Citrulline 3g oral powder sachets

The primary objective of this systematic review and meta-analysis is to investigate whether L-citrulline supplementation can counteract the adverse effects of cold environments on individual blood pressure (BP), providing scientific evidence for the clinical development and application of L-citrulline as a cardiovascular protective nutritional supplement. A comprehensive search was conducted across four electronic databases: PubMed, Cochrane Library, Embase, and Web of Science. The search period was limited from database inception to May 28, 2025. The Cochrane Risk of Bias tool and JADAD scoring scale were used to assess risk of bias and literature quality of the included randomized controlled trials (RCTs). Statistical analysis of BP data was performed using RevMan 5.4.1 software, employing both random-effects and fixed-effects models for data analysis, and forest plots were generated. The overall intervention effect was evaluated using the weighted mean difference (WMD) and its 95% confidence interval (CI). A total of 6 RCTs investigating the effects of L-citrulline intake on BP in cold environments were included, involving 162 participants (intervention group: 87; control group: 75). Results indicate that L-citrulline intake significantly reduced cold-induced SBP (-9.28 mmHg [95% CI: -10.66 to -7.90], p p = 0.01). Subgroup analysis revealed significant reductions in brachial SBP (-8.74 mmHg [95% CI: -10.61 to -6.88], p p p p = 0.13). Meta-analysis results indicate that L-citrulline supplementation can significantly improve cold exposure-induced BP elevation, providing scientific evidence for the clinical development and application of cardiovascular protective nutritional supplements.

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BackgroundPostmenopausal women are at increased risk of developing cardiovascular, muscular, and metabolic dysfunction due to hormonal changes associated with aging. Citrulline, a non-essential amino acid and precursor to nitric oxide, has gained interest as a potential dietary supplement for improving vascular health, muscle function, and metabolic parameters in this population.ObjectiveThis systematic review aims to evaluate the effects of citrulline supplementation, administered directly or via watermelon products, on cardiovascular, muscular, and metabolic outcomes in postmenopausal women.MethodsA comprehensive literature search was conducted using PubMed, Web of Science, and Scopus databases to identify randomized controlled trials (RCTs) investigating citrulline supplementation in postmenopausal women. Studies were included if they reported outcomes related to blood pressure, arterial stiffness, endothelial function, muscle strength or mass, metabolic parameters, and safety. Study quality was assessed using the Cochrane Risk of Bias Tool 2. Due to heterogeneity in study designs and reported outcomes, results were synthesized narratively.ResultsTwelve RCTs involving 360 postmenopausal women were included. all conducted in the United States, with study durations ranging from 4 to 8 weeks and participant ages between 50 and 75 years. Seven studies reported blood pressure outcomes, with most showing reductions in systolic blood pressure and mean arterial pressure. Five studies examined arterial stiffness, with mixed findings on pulse wave velocity and augmentation index. Four studies assessed endothelial function, two of which demonstrated significant improvements in flow-mediated dilation. Muscle function outcomes were investigated in two studies, suggesting improvements only when citrulline was combined with resistance training. Six studies assessed metabolic parameters, with no consistent effects observed on body weight, glucose, insulin, or lipid profiles. Across all studies, no adverse effects related to citrulline supplementation were reported.ConclusionCitrulline supplementation may offer benefits for blood pressure regulation (up to 9 mmHg SBP reduction in some studies) in hypertensive postmenopausal women, but evidence for arterial stiffness, endothelial function, and metabolic outcomes remains inconsistent. Further large-scale studies are needed before clinical recommendations can be made.

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Background: Citrulline malate (CM) is commonly used as an ergogenic supplement, but its effects on exercise performance and perceived exertion remain uncertain. This systematic review and meta-analysis evaluated the effects of CM supplementation, with attention paid to differences between acute and chronic protocols. Methods: Six databases were searched from inception to August 2025. Randomized controlled trials examining CM supplementation on exercise performance and/or perceived exertion were included. Hedges' g was synthesized using three-level random-effects models to account for dependent effect sizes. Subgroup and moderator analyses explored supplementation protocol, exercise modality, sex, training status, dosage, and ingestion timing. Risk of bias, small-study effects, sensitivity analyses, and GRADE certainty were assessed. Results: Thirty randomized controlled trials contributed 138 effect sizes from 644 participants. CM supplementation was associated with a small improvement in overall exercise performance (g = 0.16, p = 0.01); however, prediction intervals were wide and statistical power was limited. The pooled effect on perceived exertion was not statistically significant. Current evidence appeared more stable for acute than chronic supplementation, although the protocol subgroup difference remained uncertain. Among acute studies, exploratory subgroup analyses suggested possible benefits for aerobic endurance and short anaerobic tasks, but these findings were not robust across sensitivity analyses. No significant between-subgroup differences were found for sex, training status, dosage, or ingestion timing. GRADE certainty ranged from low to very low. Conclusions: CM supplementation may be associated with small, context-dependent improvements in exercise performance, but current evidence remains limited and uncertain. Reliable dosing, timing, and target populations have not been established. Larger trials with verified supplement composition and standardized protocols are needed.

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ObjectiveThis study aims to systematically evaluate the synergistic effects of long-term supplementation of L-citrulline combined with exercise on body composition in adults through a meta-analysis.MethodsThis study primarily summarized and analyzed outcome indicators including body weight (BW), body mass index (BMI), body fat (BF) (including fat mass [FM] and body fat percentage [BFP]), android fat mass (AFM), gynoid fat mass (GFM), and total lean mass (TLM). Statistical analyses were performed using RevMan (Version 5.4) software provided by the Cochrane Collaboration. For continuous variables, the pooled effect sizes were expressed as standardized mean differences (SMD) with their 95% confidence intervals (CI).ResultsA total of 9 randomized controlled trials (RCTs) were included that investigated the effects of long-term supplementation of L-citrulline combined with exercise on body composition in adults. The results indicated that, compared to exercise alone, L-citrulline supplementation combined with exercise significantly improved BF (SMD = -0.21, 95% CI: -0.40 to -0.01, P = 0.03) and AFM (SMD = -0.32, 95% CI: -0.57 to -0.07, P = 0.01). However, no significant effects were observed on BW (SMD = -0.01, 95% CI: -0.27-0.25, P = 0.95), BMI (SMD = 0.01, 95% CI: -0.31-0.33, P = 0.93), GFM (SMD = -0.17, 95% CI: -0.42-0.08, P = 0.18), and TLM (SMD = -0.02, 95% CI: -0.23-0.19, P = 0.83).ConclusionThis study is the first to demonstrate through a meta-analysis that long-term supplementation of L-citrulline combined with exercise can synergistically improve BF and AFM in adults.

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BackgroundThe gastrointestinal tract plays an important role in host defence during critical illness. Disruption of epithelial integrity, microbiome imbalance, and immune dysregulation have all been linked to the translocation of multidrug-resistant (MDR) organisms from intestinal colonization to invasive infection. However, whether these associations reflect true causal mechanisms remains uncertain, and available human evidence has not been comprehensively synthesized using current methodological standards.AimTo systematically evaluate human evidence examining the relationship between intestinal barrier dysfunction, microbial colonization, and subsequent MDR infection in adult critical illness, with particular attention to study quality, heterogeneity, and potential confounding factors.MethodsThis systematic review was conducted in accordance with PRISMA guidelines. A structured literature search was performed in PubMed, EMBASE, and the Cochrane Library (2000-2025) using predefined Boolean combinations and Medical Subject Headings. Prospective and retrospective cohort studies involving intensive care units (ICU) adults were included if they evaluated intestinal colonization, biomarkers of barrier dysfunction (citrulline and intestinal fatty acid-binding protein), microbiome alterations, or endotoxemia. Study selection and data extraction were undertaken independently by two reviewers, with disagreements resolved through discussion. Risk of bias was assessed using the Newcastle-Ottawa Scale and ROBINS-I tool. Owing to methodological and clinical heterogeneity, findings were synthesized using a structured narrative approach rather than meta-analysis.ResultsAcross the included studies, intestinal colonization with carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii, and vancomycin-resistant Enterococcus was consistently associated with an increased risk of subsequent bloodstream infection. However, progression rates varied considerably across cohorts, likely reflecting differences in patient characteristics, antimicrobial exposure, and ICU practices rather than a consistent effect size. Biomarker studies showed reduced citrulline levels and elevated intestinal fatty acid-binding protein concentrations in patients with gastrointestinal dysfunction; however, these markers indicate enterocyte injury rather than directly measuring intestinal permeability or bacterial translocation. Microbiome analyses demonstrated reduced diversity and impaired colonization resistance, although the extent and timing of these changes were not uniform across studies. Taken together, the evidence supports a biologically plausible link between epithelial injury, dysbiosis, and infection risk, but does not establish a direct causal relationship, largely due to the observational design of available studies and the influence of confounding factors such as illness severity, antimicrobial exposure, and ICU environment.ConclusionGut barrier dysfunction appears to contribute to the pathogenesis of MDR infection in critically ill adults; however, current evidence supports association rather than causation. Early recognition of intestinal colonization and strategies aimed at preserving mucosal integrity may offer potential clinical benefit, although their effectiveness requires confirmation in well-designed prospective and interventional studies.

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