포도씨 (순환)

The effect of grape (Vitis vinifera) seed extract supplementation on flow-mediated dilation, blood pressure, and heart rate: A systematic review and meta-analysis of controlled trials with duration- and dose-response analysis.

1. Pharmacol Res. 2022 Jan;175:105905. doi: 10.1016/j.phrs.2021.105905. Epub 2021 Nov 17. The effect of grape (Vitis vinifera) seed extract supplementation on flow-mediated dilation, blood pressure, and heart rate: A systematic review and meta-analysis of controlled trials with duration- and dos

Influence of Diet in Multiple Sclerosis: A Systematic Review.

2. Adv Nutr. 2017 May 15;8(3):463-472. doi: 10.3945/an.116.014191. Print 2017 May. Influence of Diet in Multiple Sclerosis: A Systematic Review. Bagur MJ(1), Murcia MA(2)(3), Jiménez-Monreal AM(2)(3), Tur JA(3)(4), Bibiloni MM(3)(4), Alonso GL(1), Martínez-Tomé M(5)(3). Author information: (1)De

Overall Survival of Glioblastoma Patients Treated With a Combination of 7 Micronutrients: A Nutraceutical Trial.

1. Anticancer Res. 2026 Mar;46(3):1599-1608. doi: 10.21873/anticanres.18055. Overall Survival of Glioblastoma Patients Treated With a Combination of 7 Micronutrients: A Nutraceutical Trial. Rooprai HK(1), Lawrence P(2), Ashkan K(3), Beaney R(4), Pilkington GJ(5), Gullan RW(1). Author information: (1)Department of Neurosurgery, King's College Hospital, London, U.K. (2)Division of Molecular Pathology, The Institute of Cancer Research, Sutton, U.K. (3)Department of Neurosurgery, King's College Hospital, London, U.K.; k.ashkan@nhs.net. (4)Department of Oncology, St Thomas' Hospital, London, U.K. (5)Brain Tumour Research Centre, University of Portsmouth, Portsmouth, U.K. BACKGROUND/AIM: There is increasing evidence for recognition of nutraceuticals as anti-tumour agents in various cancers. Over the years, anecdotal reports and our laboratory-based research have indicated their promising therapeutic potential for the management of glioblastoma. The aim of this study was to assess the effect of a combination of 7 micronutrients on overall survival of these patients. PATIENTS AND METHODS: A Nutraceutical study was conducted at King's College and St Thomas' Hospitals, London. Fifty-three newly diagnosed patients (37 males and 16 females) with glioblastoma were recruited consecutively in this randomised entry, double blind Phase II trial. The treatment (containing chokeberry extract, red grape seed extract, red clover extract, curcumin, selenium, tangeretin and lycopene) was given to two-thirds of the patients for 1 year after neurosurgery. This was consistent with the start date of their concomitant Stupp Protocol chemoradiation therapy. The patients in the placebo group had identical capsules which contained lactose only. RESULTS: Although the Kaplan - Meier analysis showed that the overall survival for the active and placebo groups was 14 and 13 months respectively, the results were not statistically significant (p=0.752). CONCLUSION: This study has limitations but it acts as a proof of principle towards larger studies, as clearly sufficiently powered trials are crucial in determining the nature and size of the treatment effect. Future trials should consider subgroup analysis, with respect to such factors as patient's age at diagnosis, gender, extent of surgery, MGMT mutation and IDH status to identify the optimal responders. Copyright © 2026 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. DOI: 10.21873/anticanres.18055 PMID: 41760279 [Indexed for MEDLINE]

Effects of grape seed extract supplementation on inflammatory biomarkers, oxidative stress, clinical symptoms, and quality of life in patients with migraine: A double-blinded randomized placebo-controlled clinical trial.

2. J Res Med Sci. 2025 Dec 30;30:65. doi: 10.4103/jrms.jrms_742_25. eCollection 2025. Effects of grape seed extract supplementation on inflammatory biomarkers, oxidative stress, clinical symptoms, and quality of life in patients with migraine: A double-blinded randomized placebo-controlled clinical trial. Eshaghian N(1), Sadeghi O(2), Foroghi A(3), Khorvash F(4), Askari G(2). Author information: (1)Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran. (2)Nutrition and Food Security Research Center, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran. (3)Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. (4)Neurosciences Research Center, Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. BACKGROUND: The current study was conducted to assess the effect of grape seed extract (GSE) supplementation on inflammatory biomarkers, oxidative stress, clinical symptoms, and quality of life in migraine patients. MATERIALS AND METHODS: In this randomized double-blinded controlled clinical trial, 50 patients with migraine were randomly allocated to receive either 200 mg/day GSE supplement (n = 25) or placebo (n = 25) for 8 weeks. Severity, frequency and duration of migraine attacks, headache daily result (HDR), quality of life, migraine disability, mental health, anthropometric indices, blood pressure, and serum levels of calcitonin gene-related peptide (CGRP), vascular cell adhesion molecules-1, total antioxidant capacity, and malondialdehyde were measured at baseline and end of the trial. RESULTS: Based on the within-group comparison, patients in the GSE group had a significant reduction in severity, frequency and duration of migraine attacks, HDR, migraine disability, systolic blood pressure, and serum levels of CGRP. GSE group also had better scores in the migraine-specific quality of life questionnaire and mental health questionnaire. When we performed the analysis using the univariate analysis of variance, the effect of GSE on serum CGRP levels (-0.07 ± 0.03 in the GSE group vs. 0.07 ± 0.03 in the placebo group, P = 0.003) remained significant. CONCLUSION: This study provides evidence supporting the beneficial effects of GSE supplement on the serum levels of CGRP. TRIAL REGISTRATION: IRCT20121216011763N56. Copyright: © 2025 Journal of Research in Medical Sciences. DOI: 10.4103/jrms.jrms_742_25 PMCID: PMC12860465 PMID: 41623439 Conflict of interest statement: There are no conflicts of interest.

Effect of 7-day dietary supplementation with grape seed extract on cardiac autonomic and hemodynamic responses in elevated and stage 1 hypertension.

3. Clin Physiol Funct Imaging. 2025 May;45(3):e70010. doi: 10.1111/cpf.70010. Effect of 7-day dietary supplementation with grape seed extract on cardiac autonomic and hemodynamic responses in elevated and stage 1 hypertension. Lira A(1), Boyer W(1), Gillum T(1), Sullivan S(1), Kim JK(1). Author information: (1)Department of Kinesiology, California Baptist University, Riverside, California, USA. BACKGROUNDS: Evidence indicated that an increase in nitric oxide (NO) bioavailability via dietary supplementation decreased sympathetic output. Grape seed extract (GSE) supplement has been known to increase NO production and improve endothelial function in individuals with elevated and stage 1 hypertension (ES1H), but no studies have assessed the effects of this extract on autonomic balance. Accordingly, the aim of the study was to investigate the effect of 7 days of dietary GSE supplementation on cardiac autonomic and hemodynamic responses. METHODS: Ten males were recruited in this study. Each subject received GSE or placebo supplementation with a 1-week wash-out period. In a double-blinded, cross-over design, hemodynamic responses (heart rate (HR), stroke volume (SV), cardiac output (CO), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean atrial pressure (MAP)), heart rate variability (HRV), and cold pressor test (CPT) were compared before and after either GSE or placebo supplementation. RESULTS: Our results indicated that GSE decreased resting DBP (75 ± 2 vs. 71 ± 3) and MAP (91 ± 2 vs. 88 ± 3) compared to the placebo (DBP:71 ± 3 vs. 74 ± 3; MAP: 89 ± 2 vs. 90 ± 2). However, MAP responses to CPT had no difference between post-PL and post-GSE supplementation when expressed as absolute increases (PL, Δ10.3 ± 1 mmHg, GSE, Δ9.1 ± 1 mmHg). There were no differences on the HR, SV, CO, SBP, and HRV between placebo and GSE treatments. CONCLUSIONS: Our study suggests that GSE can be used as a dietary nutraceutical capable of reducing blood pressure and the risk of ES1H development. The reduction of blood pressure occurs via peripheral vasodilation, not associated with cardiac autonomic reactivity. © 2025 The Author(s). Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine. DOI: 10.1111/cpf.70010 PMCID: PMC12059611 PMID: 40341867 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Vitamin E ameliorates blood cholesterol level and alters gut microbiota composition: A randomized controlled trial.

4. Nutr Metab Cardiovasc Dis. 2025 Aug;35(8):103964. doi: 10.1016/j.numecd.2025.103964. Epub 2025 Feb 25. Vitamin E ameliorates blood cholesterol level and alters gut microbiota composition: A randomized controlled trial. Chen B(1), Li Y(2), Li Z(3), Hu X(4), Zhen H(3), Chen H(3), Nie C(3), Hou Y(3), Zhu S(5), Xiao L(3), Li T(6). Author information: (1)School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China; BGI Genomics, Shenzhen, China. (2)BGI Genomics, Shenzhen, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China. (3)BGI Research, Shenzhen, China. (4)Department of Gastrointestinal Surgery, Hebei General Hospital, Shijiazhuang, China. (5)BGI Genomics, Shenzhen, China. (6)BGI Genomics, Shenzhen, China; BGI Research, Shenzhen, China. Electronic address: litao2@genomics.cn. BACKGROUND AND AIMS: Antioxidants, including vitamin E (VE) and grape seed extract (GSE), as anti-aging supplementation have been widely used to improve human health. The gut microbiota plays a crucial role in health and affects the treatment effect of various interventions. However, the role of gut microbiota in VE remains unclear. This study aimed to assess the longitudinal impact of VE treatment on body health and the gut microbiota. METHODS AND RESULTS: A randomized controlled trial was conducted with 90 healthy individuals. The participants were randomly assigned to three groups: a treatment group receiving VE, another antioxidant treatment group receiving GSE, and a control group receiving a placebo. We found that VE ameliorated blood cholesterol levels by reducing the levels of low-density lipoprotein cholesterol (LDL-C) in healthy volunteers. After the intervention, there was an increase in the relative abundance of short-chain fatty acid (SCFA)-producing bacteria and bile acid metabolizers. Specifically, the abundances of Lachnospira sp. and Faecalibacterium spp. increased in the VE. Interestingly, the gut microbiota of poor responders harbored a greater proportion of disease-associated bacterial species. CONCLUSIONS: VE could promote health by lowering LDL-C, partly and indirectly by affecting gut bacteria with the ability to produce SCFAs or metabolize bile acids. REGISTRATION NUMBER FOR CLINICAL TRIALS: The clinical trial was registered on August 28, 2021. Registration number was ChiCTR2100050567 (https://www.chictr.org.cn). Copyright © 2025 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved. DOI: 10.1016/j.numecd.2025.103964 PMID: 40087044 [Indexed for MEDLINE]

The effects of grape seed extract supplementation on cardiovascular risk factors, liver enzymes and hepatic steatosis in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study.

5. BMC Complement Med Ther. 2024 May 16;24(1):192. doi: 10.1186/s12906-024-04477-3. The effects of grape seed extract supplementation on cardiovascular risk factors, liver enzymes and hepatic steatosis in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study. Ghanbari P(1), Raiesi D(2), Alboebadi R(1), Zarejavid A(3), Dianati M(4)(5), Razmi H(6), Bazyar H(7)(8). Author information: (1)Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. (2)Department of Internal Medicine, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. (3)Nutrition and Metabolic Diseases Research Center, Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. (4)School of Medical and Life Sciences, Sunway University, Sunway City, Malaysia. (5)Department of Complex Genetics and Epidemiology, School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands. (6)Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Hamidrezarazmi95@gmail.com. (7)Department of Public Health, Sirjan School of Medical Sciences, Sirjan, Iran. hadibazyar2015@gmail.com. (8)Student Research Committee, Sirjan School of Medical Sciences, Sirjan, Iran. hadibazyar2015@gmail.com. BACKGROUND: Despite the high antioxidant potential of grape seed extract (GSE), very limited studies have investigated its effect on non-alcoholic fatty liver disease (NAFLD). Therefore, this study was conducted with the aim of investigating the effect of GSE on metabolic factors, blood pressure and steatosis severity in patients with NAFLD. METHODS: In this double-blind randomized clinical trial study, 50 NAFLD patients were divided into two groups of 25 participants who were treated with 520 mg/day of GSE or the placebo group for 2 months. The parameters of glycemic, lipid profile, blood pressure and steatohepatitis were measured before and after the intervention. RESULTS: The GSE group had an average age of 43.52 ± 8.12 years with 15 women and 10 men, while the placebo group had an average age of 44.88 ± 10.14 years with 11 women and 14 men. After 2 months of intervention with GSE, it was observed that insulin, HOMA-IR, TC, TG, LDL-c, ALT, AST, AST/ALT, SBP, DBP and MAP decreased and QUICKi and HDL-c increased significantly (p-value for all < 0.05). Also, before and after adjustment based on baseline, the average changes indicated that the levels of insulin, HOMA-IR, TC, TG, LDL-c, SBP, DBP, MAP in the GSE group decreased more than in the control group (p for all < 0.05). Furthermore, the changes in HDL-c were significantly higher in the GSE group (p < 0.05). The between-groups analysis showed a significant decrease in the HOMA-β and AST before and after adjustment based on baseline levels (p < 0.05). Moreover, the changes in QUICKi after adjustment based on baseline levels were higher in the GSE group than in the control group. Also, between-groups analysis showed that the severity of hepatic steatosis was reduced in the intervention group compared to the placebo group (P = 0.002). CONCLUSIONS: It seems that GSE can be considered one of the appropriate strategies for controlling insulin resistance, hyperlipidemia, hypertension and hepatic steatosis in NAFLD patients. TRIAL REGISTRATION: The clinical trial was registered in the Iranian Clinical Trial Registration Center (IRCT20190731044392N1). https://irct.behdasht.gov.ir/trial/61413 . (The registration date: 30/03/2022). © 2024. The Author(s). DOI: 10.1186/s12906-024-04477-3 PMCID: PMC11100156 PMID: 38755622 [Indexed for MEDLINE] Conflict of interest statement: The authors declared no conflict of interest.

Re-Esterified Triglyceride ω-3 Fatty Acids in Dry Eye Disease With Meibomian Gland Dysfunction: A Randomized Clinical Trial.

6. JAMA Ophthalmol. 2024 Jul 1;142(7):617-624. doi: 10.1001/jamaophthalmol.2024.1482. Re-Esterified Triglyceride ω-3 Fatty Acids in Dry Eye Disease With Meibomian Gland Dysfunction: A Randomized Clinical Trial. Eom Y(1)(2), Jun I(3)(4), Jeon HS(5)(6), Lim DH(7), Lee H(8), Hwang HS(9), Chung SH(10), Chung TY(7), Kim JY(8), Kim SW(11), Choi CY(12), Song JS(1)(13), Kim MK(5)(14), Seo KY(3), Hyon JY(5)(6). Author information: (1)Department of Ophthalmology, Korea University College of Medicine, Seoul, Republic of Korea. (2)Department of Ophthalmology, Korea University Ansan Hospital, Ansan, Republic of Korea. (3)The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea. (4)Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea. (5)Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea. (6)Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. (7)Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. (8)Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. (9)Department of Ophthalmology, Yeouido St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. (10)Department of Ophthalmology, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. (11)Department of Ophthalmology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea. (12)Department of Ophthalmology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. (13)Department of Ophthalmology, Korea University Guro Hospital, Seoul, Republic of Korea. (14)Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Clinical Research Institute, Republic of Korea. Comment in JAMA Ophthalmol. 2024 Jul 1;142(7):625-626. doi: 10.1001/jamaophthalmol.2024.1658. IMPORTANCE: Taking ω-3 supplements has been associated with a reduction in symptoms of dry eye disease (DED) associated with meibomian gland dysfunction (MGD). However, a recent relatively large clinical trial concluded that treating DED with ω-3 consumption was ineffective, potentially warranting additional investigations. OBJECTIVES: To investigate the effect of re-esterified triglyceride (rTG) ω-3 fatty acid supplementation on DED associated with MGD. DESIGN, SETTING, AND PARTICIPANTS: This double-masked, parallel-group, randomized clinical trial was conducted at 7 institutions from September 2020 to January 2023. Patients with DED associated with MGD were included and randomly assigned to the ω-3 group (received 1680 mg of eicosapentaenoic acid and 560 mg of docosahexaenoic acid), whereas those in the grape-seed group received 3000 mg of grape-seed oil daily. INTERVENTIONS: rTG ω-3 Fatty acid supplementation vs grape-seed oil. MAIN OUTCOME MEASURES: The primary end point was the Ocular Surface Disease Index (OSDI) from baseline to 6 and 12 weeks. The safety parameters were visual acuity and intraocular pressure change. RESULTS: A total of 132 patients (mean [SD] age, 50.6 [13.8] years; 103 female [78.0%]) were included in this study. The mean (SD) baseline OSDI scores of the ω-3 and grape-seed groups were 43.5 (16.5) and 44.1 (16.6), respectively. A total of 58 patients (87.9%) and 57 patients (86.4%) in the ω-3 and grape-seed groups, respectively, completed 12 weeks of follow-up. There were no differences in compliance with the dietary supplement intake between groups (ω-3, 95.8% and grape-seed, 95.4%). The OSDI (SD) change from baseline to 6 and 12 weeks was -20.5 (16.0) and -22.7 (15.7), respectively, in the ω-3 group and -15.1 (20.2) and -18.8 (21.7), respectively, in the grape-seed control group (difference at 6 weeks = -5.4; 95% CI, -12.15 to 1.33; P = .12 and at 12 weeks = -3.9; 95% CI, -10.90 to 3.13; P = .28). There were no changes in safety parameters or adverse events related to taking the dietary supplement in either group. CONCLUSIONS AND RELEVANCE: This randomized clinical trial did not show a benefit of the rTG form of ω-3 for ameliorating symptoms of DED associated with MGD, although fewer than 60 participants were evaluated in each group. Any secondary outcomes from this study should be considered for hypothesis generation of future evaluations of the effect of the rTG form of ω-3 on DED associated with MGD. TRIAL REGISTRATION: CRIS Identifier: KCT0004927. DOI: 10.1001/jamaophthalmol.2024.1482 PMCID: PMC11099841 PMID: 38753336 [Indexed for MEDLINE] Conflict of interest statement: Conflict of Interest Disclosures: Dr S. Chung reported receiving grants from LYS PHARMA during the conduct of the study. No other disclosures were reported.

Grape seed extract supplementation in non-alcoholic fatty liver disease.

7. Int J Vitam Nutr Res. 2024 Jun;94(5-6):365-376. doi: 10.1024/0300-9831/a000805. Epub 2024 Feb 28. Grape seed extract supplementation in non-alcoholic fatty liver disease. Ghanbari P(1), Alboebadi R(1), Bazyar H(2)(3), Raiesi D(4), ZareJavid A(5), Azadbakht MK(6), Karimi M(1), Razmi H(1). Author information: (1)Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Iran. (2)Department of Public Health, Sirjan School of Medical Sciences, Sirjan, Iran. (3)Student Research Committee, Sirjan School of Medical Sciences, Sirjan, Iran. (4)Department of Internal Medicine, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Iran. (5)Nutrition and Metabolic Diseases Research Center, Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Iran. (6)Department of Basic Sciences, Sirjan School of Medical Sciences, Sirjan, Iran. Background: Despite rising non-alcoholic fatty liver disease (NAFLD) prevalence and its impact on liver health, there's a lack of studies on grape seed extract's (GSE) effect on oxidative stress and quality of life (QoL) in NAFLD patients. This study aims to fill this gap by the potential benefits of GSE in reducing oxidative stress and improving QoL. Methods: In this randomized clinical trial study, fifty patients with NAFLD were randomly assigned to receive either 2 tablets of GSE containing 250 mg of proanthocyanidins or placebo (25 participants in each group) for two months. QoL was evaluated using the SF-36 questionnaire, and oxidative stress variables (TAC, MDA, SOD, GPx, CAT, and IL-6) were measured at the beginning and end of the study. Results: Compared with the control group, the group supplemented with GSE experienced greater reductions in IL-6 and MDA (3.14±1.43 pg/ml vs. 2.80±0.31 pg/ml; 4.16±2.09 μM vs. 4.59±1.19 μM, p for all <0.05), as well as greater increases in TAC, SOD, and GPx levels (0.18±0.08 mM vs. -0.03±0.09 mM; 10.5±6.69 U/ml vs. 8.93±1.63 U/ml; 14.7±13.4 U/ml vs. 8.24±3.03 U/ml, p for all <0.05). Furthermore, the QoL questionnaire showed that physical limitations, general health, and total physical health were significantly improved in the GSE group compared with the placebo (17.0±42.0 vs. -12.0±37.5; 3.80±14.8 vs. -3.92±9.55; 5.08 5.26 vs. -7.01±13.7, p for all <0.05). Conclusions: GSE can be effective in improving oxidative stress and QoL in patients with NAFLD. More studies are needed to confirm the results of this study. DOI: 10.1024/0300-9831/a000805 PMID: 38419408 [Indexed for MEDLINE]

A triple-masked, two-center, randomized parallel clinical trial to assess the superiority of eight weeks of grape seed flour supplementation against placebo for weight loss attenuation during perioperative period in patients with cachexia associated with colorectal cancer: a study protocol.

8. Front Endocrinol (Lausanne). 2024 Jan 19;14:1146479. doi: 10.3389/fendo.2023.1146479. eCollection 2023. A triple-masked, two-center, randomized parallel clinical trial to assess the superiority of eight weeks of grape seed flour supplementation against placebo for weight loss attenuation during perioperative period in patients with cachexia associated with colorectal cancer: a study protocol. Malta FAPS(1), Gonçalves DC(2). Author information: (1)Postgraduate Program in Nutrition, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. (2)Department of Biosciences, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. BACKGROUND: Progressive, involuntary weight and lean mass loss in cancer are linked to cachexia, a prevalent syndrome in gastrointestinal malignancies that impacts quality of life, survival and postoperative complications. Its pathophysiology is complex and believed to involve proinflammatory cytokine-mediated systemic inflammation resulting from tumor-host interaction, oxidative stress, abnormal metabolism and neuroendocrine changes. Therapeutic options for cachexia remain extremely limited, highlighting the need for clinical research targeting new interventions. Thus, this study primarily assesses the effects of grape-seed flour (GSF), rich in polyphenols and fibers, for attenuating perioperative weight loss in colorectal cancer. METHODS: This is a dual-center, triple-masked, placebo-controlled, parallel-group, phase II, randomized clinical trial designed to investigate GSF supplementation in subjects with pre- or cachexia associated with colorectal cancer during the perioperative period. Eighty-two participants will receive 8g of GSF or cornstarch (control) for 8 weeks. Assessments are scheduled around surgery: pre-intervention (4 weeks prior), day before, first week after, and post-intervention (4 weeks later). The primary endpoint is the difference in body weight mean change from baseline to week 8. The secondary endpoints describe the harms from 8-week supplementation and assess its superiority to improve body composition, post-surgical complications, quality of life, anorexia, fatigue, gastrointestinal symptoms, and handgrip strength. The study will also explore its effects on gut bacteria activity and composition, systemic inflammation, and muscle metabolism. DISCUSSION: The current trial addresses a gap within the field of cancer cachexia, specifically focusing on the potential role of a nutritional intervention during the acute treatment phase. GSF is expected to modulate inflammation and oxidative stress, both involved in muscle and intestinal dysfunction. The research findings hold substantial implications for enhancing the understanding about cachexia pathophysiology and may offer a new clinical approach to managing cachexia at a critical point in treatment, directly impacting clinical outcomes. TRIAL REGISTRATION: The Brazilian Registry of Clinical Trials (ReBEC), RBR-5p6nv8b; UTN: U1111-1285-9594. Prospectively registered on February 07, 2023. Copyright © 2024 Malta and Gonçalves. DOI: 10.3389/fendo.2023.1146479 PMCID: PMC10834683 PMID: 38313843 [Indexed for MEDLINE] Conflict of interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Grape seed extract in combination with deferasirox ameliorates iron overload, oxidative stress, inflammation, and liver dysfunction in beta thalassemia children.

9. Complement Ther Clin Pract. 2023 Nov;53:101804. doi: 10.1016/j.ctcp.2023.101804. Epub 2023 Oct 11. Grape seed extract in combination with deferasirox ameliorates iron overload, oxidative stress, inflammation, and liver dysfunction in beta thalassemia children. Mottaghi S(1), Abbaszadeh H(2). Author information: (1)Department of Pediatrics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. (2)Department of Pharmacology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address: abbaszadeh2h@gmail.com. BACKGROUND AND PURPOSE: Iron overload in the body is associated with serious and irreversible tissue damage. This study aimed to investigate the iron-chelating, antioxidant, anti-inflammatory, and hepatoprotective activities of grape seed extract (GSE) supplement as well as its safety in β-thalassemia major (β-TM) pediatric patients receiving deferasirox as a standard iron-chelation therapy. MATERIALS AND METHODS: The children were randomly allocated to either GSE group (n = 30) or control group (n = 30) to receive GSE (100 mg/day) or placebo capsules, respectively, for 4 weeks. The serum levels of iron, ferritin, total iron-binding capacity (TIBC), alanine transaminase (ALT), aspartate aminotransferase (AST), tumor necrosis factor alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and glutathione (GSH) as well as superoxide dismutase (SOD) activity and hemoglobin (Hb) concentration were measured pre-and post-intervention. RESULTS: GSE supplement significantly attenuated the serum levels of iron (p = 0.030), ferritin (p = 0.017), ALT (p = 0.000), AST (p = 0.000), TNF-α (p = 0.000), and hs-CRP (p = 0.001). The TIBC level (p = 0.020) significantly enhanced in the GSE group compared with the placebo group. Moreover, GSE supplement remarkably improved the oxidative stress markers, MDA (p = 0.000) and GSH (p = 0.001). The changes in the SOD activity (p = 0.590) and Hb concentration (p = 0.670) were not statistically different between the groups. CONCLUSION: GSE supplement possesses several health beneficial influences on children with β-TM by alleviating iron burden, oxidative stress, inflammation, and liver dysfunction. Copyright © 2023 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.ctcp.2023.101804 PMID: 37832335 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare no conflicts of interest.

The natural tannins oligomeric proanthocyanidins and punicalagin are potent inhibitors of infection by SARS-CoV-2.

10. Elife. 2023 Aug 29;12:e84899. doi: 10.7554/eLife.84899. The natural tannins oligomeric proanthocyanidins and punicalagin are potent inhibitors of infection by SARS-CoV-2. Chen HF(1)(2), Wang WJ(2)(3), Chen CY(2), Chang WC(4), Hsueh PR(5), Peng SL(6)(7), Wu CS(1)(2), Chen Y(3)(8), Huang HY(1), Shen WJ(1), Wang SC(1)(2)(4)(9)(10), Hung MC(1)(2)(4)(9)(10)(11). Author information: (1)Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan. (2)Research Center for Cancer Biology, China Medical University, Taichung, Taiwan. (3)Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan. (4)Center for Molecular Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan. (5)Departments of Laboratory Medicine and Internal Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan. (6)Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan. (7)Neuroscience and Brain Disease Center, China Medical University, Taichung, Taiwan. (8)Institute of New Drug Development, China Medical University, Taichung, Taiwan. (9)Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung, Taiwan. (10)Department of Biotechnology, Asia University, Taichung, Taiwan. (11)Institute of Biochemistry and Molecular Biology, China Medical University, Taichung, Taiwan. Update of doi: 10.1101/2023.01.12.523465. The Coronavirus Disease 2019 (COVID-19) pandemic continues to infect people worldwide. While the vaccinated population has been increasing, the rising breakthrough infection persists in the vaccinated population. For living with the virus, the dietary guidelines to prevent virus infection are worthy of and timely to develop further. Tannic acid has been demonstrated to be an effective inhibitor of coronavirus and is under clinical trial. Here we found that two other members of the tannins family, oligomeric proanthocyanidins (OPCs) and punicalagin, are also potent inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with different mechanisms. OPCs and punicalagin showed inhibitory activity against omicron variants of SARS-CoV-2 infection. The water extractant of the grape seed was rich in OPCs and also exhibited the strongest inhibitory activities for viral entry of wild-type and other variants in vitro. Moreover, we evaluated the inhibitory activity of grape seed extractants (GSE) supplementation against SARS-CoV-2 viral entry in vivo and observed that serum samples from the healthy human subjects had suppressive activity against different variants of SARS-CoV-2 Vpp infection after taking GSE capsules. Our results suggest that natural tannins acted as potent inhibitors against SARS-CoV-2 infection, and GSE supplementation could serve as healthy food for infection prevention. Plain Language Summary: Since it first surfaced in late 2019, the COVID-19 pandemic has had a significant impact on people’s lives. While several vaccines have been created, infections have not disappeared. This is largely due to new variants of the virus responsible for the disease (SARS-CoV-2) emerging, which current vaccines do not work as well against. Indeed, several reports suggest that protection from the omicron variant wanes as shortly as four to six months after vaccination. Therefore, other strategies are needed to reduce the risk of SARS-CoV-2 infections. In 2022, researchers discovered that tannic acid blocked two proteins that SARS-CoV-2 needs to enter and replicate inside human cells. Tannic acid is part of the tannin family, which includes natural molecules found in plant-based meals and beverages. Here, Chen et al. – including some of the researchers involved in the 2022 studies – set out to find whether two other tannins found in nature (OPCs and punicalagin) could also inhibit SARS-CoV-2. Chen et al. administered tannic acid, OPCs and punicalagin to human cells cultured in a laboratory that had been infected with SARS-CoV-2. This revealed that all three tannins suppress the activity of the same proteins required for viral entry and replication, but to varying degrees suggesting that they block SARS-CoV-2 infections via different mechanisms. The compounds were also able to inhibit different variants of the virus, including omicron, from infecting the lab-grown cells. Further experiments revealed that water extracted from seeded grapes, which contains high levels of OPCs, could also block SARS-CoV-2 entry in the cell culture system. To test this further, Chen et al. gave 18 healthy individuals capsules containing different concentrations of grape seed extract and collected samples of their serum. The serum samples suppressed entry of different variants of SARS-CoV-2 in the cell culture system, with serums from subjects that received the higher dose having the greatest effect. These findings suggest that naturally occurring tannins can suppress multiple variants of SARS-CoV-2 from entering and replicating in cells. Consuming supplements of grape seed extract could potentially reduce the risk of SARS-CoV-2 infections. However, further experiments, including clinical trials, are needed to test this possibility. © 2023, Chen et al. DOI: 10.7554/eLife.84899 PMCID: PMC10465125 PMID: 37642993 [Indexed for MEDLINE] Conflict of interest statement: HC, WW, WC, YC, SW, MH registered as the inventor of a patent application based on inhibiting SARS-CoV-2 infection of punicalagin and OPC (ROC Patent No.111133318), CC, PH, SP, CW, HH, WS No competing interests declared

Low Dose Monacolin K Combined with Coenzyme Q10, Grape Seed, and Olive Leaf Extracts Lowers LDL Cholesterol in Patients with Mild Dyslipidemia: A Multicenter, Randomized Controlled Trial.

11. Nutrients. 2023 Jun 9;15(12):2682. doi: 10.3390/nu15122682. Low Dose Monacolin K Combined with Coenzyme Q10, Grape Seed, and Olive Leaf Extracts Lowers LDL Cholesterol in Patients with Mild Dyslipidemia: A Multicenter, Randomized Controlled Trial. Angelopoulos N(1)(2), Paparodis RD(3)(4), Androulakis I(1)(5), Boniakos A(1), Argyrakopoulou G(1), Livadas S(1). Author information: (1)Endocrine Unit, Athens Medical Centre, 65403 Athens, Greece. (2)Private Practice, Venizelou Str., 65302 Kavala, Greece. (3)Center for Diabetes and Endocrine Research, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA. (4)Private Practice, Gerokostopoulou 24, 26221 Patra, Greece. (5)Private Practice, Tzanaki Emmanouil 17, 73134 Chania, Greece. Certain nutraceuticals, mainly containing red yeast rice, might be considered as an alternative therapy to statins in patients with dyslipidemia, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing a low dose of monacolin K combined with coenzyme Q10, grape seed and olive tree leaf extracts in patients with mild hypercholesterolemia. In total, 105 subjects with mild hypercholesterolemia (low-density lipoprotein cholesterol LDL-C levels 140-180 mg/dL) and low CV risk were randomly assigned into three treatment groups: lifestyle modification (LM), LM plus a low dosage of monacolin K (3 mg), and LM plus a high dosage of monacolin K (10 mg) and treated for 8 weeks. The primary endpoint was the reduction of LDL-C and total cholesterol (TC). LDL-C decreased by 26.46% on average (p < 0.001) during treatment with 10 mg of monacolin and by 16.77% on average during treatment with 3 mg of monacolin (p < 0.001). We observed a slight but significant reduction of the triglyceride levels only in the high-dose-treated group (mean -4.25%; 95% CI of mean -11.11 to 2.61). No severe adverse events occurred during the study. Our results confirm the LDL-C-lowering properties of monacolin are clinically meaningful even in lower doses of 3 mg/day. DOI: 10.3390/nu15122682 PMCID: PMC10303004 PMID: 37375586 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflict of interest.

A grape seed and bilberry extract reduces blood pressure in individuals at risk of developing type 2 diabetes: the PRECISE study, a double-blind placebo-controlled cross-over intervention study.

12. Front Nutr. 2023 Jun 7;10:1139880. doi: 10.3389/fnut.2023.1139880. eCollection 2023. A grape seed and bilberry extract reduces blood pressure in individuals at risk of developing type 2 diabetes: the PRECISE study, a double-blind placebo-controlled cross-over intervention study. Grohmann T(1), Walker AW(1), Russell WR(1), Hoggard N(1), Zhang X(2), Horgan G(3), de Roos B(1). Author information: (1)Rowett Institute, University of Aberdeen, Aberdeen, Scotland, United Kingdom. (2)By-Health Co., Ltd., Guangzhou, China. (3)Biomathematics and Statistics Scotland, Aberdeen, United Kingdom. BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is a major risk factor for the development of cardiometabolic diseases. T2DM prevention is largely based on weight-loss and whole diet changes, but intervention with dietary plant bioactives may also improve metabolic health. OBJECTIVE: To assess whether supplementation with bilberry and grape seed extract for 12 weeks improves cardiometabolic outcomes in individuals at risk of developing T2DM, and to determine whether individual treatment response is associated with differences in gut microbiota composition and levels of phenolic metabolites in blood and feces. METHODS: In the randomized, double-blind, placebo-controlled, cross-over PRECISE intervention study, 14 participants, aged ≥45 years, with a BMI >28 kg/m2, and having an increased risk of T2DM, received a supplement containing 250 mg of bilberry plus 300 mg of grape seed extract, or 550 mg of a control extract, per day, for 12 weeks each. Blood samples were obtained for the assessment of HbA1c, fasting glucose, oral glucose tolerance tests, insulin, glucagon levels, total, LDL and HDL cholesterol, and phenolic acids. We also assessed advanced glycation end products in the skin, ambulatory 24 hours blood pressure, 7-day dietary intake by weighed food diaries, fecal levels of phenolic metabolites using LC-MS/MS and gut microbiota composition using 16S rRNA gene sequencing analysis. RESULTS: The combined bilberry and grape seed extract did not affect glucose and cholesterol outcomes, but it decreased systolic and diastolic ambulatory blood pressure by 4.7 (p < 0.001) and 2.3 (p = 0.0009) mmHg, respectively. Eight out of fourteen participants were identified as blood pressure 'responders'. These responders had higher levels of phenylpropionic and phenyllactic acids in their fecal samples, and a higher proportional abundance of Fusicatenibacter-related bacteria (p < 0.01) in their baseline stool samples. CONCLUSION: Long-term supplementation with bilberry and grape seed extract can improve systolic and diastolic blood pressure in individuals at risk of T2DM. Individual responsiveness was correlated with the presence of certain fecal bacterial strains, and an ability to metabolize (epi)catechin into smaller phenolic metabolites.Clinical trial registry number: Research Registry (number 4084). Copyright © 2023 Grohmann, Walker, Russell, Hoggard, Zhang, Horgan and de Roos. DOI: 10.3389/fnut.2023.1139880 PMCID: PMC10283353 PMID: 37351191 Conflict of interest statement: XZ is an employee of the company By-health Co., Ltd., and BR is a member of By-Health’s academic advisory board. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Effects of Grape Seed Extract Supplementation on Endothelial Function and Endurance Performance in Basketball Players.

13. Int J Environ Res Public Health. 2022 Oct 31;19(21):14223. doi: 10.3390/ijerph192114223. Effects of Grape Seed Extract Supplementation on Endothelial Function and Endurance Performance in Basketball Players. Nho H(1), Kim KA(2). Author information: (1)Department of Liberal Arts and Science, Suwon Women's University, Onjeong Street 72, Gweonseon-gu, Suwon-si 16632, Korea. (2)Human IT Solution, Gogum Building 1F, 2F, Banpo-daero, 55, Seocho-gu, Seoul 06670, Korea. While dietary polyphenols supplements can improve endothelial function and blood flow to exercise, the effects of chronic supplementation with grape seed extract (GSE) containing a high dose of polyphenols on endurance performance are not known. Accordingly, in 12 elite athletes, we compared the effects of both GSE and placebo (PL) on submaximal VO2, time to exhaustion performance, and endothelial function during progressive cycling exercise for 14 days. Endothelial function was evaluated from the brachial artery via flow-mediated dilation (FMD). Compared to PL, GSE decreased submaximal VO2 at 80% and 120% of VO2peak and increased the time to exhaustion (p < 0.05). GSE also resulted in FMD-induced increase in brachial artery diameter (14.4 ± 5.2% vs. 17.6 ± 4.5%, p = 0.035). We demonstrated that chronic supplementation with GSE improved endurance performance and these effects may partially be due to vasodilation in active skeletal muscle mediated by enhanced endothelial function. Thus, our results suggest that GSE appears to be an ergogenic nutraceutical that can improve exercise performance in elite athletes. DOI: 10.3390/ijerph192114223 PMCID: PMC9658680 PMID: 36361103 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflict of interest.

Chemical, Manufacturing, and Standardization Controls of Grape Polyphenol Dietary Supplements in Support of a Clinical Study: Mass Uniformity, Polyphenol Dosage, and Profiles.

14. Front Nutr. 2021 Dec 16;8:780226. doi: 10.3389/fnut.2021.780226. eCollection 2021. Chemical, Manufacturing, and Standardization Controls of Grape Polyphenol Dietary Supplements in Support of a Clinical Study: Mass Uniformity, Polyphenol Dosage, and Profiles. Lyu W(1)(2), Rodriguez D(3), Ferruzzi MG(4), Pasinetti GM(5)(6), Murrough JW(5)(7), Simon JE(1)(2), Wu Q(1)(2). Author information: (1)New Use Agriculture and Natural Plant Products Program, Department of Plant Biology and Center for Agricultural Food Ecosystems, Institute of Food, Nutrition & Health, Rutgers University, New Brunswick, NJ, United States. (2)Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, United States. (3)Independent Researcher, Carlstadt, NJ, United States. (4)Department of Food, Bioprocessing and Nutrition Sciences, Plants for Human Health Institute, North Carolina State University, Kannapolis, NC, United States. (5)Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. (6)Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY, United States. (7)Depression and Anxiety Center for Discovery and Treatment, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Bioactive dietary polyphenols in grape (Vitis vinifera) have been used in Dietary Supplements (DSs) with the aim to prevent numerous diseases, including cardiovascular and neurodegenerative diseases, and to reduce depression and anxiety. Given prior recognition that DSs can be quality challenged from the purity, authentication, adulteration, and actual concentration of targeted bioactives, to ensure consumer health protection as well as the quality and safety of grape polyphenol-based DSs, the present investigation was aimed at establishing a comprehensive quality control (QC) approach for grape polyphenol-based DSs in support of a human clinical study. In this study, the manufactured grape seed polyphenol extract (GSPE) and trans-resveratrol (RSV) capsules and Concord Grape Juice (CGJ) along with the corresponding original drug materials were analyzed using the developed different liquid chromatography/UV-visible spectroscopy/mass spectrometry (LC/UV-Vis/MS) methods. The weight variation of GSPE and RSV capsules was also evaluated according to the US Pharmacopeia (USP) tests. The results indicate that the total identified polyphenol content in each grape seed extract (GSE) capsule/CGJ is very similar and all GSE/RSV capsules pass the content/weight uniformity test. Given the complexity of these and many botanical products from the issues of purity, quality, adulteration, consistency, and their coupling to the complex chemistry in each grape-derived botanical, quality assurance and the steps needed to ensure grape-derived DSs being well homogeneous and stable and containing the known and expected bioactives at specific concentration ranges are fundamental to any research study and in particular to a clinical trial. Each of these issues is essential to provide a solid foundation upon which clinical trials with botanicals can be conducted with the goal of realizing measurable mental health outcomes such as reducing depression and anxiety as well as understanding of their underlying biological mechanisms. Copyright © 2021 Lyu, Rodriguez, Ferruzzi, Pasinetti, Murrough, Simon and Wu. DOI: 10.3389/fnut.2021.780226 PMCID: PMC8716858 PMID: 34977124 Conflict of interest statement: DR was employed by company Eagle Nutritionals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The effect of grape seed extract supplementation on oxidative stress and inflammation: A systematic review and meta-analysis of controlled trials.

15. Int J Clin Pract. 2021 Nov;75(11):e14469. doi: 10.1111/ijcp.14469. Epub 2021 Jun 28. The effect of grape seed extract supplementation on oxidative stress and inflammation: A systematic review and meta-analysis of controlled trials. Foshati S(1), Rouhani MH(2), Amani R(1). Author information: (1)Department of Clinical Nutrition, School of Nutrition and Food Science, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. (2)Department of Community Nutrition, School of Nutrition and Food Science, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. BACKGROUND: Grape seed extract (GSE) seems to have antioxidant and anti-inflammatory properties due to its high polyphenolic content. Nevertheless, the scientific literature in this field is controversial and inconclusive. Therefore, we aimed to conduct a systematic review and meta-analysis of controlled trials to evaluate the effect of supplementation with GSE on biomarkers of oxidative stress and inflammation. METHODS: Medline, Scopus, Cochrane Library, Google Scholar and Web of Science databases were searched up to 10 September 2020 using appropriate keywords without restrictions. In the systematic review phase, all biomarkers of oxidative stress and inflammation were considered as outcomes. In the meta-analysis phase, six biomarkers were selected as outcomes, and weighted mean difference (WMD) or standardised mean difference (SMD) with 95% confidence interval (CI) was calculated for them using a random-effects model. RESULTS: Twenty-three studies were included in the systematic review, and 19 studies were included in the meta-analysis. GSE supplementation caused a significant decrease in malondialdehyde (SMD: -1.04, 95% CI: -1.65, -0.42), oxidised low-density lipoprotein (SMD: -0.44, 95% CI: -0.75, -0.13) and high-sensitivity C-reactive protein (WMD: -0.48 mg/L, 95% CI: -0.94, -0.03) and a marginally significant increase in total antioxidant capacity (SMD: 0.49, 95% CI: -0.05, 1.04) but did not significantly influence C-reactive protein (WMD: -0.36 mg/L, 95% CI: -1.02, 0.30) and white blood cell count (WMD: 0.12 × 109 /L, 95% CI: -0.25, 0.48). CONCLUSION: It appears that GSE supplementation can remarkably modulate the body's redox system, particularly through the inhibition of lipid peroxidation, but has neutral or mildly beneficial effects on inflammatory responses. © 2021 John Wiley & Sons Ltd. DOI: 10.1111/ijcp.14469 PMID: 34107109 [Indexed for MEDLINE]