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Effects of tree nut and groundnut consumption compared with those of l-arginine supplementation on fasting and postprandial flow-mediated vasodilation: Meta-analysis of human randomized controlled trials.
Smeets, ETHC, Mensink, RP, Joris, PJ
Clinical nutrition (Edinburgh, Scotland). 2021;(4):1699-1710
Abstract
INTRODUCTION l-arginine supplementation may improve vascular endothelial function. As tree nuts and groundnuts are a source of the amino acid l-arginine, we performed a meta-analysis of human randomized controlled trials (RCTs) to compare effects of tree nut and groundnut consumption with those of l-arginine supplementation on fasting and postprandial endothelial function as assessed by flow-mediated vasodilation of the brachial artery (FMD). METHODS Summary estimates of weighted mean differences (WMDs) in FMD and 95% confidence intervals (CIs) were calculated using random-effect meta-analyses. RESULTS A total of thirteen RCTs focusing on tree nut and groundnut consumption and nineteen RCTs investigating effects of l-arginine supplementation were included. Longer-term consumption of tree nuts and groundnuts increased fasting FMD by 1.09 %-point (PP) (95% CI: 0.49, 1.69, P < 0.001; I2: 76.7%, P < 0.001), while l-arginine supplementation (daily range: 3-21 g) increased fasting FMD by 0.53 PP (95% CI: 0.12, 0.93; P = 0.012; I2: 91.6%, P < 0.001). Effects between treatments were not statistically different (P = 0.31). Tree nut and groundnut consumption did not affect postprandial FMD responses (1.25 PP, 95% CI: -0.31, 2.81, P = 0.12; I2: 91.4%, P < 0.001), whereas l-arginine supplementation (range: 3-15 g) improved FMD during the postprandial phase by 2.02 PP (95% CI: 0.92, 3.13, P < 0.001; I2: 99.1%, P < 0.001). However, treatment effects did not differ significantly (P = 0.60). Overall, these results derive from high-quality evidence. CONCLUSION Longer-term consumption of tree nuts and groundnuts, as well as l-arginine supplementation did improve fasting endothelial function, as assessed by FMD. However, the positive effects of tree nuts and groundnuts could not be fully explained by the amount of l-arginine in these nuts. Only l-arginine supplementation did improve postprandial FMD, but effects were not different from those of tree nuts and groundnuts. Future studies should focus on the identifications of the bioactive nutrients in tree nuts and groundnuts and mechanistic pathways behind differences in postprandial and longer-term fasting changes in FMD.
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Effects of l-arginine supplementation on glycemic profile: Evidence from a systematic review and meta-analysis of clinical trials.
Yousefi Rad, E, Nazarian, B, Saboori, S, Falahi, E, Hekmatdoost, A
Journal of integrative medicine. 2020;(4):284-291
Abstract
BACKGROUND The effects of l-arginine supplementation on indices of glycemic control and the role of many factors influencing this intervention have been controversial in clinical trials. OBJECTIVE This meta-analysis was performed to assess the effects of l-arginine supplementation on indices of glycemic control, including fasting blood glucose (FBG), hemoglobin A1c (HbA1c), serum insulin and homeostatic model assessment of insulin resistance (HOMA-IR) levels in randomized controlled trials (RCTs). SEARCH STRATEGY This study conducted a systematic review of RCTs published in PubMed, Scopus, Web of Science, Cochrane Library and Embase, up to 5 May, 2018. INCLUSION CRITERIA Studies were included in this meta-analysis if they were RCTs with parallel design and reported sufficient data on participants before and after intervention, and outcomes of glycemic profile parameters in both the arginine supplementation and control groups. DATA EXTRACTION AND ANALYSIS The screening of titles and abstracts was performed independently by two reviewers. Selected articles were considered if they met the study's inclusion criteria. The quality of included studies was assessed by using the Cochrane Collaboration modified tool. From 710 articles retrieved in the initial search, only 10 trials were suitable for pooling the effects of arginine supplementation on serum glucose, insulin, HOMA-IR and HbA1c levels, with effect sizes of nine, eight, five and five, respectively. RESULTS Pooled random-effect analysis revealed that l-arginine supplementation could significantly decrease FBG level (weighted mean difference [WMD]: 3.35 mg/dL; 95% confidence interval [CI] = [-6.55, -0.16]; P = 0.04) and serum insulin level (WMD: -2.19 μIU/mL; 95% CI = [-3.70, -0.67]; P = 0.005). However, the effects of l-arginine supplementation on HOMA-IR and HbA1c were not significant. Results of subgroup analysis showed that supplementation with l-arginine could significantly decrease serum insulin levels when the dosage of l-arginine is > 6.5 g/d (WMD: -3.49 μIU/mL; 95% CI = [-5.59, -1.38]; P = 0.001), when the duration of supplementation is ≤ 12.8 weeks (WMD: -3.76; 95% CI = [-6.50, -0.98]; P = 0.008), when the participants are not diabetic patients (WMD: -2.54 μIU/mL; 95% CI = [-4.50, -0.50]; P = 0.01) and when the baseline serum level of insulin was > 20 μIU/mL (WMD: -3.98; 95% CI = [-6.31, -1.65]; P = 0.001). CONCLUSION Although the results of this study confirmed that supplementation with l-arginine could have significant effects on some glycemic profile indices of participants in clinical trials, the clinical importance of this reduction may not be meaningful.
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Effect of l-arginine supplementation on C-reactive protein and other inflammatory biomarkers: A systematic review and meta-analysis of randomized controlled trials.
Nazarian, B, Fazeli Moghadam, E, Asbaghi, O, Zeinali Khosroshahi, M, Choghakhori, R, Abbasnezhad, A
Complementary therapies in medicine. 2019;:102226
Abstract
OBJECTIVES We carried out a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of L-arginine on inflammatory biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6) and TNFα. METHODS A systematic search was carried out in PubMed, Embase, Scopus, Cochrane library databases and ISI web of sciences to retrieve the RCTs which examined the effect of L-arginine supplementation on inflammatory biomarkers up to October 2019, with no language and time restriction. Meta-analysis was performed using a random effects model, and I2 index was used to evaluate the heterogeneity. RESULTS Search yielded 2452 publications. Eleven RCTs were eligible. Results indicated that L-arginine supplementation had no significant effect on inflammatory biomarkers including CRP, IL-6 and TNFα. However, when subgroup analysis was performed, we found that L-arginine supplementation increased CRP levels in subjects with ages >60 years old, participants with baseline circulating CRP levels >3 mg/dl, patients with cancer and when used in enteral formula. CONCLUSION Results of the present meta-analysis indicated that L-arginine supplementation increased the circulating concentrations of CRP in subjects with ages >60 years old, subjects with higher levels of CRP, patients with cancer and when used in enteral formula. Therefore, L-arginine should be used with caution in these subjects. However, further well designed, large-scale studies are needed.
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Efficacy of a Disease-Specific Nutritional Support for Pressure Ulcer Healing: A Systematic Review and Meta-Analysis.
Cereda, E, Neyens, JCL, Caccialanza, R, Rondanelli, M, Schols, JMGA
The journal of nutrition, health & aging. 2017;(6):655-661
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Abstract
OBJECTIVES The aim of this systematic review was to summarize the evidence on the efficacy of high-calorie, high-protein nutritional formula enriched with arginine, zinc, and antioxidants (disease-specific support) in patients with pressure ulcers (PUs). METHODS Randomized controlled trials in English published from January 1997 until October 2015 were searched for in electronic databases (EMBASE, Medline, PubMed, and CINAHL). Studies comparing a disease-specific nutritional support (oral supplements or tube feeding) to a control nutritional intervention enabling the satisfaction of energy requirements regardless of the use of high-calorie formula or placebo or no support for at least 4 weeks were considered eligible. Study outcomes were the percentage of change in PU area, complete healing and reduction in the PU area ≥40% at 8 weeks, and the percentage of change in area at 4 weeks. RESULTS A total of 3 studies could be included in the meta-analysis. Compared with control interventions, formulas enriched with arginine, zinc and antioxidants resulted in significantly higher reduction in ulcer area (-15.7% [95%CI, -29.9, -1.5]; P=0.030; I2=58.6%) and a higher proportion of participants having a 40% or greater reduction in PU size (OR=1.72 [95%CI, 1.04, 2.84]; P=0.033; I2=0.0%) at 8 weeks. A nearly significant difference in complete healing at 8 weeks (OR=1.72 [95%CI, 0.86, 3.45]; P=0.127; I2=0.0%) and the percentage of change in the area at 4 weeks (-7.1% [95%CI, -17.4, 3.3]; P=0.180; I2=0.0%) was also observed. CONCLUSIONS This systematic review shows that the use of formulas enriched with arginine, zinc and antioxidants as oral supplements and tube feeds for at least 8 weeks are associated with improved PU healing compared with standard formulas.
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Arginine supplementation for improving maternal and neonatal outcomes in hypertensive disorder of pregnancy: a systematic review.
Gui, S, Jia, J, Niu, X, Bai, Y, Zou, H, Deng, J, Zhou, R
Journal of the renin-angiotensin-aldosterone system : JRAAS. 2014;(1):88-96
Abstract
OBJECTIVE This meta-analysis was performed to assess whether arginine supplementation could reduce preeclampsia or eclampsia incidence and improve the outcomes of hypertensive disorders in pregnancy, and to evaluate the safety of L-arginine supplementation. METHODS The Cochrane Central Register of Controlled Trials (2011), MEDLINE (1980-2011) and Embase (1980-2011) were searched through July 2012, and randomized controlled trials (RCTs) comparing intravenous and/or oral L-arginine supplementation with placebo, or RCTs comparing any treatment with arginine were included. Qualities of RCTs were assessed with the Jadad method. Meta-analyses were performed with fixed- or random-effects models according to heterogeneity of studies. RESULTS Data from seven RCTs involving 916 patients were enrolled. The meta-analysis showed L-arginine was more effective in reducing preeclampsia or eclampsia incidence (odds ratio 0.384; 95% confidence limits 0.25, 0.58) than the placebo; meanwhile, L-arginine could prolong pregnancy weeks (MD 11.54; 95% CL 5.23, 17.85) than placebo; and its effect on blood pressure was unbalanced (diastolic pressure (MD 4.86; 95% CL 4.19, 5.52) and systolic pressure (MD 3.20; 95% CL -1.54, 7.94)) while the difference in increased neonatal weight (MD 256.24; 95% CL -28.66, 541.13) was not clear. Three of these studies reported some adverse effects, and no teratogenic or lethal effects were noted. CONCLUSION This study demonstrates L-arginine supplementation is superior to placebo in lowering diastolic pressure and prolonging pregnancy in patients with gestational hypertension with or without proteinuria, but the effect on lowering systolic pressure and increasing neonatal weight was not statistically significant.
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Efficacy of arginine-enriched enteral formulas in the reduction of surgical complications in head and neck cancer: a systematic review and meta-analysis.
Vidal-Casariego, A, Calleja-Fernández, A, Villar-Taibo, R, Kyriakos, G, Ballesteros-Pomar, MD
Clinical nutrition (Edinburgh, Scotland). 2014;(6):951-7
Abstract
INTRODUCTION Arginine improves healing and modulates inflammation and the immune response. A systematic review and meta-analysis were conducted to assess whether arginine-enriched enteral formulas reduce complications (fistulas, wound infections, other infections) and hospital length of stay (LoS) in patients undergoing surgery for head and neck cancer. METHODS Medline, CENTRAL, and Trip Database were searched using the search strategy "Head and Neck Neoplasms" AND "Enteral Nutrition" AND "Arginine" OR "Immunonutrition". Inclusion criteria comprised: type of study (RCT), language (English, Spanish), outcomes (complications of surgery, LoS), and methodological quality (Jadad scale). The odds ratio (OR) and confidence intervals (95% CI) were calculated using the Mantel-Haenszel method, and the mean difference (MD) with the random effects method. Heterogeneity was assessed using Cochran's Q. RESULTS Six studies were included, with 397 patients receiving peri/postoperative enteral nutrition with different doses of arginine (6.25-18.7 g/L). Enteral formulas containing arginine were associated with a reduction in fistulas [OR = 0.36 (95% CI 0.14-0.95), p = 0.039; Q = 3.93, p = 0.269], and LoS [MD = -6.8 (95% CI -12.6 to -0.9) days, p = 0.023; Q = 2.44, p = 0.486]. There were no reductions in wound infections [OR = 1.04 (95% CI 0.49-2.17), p = 0.925; Q = 1.60, p = 0.809] or other infections [OR = 0.79 (95% CI 0.48-1.31); p = 0.369; Q = 7.94, p = 0.094]. Arginine administration did not increase the occurrence of diarrhoea [OR = 1.80 (95% CI 0.50-6.52), p = 0.375; Q = 0.16, p = 0.691]. CONCLUSIONS The administration of arginine-enriched enteral nutrition led to a significant reduction in fistulas and hospital stay in patients undergoing surgery for head and neck cancer.
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Arginine supplementation in prevention of necrotizing enterocolitis in the premature infant: an updated systematic review.
Mitchell, K, Lyttle, A, Amin, H, Shaireen, H, Robertson, HL, Lodha, AK
BMC pediatrics. 2014;:226
Abstract
BACKGROUND Hypoxic-ischemic injury is thought to play a significant role in necrotizing enterocolitis (NEC). Nitric Oxide (NO) is the principal inhibitory neurotransmitter in the gut and is involved in regulation of mucosal blood flow and maintenance of mucosal integrity. NO is synthesized from L-arginine by NO synthases. Our primary objective was to determine the effectiveness of supplemental L-arginine versus placebo in prevention of NEC in preterm infants ≤ 34 weeks gestational age by systematic review of published randomized controlled trials (RCTs). METHODS This review included RCTs in which L-arginine was administered as a supplement to neonates to prevent NEC. Searches were conducted in OVID MEDLINE, EMBASE, PubMed, and CINAHL from their dates of inception to July, 2014. Inclusion criteria were informed parental consent, neonates born at ≤ 34 weeks gestation, and birth weight ≤ 1500 g. Exclusion criteria included neonates with severe congenital anomalies and inborn errors of metabolism. Incidence of NEC was the primary outcome measure. Whole data were analyzed by RevMan 5.1 (Update Software, Oxford, UK). Outcome data were analyzed to determine risk ratios, number needed to treat, confidence intervals, and test for overall effect. RESULTS Two trials including 425 neonates were eligible for this review. Of these, 235 neonates were included in the study. L-arginine had a 59% reduction in the incidence of stage II and III NEC (RR 0.41, 95% CI 0.20 to 0.85, NNT = 9) compared with placebo (P = 0.02). A similar finding was identified for all stages of NEC (60% reduction, RR 0.40, 95% CI 0.23 to 0.69, NNT = 5) (P = 0.001). At age 3 yrs, there was no significant difference between the 2 groups in terms of any neurodevelopmental disability (RR 0.65; 95% CI 0.23-1.83, P = 0.41). CONCLUSIONS L-arginine supplementation appears to be protective in prevention of NEC in preterm infants and without any significant impact on neurodevelopmental outcomes at 36 months of corrected age. With the addition of the results of one more study to the literature, an intriguing role for L-arginine supplementation continues to gain support. However, large multi-centre RCTs are needed before this can become common practice.
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Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials.
Dong, JY, Qin, LQ, Zhang, Z, Zhao, Y, Wang, J, Arigoni, F, Zhang, W
American heart journal. 2011;(6):959-65
Abstract
BACKGROUND Previous studies suggest that L-arginine, an amino acid and a substrate of nitric oxide synthase, may have blood pressure (BP)-lowering effect. Because some studies were performed with limited number of patients with hypertension and therefore limited statistical power with sometimes inconsistent results, we aimed to examine the effect of oral L-arginine supplementation on BP by conducting a meta-analysis of randomized, double-blind, placebo-controlled trials. METHODS PubMed, Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov databases were searched through June 2011 to identify randomized, double-blind, placebo-controlled trials of oral L-arginine supplementation on BP in humans. We also reviewed reference lists of obtained articles. Either a fixed-effects or, in the presence of heterogeneity, a random-effects model was used to calculate the combined treatment effect. RESULTS We included 11 randomized, double-blind, placebo-controlled trials involving 387 participants with oral L-arginine intervention ranging from 4 to 24 g/d. Compared with placebo, L-arginine intervention significantly lowered systolic BP by 5.39 mm Hg (95% CI -8.54 to -2.25, P = .001) and diastolic BP by 2.66 mm Hg (95% CI -3.77 to -1.54, P < .001). Sensitivity analyses restricted to trials with a duration of 4 weeks or longer and to trials in which participants did not use antihypertensive medications yielded similar results. Meta-regression analysis suggested an inverse, though insignificant (P = .13), relation between baseline systolic BP and net change in systolic BP. CONCLUSIONS This meta-analysis provides further evidence that oral L-arginine supplementation significantly lowers both systolic and diastolic BP.
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Is plasma arginine concentration decreased in patients with sepsis? A systematic review and meta-analysis.
Davis, JS, Anstey, NM
Critical care medicine. 2011;(2):380-5
Abstract
INTRODUCTION L-arginine is a conditionally essential amino acid that plays an important role in immune and vascular function in sepsis. Plasma concentrations of L-arginine are decreased after trauma or surgery but have been variably reported to be normal or decreased in patients with sepsis. METHODS We searched MEDLINE and Embase from database inception until January 2010 for the MESH terms "arginine," "amino acids," and "sepsis" and reviewed all studies that reported plasma arginine concentrations in humans with sepsis. Studies were grouped according to the presence or absence of trauma and surgery. We performed a pooled quantitative analysis on the subset of studies that reported appropriate data. RESULTS We identified 285 citations, of which 16 met inclusion criteria and 10 were included in the quantitative analysis. Plasma arginine concentration was lower in sepsis patients compared with concurrent or historical controls in three of four studies of surgical sepsis, one of four of sepsis after trauma, and all eight studies of predominantly medical sepsis. In the quantitative analysis, mean plasma L-arginine concentration was 33.9 μmol/L (95% confidence interval, 41.2-26.6) lower in sepsis patients than in concurrent nonseptic controls (p < .001), which is a relative decrease of 41%. CONCLUSION Plasma concentrations of plasma L-arginine are substantially decreased in patients with sepsis in the absence of trauma or surgery. There are not enough studies of sufficient quality to determine whether this is also the case for trauma-associated or surgery-associated sepsis.
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Increase in fasting vascular endothelial function after short-term oral L-arginine is effective when baseline flow-mediated dilation is low: a meta-analysis of randomized controlled trials.
Bai, Y, Sun, L, Yang, T, Sun, K, Chen, J, Hui, R
The American journal of clinical nutrition. 2009;(1):77-84
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BACKGROUND Previous trials suggest that oral l-arginine administration affects endothelial function. However, most of these studies were small, the conclusions were inconsistent, and the precise effects are therefore debatable. OBJECTIVE The objective was to assess the effect of oral l-arginine supplementation on endothelial function, as measured with the use of fasting flow-mediated dilation (FMD). DESIGN We conducted a meta-analysis of randomized, placebo-controlled l-arginine supplementation trials that evaluated endothelial function. Trials were identified in PubMed, Cochrane Library, Embase, reviews, and reference lists of relevant papers. The weighted mean difference (WMD) was calculated for net changes in FMD by using random-effect models. Previously defined subgroup analyses and meta-regression analyses were performed to explore the influence of study characteristics. RESULTS Thirteen trials were included and evaluated. Because there was only one long-term study, we focused on short-term effects of l-arginine (12 studies, 492 participants). In an overall pooled estimate, l-arginine significantly increased FMD (WMD: 1.98%; 95% CI: 0.47, 3.48; P = 0.01). Meta-regression analysis indicated that the baseline FMD was inversely related to effect size (regression coefficient = -0.55; 95% CI: -1.00, -0.1; P = 0.016). A subgroup analysis suggested that l-arginine supplementation significantly increased FMD when the baseline FMD levels were <7% (WMD: 2.56%; 95% CI: 0.87, 4.25; P = 0.003), but had no effect on FMD when baseline FMD was >7% (WMD: -0.27%; 95% CI: -1.52, 0.97; P = 0.67). CONCLUSION Short-term oral l-arginine is effective at improving the fasting vascular endothelial function when the baseline FMD is low.