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In this trial involving patients with acute ischemic stroke treated with thrombolysis within 3 hours after symptom onset, the use of adjunctive intravenous argatroban or eptifibatide did not improve 90-day poststroke outcomes.

Recently, it was demonstrated that spermidine-induced autophagy reduces the risk of cardiovascular disease in mice. Intestinal bacteria are a major source of polyamines, including spermidine. We previously reported that the intake of both Bifidobacterium animalis subsp. lactis (Bifal) and arginine (Arg) increases the production of putrescine, a spermidine precursor, in the gut. Here, we investigated the effects of Bifal and Arg consumption on endothelial function in healthy subjects. Healthy individuals with body mass index (BMI) near the maximum value in the “healthy” range (BMI: 25) (n = 44) were provided normal yogurt containing Bifal and Arg (Bifal + Arg YG) or placebo (normal yogurt) for 12 weeks in this randomized, double-blinded, placebo-controlled, parallel-group comparative study. The reactive hyperemia index (RHI), the primary outcome, was measured using endo-peripheral arterial tone (EndoPAT). The change in RHI from week 0 to 12 in the Bifal + Arg YG group was significantly higher than that in the placebo group, indicating that Bifal + Arg YG intake improved endothelial function. At week 12, the concentrations of fecal putrescine and serum putrescine and spermidine in the Bifal + Arg YG group were significantly higher than those in the placebo group. This study suggests that consuming Bifal + Arg YG prevents or reduces the risk of atherosclerosis.

Vitamin D (vitD) and L-arginine have important antimycobacterial effects in humans. Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis (TB). In a 4-arm randomised, double-blind, placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis (PTB) in Timika, Indonesia, we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g daily or matching placebo, for 8 weeks, on proportions of participants with negative 4-week sputum culture, and on an 8-week clinical score (weight, FEV1, cough, sputum, haemoptysis). All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned. Adults with new smear-positive PTB were eligible. The trial was registered at ClinicalTrials.gov NCT00677339. 200 participants were enrolled, less than the intended sample size: 50 received L-arginine + active vitD, 49 received L-arginine + placebo vit D, 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model, 99 people received arginine, 101 placebo arginine, 101 vitamin D, 99 placebo vitamin D. Results for the primary endpoints were available in 155 (4-week culture) and 167 (clinical score) participants. Sputum culture conversion was achieved by week 4 in 48/76 (63%) participants in the active L-arginine versus 48/79 (61%) in placebo L-arginine arms (risk difference -3%, 95% CI -19 to 13%), and in 44/75 (59%) in the active vitD versus 52/80 (65%) in the placebo vitD arms (risk difference 7%, 95% CI -9 to 22%). The mean clinical outcome score also did not differ between study arms. There were no effects of the interventions on adverse event rates including hypercalcaemia, or other secondary outcomes. Neither vitD nor L-arginine supplementation, at the doses administered and with the power attained, affected TB outcomes. ClinicalTrials.gov. Registry number: NCT00677339.

PurposeThe aim of this trial was to investigate the influence of a dietetic product consisting of a unique combination of l-arginine with the vitamins B6, folic acid and B12 (Telcor® Arginin plus) on endothelial dysfunction.MethodsSubjects aged 40–65 years with mild to moderate blood pressure (BP) elevation not treated with anti-hypertensive drugs were randomly assigned to either the dietetic product (n = 40) or a matching placebo (n = 41) for 3 months with open follow-up for a further 3 months. Postprandial change in endothelial function was assessed using the validated reactive hyperaemia index (RHI) at 3 months compared to the study onset (RHI post–pre, visit 3–visit 1; ΔΔRHI). Secondary parameters included BP and plasma homocysteine concentration.ResultsThe primary efficacy analysis revealed superiority of the nutritional intervention over placebo (p = 0.0349) in reducing the deterioration of endothelial function. While in the active group ΔΔRHI increased (0.371 ± 0.122), almost no change could be detected in the placebo group (0.031 ± 0.100), thus demonstrating a significant improvement in vascular function in the intervention group. Moreover, the intervention reduced BP and homocysteine levels. Non-serious adverse events were equally distributed in both groups, and none of the events were assessed as possibly intervention-related by the investigators.ConclusionsThis trial confirmed the effective and safe use of dietary management with l-arginine in combination with B vitamins. The primary efficacy analysis demonstrated a statistically significant superiority of the combination of l-arginine with B vitamins over placebo in improving and restoring impaired endothelial function and lowering BP in patients with mild to moderate blood pressure elevation.

Cognitive function is critical for successful prolonged performance in eSports. This double-blind placebo-controlled study examined the effect of an inositol-enhanced arginine silicate oral supplement on cognitive performance and energy in eSports athletes. Sixty healthy men and women who spent 5 or more hours a week playing video games were randomly assigned to take supplement or placebo for 7 days. On day 1 and 7, before and 15 min after dosing, subjects completed the Trail Making Test (TMT), Parts A and B; Stroop Test; and Profile of Mood States (POMS) questionnaire, and then played a video game for 60 min. Immediately after, cognitive tests were repeated. Self-reported energy levels increased, anger decreased, and TMT-B test errors decreased in the supplement group compared to placebo (p < 0.05). Fatigue, TMT-B time, and TMT B-A score improved in the supplement group compared to baseline (p < 0.05). After 60 min of gaming, supplementation decreased Stroop Test errors and TMT-A time (p < 0.05). Adverse events were minimal and not different between groups. These data appear to support the use of the studies product (nooLVL®) in eSports gamers looking to improve their accuracy, decision making, and reaction time during gaming.

Decreased nitric oxide (NO) and hypoargininemia are associated with severe falciparum malaria and may contribute to severe disease. Intravenous L-arginine increases endothelial NO in moderately-severe malaria (MSM) without adverse effects. The safety, efficacy and pharmacokinetics of L-arginine or other agents to improve NO bioavailability in severe malaria have not been assessed. In an open-label pilot study of L-arginine in adults with severe malaria (ARGISM-1 Study), patients were randomized to 12 g L-arginine hydrochloride or saline over 8 hours together with intravenous artesunate. Vital signs, selected biochemical measures (including blood lactate and L-arginine) and endothelial NO bioavailability (using reactive hyperemia peripheral arterial tonometry [RH-PAT]) were assessed serially. Pharmacokinetic analyses of L-arginine concentrations were performed using NONMEM. Six patients received L-arginine and two saline infusions. There were no deaths in either group. There were no changes in mean systolic (SBP) and diastolic blood pressure (DBP) or other vital signs with L-arginine, although a transient but clinically unimportant mean maximal decrease in SBP of 14 mmHg was noted. No significant changes in mean potassium, glucose, bicarbonate, or pH were seen, with transient mean maximal increases in plasma potassium of 0.3 mmol/L, and mean maximal decreases in blood glucose of 0.8 mmol/L and bicarbonate of 2.3 mEq/L following L-arginine administration. There was no effect on lactate clearance or RH-PAT index. Pharmacokinetic modelling (n = 4) showed L-arginine concentrations 40% lower than predicted from models developed in MSM. In the first clinical trial of an adjunctive treatment aimed at increasing NO bioavailability in severe malaria, L-arginine infused at 12 g over 8 hours was safe, but did not improve lactate clearance or endothelial NO bioavailability. Future studies may require increased doses of L-arginine. ClinicalTrials.gov NCT00616304.

The risk of death from spontaneous intracerebral haemorrhage is increased for people taking antiplatelet drugs. We aimed to assess the feasibility of randomising patients on antiplatelet drug therapy with spontaneous intracerebral haemorrhage to desmopressin or placebo to reduce the antiplatelet drug effect. DASH was a phase 2, randomised, placebo-controlled, multicentre feasibility trial. Patients were recruited from ten acute stroke centres in the UK and were eligible if they had an intracerebral haemorrhage with stroke symptom onset within 24 h of randomisation, were aged 18 years or older, and were taking an antiplatelet drug. Participants were randomly assigned (1:1) to a single dose of intravenous desmopressin 20 μg or matching placebo. Treatment allocation was concealed from all staff and patients involved in the trial. The primary outcome was feasibility, which was measured as the number of eligible patients randomised and the proportion of eligible patients approached, and analysis was by intention to treat. The trial was prospectively registered with ISRCTN (reference ISRCTN67038373), and it is closed to recruitment. Between April 1, 2019, and March 31, 2022, 1380 potential participants were screened for eligibility. 176 (13%) participants were potentially eligible, of whom 57 (32%) were approached, and 54 (31%) consented and were subsequently recruited and randomly assigned to receive desmopressin (n=27) or placebo (n=27). The main reason for eligible patients not being recruited was the patient arriving out of hours (74 [61%] of 122 participants). The recruitment rate increased after the enrolment period was extended from 12 h to 24 h, but it was then impaired due to the COVID-19 pandemic. Of the 54 participants included in the analysis (mean age 76·4 years [SD 11·3]), most were male (36 [67%]) and White (50 [93%]). 53 (98%) of 54 participants received all of their allocated treatment (one participant assigned desmopressin only received part of the infusion). No participants were lost to follow-up or withdrew from the trial. Death or dependency on others for daily activities at day 90 (modified Rankin Scale score >4) occurred in six (22%) of 27 participants in the desmopressin group and ten (37%) of 27 participants in the placebo group. Serious adverse events occurred in 12 (44%) participants in the desmopressin group and 13 (48%) participants in the placebo group. The most common adverse events were expansion of the haemorrhagic stroke (four [15%] of 27 participants in the desmopressin group and six [22%] of 27 participants in the placebo group) and pneumonia (one [4%] of 27 participants in the desmopressin group and six [22%] of 27 participants in the placebo group). Our results show it is feasible to randomise patients with spontaneous intracerebral haemorrhage who are taking antiplatelet drugs to desmopressin or placebo. Our findings support the need for a definitive trial to determine if desmopressin improves outcomes in patients with intracerebral haemorrhage on antiplatelet drug therapy. National Institute for Health Research.

This randomized controlled trial aimed to evaluate the safety and efficacy of proactive versus reactive desmopressin (DDAVP) strategies in treating severe symptomatic hyponatremia. Conducted from June 20, 2022, to February 20, 2023, it involved 49 patients with serum sodium levels below 125 mmol/L. Patients were assigned to either the proactive group, receiving DDAVP immediately upon diagnosis, or the reactive group, receiving DDAVP only if the serum sodium level tended to be overcorrected. The primary outcome was the incidence of overcorrection. The study revealed no significant difference in the overcorrection incidence between the proactive (16.7%) and reactive (28%) groups (p = 0.54). The change in serum sodium levels at 1, 6, 12, and 24 h were not different, however, at 48 h, the proactive group exhibited a higher but still safe change in serum sodium levels compared to the reactive group (10.3 ± 3.6 mmol/L vs. 7.7 ± 3.6 mmol/L, p = 0.013). Other parameters including time to symptom improvement, total intravenous fluid administered, DDAVP dose, urine volume, hospital stay duration, osmotic demyelination syndrome incidence, and 28-day mortality did not significantly differ between the groups. In conclusion, our findings suggest that there was no significant disparity in overcorrection rates between proactive and reactive DDAVP strategies for treating severe symptomatic hyponatremia. However, further large-scale studies are warranted to validate these results.

Background/Aims: We aimed to discover if L-arginine and selenium alone or together can increase the effect of a hypocaloric diet enriched in legumes (HDEL) on central obesity and cardiovascular risk factors in women with central obesity. Methods: This randomized, double-blind, placebo-controlled trial was undertaken in 84 premenopausal women with central obesity. After a 2-week run-in period on an isocaloric diet, participants were randomly assigned to a control diet (HDEL), L-arginine (5 g/day) and HDEL, selenium (200 µg/day) and HDEL or L-arginine, selenium and HDEL for 6 weeks. Cardiovascular risk factors were assessed before intervention and 3 and 6 weeks afterwards. Results: After 6 weeks, L-arginine had significantly reduced waist circumference (WC); selenium had significantly lowered fasting concentrations of serum insulin and the homeostasis model assessment of insulin resistance index; the interaction between L-arginine and selenium significantly reduced the fasting concentration of nitric oxides (NO x ), and HDEL lowered triglycerides (TG) and WC and significantly increased the fasting concentration of NO x . HDEL reduced high-sensitivity C-reactive protein levels in the first half of the study and returned them to basal levels in the second half. Conclusion: These data indicate the beneficial effects of L-arginine on central obesity, selenium on insulin resistance and HDEL on serum concentrations of NO x and TG.

We evaluated the pharmacokinetics, safety, and efficacy of l-arginine α-ketoglutarate (AAKG) in trained adult men. Subjects participated in two studies that employed a randomized, double-blind, controlled design. In study 1, 10 healthy men (30–50 y old) fasted for 8 h and then ingested 4 g of time-released or non–timed-released AAKG. Blood samples were taken for 8 h after AAKG ingestion to assess the pharmacokinetic profile of l-arginine. After 1 wk the alternative supplement was ingested. In study 2, which was placebo controlled, 35 resistance-trained adult men (30–50 y old) were randomly assigned to ingest 4 g of AAKG (three times a day, i.e., 12 g daily, n = 20) or placebo ( n = 15). Participants performed 4 d of periodized resistance training per week for 8 wk. At 0, 4, and 8 wk of supplementation the following tests were performed: clinical blood markers, one repetition maximum bench press, isokinetic quadriceps muscle endurance, anaerobic power, aerobic capacity, total body water, body composition, and psychometric parameters tests. Data were analyzed by repeated measures analysis of variance. In study 1, significant differences were observed in plasma arginine levels in subjects taking non–timed-release and timed-release AAKG. In study 2, significant differences were observed in the AAKG group ( P < 0.05) for 1RM bench press, Wingate peak power, blood glucose, and plasma arginine. No significant differences were observed between groups in body composition, total body water, isokinetic quadriceps muscle endurance, or aerobic capacity. AAKG supplementation appeared to be safe and well tolerated, and positively influenced 1RM bench press and Wingate peak power performance. AAKG did not influence body composition or aerobic capacity.