Dietary glutamic acid and aspartic acid as biomarkers for predicting diabetic retinopathy.

The screening rate of diabetic retinopathy (DR) is low despite the importance of early diagnosis. We investigated the predictive value of dietary glutamic acid and aspartic acid for diagnosis of DR using the Korea National Diabetes Program cohort study. The 2067 patients with type 2 diabetes without DR were included. The baseline intakes of energy, glutamic acid and aspartic acid were assessed using a 3-day food records. The risk of DR incidence based on intake of glutamic acid and aspartic acid was analyzed. The DR group was older, and had higher HbA1c, longer DM duration, lower education level and income than non-DR group (all p < 0.05). The intake of total energy, glutamic acid and aspartic acid were lower in DR group than non-DR group (p = 0.010, p = 0.025 and p = 0.042, respectively). There was no difference in the risk of developing DR according to the intake of glutamic acid and ascorbic acid. But, aspartic acid intake had a negative correlation with PDR. Hence, the intake of glutamic acid and aspartic acid did not affect in DR incidence. However, lower aspartic acid intake affected the PDR incidence.

Aspartic acid supplementation ameliorates symptoms of diabetic kidney disease in mice.

Diabetic kidney disease (DKD) is among the most common and serious complications of both type 1 and type 2 diabetes. In this study, we used KK/Ta-Ins2Akita (KK-Akita) mice as a model of DKD and KK/Ta (KK) mice as controls to identify novel factors related to the development/progression of DKD. Capillary electrophoresis coupled with mass spectrometry analysis revealed that circulating Asp (l-aspartic acid) levels in diabetic KK-Akita mice tend to be lower than those in control KK mice. Therefore, we evaluated the effect of Asp supplementation to prevent the progression of DKD in KK-Akita mice. Mice were divided into three groups: (a) untreated KK mice (Control group), (b) untreated KK-Akita mice (DKD group), and (c) treated (double-volume Asp diet) KK-Akita mice (Tx group). Kidney sections were stained with fluorescein isothiocyanate-labeled lectins, wheat germ agglutinin (WGA), and anti-endothelial nitric oxide synthase (eNOS) antibody for evaluation of endothelial surface layer (ESL) and NO synthesis. The mesangial area and glomerular size in the DKD group were significantly larger than those in the Control group; however, there was no significant difference in those between the DKD and Tx groups. Albuminuria, the ratio of foot process effacement, and thickness of glomerular basement membrane in the Tx group were significantly lower than those in the DKD group. Furthermore, the expression levels of glomerular WGA and microvascular eNOS in the Tx group improved significantly and approached the level in the Control group. In conclusion, the improvement of albuminuria in the Tx group may be caused by the reduction of oxidative stress in the kidneys, which may lead to the subsequent improvement of glomerular ESL.

Effect of glutamate and aspartate on ischemic heart disease, blood pressure, and diabetes: a Mendelian randomization study.

BACKGROUND: Evolutionary biology suggests reproduction trades off against longevity. Genetic selection in favor of fertility and ischemic heart disease (IHD) exists in humans. Observationally, soy protects against IHD. Soy amino acids, glutamate and aspartate, may lower androgens. No large randomized controlled trials testing their health effects exist. OBJECTIVE: Using Mendelian randomization, we assessed how genetically predicted glutamate and aspartate affected IHD, blood pressure, and diabetes. METHODS: A separate sample instrumental variable analysis with genetic instruments was used to obtain unconfounded estimates using genetic variants strongly (P < 5 × 10(-8)) and solely associated with glutamate or aspartate applied to an IHD case (n ≤76,014)-control (n ≤ 264,785) study (based on a meta-analysis of CARDIoGRAMplusC4D 1000 Genomes, UK Biobank CAD SOFT GWAS and Myocardial Infarction Genetics and CARDIoGRAM Exome), blood pressure from the UK Biobank (n ≤ 361,194), and the DIAbetes Genetics Replication And Meta-analysis diabetes case (n = 26,676)-control (n = 132,532) study. A weighted median and MR-Egger were used for a sensitivity analysis. RESULTS: Glutamate was not associated with IHD, blood pressure, or diabetes after correction for multiple comparisons. Aspartate was inversely associated with IHD (odds ratio (OR) 0.92 per log-transformed standard deviation (SD); 95% confidence interval (CI) 0.88, 0.96) and diastolic blood pressure (-0.03; 95% CI -0.04, -0.02) using inverse variance weighting, but not diabetes (OR 1.00; 95% CI 0.91, 1.09). Associations were robust to the sensitivity analysis. CONCLUSIONS: Our findings suggest aspartate may play a role in IHD and blood pressure, potentially underlying cardiovascular benefits of soy. Clarifying the mechanisms would be valuable for IHD prevention and for defining a healthy diet.

Effects of Magnesium Supplementation on Unipolar Depression: A Placebo-Controlled Study and Review of the Importance of Dosing and Magnesium Status in the Therapeutic Response.

Animal studies using tests and models have demonstrated that magnesium exerts an antidepressant effect. The literature contains few studies in humans involving attempts to augment antidepressant therapy with magnesium ions. The purpose of our study was to assess the efficacy and safety of antidepressant treatment, in combination with magnesium ions. A total of 37 participants with recurrent depressive disorder who developed a depressive episode were included in this study. As part of this double-blind study, treatment with the antidepressant fluoxetine was accompanied with either magnesium ions (120 mg/day as magnesium aspartate) or placebo. During an 8-week treatment period, each patient was monitored for any clinical abnormalities. Moreover, serum fluoxetine and magnesium levels were measured, and pharmaco-electroencephalography was performed. The fluoxetine + magnesium and fluoxetine + placebo groups showed no significant differences in either Hamilton Depression Rating Scale (HDRS) scores or serum magnesium levels at any stage of treatment. Multivariate statistical analysis of the whole investigated group showed that the following parameters increased the odds of effective treatment: lower baseline HDRS scores, female gender, smoking, and treatment augmentation with magnesium. The parameters that increased the odds of remission were lower baseline HDRS scores, shorter history of disease, the presence of antidepressant-induced changes in the pharmaco-EEG profile at 6 h after treatment, and the fact of receiving treatment augmented with magnesium ions. The limitation of this study is a small sample size.

The effect of aspartate supplementation on the microbial composition and innate immunity on mice.

The study was conducted to investigate the changes of intestinal microbiota composition and innate immunity with different dietary dosages of aspartate (Asp) supplementation. Thirty-six female ICR mice were divided randomly to four groups and thereafter fed the basal diets (controls) or those supplemented with additional 0.5, 1.0 and 2.0% aspartate. After 2 week feeding, microbial composition in ileum and feces, gene expression of pro-inflammatory cytokine, and innate immune factors in ileum were determined. The ratio of Firmicutes: Bacteroidetes in ileum and feces decreased in 0.5 and 1.0% Asp-supplemented groups, whereas this ratio increased in feces in 2.0% Asp-supplemented group. Meanwhile, the gene expression of IL-17 and IFN-γ in ileum decreased in 1.0% Asp-supplemented group; the gene expression in ileum of Muc2 decreased in 0.5 and 1.0% Asp-supplemented groups. Dietary supplementation with 2.0% Asp enhanced the expression of pIgR and Crp1 as compared to the other three groups. The results indicated that dietary 1.0% Asp supplementation lowers the ratio of Firmicutes:Bacteroidetes, which affects the innate immunity by decreasing the gene expression of IL-17, IFN-γ, and Muc2 in ileum.

Pharmaceutical Composition for Improving Physical Working Capacity.

For development of a pharmaceutical composition improving physical performance, effects of various drugs and their combinations on forced swimming test performance were studied on laboratory rats. Maximum increase in animal performance was produced by a 3-component composition asparcam+mildronate+metaprote in proportion of 5.0, 10.7, and 14.3 mg/kg, respectively. No changes in blood serum biochemistry and morphological composition of the peripheral blood were detected after single intragastric administration of the composition.

Effects of dietary supplementation with glutamate and aspartate on diquat-induced oxidative stress in piglets.

This study aimed to investigate the protective effects of dietary glutamate and aspartate supplementations on diquat-induced oxidative stress in piglets. Diquat injection significantly reduced growth performance, including body weight, average daily weight gain, and feed intake (P<0.05). Meanwhile, diquat administration induced oxidative stress evidenced by the decreased serum nitric oxide (NO) and elevated malondialdeyhde (MDA) concentration (P<0.05). Furthermore, diquat-induced oxidative stress disrupted intestinal absorption system and decreased serum threonine, serine, and glycine levels. Dietary supplementation with glutamate improved final body weight, antioxidant system, and expressions of amino acids transporters and enhanced serum glutamate concentration compared with diquat group (P<0.05). While aspartate failed to alleviate diquat-induced oxidative stress, growth depression, and dysfunction of nutrients absorption except for liver relative weight. In conclusion, dietary supplementation with glutamate confers beneficial effects on diquat-induced oxidative stress in piglets, while aspartate exhibits little effects.

Blockade of spinal glutamate recycling produces paradoxical antinociception in rats with orofacial inflammatory pain.

In our current study, we investigated the role of spinal glutamate recycling in the development of orofacial inflammatory pain. DL-threo-ß-benzyloxyaspartate (TBOA) or methionine sulfoximine (MSO) was administered intracisternally to block spinal glutamate transporter and glutamine synthetase activity in astroglia. Intracisternal administration of high dose TBOA (10 µg) produced thermal hyperalgesia in naïve rats but significantly attenuated the thermal hyperalgesia in rats that had been pretreated with interleukin (IL)-1ß or Complete Freund's Adjuvant (CFA). In contrast, intracisternal injection of MSO produced anti-hyperalgesic effects against thermal stimuli in CFA-treated rats only. To confirm the paradoxical antinociceptive effects of TBOA and MSO, we examined changes in c-Fos expression in the medullary dorsal horn produced by thermal stimulation in naïve, IL-1ß-, or CFA-treated rats, after intracisternal injections of TBOA and MSO. Intracisternal administration of TBOA significantly increased c-Fos immunoreactivity in naïve rats. In contrast, intracisternal administration of TBOA significantly decreased the up-regulation of c-Fos immunoreactivity in the medullary dorsal horn of IL-1ß- and CFA-treated rats. However, intracisternal injection of MSO blocked the up-regulation of c-Fos immunoreactivity in CFA-treated rats only. We also investigated the effects of botulinum toxin type A (BoNT-A) on TBOA-induced paradoxical antinociception in CFA-treated rats, as BoNT-A inhibits the release of neurotransmitters, including glutamate. BoNT-A treatment reversed behavioral responses produced by intracisternal administration of TBOA in CFA-treated rats. These results suggest that the paradoxical responses produced by blocking glutamate transporters under inflammatory pain conditions are mediated by the modulation of glutamate release from presynaptic terminals. Moreover, blockade of glutamate reuptake could represent a new therapeutic target for the treatment of chronic inflammatory pain conditions.

Aspartate alleviates liver injury and regulates mRNA expressions of TLR4 and NOD signaling-related genes in weaned pigs after lipopolysaccharide challenge.

Pro-inflammatory cytokines play a critical role in many models of liver injury. In addition, aspartate (Asp) plays an important role in many biological and physiological processes including liver physiology. We hypothesized that Asp could alleviate lipopolysaccharide (LPS)-induced liver injury. Forty-eight weanling pigs were assigned to four treatments including: (1) non-challenged control; (2) LPS challenged control; (3) LPS+0.5% Asp; (4) LPS+1.0% Asp. After 20-d feeding with control (0% Asp), 0.5% or 1.0% Asp supplemented diets, pigs were injected with saline or LPS. At 4 (early phase) and 24 h (late phase) post-injection, blood and liver samples were obtained. Asp attenuated liver injury indicated by reduced serum aspartate aminotransferase activity and increased ratio of serum alanine aminotransferase and aspartate aminotransferase at 24 h, and less severe histological liver damage induced by LPS challenge at 4 or 24 h. In addition, Asp supplementation to LPS challenged pigs decreased mRNA expressions of tumor necrosis factor (TNF)-α and cyclooxygenase-2 linearly and quadratically at 4 h, and increased mRNA expressions of these pro-inflammatory mediators linearly and quadratically at 24 h. Finally, Asp decreased mRNA expression of toll-like receptor 4 (TLR4) signaling related genes (TLR4, myeloid differentiation factor 88, IL-1 receptor-associated kinase 1, TNF-α receptor-associated factor (6), nucleotide-binding oligomerization domain protein (NOD) signaling related genes (NOD1, NOD2 and receptor-interacting serine/threonine-protein kinase 2) and nuclear factor-κB p65 linearly or quadratically at 4 h. However, Asp increased mRNA expressions of these signaling molecules linearly or quadratically at 24 h. These results indicate that, at early and late phases of LPS challenge, Asp exerts opposite regulatory effects on mRNA expression of hepatic pro-inflammatory cytokines and TLR4 and NOD signalling related genes, and improves liver integrity.

[Physiological functions of L-ornithine and L-aspartate in the body and the efficacy of administration of L-ornithine-L-aspartate in conditions of relative deficiency]. / Fizjologiczne funkcje L-ornityny i L-asparaginianu oraz celowosc podawania asparaginianu ornityny w stanach wzglednego niedoboru.

L-ornithine-L-aspartate (LOLA) is a stable salt of two natural nonessential L-amino acids: ornithine and aspartic acid. It is formulated and marketed in low and high doses. Low doses are used as a food supplement and high doses (above 5 g) as a medicinal product to lower blood ammonia concentration and to eliminate symptoms of hepatic encephalopathy associated with liver cirrhosis. The aim of this review is to present physiological roles of L-ornithine and L-aspartate in the human body, to assess conditions under which these amino acids could be deficient, to analyze consequences of these deficiencies, and to review the current state of knowledge on the effects of LOLA administration. The data used in this publication result from searches of different electronic databases such as Cochrane Trials Register, MEDLINE, PubMed, Medscape, or Google Scholar, with a cut-off date of November 29, 2009, using terms: L-ornithine-L-aspartate, ornithine aspartate, ornithine, Hepa-Merz, ornithine deficiency, hyperammonemia, hepatic encephalopathy, and liver cirrhosis. Both amino acids play key roles in ammonia detoxification and in proline and polyamine biosyntheses. Polyamines are considered critical for DNA synthesis and cell replication and have been shown to stimulate hepatic regeneration. Supplementation with ornithine in animal models demonstrated enhanced wound breaking strength and collagen deposition. It has been shown in vitro, in vivo and in perfused organs that urea synthesis from ammonia is limited by endogenous ornithine and that ornithine can pharmacologically promote urea formation to a greater degree than any ammonia supply. Administration of LOLA in high doses reduced high blood ammonia induced either by ammonium chloride or protein ingestion or existing as a clinical complication of cirrhosis. In health and with proper diet, L-ornithine and L-aspartate are synthesized de novo in sufficient quantities, but in the states of disease, tissue damage, organ insufficiency, excessive metabolic demand, growth, pregnancy, or urea cycle enzyme deficiencies, these amino acids need to be supplemented with the food. The review of available data indicate that there is direct and indirect (resulting from physiology) scientific rationale for dietary use of LOLA, depending on an individual's physiological, metabolic or pathological conditions. In conditional ornithine deficiency, daily supplementation with LOLA at doses about 1 g/day is safe and, as demonstrated in vitro, should be sufficient to saturate tissue ornithine concentration to prevent postprandial hyperammonemia and to stimulate tissue regeneration.

Oral supplementation with L-aspartate and L-glutamate inhibits atherogenesis and fatty liver disease in cholesterol-fed rabbit.

Previous studies have shown that dietary supplementation with L-aspartate and L-glutamate inhibits fatty streak initiation in cholesterol-fed rabbit. The present study investigates the role of dicarboxylic amino acids on the progression of fatty streaks and the development of fatty liver disease, which were caused in New Zealand White rabbits after a 0.5% w/w cholesterol diet for 7 weeks. A group of animals additionally received a combination of 12.5 mM L-aspartate and 12.5 mM L-glutamate per day through drinking water. Total cholesterol (TC), high-density lipoproteins cholesterol (HDLC), non-HDLC and triacylglycerol (TAG) concentrations were measured in plasma. Serum gamma-glutamyl transferase (gamma-GT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were also determined. At the end of dietary intervention, animals were sacrificed. Aortic, hepatic and brain lesions were evaluated after staining with hematoxylin and eosin. Supplementation with dicarboxylic amino acids inhibited the progression of aortic intima thickness (P < 0.05) and the development of liver lesions (P < 0.05). TC, non-HDLC and TAG were similarly increased in both cholesterol-fed groups. Serum gamma-GT and AST activities elevated during the study in all cholesterol-fed animals but the elevation of gamma-GT was milder and significantly lower in rabbits treated with L-aspartate and L-glutamate (P < 0.05). ALT activity was not affected by cholesterol feeding. In conclusion, oral supplementation with L-aspartate and L-glutamate inhibits the progression of atherogenesis and the development of fatty liver disease in the animal model of cholesterol-fed rabbit. The beneficial effects of dicarboxylic amino acids reflect the limited elevation of serum gamma-GT activity.

DL-Aspartic acid administration improves semen quality in rabbit bucks.

Recently, D-aspartic acid (d-Asp) has been suggested as being involved in mechanisms regulating reproduction activity in animals and human. In this study we analyzed the effects of DL-Asp oral administration on sperm production in the rabbit. Bucks from 60, bred in a genetic centre and used for semen production, were divided in 2 subgroups of 6 individuals. The treated group was fed with a concentrate containing DL-Asp which assured a daily administration of 1.3g dl-Asp/head; the control group was fed with the same concentrate without DL-Asp. The treatment was carried out for 2wk and animals were monitored weekly, from 1wk before the start of the treatment to 3wk after the end of the treatment. Through the experimental period there were no significant variations in semen volume between the two groups. A significant increase in both sperm concentration and kinetic parameters, i.e., the overall percentage of motile spermatozoa, the average path velocity, the percentage of progressively motile spermatozoa, etc., was found in the supplemented group. L-Asp values in blood serum and seminal plasma did not vary through the experimental period. D-Asp concentration in blood serum increased more than 4-fold than baseline (P<0.01) at the end of the treatment and was maintained at higher than baseline values for up to 3wk after the end of the treatment. D-Asp concentration in seminal plasma was higher than in blood serum before the start of the treatment (13.7+/-1.6nM vs 3.5+/-3.3nM; P<0.01) which suggests an elective storage of D-Asp in the male genital tract. Baseline values of d-Asp concentration in seminal plasma significantly increased following treatment and were back to initial values 1wk after the end of the treatment. In conclusion, DL-Asp administration improved sperm quality in bucks and the high D-Asp content in seminal plasma suggests a primary role for this D-amino acid in regulatory mechanisms of reproductive activity.

The effect of 5 days of aspartate and asparagine supplementation on glucose transport activity in rat muscle.

The consumption of protein supplements containing amino acids is increasing around the world. Aspartate (Asp) and asparagine (Asn) are amino acids metabolized by skeletal muscle. This metabolism involves biochemical pathways that are involved in increasing Krebs cycle activity via anaplerotic reactions, resulting in higher glutamine concentrations. A connection between amino acid supplementation, glycogen concentration, and glucose uptake has been previously demonstrated. The purpose of this study was to evaluate the effect of Asp and Asn supplementation on glucose uptake in rats using three different glycogen concentrations. The results indicate that Asp and Asn supplementation in rats with high glycogen concentrations (fed state) further increased the glycogen concentration in the muscle, and decreased in vitro 2-deoxyglucose (a glucose analog) uptake by the muscle at maximal insulin concentrations. When animals had a medium glycogen concentration (consumed lard for 3 days), glucose uptake was higher in the supplemented group at sub-maximal insulin concentrations. We conclude that supplementation of Asp and Asn reduced glucose transport in rat muscle only at higher levels of glycogen. The ingestion of lard for 3 days changed the responsiveness and sensitivity to insulin, and that group had higher levels of insulin sensitivity with Asp and Asn supplementation.

Neuroprotective effects of yokukansan, a traditional Japanese medicine, on glutamate-mediated excitotoxicity in cultured cells.

To clarify the mechanism of yokukansan (TJ-54), a traditional Japanese medicine, against glutamate-mediated excitotoxicity, the effects of TJ-54 on glutamate uptake function were first examined using cultured rat cortical astrocytes. Under thiamine-deficient conditions, the uptake of glutamate into astrocytes, and the levels of proteins and mRNA expressions of glutamate aspartate transporter of astrocytes significantly decreased. These decreases were ameliorated in a dose-dependent manner by treatment with TJ-54 (100-700 microg/ml). The improvement of glutamate uptake with TJ-54 was completely blocked by the glutamate transporter inhibitor DL-threo-beta-hydroxyaspartic acid. Effects of TJ-54 on glutamate-induced neuronal death were next examined by using cultured PC12 cells as a model for neurons. Addition of 17.5 mM glutamate to the culture medium induced an approximately 50% cell death, as evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. TJ-54 (1-1000 microg/ml) inhibited the cell death in a dose-dependent manner. Furthermore, competitive binding assays to glutamate receptors showed that TJ-54 bound potently to N-methyl-D-aspartate receptors, in particular, to its glutamate and glycine recognition sites. These results suggest that TJ-54 may exert a neuroprotective effect against glutamate-induced excitotoxicity not only by amelioration of dysfunction of astrocytes but also by direct protection of neuronal cells.

Excitatory amino acids in the forebrain of the Naples high-excitability rats: neurochemical and behavioural effects of subchronic D-aspartate and its diethyl ester prodrug.

The excitatory amino acids (EAA) L-glutamate (L-Glu), L-aspartate (L-Asp) and D-aspartate (D-Asp) are thought to play a neurotransmitter/neuromodulator role in neuronal communications. Recently, a high level of EAA L-Glu, D- and L-Asp isomers has been found in the forebrain of Naples high-excitability (NHE) rat line that models the mesocortical variant of Attention-Deficit Hyperactivity Disorder (ADHD). The aim of this study was to assess the functions of D-Asp using two forms, i.e. free D-Asp or D-Asp diethyl ester (DEE) as prodrug, on brain and behaviour. Thus, prepuberal rats were given, for two weeks daily, an i.p. injection of D-Asp or DEE or vehicle. Then rats were exposed to two spatial novelties i.e. Làt and radial Olton maze. Behaviour was monitored for indices of activity, non-selective attention (NSA), selective spatial attention (SSA) and emotional reactivity. L-Glu and D- and L-Asp were detected by HPLC in cognitive and non-cognitive brain areas such as prefrontal cortex, striatum, hippocampus and hypothalamus. Results indicate that subchronic D-Asp or DEE (i) reduced EAA levels in the NHE and increased it in the random-bred controls (NRB) rats, (ii) in the Làt-maze D-Asp increased horizontal activity in NHE but DEE decreased it in NRB rats, (iii) in the Olton maze D-Asp and DEE decreased vertical activity in NHE and NRB rats respectively, (iv) D-Asp impaired attention only in NRB decreasing number of arms visited before first repetition. Therefore, data demonstrate differential effects of prepuberal subchronic D-Asp and DEE that may be related to different basal EAA levels in NHE and NRB rats.

Effects of supplementing two levels of magnesium aspartate and transportation stress on pork quality and gene expression of micro-calpain and calpastatin of finishing pigs.

The objective of this study was to investigate the effects of supplementing swine finishing diets with two levels of magnesium aspartate (MgAsp) and short-term transportation stress on blood parameters, pork quality and the mRNA abundance of p-calpain and calpastatin in muscles of finishing pigs. Thirty-six crossbred finishing pigs (mean BW 90 kg) were assigned randomly to 0, 1000, or 2000 mg supplemental Mg from MgAsp per kg of diet for five days before slaughter. Then six pigs from each dietary treatment were subjected either to no transportation stress (NTS) or 2 h of transportation stress (TS). Transportation stress resulted in higher concentrations (p < 0.01) of serum calcium, glucose and cortisol, lower pH (p < 0.01), higher Warner-Bratzler shear force (WBSF) (p < 0.05) and higher calpastatin mRNA abundance (p = 0.05) of longissimus muscle (LM) compared with NTS treatments. Supplementation of MgAsp in TS treatments increased serum Mg concentration (p < 0.05) at 2000 mg of Mg/kg, reduced drip loss (p < 0.05) and improved pork quality colour (p < 0.05) at 2000 mg of Mg/kg, and decreased 1-day and 3-day WBSF (p < 0.05) at 1000 mg of Mg/kg compared with TS treatments fed the control diet. It is concluded that supplementation of MgAsp improves water-holding capacity and pork colour, and alleviates the negative effects of transportation stress on meat tenderness.

[Effect of some organic and inorganic magnesium salts on lipoprotein state in rats fed with magnesium-deficient diet].

Low serum magnesium (Mg) concentrations have been reported in patients with atherosclerosis. From the other hand numerous clinical reports suggest the beneficial effects of Mg adjuvant therapy for the treatment of atherosclerosis. The purpose of this present study was to compare the effect of Mg L-aspartate and Mg chloride alone and in combinations with pyridoxine, Mg sulfate and Magne B6 (Mg lactate with pyridoxine) on lipid profile in rats fed with Mg deficient diet. To induce hypomagnesemia, fifty-three rats were placed on a Mg-deficient diet (ICN Biomedicals Inc. Aurora, OH) and demineralized water for 7 weeks. Seven control rats were fed a basal control diet (Mg content = 500 mg/kg) and water (with Mg content 20 mg/l) for equal duration. On the forty-ninth day of Mg-deficient diet, rats were treated one of the six supplementations: Mg chloride, Mg L-aspartate alone and in combinations with pyridoxine, Mg sulphate and Magne B6 (50 mg Mg and 5 mg vitamin B6 per kg). In our study Mg deficiency resulted in increase of triglyceride (by 35.2 %p < 0.0001), LDL (more than fourfold p < 0.0001), total cholesterol (by 38.7% p < 0.0001), apolipoprotein B (by 74.1%, p = 0.0006) levels and decrease in concentration of HDL (by 28.7% p < 0.0001). The non-HDL cholesterol/HDL cholesterol ratio was more than threefold increased (p < 0.0001). Oral magnesium salts led to normalization of lipid state with a return to pre-deficient levels. Magnesium salts in combinations with pyridoxine tended to be significantly more effective as compared with salts without pyridoxine. The hypolipidemic effect of studied salts was comparable with those observed in Magne B6 treatment and significantly higher than in magnesium sulfate treatment.

Glutamate/aspartate supplementation during cardiopulmonary bypass: effect on postoperative neurocognitive function.

In this randomized trial, we investigated the effect of glutamate/aspartate-containing cardioplegia on neurocognitive function in 70 patients undergoing first-time elective coronary artery bypass graft surgery. Half of the patients received glutamate/aspartate, and the other 35 patients served as controls and received crystalloid cardioplegia. Neurocognitive function after surgery was assessed with the Mini-Mental State Examination performed before surgery and again on postoperative day 3. Although patients in both groups scored slightly lower postoperatively (17 versus 18 of a total of 30 points), no significant group differences were found. Our results indicate that glutamate/aspartate supplementation had no impact on neurocognitive function after coronary artery bypass graft surgery.

[The role of alimentary magnesium deficiency in development of nephrolithiasis and its correction with magnesium salts in rats].

Aims of our work were to appraise the quantity and nature of renal calcifications and mineral metabolism in the magnesium-deficient rats; and to find out whether the combination of pyridoxine with Mg L-aspartate or Mg chloride will reduce the length of the treatment needed to recover rats from magnesium deficient condition and urolithiasis state. To induce hypomagnesemia, fifty rats were placed on a magnesium-deficient diet (magnesium content < or = 15 mg/kg) and demineralized water for 10 weeks. On the forty-ninth day of magnesium-deficient diet, rats were treated one of the six supplementations: MgCl2, Mg-L-Asp or their combinations with pyridoxine hydrochloride, magnesium sulfate, magne B6.

Do aspartate and asparagine acute supplementation influence the onset of fatigue in intense exercise?

AIM: Oxaloacetic acid represents a fundamental intermediary in the metabolism of energy substrate. Asparagine and aspartate constitute precursor compounds of this substance. Therefore, they could affect tricarbossilic acids cycle. Besides, it was suggested that supplementation with aspartate and asparagine determines a muscular glycogen sparing during strenuous physical exercise, even if the real effectiveness remain controversial. The aim of the present pilot study was to evaluate the hypothesis that a supplementation with oxaloacetate precursors, precisely aspartate and asparagine, could improve sport performance during high intensity endurance exercise. METHODS: We recruited 15 male trained athletes, aged from 20 to 30 years (mean age: 24.13+/-3.87 years), practicing triathlon. We administered them placebo or aspartate (7 g) and asparagine (7 g) mixture, using a double blind technique, before performing an exhaustion stress test on cycloergometer carried out to 90% of each athlete's maximum oxygen consumption, previously determined. RESULTS: We evaluated lactatemia through earlobe punctures at the end of warming up, at the maximum effort and at recovery time (3 min, 5 min, 10 min, 15 min, 30 min). Furthermore, subjects were submitted to three blood samples from brachial artery in order to assess the glycemia (before the exercise, at the end of the exercise, and 30 min after the end of the exercise). CONCLUSION: The analysis of these parameters and the results of the ergometric tests after amino acids assumption indicate that acute supplementation with aspartate and asparagine do not significantly affect physical performance in athletes practicing high intensity exercises, and that acute administration of aspartate does not cause a sparing of muscle glycogen concentration.