartate and / or other potentially ergogenic amino acids, on metabolism of substrates, endocrine parameters and in endurance and resistance athletes. Data sources: The database PUBMED was consulted, using the following keywords arginine, aspartate, performance and metabolism. The references in these articles were scanned for further relevant publications. Study section: Studies with oral or intravenous administration of arginine and / or aspartate alone or in combination with other amino acids were selected. Data extraction: Studies with at least six subjects and utilising a placebo-controlled design were analysed. Data synthesis: Seven studies with the combination of arginine aspartate and evaluation of the effect on in athletes were found and evaluated. In addition, further studies with arginine and combination with other amino acids were found and analysed in the same manner. Conclusions: No effect on selected parameters of metabolism or the endocrine system have been shown after oral or intravenous arginine aspartate or other combinations with arginine and aspartate. Neither were there any ergogenic effects in trained athletes after oral or intravenous arginine use, either alone or in combination with aspartate and / or other potentially ergogenic amino acids.

Influence of Chronic Supplementation of Arginine Aspartate in Endurance Athletes on Performance and Substrate Metabolism: A Randomized, Double-blind, Placebo-controlled Study

Influence of Chronic Supplementation of Arginine Aspartate in Endurance Athletes on Performance and Substrate Metabolism: A Randomized, Double-blind, Placebo-controlled Study

Efeitos da suplementação aguda de aspartato de arginina na fadiga muscular em voluntários treinados

A atividade física influi em mecanismos específicos responsáveis pela redução da produção de força e conseqüentemente à fadiga. A preocupação em melhorar o desempenho físico tem sido propostos; observamos que estudos dão atenção para reduzir acúmulos dos metabólitos que diminuem a fadiga durante o exercício físico intenso, usando aminoácidos conhecidos por induzir mudanças metabólicas, entre eles a arginina. O presente estudo teve como objetivo estudar o efeito da suplementação aguda de aspartato de arginina em indivíduos sadios treinados submetidos a um protocolo de exaustão em um cicloergômetro. Foram utilizados 12 indivíduos treinados do sexo masculino, idade de 22,6 ± 3,5 anos. Realizaram três testes 90 minutos após a administração em dose única do aspartato de arginina ou solução placebo, em um cicloergômetro, em que incrementos de cargas foram adicionados até a exaustão. Amostras sanguíneas foram obtidas para análises bioquímicas como: creatinina, uréia, glicose e lactato. Diferenças estatísticas não foram encontradas ao comparar os valores de Freqüência Cardíaca Máxima, Tempo Máximo e Carga Máxima e também ao comparar os resultados anteriores e posteriores ao teste para uréia, creatinina e glicose. As concentrações de lactato (mmol/l) apresentaram diferença estatística ao comparar os valores pré-teste (Controle: 2,2 ± 0,14; Arginina: 2,43 ± 0,23; Placebo: 2,26 ± 0,11) com valores pós-teste (Controle 10,35 ± 0,57; Arginina: 12,07 ± 0,88; Placebo: 12,2 ± 0,96), p &lt; 0,001. Os principais resultados deste estudo indicam que a administração aguda de aspartato de arginina não se mostrou efetiva em aumentar a tolerância à fadiga dos indivíduos avaliados e tratados no protocolo de teste incremental até a exaustão. Assim, podemos concluir que a dose utilizada não foi capaz de aumentar a tolerância à fadiga muscular.

Influence of Chronic Supplementation of Arginine Aspartate in Endurance Athletes on Performance and Substrate Metabolism

The intake of arginine aspartate has been shown to increase anabolic hormones like human growth hormone (hGH) and glucagon. The aim of our study was to investigate whether daily intake of two different dosages of arginine asparate during four weeks affects selected parameters of overtraining syndrome like performance, metabolic and endocrine parameters. Thirty male endurance-trained athletes were included in a randomized, double-blind, placebo-controlled study and divided into three groups. During four weeks, they ingested either arginine aspartate with a high concentration (H) of 5.7 g arginine and 8.7 g aspartate, with a low concentration (L) of 2.8 g arginine and 2.2 g aspartate or placebo (P).VO(2)peak and time to exhaustion were determined on a cycling ergometer in an incremental exercise test before and after supplementation. Before and after each incremental exercise test, concentrations of hGH, glucagon, testosterone, cortisol, ferritine, lactate, and urea were measured. Compared to placebo, no significant differences on endurance performance (VO(2)peak, time to exhaustion), endocrine (concentration of hGH, glucagon, cortisol, and testosterone) and metabolic parameters (concentration of lactate, ferritine, and urea) were found after chronic arginine aspartate supplementation. The chronic intake of arginine asparate during four weeks by male endurance athletes showed independent of dosage no influence on performance, selected metabolic or endocrine parameters. Consequently, there seems to be no apparent reason why the supplementation of arginine aspartate should be an effective ergogenic aid. The practice of using arginine aspartate as potential ergogenics should be critically reevaluated. Further investigations with higher dosage and extended supplementation periods should be performed.

Study of the effect of lactobacillus GG supplementation in combination with and without arginine aspartate on lipoproteins and liver peroxidation in cholesterol-fed rats

The effect of diet integration with lactobacillus GG and arginine aspartate administered singly or together to rats submitted to a cholesterol-enriched diet have been evaluated by measuring both the changes in the levels of cholesterol and tryglycerides and the variations of the most indicative parameters of peroxidation in plasma lipoproteins and livers. The administration of lactobacillus GG alone is able to induce a significant hypocholesterolaemic effect while the arginine aspartate singly or together with the lactobacillus does not seem to promote any significant hypocholesterolaemic effect. The cholesterol levels (expressed as mg × dL -1) are in fact: 45.5 for the control diet; 185.4 for the cholesterol-enriched diet; 131.1 for the cholesterol-enriched diet + lactobacillus; 178.2 for the cholesterol enriched diet + arginine aspartate and 122.4 for the cholestorol-enriched diet + lactobacillus + arginine aspartate. On the contrary, the co-administration of lactobacillus and arginine aspartate gives rise to a very high preventive activity against the cholesterol-induced peroxidation damages both in the plasma lipoproteins and in the liver. Such preventive activity is higher by far than that obtainable when lactobacillus or arginine aspartate are administered singly to the rats.

ARGININE ASPARTATE SUPPLEMENTATION IN MARATHON RUNNERS REDUCES TOTAL PLASMA AMINO ACID LEVEL

706 The metabolic influence of a 14 day long supplementation to the habitual diet with L-arginine-L-aspartate (15 g daily) was investigated in 14 endurance-trained athletes during a non-competitive marathon run. In this double-blind crossover field study, specific blood parameters and the respiratory exchange ratio were analyzed before the run, after 31 km, at the end of the run, and after a recovery period of two hours. The supplementation caused no significant change in the plasma level of carbohydrate (glucose, lactate, pyruvate) and fat metabolites (fatty acids, glycerol, β-hydroxybutyrate). However, the plasma level of urea and arginine was significantly increased, and the level of most of the remaining plasma amino acids was significantly reduced. The plasma level of ammonia, lactate dehydrogenase, and creatine kinase as well as the respiratory exchange ratio was unaffected by the treatment. The plasma level of cortisol and insulin did not change either, but somatotropic hormone and glucagon were significantly higher during the exercise bout with the arginine aspartate treatment. The metabolic impact of the supplementation had no influence on the running time. Since in humans the metabolic effects of a plasma amino acid imbalance (increased arginine, decreased total amino acid level) are not known, the practice of using single amino acid supplements as potential ergogenics should be critically reevaluated.

Theoretical study of arginine–carboxylate interactions

The importance of the guanidinium–carboxylate interactions has sprung from the observed salt bridges often present in biological systems involving the arginine–glutamate or arginine–aspartate side chains. The strength of these interactions has been explained on the basis of a great coulombic energy gain, due to the closeness of two charges of opposite sign and the occurrence of H-bond interactions. However, in some environments proton transfer, from guanidinium to carboxylate, can occur with the consequent annihilation of charge. In this work, both ab-initio (6-31G** and MP2/6-31G**) and semi-empirical (AM1) calculations were performed in vacuo on appropriate models, methylguanidinium–acetate and methylguanidine–acetic acid to simulate the zwitterionic and the neutral forms, respectively. The results obtained indicate that, in solvent-free hydrophobic environments, the neutral form should be more stable than the zwitterionic one.

Arginine stimulates wound healing and immune function in elderly human beings.

This prospective randomized trial evaluated the effect of oral supplements of arginine aspartate on wound healing and immune responses in healthy elderly (over 65 years old) volunteers. This laboratory previously demonstrated that arginine supplementation enhances wound‐breaking strength, reparative collagen synthesis, and T‐cell‐mediated immune function in healthy animals and human beings,1,2 whereas immune suppression associated with trauma is abrogated.3 Thirty subjects received daily supplements of 30 g of arginine aspartate (17 g of free arginine) and 15 individuals received placebo syrup for a 14‐day course. Wound healing was evaluated by two methods: (1) fibroplasia was measured by using subcutaneously implanted polytetrafluoroethylene catheters for the determination of collagen deposition, total protein, and DNA content, and (2) rate of wound epithelialization was assessed by using a standard partial‐thickness wound. Lymphocyte blastogenesis was measured in a microculture system by using mitogenic stimulation with standard mitogens as well as alloantigens in a mixed lymphocyte response with stimulator cells collected from pooled healthy human donors. Serum insulin‐like growth factor‐1 (IGF‐1) was determined by radioimmunoassay.Arginine supplementation enhanced wound fibroplasia as evidenced by an increase in the amount of collagen deposition and total protein content. However, DNA content and time to complete epithelialization were equivalent in both groups. The blastogenic response of peripheral blood lymphocytes to all mitogens and alloantigens was significantly enhanced in the arginine‐supplemented group. Serum IGF‐1 levels were also significantly elevated in the arginine group.

Effect of arginine aspartate on the exercise-induced hyperammoniemia in humans: A two periods cross-over trial

To investigate the effect of the ingestion of arginine aspartate (AA) in the decrease of the exercise-induced accumulation of ammonia in plasma, 11 voluntary subjects took part in a cross-over study where AA effect was tested against placebo. Both treatments were randomly administered in a double-blind procedure. To ensure the subjects would be able to present reproducible exercise-testing results during repetitive sessions, they were involved before the experiment in a cycle ergometer training program during 8 weeks. This training determined a significant 14% increase (P less than 0.001) in maximal oxygen uptake (VO2 max). The treatments were administered during 10 days and the two treatments were separated by a 10 day-wash-out period. A 45 min-cycle ergometer test was performed at 80% VO2 max during the 10th day of each treatment to measure plasma ammonia (p[NH4+]) and total blood lactate (b[lact]) concentrations at rest and at the 15th, 30th and 45th min of exercise (determinations of changes from rest; delta p[NH4+] and delta b[lact]). Both concentrations were unchanged between AA and placebo at rest but a significant lesser delta p[NH4+] was found under AA at the 15th min of exercise only (P less than 0.05). On the other hand, an order effect was found for delta p[NH4+] between the two periods of randomized treatment that was interpreted as a remaining training effect. This effect was highly significant at the 30th and 45th min of exercise (P less than 0.001). It was concluded that AA effect was minor with regard to the training effect. As it was not located at the same time of exercise, AA effect would not consequently have the same functional origin (postulated increase in the peripheral clearance of ammonia) than those of training (decrease in muscle production of ammonia).