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Vacca A, Wang R, Nambiar N, Capone F, Farrelly C, Mostafa A, Sechi LA, Schiattarella GG. Lifestyle interventions in cardiometabolic HFpEF: dietary and exercise modalities. Heart Fail Rev 2025; 30:637-655. [PMID: 39283525 DOI: 10.1007/s10741-024-10439-1] [Citation(s) in RCA: 4] [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] [Accepted: 09/05/2024] [Indexed: 06/16/2025]
Abstract
Heart failure with preserved ejection fraction (HFpEF) is rapidly growing as the most common form of heart failure. Among HFpEF phenotypes, the cardiometabolic/obese HFpEF - HFpEF driven by cardiometabolic alterations - emerges as one of the most prevalent forms of this syndrome and the one on which recent therapeutic success have been made. Indeed, pharmacological approaches with sodium-glucose cotransporter type 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have proved to be effective due to metabolic protective effects. Similarly, lifestyle changes, including diet and exercise are crucial in HFpEF management. Increasing evidence supports the important role of diet and physical activity in the pathogenesis, prognosis, and potential reversal of HFpEF. Metabolic derangements and systemic inflammation are key features of HFpEF and represent the main targets of lifestyle interventions. However, the underlying mechanisms of the beneficial effects of these interventions in HFpEF are incompletely understood. Hence, there is an unmet need of tailored lifestyle intervention modalities for patients with HFpEF. Here we present the current available evidence on lifestyle interventions in HFpEF management and therapeutics, discussing their modalities and potential mechanisms.
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Affiliation(s)
- Antonio Vacca
- Translational Approaches in Heart Failure and Cardiometabolic Disease, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Clinica Medica, Department of Medicine, University of Udine, Udine, Italy
| | - Rongling Wang
- Deutsches Herzzentrum Der Charité (DHZC), Charité-Universitätsmedizin Berlin, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Translational Approaches in Heart Failure and Cardiometabolic Disease, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
| | - Natasha Nambiar
- Translational Approaches in Heart Failure and Cardiometabolic Disease, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
| | - Federico Capone
- Translational Approaches in Heart Failure and Cardiometabolic Disease, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Division of Internal Medicine, Department of Medicine-DIMED, University of Padua, Padua, Italy
| | - Catherine Farrelly
- Translational Approaches in Heart Failure and Cardiometabolic Disease, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
| | - Ahmed Mostafa
- Translational Approaches in Heart Failure and Cardiometabolic Disease, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
| | - Leonardo A Sechi
- Clinica Medica, Department of Medicine, University of Udine, Udine, Italy
| | - Gabriele G Schiattarella
- Deutsches Herzzentrum Der Charité (DHZC), Charité-Universitätsmedizin Berlin, Berlin, Germany.
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.
- Translational Approaches in Heart Failure and Cardiometabolic Disease, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
- Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
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Vrentzos E, Pavlidis G, Korakas E, Kountouri A, Pliouta L, Dimitriadis GD, Lambadiari V. Nutraceutical Strategies for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Path to Liver Health. Nutrients 2025; 17:1657. [PMID: 40431398 PMCID: PMC12113997 DOI: 10.3390/nu17101657] [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: 04/08/2025] [Revised: 05/05/2025] [Accepted: 05/09/2025] [Indexed: 05/29/2025] Open
Abstract
MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease) is a growing global concern. Nutraceuticals offer an appealing approach by targeting key mechanisms, such as oxidative stress, inflammation, lipid metabolism, and insulin resistance. This narrative review examines the role of various nutraceuticals in MASLD treatment, including silymarin, vitamin E, omega-3, curcumin, berberine, and coenzyme Q10. Some of them show promising biochemical and metabolic changes, while others produce conflicting results due to relevant studies' design and endpoints. To bridge the gap between research and reality, we summarize the data, create an interpretation heatmap, and develop a practical supplement guide. Regardless of their potential, nutraceuticals should be viewed as add-ons to lifestyle interventions rather than standalone treatments. Future research should focus on well-designed, long-term studies to prove efficacy, dosing, and combination strategies for personalized MASLD management.
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Affiliation(s)
- Emmanouil Vrentzos
- 4th Department of Internal Medicine, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (E.V.); (G.P.)
| | - George Pavlidis
- 4th Department of Internal Medicine, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (E.V.); (G.P.)
| | - Emmanouil Korakas
- 2nd Department of Internal Medicine, Research Unit and Diabetes Center, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (E.K.); (A.K.); (L.P.); (G.D.D.)
| | - Aikaterini Kountouri
- 2nd Department of Internal Medicine, Research Unit and Diabetes Center, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (E.K.); (A.K.); (L.P.); (G.D.D.)
| | - Loukia Pliouta
- 2nd Department of Internal Medicine, Research Unit and Diabetes Center, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (E.K.); (A.K.); (L.P.); (G.D.D.)
| | - George D. Dimitriadis
- 2nd Department of Internal Medicine, Research Unit and Diabetes Center, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (E.K.); (A.K.); (L.P.); (G.D.D.)
| | - Vaia Lambadiari
- 2nd Department of Internal Medicine, Research Unit and Diabetes Center, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (E.K.); (A.K.); (L.P.); (G.D.D.)
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Pezzoli A, Abenavoli L, Scarcella M, Rasetti C, Svegliati Baroni G, Tack J, Scarpellini E. The Management of Cardiometabolic Risk in MAFLD: Therapeutic Strategies to Modulate Deranged Metabolism and Cholesterol Levels. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:387. [PMID: 40142198 PMCID: PMC11944025 DOI: 10.3390/medicina61030387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Revised: 02/19/2025] [Accepted: 02/21/2025] [Indexed: 03/28/2025]
Abstract
Background and Objectives: Fatty Liver Disease is a major health problem worldwide. We can distinguish liver steatosis as non-associated or associated with chronic/acute alcohol consumption. These two entities share similar stages ranging from hepatic fat storage (namely, steatosis) to inflammation, necrosis, and fibrosis until hepatocellular carcinoma (HCC). Over time, "Metabolic Associated Fatty Liver Disease" (MAFLD) has replaced nonalcoholic fatty liver disease (NAFLD) nomenclature and has included cardiometabolic criteria in these patients definition. Thus, obesity, type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia are MAFLD features and are of the metabolic syndrome. Importantly, there is not a specific treatment for MAFLD, but there are therapeutic strategies that act on metabolic dysfunction related to MAFLD. They can reduce the progression of liver fibrosis and its complications. Materials and Methods: For all these reasons, we conducted a narrative review of the literature, and we focused on metabolic dysfunction related to MAFLD, with a special regard for cholesterol metabolism. Results: MAFLD is a recently redefined condition that better describes the metabolism derangement responsible for fatty liver disease. This distinguishes MAFLD from NAFLD. In fact, the diagnostic criteria for MAFLD require the presence of liver steatosis together with at least one of the following: obesity, T2DM, or evidence of metabolic disorder such as hypertriglyceridemia, low high-density lipoprotein cholesterol, or hypertension. As a result, MAFLD is closely linked to an increased cardiometabolic risk. Current therapeutic approaches can be used to reduce this risk, focusing on lifestyle interventions and pharmacological strategies. Several treatments in patients diagnosed with MAFLD are mainly cholesterol-lowering remedies. Among these, Pro-protein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9i) show the most promising efficacy profile but data on liver fibrosis are lacking. Agonists of GLP-1 receptor, Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and Dipeptidyl Peptidase-4 inhibitors (DPP-4i) have a " multi-hit " action allowing their use also in diabetic patients with MAFLD. Conclusions: Lifestyle modifications, some nutraceuticals, statins, incretins, and PCSK9i have changed the natural course and significantly improved the cardiometabolic outcomes of MAFLD. Emerging cholesterol-lowering drugs, such as Bempedoic acid, can overcome low compliance to statins' use and their controversial effect on liver fibrosis. Finally, medications targeting insulin resistance allow for strategic interventions of the convoluted pathophysiology of MAFLD in multiple steps, with the potential to reduce liver steatosis, inflammation, and necrosis and, sometimes even to reverse liver fibrosis.
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Affiliation(s)
- Annalisa Pezzoli
- Internal Medicine Unit, “ Madonna del Soccorso” General Hospital, 63074 San Benedetto del Tronto, Italy; (A.P.); (C.R.)
| | - Ludovico Abenavoli
- Department of Health Sciences, University “Magna Graecia”, 88100 Catanzaro, Italy;
| | - Marialaura Scarcella
- Anesthesia, Intensive Care and Nutritional Science, Azienda Ospedaliera “Santa Maria”, Via Tristano di Joannuccio, 05100 Terni, Italy;
| | - Carlo Rasetti
- Internal Medicine Unit, “ Madonna del Soccorso” General Hospital, 63074 San Benedetto del Tronto, Italy; (A.P.); (C.R.)
| | | | - Jan Tack
- Translational Research in Gastroeintestinal Disorders, Gasthuisberg University Hospital, KULeuven, Herestraat 49, 3000 Leuven, Belgium;
| | - Emidio Scarpellini
- Internal Medicine Unit, “ Madonna del Soccorso” General Hospital, 63074 San Benedetto del Tronto, Italy; (A.P.); (C.R.)
- Translational Research in Gastroeintestinal Disorders, Gasthuisberg University Hospital, KULeuven, Herestraat 49, 3000 Leuven, Belgium;
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Aydin I, Erisgin Z, Cinar E, Barak MZ, Tekelioglu Y, Usta M, Mutlu HS, Turkoglu I. Should combined MTX and CoQ10 use be reconsidered in terms of steatosis? A biochemical, flow cytometry, histopathological experimental study. Drug Chem Toxicol 2024:1-14. [PMID: 39734089 DOI: 10.1080/01480545.2024.2442660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 11/26/2024] [Accepted: 12/10/2024] [Indexed: 12/31/2024]
Abstract
In the present study, the effects of coenzyme Q10 (CoQ10), which is widely used in daily life, on the methotrexate (MTX)-induced hepatotoxicity, which is widely used today in malignancies and autoimmune diseases, were examined. Twenty-four female Wistar albino rats were divided into four groups. The group 1 (n = 6) was given 1 mL corn oil by oral gavage (p.o.) during seven days. Group 2 was given 20 mg/kg intraperitoneal (i.p.) MTX only on the first day of the experiment. Group 3 was given 20 mg/kg (i.p.) MTX on the first day of the experiment and 100 mg/kg CoQ10 dissolved in 1 mL corn oil were given by oral gavage during seven days, and group 4 was given 100 mg/kg CoQ10 dissolved in 1 mL corn oil by oral gavage during seven days. At the end of experiment, all animals were euthanized under anesthesia. In the liver tissue, histopathologic analysis on the hematoxylin and eosin (H&E), Masson trichrome, and periodic acid Schiff (PAS) stained sections, apoptotic analysis (% Annexin V positivity) by flow cytometry, and biochemical analysis for oxidative stress markers (GSH, CAT, and TBARS) was performed. According to histopathological analysis, apoptosis, concession, fibrosis, and inflammatory cell infiltration increased in the MTX group and those results significantly decreased in the MTX + CoQ10 groups. As an interesting result, fatty degeneration and TBARS elevation were observed in the MTX + CoQ10 group. As a result, although CoQ10 has protective effects on MTX-induced hepatotoxicity, fatty degeneration due to the combined usage of MTX and CoQ10 should be investigated with further studies.
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Affiliation(s)
- Ismail Aydin
- Department of General Surgery, Faculty of Medicine, Giresun University, Giresun, Turkiye
| | - Zuleyha Erisgin
- Department of Histology and Embryology, Faculty of Medicine, Giresun University, Giresun, Turkiye
| | - Esma Cinar
- Department of Pathology, Faculty of Medicine, Giresun University, Giresun, Turkiye
| | - M Zuhal Barak
- Department of Business, Adana Science and Technic University, Adana, Turkiye
| | - Yavuz Tekelioglu
- Department of Histology and Embryology, Faculty of Medicine, Black Sea Technical University, Trabzon, Turkiye
| | - Murat Usta
- Department of Medical Biochemistry, Faculty of Medicine, Giresun University, Giresun, Turkiye
| | - Hasan Serdar Mutlu
- Department of Histology and Embryology, Faculty of Medicine, Giresun University, Giresun, Turkiye
| | - Ismail Turkoglu
- Department of Histology and Embryology, Faculty of Medicine, Giresun University, Giresun, Turkiye
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Yoladi FB, Palabiyik-Yucelik SS, Bahador Zirh E, Halici Z, Baydar T. Effects of idebenone and coenzyme Q10 on NLRP3/caspase-1/IL-1β pathway regulation on ethanol-induced hepatotoxicity in rats. Drug Chem Toxicol 2024; 47:1205-1217. [PMID: 38804209 DOI: 10.1080/01480545.2024.2351191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 04/29/2024] [Indexed: 05/29/2024]
Abstract
Chronic and excessive alcohol consumption leads to liver toxicity. There is a need to investigate effective therapeutic strategies to alleviate alcohol-induced liver injury, which remains the leading cause of liver-related morbidity and mortality worldwide. Therefore here, we looked into and evaluated how ethanol-induced hepatotoxicity was affected by coenzyme Q10 (CoQ10) and its analog, idebenone (IDE), on the NLRP3/caspase-1/IL-1 pathway. Hepatotoxicity induced in rats through the oral administration of gradually increasing dosages of ethanol (from 2 to 6 g/kg/day) over 30 days and the effect of CoQ10 (10 or 20 mg/kg) and IDE (50 or 100 mg/kg) were evaluated. Serum hepatotoxicity markers (ALT, AST, GGT, ALP, and TBIL), tissue oxidative stress markers and the mRNA expressions of IL-1β, IL-18, TGF-β, NF-κB, NLRP3, and caspase-1 were evaluated. Masson's trichrome staining was also used to visualize fibrosis in the liver tissue. The results indicated that ethanol exposure led to hepatotoxicity as well as considerable NLRP3/caspase-1/IL-1β pathway activation. Moreover, CoQ10 or IDE treatment reduced measured parameters in a dosage-dependent manner. Thus, by inhibiting the NLRP3/caspase-1/IL-1 pathway, CoQ10 and IDE can prevent the hepatotoxicity caused by ethanol, although CoQ10 is more effective than IDE. This study will provide insight into new therapeutic avenues that take advantage of the anti-inflammatory and antioxidant properties of CoQ10 and IDE in ethanol-induced liver diseases.
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Affiliation(s)
- Fatma Betül Yoladi
- Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Atatürk University, Erzurum, Turkey
- Department of Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
| | - Saziye Sezin Palabiyik-Yucelik
- Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Atatürk University, Erzurum, Turkey
- Clinical Research, Development and Design Application and Research Center, Atatürk University, Erzurum, Turkey
- Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Ondokuz Mayıs University, Samsun, Turkey
| | - Elham Bahador Zirh
- Department of Histology and Embryology, Faculty of Medicine, TOBB University of Economics and Technology, Ankara, Turkey
| | - Zekai Halici
- Clinical Research, Development and Design Application and Research Center, Atatürk University, Erzurum, Turkey
- Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey
| | - Terken Baydar
- Department of Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
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Perva IT, Simina IE, Bende R, Motofelea AC, Chirita Emandi A, Andreescu N, Sima A, Vlad A, Sporea I, Zimbru C, Tutac PC, Puiu M, Niculescu MD. Use of a Micronutrient Cocktail to Improve Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Adults with Obesity: A Randomized, Double-Blinded Pilot Clinical Trial. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1366. [PMID: 39202647 PMCID: PMC11356300 DOI: 10.3390/medicina60081366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 08/06/2024] [Accepted: 08/20/2024] [Indexed: 09/03/2024]
Abstract
Background and Objectives: The goal of this study was to assess the impact of supplementation with a combination of nutrients on metabolic-dysfunction-associated steatotic liver disease (MASLD)-related liver parameters, and other parameters related to metabolic syndrome in adults with obesity. These measurements included anthropometric and lipid profiling, and FibroScan technology (controlled attenuation parameter (CAP) and transient elastography (TE) values). Materials and Methods: A double-blind, placebo-controlled pilot clinical trial was conducted over a three-month treatment period. Adults with metabolic syndrome and obesity were allocated to receive either a cocktail of nutrients with defined daily dosages (5-MTHF, betaine, alpha-linolenic acid, eicosapentaenoic acid, choline bitartrate, docosahexaenoic acid, and vitamin B12) or a placebo. The participants were evaluated at the start and the end of the three-month treatment period. Results: A total of 155 participants entered the study, comprising 84 in the treatment group and 71 in the placebo group. The administration of the nutritional supplement resulted in a notable reduction in both CAP and TE scores when compared to the placebo group. The treatment group exhibited a mean reduction in CAP of 4% (p < 0.05) and a mean reduction in TE of 7.8% (p < 0.05), indicative of a decline in liver fat content and fibrosis. Conclusions: The supplementation over a period of three months led to a significant amelioration of liver fibrosis and steatosis parameters in adults with metabolic syndrome and obesity. These findings suggest that this supplementation regimen could be a beneficial adjunct therapy for improving liver health in adults with obesity-induced MASLD.
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Affiliation(s)
- Iulia Teodora Perva
- Department of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (I.T.P.); (A.C.E.); (N.A.); (M.P.); (M.D.N.)
- Regional Center of Medical Genetics Timiș, Clinical Emergency Hospital for Children “Louis Țurcanu”, Iosif Nemoianu Street N°2, 300011 Timisoara, Romania
- Department of Medical Genetics, Asociatia Oncohelp, 300239 Timișoara, Romania
| | - Iulia Elena Simina
- Department of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (I.T.P.); (A.C.E.); (N.A.); (M.P.); (M.D.N.)
- Department of Medical Genetics, Asociatia Oncohelp, 300239 Timișoara, Romania
| | - Renata Bende
- Department of Gastroenterology and Hepatology, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (R.B.); (I.S.)
- Center of Advanced Research in Gastroenterology and Hepatology, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania
| | - Alexandru Cătălin Motofelea
- Department of Internal Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania;
| | - Adela Chirita Emandi
- Department of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (I.T.P.); (A.C.E.); (N.A.); (M.P.); (M.D.N.)
- Regional Center of Medical Genetics Timiș, Clinical Emergency Hospital for Children “Louis Țurcanu”, Iosif Nemoianu Street N°2, 300011 Timisoara, Romania
| | - Nicoleta Andreescu
- Department of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (I.T.P.); (A.C.E.); (N.A.); (M.P.); (M.D.N.)
- Regional Center of Medical Genetics Timiș, Clinical Emergency Hospital for Children “Louis Țurcanu”, Iosif Nemoianu Street N°2, 300011 Timisoara, Romania
| | - Alexandra Sima
- Department of Internal Medicine II, Division of Diabetes, Nutrition and Metabolic Diseases, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (A.S.); (A.V.)
- Center for Research in Preventive Medicine, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania
| | - Adrian Vlad
- Department of Internal Medicine II, Division of Diabetes, Nutrition and Metabolic Diseases, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (A.S.); (A.V.)
- Center for Molecular Research in Nephrology and Vascular Disease, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania
| | - Ioan Sporea
- Department of Gastroenterology and Hepatology, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (R.B.); (I.S.)
- Center of Advanced Research in Gastroenterology and Hepatology, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania
| | - Cristian Zimbru
- Department of Automation and Applied Informatics, Politehnica University Timișoara, 300223 Timișoara, Romania;
| | - Paul Calin Tutac
- Toxicology and Molecular Biology Department, “Pius Brinzeu” Clinical Emergency County Hospital, 300723 Timisoara, Romania;
| | - Maria Puiu
- Department of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (I.T.P.); (A.C.E.); (N.A.); (M.P.); (M.D.N.)
- Regional Center of Medical Genetics Timiș, Clinical Emergency Hospital for Children “Louis Țurcanu”, Iosif Nemoianu Street N°2, 300011 Timisoara, Romania
| | - Mihai Dinu Niculescu
- Department of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (I.T.P.); (A.C.E.); (N.A.); (M.P.); (M.D.N.)
- Advanced Nutrigenomics LLC, Durham, NC 27703, USA
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Vrentzos E, Ikonomidis I, Pavlidis G, Katogiannis K, Korakas E, Kountouri A, Pliouta L, Michalopoulou E, Pelekanou E, Boumpas D, Lambadiari V. Six-month supplementation with high dose coenzyme Q10 improves liver steatosis, endothelial, vascular and myocardial function in patients with metabolic-dysfunction associated steatotic liver disease: a randomized double-blind, placebo-controlled trial. Cardiovasc Diabetol 2024; 23:245. [PMID: 38987784 PMCID: PMC11238408 DOI: 10.1186/s12933-024-02326-8] [Citation(s) in RCA: 4] [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] [Received: 03/17/2024] [Accepted: 06/18/2024] [Indexed: 07/12/2024] Open
Abstract
BACKROUND Metabolic-dysfunction Associated Steatotic Liver Disease (MASLD) has been associated with increased cardiovascular risk. The aim of this Randomized Double-blind clinical Trial was to evaluate the effects of coenzyme-Q10 supplementation in patients with MASLD in terms of endothelial, vascular and myocardial function. METHODS Sixty patients with MASLD were randomized to receive daily 240 mg of coenzyme-Q10 or placebo. At baseline and at 6-months, the a)Perfused boundary region of sublingual vessels using the Sideview Darkfield imaging technique, b)pulse-wave-velocity, c)flow-mediated dilation of the brachial artery, d)left ventricular global longitudinal strain, e)coronary flow reserve of the left anterior descending coronary artery and f)controlled attenuation parameter for the quantification of liver steatosis were evaluated. RESULTS Six months post-treatment, patients under coenzyme-Q10 showed reduced Perfused boundary region (2.18 ± 0.23vs.2.29 ± 0.18 μm), pulse-wave-velocity (9.5 ± 2vs.10.2 ± 2.3 m/s), controlled attenuation parameter (280.9 ± 33.4vs.304.8 ± 37.4dB/m), and increased flow-mediated dilation (6.1 ± 3.8vs.4.3 ± 2.8%), global longitudinal strain (-19.6 ± 1.6vs.-18.8 ± 1.9%) and coronary flow reserve (3.1 ± 0.4vs.2.8 ± 0.4) compared to baseline (p < 0.05). The placebo group exhibited no improvement during the 6-month follow-up period (p > 0.05). In patients under coenzyme-Q10, the reduction in controlled attenuation parameter score was positively related to the reduction in Perfused boundary region and pulse wave velocity and reversely related to the increase in coronary flow reserve and flow-mediated dilation (p < 0.05 for all relations). CONCLUSIONS Six-month treatment with high-dose coenzyme-Q10 reduces liver steatosis and improves endothelial, vascular and left ventricle myocardial function in patients with MASLD, demonstrating significant improvements in micro- and macro-vasculature function. TRIAL REGISTRATION NCT05941910.
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Affiliation(s)
- Emmanouil Vrentzos
- 4th Department of Internal Medicine, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Ignatios Ikonomidis
- Laboratory of Preventive Cardiology and Echocardiography, 2nd Cardiology Department, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - George Pavlidis
- Laboratory of Preventive Cardiology and Echocardiography, 2nd Cardiology Department, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Konstantinos Katogiannis
- Laboratory of Preventive Cardiology and Echocardiography, 2nd Cardiology Department, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Emmanouil Korakas
- 2nd Department of Internal Medicine, Research Unit and Diabetes Center, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Aikaterini Kountouri
- 2nd Department of Internal Medicine, Research Unit and Diabetes Center, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Loukia Pliouta
- 2nd Department of Internal Medicine, Research Unit and Diabetes Center, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Eleni Michalopoulou
- Laboratory of Preventive Cardiology and Echocardiography, 2nd Cardiology Department, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Emilia Pelekanou
- 4th Department of Internal Medicine, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios Boumpas
- 4th Department of Internal Medicine, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Vaia Lambadiari
- 2nd Department of Internal Medicine, Research Unit and Diabetes Center, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
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Al Hashmi K, Giglio RV, Pantea Stoian A, Patti AM, Al Waili K, Al Rasadi K, Ciaccio M, Rizzo M. Metabolic dysfunction-associated fatty liver disease: current therapeutic strategies. Front Nutr 2024; 11:1355732. [PMID: 38567250 PMCID: PMC10985255 DOI: 10.3389/fnut.2024.1355732] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 03/11/2024] [Indexed: 04/04/2024] Open
Abstract
The definition of "Metabolic Associated Fatty Liver Disease - MAFLD" has replaced the previous definition of Nonalcoholic Fatty Liver Disease (NAFLD), because cardiometabolic criteria have been added for the prevention of cardiological risk in these patients. This definition leads to an in-depth study of the bidirectional relationships between hepatic steatosis, Type 2 Diabetes Mellitus (T2DM), Cardiovascular Disease (CVD) and/or their complications. Lifestyle modification, which includes correct nutrition combined with regular physical activity, represents the therapeutic cornerstone of MAFLD. When therapy is required, there is not clear accord on how to proceed in an optimal way with nutraceutical or pharmacological therapy. Numerous studies have attempted to identify nutraceuticals with a significant benefit on metabolic alterations and which contribute to the improvement of hepatic steatosis. Several evidences are supporting the use of silymarin, berberine, curcumin, Nigella sativa, Ascophyllum nodosum, and Fucus vesiculosus, vitamin E, coenzyme Q10 and Omega-3. However, more evidence regarding the long-term efficacy and safety of these compounds are required. There is numerous evidence that highlights the use of therapies such as incretins or the use of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors or other similar therapies which, by assisting existing therapies for pathologies such as diabetes, hypertension, insulin resistance, have given a breakthrough in prevention and the reduction of cardiometabolic risk. This review gave an overview of the current therapeutic strategies that are expected to aid in the treatment and prevention of MAFLD.
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Affiliation(s)
- Khamis Al Hashmi
- Department of Physiology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
| | - Rosaria Vincenza Giglio
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy
- Department of Laboratory Medicine, University Hospital, Palermo, Italy
| | - Anca Pantea Stoian
- Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Angelo Maria Patti
- Internal Medicine Unit, “Vittorio Emanuele II” Hospital, Castelvetrano, Italy
| | - Khalid Al Waili
- Department of Biochemistry, Sultan Qaboos University Hospital, Muscat, Oman
| | - Khalid Al Rasadi
- Department of Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
- Medical Research Center, Sultan Qaboos University, Muscat, Oman
| | - Marcello Ciaccio
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy
- Department of Laboratory Medicine, University Hospital, Palermo, Italy
| | - Manfredi Rizzo
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
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9
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Kiani Z, Khorsand N, Beigi F, Askari G, Sharma M, Bagherniya M. Coenzyme Q10 supplementation in burn patients: a double-blind placebo-controlled randomized clinical trial. Trials 2024; 25:160. [PMID: 38431600 PMCID: PMC10908042 DOI: 10.1186/s13063-024-08006-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Accepted: 02/22/2024] [Indexed: 03/05/2024] Open
Abstract
BACKGROUND Burn injuries are important medical problems that, aside from skin damage, cause a systemic response including inflammation, oxidative stress, endocrine disorders, immune response, and hypermetabolic and catabolic responses which affect all the organs in the body. The aim of this study was to determine the effect of coenzyme Q10 (CoQ10) supplementation on inflammation, oxidative stress, and clinical outcomes in burn patients. METHODS In a double-blind placebo-controlled randomized clinical trial, 60 burn patients were randomly assigned to receive 100 mg CoQ10 three times a day (total 300 mg/day) or a placebo for 10 days. Inflammatory markers including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), oxidative stress markers including total antioxidant capacity (TAC), malondialdehyde (MDA) and superoxide dismutase (SOD) activity, fasting blood glucose (FBG), blood urea nitrogen (BUN), creatinine, white blood cells (WBC), and body temperature were assessed as primary outcomes and albumin, prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR), other hematological parameters, blood pressure, O2 saturation, ICU duration, and 28-mortality rate were assessed as secondary outcomes. RESULTS Fifty-two participants completed the trial. CRP and ESR levels were not significantly different between CoQ10 and placebo groups at the end of the study (P = 0.550 and P = 0.306, respectively). No significant differences between groups were observed for TAC (P = 0.865), MDA (P = 0.692), and SOD activity (P = 0.633) as well. Administration of CoQ10 resulted in a significant increase in albumin levels compared to placebo (P = 0.031). There was no statistically significant difference between the two groups in other measured outcomes (P > 0.05). CONCLUSION Results showed that in patients with burn injury, CoQ10 administration had no effect on inflammatory markers and oxidative stress, although serum albumin levels were improved after supplementation. Further studies with albumin as the primary outcome are needed to confirm this finding.
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Affiliation(s)
- Zahra Kiani
- Nutrition and Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Nadereh Khorsand
- Department of Internal Medicine, Imam Musa Kazem Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Fahimeh Beigi
- Pharmaceutical Biotechnology Department, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Science, Isfahan, Iran
- Research and Development Unit, Imam Muss Kazim Hospital, Isfahan University of Medical Science, Isfahan, Iran
| | - Gholamreza Askari
- Nutrition and Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
- Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Manoj Sharma
- Department of Social and Behavioral Health, School of Public Health, University of Nevada, Las Vegas, Las Vegas, NV, USA
| | - Mohammad Bagherniya
- Nutrition and Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.
- Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
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Majeed M, Nagabhushanam K, Noureddin M, Paulose S, Barik C, Saklecha S, Mundkur L. A scientifically validated combination of garcinol, curcuminoids, and piperine for mild to moderate nonalcoholic steatohepatitis patients-results from a randomized, double-blind, placebo-controlled study. Front Nutr 2023; 10:1201186. [PMID: 38170037 PMCID: PMC10760641 DOI: 10.3389/fnut.2023.1201186] [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] [Received: 04/06/2023] [Accepted: 11/30/2023] [Indexed: 01/05/2024] Open
Abstract
Background Garcinol is a naturally occurring compound from the fruit rind of the Garcinia indica, with antioxidant, anti-inflammatory, and anticancer properties. Curcuminoids are the active molecule from the rhizome of Curcuma longa, studied extensively for its health benefits as an anti-inflammatory and antioxidant activities. Non-alcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic steatohepatitis characterized by liver fat and inflammation. Objective To evaluate the clinical efficacy and safety of Garcinol, Curcuminoids and piperine (GCP) combination in patients with mild to moderate NASH in a randomized, double-blind, placebo-controlled study. Methods The patients received one tablet (450 mg) of GCP containing garcinol-50 mg, curcuminoids -250 mg and piperine 5 mg or a placebo (450 mg of microcrystalline cellulose) twice daily for 90 days. Changes in circulating aspartate aminotransferase (AST), alanine transaminase (ALT) levels, liver stiffness measurement (LSM), and controlled attenuation parameter (CAP) using Fibroscan were compared from baseline to day 90. Anthropometric parameters, serum levels of lipids, Interleukin (IL-6), hsCRP, and adiponectin were estimated. Safety was evaluated by laboratory parameters and by monitoring adverse events. Results Seventy-two patients were randomized and 63 (GCP = 32, Placebo = 31) completed the study. The mean age of the patients was 48.3 ± 8.7 years (36 males and 27 females). The mean reduction in AST (U/L) was 9.53 in GCP and 3.16 in placebo (p < 0.001) and that of ALT (U/L) was 13.47 in GCP and 7.43 in Placebo (p = 0.002). The liver stiffness and CAP scores showed a better reduction in GCP (0.56 kPa and 12.38 db/m) compared to placebo (0.064 kPa and 10.42 db/m) p < 0.05. Consequently, the noninvasive Fibroscan-AST (FAST) score reduction was also found to be significant in GCP compared to placebo. Additionally, body weight, lipid levels, hsCRP, and IL-6 in serum decreased, while adiponectin levels increased in GCP-supplemented participants compared to placebo. The combination of garcinol and curcuminoids was well tolerated with no significant changes in hematological and clinical laboratory parameters during the 90-day supplementation. Conclusion Our results suggest that GCP could be a possible supplement for the management of NASH.Clinical trial registration: https://clinicaltrials.gov/, identifier CTRI/2019/11/022147.
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Affiliation(s)
- Muhammed Majeed
- Sami-Sabinsa Group Limited, Bangalore, Karnataka, India
- Sabinsa Corporation, East Windsor, NJ, United States
| | | | - Mazen Noureddin
- Houston Liver Institute, Houston Research Institute, Houston, TX, United States
| | - Shaji Paulose
- Sami-Sabinsa Group Limited, Bangalore, Karnataka, India
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11
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Fernandes MSDS, Fidelis DEDS, Aidar FJ, Badicu G, Greco G, Cataldi S, Santos GCJ, de Souza RF, Ardigò LP. Coenzyme Q10 Supplementation in Athletes: A Systematic Review. Nutrients 2023; 15:3990. [PMID: 37764774 PMCID: PMC10535924 DOI: 10.3390/nu15183990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Revised: 08/31/2023] [Accepted: 09/12/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND To summarize available evidence in the literature on the impacts of CoQ10 supplementation on metabolic, biochemical, and performance outcomes in athletes. METHODS Six databases, Cochrane Library (33 articles), PubMed (90 articles), Scopus (55 articles), Embase (60 articles), SPORTDiscus (1056 articles), and Science Direct (165 articles), were researched. After applying the eligibility criteria, articles were selected for peer review independently as they were identified by June 2022. The protocol for this systematic review was registered on PROSPERO (CRD42022357750). RESULTS Of the 1409 articles found, 16 were selected for this systematic review. After CoQ10 supplementation, a decrease in oxidative stress markers was observed, followed by higher antioxidant activity. On the other hand, lower levels of liver damage markers (ALT); Aspartate aminotransferase (AST); and Gamma-glutamyl transpeptidase (γGT) were identified. Finally, we found a reduction in fatigue indicators such as Creatine Kinase (CK) and an increase in anaerobic performance. CONCLUSIONS This systematic review concludes that supplementation with orally administered CoQ10 (30-300 mg) was able to potentiate plasma antioxidant activity and anaerobic performance, reducing markers linked to oxidative stress and liver damage in athletes from different modalities aged 17 years old and older.
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Affiliation(s)
- Matheus Santos de Sousa Fernandes
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife 50740-600, Pernambuco, Brazil;
- Programa de Pós-Graduação em Biologia Aplicada à Saúde, Centro de Biociências, Universidade Federal de Pernambuco, Recife 50740-600, Pernambuco, Brazil;
| | - Débora Eduarda da Silvia Fidelis
- Programa de Pós-Graduação em Biologia Aplicada à Saúde, Centro de Biociências, Universidade Federal de Pernambuco, Recife 50740-600, Pernambuco, Brazil;
| | - Felipe J. Aidar
- Department of Physical Education, Federal University of Sergipe, São Cristovão 49100-000, Sergipe, Brazil; (F.J.A.); (R.F.d.S.)
| | - Georgian Badicu
- Department of Physical Education and Special Motricity, Faculty of Physical Education and Mountain Sports, Transilvania University of Braşov, 500068 Braşov, Romania
| | - Gianpiero Greco
- Department of Translational Biomedicine and Neuroscience (DiBraiN), University of Study of Bari, 70124 Bari, Italy; (G.G.); (S.C.)
| | - Stefania Cataldi
- Department of Translational Biomedicine and Neuroscience (DiBraiN), University of Study of Bari, 70124 Bari, Italy; (G.G.); (S.C.)
| | | | - Raphael Frabrício de Souza
- Department of Physical Education, Federal University of Sergipe, São Cristovão 49100-000, Sergipe, Brazil; (F.J.A.); (R.F.d.S.)
| | - Luca Paolo Ardigò
- Department of Teacher Education, NLA University College, 5812 Oslo, Norway;
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12
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Soleimani Damaneh M, Fatahi S, Aryaeian N, Bavi Behbahani H. The effect of coenzyme Q10 supplementation on liver enzymes: A systematic review and meta-analysis of randomized clinical trials. Food Sci Nutr 2023; 11:4912-4925. [PMID: 37701221 PMCID: PMC10494615 DOI: 10.1002/fsn3.3478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 05/12/2023] [Accepted: 05/24/2023] [Indexed: 09/14/2023] Open
Abstract
Coenzyme Q10 is a potent antioxidant and is necessary for energy production in mitochondria. Clinical data have suggested that coenzyme Q10 (CoQ10) has some beneficial effects on liver function. However, these results are equivocal. This systematic review and meta-analysis aimed to clarify the effect of coenzyme Q10 supplementation on the serum concentration of liver function enzymes. We searched the online databases using relevant keywords up to April 2022. Randomized clinical trials (RCTs) investigating the effect of CoQ10, compared with a control group, on serum concentrations of liver enzymes were included. We found a significant reduction following supplementation with CoQ10 on serum concentrations of alanine aminotransferase (ALT) based on 15 effect sizes from 13 RCTs (weighted mean difference [WMD] = -5.33 IU/L; 95% CI: -10.63, -0.03; p = .04), aspartate aminotransferase (AST) based on 15 effect sizes from 13 RCTs (WMD = -4.91 IU/L; 95% CI: -9.35, -0.47; p = .03) and gamma-glutamyl transferase (GGT) based on eight effect sizes from six RCTs (WMD = -8.07 IU/L; 95% CI: -12.82, -3.32; p = .001; I 2 = 91.6%). However, we found no significant effects of CoQ10 supplementation on alkaline phosphatase concentration (WMD = 1.10 IU/L; 95% CI: -5.98, 8.18; p = .76). CoQ10 supplementation significantly improves circulating ALT, AST, and GGT levels; therefore, it might positively affect liver function. Further high-quality RCTs with more extended intervention periods and larger sample sizes are recommended to confirm our results.
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Affiliation(s)
| | - Somaye Fatahi
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food TechnologyShahid Beheshti University of Medical SciencesTehranIran
- Pediatric Gastroenterology, Hepatology, and Nutrition Research Center, Research Institute for Children's HealthShahid Beheshti University of Medical SciencesTehranIran
| | - Naheed Aryaeian
- Department of Nutrition, School of Public HealthIran University of Medical SciencesTehranIran
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13
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Cogorno L, Formisano E, Vignati A, Prigione A, Tramacere A, Borgarelli C, Sukkar SG, Pisciotta L. Non-alcoholic fatty liver disease: Dietary and nutraceutical approaches. LIVER RESEARCH 2023; 7:216-227. [PMID: 39958388 PMCID: PMC11791914 DOI: 10.1016/j.livres.2023.08.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 07/20/2023] [Accepted: 08/24/2023] [Indexed: 02/18/2025]
Abstract
Non-alcoholic fatty liver disease (NAFLD), defined as the presence of fat accumulation in imaging or histology in more than 5% of hepatocytes and exclusion of other causes for secondary hepatic fat accumulation, is one of the major causes of chronic liver disease worldwide. Metabolic syndrome is associated with an increased risk of progression from NAFLD to non-alcoholic steatohepatitis (NASH), fibrosis, and forthcoming liver failure. Also, genetic predisposition contributes to the risk of NAFLD development. This review explores the role of diets and nutraceuticals in delaying the development and the evolution of NAFLD to chronic liver disease. The Mediterranean diet, high-protein diet, low-carbohydrate/high-fat diet, high-carbohydrate/low-fat diet, and intermittent fasting are the dietary approaches investigated given the presence of relevant literature data. Moreover, this review focused on nutraceuticals with proven efficacy in ameliorating NAFLD and grouped them into four different categories: plant-based nutraceuticals (Ascophyllum nodosum and Fucus vesiculosus, Silymarin, Berberine, Curcumin, Resveratrol, Nigella sativa, Quercetin), vitamin-like substances (vitamin E, vitamin D, vitamin C, coenzyme Q10, inositol), fatty acids (omega-3), and microbiota-management tools (probiotics).
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Affiliation(s)
- Ludovica Cogorno
- Department of Experimental Medicine-Medical Pathophysiology, Food Science and Endocrinology Section, Sapienza University of Rome, Rome, Italy
| | - Elena Formisano
- Department of Internal Medicine, University of Genoa, Genoa, Italy
- Dietetics and Clinical Nutrition Unit, IRCCS Policlinic Hospital San Martino, Genoa, Italy
| | - Andrea Vignati
- Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Amalia Prigione
- Department of Internal Medicine, University of Genoa, Genoa, Italy
| | | | | | - Samir Giuseppe Sukkar
- Dietetics and Clinical Nutrition Unit, IRCCS Policlinic Hospital San Martino, Genoa, Italy
| | - Livia Pisciotta
- Department of Internal Medicine, University of Genoa, Genoa, Italy
- Dietetics and Clinical Nutrition Unit, IRCCS Policlinic Hospital San Martino, Genoa, Italy
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da Silva RHS, de Moura M, de Paula L, Arantes KC, da Silva M, de Amorim J, Miguel MP, Martins DB, de Melo e Silva D, Melo MM, Botelho AFM. Effects of coenzyme Q10 and N-acetylcysteine on experimental poisoning by paracetamol in Wistar rats. PLoS One 2023; 18:e0290268. [PMID: 37607187 PMCID: PMC10443853 DOI: 10.1371/journal.pone.0290268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 08/05/2023] [Indexed: 08/24/2023] Open
Abstract
Paracetamol (PAR) is a drug widely used in human and veterinary medicine as an analgesic and antipyretic, often involved in cases of intoxication. The most common clinical signs result from damage to red blood cells and hepatocytes, and this intoxication is considered a model for the induction of acute liver failure. In the present study, the hepatoprotective effects of coenzyme Q10 (CoQ10) and N-acetylcysteine (NAC) against experimental paracetamol (PAR) poisoning were analysed. Thirty-five adult Wistar rats (Rattus novergicus albinus) were randomly assigned to five groups, and thirty-one of these survived the treatments. Negative control group (CON-) received 1mL of 0.9% NaCl orally (PO). Other groups received 1.2g/kg of PAR (PO). Positive control group (CON+) received only PAR. NAC group received 800 mg/kg intraperitoneally (IP) of NAC 1h after the administration of PAR and at 12 h received 1mL of 0.9% NaCl, IP. The fourth group (CoQ10) received 1h and 12 h after intoxication, CoQ10 (10mg/kg IP). And the fifth group (NAC+CoQ10) received NAC (800mg/kg, IP) and CoQ10 (10mg/kg, IP). After 12 hours, the rats were euthanized and necropsied to collect liver and kidney tissues for histopathological evaluation and electronic microscopy. A single dose of PAR caused severe acute hepatitis. NAC couldn't reverse the liver and kidney damages. The group that received CoQ10 and NAC had moderate liver damage, while the group that received only CoQ10 had lower values of liver enzymes and mild liver and kidney damage. Animals that received treatment with CoQ10 or NAC+CoQ10 presented normal hepatocyte mitochondria and nuclei. Although CoQ10 couldn't reverse PAR organ damage, results indicate promising hepatoprotection in Wistar rats.
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Affiliation(s)
- Rayanne Henrique Santana da Silva
- Veterinary Toxicology Laboratory, Veterinary Hospital, Veterinary and Animal Science School, Federal University of Goiás, Goiânia, Goiás, Brazil
| | - Mariana de Moura
- Department of Genetics, Laboratory of Mutagenesis, Federal University of Goiás, Goiânia, Goiás, Brazil
| | - Larissa de Paula
- Pathology Sector, Instituto de Patologia Tropical e Saúde Pública, Federal University of Goiás, Goiânia, Goiás, Brazil
| | - Kelly Carolina Arantes
- Veterinary Toxicology Laboratory, Veterinary Hospital, Veterinary and Animal Science School, Federal University of Goiás, Goiânia, Goiás, Brazil
| | - Marina da Silva
- Veterinary Clinical Pathology Laboratory, Veterinary Hospital, Veterinary and Animal Science School, Federal University of Goiás, Goiânia, Goiás, Brazil
| | - Jaqueline de Amorim
- Veterinary Clinical Pathology Laboratory, Veterinary Hospital, Veterinary and Animal Science School, Federal University of Goiás, Goiânia, Goiás, Brazil
| | - Marina Pacheco Miguel
- Pathology Sector, Instituto de Patologia Tropical e Saúde Pública, Federal University of Goiás, Goiânia, Goiás, Brazil
| | - Danieli Brolo Martins
- Veterinary Clinical Pathology Laboratory, Veterinary Hospital, Veterinary and Animal Science School, Federal University of Goiás, Goiânia, Goiás, Brazil
| | - Daniela de Melo e Silva
- Department of Genetics, Laboratory of Mutagenesis, Federal University of Goiás, Goiânia, Goiás, Brazil
| | - Marília Martins Melo
- Veterinary Toxicology Laboratory, Veterinary Hospital, Veterinary and Animal Science School, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Ana Flávia Machado Botelho
- Veterinary Toxicology Laboratory, Veterinary Hospital, Veterinary and Animal Science School, Federal University of Goiás, Goiânia, Goiás, Brazil
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15
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Alhusaini AM, Alsoghayer R, Alhushan L, Alanazi AM, Hasan IH. Acetyl-L-Carnitine and Liposomal Co-Enzyme Q 10 Attenuate Hepatic Inflammation, Apoptosis, and Fibrosis Induced by Propionic Acid. Int J Mol Sci 2023; 24:11519. [PMID: 37511276 PMCID: PMC10380200 DOI: 10.3390/ijms241411519] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 07/03/2023] [Accepted: 07/12/2023] [Indexed: 07/30/2023] Open
Abstract
Propionic acid (PRA) is a metabolic end-product of enteric bacteria in the gut, and it is commonly used as a food preservative. Despite the necessity of PRA for immunity in the body, excessive exposure to this product may result in disruptive effects. The purpose of this study is to examine the hepatoprotective effects of acetyl-L-carnitine (A-CAR) and liposomal-coenzyme Q10 (L-CoQ10) against PRA-induced injury. Liver injury in rats was induced by oral administration of PRA, and A-CAR and L-CoQ10 were administered concurrently with PRA for 5 days. Oxidative stress, inflammatory, apoptotic, and fibrotic biomarkers were analyzed; the histology of liver tissue was assessed as well to further explore any pathological alterations. PRA caused significant increases in the levels of serum liver enzymes and hepatic oxidative stress, inflammatory, and apoptotic biomarker levels, along with histopathological alterations. Concurrent treatment with A-CAR and/or L-CoQ10 with PRA prevented tissue injury and decreased the levels of oxidative stress, proinflammatory cytokines, and apoptotic markers. Additionally, A-CAR and/or L-CoQ10 modulated the expression of high-mobility group box-1, cytokeratin-18, transforming growth factor-beta1, and SMAD3 in liver tissue. In conclusion, A-CAR and/or L-CoQ10 showed hepatoprotective efficacy by reducing oxidative stress, the inflammatory response, apoptosis, and fibrosis in liver tissue.
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Affiliation(s)
- Ahlam M Alhusaini
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11459, Saudi Arabia
| | - Rahaf Alsoghayer
- Pharm D Program, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11459, Saudi Arabia
| | - Lina Alhushan
- Pharm D Program, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11459, Saudi Arabia
| | - Abeer M Alanazi
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11459, Saudi Arabia
| | - Iman H Hasan
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11459, Saudi Arabia
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16
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Hou S, Tian Z, Zhao D, Liang Y, Dai S, Ji Q, Fan Z, Liu Z, Liu M, Yang Y. Efficacy and Optimal Dose of Coenzyme Q10 Supplementation on Inflammation-Related Biomarkers: A GRADE-Assessed Systematic Review and Updated Meta-Analysis of Randomized Controlled Trials. Mol Nutr Food Res 2023; 67:e2200800. [PMID: 37118903 DOI: 10.1002/mnfr.202200800] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 03/23/2023] [Indexed: 04/30/2023]
Abstract
SCOPE Coenzyme Q10 (CoQ10) has become a popular nutritional supplement due to its wide range of beneficial biological effects. Previous meta-analyses show that the attenuation of CoQ10 on inflammatory biomarkers remains controversial. This meta-analysis aims to assess the efficacy and optimal dose of CoQ10 supplementation on inflammatory indicators in the general population. METHODS AND RESULTS Databases are searched up to December 2022 resulting in 6713 articles, of which 31 are retrieved for full-text assessment and included 1517 subjects. Double-blind randomized controlled trials (RCTs) of CoQ10 supplementation are eligible if they contain C reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). CoQ10 supplementation can significantly reduce the levels of circulating CRP (SMD: -0.40, 95% CI: [-0.67 to -0.13], p = 0.003), IL-6 (SMD: -0.67, 95% CI: [-1.01 to -0.33], p < 0.001), and TNF-α (SMD: -1.06, 95% CI: [-1.59 to -0.52], p < 0.001) and increase the concentration of circulating CoQ10. CONCLUSION This meta-analysis provides evidence for CoQ10 supplementation to reduce the level of inflammatory mediators in the general population and proposes that daily supplementation of 300-400 mg CoQ10 show superior inhibition of inflammatory factors.
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Affiliation(s)
- Shanshan Hou
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong Province, 518107, P. R. China
- Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
- Guangdong Engineering Technology Center of Nutrition Transformation, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
| | - Zezhong Tian
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong Province, 518107, P. R. China
- Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
- Guangdong Engineering Technology Center of Nutrition Transformation, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
| | - Dan Zhao
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong Province, 518107, P. R. China
- Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
- Guangdong Engineering Technology Center of Nutrition Transformation, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
| | - Ying Liang
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong Province, 518107, P. R. China
- Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
- Guangdong Engineering Technology Center of Nutrition Transformation, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
| | - Suming Dai
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong Province, 518107, P. R. China
- Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
- Guangdong Engineering Technology Center of Nutrition Transformation, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
| | - Qiuhua Ji
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong Province, 518107, P. R. China
- Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
- Guangdong Engineering Technology Center of Nutrition Transformation, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
| | - Zhiying Fan
- School of Public Health, Baotou Medical College, Baotou, Inner Mongolia, 014040, P. R. China
| | - Zhihao Liu
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong Province, 518107, P. R. China
- Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
- Guangdong Engineering Technology Center of Nutrition Transformation, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
| | - Meitong Liu
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong Province, 518107, P. R. China
- Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
- Guangdong Engineering Technology Center of Nutrition Transformation, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
| | - Yan Yang
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong Province, 518107, P. R. China
- Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
- Guangdong Engineering Technology Center of Nutrition Transformation, Sun Yat-sen University, Guangzhou, Guangdong Province, 510000, P. R. China
- China-DRIs Expert Committee, Beijing, P. R. China
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17
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McRae MP. Coenzyme Q10 Supplementation in Reducing Inflammation: An Umbrella Review. J Chiropr Med 2023; 22:131-137. [PMID: 37346240 PMCID: PMC10280088 DOI: 10.1016/j.jcm.2022.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 06/28/2022] [Accepted: 07/08/2022] [Indexed: 11/29/2022] Open
Abstract
Objective The purpose of this study was to review meta-analyses on the effectiveness of coenzyme Q10 supplementation in reducing inflammation through changes in the inflammatory biomarkers C-reactive protein, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α). Methods An umbrella review of all published meta-analyses was performed. A PubMed search from January 1, 1980, to December 31, 2021, was conducted using the following search strategy: "(coenzyme q10 OR CoQ10 OR ubiquinone OR ubiquinol) AND (meta-analysis OR systematic review)". Only English language publications that provided quantitative statistical analysis on coenzyme Q10 supplementation and markers of inflammation were retrieved. Results Seven meta-analyses were retrieved for inclusion in this umbrella review, and for all 3 inflammatory biomarker marker groups, the median intake of supplemental coenzyme Q10 was 200 mg/d for a median duration of 12 weeks. For C-reactive protein, only 3 of the 7 meta-analyses presented with statistically significant reductions, while statistically significant reductions in IL-6 and TNF-α for were observed in 4 of the 5 meta-analyses and 3 of the 4 meta-analyses, respectively. However, statistically significant heterogeneity was observed in the majority of these meta-analyses. Conclusion The majority of included meta-analyses showed that coenzyme Q10 supplementation significantly decreased the proinflammatory cytokines IL-6 and TNF-α. However, heterogeneity was observed in the majority of these meta-analyses, and therefore the results should be interpreted with caution.
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Affiliation(s)
- Marc P. McRae
- Department of Basic Sciences, National University of Health Sciences, Lombard, Illinois
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18
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Ardekani A, Tabrizi R, Maleki E, Bagheri Lankarani K, Heydari ST, Moradinazar M, Akbari M. Effects of coenzyme Q10 supplementation on lipid profiles and liver enzymes of nonalcoholic fatty liver disease (NAFLD) patients: A systematic review and meta-analysis of randomized controlled trials. Food Sci Nutr 2023; 11:2580-2588. [PMID: 37324909 PMCID: PMC10261764 DOI: 10.1002/fsn3.3315] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 02/17/2023] [Accepted: 02/26/2023] [Indexed: 03/16/2023] Open
Abstract
As an antioxidant, coenzyme Q 10 (CoQ10) has been proposed as a possible treatment for non-alcoholic fatty liver disease (NAFLD). In the present meta-analysis, we aimed to determine the effects of CoQ10 supplementation on lipid profiles and liver enzymes of NAFLD patients. We searched PubMed, Web of Science, Scopus, and Cochrane Library on 21 April 2022 to retrieve randomized controlled trials on NAFLD patients in which CoQ10 was utilized as a treatment. Data were pooled using the random-effects model and weighted mean difference (WMD) was considered as the summary effect size. The analysis of the six included studies indicated an overall non-significant decrease in the lipid profiles (total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG)), and liver enzymes (aspartate transaminase (AST), alanine transaminase (ALT), and gamma-glutamyltransferase (GGT)) of NAFLD patients who received CoQ10. Sensitivity analysis using "leave-one out" method showed a significant reduction in AST, and GGT after excluding certain studies. Also, subgroup analyses showed significant difference based on CoQ10 dose for TC, AST, and GGT, and also a significant decrease in AST based on the duration of the intervention. No publication bias was found between the studies. Although an overall non-significant decrease was observed in lipid profiles and liver enzymes of NAFLD patients, the results of sensitivity and subgroup analyses showed significant effects of CoQ10 in certain conditions. Further RCTs should be done in light of our findings.
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Affiliation(s)
- Ali Ardekani
- Health Policy Research CenterInstitute of Health, Shiraz University of Medical SciencesShirazIran
| | - Reza Tabrizi
- Noncommunicable Diseases Research CenterFasa University of Medical SciencesFasaIran
- Clinical Research Development Unit, Valiasr HospitalFasa University of Medical SciencesFasaIran
| | - Elham Maleki
- Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology SciencesKerman University of Medical SciencesKermanIran
| | - Kamran Bagheri Lankarani
- Health Policy Research CenterInstitute of Health, Shiraz University of Medical SciencesShirazIran
| | - Seyed Taghi Heydari
- Health Policy Research CenterInstitute of Health, Shiraz University of Medical SciencesShirazIran
| | - Mehdi Moradinazar
- Research Center for Environmental Determinants of Health (RCEDH)Kermanshah University of Medical SciencesKermanshahIran
| | - Maryam Akbari
- Health Policy Research CenterInstitute of Health, Shiraz University of Medical SciencesShirazIran
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19
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Rizzo M, Colletti A, Penson PE, Katsiki N, Mikhailidis DP, Toth PP, Gouni-Berthold I, Mancini J, Marais D, Moriarty P, Ruscica M, Sahebkar A, Vinereanu D, Cicero AFG, Banach M, Al-Khnifsawi M, Alnouri F, Amar F, Atanasov AG, Bajraktari G, Banach M, Gouni-Berthold I, Bhaskar S, Bielecka-Dąbrowa A, Bjelakovic B, Bruckert E, Bytyçi I, Cafferata A, Ceska R, Cicero AF, Chlebus K, Collet X, Daccord M, Descamps O, Djuric D, Durst R, Ezhov MV, Fras Z, Gaita D, Gouni-Berthold I, Hernandez AV, Jones SR, Jozwiak J, Kakauridze N, Kallel A, Katsiki N, Khera A, Kostner K, Kubilius R, Latkovskis G, John Mancini G, David Marais A, Martin SS, Martinez JA, Mazidi M, Mikhailidis DP, Mirrakhimov E, Miserez AR, Mitchenko O, Mitkovskaya NP, Moriarty PM, Mohammad Nabavi S, Nair D, Panagiotakos DB, Paragh G, Pella D, Penson PE, Petrulioniene Z, Pirro M, Postadzhiyan A, Puri R, Reda A, Reiner Ž, Radenkovic D, Rakowski M, Riadh J, Richter D, Rizzo M, Ruscica M, Sahebkar A, Serban MC, Shehab AM, Shek AB, Sirtori CR, Stefanutti C, Tomasik T, Toth PP, Viigimaa M, Valdivielso P, Vinereanu D, Vohnout B, von Haehling S, Vrablik M, Wong ND, Yeh HI, Zhisheng J, Zirlik A. Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP). Pharmacol Res 2023; 189:106679. [PMID: 36764041 DOI: 10.1016/j.phrs.2023.106679] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Revised: 01/25/2023] [Accepted: 01/26/2023] [Indexed: 02/11/2023]
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.
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Affiliation(s)
- Manfredi Rizzo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, Via del Vespro 141, 90127 Palermo, Italy.
| | - Alessandro Colletti
- Department of Science and Drug Technology, University of Turin, Turin, Italy
| | - Peter E Penson
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK; Liverpool Centre for Cardiovascular Science, Liverpool, UK
| | - Niki Katsiki
- Department of Nutritional Sciences and Dietetics, International Hellenic University, Thessaloniki, Greece; School of Medicine, European University Cyprus, Nicosia, Cyprus
| | - Dimitri P Mikhailidis
- Department of Clinical Biochemistry, Royal Free Campus, Medical School, University College London (UCL), London, UK
| | - Peter P Toth
- The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA; Preventive Cardiology, CGH Medical Center, Sterling, IL, USA
| | - Ioanna Gouni-Berthold
- Department of Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Germany
| | - John Mancini
- Department of Medicine, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada
| | - David Marais
- Chemical Pathology Division of the Department of Pathology, University of Cape Town Health Science Faculty, Cape Town, South Africa
| | - Patrick Moriarty
- Division of Clinical Pharmacology, Division of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Massimiliano Ruscica
- Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Dragos Vinereanu
- Cardiology Department, University and Emergency Hospital, Bucharest, Romania, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania
| | - Arrigo Francesco Giuseppe Cicero
- Hypertension and Cardiovascular disease risk research center, Medical and Surgical Sciences Department, University of Bologna, Bologna, Italy; IRCCS Policlinico S. Orsola-Malpighi, Bologna, Italy
| | - Maciej Banach
- Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Poland; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland.
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Wang LL, Zhang PH, Yan HH. Functional foods and dietary supplements in the management of non-alcoholic fatty liver disease: A systematic review and meta-analysis. Front Nutr 2023; 10:1014010. [PMID: 36866059 PMCID: PMC9971819 DOI: 10.3389/fnut.2023.1014010] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 01/30/2023] [Indexed: 02/16/2023] Open
Abstract
Objective In this systematic review and meta-analysis, we aimed to clarify the overall effects of functional foods and dietary supplements in non-alcoholic fatty liver disease (NAFLD) patients. Methods Randomized controlled trials (RCTs) published in PubMed, ISI Web of Science, Cochrane library, and Embase from January 1, 2000 to January 31, 2022 were systematically searched to assess the effects of functional foods and dietary supplements in patients with NAFLD. The primary outcomes were liver-related measures, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic fibrosis and steatosis, while the secondary outcomes included body mass index (BMI), waist circumference (WC), triacylglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). These indexes were all continuous variables, so the mean difference (MD) was used for calculating the effect size. Random-effects or fixed-effects models were used to estimate the mean difference (MD). The risk of bias in all studies was assessed with guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions. Results Twenty-nine articles investigating functional foods and dietary supplements [antioxidants (phytonutrients and coenzyme Q10) = 18, probiotics/symbiotic/prebiotic = 6, fatty acids = 3, vitamin D = 1, and whole grain = 1] met the eligibility criteria. Our results showed that antioxidants could significantly reduce WC (MD: -1.28 cm; 95% CI: -1.58, -0.99, P < 0.05), ALT (MD: -7.65 IU/L; 95% CI: -11.14, -4.16, P < 0.001), AST (MD: -4.26 IU/L; 95% CI: -5.76, -2.76, P < 0.001), and LDL-C (MD: -0.24 mg/dL; 95% CI: -0.46, -0.02, P < 0.05) increased in patients with NAFLD but had no effect on BMI, TG, and TC. Probiotic/symbiotic/prebiotic supplementation could decrease BMI (MD: -0.57 kg/m2; 95% CI: -0.72, -0.42, P < 0.05), ALT (MD: -3.96 IU/L; 95% CI: -5.24, -2.69, P < 0.001), and AST (MD: -2.76; 95% CI: -3.97, -1.56, P < 0.0001) levels but did not have beneficial effects on serum lipid levels compared to the control group. Moreover, the efficacy of fatty acids for treating NAFLD was full of discrepancies. Additionally, vitamin D had no significant effect on BMI, liver transaminase, and serum lipids, while whole grain could reduce ALT and AST but did not affect serum lipid levels. Conclusion The current study suggests that antioxidant and probiotic/symbiotic/prebiotic supplements may be a promising regimen for NAFLD patients. However, the usage of fatty acids, vitamin D, and whole grain in clinical treatment is uncertain. Further exploration of the efficacy ranks of functional foods and dietary supplements is needed to provide a reliable basis for clinical application. Systematic review registration https://www.crd.york.ac.uk/prospero, identifier: CRD42022351763.
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Affiliation(s)
- Lei-lei Wang
- Department of Clinical Nutrition, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Pian-hong Zhang
- Department of Clinical Nutrition, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Hui-hui Yan
- Department of Gastroenterology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
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21
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Kadry MO, Ammar NM, Hassan HA, Abdel Megeed RM. Insights on attenuating autophagy cellular and molecular pathways versus methotrexate-induced toxicity via liposomal turmeric therapy. J Genet Eng Biotechnol 2022; 20:147. [DOI: 10.1186/s43141-022-00430-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 10/11/2022] [Indexed: 11/10/2022]
Abstract
Abstract
Background
Methotrexate (MX), a competitive inhibitor of dihydrofolate reductase, can inhibit DNA and RNA production and is a powerful anticancer agent widely utilized in clinical practice for treating nonneoplastic maladies, as psoriasis and rheumatoid arthritis; meanwhile, its probable prescription dose and interval of administration are strictly limited due to dose-related organ damage. Former studies verified that kidney, brain, liver, and lung harms are prospective obstacles of methotrexate administration. To understand the machinery of methotrexate-prompt toxicity, various mechanisms were investigated. The former is an autophagy defense mechanism; autophagy is a self-digesting mechanism responsible for the removal of damaged organelles and malformed proteins by lysosome. The contemporary article hypothesized that turmeric or its liposomal analog could defeat autophagy of MX-induced acute toxicity. Methotrexate, in a dose of 1.5 mg/kg, was administered intravenously followed by turmeric and liposomal turmeric treatment in a dose of 5 mg/kg for 30 days in rats.
Results
Increment in autophagy (AUTP) consent by MX administration was attenuated by concurrent treatment via turmeric and liposomal turmeric that was reliable on the alteration in apoptotic markers. The assembly of FOXO-3 in serum post methotrexate administration was suppressed by concurrent treatment via liposomal turmeric. Apoptosis/autophagic marker investigation was evaluated through the gene expression of Bax (BCL2-associated X protein)/Bcl2 (B-cell lymphoma 2)/P53 (tumor protein P53)/SiRT-1 (sirtuin silent mating-type information regulation 2 homolog 1) and FOXO-3 (forkhead box transcription factor-3)/ERDJ-4 (endoplasmic reticulum localized DnaJ homologs)/BNP (brain natriuretic peptide B) signaling. The cell death of all cells was categorized to achieve autophagy. Interestingly, Bax/Bcl2/P53/SiRT-1 signaling pathways were downregulated, contributing to inhibiting the initiation of autophagy. Meanwhile, FOXO-3/BNP/ERDJ-4 reduction-implicated noncanonical autophagy pathways were involved in methotrexate-induced autophagy, whereas this change was suppressed when turmeric was administered in liposomal form.
Conclusion
These outcomes recommended that liposomal turmeric prevents MX-induced acute toxicity through its autophagy, antioxidant, and antiapoptotic properties.
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22
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Tippairote T, Bjørklund G, Gasmi A, Semenova Y, Peana M, Chirumbolo S, Hangan T. Combined Supplementation of Coenzyme Q 10 and Other Nutrients in Specific Medical Conditions. Nutrients 2022; 14:4383. [PMID: 36297067 PMCID: PMC9609170 DOI: 10.3390/nu14204383] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 10/07/2022] [Accepted: 10/15/2022] [Indexed: 07/23/2023] Open
Abstract
Coenzyme Q10 (CoQ10) is a compound with a crucial role in mitochondrial bioenergetics and membrane antioxidant protection. Despite the ubiquitous endogenous biosynthesis, specific medical conditions are associated with low circulating CoQ10 levels. However, previous studies of oral CoQ10 supplementation yielded inconsistent outcomes. In this article, we reviewed previous CoQ10 trials, either single or in combination with other nutrients, and stratified the study participants according to their metabolic statuses and medical conditions. The CoQ10 supplementation trials in elders reported many favorable outcomes. However, the single intervention was less promising when the host metabolic statuses were worsening with the likelihood of multiple nutrient insufficiencies, as in patients with an established diagnosis of metabolic or immune-related disorders. On the contrary, the mixed CoQ10 supplementation with other interacting nutrients created more promising impacts in hosts with compromised nutrient reserves. Furthermore, the results of either single or combined intervention will be less promising in far-advanced conditions with established damage, such as neurodegenerative disorders or cancers. With the limited high-level evidence studies on each host metabolic category, we could only conclude that the considerations of whether to take supplementation varied by the individuals' metabolic status and their nutrient reserves. Further studies are warranted.
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Affiliation(s)
- Torsak Tippairote
- Department of Nutritional and Environmental Medicine, HP Medical Center, Bangkok 10540, Thailand
| | - Geir Bjørklund
- Council for Nutritional and Environmental Medicine, Toften 24, 8610 Mo i Rana, Norway
| | - Amin Gasmi
- Société Francophone de Nutrithérapie et de Nutrigénétique Appliquée, 69100 Villeurbanne, France
| | - Yuliya Semenova
- School of Medicine, Nazarbayev University, Astana 020000, Kazakhstan
| | - Massimiliano Peana
- Department of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, via Vienna 2, 07100 Sassari, Italy
| | - Salvatore Chirumbolo
- Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy
- CONEM Scientific Secretary, Strada Le Grazie 9, 37134 Verona, Italy
| | - Tony Hangan
- Faculty of Medicine, Ovidius University of Constanta, 900470 Constanta, Romania
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23
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Berger MM, Shenkin A, Schweinlin A, Amrein K, Augsburger M, Biesalski HK, Bischoff SC, Casaer MP, Gundogan K, Lepp HL, de Man AME, Muscogiuri G, Pietka M, Pironi L, Rezzi S, Cuerda C. ESPEN micronutrient guideline. Clin Nutr 2022; 41:1357-1424. [PMID: 35365361 DOI: 10.1016/j.clnu.2022.02.015] [Citation(s) in RCA: 287] [Impact Index Per Article: 95.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 02/16/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND Trace elements and vitamins, named together micronutrients (MNs), are essential for human metabolism. Recent research has shown the importance of MNs in common pathologies, with significant deficiencies impacting the outcome. OBJECTIVE This guideline aims to provide information for daily clinical nutrition practice regarding assessment of MN status, monitoring, and prescription. It proposes a consensus terminology, since many words are used imprecisely, resulting in confusion. This is particularly true for the words "deficiency", "repletion", "complement", and "supplement". METHODS The expert group attempted to apply the 2015 standard operating procedures (SOP) for ESPEN which focuses on disease. However, this approach could not be applied due to the multiple diseases requiring clinical nutrition resulting in one text for each MN, rather than for diseases. An extensive search of the literature was conducted in the databases Medline, PubMed, Cochrane, Google Scholar, and CINAHL. The search focused on physiological data, historical evidence (published before PubMed release in 1996), and observational and/or randomized trials. For each MN, the main functions, optimal analytical methods, impact of inflammation, potential toxicity, and provision during enteral or parenteral nutrition were addressed. The SOP wording was applied for strength of recommendations. RESULTS There was a limited number of interventional trials, preventing meta-analysis and leading to a low level of evidence. The recommendations underwent a consensus process, which resulted in a percentage of agreement (%): strong consensus required of >90% of votes. Altogether the guideline proposes sets of recommendations for 26 MNs, resulting in 170 single recommendations. Critical MNs were identified with deficiencies being present in numerous acute and chronic diseases. Monitoring and management strategies are proposed. CONCLUSION This guideline should enable addressing suboptimal and deficient status of a bundle of MNs in at-risk diseases. In particular, it offers practical advice on MN provision and monitoring during nutritional support.
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Affiliation(s)
- Mette M Berger
- Department of Adult Intensive Care, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
| | - Alan Shenkin
- Institute of Aging and Chronic Disease, University of Liverpool, Liverpool, UK.
| | - Anna Schweinlin
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Karin Amrein
- Medical University of Graz, Department of Internal Medicine, Division of Endocrinology and Diabetology, Austria.
| | - Marc Augsburger
- University Centre of Legal Medicine Lausanne-Geneva, Lausanne University Hospital and University of Lausanne, Geneva University Hospital and University of Geneva, Lausanne-Geneva, Switzerland.
| | | | - Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Michael P Casaer
- KU Leuven, Department of Cellular and Molecular Medicine, Laboratory of Intensive Care Medicine, Leuven, Belgium.
| | - Kursat Gundogan
- Division of Intensive Care Medicine, Department of Internal Medicine, Erciyes University School of Medicine, Kayseri, Turkey.
| | | | - Angélique M E de Man
- Department of Intensive Care Medicine, Research VUmc Intensive Care (REVIVE), Amsterdam Cardiovascular Science (ACS), Amsterdam Infection and Immunity Institute (AI&II), Amsterdam Medical Data Science (AMDS), Amsterdam UMC, Location VUmc, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands.
| | - Giovanna Muscogiuri
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università di Napoli (Federico II), Naples, Italy; United Nations Educational, Scientific and Cultural Organization (UNESCO) Chair for Health Education and Sustainable Development, Federico II, University, Naples, Italy.
| | - Magdalena Pietka
- Pharmacy Department, Stanley Dudrick's Memorial Hospital, Skawina, Poland.
| | - Loris Pironi
- Alma Mater Studiorum - University of Bologna, Department of Medical and Surgical Sciences, Italy; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Centre for Chronic Intestinal Failure - Clinical Nutrition and Metabolism Unit, Italy.
| | - Serge Rezzi
- Swiss Nutrition and Health Foundation (SNHf), Epalinges, Switzerland.
| | - Cristina Cuerda
- Departamento de Medicina, Universidad Complutense de Madrid, Nutrition Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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KIANI AYSHAKARIM, DONATO KEVIN, DHULI KRISTJANA, STUPPIA LIBORIO, BERTELLI MATTEO. Dietary supplements for polycystic ovary syndrome. JOURNAL OF PREVENTIVE MEDICINE AND HYGIENE 2022; 63:E206-E213. [PMID: 36479481 PMCID: PMC9710389 DOI: 10.15167/2421-4248/jpmh2022.63.2s3.2762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Polycystic ovary syndrome (PCOS) is one of the most prevalent female endocrine reproductive disorders, affecting between 4 to 18% of the women in their reproductive age. It is generally characterized by several clinical aspects, among which anovulation, inflammation and infertility. Moreover, PCOS has several health implications, including increased metabolic, reproductive, and psychological risks. Previously, metformin and to some extent thiazolidinediones were considered as drug of choice for PCOS management, but they had several side-effects, and controversial results were obtained about their efficiency, especially in non-insulin-resistant non-obese patients. Thus, alternative treatment options are now being studied for PCOS, including different natural molecules and complementary medicines (CM) for the improvement of their health, wellbeing and fertility. Recently, treatment of PCOS patients with different natural molecules, coming from nutritional supplements and herbal medicines, has attained satisfactory results with the absence of any side effects. In this review, four natural molecules, curcumin, vitamin D, inositol and CoQ10 are discussed for their therapeutic ability. These molecules proved to decrease insulin sensitivity and inflammation, to improve the restoration of ovarian function, and they could restore hormonal balance and regulate the menstrual cycle, all of which are the main features and major concerns for women suffering from PCOS.
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Affiliation(s)
| | | | | | - LIBORIO STUPPIA
- Department of Psychological, Health and Territorial Sciences, School of Medicine and Health Sciences, “G. d’Annunzio” University, Chieti, Italy
| | - MATTEO BERTELLI
- MAGI Euregio, Bolzano, Italy
- MAGI’s Lab, Rovereto, Italy
- MAGISNAT, Peachtree Corners, USA
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Ghiasi S, Bashiri J, Pourrazi H, Jadidi RP. The effect of high-intensity interval training and CoQ10 administration on hepatic CEACAM1 and PDGFA proteins in diet-induced obese rats. SPORT SCIENCES FOR HEALTH 2022. [DOI: 10.1007/s11332-022-00922-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Mantle D, Turton N, Hargreaves IP. Lyme Disease: A Role for Coenzyme Q10 Supplementation? Antioxidants (Basel) 2022; 11:667. [PMID: 35453352 PMCID: PMC9027459 DOI: 10.3390/antiox11040667] [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: 03/03/2022] [Revised: 03/24/2022] [Accepted: 03/28/2022] [Indexed: 11/29/2022] Open
Abstract
Lyme disease results from a bacterial infection following a bite from an infected tick. Patients are initially treated with antibiotics; however, in cases where antibiotic treatment is delayed, or when patients do not respond to antibiotic treatment, fatigue may develop alongside problems affecting the nervous system, cardiovascular system, and joints. It is thought that most of the damage to these tissues results from the excessive inflammatory response of the host, involving a self-reinforcing cycle of mitochondrial dysfunction, oxidative stress and inflammation. In this article, we review the potential role of supplementary coenzyme Q10 (CoQ10) in mediating the pathogenic mechanism underlying Lyme disease, on the basis of its role in mitochondrial function, as well as its anti-inflammatory and antioxidant actions.
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Affiliation(s)
| | - Nadia Turton
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK;
| | - Iain P. Hargreaves
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK;
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Antioxidant and Anti-Inflammatory Effects of Coenzyme Q10 Supplementation on Infectious Diseases. Healthcare (Basel) 2022; 10:healthcare10030487. [PMID: 35326965 PMCID: PMC8953254 DOI: 10.3390/healthcare10030487] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 02/25/2022] [Accepted: 03/02/2022] [Indexed: 12/14/2022] Open
Abstract
With the appearance of new viruses and infectious diseases (ID) such as COVID-19 in 2019, as well as the lack of specific pharmacological tools for the management of patients with severe complications or comorbidities, it is important to search for adjuvant treatments that help improve the prognosis of infectious disease patients. It is also important that these treatments limit the oxidative and hyperinflammatory damage caused as a response to pathogenic agents, since, in some cases, an inflammatory syndrome may develop that worsens the patient’s prognosis. The potential benefits of complementary nutrients and dietary interventions in the treatment of pathological processes in which oxidative stress and inflammation play a fundamental role have been widely evaluated. Coenzyme Q10 (CoQ10) is a supplement that has been shown to protect cells and be effective in cardiovascular diseases and obesity. Additionally, some studies have proposed it as a possible adjuvant treatment in viral infections. Preclinical and clinical studies have shown that CoQ10 has anti-inflammatory and antioxidant effects, and effects on mitochondrial dysfunction, which have been linked to the inflammatory response.
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Zhang P, Chen K, He T, Guo H, Chen X. Coenzyme Q10 supplementation improves adipokine profile in dyslipidemic individuals: a randomized controlled trial. Nutr Metab (Lond) 2022; 19:13. [PMID: 35241098 PMCID: PMC8896379 DOI: 10.1186/s12986-022-00649-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 02/15/2022] [Indexed: 11/10/2022] Open
Abstract
Background In previous study, we found that coenzyme Q10 (CoQ10) improved glucolipid profile in dyslipidemic individuals, but the mechanism is not yet clear. Adipokines have been demonstrated to be vital targets of metabolic diseases. The hypothesis that adipokines mediate the association of CoQ10 on glucolipid metabolism needs to be further studied in human. Methods In this randomized, double-blinded, placebo-controlled trial, 101 dyslipidemic individuals were administrated to 120 mg CoQ10 or placebo for 24 weeks. Anthropometric parameters, glucolipid profile, serum total adiponectin, leptin, and resistin were evaluated at baseline, week 12 and week 24. Results CoQ10 treatment significantly increased serum adiponectin levels at week 12 (165 [0, 362] ng/mL, p < 0.001) and at week 24 (523 [0, 1056] ng/mL, p < 0.001]), which was significant different compared with placebo (p < 0.001). The increase of adiponectin was negative associated with decrease in index of homeostasis model assessment of insulin resistance (HOMA-IR, r = − 0.465, p = 0.001), triglyceride (TG, r = − 0.297, p = 0.047), and low-density lipoprotein cholesterol (LDL-c, r = − 0.440, p = 0.002) at week 24 only in CoQ10-treated group. Resistin was reduced by CoQ10 only at week 24 (− 1.19 [− 4.35, 0.00] ng/mL, p < 0.001), which was significant different compared with placebo (p < 0.001). Reduction of resistin was positively correlated with the change in HOMA-IR (r = 0.343, p = 0.021) and TG (r = 0.323, p = 0.030) at week 24 in CoQ10-treated group but not placebo group. Leptin was not influenced by CoQ10 treatment. Mediation analysis indicated that the improvement of HOMA-IR, TG and LDL-c by CoQ10 was mediated by adiponectin but not resistin. Conclusions Our study shows that CoQ10 ameliorates glucolipid profile and adipokines dysfunction in dyslipidemic patients in 24 weeks’ intervention. The beneficial effect of CoQ10 on glucolipid profile was mediated by adiponectin. Trial registration: ClinicalTrials.gov, NCT02407548. Registered on April 3, 2015, https://clinicaltrials.gov/ct2/show/NCT02407548. Supplementary Information The online version contains supplementary material available at 10.1186/s12986-022-00649-5.
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Affiliation(s)
- Peiwen Zhang
- Department of Nutrition, School of Public Health, Guangdong Medical University, Dongguan, People's Republic of China.,School of Public Health, Dongguan Key Laboratory of Environmental Medicine, Guangdong Medical University, Dongguan, People's Republic of China
| | - Ke Chen
- Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Taiping He
- Department of Nutrition, School of Public Health, Guangdong Medical University, Dongguan, People's Republic of China.,School of Public Health, Dongguan Key Laboratory of Environmental Medicine, Guangdong Medical University, Dongguan, People's Republic of China
| | - Honghui Guo
- Department of Nutrition, School of Public Health, Guangdong Medical University, Dongguan, People's Republic of China. .,School of Public Health, Dongguan Key Laboratory of Environmental Medicine, Guangdong Medical University, Dongguan, People's Republic of China.
| | - Xu Chen
- Department of Nutrition, School of Public Health, Guangdong Medical University, Dongguan, People's Republic of China. .,Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People's Republic of China.
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DiNicolantonio JJ, McCarty MF, O'Keefe JH. Coenzyme Q10 deficiency can be expected to compromise Sirt1 activity. Open Heart 2022; 9:e001927. [PMID: 35296520 PMCID: PMC8928362 DOI: 10.1136/openhrt-2021-001927] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 02/28/2022] [Indexed: 12/11/2022] Open
Abstract
For reasons that remain unclear, endogenous synthesis and tissue levels of coenzyme Q10 (CoQ10) tend to decline with increasing age in at least some tissues. When CoQ10 levels are sufficiently low, this compromises the efficiency of the mitochondrial electron transport chain, such that production of superoxide by site 2 increases and the rate of adenosine triphosphate production declines. Moreover, CoQ10 deficiency can be expected to decrease activities of Sirt1 and Sirt3 deacetylases, believed to be key determinants of health span. Reduction of the cytoplasmic and mitochondrial NAD+/NADH ratio consequent to CoQ10 deficit can be expected to decrease the activity of these deacetylases by lessening availability of their obligate substrate NAD+ The increased oxidant production induced by CoQ10 deficiency can decrease the stability of Sirt1 protein by complementary mechanisms. And CoQ10 deficiency has also been found to lower mRNA expression of Sirt1. An analysis of the roles of Sirt1/Sirt3 in modulation of cellular function helps to rationalise clinical benefits of CoQ10 supplementation reported in heart failure, hypertension, non-alcoholic fatty liver disease, metabolic syndrome and periodontal disease. Hence, correction of CoQ10 deficiency joins a growing list of measures that have potential for amplifying health protective Sirt1/Sirt3 activities.
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Affiliation(s)
- James J DiNicolantonio
- Department of Preventive Cardiology, Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA
| | | | - James H O'Keefe
- Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri, USA
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Crommen S, Rheinwalt KP, Plamper A, Simon MC, Rösler D, Fimmers R, Egert S, Metzner C. A Specifically Tailored Multistrain Probiotic and Micronutrient Mixture Affects Nonalcoholic Fatty Liver Disease-Related Markers in Patients with Obesity after Mini Gastric Bypass Surgery. J Nutr 2022; 152:408-418. [PMID: 34919684 DOI: 10.1093/jn/nxab392] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 10/31/2021] [Accepted: 11/17/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is frequent among patients undergoing bariatric surgery. Beyond weight reduction, dietary supplements like micronutrients or probiotics that modify insulin resistance and lipotoxicity can be used to prevent or delay the progression of liver disease. OBJECTIVES We evaluated the effect of a dietary approach with a specifically tailored multistrain probiotic and micronutrient mixture compared with a basic care micronutrient supplement on serum alanine aminotransferase (ALAT) in obese patients after mini gastric bypass (MGB) surgery. METHODS This randomized, double-blind, controlled trial included 60 obese patients (age: 40 ± 10 y; BMI: 44 ± 3 kg/m²). Patients received a combination of specifically tailored multistrain probiotic powder and a specific micronutrient mixture (Pro+SM) or a control treatment consisting of a placebo and a basic care micronutrient mixture (Con+BM), with some micronutrients in lower doses than SM, for 12 wk after hospital discharge. Primary (serum ALAT) and secondary outcomes [serum aspartate aminotransferase (ASAT), fatty liver index, NAFLD fibrosis score, glucose metabolism, blood pressure (BP), heart rate] were assessed at week 0 and week 12. Data were analyzed using unpaired Student's t-tests or Mann-Whitney U tests to compare the changes due to each treatment to one another. RESULTS A total of 48 patients were included in the analyses. Changes in serum ALAT concentrations did not differ between groups. Compared with Con+BM, Pro+SM improved serum ASAT (difference: -8.0 U/L, 95% CI: -17.0, -4.0; P = 0.043), NAFLD fibrosis score (difference: -0.39; 95% CI: -0.78, 0; P = 0.048), serum triglycerides (difference: -22.8 mg/dL; 95% CI: -45.6, -0.1; P = 0.049) and the visceral adiposity index (difference: -0.70; 95% CI: -1.31, -0.08; P = 0.027). CONCLUSION Supplementation with a specifically tailored probiotic and micronutrient mixture improved NAFLD-related markers more than a basic micronutrient mixture in obese patients following MGB surgery. The trial was registered under clinicaltrials.gov as NCT03585413.
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Affiliation(s)
- Silke Crommen
- Department of Nutrition and Food Science, Nutritional Physiology, University of Bonn, Bonn, Germany
| | - Karl Peter Rheinwalt
- Department of Bariatric, Metabolic and Plastic Surgery, St. Franziskus Hospital, Cologne, Germany
| | - Andreas Plamper
- Department of Bariatric, Metabolic and Plastic Surgery, St. Franziskus Hospital, Cologne, Germany
| | - Marie-Christine Simon
- Department of Nutrition and Food Science, Nutrition and Microbiome, University of Bonn, Bonn, Germany
| | - Daniela Rösler
- Bonn Education Association for Dietetics r.A., Cologne, Germany
| | - Rolf Fimmers
- Institute of Medical Biometry, Informatics and Epidemiology, University Hospital Bonn, Bonn, Germany
| | - Sarah Egert
- Department of Nutrition and Food Science, Nutritional Physiology, University of Bonn, Bonn, Germany.,Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany
| | - Christine Metzner
- Bonn Education Association for Dietetics r.A., Cologne, Germany.,Department of Gastroenterology, Metabolic Disorders and Internal Intensive Care (Department of Medicine III), University Hospital RWTH Aachen, Aachen, Germany
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Naeini F, Namkhah Z, Tutunchi H, Rezayat SM, Mansouri S, Jazayeri-Tehrani SA, Yaseri M, Hosseinzadeh-Attar MJ. Effects of naringenin supplementation in overweight/obese patients with non-alcoholic fatty liver disease: study protocol for a randomized double-blind clinical trial. Trials 2021; 22:801. [PMID: 34774104 PMCID: PMC8590238 DOI: 10.1186/s13063-021-05784-7] [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: 03/22/2021] [Accepted: 11/02/2021] [Indexed: 11/30/2022] Open
Abstract
Introduction Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of chronic liver disease worldwide. Flavonoids, a group of natural compounds, have garnered a great deal of attention in the management of NAFLD because of their profitable effects on glucose and lipid metabolism, inflammation, and oxidative stress which are the pivotal pathophysiological pathways in NAFLD. Naringenin is a citrus-derived flavonoid with a broad spectrum of potential biological effects including anti-inflammatory and antioxidant properties, which may exert protective effects against NAFLD. The present clinical trial aims to examine the efficacy of naringenin supplementation on plasma adiponectin and neurogulin-4 (NRG-4) concentrations, metabolic parameters, and liver function indices in overweight/obese patients with NAFLD. Methods and analysis This is a double-blind, randomized, placebo-controlled clinical study that will investigate the impacts of naringenin supplementation in overweight/obese patients with NAFLD. Liver ultrasonography will be applied to diagnose NAFLD. Forty-four eligible overweight/obese subjects with NAFLD will be selected and randomly assigned to receive naringenin capsules or identical placebo (each capsule contains 100 mg of naringenin or cellulose), twice daily for 4 weeks. Participants will be asked to remain on their usual diet and physical activity. Safety of naringenin supplementation was confirmed by the study pharmacist. The primary outcome of this study is changes in adiponectin circulating levels. The secondary outcomes include changes in NRG-4 levels, liver function indices, metabolic parameters, body weight, body mass index (BMI), waist circumference (WC), blood pressure, and hematological parameters. Statistical analysis will be conducted using the SPSS software (version 25), and P value less than 0.05 will be regarded as statistically significant. Discussion We hypothesize that naringenin administration may be useful for treating NAFLD by modulating energy balance, glucose and lipid metabolism, oxidative stress, and inflammation through different mechanisms. The current trial will exhibit the effects of naringenin, whether negative or positive, on NAFLD status. Ethical aspects The current trial received approval from the Medical Ethics Committee of Tehran University of Medical Sciences, Tehran, Iran (IR.TUMS.MEDICNE.REC.1399.439). Trial registration Iranian Registry of Clinical Trials IRCT201311250155336N12. Registered on 6 June 2020 Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05784-7.
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Affiliation(s)
- Fatemeh Naeini
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Namkhah
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Helda Tutunchi
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyed Mahdi Rezayat
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Siavash Mansouri
- National Iranian Oil Company (NIOC) Health and Family Research Center, Tehran, Iran
| | | | - Mehdi Yaseri
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Javad Hosseinzadeh-Attar
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
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Jadhav S, Protchenko O, Li F, Baratz E, Shakoury-Elizeh M, Maschek A, Cox J, Philpott CC. Mitochondrial dysfunction in mouse livers depleted of iron chaperone PCBP1. Free Radic Biol Med 2021; 175:18-27. [PMID: 34455040 PMCID: PMC9137418 DOI: 10.1016/j.freeradbiomed.2021.08.232] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 08/05/2021] [Accepted: 08/25/2021] [Indexed: 12/20/2022]
Abstract
Iron is an essential nutrient that forms cofactors required for the activity of hundreds of cellular proteins. However, iron can be toxic and must be precisely managed. Poly r(C) binding protein 1 (PCBP1) is an essential, multifunctional protein that binds both iron and nucleic acids, regulating the fate of both. As an iron chaperone, PCBP1 binds cytosolic iron and delivers it to iron enzymes for activation and to ferritin for storage. Mice deleted for PCBP1 in the liver exhibit dysregulated iron balance, with lower levels of liver iron stores and iron enzymes, but higher levels of chemically-reactive iron. Unchaperoned iron triggers the formation of reactive oxygen species, leading to lipid peroxidation and ferroptotic cell death. Hepatic PCBP1 deletion produces chronic liver disease in mice, with steatosis, triglyceride accumulation, and elevated plasma ALT levels. Human and mouse models of fatty liver disease are associated with mitochondrial dysfunction. Here we show that, although deletion of PCBP1 does not affect mitochondrial iron balance, it does affect mitochondrial function. PCBP1 deletion affected mitochondrial morphology and reduced levels of respiratory complexes II and IV, oxygen consumption, and ATP production. Depletion of mitochondrial lipids cardiolipin and coenzyme Q, along with reduction of mitochondrial oxygen consumption, were the first manifestations of mitochondrial dysfunction. Although dietary supplementation with vitamin E ameliorated the liver disease in mice with hepatic PCBP1 deletion, supplementation with coenzyme Q was required to fully restore mitochondrial lipids and function. In conclusion, our studies indicate that mitochondrial function can be restored in livers subjected to ongoing oxidative damage from unchaperoned iron by supplementation with coenzyme Q, a mitochondrial lipid essential for respiration that also functions as a lipophilic radical-trapping agent.
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Affiliation(s)
| | - Olga Protchenko
- Genetics and Metabolism Section, NIDDK, NIH, Bethesda, MD, USA
| | - Fengmin Li
- Genetics and Metabolism Section, NIDDK, NIH, Bethesda, MD, USA
| | - Ethan Baratz
- Genetics and Metabolism Section, NIDDK, NIH, Bethesda, MD, USA
| | | | - Alan Maschek
- Dept. of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - James Cox
- Dept. of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA
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Jarhahzadeh M, Alavinejad P, Farsi F, Husain D, Rezazadeh A. The effect of turmeric on lipid profile, malondialdehyde, liver echogenicity and enzymes among patients with nonalcoholic fatty liver disease: a randomized double blind clinical trial. Diabetol Metab Syndr 2021; 13:112. [PMID: 34663438 PMCID: PMC8524923 DOI: 10.1186/s13098-021-00731-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 10/05/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of liver transaminases elevation and a global health concern. PURPOSE This study designed to evaluate the effects of turmeric rhizomes (Curcumalonga Linn.) on liver enzymes, Lipid profiles and Malondialdehyde (MDA) in patients with NAFLD. STUDY DESIGN Randomized double-blind placebo controlled trial. METHODS 64 cases of NAFLD randomly assigned to receive either turmeric (2 gr/day) or placebo for 8 weeks. The changes of liver transaminases, lipid profiles and MDA were measured before and after study period and compared between two groups (IRCT 2015092924262N1). RESULTS At the end of the study, the Turmeric group showed a significant reduction in liver enzymes (AST before 26.81 ± 10.54 after 21.19 ± 5.67, P = 0.044, ALT before 39.56 ± 22.41, after 30.51 ± 12.61, P = 0.043 and GGT before33.81 ± 17.50, after 25.62 ± 9.88, P = 0.046) compared with the placebo group. The serum levels of triglycerides, LDL, HDL and MDA had also a significant decrease among turmeric group as compared to baseline while there was no significant change in placebo group (P < 0.05). The serum cholesterol, VLDL level and sonographic grades of NAFLD had not any significant change in both groups. CONCLUSION In conclusion this study suggests that daily consumption of turmeric (and its active phenolic ingredients as curcumin) supplementation could be effective in management of NAFLD and decreasing serum level of liver transaminases.
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Affiliation(s)
- Maryam Jarhahzadeh
- Department of Nutrition, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Pezhman Alavinejad
- Alimentary Tract Research Center, Ahvaz Jundishapur University of Medical Sciences, Azadegan Avenue, Ahvaz, Iran.
| | - Farnaz Farsi
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Durdana Husain
- Department of Nutrition, School of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Afshin Rezazadeh
- Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Targeting miRNA by Natural Products: A Novel Therapeutic Approach for Nonalcoholic Fatty Liver. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:6641031. [PMID: 34426744 PMCID: PMC8380168 DOI: 10.1155/2021/6641031] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 08/02/2021] [Indexed: 02/07/2023]
Abstract
The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) as multifactorial chronic liver disease and the lack of a specific treatment have begun a new era in its treatment using gene expression changes and microRNAs. This study aimed to investigate the potential therapeutic effects of natural compounds in NAFLD by regulating miRNA expression. MicroRNAs play essential roles in regulating the cell's biological processes, such as apoptosis, migration, lipid metabolism, insulin resistance, and adipocyte differentiation, by controlling the posttranscriptional gene expression level. The impact of current NAFLD pharmacological management, including drug and biological therapies, is uncertain. In this context, various dietary fruits or medicinal herbal sources have received worldwide attention versus NAFLD development. Natural ingredients such as berberine, lychee pulp, grape seed, and rosemary possess protective and therapeutic effects against NAFLD by modifying the gene's expression and noncoding RNAs, especially miRNAs.
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Cirilli I, Damiani E, Dludla PV, Hargreaves I, Marcheggiani F, Millichap LE, Orlando P, Silvestri S, Tiano L. Role of Coenzyme Q 10 in Health and Disease: An Update on the Last 10 Years (2010-2020). Antioxidants (Basel) 2021; 10:antiox10081325. [PMID: 34439573 PMCID: PMC8389239 DOI: 10.3390/antiox10081325] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 08/17/2021] [Accepted: 08/20/2021] [Indexed: 12/11/2022] Open
Abstract
The present review focuses on preclinical and clinical studies conducted in the last decade that contribute to increasing knowledge on Coenzyme Q10's role in health and disease. Classical antioxidant and bioenergetic functions of the coenzyme have been taken into consideration, as well as novel mechanisms of action involving the redox-regulated activation of molecular pathways associated with anti-inflammatory activities. Cardiovascular research and fertility remain major fields of application of Coenzyme Q10, although novel applications, in particular in relation to topical application, are gaining considerable interest. In this respect, bioavailability represents a major challenge and the innovation in formulation aspects is gaining critical importance.
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Affiliation(s)
- Ilenia Cirilli
- School of Pharmacy, University of Camerino, 62032 Camerino, Italy;
| | - Elisabetta Damiani
- Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy; (E.D.); (F.M.); (L.E.M.); (P.O.); (S.S.)
| | - Phiwayinkosi Vusi Dludla
- Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa;
| | - Iain Hargreaves
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK;
| | - Fabio Marcheggiani
- Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy; (E.D.); (F.M.); (L.E.M.); (P.O.); (S.S.)
| | - Lauren Elizabeth Millichap
- Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy; (E.D.); (F.M.); (L.E.M.); (P.O.); (S.S.)
| | - Patrick Orlando
- Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy; (E.D.); (F.M.); (L.E.M.); (P.O.); (S.S.)
| | - Sonia Silvestri
- Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy; (E.D.); (F.M.); (L.E.M.); (P.O.); (S.S.)
| | - Luca Tiano
- Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy; (E.D.); (F.M.); (L.E.M.); (P.O.); (S.S.)
- Correspondence: ; Tel.: +39-071-220-4394
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Komolafe O, Buzzetti E, Linden A, Best LM, Madden AM, Roberts D, Chase TJ, Fritche D, Freeman SC, Cooper NJ, Sutton AJ, Milne EJ, Wright K, Pavlov CS, Davidson BR, Tsochatzis E, Gurusamy KS. Nutritional supplementation for nonalcohol-related fatty liver disease: a network meta-analysis. Cochrane Database Syst Rev 2021; 7:CD013157. [PMID: 34280304 PMCID: PMC8406904 DOI: 10.1002/14651858.cd013157.pub2] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND The prevalence of non-alcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases risks of liver cirrhosis, hepatocellular carcinoma, and the requirement for liver transplantation. Uncertainty surrounds relative benefits and harms of various nutritional supplements in NAFLD. Currently no nutritional supplement is recommended for people with NAFLD. OBJECTIVES • To assess the benefits and harms of different nutritional supplements for treatment of NAFLD through a network meta-analysis • To generate rankings of different nutritional supplements according to their safety and efficacy SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, the World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021 to identify randomised clinical trials in people with NAFLD. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or status) for people with NAFLD, irrespective of method of diagnosis, age and diabetic status of participants, or presence of non-alcoholic steatohepatitis (NASH). We excluded randomised clinical trials in which participants had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS We performed a network meta-analysis with OpenBUGS using Bayesian methods whenever possible and calculated differences in treatments using hazard ratios (HRs), odds ratios (ORs), and rate ratios with 95% credible intervals (CrIs) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS We included in the review a total of 202 randomised clinical trials (14,200 participants). Nineteen trials were at low risk of bias. A total of 32 different interventions were compared in these trials. A total of 115 trials (7732 participants) were included in one or more comparisons. The remaining trials did not report any of the outcomes of interest for this review. Follow-up ranged from 1 month to 28 months. The follow-up period in trials that reported clinical outcomes was 2 months to 28 months. During this follow-up period, clinical events related to NAFLD such as mortality, liver cirrhosis, liver decompensation, liver transplantation, hepatocellular carcinoma, and liver-related mortality were sparse. We did not calculate effect estimates for mortality because of sparse data (zero events for at least one of the groups in the trial). None of the trials reported that they measured overall health-related quality of life using a validated scale. The evidence is very uncertain about effects of interventions on serious adverse events (number of people or number of events). We are very uncertain about effects on adverse events of most of the supplements that we investigated, as the evidence is of very low certainty. However, people taking PUFA (polyunsaturated fatty acid) may be more likely to experience an adverse event than those not receiving an active intervention (network meta-analysis results: OR 4.44, 95% CrI 2.40 to 8.48; low-certainty evidence; 4 trials, 203 participants; direct evidence: OR 4.43, 95% CrI 2.43 to 8.42). People who take other supplements (a category that includes nutritional supplements other than vitamins, fatty acids, phospholipids, and antioxidants) had higher numbers of adverse events than those not receiving an active intervention (network meta-analysis: rate ratio 1.73, 95% CrI 1.26 to 2.41; 6 trials, 291 participants; direct evidence: rate ratio 1.72, 95% CrI 1.25 to 2.40; low-certainty evidence). Data were sparse (zero events in all groups in the trial) for liver transplantation, liver decompensation, and hepatocellular carcinoma. So, we did not perform formal analysis for these outcomes. The evidence is very uncertain about effects of other antioxidants (antioxidants other than vitamins) compared to no active intervention on liver cirrhosis (HR 1.68, 95% CrI 0.23 to 15.10; 1 trial, 99 participants; very low-certainty evidence). The evidence is very uncertain about effects of interventions in any of the remaining comparisons, or data were sparse (with zero events in at least one of the groups), precluding formal calculations of effect estimates. Data were probably because of the very short follow-up period (2 months to 28 months). It takes follow-up of 8 to 28 years to detect differences in mortality between people with NAFLD and the general population. Therefore, it is unlikely that differences in clinical outcomes are noted in trials providing less than 5 to 10 years of follow-up. AUTHORS' CONCLUSIONS The evidence indicates considerable uncertainty about effects of nutritional supplementation compared to no additional intervention on all clinical outcomes for people with non-alcohol-related fatty liver disease. Accordingly, high-quality randomised comparative clinical trials with adequate follow-up are needed. We propose registry-based randomised clinical trials or cohort multiple randomised clinical trials (study design in which multiple interventions are trialed within large longitudinal cohorts of patients to gain efficiencies and align trials more closely to standard clinical practice) comparing interventions such as vitamin E, prebiotics/probiotics/synbiotics, PUFAs, and no nutritional supplementation. The reason for the choice of interventions is the impact of these interventions on indirect outcomes, which may translate to clinical benefit. Outcomes in such trials should be mortality, health-related quality of life, decompensated liver cirrhosis, liver transplantation, and resource utilisation measures including costs of intervention and decreased healthcare utilisation after minimum follow-up of 8 years (to find meaningful differences in clinically important outcomes).
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Affiliation(s)
| | - Elena Buzzetti
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Audrey Linden
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Lawrence Mj Best
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Angela M Madden
- School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK
| | - Danielle Roberts
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Thomas Jg Chase
- Department of General Surgery, Homerton University Hospital NHS Foundation Trust, London, UK
| | | | - Suzanne C Freeman
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Nicola J Cooper
- Department of Health Sciences, University of Leicester, Leicester, UK
| | - Alex J Sutton
- Department of Health Sciences, University of Leicester, Leicester, UK
| | | | - Kathy Wright
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region of Denmark, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Chavdar S Pavlov
- Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
| | - Brian R Davidson
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Emmanuel Tsochatzis
- Sheila Sherlock Liver Centre, Royal Free Hospital and the UCL Institute of Liver and Digestive Health, London, UK
| | - Kurinchi Selvan Gurusamy
- Division of Surgery and Interventional Science, University College London, London, UK
- Department of Therapy, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
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L-Carnosine Stimulation of Coenzyme Q10 Biosynthesis Promotes Improved Mitochondrial Function and Decreases Hepatic Steatosis in Diabetic Conditions. Antioxidants (Basel) 2021; 10:antiox10050793. [PMID: 34067694 PMCID: PMC8156016 DOI: 10.3390/antiox10050793] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 04/27/2021] [Accepted: 05/11/2021] [Indexed: 11/17/2022] Open
Abstract
Mitochondrial dysfunction in type 2 diabetes leads to oxidative stress, which drives disease progression and diabetes complications. L-carnosine, an endogenous dipeptide, improves metabolic control, wound healing and kidney function in animal models of type 2 diabetes. Coenzyme Q (CoQ), a component of the mitochondrial electron transport chain, possesses similar protective effects on diabetes complications. We aimed to study the effect of carnosine on CoQ, and assess any synergistic effects of carnosine and CoQ on improved mitochondrial function in a mouse model of type 2 diabetes. Carnosine enhanced CoQ gene expression and increased hepatic CoQ biosynthesis in db/db mice, a type 2 diabetes model. Co-administration of Carnosine and CoQ improved mitochondrial function, lowered ROS formation and reduced signs of oxidative stress. Our work suggests that carnosine exerts beneficial effects on hepatic CoQ synthesis and when combined with CoQ, improves mitochondrial function and cellular redox balance in the liver of diabetic mice. (4) Conclusions: L-carnosine has beneficial effects on oxidative stress both alone and in combination with CoQ on hepatic mitochondrial function in an obese type 2 diabetes mouse model.
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Mantle D, Heaton RA, Hargreaves IP. Coenzyme Q10 and Immune Function: An Overview. Antioxidants (Basel) 2021; 10:759. [PMID: 34064686 PMCID: PMC8150987 DOI: 10.3390/antiox10050759] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 04/27/2021] [Accepted: 05/08/2021] [Indexed: 12/13/2022] Open
Abstract
Coenzyme Q10 (CoQ10) has a number of important roles in the cell that are required for optimal functioning of the immune system. These include its essential role as an electron carrier in the mitochondrial respiratory chain, enabling the process of oxidative phosphorylation to occur with the concomitant production of ATP, together with its role as a potential lipid-soluble antioxidant, protecting the cell against free radical-induced oxidation. Furthermore, CoQ10 has also been reported to have an anti-inflammatory role via its ability to repress inflammatory gene expression. Recently, CoQ10 has also been reported to play an important function within the lysosome, an organelle central to the immune response. In view of the differing roles CoQ10 plays in the immune system, together with the reported ability of CoQ10 supplementation to improve the functioning of this system, the aim of this article is to review the current literature available on both the role of CoQ10 in human immune function and the effect of CoQ10 supplementation on this system.
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Affiliation(s)
| | - Robert A. Heaton
- School of Pharmacy, Liverpool John Moores University, Liverpool L3 3AF, UK;
| | - Iain P. Hargreaves
- School of Pharmacy, Liverpool John Moores University, Liverpool L3 3AF, UK;
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Heda R, Yazawa M, Shi M, Bhaskaran M, Aloor FZ, Thuluvath PJ, Satapathy SK. Non-alcoholic fatty liver and chronic kidney disease: Retrospect, introspect, and prospect. World J Gastroenterol 2021; 27:1864-1882. [PMID: 34007127 PMCID: PMC8108029 DOI: 10.3748/wjg.v27.i17.1864] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 03/07/2021] [Accepted: 04/07/2021] [Indexed: 02/06/2023] Open
Abstract
With the growing prevalence of obesity and diabetes in the United States and across the world, a rise in the overall incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) is expected. The risk factors for NAFLD are also associated with the development of chronic kidney disease (CKD). We review the epidemiology, risk factors, genetics, implications of gut dysbiosis, and specific pathogenic mechanisms linking NAFLD to CKD. Mechanisms such as ectopic lipid accumulation, cellular signaling abnormalities, and the interplay between fructose consumption and uric acid accumulation have led to the emergence of potential therapeutic implications for this patient population. Transplant evaluation in the setting of both NAFLD and CKD is also reviewed. Potential strategies for surveillance and management include the monitoring of comorbidities, the use of non-invasive fibrosis scoring systems, and the measurement of laboratory markers. Lastly, we discuss the management of patients with NAFLD and CKD, from preventative measures to experimental interventions.
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Affiliation(s)
- Rajiv Heda
- Department of Internal Medicine, Tulane University School of Medicine, New Orleans, LA 70112, United States
| | - Masahiko Yazawa
- Department of Nephrology and Hypertension, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan
| | - Michelle Shi
- Department of Internal Medicine, Donald and Barbara Zucker School of Medicine, Northwell Health, Manhasset, NY 11030, United States
| | - Madhu Bhaskaran
- Department of Nephrology, Northwell Health/Zucker School of Medicine at Hosftra, Manhasset, NY 11030, United States
| | - Fuad Zain Aloor
- Department of Internal Medicine, Baylor College of Medicine, Houston, TX 77030, United States
| | - Paul J Thuluvath
- Institute of Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore, MD 21202, United States
| | - Sanjaya K Satapathy
- Department of Internal Medicine, Donald and Barbara Zucker School of Medicine, Northwell Health, Manhasset, NY 11030, United States
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40
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Abiri B, Vafa M. Impact of coenzyme Q10 on inflammatory biomarkers and its role in future therapeutic strategies. Clin Nutr ESPEN 2021; 43:25-30. [PMID: 34024523 DOI: 10.1016/j.clnesp.2021.04.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/12/2021] [Accepted: 04/07/2021] [Indexed: 11/15/2022]
Abstract
Coenzyme Q (CoQ) is an important component of the mitochondrial electron transport chain. The finding that multiple chronic diseases show lower levels of CoQ10 has led to the possibility that CoQ10 supplementation could be an effective approach to ameliorate or prevent disease progression. In this review, we discuss the state of the art regarding the role of CoQ10 in health and disease and describe the latest clinical studies which have tested the effects of CoQ10 supplementation in inflammatory diseases. The results of these studies indicate that individuals suffering from inflammation-related diseases show improvement under the CoQ10 supplementation protocol. However, these results have been inconsistent, leading to the need for additional studies at the preclinical and clinical levels, involving a greater number of subjects and different treatment regimes.
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Affiliation(s)
- Behnaz Abiri
- Nutritional Sciences, Department of Nutrition, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammadreza Vafa
- Nutritional Sciences, Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.
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41
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Zozina VI, Covantev S, Kukes VG, Corlateanu A. Coenzyme Q10 in COPD: An Unexplored Opportunity? COPD 2021; 18:114-122. [PMID: 33441012 DOI: 10.1080/15412555.2020.1849084] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 11/04/2020] [Accepted: 11/06/2020] [Indexed: 02/08/2023]
Abstract
COPD represents a major cause of mortality and morbidity worldwide, is linked to systemic inflammation and tends to coexist with a variety of comorbidities. Inflammation, oxidative stress and protease-antiprotease imbalance represent the pathogenic triad of COPD. Even though oxidative stress and mitochondrial dysfunction is a well-studied phenomenon in COPD and there is a variety of studies that aim to counteract its effect, there is limited data available on the use of coenzyme Q10 in COPD. The aim of the current review is to analyze the current data on the use of coenzyme Q10 in the management of COPD and frequently encountered comorbidities.
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Affiliation(s)
- V I Zozina
- Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
| | - S Covantev
- Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation
| | - V G Kukes
- Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
| | - A Corlateanu
- Department of Respiratory Medicine, State University of Medicine and Pharmacy N. Testemitanu, Chisinau, Republic of Moldova
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42
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Ghavami A, Mohammadi H, Hadi A, Ziaei R, Nattagh-Eshtivani E, Sheykhrobat MV, Askari G. Effects of Coenzyme Q10 Supplementation on Anthropometric Indices in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Int J Prev Med 2021; 11:181. [PMID: 33456737 PMCID: PMC7804873 DOI: 10.4103/ijpvm.ijpvm_179_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2019] [Accepted: 09/14/2019] [Indexed: 11/30/2022] Open
Abstract
Background: Obesity is related to increase in the incidence of morbidity and mortality. Previous studies have led to conflicting results regarding the effect of coenzyme Q10 (CoQ10) supplementation on anthropometric indices. This study aimed to evaluate the efficacy of CoQ10 supplementation on body weight, body mass index (BMI), and waist circumference (WC) through a systematic review and meta-analysis of randomized controlled trials (RCTs). Methods: PubMed, Scopus, Web of Science, and Cochrane Library as well as the reference lists of the identified relevant RCTs were searched up to March 2019, and weighted mean differences (WMDs) were pooled by using the random-effects model. Results: Twenty RCTs (976 participants) were eligible to be included in the systematic review. The meta-analysis revealed that CoQ10 supplementation had no effect on body weight (WMD = −0.04 kg; 95% confidence interval [CI]: −1.96, 1.6; I2 = 0.0%), BMI (WMD = −0.06 kg/m2; 95% CI: −0.54, 0.42; I2 = 0.0%), and WC (WMD = 0.79 cm; 95% CI: −2.83, 0.04; I2 = 0.0%). Conclusions: CoQ10 supplementation might not improve anthropometric indices. Future well-designed trials are still needed to confirm these results.
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Affiliation(s)
- Abed Ghavami
- Student Research Committee, Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hamed Mohammadi
- Department of Community Nutrition, Food Security Research Center, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amir Hadi
- Halal Research Center of IRI, FDA, Tehran, Iran
| | - Rahele Ziaei
- Department of Community Nutrition, Food Security Research Center, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | | | - Gholamreza Askari
- Department of Community Nutrition, Food Security Research Center, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
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Taghizadeh S, Izadi A, Shirazi S, Parizad M, Pourghassem Gargari B. The effect of coenzyme Q10 supplementation on inflammatory and endothelial dysfunction markers in overweight/obese polycystic ovary syndrome patients. Gynecol Endocrinol 2021; 37:26-30. [PMID: 32544011 DOI: 10.1080/09513590.2020.1779689] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
Abstract
BACKGROUND This study aimed at determining the effects of coenzyme Q10 (CoQ10) supplementation on the inflammatory and endothelial dysfunction indices among overweight and obese women with polycystic ovary syndrome (PCOS). METHODS This randomized double-blind, placebo-controlled clinical trial was performed among overweight and obese women diagnosed with PCOS. Forty three PCOS women were randomly assigned to two groups: one group received 200 mg CoQ10 capsules per day (n = 22) and the other received placebo (n = 21) for 8 weeks. Biomarkers of inflammation and endothelial dysfunction including high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin were measured and compared before and after the intervention. RESULTS At the end of study, compared with pldacebo, CoQ10 supplementation resulted in significant decreases in serum levels of TNF-α (p = 0.009), hs-CRP and IL-6 (p = 0.001, p = 0.007, respectively). In addition, supplementation with CoQ10 resulted in a significant reduction in serum VCAM-1 (p = .002) and E-selectin (p = .006) compared with the control group. There were no significant differences for serum ICAM-1. CONCLUSIONS The present study showed that CoQ10 supplementation for 8 weeks had a beneficial effect on inflammatory and endothelial dysfunction markers in overweight and obese patients with PCOS.
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Affiliation(s)
- Shiva Taghizadeh
- Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Azimeh Izadi
- Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Shabnam Shirazi
- Department of Biochemistry and Diet Therapy, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Marziyeh Parizad
- Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Bahram Pourghassem Gargari
- 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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Zhang P, Chen S, Tang H, Fang W, Chen K, Chen X. CoQ10 protects against acetaminophen-induced liver injury by enhancing mitophagy. Toxicol Appl Pharmacol 2020; 410:115355. [PMID: 33271250 DOI: 10.1016/j.taap.2020.115355] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 11/11/2020] [Accepted: 11/26/2020] [Indexed: 12/24/2022]
Abstract
Coenzyme Q10 (CoQ10), which is a key cofactor of the electron transport chain in the mitochondria has shown many beneficial effects on liver diseases. However, the mechanisms of CoQ10 protective role on the acetaminophen (APAP)-induced liver injury are elusive and unclear. In this study, we further investigated the CoQ10 therapeutic effects on APAP-overdose liver injury. C57BL/6 J mice were intraperitoneally treated with APAP to induce liver injury. CoQ10 (5 mg/kg) was given to mice at 1.5 h after APAP treatment. The results showed that hepatic CoQ10 levels were decreased during the APAP-induced hepatotoxicity and preceded serum ALT elevation. Treatment of CoQ10 significantly improved the liver injury induced by APAP. Moreover, CoQ10 treatment decreased the ROS levels and promoted the antioxidative related gene expression in APAP overdose mice. Importantly, results showed that even though CoQ10 had no effects on the mtDNA copy number and the expression of genes related to mitochondrial biogenesis, it significantly improved the mitochondrial complex I and V activities and promoted the mitophagy in APAP-overdose mice. To further authenticate mitophagy role in CoQ10-mediated improved liver injury in vivo, we administrated APAP-overdose mice with chloroquine 1 h prior to APAP treatment and found that chloroquine treatment functionally abrogated the CoQ10 protective role on APAP overdose mice. To conclude, this study provides evidence that CoQ10 activates mitophagy to protect against APAP-induced liver injury. Therefore, CoQ10 may represent a novel therapeutic option for the prevention and treatment of drug-induced liver injury.
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Affiliation(s)
- Peiwen Zhang
- Department of Nutrition, School of Public Health, Guangdong Medical University, People's Republic of China; School of Public Health, Dongguan Key Laboratory of Environmental Medicine, Guangdong Medical University, People's Republic of China
| | - Shen Chen
- Department of Nutrition, School of Public Health, Guangdong Medical University, People's Republic of China; Department of Toxicology, School of Public Health, Sun Yat-sen University, People's Republic of China
| | - Huanwen Tang
- School of Public Health, Dongguan Key Laboratory of Environmental Medicine, Guangdong Medical University, People's Republic of China
| | - Wanjun Fang
- Department of Clinical Nutrition, Ningbo Women and Children's Hospital, Ningbo, People's Republic of China
| | - Ke Chen
- Department of Clinical Nutrition, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, People's Republic of China; Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Xu Chen
- Department of Nutrition, School of Public Health, Guangdong Medical University, People's Republic of China; Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People's Republic of China.
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45
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Gutierrez-Mariscal FM, Arenas-de Larriva AP, Limia-Perez L, Romero-Cabrera JL, Yubero-Serrano EM, López-Miranda J. Coenzyme Q 10 Supplementation for the Reduction of Oxidative Stress: Clinical Implications in the Treatment of Chronic Diseases. Int J Mol Sci 2020; 21:ijms21217870. [PMID: 33114148 PMCID: PMC7660335 DOI: 10.3390/ijms21217870] [Citation(s) in RCA: 91] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 10/15/2020] [Accepted: 10/22/2020] [Indexed: 02/06/2023] Open
Abstract
Apart from its main function in the mitochondria as a key element in electron transport, Coenzyme Q10 (CoQ10) has been described as having multiple functions, such as oxidant action in the generation of signals and the control of membrane structure and phospholipid and cellular redox status. Among these, the most relevant and most frequently studied function is the potent antioxidant capability of its coexistent redox forms. Different clinical trials have investigated the effect of CoQ10 supplementation and its ability to reduce oxidative stress. In this review, we focused on recent advances in CoQ10 supplementation, its role as an antioxidant, and the clinical implications that this entails in the treatment of chronic diseases, in particular cardiovascular diseases, kidney disease, chronic obstructive pulmonary disease, non-alcoholic fatty liver disease, and neurodegenerative diseases. As an antioxidant, CoQ10 has proved to be of potential use as a treatment in diseases in which oxidative stress is a hallmark, and beneficial effects of CoQ10 have been reported in the treatment of chronic diseases. However, it is crucial to reach a consensus on the optimal dose and the use of different formulations, which vary from ubiquinol or ubiquinone Ubisol-Q10 or Qter®, to new analogues such as MitoQ, before we can draw a clear conclusion about its clinical use. In addition, a major effort must be made to demonstrate its beneficial effects in clinical trials, with a view to making the implementation of CoQ10 possible in clinical practice.
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Affiliation(s)
- Francisco Miguel Gutierrez-Mariscal
- Unidad de Gestión Clinica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, Spain; (F.M.G.-M.); (A.P.A.-d.L.); (L.L.-P.); (J.L.R.-C.)
- CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, 28029 Madrid, Spain
| | - Antonio Pablo Arenas-de Larriva
- Unidad de Gestión Clinica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, Spain; (F.M.G.-M.); (A.P.A.-d.L.); (L.L.-P.); (J.L.R.-C.)
- CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, 28029 Madrid, Spain
| | - Laura Limia-Perez
- Unidad de Gestión Clinica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, Spain; (F.M.G.-M.); (A.P.A.-d.L.); (L.L.-P.); (J.L.R.-C.)
- CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, 28029 Madrid, Spain
| | - Juan Luis Romero-Cabrera
- Unidad de Gestión Clinica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, Spain; (F.M.G.-M.); (A.P.A.-d.L.); (L.L.-P.); (J.L.R.-C.)
- CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, 28029 Madrid, Spain
| | - Elena Maria Yubero-Serrano
- Unidad de Gestión Clinica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, Spain; (F.M.G.-M.); (A.P.A.-d.L.); (L.L.-P.); (J.L.R.-C.)
- CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, 28029 Madrid, Spain
- Correspondence: (E.M.Y.-S.); (J.L.-M.); Tel.: +34-957213733 (E.M.Y.-S.); +34-957010947 (J.L.-M.); Fax: +34-957218250 (J.L.-M.)
| | - Jose López-Miranda
- Unidad de Gestión Clinica Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, Spain; (F.M.G.-M.); (A.P.A.-d.L.); (L.L.-P.); (J.L.R.-C.)
- CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, 28029 Madrid, Spain
- Correspondence: (E.M.Y.-S.); (J.L.-M.); Tel.: +34-957213733 (E.M.Y.-S.); +34-957010947 (J.L.-M.); Fax: +34-957218250 (J.L.-M.)
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Curcio A, Romano A, Cuozzo S, Di Nicola A, Grassi O, Schiaroli D, Nocera GF, Pironti M. Silymarin in Combination with Vitamin C, Vitamin E, Coenzyme Q10 and Selenomethionine to Improve Liver Enzymes and Blood Lipid Profile in NAFLD Patients. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:E544. [PMID: 33080906 PMCID: PMC7603183 DOI: 10.3390/medicina56100544] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 10/07/2020] [Accepted: 10/13/2020] [Indexed: 02/07/2023]
Abstract
Background and Objectives: Non-Alcoholic Fatty Liver Disease (NAFLD) is an emerging cause of hepatopathy that is showing an increasing trend and where the recommendations of lifestyle modification are often not sufficient. The aim of this study is to evaluate the efficacy and tolerability profile of the association of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®) by analyzing liver enzymes, along with the lipidic profile, as markers of liver function, and ultrasound results in NAFLD patients. Materials and Methods: This study enrolled 81 patients with mild to severe NAFLD, divided into two groups: Group A (N = 41) received two capsules a day of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®), and Group B (N = 40) received only recommendations for lifestyle modification including hypocaloric diet, physical exercise and encouragement for weight loss. Patients have been evaluated at three timepoints: baseline (T0), after 45 days of treatment (T1) and after 90 days of treatment (T2), by collecting blood parameters of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and the lipid blood profile. Ultrasonographic results have been analyzed at T0 and T2, along with the tolerability profile and side effects, registered at time T2. Results: The administration of the association of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®) was effective since it showed a significant reduction of the evaluated parameters of ALT, AST, ALP and GGT, a significant improvement of lipid parameters, evaluated as markers of liver function, and improvements of ultrasonographic results. The use of this formulation at the dosage of two capsules a day has been well tolerated and no adverse events have been reported during study period of three months. Conclusions: The administration of the association of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®) was effective and well tolerated in the improvement of hepatic function of NAFLD patients.
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Affiliation(s)
| | - Adriana Romano
- Medical Department, Merqurio Pharma S.r.l., 80138 Naples, Italy; (A.R.); (S.C.)
| | - Simona Cuozzo
- Medical Department, Merqurio Pharma S.r.l., 80138 Naples, Italy; (A.R.); (S.C.)
| | - Antonio Di Nicola
- Infectious Disease Department, Cardarelli Public Hospital, 86100 Campobasso, Italy; (A.D.N.); (O.G.)
| | - Orazio Grassi
- Infectious Disease Department, Cardarelli Public Hospital, 86100 Campobasso, Italy; (A.D.N.); (O.G.)
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Disorders of Human Coenzyme Q10 Metabolism: An Overview. Int J Mol Sci 2020; 21:ijms21186695. [PMID: 32933108 PMCID: PMC7555759 DOI: 10.3390/ijms21186695] [Citation(s) in RCA: 93] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 09/08/2020] [Accepted: 09/11/2020] [Indexed: 12/11/2022] Open
Abstract
Coenzyme Q10 (CoQ10) has a number of vital functions in all cells, both mitochondrial and extramitochondrial. In addition to its key role in mitochondrial oxidative phosphorylation, CoQ10 serves as a lipid soluble antioxidant, plays an important role in fatty acid, pyrimidine and lysosomal metabolism, as well as directly mediating the expression of a number of genes, including those involved in inflammation. In view of the central role of CoQ10 in cellular metabolism, it is unsurprising that a CoQ10 deficiency is linked to the pathogenesis of a range of disorders. CoQ10 deficiency is broadly classified into primary or secondary deficiencies. Primary deficiencies result from genetic defects in the multi-step biochemical pathway of CoQ10 synthesis, whereas secondary deficiencies can occur as result of other diseases or certain pharmacotherapies. In this article we have reviewed the clinical consequences of primary and secondary CoQ10 deficiencies, as well as providing some examples of the successful use of CoQ10 supplementation in the treatment of disease.
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Coenzyme Q 10 Supplementation Improves Adipokine Levels and Alleviates Inflammation and Lipid Peroxidation in Conditions of Metabolic Syndrome: A Meta-Analysis of Randomized Controlled Trials. Int J Mol Sci 2020; 21:ijms21093247. [PMID: 32375340 PMCID: PMC7247332 DOI: 10.3390/ijms21093247] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 04/29/2020] [Accepted: 04/29/2020] [Indexed: 12/12/2022] Open
Abstract
Evidence from randomized controlled trials (RCTs) suggests that coenzyme Q10 (CoQ10) can regulate adipokine levels to impact inflammation and oxidative stress in conditions of metabolic syndrome. Here, prominent electronic databases such as MEDLINE, Cochrane Library, and EMBASE were searched for eligible RCTs reporting on any correlation between adipokine levels and modulation of inflammation and oxidative stress in individuals with metabolic syndrome taking CoQ10. The risk of bias was assessed using the modified Black and Downs checklist, while the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to evaluate the quality of evidence. Results from the current meta-analysis, involving 318 participants, showed that CoQ10 supplementation in individuals with metabolic syndrome increased adiponectin levels when compared to those on placebo (SMD: 1.44 [95% CI: -0.13, 3.00]; I2 = 96%, p < 0.00001). Moreover, CoQ10 supplementation significantly lowered inflammation markers in individuals with metabolic syndrome in comparison to those on placebo (SMD: -0.31 [95% CI: -0.54, -0.08]; I2 = 51%, p = 0.07). Such benefits with CoQ10 supplementation were related to its ameliorative effects on lipid peroxidation by reducing malondialdehyde levels, concomitant to improving glucose control and liver function. The overall findings suggest that optimal regulation of adipokine function is crucial for the beneficial effects of CoQ10 in improving metabolic health.
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Martelli A, Testai L, Colletti A, Cicero AFG. Coenzyme Q 10: Clinical Applications in Cardiovascular Diseases. Antioxidants (Basel) 2020; 9:antiox9040341. [PMID: 32331285 PMCID: PMC7222396 DOI: 10.3390/antiox9040341] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 04/18/2020] [Accepted: 04/20/2020] [Indexed: 02/06/2023] Open
Abstract
Coenzyme Q10 (CoQ10) is a ubiquitous factor present in cell membranes and mitochondria, both in its reduced (ubiquinol) and oxidized (ubiquinone) forms. Its levels are high in organs with high metabolism such as the heart, kidneys, and liver because it acts as an energy transfer molecule but could be reduced by aging, genetic factors, drugs (e.g., statins), cardiovascular (CV) diseases, degenerative muscle disorders, and neurodegenerative diseases. As CoQ10 is endowed with significant antioxidant and anti-inflammatory features, useful to prevent free radical-induced damage and inflammatory signaling pathway activation, its depletion results in exacerbation of inflammatory processes. Therefore, exogenous CoQ10 supplementation might be useful as an adjuvant in the treatment of cardiovascular diseases such as heart failure, atrial fibrillation, and myocardial infarction and in associated risk factors such as hypertension, insulin resistance, dyslipidemias, and obesity. This review aims to summarize the current evidences on the use of CoQ10 supplementation as a therapeutic approach in cardiovascular diseases through the analysis of its clinical impact on patients' health and quality of life. A substantial reduction of inflammatory and oxidative stress markers has been observed in several randomized clinical trials (RCTs) focused on several of the abovementioned diseases, even if more RCTs, involving a larger number of patients, will be necessary to strengthen these interesting findings.
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Affiliation(s)
- Alma Martelli
- Department of Pharmacy, University of Pisa, 56120 Pisa, Italy; (A.M.); (L.T.)
- Interdepartmental Research Centre “Nutraceuticals and Food for Health (NUTRAFOOD)”, University of Pisa, 56120 Pisa, Italy
- Interdepartmental Research Centre of Ageing, Biology and Pathology, University of Pisa, 56120 Pisa, Italy
| | - Lara Testai
- Department of Pharmacy, University of Pisa, 56120 Pisa, Italy; (A.M.); (L.T.)
- Interdepartmental Research Centre “Nutraceuticals and Food for Health (NUTRAFOOD)”, University of Pisa, 56120 Pisa, Italy
- Interdepartmental Research Centre of Ageing, Biology and Pathology, University of Pisa, 56120 Pisa, Italy
| | - Alessandro Colletti
- Department of Science and Drug Technology, University of Turin, 10125 Turin, Italy;
- Italian Nutraceutical Society (SINut), Via Guelfa 9, 40138 Bologna, Italy
| | - Arrigo F. G. Cicero
- Italian Nutraceutical Society (SINut), Via Guelfa 9, 40138 Bologna, Italy
- Medical and Surgical Sciences Department, University of Bologna, 40126 Bologna, Italy
- Correspondence: ; Tel.: +39-512142224
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Elshazly SM, Alsemeh AE, Ahmad EAA, Rezq S. CoQ10 exerts hepatoprotective effect in fructose-induced fatty liver model in rats. Pharmacol Rep 2020; 72:922-934. [PMID: 32157594 DOI: 10.1007/s43440-020-00075-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2019] [Revised: 11/02/2019] [Accepted: 12/30/2019] [Indexed: 12/27/2022]
Abstract
BACKGROUND Excess dietary sugar is associated with deleterious metabolic effects, liver injury, and coenzyme-Q10 (CoQ10) deficiency. This study investigates the ability of CoQ10 to protect against fructose-induced hepatic damage. METHODS Rats were fed tap water or 30% fructose for 12 weeks with or without CoQ10 (10 mg/kg, po). An additional group of rats were allowed to feed on either water or 30% fructose for 12 weeks, followed by four weeks of treatment with either the vehicle or CoQ10. RESULTS Fructose-fed rats showed lower CoQ10 levels, increased systolic pressure, increased body weight, higher liquid consumption, decreased food intake and hyperglycemia. Fructose-fed rats also showed deteriorated serum and liver lipid profiles, impaired liver function tests and oxidative status, and lower expression of adiponectin receptor 1 and 2 along with higher GLUT-2 levels. Furthermore, following fructose treatment, tyrosine kinase-PI3K pathway was inhibited. Additionally, there was an increase in the levels of apoptotic markers and serum visfatin and a decrease in the levels of adiponectin and soluble receptor of the advanced glycated end product. Consequently, several histopathological changes were detected in the liver. Concurrent or three months post-exposure administration of CoQ10 in fructose rats significantly reversed or attenuated all the measured parameters and hepato-cytoarchitecture alterations. CONCLUSION This study suggests CoQ10 supplement as a possible prophylaxis or treatment candidate for fructose-induced liver injury.
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Affiliation(s)
- Shimaa M Elshazly
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
| | - Amira E Alsemeh
- Department of Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Enssaf A A Ahmad
- Department of Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Samar Rezq
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt. .,Department of Cell and Molecular Biology, UMMC, 2500 N state St., Jackson, MS, 39216, USA.
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