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Fallah F, Mahdavi R. Modulatory Effects of Multi-species/Multi-strain Synbiotic and L-carnitine Concomitant Supplementation on Atherogenic-Indices, Body Composition, Visceral Obesity, and Appetite in Metabolically Healthy Women with Obesity: A Double-Blind Randomized Controlled Clinical Trial. Probiotics Antimicrob Proteins 2025:10.1007/s12602-025-10460-2. [PMID: 39921845 DOI: 10.1007/s12602-025-10460-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/13/2025] [Indexed: 02/10/2025]
Abstract
Obesity, a chronic disease with pandemic proportions, is recognized as a major risk factor for cardiometabolic disorders due to its association with atherogenic dyslipidemia, a common characteristic attributed to visceral adiposity in patients with obesity. Atherogenic and visceral-obesity indices have been conceded as surrogate cardiovascular diseases (CVD) indicators surpassing the conventional markers due to stronger predictive power for obesity-induced cardiometabolic risk and CVD mortality rate. Nutraceuticals have been suggested as emerging approaches to counteract obesity-associated cardiometabolic disorders. Considering the evidence addressing the ameliorating effects of either L-carnitine or biotics on metabolic indices, also the reports addressing higher efficacy of concomitant supplementation versus single-therapies, this clinical trial was conducted to assess the effects of L-carnitine + multi-species/multi-strain synbiotic combined supplementation compared to L-carnitine mono-therapy on atherogenic-indices, body composition, visceral obesity, and appetite sensations in 46 metabolically healthy women with obesity, randomly assigned to co-supplementation (L-carnitine-tartrate (2 × 500 mg/dl) + synbiotic (one capsule/day)) or mono-therapy (L-carnitine-tartrate (2 × 500 mg/dl) + maltodextrin (one capsule/day)) groups for 8 weeks. L-carnitine + synbiotic co-supplementation led to a significantly greater reduction in atherogenic-indices including atherogenic-index-of-plasma (AIP), Castelli's-risk-index-I (CRI-I), Castelli's-risk-index-II (CRI-II), atherogenic-coefficient (AC), lipoprotein-combine index (LCI), systolic blood pressure (SBP), fat-mass (FM) weight/percent, visceral-adiposity index (VAI), waste-to-height ratio (WHtR), body-adiposity index (BAI), and appetite sensation scores compared to L-carnitine mono-therapy. L-carnitine + synbiotic combined supplementation was more efficient in improving atherogenic-indices as cardiovascular risk markers, body composition, visceral obesity, and appetite sensations in metabolically healthy women with obesity. Therefore, simultaneous supplementation of L-carnitine + synbiotic might be considered a promising approach to ameliorate cardiometabolic risk factors in healthy individuals with obesity. Further longer period studies are required to confirm these findings. (Iranian Registry of Clinical Trials (IRCT; https://irct.behdasht.gov.ir/trial/28048 ).
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Affiliation(s)
- Farnoush Fallah
- Student Research Committee, Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Mahdavi
- Nutrition Research Center, Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
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Elantary R, Othman S. Role of L-carnitine in Cardiovascular Health: Literature Review. Cureus 2024; 16:e70279. [PMID: 39329040 PMCID: PMC11427024 DOI: 10.7759/cureus.70279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/26/2024] [Indexed: 09/28/2024] Open
Abstract
Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. Secondary preventive measures, like anti-platelet medications, B-blockers, and angiotensin-converting enzyme (ACE) inhibitors, have been found to dramatically lower the risk of cardiovascular disease. However, prolonged usage of these drugs has been linked to multiple adverse impacts. Hence, finding more efficient treatments, especially dietary strategies for long-term use in daily life, is advantageous for primary prevention and treatment. L-carnitine, a naturally occurring amino acid derivative normally synthesized in the liver and kidney, is believed to have a considerable influence on cardiovascular health. L-carnitine can enhance both contractile performance and structural integrity of the cardiac muscle by maintaining efficient energy production and reducing oxidative stress. This literature review aims to address several pressing questions regarding the role of L-carnitine in cardiovascular health: what are the physiological functions of L-carnitine, particularly in relation to cardiovascular health; how effective and safe is L-carnitine supplementation in the management of various cardiovascular diseases, primarily ischemic heart disease, heart failure, and peripheral vascular disease; what are the underlying mechanisms through which L-carnitine exerts its cardioprotective effects; what controversies exist in the current research; and finally, what should be the future directions? Through this comprehensive analysis, the review aims to enrich our understanding of L-carnitine's role in cardiovascular health, providing a robust foundation for future academic and clinical endeavors. PubMed, Embase, and Google Scholar have been used to search the following keywords: L-carnitine, cardiovascular health, mitochondrial function, and L-carnitine side effects. Then, using the existing search engine formats, some keyword combinations were used to find the related articles included and every possibility, including using every first keyword combination with another keyword, using every keyword in every place at each given box, etc. Around 308 articles were reviewed using this process, including systemic reviews, meta-analysis studies, randomized controlled trials, and literature review articles. In the end, after leaving the pure articles related to the topic as 35 articles, which are attached below with direct citation, the majority of them were very fresh articles, as recent as 2010, and back words, except just one paper related to the impact of L-carnitine post-myocardial infarction, as its data provided us with a positive and promising impact of L-carnitine in this field. L‑carnitine seems to have a pivotal role in cardiovascular health due to its energy metabolism, anti-oxidative stress, and endothelial role. The safety and effectiveness of L-carnitine administration remain an issue for scientific investigation. One of the major concerns is that the intestinal metabolism of L-carnitine generates trimethylamine-N-oxide (TMAO), a compound that has been linked with faster atherosclerosis progression.
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Affiliation(s)
- Ramy Elantary
- Department of Acute Medicine, Royal Liverpool University Hospital, Liverpool, GBR
| | - Samar Othman
- Department of Diabetes and Endocrinology, Countess of Chester Hospital, Chester, GBR
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Wang W, Pan D, Liu Q, Chen X, Wang S. L-Carnitine in the Treatment of Psychiatric and Neurological Manifestations: A Systematic Review. Nutrients 2024; 16:1232. [PMID: 38674921 PMCID: PMC11055039 DOI: 10.3390/nu16081232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 04/13/2024] [Accepted: 04/19/2024] [Indexed: 04/28/2024] Open
Abstract
OBJECTIVE L-carnitine (LC), a vital nutritional supplement, plays a crucial role in myocardial health and exhibits significant cardioprotective effects. LC, being the principal constituent of clinical-grade supplements, finds extensive application in the recovery and treatment of diverse cardiovascular and cerebrovascular disorders. However, controversies persist regarding the utilization of LC in nervous system diseases, with varying effects observed across numerous mental and neurological disorders. This article primarily aims to gather and analyze database information to comprehensively summarize the therapeutic potential of LC in patients suffering from nervous system diseases while providing valuable references for further research. METHODS A comprehensive search was conducted in PubMed, Web Of Science, Embase, Ovid Medline, Cochrane Library and Clinicaltrials.gov databases. The literature pertaining to the impact of LC supplementation on neurological or psychiatric disorders in patients was reviewed up until November 2023. No language or temporal restrictions were imposed on the search. RESULTS A total of 1479 articles were retrieved, and after the removal of duplicates through both automated and manual exclusion processes, 962 articles remained. Subsequently, a meticulous re-screening led to the identification of 60 relevant articles. Among these, there were 12 publications focusing on hepatic encephalopathy (HE), while neurodegenerative diseases (NDs) and peripheral nervous system diseases (PNSDs) were represented by 9 and 6 articles, respectively. Additionally, stroke was addressed in five publications, whereas Raynaud's syndrome (RS) and cognitive disorder (CD) each had three dedicated studies. Furthermore, migraine, depression, and amyotrophic lateral sclerosis (ALS) each accounted for two publications. Lastly, one article was found for other symptoms under investigation. CONCLUSION In summary, LC has demonstrated favorable therapeutic effects in the management of HE, Alzheimer's disease (AD), carpal tunnel syndrome (CTS), CD, migraine, neurofibromatosis (NF), PNSDs, RS, and stroke. However, its efficacy appears to be relatively limited in conditions such as ALS, ataxia, attention deficit hyperactivity disorder (ADHD), depression, chronic fatigue syndrome (CFS), Down syndrome (DS), and sciatica.
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Affiliation(s)
- Wenbo Wang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China; (W.W.); (D.P.); (X.C.)
| | - Da Pan
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China; (W.W.); (D.P.); (X.C.)
| | - Qi Liu
- Department of Public Health, School of Medicine, Xizang Minzu University, Xianyang 712082, China;
| | - Xiangjun Chen
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China; (W.W.); (D.P.); (X.C.)
- Department of Public Health, School of Medicine, Xizang Minzu University, Xianyang 712082, China;
| | - Shaokang Wang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China; (W.W.); (D.P.); (X.C.)
- Department of Public Health, School of Medicine, Xizang Minzu University, Xianyang 712082, China;
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Fallah F, Mahdavi R. Ameliorating effects of L-carnitine and synbiotic co-supplementation on anthropometric measures and cardiometabolic traits in women with obesity: a randomized controlled clinical trial. Front Endocrinol (Lausanne) 2023; 14:1237882. [PMID: 37929031 PMCID: PMC10622781 DOI: 10.3389/fendo.2023.1237882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Accepted: 09/11/2023] [Indexed: 11/07/2023] Open
Abstract
Background Obesity, a multifactorial disorder with pandemic dimensions, is conceded a major culprit of morbidity and mortality worldwide, necessitating efficient therapeutic strategies. Nutraceuticals and functional foods are considered promising adjuvant/complementary approaches for weight management in individuals with obesity who have low adherence to conventional treatments. Current literature supports the weight-reducing efficacy of pro/pre/synbiotics or L-carnitine; however, the superiority of the nutraceutical joint supplementation approach over common single therapies to counter obesity and accompanying comorbidities is well documented. This study was designed to assess the effects of L-carnitine single therapy compared with L-carnitine and multistrain/multispecies synbiotic co-supplementation on anthropometric and cardiometabolic indicators in women with obesity. Methods The current placebo-controlled double-blind randomized clinical trial was performed on 46 women with obesity, randomly allocated to either concomitant supplementation [L-carnitine tartrate (2 × 500 mg/day) + multistrain/multispecies synbiotic (1 capsule/day)] or monotherapy [L-carnitine tartrate (2 × 500 mg/day) + maltodextrin (1 capsule/day)] groups for 8 weeks. Participants in both groups received healthy eating dietary advice. Results Anthropometric, lipid, and glycemic indices significantly improved in both intervention groups; however, L-carnitine + synbiotic co-administration elicited a greater reduction in the anthropometric measures including body mass index (BMI), body weight, and neck, waist, and hip circumferences (p < 0.001, <0.001, <0.001, = 0.012, and =0.030, respectively) after adjusting for probable confounders. Moreover, L-carnitine + synbiotic joint supplementation resulted in a greater reduction in fasting blood sugar (FBS), insulin (though marginal), and homeostatic model assessment of insulin resistance (HOMA-IR) and more increment in quantitative insulin sensitivity check index (QUICKI; p = 0.014, 0.051, 0.024, and 0.019, respectively) compared with the L-carnitine + placebo monosupplementation. No significant intergroup changes were found for the lipid profile biomarkers, except for a greater increase in high-density lipoprotein-cholesterol concentrations (HDL-C) in the L-carnitine + synbiotic group (p = 0.009). Conclusion L-carnitine + synbiotic co-supplementation was more beneficial in ameliorating anthropometric indices as well as some cardiometabolic parameters compared with L-carnitine single therapy, suggesting that it is a promising adjuvant approach to ameliorate obesity or associated metabolic complications through potential synergistic or complementary mechanisms. Further longer duration clinical trials in a three-group design are demanded to verify the complementary or synergistic mechanisms. Clinical trial registration www.irct.ir, Iranian Registry of Clinical Trials IRCT20080904001197N13.
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Affiliation(s)
- Farnoush Fallah
- Student Research Committee, Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Mahdavi
- Nutrition Research Center, Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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Fallah F, Mahdavi R. L-Carnitine and synbiotic co-supplementation: beneficial effects on metabolic-endotoxemia, meta-inflammation, and oxidative-stress biomarkers in obese patients: a double blind, randomized, controlled clinical trial. Food Funct 2023; 14:2172-2187. [PMID: 36752775 DOI: 10.1039/d2fo03348h] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Obesity, a chronic pandemic disease, is characterized by low-grade chronic inflammation, accompanied by over-expression of pro-inflammatory cytokines, thereby contributing to metabolic disorders pathogenesis. Oxidative-stress, an adverse cellular response to adipocyte hypertrophy, promotes inflammation. Furthermore, gut-microbiota dysbiosis may induce oxidative-stress, low-grade inflammation, and metabolic-endotoxemia as major drivers of obesity. Functional-foods/nutraceuticals have attracted extensive attention due to their plausible anti-inflammatory/anti-oxidative properties; evidence supports the superiority of the nutraceutical combined-supplementation approach versus conventional mono-therapies. Current data suggest the anti-oxidative/anti-inflammatory properties of either L-carnitine or pre/pro/synbiotics. This trial compared the effects of co-supplementing L-carnitine and multi-species/multi-strain synbiotic versusL-carnitine mono-therapy on inflammatory/anti-inflammatory, oxidative-stress, and metabolic-endotoxemia biomarkers in 46 female obese patients, receiving either co-supplementation (L-carnitine-tartrate (2 × 500 mg d-1) + multi-species/multi-strain synbiotic (1 capsule per day)) or mono-therapy (L-carnitine-tartrate (2 × 500 mg d-1) + maltodextrin (1 capsule per day)) for eight weeks. L-Carnitine + synbiotic co-supplementation significantly decreased interleukin-6 (IL-6, -33.98%), high-sensitivity-C-reactive-protein (hs-CRP, -10%), tumor-necrosis-factor-alpha (TNF-α, -18.73%), malondialdehyde (MDA, -21.73%), and lipopolysaccharide (LPS, -10.14%), whereas the increase in interleukin-10 (IL-10, 7.69%) and total-antioxidant-capacity (TAC, 4.13%) levels was not significant. No significant changes were observed for the above-mentioned parameters in the L-carnitine + placebo group, except for a significant reduction in IL-10 (-17.59%) and TNF-α (-14.78%); however, between-group differences did not reach the significant threshold. Co-supplementing L-carnitine + multi-strain synbiotic led to significant amelioration of inflammatory, oxidative, and metabolic-endotoxemia responses in female obese patients; nevertheless, no improving effects were observed in patients receiving single-supplementation, suggesting that L-carnitine + synbiotic co-supplementation might represent an adjuvant approach to improve oxidative-stress/pro-inflammatory indicators in women with obesity, possibly through beneficial effects of the synbiotic alone. Further longer duration studies with higher doses of L-carnitine in a three-group setting are warranted to elucidate the possibility of synergistic or complementary mechanisms.
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Affiliation(s)
- Farnoush Fallah
- Student Research Committee, Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Reza Mahdavi
- Nutrition Research Center, Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
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Nachvak SM, Shabanpur M, Mostafai R, Heidari Moghaddam R, Moludi J. L-Carnitine supplementation reduces biomarkers of inflammatory and oxidative stress in patients with coronary artery disease: a randomised controlled trial. Arch Physiol Biochem 2023; 129:61-68. [PMID: 32816578 DOI: 10.1080/13813455.2020.1797102] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE l-Carnitine has been suggested as a potential nutrient that alleviates the oxidative and inflammatory damages of coronary artery disease (CAD), but the results of the previous studies of the importance of this supplementation remains unclear. This study attempts to evaluate the effects of l-carnitine (LC) supplementation on oxidative stress and inflammatory biomarkers in patients with CAD. METHODS A double-blind, randomised, placebo-trial was conducted on 75 CAD subjects. Patients were randomly assigned to receive LC (1000 mg/day) or placebo capsules over 3 months. Sera high-sensitivity C-reactive protein (hs-CRP), myeloperoxidase (MPO), nitrotyrosine (NT) and total antioxidant capacity (TAC) were assayed. RESULTS A significant increase in serum TAC and a significant decrease in MPO, NT, and hs-CRP levels were detected following 12 weeks of LC supplementation, compared to the placebo. CONCLUSIONS These results suggest that LC supplementation may exert beneficial effect on cardiovascular health through attenuate oxidative and inflammatory markers in CAD patients.
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Affiliation(s)
- Seyed Mostafa Nachvak
- Nutritional Sciences Department, School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Maryam Shabanpur
- Student Research Committee, School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Roghayeh Mostafai
- Nutritional Sciences Department, School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Reza Heidari Moghaddam
- Department of Cardiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Jalal Moludi
- Nutritional Sciences Department, School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran
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An BC, Yoon YS, Park HJ, Park S, Kim TY, Ahn JY, Kwon D, Choi O, Heo JY, Ryu Y, Kim JH, Eom H, Chung MJ. Toxicological Evaluation of a Probiotic-Based Delivery System for P8 Protein as an Anti-Colorectal Cancer Drug. Drug Des Devel Ther 2021; 15:4761-4793. [PMID: 34866901 PMCID: PMC8637785 DOI: 10.2147/dddt.s319930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 10/23/2021] [Indexed: 11/24/2022] Open
Abstract
Purpose This study aimed to toxicological evaluate a probiotics-based delivery system for p8 protein as an anti-colorectal cancer drug. Introduction Lactic acid bacteria (LAB) have been widely ingested for many years and are regarded as very safe. Recently, a Pediococcus pentosaceus SL4 (PP) strain that secretes the probiotic-derived anti-cancer protein P8 (PP-P8) has been developed as an anti-colorectal cancer (CRC) biologic by Cell Biotech. We initially identified a Lactobacillus rhamnosus (LR)-derived anti-cancer protein, P8, that suppresses CRC growth. We also showed that P8 penetrates specifically into CRC cells (DLD-1 cells) through endocytosis. We then confirmed the efficacy of PP-P8, showing that oral administration of this agent significantly decreased tumor mass (~42%) relative to controls in a mouse CRC xenograft model. In terms of molecular mechanism, PP-P8 induces cell-cycle arrest in G2 phase through down-regulation of Cyclin B1 and Cdk1. In this study, we performed in vivo toxicology profiling to obtain evidence that PP-P8 is safe, with the goal of receiving approval for an investigational new drug application (IND). Methods Based on gene therapy guidelines of the Ministry of Food and Drug Safety (MFDS) of Korea, the potential undesirable effects of PP-P8 had to be investigated in intact small rodent or marmoset models prior to first-in-human (FIH) administration. The estimated doses of PP-P8 for FIH are 1.0×1010 – 1.0×1011 CFU/person (60 kg). Therefore, to perform toxicological investigations in non-clinical animal models, we orally administered PP-P8 at doses of 3.375 × 1011, 6.75 × 1011, and 13.5×1011 CFU/kg/day; thus the maximum dose was 800–8000-fold higher than the estimated dose for FIH. Results In our animal models, we observed no adverse effects of PP-P8 on clinicopathologic findings, relative organ weight, or tissue pathology. In addition, we observed no inflammation or ulceration during pathological necropsy. Conclusion These non-clinical toxicology studies could be used to furnish valuable data for the safety certification of PP-P8.
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Affiliation(s)
- Byung Chull An
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Yeo-Sang Yoon
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Ho Jin Park
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Sangkyun Park
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Tai Yeub Kim
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Jun Young Ahn
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Daebeom Kwon
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Oksik Choi
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Jin Young Heo
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Yongku Ryu
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
| | - Joong-Hyun Kim
- Laboratory Animal Center, Osong Medical Innovation Foundation, Chungbuk, Cheongju, 28160, Korea
| | - Heejong Eom
- Laboratory Animal Center, Osong Medical Innovation Foundation, Chungbuk, Cheongju, 28160, Korea
| | - Myung Jun Chung
- R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea
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Aponte M, Murru N, Shoukat M. Therapeutic, Prophylactic, and Functional Use of Probiotics: A Current Perspective. Front Microbiol 2020; 11:562048. [PMID: 33042069 PMCID: PMC7516994 DOI: 10.3389/fmicb.2020.562048] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 08/12/2020] [Indexed: 12/12/2022] Open
Abstract
Probiotics are considered as the twenty-first century panpharmacon due to their competent remedial power to cure from gastrointestinal dysbiosis, systematic metabolic diseases, and genetic impairments up to complicated neurodegenerative disorders. They paved the way for an innovative managing of various severe diseases through palatable food products. The probiotics' role as a "bio-therapy" increased their significance in food and medicine due to many competitive advantages over traditional treatment therapies. Their prophylactic and therapeutic potential has been assessed through hundreds of preclinical and clinical studies. In addition, the food industry employs probiotics as functional and nutraceutical ingredients to enhance the added value of food product in terms of increased health benefits. However, regardless of promising health-boosting effects, the probiotics' efficacy still needs an in-depth understanding of systematic mechanisms and factors supporting the healthy actions.
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Affiliation(s)
- Maria Aponte
- Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy
| | - Nicoletta Murru
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Naples, Italy
| | - Mahtab Shoukat
- Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy
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Metabolomic Analysis of the Liver of a Dextran Sodium Sulfate-Induced Acute Colitis Mouse Model: Implications of the Gut-Liver Connection. Cells 2020; 9:cells9020341. [PMID: 32024178 PMCID: PMC7072179 DOI: 10.3390/cells9020341] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Revised: 01/21/2020] [Accepted: 01/29/2020] [Indexed: 01/18/2023] Open
Abstract
The incidence of ulcerative colitis (UC) is increasing worldwide, and it has become a growing problem in Asia. Previous research on UC has focused on serum, plasma, urine, gut tissues, and fecal metabolic profiling, but a comprehensive investigation into the correlation between the severity of colitis and changes in liver metabolism is still lacking. Since the liver and gut exchange nutrients and metabolites through a complex network, intestinal diseases can affect both the liver and other organs. In the present study, concentration-dependent dextran sodium sulfate (DSS)-induced ulcerative colitis was employed to examine changes in liver metabolism using a proton nuclear magnetic resonance spectroscopy (1H-NMR)-and ultra-performance liquid chromatography time of flight mass spectroscopy (UPLC-TOF MS)-based metabolomics study. Using the multivariate statistical analysis method orthogonal projections to latent structures discriminant analysis (OPLS-DA), changes in metabolites depending on the DSS dose could be clearly distinguished. Specifically, hepatic metabolites involved in one-carbon metabolism, carnitine-related metabolism, and nucleotide synthesis were found to be affected by intestinal inflammation, implying the existence of a metabolic connection between the gut and liver. We are currently investigating the significance of this metabolic condition in UC.
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Importance of release location on the mode of action of butyrate derivatives in the avian gastrointestinal tract. WORLD POULTRY SCI J 2019. [DOI: 10.1017/s004393391500269x] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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Abu-El-Zahab HSH, Hamza RZ, Montaser MM, El-Mahdi MM, Al-Harthi WA. Antioxidant, antiapoptotic, antigenotoxic, and hepatic ameliorative effects of L-carnitine and selenium on cadmium-induced hepatotoxicity and alterations in liver cell structure in male mice. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2019; 173:419-428. [PMID: 30798185 DOI: 10.1016/j.ecoenv.2019.02.041] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 02/08/2019] [Accepted: 02/13/2019] [Indexed: 06/09/2023]
Abstract
L-carnitine (LC) and selenium (Se) have significant protective and antioxidant effects on several tissues. Cadmium (Cd), widely used in some industries and emitted from fossil fuels, is a heavy metal having a number of side effects, including hepatotoxicity. This study aims to assess the ameliorative function of both LC and SeCl4 on cadmium chloride (CdCl2)-induced liver toxicity. In total, 70 male mice included in this study were allocated to seven groups: control, CdCl2, LC, SeCl4, CdCl2 plus SeCl4, CdCl2 plus LC, CdCl2 plus SeCl4 and LC groups. Hepatic aminotransferase (aspartate aminotransferase [AST] and alanine transaminase [ALT]) activity and tumor necrosis factor-alpha [TNF-α] levels, as well as the antioxidant biomarkers (superoxide dismutase [SOD], glutathione reductase [GRx], glutathione-S-transferase [GST] and catalase [CAT], were examined. Histological and transmission electron microscopic [TEM] variations in the liver were used as indicators of liver damage after the administration of CdCl2-alone or CdCl2 with LC, SeCl4, or both. Genotoxic effects of CdCl2 were also evaluated and the possible roles of SeCl4 and/or LC on the expression of the antioxidant enzymes were studied. Results showed that administration of LC and SeCl4 decreased CdCl2-induced increase in ALT and AST levels and reduced oxidative stress to normal levels. In addition, LC combined with SeCl4 had a highly synergistic effect and elevated significantly the enzymatic antioxidants and decreased lipid peroxidation levels compared with those in the CdCl2-treated group. It is clear from the data that both LC and SeCl4 inhibit liver injury and improve the redox state in mice.
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Affiliation(s)
| | - Reham Z Hamza
- Zoology Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt; Biology Department, Faculty of Science, Taif University, Taif 888, Saudi Arabia.
| | - Metwally M Montaser
- Biotechnology Department, Faculty of Science, Taif University, Taif 888, Saudi Arabia; Zoology Department, Faculty of Science, Al-Azhar University, Cairo, Egypt
| | - Magda M El-Mahdi
- Zoology Department, Faculty of Science, Cairo University, Cairo, Egypt; Biology Department, Faculty of Science, Taif University, Taif 888, Saudi Arabia
| | - Wed A Al-Harthi
- Biology Department, Faculty of Science, Taif University, Taif 888, Saudi Arabia
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12
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The effect of L-carnitine on inflammatory mediators: a systematic review and meta-analysis of randomized clinical trials. Eur J Clin Pharmacol 2019; 75:1037-1046. [PMID: 30915521 DOI: 10.1007/s00228-019-02666-5] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2019] [Accepted: 03/07/2019] [Indexed: 12/28/2022]
Abstract
AIM AND BACKGROUND Reducing inflammation by nutritional supplements may help to reduce the risk of many chronic diseases. Our aim in this meta-analysis was to determine the effect of L-carnitine on inflammatory mediators including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). METHODS Our systematic search to find relevant randomized clinical trials (RCTs) was performed up to October 2018 using ISI Web of Science, Google Scholar, PubMed/Medline, and SCOPUS. In this meta-analysis, the weighted mean differences (WMD) with standard errors (SE) were used to pool the data. WMD was calculated by subtracting change-from-baseline mean values in the control group from change-from-baseline mean values in the intervention group in each study. To identify heterogeneity among studies, the I2 statistic was employed. The protocol was registered with PROSPERO (No. CRD42019116695). RESULTS Thirteen articles were included in our systematic review and meta-analysis. The results of the meta-analysis indicated that L-carnitine supplementation was significantly associated with lower levels of CRP in comparison to controls (WMD = -1.23 mg/L; 95% CI: -1.73, -0.72 mg/dL; P < 0.0001). Also, a slight but statistically significant decrease was observed in IL-6 and TNF-α levels (WMD = -0.85 pg/dL; 95% CI: -1.38, -0.32 pg/dL; P = 0.002 and WMD = -0.37 pg/dL; 95% CI: -0.68, -0.06 pg/dL; P = 0.018, respectively). CONCLUSION Our results indicate that L-carnitine reduced inflammatory mediators, especially in studies with a duration of more than 12 weeks. Further studies with different doses and intervention durations and separately in men and women are necessary.
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13
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Adefisayo MA, Adeyemi WJ, Alabi QK. Combined but not single administration of vitamin C and l-carnitine ameliorates cisplatin-induced gastric mucosa damage in male rats. Can J Physiol Pharmacol 2018; 96:830-838. [PMID: 29677454 DOI: 10.1139/cjpp-2017-0751] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Although cisplatin is a potent anticancer drug, it instigates oxidative and pro-inflammatory reactions that pose significant and distressing clinical symptoms. Therefore, this study investigated the effects of vitamin C and (or) l-carnitine on cisplatin-induced gastric mucosa damage in rat. The rats were allocated into 6 groups (n = 5). The control group received distilled water, while the treatment groups received cisplatin alone (CIP), or cisplatin with vitamin C, l-carnitine, or their combination. Cisplatin caused disruption of the gastric mucosa histoarchitecture and altered the mucus barrier function. Moreover, the stomach tissue of the CIP-treated group showed increased levels of oxidative stress markers (malondialdehyde and H2O2) and decreased activities of antioxidant (superoxide dismutase, glutathione peroxidase, catalase, glutathione S-transferase) and non-antioxidant (reduced glutathione) enzymes. These deleterious events were accompanied with significant increases in pro-inflammatory cytokines and inflammatory infiltration markers, myeloperoxidase and inducible nitric oxide synthase. However, the administration of both vitamin C and l-carnitine, and not either of the two showed additive effects in attenuating the adverse effects of cisplatin. The histological results agreed with the biochemical assays. The study concluded that the combined administration of vitamin C and l-carnitine, but not the single therapy, could prevent the adverse effects of cisplatin on gastric tissue.
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Affiliation(s)
- Modinat Adebukola Adefisayo
- a Department of Physiology, Faculty of Basic Medical Sciences, University of Medical Sciences, Ondo State, Nigeria.,b Department of Physiological Sciences, Faculty of Basic Medical Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria
| | - Wale Johnson Adeyemi
- c Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Kwara State, Nigeria
| | - Quadri Kunle Alabi
- b Department of Physiological Sciences, Faculty of Basic Medical Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.,d Department of Haematology and Blood Transfusion, Faculty of Basic Medical Sciences, College of Medicine, Afe Babalola University, Ado Ekiti, Ekiti State, Nigeria
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14
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Potential Use of Chemoprotectants against the Toxic Effects of Cyanotoxins: A Review. Toxins (Basel) 2017; 9:toxins9060175. [PMID: 28545227 PMCID: PMC5488025 DOI: 10.3390/toxins9060175] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Revised: 04/21/2017] [Accepted: 05/17/2017] [Indexed: 12/16/2022] Open
Abstract
Cyanobacterial toxins, particularly microcystins (MCs) and cylindrospermopsin (CYN), are responsible for toxic effects in humans and wildlife. In order to counteract or prevent their toxicity, various strategies have been followed, such as the potential application of chemoprotectants. A review of the main substances evaluated for this aim, as well as the doses and their influence on cyanotoxin-induced toxicity, has been performed. A search of the literature shows that research on MCs is much more abundant than research on CYN. Among chemoprotectants, antioxidant compounds are the most extensively studied, probably because it is well known that oxidative stress is one of the toxic mechanisms common to both toxins. In this group, vitamin E seems to have the strongest protectant effect for both cyanotoxins. Transport inhibitors have also been studied in the case of MCs, as CYN cellular uptake is not yet fully elucidated. Further research is needed because systematic studies are lacking. Moreover, more realistic exposure scenarios, including cyanotoxin mixtures and the concomitant use of chemoprotectants, should be considered.
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15
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Pandey KR, Naik SR, Vakil BV. Probiotics, prebiotics and synbiotics- a review. JOURNAL OF FOOD SCIENCE AND TECHNOLOGY 2015; 52:7577-87. [PMID: 26604335 PMCID: PMC4648921 DOI: 10.1007/s13197-015-1921-1] [Citation(s) in RCA: 631] [Impact Index Per Article: 63.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Revised: 06/07/2015] [Accepted: 06/18/2015] [Indexed: 02/06/2023]
Abstract
The health benefits imparted by probiotics and prebiotics as well as synbiotics have been the subject of extensive research in the past few decades. These food supplements termed as functional foods have been demonstrated to alter, modify and reinstate the pre-existing intestinal flora. They also facilitate smooth functions of the intestinal environment. Most commonly used probiotic strains are: Bifidobacterium, Lactobacilli, S. boulardii, B. coagulans. Prebiotics like FOS, GOS, XOS, Inulin; fructans are the most commonly used fibers which when used together with probiotics are termed synbiotics and are able to improve the viability of the probiotics. Present review focuses on composition and roles of Probiotics, Prebiotics and Synbiotics in human health. Furthermore, additional health benefits like immune-modulation, cancer prevention, inflammatory bowel disease etc. are also discussed. Graphical abstractPictorial summary of health benefits imparted by probiotics, prebiotics and synbiotics.
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Affiliation(s)
- Kavita. R. Pandey
- GNIRD, Guru Nanak Khalsa College of arts science and Commerce, NP Marg, Opp. Don Bosco school, Matunga east, Mumbai, 400019 India
| | - Suresh. R. Naik
- GNIRD, Guru Nanak Khalsa College of arts science and Commerce, NP Marg, Opp. Don Bosco school, Matunga east, Mumbai, 400019 India
| | - Babu. V. Vakil
- GNIRD, Guru Nanak Khalsa College of arts science and Commerce, NP Marg, Opp. Don Bosco school, Matunga east, Mumbai, 400019 India
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Moeinian M, Ghasemi-Niri SF, Mozaffari S, Abdolghaffari AH, Baeeri M, Navaea-Nigjeh M, Abdollahi M. Beneficial effect of butyrate, Lactobacillus casei and L-carnitine combination in preference to each in experimental colitis. World J Gastroenterol 2014; 20:10876-10885. [PMID: 25152589 PMCID: PMC4138466 DOI: 10.3748/wjg.v20.i31.10876] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2013] [Revised: 02/11/2014] [Accepted: 04/05/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the beneficial effect of the combination of butyrate, Lactobacillus casei, and L-carnitine in a rat colitis model. METHODS Rats were divided into seven groups. Four groups received oral butyrate, L-carnitine, Lactobacillus casei and the combination of three agents for 10 consecutive days. The remaining groups included negative and positive controls and a sham group. Macroscopic, histopathological examinations, and biomarkers such as tumor necrosis factor-alpha (TNF-α) and interlukin-1β (IL-1β), myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), and ferric reduced ability of plasma (FRAP) were determined in the colon. RESULTS The combination therapy exhibited a significant beneficial effect in alleviation of colitis compared to controls. Overall changes in reduction of TNF-α (114.66 ± 18.26 vs 171.78 ± 9.48 pg/mg protein, P < 0.05), IL-1β (24.9 ± 1.07 vs 33.06 ± 2.16 pg/mg protein, P < 0.05), TBARS (0.2 ± 0.03 vs 0.49 ± 0.04 μg/mg protein, P < 0.01), MPO (15.32 ± 0.4 vs 27.24 ± 3.84 U/mg protein, P < 0.05), and elevation of FRAP (23.46 ± 1.2 vs 15.02 ± 2.37 μmol/L, P < 0.05) support the preference of the combination therapy in comparison to controls. Although the monotherapies were also effective in improvement of colitis markers, the combination therapy was much better in improvement of colon oxidative stress markers including FRAP, TBARS, and MPO. CONCLUSION The present combination is a suitable mixture in control of experimental colitis and should be trialed in the clinical setting.
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