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Postoperative arginine-enriched immune modulating nutrition: Long-term survival results from a randomised clinical trial in patients with oesophagogastric and pancreaticobiliary cancer.
Adiamah, A, Rollins, KE, Kapeleris, A, Welch, NT, Iftikhar, SY, Allison, SP, Lobo, DN
Clinical nutrition (Edinburgh, Scotland). 2021;(11):5482-5485
Abstract
BACKGROUND & AIMS Immune modulating nutrition (IMN) has been shown to reduce postoperative infectious complications and length of stay in patients with gastrointestinal cancer. Two studies of IMN in patients undergoing surgery for head and neck cancer also suggested that this treatment might improve long-term survival and progression-free survival. In the present study, we analysed follow-up data from our previous randomised controlled trial of IMN, in patients undergoing surgery for oesophagogastric and pancreaticobiliary cancer, in order to evaluate the long-term impact on survival of postoperative IMN versus an isocaloric, isonitrogenous control feed. METHODS This study included patients undergoing surgery for cancers of the pancreas, oesophagus and stomach, who had been randomised in a double-blind manner to receive postoperative jejunostomy feeding with IMN (Stresson, Nutricia Ltd.) or an isonitrogenous, isocaloric feed (Nutrison High Protein, Nutricia) for 10-15 days. The primary outcome was long-term overall survival. RESULTS There was complete follow-up for all 108 patients, with 54 patients randomised to each group. There were no statistically significant differences between groups by demographics [(age, p = 0.63), sex (p = 0.49) or site of cancer (p = 0.25)]. 30-day mortality was 11.1% in both groups. Mortality in the intervention group was 13%, 31.5%, 70.4%, 85.2%, 88.9%, and 96.3% at 90 days, and 1, 5, 10, 15 and 20 years respectively. Corresponding mortality in the control group was 14.8%, 35.2%, 68.6%, 79.6%, 85.2% and 98.1% (p > 0.05 for all comparisons). CONCLUSION Early postoperative feeding with arginine-enriched IMN had no impact on long-term survival in patients undergoing surgery for oesophagogastric and pancreaticobiliary cancer.
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Acute Inositol-Stabilized Arginine Silicate Improves Cognitive Outcomes in Healthy Adults.
Gills, JL, Campitelli, A, Jones, M, Paulson, S, Myers, JR, Madero, EN, Glenn, JM, Komorowski, J, Gray, M
Nutrients. 2021;(12)
Abstract
Inositol-stabilized arginine silicate (ASI) is an ergogenic aid that upregulates nitric oxide. Acute ASI supplementation improves working memory and processing speed in young adults but there is a lack of data examining other cognitive tasks. Therefore, the purpose of this study was to examine acute ASI effects on young healthy adults by assessing multiple cognitive domains. Nineteen young adults (20.9 ± 3.2 years) completed this randomized, double-blind, crossover study consuming ASI (1.5 g ASI + 12 g dextrose) and placebo (12 g dextrose). The participants completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and two digital cognitive assessments before consuming the supplement and then completed the same battery of tests 60 min post-supplementation. Repeated measures ANOVA demonstrated that ASI consumption significantly improved total RBANS and immediate memory scores compared to the placebo (p < 0.05). However, no significant differences were displayed between trials for other cognitive domains (p > 0.05). Acute ASI ingestion increased overall RBANS scores and immediate memory scores in young adults. More research is needed to examine the acute effects of ASI on other domains of cognition, in older populations, and its long-term effects on cognition.
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Effect of l-arginine on cardiac reverse remodeling and quality of life in patients with heart failure.
Salmani, M, Alipoor, E, Navid, H, Farahbakhsh, P, Yaseri, M, Imani, H
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3037-3044
Abstract
BACKGROUND & AIMS Heart failure (HF), as a major cardiac disease, is associated with considerable mortality, morbidities and poor quality of life. The aim of this study was to investigate the effect of l-arginine supplementation on cardiac outcomes and quality of life in patients with ischemic HF. METHODS This double-blind randomized controlled clinical trial was conducted in 50 patients with ischemic HF. Patients were randomly assigned to receive either 3 gr/d l-arginine or placebo, for 10 weeks. Cardiac function (based on echocardiography and six-minute walk test), blood pressure, and quality of life (based on the Minnesota living with heart failure questionnaire) were assessed. RESULTS The results showed significant improvements in ejection fraction (-6.5 ± 8.7 vs. -0.7 ± 7.8%, P = 0.037), left ventricular function (P = 0.043), diastolic dysfunction (P = 0.01) and marginally improvement in changes of left ventricular dimension during diastole (LVDd) (4 ± 6 vs. 0.3 ± 6.9 mm, P = 0.065) in the l-arginine compared to the placebo group. At the end of the study, physical aspect (5.7 ± 3.3 vs. 1.2 ± 6.1, P = 0.002) and total score (10 ± 6.7 vs. 4.1 ± 9.4, P = 0.011) of quality of life improved significantly in the l-arginine compared with the placebo group. Additionally, pre-to post-values of diastolic blood pressure, mean arterial pressure, LVDd, LV ejection fraction, left ventricular function, diastolic dysfunction as well as physical and total scores of quality of life improved significantly within the intervention, but not the placebo, group (all P < 0.05). CONCLUSION This study showed that 3 gr/d l-arginine supplementation for 10 weeks could improve cardiac recovery and function, and quality of life in patients with HF. This study was registered at the Iranian Clinical Trial Registration Center (www.irct.ir) with IRCT20170202032367N4 code.
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Effects of Inositol-Enhanced Bonded Arginine Silicate Ingestion on Cognitive and Executive Function in Gamers.
Sowinski, R, Gonzalez, D, Xing, D, Yoo, C, Jenkins, V, Nottingham, K, Dickerson, B, Humphries, M, Leonard, M, Ko, J, et al
Nutrients. 2021;(11)
Abstract
Inositol stabilized arginine silicate (ASI) ingestion has been reported to increase nitric oxide levels while inositol (I) has been reported to enhance neurotransmission. The current study examined whether acute ASI + I (Inositol-enhanced bonded arginine silicate) ingestion affects cognitive function in e-sport gamers. In a double blind, randomized, placebo controlled, and crossover trial, 26 healthy male (n = 18) and female (n = 8) experienced gamers (23 ± 5 years, 171 ± 11 cm, 71.1 ± 14 kg, 20.7 ± 3.5 kg/m2) were randomly assigned to consume 1600 mg of ASI + I (nooLVL®, Nutrition 21) or 1600 mg of a maltodextrin placebo (PLA). Prior to testing, participants recorded their diet, refrained from consuming atypical amounts of stimulants and foods high in arginine and nitrates, and fasted for 8 h. During testing sessions, participants completed stimulant sensitivity questionnaires and performed cognitive function tests (i.e., Berg-Wisconsin Card Sorting task test, Go/No-Go test, Sternberg Task Test, Psychomotor Vigilance Task Test, Cambridge Brain Sciences Reasoning and Concentration test) and a light reaction test. Participants then ingested treatments in a randomized manner. Fifteen minutes following ingestion, participants repeated tests (Pre-Game). Participants then played their favorite video game for 1-h and repeated the battery of tests (Post-Game). Participants observed a 7-14-day washout period and then replicated the study with the alternative treatment. Data were analyzed by General Linear Model (GLM) univariate analyses with repeated measures using weight as a covariate, paired t-tests (not adjusted to weight), and mean changes from baseline with 95% Confidence Intervals (CI). Pairwise comparison revealed that there was a significant improvement in Sternberg Mean Present Reaction Time (ASI + I vs. PLA; p < 0.05). In Post-Game assessments, 4-letter Absent Reaction Time (p < 0.05), 6-letter Present Reaction Time (p < 0.01), 6-letter Absent Reaction Time (p < 0.01), Mean Present Reaction Time (p < 0.02), and Mean Absent Reaction Time (p < 0.03) were improved with ASI + I vs. PLA. There was a non-significant trend in Pre-Game Sternberg 4-letter Present Reaction time in ASI + I vs. PLA (p < 0.07). ASI + I ingestion better maintained changes in Go/No-Go Mean Accuracy and Reaction Time, Psychomotor Vigilance Task Reaction Time, and Cambridge Post-Game Visio-spatial Processing and Planning. Results provide evidence that ASI + I ingestion prior to playing video games may enhance some measures of short-term and working memory, reaction time, reasoning, and concentration in experienced gamers.
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L-Arginine Improves Endurance to High-Intensity Interval Exercises in Overweight Men.
Daraei, A, Ahmadizad, S, Rahmani, H, Hackney, AC, Johnson, KE, Laher, I, Saeidi, A, Zouhal, H
International journal of sport nutrition and exercise metabolism. 2021;(1):46-54
Abstract
The effects of acute consumption of L-Arginine (L-Arg) in healthy young individuals are not clearly defined, and no studies on the effects of L-Arg in individuals with abnormal body mass index undertaking strenuous exercise exist. Thus, we examined whether supplementation with L-Arg diminishes cardiopulmonary exercise testing responses, such as ventilation (VE), VE/VCO2, oxygen uptake (VO2), and heart rate, in response to an acute session of high-intensity interval exercise (HIIE) in overweight men. A double-blind, randomized crossover design was used to study 30 overweight men (age, 26.5 ± 2.2 years; body weight, 88.2 ± 5.3 kilogram; body mass index, 28.0 ± 1.4 kg/m2). Participants first completed a ramped-treadmill exercise protocol to determine VO2max velocity (vVO2max), after which they participated in two sessions of HIIE. Participants were randomly assigned to receive either 6 g of L-Arg or placebo supplements. The HIIE treadmill running protocol consisted of 12 trials, including exercise at 100% of vVO2max for 1 min interspersed with recovery intervals of 40% of vVO2max for 2 min. Measurements of VO2 (ml·kg-1·min-1), VE (L/min), heart rate (beat per min), and VE/VCO2 were obtained. Supplementation with L-Arg significantly decreased all cardiorespiratory responses during HIIE (placebo+HIIE vs. L-Arg+HIIE for each measurement: VE [80.9 ± 4.3 L/min vs. 74.6 ± 3.5 L/min, p < .05, ES = 1.61], VE/VCO2 [26.4 ± 1.3 vs. 24.4 ± 1.0, p < .05, ES = 1.8], VO2 [26.4 ± 0.8 ml·kg-1·min-1 vs. 24.4 ± 0.9 ml·kg-1·min-1, p < .05, ES = 2.2], and heart rate [159.7 ± 6.3 beats/min vs. 155.0 ± 3.7 beats/min, p < .05, d = 0.89]). The authors conclude consuming L-Arg before HIIE can alleviate the excessive physiological strain resulting from HIIE and help to increase exercise tolerance in participants with a higher body mass index who may need to exercise on a regular basis for extended periods to improve their health.
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Safety, Tolerability, and Biologic Activity of AXA1125 and AXA1957 in Subjects With Nonalcoholic Fatty Liver Disease.
Harrison, SA, Baum, SJ, Gunn, NT, Younes, ZH, Kohli, A, Patil, R, Koziel, MJ, Chera, H, Zhao, J, Chakravarthy, MV
The American journal of gastroenterology. 2021;(12):2399-2409
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Abstract
INTRODUCTION AXA1125 and AXA1957 are novel, orally administered endogenous metabolic modulator compositions, specifically designed to simultaneously support multiple metabolic and fibroinflammatory pathways associated with nonalcoholic fatty liver disease (NAFLD). This study assessed safety, tolerability, and biologic activity of AXA1125 and AXA1957 in NAFLD. METHODS In this multicenter, 16-week, placebo-controlled, single-blind, randomized clinical study in subjects with NAFLD stratified by type 2 diabetes, AXA1125 24 g, AXA1957 13.5 g or 20.3 g, or placebo was administered twice daily. Key metabolism (MRI-proton density fat fraction [MRI-PDFF] and homeostasis model assessment of insulin resistance [HOMA-IR]) and fibroinflammation markers (alanine aminotransferase [ALT], corrected T1 [cT1], keratin-18 [K-18] M65, and N-terminal type III collagen propeptide [Pro-C3]) were evaluated. Safety outcomes included adverse events and standard laboratory assessments. RESULTS Baseline characteristics of the 102 enrolled subjects, including 40 with type 2 diabetes, were consistent with presumed nonalcoholic steatohepatitis. AXA1125 showed consistently greater biologic activity than AXA1957 or placebo. Week 16 changes from baseline with AXA1125 vs placebo: MRI-PDFF -22.9% vs -5.7%, HOMA-IR -4.4 vs +0.7, ALT -21.9% vs -7.2%, K-18 M65 -13.6% vs +20.1%, cT1 -69.6 vs +18.3 ms (P < 0.05), and Pro-C3 -13.6% vs -3.6%. Week 16 changes from baseline with AXA1957 20.3 g: MRI-PDFF -8.1%, HOMA-IR +8.4, ALT -20.7%, K-18 M65 6.6%, cT1 -34.7 ms, and Pro-C3 -15.6%. A greater proportion of subjects treated with AXA1125 achieved clinically relevant thresholds: ≥30% MRI-PDFF, ≥17-IU/L ALT, and ≥80-ms cT1 reductions at week 16. Study products were safe and well tolerated with stable lipid and weight profiles. DISCUSSION Both compositions showed multitargeted activity on relevant NAFLD pathways. AXA1125 demonstrated the greatest activity over 16 weeks, warranting continued clinical investigation in nonalcoholic steatohepatitis subjects.
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Pharmacokinetic Parameters of Watermelon (Rind, Flesh, and Seeds) Bioactive Components in Human Plasma: A Pilot Study to Investigate the Relationship to Endothelial Function.
Fan, J, Park, E, Zhang, L, Edirisinghe, I, Burton-Freeman, B, Sandhu, AK
Journal of agricultural and food chemistry. 2020;(28):7393-7403
Abstract
This study aimed to investigate the metabolic fate of bioactive components in watermelon and explore their effect on endothelial function. Six healthy overweight/obese (BMI: 28.7 ± 1.6 kg/m2) adults received 100 kcal of watermelon flesh (WF), rind (WR), seeds (WS), or control meal. l-Citrulline, arginine, and (poly)phenolic metabolites were characterized in plasma over 24 h using UHPLC-MS. Endothelial function was assessed using a flow mediated dilation (FMD) technique over 7 h. Maximum concentration (Cmax) and area under the curve (AUC0-8h) of l-citrulline were significantly higher after WF- and WR-containing test meals compared to control (p < 0.05). Likewise, several individual phenolic metabolites in plasma had significantly higher Cmax after WR, WF, or WS intake compared to control. FMD responses were not different among test meals. Our results provide insights on circulating metabolites from watermelon flesh, seed, and rind and lay the foundation for future clinical trials on vascular benefits of watermelon.
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Effects of Beetroot Powder with or without L-Arginine on Postprandial Vascular Endothelial Function: Results of a Randomized Controlled Trial with Abdominally Obese Men.
Smeets, ETHC, Mensink, RP, Hoeks, J, de Vogel-Van den Bosch, J, Hageman, RJJ, Joris, PJ
Nutrients. 2020;(11)
Abstract
BACKGROUND Through effects on nitric oxide bioavailability, vascular endothelial function is improved after the intake of a high amount of nitrate or L-arginine, but decreased after the intake of a high-fat meal. Therefore, we compared the effects of beetroot powder with or without L-arginine on postprandial brachial artery flow-mediated vasodilation (FMD) after consumption of a high-fat mixed-meal. METHODS Eighteen abdominally obese men completed this randomized, double-blinded, cross-over trial. The study consisted of five test days, each separated by a wash-out period of at least one week. Participants received in random order, a blended meal with a control or nutritional supplement consisting of beetroot powder providing 200 mg nitrate, beetroot with 0.8 g of L-arginine, beetroot with 1.5 g of L-arginine, or 3.0 g of L-arginine. Participants then fasted and 2 h postprandial FMD measurements were performed. RESULTS No significant differences between meals were observed for postprandial FMD (p = 0.45) levels. However, there was a non-significant trend towards a more beneficial postprandial FMD response with the beetroot-containing meals as compared with meals without beetroot. CONCLUSION This trial could not provide evidence for beneficial additive effects of a single dose of beetroot powder combined with L-arginine on postprandial endothelial function in abdominally obese men.
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Intermittent Hypoxic Exposure with High Dose of Arginine Impact on Circulating Mediators of Tissue Regeneration.
Zembron-Lacny, A, Gramacki, A, Wawrzyniak-Gramacka, E, Tylutka, A, Hertmanowska, N, Kasperska, A, Czuba, M
Nutrients. 2020;(7)
Abstract
Intermittent exposure to hypoxia (IHE) increases production of reactive oxygen and nitrogen species which, as signalling molecules, participate in tissue injury-repair-regeneration cascade. The process is also stimulated by arginine whose bioavailability is a limiting factor for NO synthesis. The effects of IHE in combination with arginine (Arg) intake on myogenesis and angiogenesis mediators were examined in a randomized and placebo-controlled trial. Blood samples were collected from 38 elite athletes on the 1st, 7th and 14th days during the training camp. The oral doses of arginine (2 × 6 g/day) and/or IHE using hypoxicator GO2Altitude (IHE and Arg/IHE) were applied. Serum NO and H2O2 concentrations increased significantly and were related to muscle damage (CK activity >900 IU/mL) in IHE and Arg/IHE compared to placebo. The changes in NO and H2O2 elevated the levels of circulating growth factors such as HGF, IHG-1, PDGFBB, BDNF, VEGF and EPO. Modification of the lipid profile, especially reduced non-HDL, was an additional beneficial effect of hypoxic exposure with arginine intake. Intermittent hypoxic exposure combined with high-dose arginine intake was demonstrated to affect circulating mediators of injury-repair-regeneration. Therefore, a combination of IHE and arginine seems to be a potential therapeutic and non-pharmacological method to modulate the myogenesis and angiogenesis in elite athletes.
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Acute supplementation with an amino acid mixture suppressed the exercise-induced cortisol response in recreationally active healthy volunteers: a randomized, double-blinded, placebo-controlled crossover study.
Tsuda, Y, Murakami, R, Yamaguchi, M, Seki, T
Journal of the International Society of Sports Nutrition. 2020;(1):39
Abstract
BACKGROUND Few studies have demonstrated the suppressive effects of amino acids (AAs) on the level of cortisol during exercise in humans. We hypothesized that an AA mixture containing arginine, which promotes lipid metabolism, valine, which effectively decreases the level of glucocorticoid, and serine, a substrate in the production of phosphatidylserine that is reported to blunt increases in cortisol, would suppress the exercise-induced cortisol response by combining the positive effects of the AAs synergistically. METHODS A randomized, double-blinded, placebo-controlled crossover trial was conducted. Twenty healthy recreationally active males ingested either an AA mixture containing 1.8 g of arginine, 1.1 g of valine, and 0.1 g of serine or a placebo. Thirty minutes after ingestion, subjects performed an exercise trial on a cycle ergometer for 80 min at 50% maximal oxygen consumption. Plasma cortisol and other blood parameters immediately before and after the exercise were evaluated. RESULTS Plasma cortisol concentrations after exercise were significantly higher than those before exercise in the placebo condition (9.51 ± 0.85 vs 14.39 ± 2.15, p < 0.05), while there was no significant difference in the AA condition (9.71 ± 0.93 vs 9.99 ± 1.23, p = 0.846). In addition, the increase in plasma cortisol before and after exercise was significantly lower in the AA condition than in the placebo condition (0.28 [- 2.75, 3.31] vs 4.87 [0.89, 8.86], p < 0.05). For the level of adrenocorticotropin, there was a significant difference between before and after exercise only in the placebo condition (24.21 ± 2.91 vs 53.17 ± 6.97, p < 0.01) but not in the AA condition (27.33 ± 3.60 vs 46.92 ± 10.41, p = 0.057). Blood glucose, plasma lactate, plasma ammonia, serum creatine phosphokinase, serum total ketone body, and serum free fatty acid were also significantly changed by the exercise load in both conditions, but no significant differences were observed between the two conditions. CONCLUSIONS The present study demonstrated that the AA mixture suppressed the cortisol response during exercise without affecting exercise-related biological parameters such as glucose or lipid metabolism. TRIAL REGISTRATION UMIN Clinical Trials Registry, UMIN000023587 . Registered 19 August 2016.