산화질소 부스터

Impact of Chronic Nitrate and Citrulline Malate Supplementation on Performance and Recovery in Spanish Professional Female Soccer Players: A Randomized Controlled Trial.

1. Nutrients. 2025 Jul 21;17(14):2381. doi: 10.3390/nu17142381. Impact of Chronic Nitrate and Citrulline Malate Supplementation on Performance and Recovery in Spanish Professional Female Soccer Players: A Randomized Controlled Trial. Ramírez-Munera M(1), Arcusa R(1), López-Román FJ(2)(3), Ávila-

Contrast-enhanced ultrasound for determining muscular perfusion after oral intake of L-citrulline, L-arginine, and galloylated epicatechines: A study protocol.

1. Medicine (Baltimore). 2020 Oct 9;99(41):e22318. doi: 10.1097/MD.0000000000022318. Contrast-enhanced ultrasound for determining muscular perfusion after oral intake of L-citrulline, L-arginine, and galloylated epicatechines: A study protocol. Doll J(1), Bürkle F(1), Neide A(1), Tsitlakidis S(1), Bruckner T(2), Schmidmaier G(1), Fischer C(1). Author information: (1)Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Ultrasound Center, HTRG - Heidelberg Trauma Research Group, Heidelberg University Hospital. (2)Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany. INTRODUCTION: The market for dietary supplements in the sports sector has been growing rapidly for several years, though there is still lacking evidence regarding their claimed benefits. One group is that of nitric oxide increasing supplements, so-called "NO-boosters," which are claimed to improve the supply of oxygen and nutrients to the muscle by enhancing vasodilation.The aim of this study was to investigate 3 of these supplements in healthy male athletes for their muscle perfusion-enhancing potential using contrast-enhanced ultrasound (CEUS). METHODS: This placebo-controlled, double-blind, randomized cross-over trial will be carried out at the Center for Orthopedics, Trauma Surgery and Spinal Cord Injury of the University Hospital Heidelberg. Three commercial NO enhancing products including 300 mg of the specific green tea extract VASO6 and a combination of 8 g L-citrulline malate and 3 g L-arginine hydrochloride will be examined for their potential to increase muscular perfusion in 30-male athletes between 18 and 40 years and will be compared with a placebo. On each of the 3 appointments CEUS of the dominant biceps muscle will be performed at rest and after a standardized resistance training. Every athlete receives each of the 3 supplements once after a wash-out period of at least 1 week. Perfusion will be quantified via VueBox quantification software. The results of CEUS perfusion measurements will be compared intra- and interindividually and correlated with clinical parameters. DISCUSSION: The results of this study may help to establish CEUS as a suitable imaging modality for the evaluation of potentially vasodilatory drugs in the field of sports. Other supplements could also be evaluated in this way to verify the content of their advertising claims. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), ID: DRKS00016972, registered on 25.03.2019. DOI: 10.1097/MD.0000000000022318 PMCID: PMC7544292 PMID: 33031270 [Indexed for MEDLINE]

Flavonoid Composition and Molecular Basis of the Potential Sexual-Enhancing Properties of a Turnera diffusa Extract (Liboost(®)).

1. Pharmaceuticals (Basel). 2026 Apr 8;19(4):597. doi: 10.3390/ph19040597. Flavonoid Composition and Molecular Basis of the Potential Sexual-Enhancing Properties of a Turnera diffusa Extract (Liboost(®)). Benito-Vázquez I(1)(2), Morán-Valero MI(2), Díez-Municio M(2), Mena-García A(2). Author information: (1)Instituto de Investigación en Ciencias de la Alimentación, CIAL (CSIC-UAM), Nicolás Cabrera 9, 28049 Madrid, Spain. (2)Pharmactive Biotech Products SLU, Faraday, 7, 28049 Madrid, Spain. Background/Objectives: Sexual dysfunction is a prevalent and multifactorial condition affecting a large proportion of the global population, with limited therapeutic options beyond pharmacological approaches primarily targeting erectile dysfunction. This has increased interest in botanical supplements for sexual health, although mechanistic evidence and clear links between phytochemical composition and biological activity remain scarce. The present study provides an integrative evaluation of a commercial Turnera diffusa extract (Liboost®) formulated to support sexual health by combining detailed phytochemical characterization with targeted in vitro mechanistic assays. Methods: The extract was characterized by HPLC-DAD-HRMS, enabling the identification and semi-quantification of its major constituents. A total of 49 compounds were detected, predominantly flavonoids, including luteolin- and apigenin-derived glycosides, flavonols, methoxyflavones, flavanones, and coumaroyl derivatives, with a total quantified flavonoid content of 15.9 mg·g-1. Biological activity was evaluated in human cell models without cytotoxic effects at the tested concentrations. Results: Liboost® significantly reduced PDE5 expression, inhibited aromatase activity, and moderately increased nitric oxide production. These complementary effects suggest a multi-target modulation of pathways involved in sexual function, integrating vascular, endocrine, and nitrergic mechanisms. Conclusions: Although limited to in vitro models, the findings provide mechanistic support for the biological activity of T. diffusa extracts and highlight the importance of linking phytochemical composition with functional evidence when evaluating botanical supplements. DOI: 10.3390/ph19040597 PMID: 42075853

Effect of Beetroot Nitrate Supplementation on Nitric Oxide Pathways and Oxy-Inflammatory Biomarkers in Amateur Triathletes: A Randomized Cross-Over Pilot Study.

2. Nutrients. 2026 Apr 12;18(8):1215. doi: 10.3390/nu18081215. Effect of Beetroot Nitrate Supplementation on Nitric Oxide Pathways and Oxy-Inflammatory Biomarkers in Amateur Triathletes: A Randomized Cross-Over Pilot Study. Mrakic-Sposta S(1), Vezzoli A(1), Parenza M(2), Magno M(2), D'Angelo G(2), Nannipieri F(3), Battaglia S(3), Solfanelli L(3), Tacconi E(4), Dellanoce C(1), Montorsi M(1)(5), Pratali L(2). Author information: (1)Institute of Clinical Physiology, National Research Council (IFC-CNR), Piazza dell'Ospedale Maggiore, 3, 20162 Milan, Italy. (2)Institute of Clinical Physiology, National Research Council (IFC-CNR), Via Giuseppe Moruzzi 1, 56124 Pisa, Italy. (3)Medical Research, Abiogen Pharma, Via Antonio Meucci, 36, 56121 Pisa, Italy. (4)Private Practice, Via Matteo Degli Organi 1, 59100 Prato, Italy. (5)Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, Via di Val Cannuta, 247, 00166 Roma, Italy. Background/Objectives: Nitric oxide (NO) is a key mediator of vascular, metabolic, and redox pathways, influencing exercise performance. Beetroot, a natural source of inorganic nitrate, increases NO bioavailability and may modulate oxidative stress and inflammation, though data in endurance athletes remain limited. The aim of this study was to assess the effects of a novel beetroot-based nitrate supplement (B-bNs) on NO metabolism, oxidative stress, and inflammation in non-professional triathletes. Methods: This was a randomized 2 × 2 cross-over pilot study with two 7-day periods (B-bNs vs. No treatment), separated by a 15-day washout (4 visits: Day 1, 7, 22 and 28). Samples were collected at baseline (T0), 2 h post-first dose (T1), and after 7 days (T2) for the supplementation period (B-bNs) and at T0 and T2 for the "no treatment" period. The following biomarkers from plasma and urine were evaluated: NO pathway (NO metabolites (NOx), nitrite (NO2), inducible nitric oxide synthase (iNOS), peroxynitrite, 3-nitrotyrosine (3-NT)), oxidative stress (reactive oxygen species (ROS) production, 8-isoprostane, superoxide dismutase (SOD) activity), and cytokines (IL-6, IL-10). A total of 10 male triathletes (mean age 48.1 ± 9.8 years and BMI 23.9 ± 2.2 kg/m2) participated in this study. Results: No adverse events were reported. After 7 days of supplementation (T2 vs. T0), significant increases in NOx in plasma and urine (about +155%), iNOS (+56%), peroxynitrite (+60%), 3-NT (+8.6%), ROS (+413%) and IL-6 (+73%) were recorded. These values resulted significantly higher compared to "no treatment" (all p = 0.002), with no significant differences for 3-NT, SOD, 8-isoprostane, IL-6, and IL-10. Conclusions: Beetroot-based nitrate supplementation may enhance the NO-related pathway in non-professional endurance athletes with nitric-peroxydation activation, occurring without evidence of lipid oxidative damage. Larger placebo-controlled trials with standardized diet/training and performance outcomes are needed to determine the functional significance of these preliminary findings. This study was registered in the ISRCTN registry (ISRCTN10885376). DOI: 10.3390/nu18081215 PMID: 42075028 [Indexed for MEDLINE]

Protective effects of Lactiplantibacillus plantarum YC225 Mixture Are associated with Gut Microbiota in Vulvovaginal Candidiasis.

3. J Microbiol Biotechnol. 2026 Apr 27;36:e2601030. doi: 10.4014/jmb.2601.01030. Protective effects of Lactiplantibacillus plantarum YC225 Mixture Are associated with Gut Microbiota in Vulvovaginal Candidiasis. Kim HJ(1), Kim DG(2), Go SW(3), Park JH(4), Jin JS(4), Choi H(4), Ahn JH(5), Park I(6), Park ES(6). Author information: (1)Kimchi Functionality Research Group, World Institute of Kimchi, Gwangju 61755, Republic of Korea. (2)Departments of Korean Medicine, Dong-eui University, Busan 47340, Republic of Korea. (3)Department of Pharmacy, Jeonbuk National University, Jeonju-si 54896, Republic of Korea. (4)Department of Oriental Medicine Resources, Jeonbuk National University, Iksan-si 54596, Republic of Korea. (5)Department of Korean Pharmacy, Woosuk University, Jeonbuk 55338, Republic of Korea. (6)Yuhan care Co., Ltd., Seoul 07335, Republic of Korea. Vulvovaginal candidiasis (VVC) is a prevalent mucosal infection predominantly caused by Candida albicans (C. albicans). Vaginal lactobacilli contribute to colonization resistance and epithelial barrier integrity. However, therapeutic options remain limited and recurrence is common. In this study, we investigated the effects of a lactic acid bacteria mixture (LM; InoRexyne®) enriched with Lactiplantibacillus plantarum YC225 on antifungal activity and inflammation in vitro and in an estrogenized murine VVC model. In RAW264.7 macrophages and VK2/E6E7 vaginal epithelial cells, the LM cell-free supernatant inhibited C. albicans growth and reduced inflammatory readouts induced by lipopolysaccharide or C. albicans. In vivo, oral LM administration for 14 d attenuated VVC-associated histopathological damage, reduced vaginal IL-6 and nitric oxide levels, and decreased fungal burden compared with infected controls. LM also increased the expression of the tight junction marker gene Tjp1 and modulated inflammatory gene expression in vaginal tissue (NanoString panel), including downregulation of selected pro-inflammatory pathways and upregulation of the anti-fibrotic regulator Smad7. 16S rRNA profiling of fecal samples showed LM-associated shifts in gut microbial composition, including increased abundance of Lactobacillus/L. plantarum and decreased abundance of several opportunistic taxa. Correlation analysis suggested associations between specific gut taxa and VVC parameters. Collectively, these findings indicate that oral LM may mitigate VVC-associated inflammation, epithelial damage, and fungal burden, and these effects are accompanied by changes in gut microbiota composition. DOI: 10.4014/jmb.2601.01030 PMID: 42049691 [Indexed for MEDLINE]

The protective influence of orange essential oil nano-emulsion on growth performance, antioxidant activity, immune status, inflammatory response, and hepato-renal function in heat-stressed growing rabbits.

4. Trop Anim Health Prod. 2026 Apr 17;58(4):230. doi: 10.1007/s11250-026-05005-w. The protective influence of orange essential oil nano-emulsion on growth performance, antioxidant activity, immune status, inflammatory response, and hepato-renal function in heat-stressed growing rabbits. Areda HA(1), Hassan MAE(2), Embaby EM(3), Megahed A(4), Hamed SE(5), El-Said EA(1). Author information: (1)Animal, Poultry and Fish Production Department, Faculty of Agriculture, Damietta University, Damietta, Egypt. (2)Animal Production Research Institute (APRI), Agriculture Research Center, Ministry of Agriculture, Dokki, Giza, 12619, Egypt. (3)Department of Physiology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt. emanmohamed@mans.edu.eg. (4)Department of Clinical Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt. (5)Department of Agricultural Biotechnology, Faculty of Agriculture, Damietta University, Damietta, Egypt. Heat stress (HS) adversely affects rabbit production, reducing growth performance, physiological responses, and farm profitability. Nanoemulsified orange essential oil (NOEO) is a natural antioxidant with anti-inflammatory properties that may mitigate oxidative stress and enhance cellular defense mechanisms. This study evaluated the effects of dietary NOEO on growth performance, blood biochemistry, antioxidant status, immune and inflammatory responses, and liver and kidney histomorphology in heat-stressed rabbits. Forty-eight six-week-old male New Zealand White rabbits (752.91 ± 17.40 g) were randomly assigned to four groups: a control group fed a basal diet and three treatment groups receiving the same diet supplemented with 100, 200, or 400 mg NOEO/kg feed. Heat-stressed rabbits supplemented with NOEO showed significant (p < 0.05) improvements in body weight, feed conversion ratio, and performance index. Blood hematology and serum levels of total protein, albumin, total cholesterol, triglycerides, low-density lipoprotein, and very low-density lipoprotein were also enhanced in all treated groups compared with the control. NOEO supplementation improved antioxidant defenses, as indicated by increased total antioxidant capacity and elevated activities of key antioxidant enzymes (glutathione peroxidase, catalase, and superoxide dismutase), particularly in the NOEO400 treated group (p < 0.05). Nitric oxide levels were significantly higher, while malondialdehyde concentrations were significantly lower in NOEO200 and NOEO400 groups, reflecting reduced oxidative stress (p < 0.05). Immune responses were strengthened, with higher serum IgM and IgA levels, accompanied by downregulation of pro-inflammatory cytokines IL-6 and IFN-γ (p < 0.05). Furthermore, liver and kidney function and tissue structure were improved in NOEO-supplemented rabbits. In conclusion, dietary NOEO, particularly at 400 mg/kg, enhanced growth performance, antioxidant status, immune competence, and hepato-renal health in heat-stressed rabbits, likely through improved cellular defense mechanisms that protect against oxidative and inflammatory damage. DOI: 10.1007/s11250-026-05005-w PMCID: PMC13086674 PMID: 41991733 Conflict of interest statement: Declarations. Ethical approval: All animal experiments and procedures were conducted in accordance with the U.K. Animals (Scientific Procedures) Act, 1986 and associated guidelines, EU Directive 2010/63/EU for animal experiments, in comply with the ARRIVE guidelines. Mansoura University’s Institutional Review Board (IRB) approved the study with code number (MU-ACUC; VM.R.24.11.193). Conflict of interest: No conflict of interest.

Ganoderma lucidum mediates microglial polarization and ameliorates experimental autoimmune encephalomyelitis by reducing oxidative stress and inhibiting NF-κB/STAT3 pathway.

5. Chin Med. 2026 Apr 10;21(1):114. doi: 10.1186/s13020-026-01327-x. Ganoderma lucidum mediates microglial polarization and ameliorates experimental autoimmune encephalomyelitis by reducing oxidative stress and inhibiting NF-κB/STAT3 pathway. Zhang L(#)(1), Chen J(#)(1)(2), Yuen S(1), Wu M(1), Li W(1), Yan S(1), Shen J(3)(4). Author information: (1)School of Chinese Medicine, State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong, 3 Sassoon Road, Pokfulam, Hong Kong SAR, China. (2)Department of Orthopedics, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. (3)School of Chinese Medicine, State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, The University of Hong Kong, 3 Sassoon Road, Pokfulam, Hong Kong SAR, China. shenjg@hku.hk. (4)Department of Orthopedics, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. shenjg@hku.hk. (#)Contributed equally Multiple Sclerosis (MS) is a neuroinflammatory disease affecting the central nervous system (CNS), for which effective therapeutic strategies remain limited. Ganoderma Lucidum (GL) is a nature healthy food supplement whose effects on MS remain unknown. Using an experimental autoimmune encephalomyelitis (EAE) mouse model, we tested the hypothesis that GL could mitigate MS by inhibiting microglial activation and promoting a shift toward an anti-inflammatory M2-like phenotype. We demonstrate that early preventive administration of GL significantly reduced disease severity, inflammatory infiltration, demyelination, and microglial activation and polarization by promoting M2-like polarization in the spinal cord of EAE mice. Furthermore, using in vitro cellular experiments, GL revealed antioxidant and anti-inflammatory effects by scavenging superoxide (O2·-), nitric oxide (NO·) and peroxynitrite (ONOO-) and down-regulated the expression of IL-1β, TNF-α, IL-6, COX2, and iNOS in the LPS-stimulated microglial cells. GL inhibited the expression of nuclear factor-κB/signal transducer and activator of transcription 3 (NF-κB/STAT3). Taken together, Ganoderma lucidum is a promoting antioxidant and anti-inflammatory healthy supplement to inhibit microglial activation and attenuate the severity and progress of MS pathogenesis by reducing oxidative stress and modulating NF-κB/STAT3 signaling pathways. © 2026. The Author(s). DOI: 10.1186/s13020-026-01327-x PMCID: PMC13067805 PMID: 41957858 Conflict of interest statement: Declarations. Ethics approval and consent to participate: This study was carried out under the guidance of experimental animals, and the committee approved all animal procedures on the Use of Live Animals in Teaching and Research, at HKU. Competing interests: The authors declare no competing interests.

Multifaceted evaluation of cysteamine-loaded nanoliposomes in buffalo sperm cryopreservation: Impacts on motility, ultrastructural integrity, oxidative balance, apoptotic gene expression, and fertility.

6. Cryobiology. 2026 Apr 6;123:105629. doi: 10.1016/j.cryobiol.2026.105629. Online ahead of print. Multifaceted evaluation of cysteamine-loaded nanoliposomes in buffalo sperm cryopreservation: Impacts on motility, ultrastructural integrity, oxidative balance, apoptotic gene expression, and fertility. Elmorsy EM(1), Mohammed AK(2), Hifni BA(3), Alyamani SA(3), Al-Ghafari AB(4), Al Doghaither HA(5), Hassan MAE(6), El-Dein MA(7). Author information: (1)Center for Health Research, Northern Border University, P.O. Box 1321, Arar, 91431, Saudi Arabia. Electronic address: Ekramy.elmorsy@nbu.edu.sa. (2)Department of Animal Production, College of Agriculture, University of Kerbala, Kerbala, Iraq. (3)Department of Biology, Preparatory Year Program, Batterjee Medical College, Jeddah, 21442, Saudi Arabia. (4)Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia. (5)Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia. (6)Animal Production Research Institute (APRI), Agriculture Research Center, Ministry of Agriculture, Dokki, Giza, 12619, Egypt. (7)Zoology Department, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt. This study aimed to evaluate the impact of incorporating cysteamine-loaded nanoliposomes (CY-NPs) into a semen extender on semen quality, sperm kinematics, redox status, apoptosis-like changes, ultrastructure, and fertility outcomes. Semen was collected from seven healthy, fertile bulls (4-6 years old) using the artificial vagina technique, and a total of 42 ejaculates were obtained over six weeks. Each sample was analyzed in three replicates. Pooled ejaculates were cryopreserved in a Tris-based extender supplemented with 0, 25, 50, or 100 μg/mL of CY-NPs. Polynomial regression analysis showed that progressive motility, membrane functionality, and viability peaked at 60-75 μg/mL. CY-NPs supplementation enhanced sperm kinematics, increased total antioxidant capacity, and elevated activities of key antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase, while significantly reducing malondialdehyde, nuclear factor kappa B, and nitric oxide levels in seminal plasma (p < 0.05). The percentage of apoptotic sperm cells decreased significantly, accompanied by upregulation of the anti-apoptotic Bcl-2 gene and downregulation of pro-apoptotic genes Bax and caspase 3. Electron microscopy confirmed that CY-NPs protect sperm ultrastructure, including the plasma membrane, acrosome, and mitochondria. Notably, supplementation with 50 μg/mL CY-NPs improved frozen-thawed semen fertility, increasing buffalo cow pregnancy rates by 23.33 % compared to controls (p = 0.0001). Overall, adding CY-NPs to the freezing extender enhanced semen quality, velocity, antioxidant status, and enzymatic balance, reduced apoptosis, preserved structural integrity, and improved fertility of cryopreserved buffalo sperm. Copyright © 2026. Published by Elsevier Inc. DOI: 10.1016/j.cryobiol.2026.105629 PMID: 41946112 Conflict of interest statement: Conflict of interest The authors declare that there is no conflict of interest with any financial organization regarding the materials discussed in the manuscript.

A high-fat diet with vitamin D and propylthiouracil produces a pro-atherogenic phenotype in rats.

7. Animal Model Exp Med. 2026 Apr 1. doi: 10.1002/ame2.70178. Online ahead of print. A high-fat diet with vitamin D and propylthiouracil produces a pro-atherogenic phenotype in rats. Lewies A(1), Kodogo V(1), Wentzel JF(2), Smit FE(1). Author information: (1)Department of Cardiothoracic Surgery, Robert WM Frater Cardiovascular Research Centre, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa. (2)Department of Genetics, Faculty of Natural and Agricultural Sciences, University of the Free State, Bloemfontein, South Africa. BACKGROUND: Atherosclerosis begins with dyslipidemia, vascular inflammation, and endothelial dysfunction. Rodent models that capture these early events are needed for mechanistic and interventional studies. This study evaluated whether a cholesterol-rich, high-fat diet (HFD) supplemented with vitamin D and propylthiouracil (PTU) promotes a pro-atherogenic phenotype in rats, as evidenced by dyslipidemia, inflammation, markers of endothelial dysfunction, and early vascular remodeling. METHODS: Male Sprague-Dawley rats (n = 18) received standard chow or a HFD containing 2% cholesterol, 3% lard, 0.5% cholate, vitamin D (200 000 IU/kg), and PTU (0.2% w/w) for 11 weeks. Terminal serum total cholesterol, high-density lipoprotein, low-density lipoprotein (LDL)/very low-density lipoprotein (VLDL), triglycerides, calcium, interleukin-6 (IL-6), C-reactive protein, serum amyloid A (SAA), circulating endothelial nitric oxide synthase (eNOS), and intracellular adhesion molecule-1 (ICAM-1) were measured. The aorta, the coronary arteries, and the liver were examined histologically. RESULTS: HFD-fed rats developed significant hypercholesterolemia with higher total cholesterol and LDL/VLDL (p < 0.0001) and lower triglycerides (p < 0.0001) versus controls. Serum calcium was higher (p < 0.0001) without vascular calcification. Aortae exhibited wall thickening, smooth-muscle disarray, mononuclear infiltrates, and focal foam cell-like changes; coronary arteries exhibited endothelial irregularities and perivascular infiltrates. Livers exhibited micro- and macrovesicular steatosis. IL-6 and SAA were higher (p < 0.05), and circulating eNOS was lower (p < 0.05); ICAM-1 did not differ significantly. CONCLUSION: An 11-week vitamin D/PTU-supplemented HFD induces an LDL-dominant dyslipidemia with systemic inflammation and evidence consistent with endothelial dysfunction, alongside histological features of early vascular remodeling and hepatic steatosis. This nongenetic model may be useful for studying early atherogenic changes. © 2026 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences. DOI: 10.1002/ame2.70178 PMID: 41923301

Influence of Acute Beetroot Juice Intake on Agility Performance Immediately Post-Repeated Maximal Sprinting in Soccer Players.

8. Nutrients. 2026 Mar 12;18(6):897. doi: 10.3390/nu18060897. Influence of Acute Beetroot Juice Intake on Agility Performance Immediately Post-Repeated Maximal Sprinting in Soccer Players. Yang X(1), Nakao T(2), Saito A(3). Author information: (1)Graduate School of Human-Environment Studies, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan. (2)Faculty of Human Science, Kyushu Sangyo University, 3-1 Matsukadai 2, Higashi-ku, Fukuoka 813-8503, Japan. (3)Faculty of Human-Environment Studies, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan. BACKGROUND/OBJECTIVES: Acute beetroot juice (BJ) nitrate supplementation may enhance agility and change of direction performance by increasing nitric oxide bioavailability and improving cognitive and skeletal muscle functions, thereby potentially attenuating post-sprint performance decrements. METHODS: We investigated whether a single dose of BJ improves agility immediately after repeated maximal sprinting compared with a placebo (PL) in soccer players. Twenty-one male soccer players (competitive players: n = 8; recreational players: n = 13) completed a double-blind randomised crossover trial. Participants ingested 70 mL of BJ or PL; afterwards, they performed three sets of 6 × 20-m all-out sprints. Agility outcomes included simple response time (SRT), choice response time (CRT), and change-of-direction speed (CODS). Non-parametric analyses (Wilcoxon signed-rank test with effect size r) were applied. RESULTS: Compared with PL, BJ improved CRT (BJ: 2.376 ± 0.255; PL: 2.534 ± 0.322; p < 0.001; r = 0.74; Z = -5.881) and CODS (BJ: 13.046 ± 1.512; PL: 13.651 ± 1.811; p < 0.001; r = 0.47; Z = -4.314). SRT was unchanged overall (BJ: 1.671 ± 0.195; PL: 1.707 ± 0.261; p = 0.185; r = 0.05; Z = -1.327). CONCLUSIONS: Under practical field-based conditions, acute BJ intake enhanced post-sprint agility and change-of-direction performance, particularly CRT and CODS. DOI: 10.3390/nu18060897 PMCID: PMC13028686 PMID: 41901071 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Oxidative Stress and the KEAP1/NRF2 Axis in Saphenous Vein: Implications for Graft Patency.

9. Cells. 2026 Mar 20;15(6):563. doi: 10.3390/cells15060563. Oxidative Stress and the KEAP1/NRF2 Axis in Saphenous Vein: Implications for Graft Patency. Layton GR(1)(2)(3), Marston E(1)(3), Musa HL(1), Ladak S(1)(3), Copperwheat A(2), Oluwanifemi A(2), Antoun I(1)(4), Zakkar M(1)(2)(3). Author information: (1)Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP, UK. (2)Department of Cardiac Surgery, University Hospitals of Leicester NHS Trust, Leicester LE3 9QP, UK. (3)Leicester British Heart Foundation Centre of Research Excellence, Leicester LE3 9QP, UK. (4)Department of Cardiology, University Hospitals of Leicester NHS Trust, Leicester LE1 5WW, UK. Vein graft disease remains a significant limitation to the long-term patency of venous conduits following coronary artery bypass grafting. Early oxidative stress, triggered by ischaemia-reperfusion injury and haemodynamic changes following the implantation of veins into the arterial circulation, disrupts endothelial integrity and initiates inflammation, apoptosis, and maladaptive remodelling. The KEAP1-NRF2 axis is a central regulator of cellular antioxidant responses; however, its role in the development of vein graft disease remains poorly defined. This narrative review aimed to summarise what is known about NRF2/KEAP1 signalling in modulating vein graft pathology. METHODS: A systematic search of PubMed was conducted to identify original research studies examining the NRF2/KEAP1 pathway in human saphenous vein tissue in vivo or ex vivo. Narrative synthesis was performed due to limited evidential availability and study heterogeneity. RESULTS: Only one study has directly evaluated NRF2 pathway activation directly in human saphenous vein tissue, and it demonstrated that Protandim (a herbal dietary supplement) treatment increased antioxidant enzyme activity and reduced oxidative stress markers, including superoxide and 4-hydroxynonenal, both known activators of MAPK-dependent smooth muscle proliferation. Adjacent studies in other cells and tissues reveal that NRF2 intersects with multiple pathways central to vein graft pathology: it suppresses NFκB-mediated inflammation, modulates eNOS-NO signalling, inhibits NADPH oxidase expression, regulates MAPK activation, and influences angiogenic responses. However, context-dependent activation of NRF2 under arterial cyclic stretch can paradoxically drive proliferation through p62-mediated KEAP1 sequestration and enhanced glutathione synthesis. CONCLUSIONS: The NRF2/KEAP1 pathway serves as a central integrator of oxidative stress responses that directly intersect with established mechanisms of intimal hyperplasia and pathological angiogenesis. Post-translational KEAP1 inhibition may offer a targeted intervention point to limit these processes. Critical gaps remain regarding our understanding of the role of NRF2 in human saphenous vein under physiological arterial conditions and sex-specific pathway regulation. Mechanistic studies in vein-specific models are essential for advancing our understanding and any potential therapeutic translation. DOI: 10.3390/cells15060563 PMCID: PMC13025489 PMID: 41892352 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Taurine supplementation and systemic lupus erythematosus in preclinical studies: a systematic review of clinical outcomes and underlying mechanisms.

10. Amino Acids. 2026 Mar 24;58(1):24. doi: 10.1007/s00726-026-03516-2. Taurine supplementation and systemic lupus erythematosus in preclinical studies: a systematic review of clinical outcomes and underlying mechanisms. Malek Mahdavi A(#)(1), Javadivala Z(2), Orooji N(#)(3). Author information: (1)Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. aidamalek@gmail.com. (2)Department of Health Education and Promotion, Tabriz University of Medical Sciences, Tabriz, Iran. (3)Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. nilufar.oruji77923@gmail.com. (#)Contributed equally Taurine (Tau) is a sulfur-containing amino acid that has therapeutic roles in several diseases, including inflammatory conditions. The involvement of Tau in modulating systemic lupus erythematosus (SLE) autoimmunity has been indicated in preclinical models, but reports are contradictory. This systematic review aimed to summarize current research regarding the potential role of Tau in SLE, to notice knowledge gaps, and to offer suggestions for the way ahead. The literature search was carried out using PubMed, Scopus, Web of Science, and Google Scholar databases until October 2025. Search alert services were also applied to notice related papers published after the primary search. All studies investigating the effects of Tau in SLE that met the inclusion criteria were eligible. Out of 77 articles initially found, only six preclinical studies (animal and in-vitro) were eligible, and no qualified clinical study was identified. Five studies indicated that Tau was helpful in improving clinical parameters, decreasing T helper 1 (Th1) and Th17 cells and inflammatory mediators (e.g., tumor necrosis factor-α, C-reactive protein, and inducible nitric oxide synthase), removing reactive oxygen species and decreasing oxidative markers like malondialdehyde, increasing regulatory T (Treg) and Th2 cells and anti-inflammatory interleukin-4 and interleukin-10 cytokines, increasing antioxidant enzymes superoxide dismutase and glutathione peroxidase, and inhibiting both FAS- and mitochondrial-dependent apoptotic signaling components. However, only one preclinical study reported that Tau aggravated SLE progression characterized by increased generation of type I interferons, enhanced autoantibodies and proteinuria, further lymphocyte activation, and critical nephritis. The current review provides evidence about the role of Tau in SLE and highlights the importance of further well-designed clinical trials to confirm these results, establish optimal dose and assess safety and long-term efficacy. © 2026. The Author(s). DOI: 10.1007/s00726-026-03516-2 PMCID: PMC13038805 PMID: 41874670 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Conflict of interest: The authors declare no competing interests.

Acute effect of citrulline malate on flow-mediated dilation and serum pharmacodynamics in healthy young males.

11. Front Physiol. 2026 Mar 6;17:1773582. doi: 10.3389/fphys.2026.1773582. eCollection 2026. Acute effect of citrulline malate on flow-mediated dilation and serum pharmacodynamics in healthy young males. Grannes J(1), Callender NA(2), Gonzalez AM(3), Hisdal J(2)(4), Vårvik FT(1)(5), Bjørnsen T(5)(6). Author information: (1)Department of Sports Science and Physical Education, University of Agder, Kristiansand, Norway. (2)Department of Vascular Surgery, Oslo University Hospital, Oslo, Norway. (3)Department of Allied Health and Kinesiology, Hofstra University, Hempstead, NY, United States. (4)Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. (5)Norwegian Olympic and Paralympic Committee and Confederation of Sports, Oslo, Norway. (6)Department of Education and Sports Science, University of Stavanger, Stavanger, Norway. INTRODUCTION: The use of ergogenic compounds has gained increasing popularity among individuals who wish to improve performance and recover faster from their workouts. Among these products is citrulline malate (CitMal), a popular dietary supplement that is suggested to enhance nitric oxide (NO)-mediated vasodilation and muscle blood flow. METHODS: To evaluate effects on arterial function, flow-mediated dilation (FMD) of the brachial artery during active hyperemia was measured in 12 healthy, recreationally active males (23 ± 3 years) before and after (60- and 120-min post) consuming either 6 g CitMal, 12 g CitMal, or a taste-matched placebo. The study used a randomized, double-blind, placebo-controlled, within-subject counterbalanced crossover design with ≥7-day washouts. RESULTS: Repeated measures ANOVA revealed no significant interaction (p = 0.315) or time effect (p = 0.649) in corrected FMD% at 60- and 120-min after intake of placebo, 6 g CitMal, and 12 g CitMal. There were also no significant differences (p = 0.301) between doses at any timepoint. A subgroup of six participants completed two additional visits to assess the effect of CitMal ingestion on serum markers involved in NO production. Over 120-min post-consumption, both doses significantly increased peak serum concentrations of citrulline (6 g: 504.7 ± 139.7; 12 g: 881.9 ± 216.7 μM), arginine (6 g: 70.2 ± 20.4; 12 g: 101.8 ± 36.2 μM), and ornithine (6 g: 27.9 ± 14.2; 12 g: 56.5 ± 30.0 μM) from baseline (all p < 0.001), with greater increases following 12 g (all p < 0.05). Likewise, arginine-to-dimethylarginine ratios (SDMA and ADMA) increased from baseline (SDMA, 6 g: 114.1 ± 24.2; 12 g: 166.2 ± 43.7; ADMA, 6 g: 119.2 ± 31.8; 12 g: 169.1 ± 29.1; all p < 0.001), with greater increases following 12 g (p < 0.05). DISCUSSION: Collectively, these findings suggest that neither 6 g nor 12 g of CitMal significantly enhance FMD within 120 min, despite marked increases in biochemical markers favorable to NO production. To our knowledge, this is the first study to compare acute doses of CitMal up to 12 g in relation to brachial artery FMD. These results indicate that acute vascular responses to CitMal may be limited by physiological ceiling effects and that potential vascular benefits may depend on longer-term supplementation, the presence of an exercise stimulus, or populations with impaired endothelial function. Copyright © 2026 Grannes, Callender, Gonzalez, Hisdal, Vårvik and Bjørnsen. DOI: 10.3389/fphys.2026.1773582 PMCID: PMC13002379 PMID: 41867246 Conflict of interest statement: AG declares that he serves as the Chief Scientific Officer for the dietary supplement company, SHIFTED LLC. The remaining author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Lactiplantibacillus plantarum WB4201, WB4202, and WB4203 alleviate gut inflammatory responses and strengthen barrier function in LPS-stimulated HT-29 cells.

12. Microb Pathog. 2026 Jun;215:108452. doi: 10.1016/j.micpath.2026.108452. Epub 2026 Mar 19. Lactiplantibacillus plantarum WB4201, WB4202, and WB4203 alleviate gut inflammatory responses and strengthen barrier function in LPS-stimulated HT-29 cells. Song SY(1), Lee NK(2), Paik HD(3). Author information: (1)Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, Republic of Korea. (2)Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, Republic of Korea; Research Institute, WithBio Inc., Seoul, 05029, Republic of Korea. Electronic address: lnk11@konkuk.ac.kr. (3)Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, Republic of Korea; Research Institute, WithBio Inc., Seoul, 05029, Republic of Korea. Electronic address: hdpaik@konkuk.ac.kr. Lactiplantibacillus plantarum WB4201, WB4202, and WB4203, which are known to possess probiotic properties, were assessed for their ability to alleviate intestinal inflammation and reinforce epithelial barrier function. These strains exhibited antimicrobial and anti-adhesion properties against pathogens. In HT-29 cells, the strains significantly reduced sodium nitroprusside-induced nitric oxide (NO) overproduction, thus indicating their capacity to mitigate nitrosative stress. In lipopolysaccharide (LPS)-stimulated cells, the strains markedly suppressed pro-inflammatory responses by downregulating interleukin (IL)-8, IL-6, IL-1β, cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α). Furthermore, barrier integrity was preserved through the restoration of tight junction proteins, including Occludin, Claudin-1, zonula occludens-1 (ZO-1), and mucin 2 (MUC2). Mechanistic analyses revealed that these protective effects were associated with the inhibition of nuclear factor-kappa B activation and the suppression of mitogen-activated protein kinase phosphorylation cascades. These findings demonstrate the anti-inflammatory and barrier-protective potential of L. plantarum WB4201, WB4202, and WB4203, thus underscoring their potential as probiotic-based interventions for intestinal health. Copyright © 2026 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.micpath.2026.108452 PMID: 41864368 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors have not conflicts of interest to declare.

Carbohydrate-Rich Extract from Pereskia aculeata Leaves: In Vitro Prebiotic-Related Properties and Metabolic Effects in an Experimental Model of Obesity.

13. Plant Foods Hum Nutr. 2026 Mar 21;81(2):36. doi: 10.1007/s11130-026-01486-0. Carbohydrate-Rich Extract from Pereskia aculeata Leaves: In Vitro Prebiotic-Related Properties and Metabolic Effects in an Experimental Model of Obesity. de Bessa ME(1), Andrade VT(1), Guimarães GM(2), Cerqueira AFLW(3), Viana CCR(4)(5), Furtado MM(6), de Freitas Mendes R(1), Rodarte MP(3), Sant'Ana AS(6), Bell MJV(4), Castañon MCMN(7), Alves MS(3), Neumann E(2), Scio E(8). Author information: (1)Laboratory of Bioactive Natural Products, Department of Biochemistry, Biological Sciences Institute, Federal University of Juiz de Fora, Juiz de Fora, 36.036-900, MG, Brazil. (2)Department of Microbiology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil. (3)Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Juiz de Fora, Juiz de Fora, MG, 36.036-900, Brazil. (4)Department of Physics, Institute of Exact Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG, 36036-900, Brazil. (5)Cândido Tostes Dairy Institute, Juiz de Fora, MG, 36045-560, Brazil. (6)Department of Food Science and Nutrition, Faculty of Food Engineering, University of Campinas, Campinas, SP, 13083-862, Brazil. (7)Department of Morphology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG, 36036-900, Brazil. (8)Laboratory of Bioactive Natural Products, Department of Biochemistry, Biological Sciences Institute, Federal University of Juiz de Fora, Juiz de Fora, 36.036-900, MG, Brazil. elita.scio@ufjf.br. Pereskia aculeata Mill. is a leafy cactus native to Brazil, whose leaves are traditionally used as food and are characterized by high nutritional value and significant mucilage content. This study aimed to evaluate the functional potential of the carbohydrate-rich extract obtained from leaves and to investigate its metabolic effects in obese male rats subjected to a litter-size reduction model. The extract was chemically characterized by physicochemical analysis and FTIR-MIR spectroscopy, which revealed spectral features consistent with arabinogalactan-type carbohydrates (absorption bands between 1,000 and 1,050 cm⁻¹). In vitro assays demonstrated antioxidant activity, with DPPH radical inhibition exceeding 60% and nitric oxide reduction exceeding 30%. In addition to promoting the growth of lactic acid bacteria in culture medium supplemented with the extract, it also showed antagonistic activity against selected Gram-negative pathogens. FTIR-MIR analysis during an in vitro gastrointestinal simulation indicated relative spectral stability. In vivo, obese rats were supplemented with the extract for 75 days (0.3%, w/v, in drinking water; 300 mg/kg body weight/day). Supplemented animals showed a reduction in visceral adiposity (-20%) and serum triglycerides (-31%) compared to obese controls (p < 0.05). The obesity model increased fasting blood glucose by approximately 19%, and supplementation reduced blood glucose by approximately 10%. Data were analyzed using appropriate parametric tests (p < 0.05). Liver parameters and histological analyses indicated protection against non-alcoholic fatty liver disease. Overall, these results corroborate the functional potential of carbohydrate fractions and provide a basis for future studies addressing microbiota-mediated mechanisms and metabolic effects. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11130-026-01486-0. DOI: 10.1007/s11130-026-01486-0 PMCID: PMC13005867 PMID: 41863557 Conflict of interest statement: Declarations. Competing Interests: The authors declare no competing interests.

Probiotic and immune-modulatory capacities of three human gut-derived strains of Parabacteroides distasonis.

14. Arch Microbiol. 2026 Mar 17;208(6):274. doi: 10.1007/s00203-026-04804-x. Probiotic and immune-modulatory capacities of three human gut-derived strains of Parabacteroides distasonis. Shamsuzzaman M(1)(2), Dahal RH(3), Kim J(4)(5)(6). Author information: (1)Untreatable Infectious Disease Institute, Kyungpook National University, Daegu, Republic of Korea. (2)Department of Microbiology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. (3)Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, USA. (4)Untreatable Infectious Disease Institute, Kyungpook National University, Daegu, Republic of Korea. minkim@knu.ac.kr. (5)Department of Microbiology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. minkim@knu.ac.kr. (6)Department of Microbiology, Kyungpook National University School of Medicine ADD, 680-gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea. minkim@knu.ac.kr. The human gut microbiome harbors diverse beneficial bacteria with potential roles in supporting host health. Parabacteroides distasonis has recently attracted interest as a next-generation probiotic (NGP) candidate; however, functional evidence for human-derived strains remains limited. Here, three human gut-derived P. distasonis strains (B2-S-102, B2-Q-110, and Y3-G-102) were isolated from healthy individuals and characterized using comparative genomics and in vitro functional assays. Species-level identity was supported by 16S rRNA gene analysis and whole-genome relatedness metrics (ANI > 97% and dDDH > 70%), consistent with established species delineation thresholds. Under controlled laboratory conditions, the strains showed tolerance to acidic pH (pH 2.0), bile salts (0.3%), and simulated gastric and intestinal fluids. Functionally, the strains exhibited measurable antioxidant activity (35.03 ± 7.76% to 51.22 ± 5.60% DPPH inhibition) and α-amylase inhibitory activity (51.03 ± 32.12% to 69.23 ± 4.26%) in vitro. Cell-free supernatants inhibited albumin denaturation (47.65 ± 3.56% to 65.26 ± 4.15%), while live bacteria reduced nitric oxide production and pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ, and IL-1β) in LPS-stimulated RAW 264.7 macrophages (p < 0.05). The strains also displayed in vitro growth-inhibitory activity against Escherichia coli, Acinetobacter baumannii, and Salmonella enteritidis. Genome mining identified multiple biosynthetic gene clusters, indicating genetic potential for secondary metabolite production; however, expression and metabolite identity were not experimentally validated. No haemolytic activity was observed, supporting a favorable preliminary safety profile. Overall, these findings provide preliminary in vitro evidence supporting the potential of human-derived P. distasonis strains as NGP candidates for further evaluation. © 2026. The Author(s). DOI: 10.1007/s00203-026-04804-x PMCID: PMC12996385 PMID: 41843167 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Conflict of interest: The authors declare no competing interests.

Arthrospira platensis prevents impairment of intestinal smooth muscle relaxation in diet-induced obesity via modulation of nitric oxide, prostanoid and oxidative stress pathways.

15. J Ethnopharmacol. 2026 Jun 12;364:121507. doi: 10.1016/j.jep.2026.121507. Epub 2026 Mar 13. Arthrospira platensis prevents impairment of intestinal smooth muscle relaxation in diet-induced obesity via modulation of nitric oxide, prostanoid and oxidative stress pathways. Alves Arruda RR(1), Benício de Melo M(2), Cavalcanti de Sousa Filho JE(2), Araújo da Silva JM(3), Barros BC(3), Freire de Oliveira Claudino B(3), Felismino da Silva Soares M(3), Avelino Diniz AF(4), Vasconcelos da Rocha Gomes U(5), Araújo da Silva B(6). Author information: (1)Postgraduate Program in Natural and Synthetic Products Bioactive/Health Sciences Center, Federal University of Paraiba, João Pessoa, Paraíba, Brazil. Electronic address: rayravilly@ltf.ufpb.br. (2)Health Sciences Center, Federal University of Paraiba, João Pessoa, Paraíba, Brazil. (3)Postgraduate Program in Natural and Synthetic Products Bioactive/Health Sciences Center, Federal University of Paraiba, João Pessoa, Paraíba, Brazil. (4)Postdoctoral Researcher in the Postgraduate Program in Natural and Synthetic Bioactive Products Health Sciences Center, Federal University of Paraiba, João Pessoa, Paraíba, Brazil. Electronic address: andersonfellyp@ltf.ufpb.br. (5)Postgraduate Program in Natural and Synthetic Products Bioactive/Health Sciences Center, Federal University of Paraiba, João Pessoa, Paraíba, Brazil; Biotechnology Department/Biotechnology Center/ Federal University of Paraiba, João Pessoa, Paraíba, Brazil. Electronic address: u.vasconcelos@cbiotec.ufpb.br. (6)Postgraduate Program in Natural and Synthetic Products Bioactive/Health Sciences Center, Federal University of Paraiba, João Pessoa, Paraíba, Brazil; Pharmaceutical Sciences Department/Health Sciences Center/Federal University of Paraiba, João Pessoa, Paraíba, Brazil. Electronic address: bagnolia@ltf.ufpb.br. ETHNOPHARMACOLOGICAL RELEVANCE: Arthrospira platensis (Spirulina) has been traditionally consumed in Africa, Asia and Central America as a nutrient-rich restorative food associated with metabolic balance and gastrointestinal health. Its longstanding ethnopharmacological use suggests biological activities related to antioxidant and anti-inflammatory effects, which are relevant in conditions associated with metabolic disorders. AIM OF THE STUDY: This study investigated whether A. platensis supplementation prevents the reduction in ileal relaxant reactivity induced by a hypercaloric diet (HCD) in rats and explored the involvement of prostanoid, nitric oxide and NADPH oxidase pathways in this response. MATERIALS AND METHODS: Male Wistar rats were fed standard or hypercaloric diets for eight weeks and treated with A. platensis (25 mg kg-1·day-1). Isolated ileum segments were subjected to cumulative concentration-response curves to verapamil in the absence or presence of indomethacin, tempol, L-NAME, 1400W, apocynin or combined L-NAME plus apocynin. Relaxant reactivity was assessed by maximal effect and potency parameters. RESULTS: The hypercaloric diet markedly reduced verapamil-induced relaxant potency, whereas A. platensis supplementation completely prevented this dysfunction without altering responses in healthy animals. In HCD-fed rats, indomethacin, tempol, L-NAME, 1400W and apocynin each fully restored relaxant potency, demonstrating the contribution of prostanoid overactivity, oxidative stress, excessive iNOS-derived nitric oxide and NADPH oxidase-dependent reactive oxygen species to the observed impairment. In supplemented animals, relaxant responses were fully or partially preserved across all pharmacological conditions. CONCLUSIONS: These findings provide mechanistic support for the traditional use of A. platensis, demonstrating that its protective effects on intestinal smooth muscle function are mediated by the modulation of convergent inflammatory and redox pathways. The results highlight A. platensis as an ethnopharmacologically relevant natural product with potential for preventing obesity-associated gastrointestinal dysmotility. Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved. DOI: 10.1016/j.jep.2026.121507 PMID: 41833761 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors also confirm that no commercial, financial, or organizational support was received that could bias the results presented in this manuscript.

Long-Term Beetroot Extract Supplementation Improves Morphological Muscle Quality and Rate of Force Development in Postmenopausal Women: A Randomized Clinical Trial.

16. Nutrients. 2026 Mar 7;18(5):860. doi: 10.3390/nu18050860. Long-Term Beetroot Extract Supplementation Improves Morphological Muscle Quality and Rate of Force Development in Postmenopausal Women: A Randomized Clinical Trial. Ramos Junior OJF(1)(2), de Souza Filho CA(1)(2), Majeed S(3), Alvares TS(1)(2)(4). Author information: (1)Nutrition and Exercise Metabolism Research Group, Multidisciplinary Center UFRJ-Macaé, Federal University of Rio de Janeiro, Macaé 21941-901, Rio de Janeiro, Brazil. (2)Multicenter Graduate Program in Physiological Sciences, Federal University of Rio de Janeiro, Macaé 21941-901, Rio de Janeiro, Brazil. (3)Sabinsa Corporation, 20 Lake Drive, East Windsor, NJ 08520, USA. (4)Food and Nutrition Institute, Multidisciplinary Center UFRJ-Macaé, Federal University of Rio de Janeiro, Macaé 21941-901, Rio de Janeiro, Brazil. Background: Low estrogen levels during menopause reduce nitric oxide (NO) production, contributing to decline in skeletal muscle quality and function. Although acute and short-term dietary nitrate supplementation has demonstrated promising effects, long-term benefits, particularly on muscle quality in postmenopausal women, are not well established. Objectives: The objective was to investigate the effects of long-term (12-week) nitrate-rich beetroot extract supplementation on morphological and functional muscle quality, rate of force development (RFD), maximal strength, and circulating nitrate/nitrite concentrations in postmenopausal women. Methods: In a randomized, double-blind, placebo-controlled design, 20 postmenopausal women (21 years ± 7 since menopause) consumed 20 g/day of a nitrate-rich beetroot extract (BET; 548 mg nitrate/day) or a nitrate-depleted beetroot extract (PLA; 43 mg nitrate/day) for 12 weeks. Outcome measures, including muscle quality (functional via muscle strength/thickness ratio; morphological via ultrasound echo intensity), RFD, maximal voluntary isometric contraction (MVIC), and serum nitrate/nitrite levels, were evaluated at baseline, 8 weeks, and 12 weeks. Results: BET significantly increased serum nitrate (0.005) and nitrite (0.022) levels compared to PLA at both week 8 and week 12. Morphological muscle quality also improved significantly in the BET group (interaction effect, p = 0.014). Early-phase rate of force development (RFD) increased between 30 and 100 ms, whereas late-phase RFD increased between 100 and 200 ms. RFDpeak also improved by week 8, and these gains were maintained through week 12 (interaction effect, p < 0.05). Although there was no significant difference between groups for functional muscle quality, MVIC increased at week 12 in the BET group, but no significant Time × Group interaction was observed. Conclusions: Twelve weeks of nitrate-rich beetroot extract supplementation improved morphological muscle quality and RFD, suggesting potential clinical relevance for preventing structural and neuromuscular function decline in postmenopausal women. This study was registered with ReBEC (RBR-87qh649) and approved on 8 October 2024. DOI: 10.3390/nu18050860 PMCID: PMC12986568 PMID: 41830030 [Indexed for MEDLINE] Conflict of interest statement: S.M. was employed by the company Sabinsa Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Chicken feather protein hydrolysate: An alternative for the prevention of indomethacin-induced gastric ulcer formation in rats.

17. Food Res Int. 2026 May 1;231(Pt 2):118789. doi: 10.1016/j.foodres.2026.118789. Epub 2026 Feb 21. Chicken feather protein hydrolysate: An alternative for the prevention of indomethacin-induced gastric ulcer formation in rats. Doymus M(1), Dasdemir E(2), Sengul E(3), Yildirim S(4), Tekin S(3), Arslan NP(5), Bolat I(6), Kiliclioglu M(6), Ozkan H(2), Taskin M(7). Author information: (1)Vocational School of Health Services of Hinis, Ataturk University, Erzurum, Türkiye. (2)Department of Molecular Biology and Genetics, Faculty of Science, Ataturk University, Erzurum, Türkiye. (3)Department of Physiology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Türkiye. (4)Department of Pathology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Türkiye; Department of Pathology, Faculty of Veterinary Medicine, Kyrgyzstan-Turkey Manas University, Bishkek, Kyrgyzstan. (5)Vocational School of Health Services, Bingol University, Bingol, Türkiye. (6)Department of Pathology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Türkiye. (7)Department of Molecular Biology and Genetics, Faculty of Science, Ataturk University, Erzurum, Türkiye; Institute of Medicine, Vaccine and Biotechnology, Ataturk University, Erzurum, Türkiye. Electronic address: mesut.taskin@atauni.edu.tr. This study examined the anti-ulcer potential of chicken feather protein hydrolysate (Hyd) against indomethacin (Ind)-induced gastric ulcer. Hyd was prepared from feathers by microbial fermentation technique using locally isolated Bacillus licheniformis EYT2 (GenBank accession number: PV612017). Hyd was orally administrated to the rats at the doses of 100 mg/kg BW (low-dose group, Hyd100) and 200 mg/kg BW (high-dose group, Hyd200) before Ind treatment. The effectiveness of Hyd was compared with Ranitidin (Ran). Six experimental groups were designed: Control, Ind, Ran+Ind, Hyd100 + Ind, Hyd200 + Ind, and Ran+Hyd200 + Ind. Hyd was determined to have a high protein content (81.6%) and exhibit high water solubility in a wide pH range from 1 to 10. Ind-treatment caused severe erosion, ulceration, and degeneration in gastric tissue, elevated the levels of malondialdehyde, pro-inflammatory cytokines, inducible nitric oxide synthase, 8 hydroxy-2'-deoxyguanosine, Bax, caspase-3, nuclear factor kappa B (NF-kB) and mitogen-activated protein kinase-38 (MAPK-38) and reduced the levels of glutathione, antioxidant enzymes, anti-inflammatory cytokine IL-10, prostaglandin E2, anti-apoptotic gene Bcl-2 and nuclear factor erythroid 2-related factor 2 (Nrf2). Conversely, Hyd administration, especially high dose Hyd (Hyd200 + Ind group) reversed these alterations. Furthermore, a combination of Ran and high-dose Hyd (Ran+Hyd200 + Ind) completely prevented Ind toxicity. The protective effect of Hyd was attributed to its antioxidant, antiapoptotic and anti-inflammatory activites as well as prostaglandin synthesis-enhancing property. These results imply that Hyd may be used as a supplement with anti-ulcer activity in alternative medicine and/or as a protein source in animal and human nutrition. This is the first report on anti-ulcer potential of Hyd. Copyright © 2026 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.foodres.2026.118789 PMID: 41819898 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this studies.

Protective Effects of Spirulina Supplementation on Chondrocytes Under Moderate Acute Dynamic Compression.

18. Cartilage. 2026 Mar 9:19476035261430274. doi: 10.1177/19476035261430274. Online ahead of print. Protective Effects of Spirulina Supplementation on Chondrocytes Under Moderate Acute Dynamic Compression. Golestani N(1), Rafieian S(2)(3), Waldman SD(4)(5)(6), Zila L(4)(6), Pearson W(1). Author information: (1)Department of Animal Biosciences, University of Guelph, Guelph, ON, Canada. (2)Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada. (3)Physical Platform, Holland Bone and Joint Program, Sunnybrook Research Institute, Toronto, ON, Canada. (4)Institute of Biomedical Engineering, Science and Technology (iBEST), Unity Health and Toronto Metropolitan University, Toronto, ON, Canada. (5)Department of Chemical Engineering, Toronto Metropolitan University, Toronto, ON, Canada. (6)Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada. ObjectiveTo determine the influence of Spirulina supplementation on the response of bovine chondrocytes to mechanical compression with respect to extracellular matrix dynamics (proteoglycan and collagen) and inflammation [nitric oxide (NO)].MethodsBovine chondrocytes were embedded in agarose constructs and cultured for 14 days in basal media or media supplemented with Spirulina (30 or 90 µg/mL). Constructs were exposed to 10% dynamic compression. DNA content, NO levels, proteoglycan content and release, and collagen synthesis were measured to assess extracellular matrix (ECM) responses.ResultsDNA content did not differ among groups. Spirulina supplementation increased NO levels in constructs and media, with the highest effect observed at 90 µg/mL. Proteoglycan content decreased in Spirulina-treated constructs and declined further after compression, while proteoglycan release increased across all groups. Collagen synthesis and content were elevated by Spirulina, particularly at 90 µg/mL, and further increased following dynamic compression.ConclusionsSpirulina supplementation, particularly at higher concentrations, enhances ECM turnover and increases NO production in chondrocytes under mechanical loading, indicating potential modulation of matrix dynamics that may be beneficial. However, these results are derived from an in vitro model and may not fully represent in vivo physiological conditions. DOI: 10.1177/19476035261430274 PMCID: PMC12975531 PMID: 41802934 Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Integrated computational, pharmacological and molecular investigations of piperitone in mitigating Alzheimer disease pathology by targeting cholinesterases, β-secretase and neuroinflammation.

19. Inflammopharmacology. 2026 Apr;34(4):2673-2692. doi: 10.1007/s10787-026-02177-7. Epub 2026 Mar 9. Integrated computational, pharmacological and molecular investigations of piperitone in mitigating Alzheimer disease pathology by targeting cholinesterases, β-secretase and neuroinflammation. Anwer R(1)(2), Ullah I(3), Khan AU(4), Mir MA(5), Bashir N(5), Shah SUA(1), Ayaz M(6). Author information: (1)Department of Pharmacy, Faculty of Sciences, University of Swabi, Swabi, Khyber Pakhtunkhwa, Pakistan. (2)Faculty of Pharmacy, IBADAT International University, Islamabad, Pakistan. (3)Department of Pharmacy, Faculty of Sciences, University of Swabi, Swabi, Khyber Pakhtunkhwa, Pakistan. Ihsanmkd@gmail.com. (4)Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan. (5)Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, 61421, Saudi Arabia. (6)Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Chakdara, Dir (L), 18800, KP, Pakistan. mayaz@uom.edu.pk. Alzheimer's disease (AD) is a progressive neurodegenerative disorder linked with oxidative imbalance, cholinergic dysfunction and neuroinflammation, necessitates developing new multitarget natural compounds with potential disease-modifying action. Piperitone was evaluated using in-silico, in-vitro and in-vivo methods. In-silico study identified the pharmacokinetic parameters (PK) and the interaction stability of piperitone with acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase. In-vivo assessment of spatial memory in scopolamine-induced rat model was identified by behavioral assays with donepezil as a reference standard. In-vitro assays identified activity of cholinesterases, oxidative stress markers, levels of antioxidants and neuroinflammatory substrates, quantified with Reverse Transcription Polymerase Chain Reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Piperitone demonstrated favorable PK properties & docking scores comparable to Donepezil, Tacrine & QUD. Molecular dynamics simulations (MDS) confirmed stable associations with catalytic residues of cholinesterases and beta-secretase. Dose dependent reduction was recorded in cholinesterases, improvement in behavioral outcomes, and supplemented defenses of antioxidants including Glutathione (Reduced Form (GSH), Glutathione S-Transferase (GST), Catalase (CAT), Superoxide Dismutase (SOD), and diminished Lipid Peroxidation (LPO), Nitric Oxide (NO), Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-1β, IL-18, Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), NOD-like Receptor Family Pyrin Domain Containing 3 (NLRP3) and amyloid-β production, while improving Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Piperitone showed significant neuroprotective and cognitive enhancement benefits by modulating cholinergic signaling, oxidative stress, and neuroinflammation. These multitarget actions advocate piperitone as a prospective lead candidate for the development of disease modifying treatments for AD. © 2026. The Author(s), under exclusive licence to Springer Nature Switzerland AG. DOI: 10.1007/s10787-026-02177-7 PMID: 41801601 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Ethics approval and consent to participate: All animal experiments received approval from the Institutional Animal Ethics Committee of the University of Swabi, Pakistan with reference no.PH09MAR2023-A056 (dated: 9th March, 2023), and were conducted in compliance with the ARRIVE 2.0 standards and the NIH Guide for the Care and Use of Laboratory Animals. The research was conducted at the animal facility of Riphah Institute of Pharmaceutical Sciences, Islamabad. Consent to participation is not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Use of AI: The authors recognize the utilization of generative AI tools, specifically QuillBot and Jennie AI that were utilized only for language enhancement, grammatical correction, and manuscript readability improvement. No segment of the logical or interpretive substance was produced by these tools. The authors assume full accountability for the reliability and validity of the finalized version of this manuscript.

Anti-Inflammatory and Neuroprotective Potential of Indigenous Lactiplantibacillus Plantarum Strains.

20. Mol Nutr Food Res. 2026 Mar;70(5):e70422. doi: 10.1002/mnfr.70422. Anti-Inflammatory and Neuroprotective Potential of Indigenous Lactiplantibacillus Plantarum Strains. Debnath N(1), Yadav P(1), Tyagi N(2), Mehta PK(1), Yadav ML(3), Yadav AK(4). Author information: (1)Centre for Molecular Biology, Central University of Jammu, Samba, Jammu & Kashmir, India. (2)Department of Physiology, School of Medicine, Health Sciences Centre, University of Louisville, Louisville, Kentucky, USA. (3)Discovery Research Division, Indian Council of Medical Research (ICMR), New Delhi, India. (4)Department of Zoology, Central University of Jammu, Samba, Jammu & Kashmir, India. The anti-inflammatory and neuroprotective potential of probiotic Lactobacillus strains has gained significant attention due to their ability to modulate oxidative stress and inflammation. In this study, two indigenous Lactiplantibacillus plantarum, LpJ5 and LpJ8, were evaluated for their anti-inflammatory and neuroprotective properties to mitigate oxidative stress and enhance cell viability in neuroinflammatory models. Results indicate that LpJ5 significantly upregulated glutathione peroxidase (gpx) and glutathione (gsh) expression at 0.9 mM hydrogen peroxide (H2O2). The probiotic strains also demonstrated significant anti-inflammatory effects in lipopolysaccharide (LPS)-induced BV2 and SH-SY5Y cell models. Pretreatment with LpJ5 resulted in a 59.7% reduction in nitric oxide (NO) production in BV2 cells and a 56.7% reduction in SH-SY5Y cells. LpJ8 showed comparable reductions of 49.2% and 47.3%, respectively. Additionally, LpJ5 pretreatment led to an increase in cell viability in BV2 and SH-SY5Y cells. Both strains also reduced the expression of inflammatory markers such as iNOS, COX-2, TNF-α, IL-1β, and upregulated BCL-2 and IL-10, with LpJ5 exhibiting stronger effects, particularly in the pretreatment phase. These findings demonstrate the antioxidant and anti-inflammatory capabilities of LpJ5 and LpJ8 and thereby highlight potential mechanistic links and lay the groundwork for subsequent translational and clinical investigations. Thus making them promising candidates for therapeutic applications. © 2026 Wiley‐VCH GmbH. DOI: 10.1002/mnfr.70422 PMID: 41792960 [Indexed for MEDLINE]

Targeting muscle-vasculature crosstalk in aging through the integrative roles of L-citrulline, leucine, and exercise: focus on muscle metabolism, vascular function, and sarcopenia prevention.

21. Front Nutr. 2026 Apr 2;12:1739173. doi: 10.3389/fnut.2025.1739173. eCollection 2025. Targeting muscle-vasculature crosstalk in aging through the integrative roles of L-citrulline, leucine, and exercise: focus on muscle metabolism, vascular function, and sarcopenia prevention. Lin X(1), Zhang Y(2), Pu J(3), Peng Y(3). Author information: (1)Faculty of Health Science and Sport, Macao Polytechnic University, Macao, China. (2)Institute of Brain and Psychological Sciences, Sichuan Normal University, Chengdu, Sichuan, China. (3)Sichuan Vocational College of Culture and Communication, Chengdu, Sichuan, China. Aging is characterized by a gradual deterioration in skeletal muscle mass, strength, and vascular functionality, which ultimately leads to the development of sarcopenia and the subsequent loss of physical autonomy. Nutritional and exercise-based interventions that specifically address this interplay may offer viable, non-pharmacological approaches to maintaining both muscular and vascular integrity. L-citrulline (CIT), recognized as a precursor to nitric oxide (NO), has been demonstrated to enhance endothelial functionality, improve oxygen transport, and increase muscle perfusion, while leucine has been shown to stimulate muscle protein synthesis. Furthermore, exercise serves to modulate both NO availability and anabolic signaling pathways, thereby amplifying the effects of these amino acids. Recent clinical and experimental research indicates that the concurrent administration of CIT and leucine supplementation, in conjunction with structured exercise regimens, yields superior enhancements in muscle mass, vascular reactivity, and physical performance compared to isolated interventions alone. The aforementioned synergistic effects are facilitated through a comprehensive regulation of mitochondrial biogenesis, alongside a reduction in inflammation and oxidative stress. This review consolidates existing empirical evidence regarding the collective contributions of CIT, leucine, and physical exercise in fostering healthy aging, while also delineating prospective research avenues for the formulation of personalized nutritional and physical strategies aimed at enhancing both muscular and vascular well-being in the elderly population. Copyright © 2026 Lin, Zhang, Pu and Peng. DOI: 10.3389/fnut.2025.1739173 PMCID: PMC13083166 PMID: 42005822 Conflict of interest statement: The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acute effects of combined supplementation of L-arginine and citrulline malate on aerobic, anaerobic, and CrossFit exercise performance.

22. Sci Rep. 2025 Sep 26;15(1):33067. doi: 10.1038/s41598-025-16374-x. Acute effects of combined supplementation of L-arginine and citrulline malate on aerobic, anaerobic, and CrossFit exercise performance. Selvaraj S(1), Petridis L(2), Majtényi H(3), Bartha H(3), Tóth Á(3), Utczás K(3), Szilágyi-Utczás M(4), Kimble R(5), Zare R(6), Akbari A(7), Heinrich KM(8)(9). Author information: (1)Department of Chemistry, Faculty of Applied Sciences, University of Sri Jayewardenepura, Gangodawila, Nugegoda, Sri Lanka. (2)Research Centre for Sport Physiology, Hungarian University of Sport Science, Budapest, 1123, Hungary. petridis.leonidas@tf.hu. (3)Research Centre for Sport Physiology, Hungarian University of Sport Science, Budapest, 1123, Hungary. (4)Centre for Sports Nutrition Science, Hungarian University of Sport Science, Budapest, 1123, Hungary. (5)Division of Sport, Exercise and Health, School of Health and Life Sciences, University of the West of Scotland, Blantyre, G720LH, UK. (6)SRH Campus Hamburg, SRH University of Applied Sciences Heidelberg, 20095, Hamburg, Germany. (7), Damavand, Tehran Province, Iran. (8)Department of Kinesiology, Kansas State University, Manhattan, KS, 66506, USA. (9)Department of Research and Evaluation, The Phoenix, Denver, CO, 80205, USA. This study investigated the effects of combined L-arginine (Arg) and citrulline-malate (CM) supplementation on aerobic, anaerobic, and high-intensity interval training in healthy, trained men. Both Arg and CM are widely marketed for their potential ergogenic effects, as Arg serves as a precursor to nitric oxide (NO), which may support vasodilation, muscle contractility, and exercise performance. Arg and CM are hypothesized to exert synergistic effects due to their complementary roles in NO synthesis. Citrulline can potentially enhance and prolong Arg availability, thereby amplifying NO-mediated vasodilation, nutrient delivery, and muscle performance during exercise. In this randomized, double-blind, placebo-controlled trial, 46 healthy, trained men aged 24.8 ± 5.0 years were divided into 3 exercise groups subjected to consuming 0.15 g/kg bodyweight of Arg and 0.1 g/kg bodyweight of CM prior. The participants were then randomly divided into three groups based on the exercise protocol:: the Wingate Anaerobic Test (n = 16), a 20 min CrossFit workout 'Cindy' (n = 16) consisting of continuous rounds of pull-ups, push-ups, and air squats to measure functional fitness and muscular endurance, or the Harvard Step Test (n = 14) a measurement of cardiovascular endurance and recovery. This design allowed for the evaluation of supplementation effects across multiple exercise modalities. The results revealed no significant improvement in performance with supplementation in comparison to placebo, except for a shorter time to reach peak power in the Wingate test. Findings suggest that the combined acute supplementation of Arg and CM, at the given dosages, may not provide substantial benefits for aerobic and anaerobic or CrossFit performance in active individuals. Future research with larger sample sizes and higher dosages, potentially adjusted for muscle mass, is recommended to determine whether chronic supplementation might yield greater ergogenic effects. © 2025. The Author(s). DOI: 10.1038/s41598-025-16374-x PMCID: PMC12475454 PMID: 41006371 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This research was carried out in accordance with the principles of the Declaration of Helsinki and was approved by the Ethics Committee of the Hungarian University of Sports Science (protocol code TE-KEB/22/2023; approval date: 30 June 2023). Informed consent: Informed written consent was obtained from all participants for publication of this study.

Ergogenic effects of a 10-day L-citrulline supplementation on time to exhaustion and cardiorespiratory and metabolic responses in healthy individuals: a double-blind, randomised, placebo-controlled crossover trial.

23. Front Sports Act Living. 2025 Sep 5;7:1627743. doi: 10.3389/fspor.2025.1627743. eCollection 2025. Ergogenic effects of a 10-day L-citrulline supplementation on time to exhaustion and cardiorespiratory and metabolic responses in healthy individuals: a double-blind, randomised, placebo-controlled crossover trial. Schierbauer J(1), Francis L(1), Greco F(1)(2), Zimmermann P(1), Moser O(1)(3). Author information: (1)Division of Exercise Physiology and Metabolism, Bayreuth Centre of Sport Science, University of Bayreuth, Bayreuth, Germany. (2)Department of Movement, Human and Health Sciences, University of Rome Foro Italico, Rome, Italy. (3)Interdisciplinary Metabolic Medicine Trials Unit, Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria. INTRODUCTION: L-Citrulline supplementation has been a topic of debate due to its potential to augment L-arginine bioavailability and nitric oxide production. However, it remains uncertain whether it can truly serve as an ergogenic aid in endurance exercise performance. While it was previously recommended to include higher continuous doses of L-citrulline over ≥7 days, this study aimed to investigate whether a relative dosing strategy using 100 mg·kg-1 per day over 10 days could improve time to exhaustion (TTE) in healthy young adults. METHODS: Twenty healthy, moderately active adult participants (nine females; age, 24.4 ± 0.9 years; BMI, 24.0 ± 2.5 kg·m-2; V̇O2max, 43.5 ± 6.3 mL·min-1·kg-1) received either 100 mg·kg-1 per day of L-citrulline (CIT) or a placebo (PLA) for 10 days in a double-blind, randomised, placebo-controlled crossover trial, before they performed two TTE tests at 5% above the second lactate turnpoint (LTP2). Cardiac output (Q̇), oxygen uptake (V̇O2), blood glucose ([Glu-]) and lactate concentrations ([La-]), and rating of perceived exertion (RPE) were quantified during each test. RESULTS: There was no statistically significant difference in TTE between the trial arms (CIT vs. PLA: 20.5 ± 7.3 vs. 19.8 ± 5.7 min, p = 0.43). However, a trend was observed in the female subgroup (24.4 ± 6.2 vs. 21.9 ± 4.8 min, p = 0.06). Cardiac output (Q̇) also did not show significant differences between mean (CIT, 18.3 ± 3.7 L·min-1; PLA, 19.0 ± 4.5 L·min-1; p = 0.40) and maximum values (CIT, 28.7 ± 5.7 L·min-1; PLA, 26.6 ± 4.9 L·min-1; p = 0.22) in both trial arms. Mean V̇O2 was 1.77 ± 0.28 and 1.84 ± 0.25 L·min-1 (p = 0.06) for CIT and PLA, respectively. Similarly, mean maximum systolic (165 ± 17 vs. 171 ± 18 mmHg, p = 0.23) and diastolic (81 ± 6 vs. 83 ± 6 mmHg, p = 0.19) blood pressure levels were not significantly different between CIT and PLA trial arms. DISCUSSION: Higher continuous doses of L-citrulline over 10 days do not increase TTE in healthy, moderately active individuals when compared with a placebo. Therefore, it is reasonable to assume that L-citrulline does not offer an ergogenic benefit for endurance performance. However, future research may focus on female populations or exercise protocols that involve longer distances to simulate competition. © 2025 Schierbauer, Francis, Greco, Zimmermann and Moser. DOI: 10.3389/fspor.2025.1627743 PMCID: PMC12446285 PMID: 40980088 Conflict of interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Changes in resistance training performance, rating of perceived exertion, and blood biomarkers after six weeks of supplementation with L-citrulline vs. L-citrulline DL-malate in resistance-trained men: a double-blind placebo-controlled trial.

24. J Int Soc Sports Nutr. 2025 Dec;22(1):2513944. doi: 10.1080/15502783.2025.2513944. Epub 2025 Jun 5. Changes in resistance training performance, rating of perceived exertion, and blood biomarkers after six weeks of supplementation with L-citrulline vs. L-citrulline DL-malate in resistance-trained men: a double-blind placebo-controlled trial. Bayat D(1), Azizi M(1), Behpour N(1), Tinsley GM(2). Author information: (1)Razi University, Department of Exercise Physiology, Faculty of Sport Sciences, Kermanshah, Iran. (2)Texas Tech University, Department of Kinesiology & Sport Management, Lubbock, TX, USA. PURPOSE: This study aimed to investigate and compare the effects of chronic supplementation with L-Citrulline (LC) vs. L-Citrulline DL-malate (CM) on resistance training (RT) performance. METHODS: Thirty-three resistance-trained men were randomly assigned to ingest LC (8 g), CM (12 g), or Placebo (PL) daily, along with participation in a 6-week RT protocol. Muscular strength (1-repetition maximum [1RM] for hack squat [HS] and bench press [BP]), muscular endurance (repetitions to failure [RTF] for HS, leg extension [LE], BP, and incline press [IP]), rating of perceived exertion (RPE), and blood biomarkers (lactate, urea, and nitric oxide metabolites [NOX]) were assessed before and after the intervention. This study was registered on irct.ir (IRCTID: IRCT20221128056642N1). RESULTS: Comparing mean ∆ scores revealed a significant difference between LC and PL (p < 0.001) and between CM and PL (p = 0.026) for total upper body (the sum of BP and IP) RTF, but only a trend for difference between LC and PL (p = 0.070) for total lower body (the sum of HS and LE) RTF. A significant time effect for NOX was detected only for LC (p = 0.014) and CM (p = 0.003). In addition, a significant difference between CM and PL (p = 0.009) and a marginally significant difference between LC and PL (p = 0.057) was detected regarding post-exercise NOX values at post-intervention. There were no other between-group differences for any outcome measure. CONCLUSION: Chronic citrulline supplementation seems to enhance upper body muscular endurance and post-exercise NOX response to RT, but there is no apparent difference between LC and CM in these aspects. DOI: 10.1080/15502783.2025.2513944 PMCID: PMC12143003 PMID: 40470618 [Indexed for MEDLINE] Conflict of interest statement: DB is the founder and owner of Iran Fit Gym where training sessions and some experimental procedures were conducted, but he has no conflicts of interest to disclose. GMT provides consulting services to dietary supplement manufacturers through Tinsley Consulting LLC but has no affiliation with the supplement manufacturers whose products were used in the present study. The remaining authors have no competing financial interests to disclose.

Prolonged disturbances in citrulline metabolism following resistance exercise in COPD.

25. Clin Nutr. 2025 Jun;49:21-32. doi: 10.1016/j.clnu.2025.03.021. Epub 2025 Apr 8. Prolonged disturbances in citrulline metabolism following resistance exercise in COPD. Sontam T(1), Deutz NEP(2), Cruthirds CL(3), Mbilinyi R(1), Ruebush LE(3), Ten Have GA(3), Thaden JJ(3), Engelen MPKJ(4). Author information: (1)Center for Translational Research in Aging & Longevity, Dept of Kinesiology and Sport Management, Texas A&M University, College Station, TX, USA; Department of Medical Education, Texas A&M School of Medicine, College Station, TX, USA. (2)Center for Translational Research in Aging & Longevity, Dept of Kinesiology and Sport Management, Texas A&M University, College Station, TX, USA; Department of Primary Care & Rural Medicine, Texas A&M School of Medicine, College Station, TX, USA. (3)Center for Translational Research in Aging & Longevity, Dept of Kinesiology and Sport Management, Texas A&M University, College Station, TX, USA. (4)Center for Translational Research in Aging & Longevity, Dept of Kinesiology and Sport Management, Texas A&M University, College Station, TX, USA; Department of Primary Care & Rural Medicine, Texas A&M School of Medicine, College Station, TX, USA. Electronic address: mpkj.engelen@ctral.org. BACKGROUND & AIMS: Disturbances in arginine (ARG) and protein metabolism, as well as in gut function have been observed in response to an endurance exercise session in patients with Chronic Obstructive Pulmonary Disease (COPD). We studied whether resistance exercise also affects the acute response in arginine (role in nitric oxide synthesis), citrulline (CIT, marker of gut health), and (muscle) protein metabolism differently in COPD as compared to healthy older adults. METHODS: Patients with stable moderate to severe COPD (n = 24) and healthy controls (n = 25) completed a high-intensity resistance exercise session in the postabsorptive state. We administered a pulse of multiple stable isotopes of amino acids before, and 1 h and 24 h post-resistance exercise to assess the whole body production (WBP) and intracellular productions by compartmental analysis of ARG and CIT, and of tau-methylhistidine (TauMETHIS), phenylalanine (PHE), tyrosine (TYR), and PHE > TYR conversion as markers of muscle (myofibrillar) protein breakdown and whole body (net) protein breakdown, respectively. Muscle fatigue was determined by assessing the decay in peak leg extension torque post-resistance exercise. RESULTS: COPD patients overall exhibited lower WBP ARG (p < 0.0001), CIT (p < 0.0001), PHE (p = 0.0001), TYR (p < 0.0001), and tau-METHIS (p = 0.0004) compared to controls. Resistance exercise did not change WBP of PHE, tau-METHIS, or PHE > TYR conversion, despite prolonged muscle fatigue in COPD. WBP CIT was increased at 1- and 24-h post-exercise in both groups (p < 0.003). Plasma CIT concentrations were reduced in both groups (p < 0.006) and remained lower at 24 h post-exercise in COPD only (p < 0.05) despite a third less work performed. CONCLUSIONS: Both COPD and healthy participants exhibited upregulated whole-body citrulline production following resistance exercise. However, in COPD, this increase was insufficient to counteract the sustained reduction in plasma citrulline concentration, despite performing significantly less work during the exercise session. This prolonged disturbance in citrulline metabolism in COPD points to a potential exercise-induced enterocyte dysfunction, highlighting a novel area for understanding the impact of resistance exercise on gut health in this population. CLINICAL TRIAL REGISTRY: Trial registration ClinicalTrials.gov: NCT02780219. Copyright © 2025 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. DOI: 10.1016/j.clnu.2025.03.021 PMID: 40233541 [Indexed for MEDLINE] Conflict of interest statement: Conflict of interest None of the authors had any financial or personal interest in any company or organization sponsoring the research.

The Antioxidant Power of Bergamot Polyphenolic Fraction Gold Potentiates the Effects of L-Citrulline in Athlete Performance and Vasodilation in a Pilot Study.

26. Nutrients. 2025 Mar 21;17(7):1106. doi: 10.3390/nu17071106. The Antioxidant Power of Bergamot Polyphenolic Fraction Gold Potentiates the Effects of L-Citrulline in Athlete Performance and Vasodilation in a Pilot Study. Mollace R(1)(2), Macrì R(1), Serra M(1), Ritorto G(1), Ussia S(1), Scarano F(1), Cardamone A(1), Musolino V(3), Coppoletta AR(1), Gliozzi M(1), Scipione G(1), Carresi C(1), Pozharova K(1), Muscoli C(1), Barillà F(2), Volterrani M(4), Mollace V(1)(5). Author information: (1)Institute of Research for Food Safety and Health (IRC-FSH), Department of Health Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy. (2)Department of Experimental Medicine, University "Tor Vergata" of Rome, 00133 Rome, Italy. (3)Laboratory of Pharmaceutical Biology, Institute of Research for Food Safety and Health (IRC-FSH), Department of Health Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy. (4)IRCCS San Raffaele Roma, 00163 Rome, Italy. (5)Renato Dulbecco Institute, 88046 Lamezia Terme, Italy. Background: The dietary supplement citrulline might increase nitric oxide levels, leading to vasodilation and improved blood flow, potentially benefiting athletes' aerobic exercise performance. However, rapid oxidative impairment of the L-arginine/nitric oxide (NO) pathway limits these effects. This is countered by Bergamot Polyphenolic Fraction Gold® (BPFG), a strong natural antioxidant. To investigate L-citrulline + BPFG supplementation's effects, we performed a randomized, double-blind, placebo-controlled pilot trial on athletic performance and blood flow in trained athletes (cyclists). Methods: Random assignment of 90 male athletes resulted in nine different groups: placebo for Group 1, BPFG at 500 and 1000 mg daily for Groups 2 and 3, L-citrulline at 1000 and 2000 mg/daily for Groups 4 and 5, and the combination product of BPFG plus citrulline (N.O. Max) for Groups 6-9. Baseline and 3-month pre- and post-exercise biochemical, reactive vasodilation (RHI), and maximal oxygen consumption measurements were taken for all subjects. Results: Three months of the combination of BPFG and L-citrulline (N.O. Max) produced a significant synergistic effect, markedly increasing NO (p < 0.001 vs. placebo) release and RHI (p < 0.001 vs. placebo). Cardiorespiratory fitness improved significantly with the BPFG and L-citrulline combination, resulting in substantially higher VO2 max, VT1, VT2, and peak power and a significantly lower heart rate (p < 0.01 vs. placebo). No harmful adverse effects were observed. Conclusions: N.O. Max supplementation, providing beneficial effects on the antioxidant state and preserving the vascular endothelium might be a supplementation strategy to improve athletic performance and potentiate results. Given the small sample size, this study serves as a pilot, and further research is needed to validate these findings on a larger scale. DOI: 10.3390/nu17071106 PMCID: PMC11990273 PMID: 40218864 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Overview of mechanisms related to citrulline malate supplementation and different methods of high-intensity interval training on sports performance: A narrative review.

27. Heliyon. 2025 Feb 11;11(4):e42649. doi: 10.1016/j.heliyon.2025.e42649. eCollection 2025 Feb 28. Overview of mechanisms related to citrulline malate supplementation and different methods of high-intensity interval training on sports performance: A narrative review. Nobari H(1)(2), Samadian L(3), Saedmocheshi S(4), Prieto-González P(5), MacDonald C(6). Author information: (1)LFE Research Group, Department of Health and Human Performance, Faculty of Physical Activity and Sport Science (INEF), Universidad Politécnica de Madrid, Madrid, Spain. (2)Department of Exercise Physiology, Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil 56199-11367, Iran. (3)Department of Public Health, School of Public Health, Urmia University of Medical Sciences, Urmia, Iran. (4)Department of Physical Education and Sport Sciences, Faculty of Humanities and Social Sciences, University of Kurdistan, 66177-15175 Sanandaj, Kurdistan, Iran. (5)Sport Sciences and Diagnostics Research Group, Prince Sultan University, Riyadh 11586, Saudi Arabia. (6)Conway Medical Center College of Health and Human Performance, Coastal Carolina University, USA. Erratum in Heliyon. 2025 Oct 01;11(15):e43913. doi: 10.1016/j.heliyon.2025.e43913. Regular exercise is a practical non-pharmacological approach to maintaining physical and mental health through rehabilitation and prevention of chronic diseases due to its cardiovascular, cardiorespiratory, neurological, and neuromuscular benefits. Despite awareness of the benefits of exercise, a "lack of time" has proven to be the most common impediment to regular activity. Thus, a time-efficient and potentially enjoyable training modality with growing popularity is high-intensity interval training (HIIT). HIIT incorporates intermittent bouts of work and recovery intervals performed at an intensity close to maximal oxygen consumption (VO2max). HIIT is considered to have equivalent or superior benefits compared to moderate-intensity continuous training (MICT). This narrative review focuses on the mechanisms of Citrulline Malate (CM) supplementation and various modes of HIIT on exercise performance. CM serves as a nitric-oxide enhancer leading to improved aerobic and anaerobic exercise performance by increasing muscle adenosine triphosphate (ATP) production, vasodilation, and blood flow to the active musculature and boosting work capacity. This article reviews the mechanisms related to CM supplementation and different modes of HIIT on exercise performance. Even though a single, acute 8 g dose of CM has been recommended, its mechanism of action remains to be seen due to the synergistic impact of both components (citrulline and malate). Moreover, the limited evidence for the standard level of supplement use and source of purchase results in athletes' self-prescription of supplements. Therefore, to reduce the risk of accidental doping or toxicity, further studies should continue to investigate the optimal dose, timing, mechanism of action, as well as reliable sources of purchase for CM consumption. © 2025 The Author(s). DOI: 10.1016/j.heliyon.2025.e42649 PMCID: PMC11876876 PMID: 40040998 Conflict of interest statement: The researchers have no other conflicts of interest. And they promise not to send the article anywhere until the review is complete.

Impact of L-Citrulline Supplementation and HIIT on Lipid Profile, Arterial Stiffness, and Fat Mass in Obese Adolescents with Metabolic-Dysfunction-Associated Fatty Liver Disease: A Randomized Clinical Trial.

28. Nutrients. 2025 Jan 23;17(3):402. doi: 10.3390/nu17030402. Impact of L-Citrulline Supplementation and HIIT on Lipid Profile, Arterial Stiffness, and Fat Mass in Obese Adolescents with Metabolic-Dysfunction-Associated Fatty Liver Disease: A Randomized Clinical Trial. Rodríguez-Carrillo AA(1), Espinoza-Vargas MR(1), Vargas-Ortiz K(1), Ibarra-Reynoso LDR(1), Olvera-Juárez M(1), Gómez-Ojeda A(1), Garay-Sevilla ME(1), Figueroa A(2). Author information: (1)Department of Medical Sciences, Division of Health Sciences, University of Guanajuato, Campus León, León CP. 37320, Guanajuato, Mexico. (2)Department of Kinesiology and Sport Management, Texas Tech University, Lubbock, TX 79409, USA. BACKGROUND: Metabolic-dysfunction-associated steatotic liver disease (MASLD) and obesity contribute to vascular dysfunction through oxidative stress, heightening cardiovascular risk. Oral supplementation with L-citrulline (L-cit), a precursor of L-arginine (L-arg) and nitric oxide, and high-intensity interval training (HIIT) may improve vascular function and cardiometabolic health. OBJECTIVES: This study aimed to evaluate the combined effects of L-cit supplementation and HIIT on arterial stiffness, body composition, glucose metabolism, lipid profile, and blood pressure (BP) in adolescents with MASLD and obesity. METHODS: In this double-blind, placebo-controlled, randomized clinical trial (ClinicalTrials.gov (NCT05778266), 44 adolescents (15-19 years) with MASLD and obesity were assigned to HIIT + L-cit (n = 14), HIIT + placebo (n = 14), or L-cit (n = 15) for 12 weeks. HIIT sessions (85% and 60% peak heart rate during intense and recovery periods) occurred thrice weekly. Training volume progressively increased, and participants performed 20 min of HITT per session in the last 8 weeks. RESULTS: Outcomes included pulse wave velocity (PWV), augmentation index (Aix75), VO2peak, body composition, BP, glucose and lipid profiles, and hepatic steatosis. Compared to L-cit, HIIT + L-cit improved non-high-density lipoprotein cholesterol (p = 0.04), very-low-density lipoprotein cholesterol (p = 0.01), triglycerides (p = 0.02), and VO2peak (p = 0.001). No significant between-group changes were found in PWV, AIx75, hepatic steatosis, and body composition. HIIT + placebo improved VO2peak (p = 0.002), and L-cit decreased the degree of steatosis (p = 0.038). CONCLUSIONS: HIIT + L-cit supplementation enhanced lipid profile and cardiorespiratory fitness, while HIIT + placebo improved cardiorespiratory capacity, and L-cit alone decreased hepatic steatosis. Thus, L-cit could be an adjuvant strategy to manage obesity-related MASLD in adolescents. DOI: 10.3390/nu17030402 PMCID: PMC11820369 PMID: 39940261 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Effects of Quercetin and Citrulline on Nitric Oxide Metabolites and Antioxidant Biomarkers in Trained Cyclists.

29. Nutrients. 2025 Jan 9;17(2):224. doi: 10.3390/nu17020224. Effects of Quercetin and Citrulline on Nitric Oxide Metabolites and Antioxidant Biomarkers in Trained Cyclists. Kurtz JA(1), Feresin RG(2), Grazer J(3), Otis J(4), Wilson KE(4), Doyle JA(4), Zwetsloot KA(1)(5). Author information: (1)Department of Public Health & Exercise Science, Appalachian State University, Boone, NC 28607, USA. (2)Department of Nutrition, Georgia State University, Atlanta, GA 30203, USA. (3)Department of Exercise Science and Sport Management, Kennesaw State University, Kennesaw, GA 30144, USA. (4)Department of Kinesiology & Health, Georgia State University, Atlanta, GA 30303, USA. (5)Department of Biology, Appalachian State University, Boone, NC 28607, USA. BACKGROUND: Quercetin (QCT) and citrulline (CIT) have been independently associated with improved antioxidant capacity and nitric oxide (NO) production, potentially enhancing cardiovascular function and exercise performance. This study aimed to evaluate the combined and independent effects of QCT and CIT supplementation on NO metabolites and antioxidant biomarkers in 50 trained cyclists undergoing a 20 km cycling time trial (TT). METHODS: In a randomized, double-blind, placebo-controlled design, forty-two male and eight female trained cyclists were assigned to QCT + CIT, QCT, CIT, or placebo (PL) groups. Supplements were consumed twice daily for 28 days. Biochemical assessments included NO metabolites (nitrate/nitrite), ferric reducing antioxidant power (FRAP), superoxide dismutase (SOD) activity, and antioxidant capacity, measured pre- and post-TT. RESULTS: NO metabolites were significantly elevated post-supplementation (p = 0.03); however, no significant interaction effects were observed for NO metabolites, FRAP, SOD, or antioxidant capacity across the groups (p > 0.05). Post-hoc analyses revealed that QCT significantly reduced FRAP concentrations compared to PL (p = 0.01), while no significant changes in SOD or antioxidant capacity were found across any groups. CONCLUSIONS: These findings suggest that combined and independent QCT and CIT supplementation did not significantly improve these biomarkers, suggesting that baseline training adaptations, supplementation timing, and individual variability may influence the efficacy of these compounds in enhancing exercise performance and oxidative stress markers. The ergogenic efficacy of QCT + CIT on antioxidant-related markers remains inconclusive. DOI: 10.3390/nu17020224 PMCID: PMC11767657 PMID: 39861353 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Malate or Not? Acute Effects of L-Citrulline Versus Citrulline Malate on Neuromuscular Performance in Young, Trained Adults: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial.

30. Int J Sport Nutr Exerc Metab. 2024 Dec 11;35(2):89-98. doi: 10.1123/ijsnem.2024-0006. Print 2025 Mar 1. Malate or Not? Acute Effects of L-Citrulline Versus Citrulline Malate on Neuromuscular Performance in Young, Trained Adults: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial. Martín-Olmedo JJ(1)(2)(3), Miras-Moreno S(4), Cuadra-Montes K(1), García-Ramos A(4), Ruiz JR(1)(5)(6), Jurado-Fasoli L(1)(2)(3). Author information: (1)Department of Physical and Sports Education, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS), University of Granada, Granada, Spain. (2)ICEN Institute, Madrid, Spain. (3)Department of Physiology, Faculty of Medicine, University of Granada, Granada, Spain. (4)Faculty of Sport Sciences, Department of Physical Education and Sport, University of Granada, Granada, Spain. (5)ibs.GRANADA - Instituto de Investigación Biosanitaria, Granada, Spain. (6)CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Granada, España. L-citrulline (CIT) supplementation seems to improve resistance training performance; yet, whether malate has additive ergogenic effects when combined with CIT is unknown. This randomized, double-blind, placebo-controlled crossover trial aimed to compare the acute effects of CIT versus citrulline malate (CMA) supplementation on neuromuscular performance and exertion and emotional perceptions in young, trained men and women. 43 (21 women; 24.2 ± 3.7 years) participants ingested a placebo, CIT (5.3 g of CIT), or CMA (5.3 g of CIT, 2.7 g of malate) 45 min before three experimental sessions in a counterbalanced manner. We evaluated the upper and lower limb maximal neuromuscular and ballistic performance through the two-point method and countermovement jump. Strength-endurance was assessed across three sets of 10 repetitions in the squat and bench press exercises. Exertion and emotional perceptions were evaluated before and after the assessment and during the strength-endurance assessment. CIT and CMA supplementation did not enhance maximal neuromuscular performance (all p ≥ .061, ηp2≤.066), or ballistic strength (all p ≥ .348, ηp2≤.025). Neither CIT nor CMA supplementation improved strength-endurance as observed in the total number of repetitions (all p ≥ .590, ηp2≤.013), repetitions before reaching velocity loss threshold (all p ≥ .623, ηp2≤.010), mean velocity (all p ≥ .792, ηp2≤.004), mean velocity decline (all p ≥ .293, ηp2≤.029), and mean velocity maintenance (all p ≥ .393 ηp2≤.022), or exertion and emotional perceptions (both p ≥ .306, ηp2≤.028). In conclusion, CIT and CMA supplementation may not increase the neuromuscular performance during low- to moderate-volume resistance training sessions in young, trained adults. This trial was registered at ClinicalTrials.gov (No. NCT05183893). DOI: 10.1123/ijsnem.2024-0006 PMID: 39662304 [Indexed for MEDLINE]

Effects of Acute Citrulline Malate Supplementation on CrossFit(®) Exercise Performance: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study.

31. Nutrients. 2024 Sep 24;16(19):3235. doi: 10.3390/nu16193235. Effects of Acute Citrulline Malate Supplementation on CrossFit(®) Exercise Performance: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study. Devrim-Lanpir A(1)(2), Ihász F(3), Demcsik M(3), Horváth AC(3), Góczán P(3), Czepek P(3), Takács J(4), Kimble R(5), Zare R(6)(7), Gunes FE(2), Knechtle B(8)(9), Weiss K(8), Rosemann T(8), Heinrich KM(10)(11). Author information: (1)School of Health and Human Performance, Dublin City University, D09 V209 Dublin, Ireland. (2)Department of Nutrition and Dietetics, Faculty of Health Sciences, Istanbul Medeniyet University, 34862 Istanbul, Turkey. (3)Faculty of Education and Psychology, Institute of Sport Sciences, Eötvös Lóránd University, 1075 Szombathely, Hungary. (4)Department of Social Sciences, Faculty of Health Sciences, Semmelweis University, 1085 Budapest, Hungary. (5)Division of Sport, Exercise and Health, School of Health and Life Sciences, University of the West of Scotland, Blantyre G720LH, UK. (6)Meshkat Sports Complex, Karaj 3149645179, Alborz Province, Iran. (7)Arses Sports Complex, Karaj 3149645179, Alborz Province, Iran. (8)Institute of Primary Care, University Hospital Zurich, 8091 Zurich, Switzerland. (9)Medbase St. Gallen Am Vadianplatz, 9000 St. Gallen, Switzerland. (10)Department of Kinesiology, Kansas State University, Manhattan, KS 66506, USA. (11)Department of Research and Evaluation, The Phoenix, Manhattan, KS 66502, USA. Given the increasing popularity of CrossFit® as a high-intensity functional training program and the potential benefits of citrulline malate (CM) in enhancing exercise performance through its role as a precursor to L-arginine and nitric oxide production, this study aimed to investigate the acute effects of CM supplementation on CrossFit® performance and cardiovascular function. Using a randomized, double-blind, placebo-controlled, cross-over design, 21 recreationally active participants (mean age 22.2 ± 2.6 years, mean body weight 75.9 ± 10.4 kg) with CrossFit® experience completed the "Cindy" workout under CM and placebo conditions. Participants consumed 4.4 g of CM or a placebo 60 min before the workout, and the performance was measured by the number of rounds completed. Secondary outcomes included heart rate response, time spent in different heart rate intensity zones, and post-exercise recovery time. The results indicated no significant difference in the number of rounds completed between the CM and placebo conditions (13.5 ± 5.2 vs. 13.8 ± 6.7 rounds, respectively; p = 0.587). However, the time spent in zone 4 (80-90% of HR max) was significantly increased in the CM condition (527 ± 395 s vs. 453 ± 334 s; p = 0.017), suggesting a potential benefit for aerobic capacity and anaerobic threshold. No significant differences in post-exercise recovery time were observed (6.6 ± 4.7 h vs. 6.9 ± 4.7 h; p = 0.475). This study highlights the need for further research with larger sample sizes, both genders, and different CM dosages to clarify these findings and better understand CM's role in enhancing athletic performance. DOI: 10.3390/nu16193235 PMCID: PMC11478471 PMID: 39408204 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

No evidence of improvements in energy metabolism after 1 week of nitrate and citrulline co-supplementation in elite rowers.

32. Eur J Appl Physiol. 2025 Mar;125(3):715-728. doi: 10.1007/s00421-024-05636-7. Epub 2024 Oct 9. No evidence of improvements in energy metabolism after 1 week of nitrate and citrulline co-supplementation in elite rowers. Viribay A(#)(1)(2), Alcantara JMA(#)(3)(4)(5), López I(6), Mielgo-Ayuso J(7), Castañeda-Babarro A(8). Author information: (1)Glut4Science, Physiology, Nutrition and Sport, 01004, Vitoria-Gasteiz, Spain. aitor@glut4science.com. (2)Institute of Biomedicine (IBIOMED), University of Leon, 24071, Leon, Spain. aitor@glut4science.com. (3)Institute for Sustainability & Food Chain Innovation, Department of Health Sciences, Public University of Navarre, Pamplona, Spain. (4)Navarra Institute for Health Research, IdiSNA, Pamplona, Spain. (5)Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029, Madrid, Spain. (6), San Ignacio Auzunea Etxetaldea 5, 48200, Durango, Spain. (7)Department of Health Sciences, Faculty of Health Sciences, University of Burgos, 09001, Burgos, Spain. (8)Health, Physical Activity, and Sports Science Laboratory, Department of Physical Activity and Sports, Faculty of Education and Sport, University of Deusto, 48007, Bizkaia, Spain. (#)Contributed equally PURPOSE: Citrulline (CIT) and beetroot extract (BR) supplements positively impacts exercise performance in elite rowers. However, its influence on metabolic outcomes such as whole-body volumes of oxygen consumption (VO2) and carbon dioxide production (VCO2), substrate oxidation, energy expenditure (EE), and gross efficiency remains unknown. We studied the effects of 1 week of daily co-supplementation of 3.5 g BR (500 mg NO3-) plus 6 g CIT on VO2 and VCO2 kinetics, substrate utilization, EE, and gross efficiency in elite male rowers compared to a placebo and to a BR supplementation. METHODS: Twenty elite rowers participated in this randomized, double-blind, placebo-controlled crossover trial completing 1 week of supplementation in each group of study: Placebo (PLAG); BRG; and BR-CITG. Efficiency (70% VO2max) and performance (incremental maximal) tests were performed, and gas-exchange data were collected via indirect calorimetry. RESULTS: Analysis of covariance (ANCOVA) showed no mean between-condition differences on respiratory exchange ratio (RER), EE, and gross efficiency in the efficiency test (all P > 0.06), and in the performance test (all P > 0.28). Moreover, in both tests no interaction Time × Supplement effects were observed for VO2, VCO2, RER, EE, substrate oxidation, and, gross efficiency (all P > 0.12). CONCLUSION: After 1 week, no effects on energy metabolism and substrate utilization were observed after the daily co-ingestion of BR extract plus CIT supplement, therefore longer (> 7 days) and higher doses of supplementation might be needed to influence metabolism. © 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. DOI: 10.1007/s00421-024-05636-7 PMID: 39382670 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Conflict of interest: The authors affirm no conflict of interest. Ethical approval: This trial was designed in accordance with the Declaration of Helsinki (2008) and the Fortaleza update (2013) and was approved human Research Ethics Committee at the University of Deusto, Bilbao, Spain (ETK-13/18–19).

Gut microbial alterations in arginine metabolism determine bone mechanical adaptation.

33. Cell Metab. 2024 Jun 4;36(6):1252-1268.e8. doi: 10.1016/j.cmet.2024.04.004. Epub 2024 May 7. Gut microbial alterations in arginine metabolism determine bone mechanical adaptation. Wang D(1), Cai J(2), Pei Q(3), Yan Z(3), Zhu F(4), Zhao Z(4), Liu R(3), Guo X(3), Sun T(3), Liu J(3), Tian Y(3), Liu H(5), Shao X(3), Huang J(6), Hao X(3), Chang Q(7), Luo Z(8), Jing D(9). Author information: (1)Department of Biomedical Engineering, Fourth Military Medical University, Xi'an 710032, China; Faculty of Life Sciences, Northwest University, Xi'an 710069, China. (2)College of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China. Electronic address: 1988cai@163.com. (3)Department of Biomedical Engineering, Fourth Military Medical University, Xi'an 710032, China. (4)Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. (5)Department of Hematology, Affiliated Hospital of Northwest University Xi'an Third Hospital, Xi'an 710016, China. (6)Institute of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. (7)Department of Orthopaedics, The 989(th) Hospital of the People's Liberation Army Joint Service Support Force, Luoyang 471031, China. Electronic address: changqi11271@126.com. (8)Institute of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: zjluo@fmmu.edu.cn. (9)Department of Biomedical Engineering, Fourth Military Medical University, Xi'an 710032, China; Institute of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environment, Fourth Military Medical University, Xi'an 710032, China. Electronic address: jingdaasq@126.com. Although mechanical loading is essential for maintaining bone health and combating osteoporosis, its practical application is limited to a large extent by the high variability in bone mechanoresponsiveness. Here, we found that gut microbial depletion promoted a significant reduction in skeletal adaptation to mechanical loading. Among experimental mice, we observed differences between those with high and low responses to exercise with respect to the gut microbial composition, in which the differential abundance of Lachnospiraceae contributed to the differences in bone mechanoresponsiveness. Microbial production of L-citrulline and its conversion into L-arginine were identified as key regulators of bone mechanoadaptation, and administration of these metabolites enhanced bone mechanoresponsiveness in normal, aged, and ovariectomized mice. Mechanistically, L-arginine-mediated enhancement of bone mechanoadaptation was primarily attributable to the activation of a nitric-oxide-calcium positive feedback loop in osteocytes. This study identifies a promising anti-osteoporotic strategy for maximizing mechanical loading-induced skeletal benefits via the microbiota-metabolite axis. Copyright © 2024 Elsevier Inc. All rights reserved. DOI: 10.1016/j.cmet.2024.04.004 PMID: 38718794 [Indexed for MEDLINE] Conflict of interest statement: Declaration of interests The authors declare no competing interests.

Short-Term L-Citrulline Supplementation Does Not Affect Blood Pressure, Pulse Wave Reflection, or Arterial Stiffness at Rest and during Isometric Exercise in Older Males.

34. Sports (Basel). 2023 Sep 7;11(9):177. doi: 10.3390/sports11090177. Short-Term L-Citrulline Supplementation Does Not Affect Blood Pressure, Pulse Wave Reflection, or Arterial Stiffness at Rest and during Isometric Exercise in Older Males. Tryfonos A(1)(2), Christodoulou F(1), Pamboris GM(1), Christodoulides S(1)(3), Theodorou AA(1). Author information: (1)Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia 1516, Cyprus. (2)Department of Laboratory Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden. (3)School of Medicine, European University Cyprus, Nicosia 1516, Cyprus. Hypertension and arterial stiffness are significant factors contributing to cardiovascular disease. L-citrulline, a nitric oxide precursor, has been proposed as a nutritional, non-pharmacological blood pressure-lowering intervention. This study aimed to investigate the impact of L-citrulline on central and peripheral blood pressure, pulse wave reflection, and central arterial stiffness at rest and during an isometric knee extension exercise protocol. Twelve older males received 6 g of L-citrulline or a placebo for six days using a double-blind crossover design. Blood hemodynamics parameters (i.e., aortic and brachial systolic and diastolic blood pressure, mean arterial pressure, pulse pressure, heart rate), pulse wave reflection (i.e., augmented pressure, augmentation index, forward/backward wave pressure), and arterial stiffness (i.e., carotid-femoral pulse wave velocity) were measured at baseline, post-supplementation, and during isometric exercise. No significant effects of L-citrulline supplementation were observed at rest or during exercise on blood pressure, pulse wave reflection, or arterial stiffness. Both central and peripheral blood pressure were increased during the exercise, which is consistent with isometric contractions. The results of the present study do not support any blood pressure-lowering effect of short-term L-citrulline at rest or during low-intensity isometric exercise compared to the pre-exercise values in older males. DOI: 10.3390/sports11090177 PMCID: PMC10535063 PMID: 37755854 Conflict of interest statement: The authors declare no conflict of interest.

L-Citrulline supplementation attenuates aortic pressure and pressure waves during metaboreflex activation in postmenopausal women.

35. Br J Nutr. 2024 Feb 14;131(3):474-481. doi: 10.1017/S000711452300199X. Epub 2023 Sep 4. L-Citrulline supplementation attenuates aortic pressure and pressure waves during metaboreflex activation in postmenopausal women. Dillon KN(1), Kang Y(1), Maharaj A(1)(2), Martinez MA(1), Fischer SM(1), Figueroa A(1). Author information: (1)Department of Kinesiology and Sport Management, Texas Tech University, Lubbock, TX79409, USA. (2)Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA. Postmenopausal women have augmented pressure wave responses to low-intensity isometric handgrip exercise (IHG) due to an overactive metaboreflex (postexercise muscle ischaemia, PEMI), contributing to increased aortic systolic blood pressure (SBP). Menopause-associated endothelial dysfunction via arginine (ARG) and nitric oxide deficiency may contribute to exaggerated exercise SBP responses. L-Citrulline supplementation (CIT) is an ARG precursor that decreases SBP, pulse pressure (PP) and pressure wave responses to cold exposure in older adults. We investigated the effects of CIT on aortic SBP, PP, and pressure of forward (Pf) and backward (Pb) waves during IHG and PEMI in twenty-two postmenopausal women. Participants were randomised to CIT (10 g/d) or placebo (PL) for 4 weeks. Aortic haemodynamics were assessed via applanation tonometry at rest, 2 min of IHG at 30 % of maximal strength, and 3 min of PEMI. Responses were analysed as change (Δ) from rest to IHG and PEMI at 0 and 4 weeks. CIT attenuated ΔSBP (−9 ± 2 v. −1 ± 1 mmHg, P = 0·006), ΔPP (−5 ± 2 v. 0 ± 1 mmHg, P = 0·03), ΔPf (−6 ± 2 v. −1 ± 1 mmHg, P = 0·01) and ΔPb (−3 ± 1 v. 0 ± 1 mmHg, P = 0·02) responses to PEMI v. PL. The ΔPP during PEMI was correlated with ΔPf (r = 0·743, P < 0·001) and ΔPb (r = 0·724, P < 0·001). Citrulline supplementation attenuates the increase in aortic pulsatile load induced by muscle metaboreflex activation via reductions in forward and backward pressure wave amplitudes in postmenopausal women. DOI: 10.1017/S000711452300199X PMID: 37664994 [Indexed for MEDLINE]

Acute Effect of L-Citrulline Supplementation on Resistance Exercise Performance and Muscle Oxygenation in Recreationally Resistance Trained Men and Women.

36. J Funct Morphol Kinesiol. 2023 Jun 22;8(3):88. doi: 10.3390/jfmk8030088. Acute Effect of L-Citrulline Supplementation on Resistance Exercise Performance and Muscle Oxygenation in Recreationally Resistance Trained Men and Women. Gonzalez AM(1), Yang Y(1), Mangine GT(2), Pinzone AG(3), Ghigiarelli JJ(1), Sell KM(1). Author information: (1)Department of Allied Health and Kinesiology, Hofstra University, Hempstead, NY 11549, USA. (2)Department of Exercise Science and Sport Management, Kennesaw State University, Kennesaw, GA 30144, USA. (3)Program in Exercise Science and Exercise Physiology, Kent State University, Kent, OH 44242, USA. L-citrulline serves as a nitric oxide precursor with the potential to increase blood flow and improve resistance exercise performance, yet more research is needed to examine its ergogenic potential. To examine the effect of L-citrulline supplementation on resistance exercise performance, muscle oxygenation, and the subjective perception of effort, energy, focus, fatigue, and muscle pump, eighteen resistance-trained men (n = 11) and women (n = 7) (21.4 ± 1.8 years; 172.3 ± 7.5 cm; 76.9 ± 10.8 kg) were randomly assigned for supplementation with 8 g of L-citrulline (CIT) or a placebo (PL) in a cross-over fashion one hour prior to testing. Participants completed an isometric mid-thigh pull test (IMTP), a ballistic bench press protocol [two sets of two repetitions at 75% 1-repetition maximum (1 RM) with maximum ballistic intent], and a strength-endurance bench press protocol [five repetition-maximum sets at 75% 1RM]. Barbell velocity and power were measured via a linear position transducer during the ballistic protocol, while the repetitions completed, volume load and muscle oxygenation were quantified during the strength-endurance protocol. Subjective measures were assessed at the baseline and immediately pre- and post-exercise. Repeated measures of the analysis of variance and Bayesian equivalents revealed no significant interactions, providing evidence favoring the null hypothesis (BF10 < 1) for IMTP (PL 497.5 ± 133.6 vs. CIT 492.5 ± 129.4 N), barbell velocity, and power, and repetitions completed (PL 36.7 ± 7.2 vs. CIT 36.9 ± 8.1 repetitions). There were also no significant interactions for muscle oxygenation parameters or subjective measures except perceived fatigue. Women reported greater fatigue across all time points compared to men (~1.88 au, p = 0.045, BF10 = 0.2). The results indicate that a single 8 g dose of L-citrulline did not enhance isometric force production, muscle endurance, or muscle oxygenation parameters during the protocol implemented in this study. DOI: 10.3390/jfmk8030088 PMCID: PMC10366749 PMID: 37489301 Conflict of interest statement: A.M.G. declares that he serves as a Scientific Advisor for Shifted LLC: a manufacturer of sports supplements. All other authors report no conflict of interest.

Effect of Combined Grape Seed Extract and L-Citrulline Supplementation on Hemodynamic Responses to Exercise in Young Males.

37. J Diet Suppl. 2023;20(4):531-542. doi: 10.1080/19390211.2021.2023246. Epub 2022 Jan 4. Effect of Combined Grape Seed Extract and L-Citrulline Supplementation on Hemodynamic Responses to Exercise in Young Males. Shariffi B(1), Dillon K(1), Gillum T(1), Boyer W(1), Sullivan S(1), Lee E(2), Kim JK(1). Author information: (1)Department of Kinesiology, California Baptist University, Riverside, CA, USA. (2)Division of Natural and Mathematical Sciences, California Baptist University, Riverside, CA, USA. Grape seed extract (GSE) or L-citrulline supplement has been known to increase nitric oxide (NO) bioavailability and enhance endothelial-mediated vasodilation. Accordingly, to examine the additive benefits of combination of the two supplementations on hemodynamic responses to dynamic exercise, young, healthy males were recruited for this study. Effects of 7 days of 1) GSE + L-citrulline, 2) GSE, 3) L-citrulline, and 4) placebo supplementation on systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), cardiac output, total vascular conductance (TVC), and oxygen (O2) consumption were examined at rest and during cycling exercise. Compared with placebo, GSE, L-citrulline, and combined supplementations did not reduce SBP, DBP, and MAP, while cardiac output (placebo; 23.6 ± 1.3 L/min, GSE; 25.7 ± 1.1 L/min; L-citrulline, 25.2 ± 1.2 L/min; GSE + L-citrulline; 25.3 ± 0.9 L/min) and TVC (placebo; 234.7 ± 11.3 ml/min/mmHg, GSE; 258.3 ± 10.6 ml/min/mmHg; L-citrulline, 255.2 ± 10.6 ml/min/mmHg; GSE + L-citrulline; 260.4 ± 8.9 ml/min/mmHg) were increased at only the 80% workload (p < 0.05). Compared with placebo and L-citrulline, GSE and combined supplementations had a reduction in VO2 across workloads (p < 0.05). However, there was no additive benefits on these variables. We conclude that supplementation with GSE, L-citrulline, and combined supplementations increased cardiac output due partially to decreased vascular resistance. Our findings suggest that GSE may act as an ergogenic aid that can improve O2 delivery to exercising muscles. DOI: 10.1080/19390211.2021.2023246 PMID: 37293750 [Indexed for MEDLINE]

The Effect of Acute Pre-Workout Supplement Ingestion on Basketball-Specific Performance of Well-Trained Athletes.

38. Nutrients. 2023 May 14;15(10):2304. doi: 10.3390/nu15102304. The Effect of Acute Pre-Workout Supplement Ingestion on Basketball-Specific Performance of Well-Trained Athletes. Douligeris A(1), Methenitis S(1)(2)(3), Lazou A(4), Panayiotou G(5), Feidantsis K(1), Voulgaridou G(1), Manios Y(6)(7), Jamurtas AZ(8), Giaginis C(9), Papadopoulou SK(1). Author information: (1)Department of Nutrition Sciences and Dietetics, Faculty of Health Sciences, International Hellenic University, 57400 Thessaloniki, Greece. (2)Sports Performance Laboratory, School of Physical Education & Sports Science, National and Kapodistrian University of Athens, 15772 Athens, Greece. (3)Theseus, Physical Medicine and Rehabilitation Center, 17671 Athens, Greece. (4)Nutrition and Dietetics, School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL109AB, UK. (5)Laboratory of Exercise, Health and Human Performance, Applied Sport Science Postgraduate Program, Department of Life Sciences, School of Sciences, European University Cyprus, 1516 Nicosia, Cyprus. (6)Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University, 17671 Athens, Greece. (7)Institute of Agri-food and Life Sciences, Hellenic Mediterranean University Research Centre, 71410 Heraklion, Greece. (8)Department of Physical Education & Sport Science, University of Thessaly, 42100 Trikala, Greece. (9)Department of Food Science and Nutrition, School of Environment, University of the Aegean, 81400 Myrina, Greece. A pre-workout supplement's (PWS; 200 mg caffeine, 3.3 g creatine monohydrate, 3.2 g β-alanine, 6 g citrulline malate and 5 g branched chained amino acid (BCAA) per dose) acute effects on the alactic (jumping, sprinting, agility), lactic (Running-Based Anaerobic Sprint Test, RAST) and aerobic performance (Yo-Yo Intermittent Recovery Test Level 1, Yo-Yo IRL1 VO2max) of well-trained basketball players was investigated in this double-blind placebo-controlled study. Thirty players (age 18-31 years, height 166-195 cm, weight 70.2-116.7 kg, body fat 10.6-26.4%) were allocated to pre-workout (PWS, n = 15) or placebo (PL, n = 15) groups. Half of the participants in each group performed the evaluations without PWS or PL, while the rest consumed PWS or PL 30 min before the assessments (1st trial) and vice versa (2nd trial). Significant improvements in counter-movement jump (CMJ) (PWS: 4.3 ± 2.1%; PL: 1.2 ± 1.0%), agility (PWS: -2.9 ± 1.8%; PL: 1.8 ± 1.7%), RAST average (PWS: 18.3 ± 9.1%; PL: -2.2 ± 2.0%), minimum power (PWS: 13.7 ± 8.9%; PL: -7.5 ± 5.9%), and fatigue index (PWS: -25.0 ± 0.9%; PL: -4.6 ± 0.6%) were observed in the PWS group vs. the PL group (p < 0.05). No differences were found regarding sprinting, aerobic performance, and blood lactate concentrations. Thus, although players' alactic and lactic anaerobic performance could be improved, peak power, sprinting and aerobic performance are not. DOI: 10.3390/nu15102304 PMCID: PMC10220844 PMID: 37242187 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflict of interest.

Effects of citrulline on endurance performance in young healthy adults: a systematic review and meta-analysis.

39. J Int Soc Sports Nutr. 2023 Dec;20(1):2209056. doi: 10.1080/15502783.2023.2209056. Effects of citrulline on endurance performance in young healthy adults: a systematic review and meta-analysis. Harnden CS(1), Agu J(1), Gascoyne T(1). Author information: (1)University of Nottingham, Department of Sports and Exercise Medicine, Faculty of Medicine and Health Sciences, Nottingham, UK. BACKGROUND: Citrulline is a popular dietary supplement, primarily thought to exert ergogenic effects on exercise performance through the enhancement of nitric oxide (NO) synthesis and ammonia buffering. However, recent findings surrounding citrulline's effect on endurance performance have been inconsistent. A systematic review and meta-analysis of the relevant literature have yet to be undertaken. AIM: To determine if acute ingestion of citrulline has an ergogenic effect on endurance performance in young healthy adults. METHODS: A systematic search of three databases was undertaken to find peer-reviewed randomized controlled trials (RCTs) published in English investigating the effects of citrulline supplementation on endurance performance in young healthy adults. Two independent investigators completed a three-phased screening procedure against pre-determined eligibility criteria. Included studies evaluated loading or bolus dosage regimes of citrulline in participants aged 18 or over that were at least recreationally active. Outcome measures focused on time-to-completion (TTC) or time-to-exhaustion (TTE) in continuous submaximal intensity exercise. Cochrane's Risk of Bias 2 (RoB 2) tool was used to assess the risk of bias in individual studies. Meta-analysis was conducted using a fixed-effects model to pool the weighted estimate of standardized mean differences (SMD) across studies. A chi-squared test assessed heterogeneity between studies. This review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Nine studies (n = 158 participants) met the eligibility criteria; five reported TTE outcomes (I2 = 0%, χ2 = 0.37, df = 4, P = 0.99) and four reported TTC outcomes (I2 = 0%, χ2 = 0.46, df = 3, P = 0.93), both with a low between-study heterogeneity. The results of the meta-analyses showed no significant difference in the endurance performance measures, TTE (pooled SMD = 0.03 [-0.27, 0.33]) and TTC (pooled SMD = -0.07 [-0.50, 0.15]), after acute ingestion of citrulline supplementation or a control in young healthy adults. DISCUSSION: The current evidence suggests no significant benefit of citrulline supplementation for endurance performance. However, the small evidence base requires further research to fully evaluate this topic. Recommendations include a focus on female populations; higher continuous doses of citrulline over seven days; and TTC outcome measures over longer distances to simulate competition. DOI: 10.1080/15502783.2023.2209056 PMCID: PMC10167868 PMID: 37155582 [Indexed for MEDLINE] Conflict of interest statement: No potential conflict of interest was reported by the author(s).