Grape Seed (Circulation)

The objective of this systematic review and meta-analysis of controlled trials was to assess the long-term effect of grape seed extract (GSE) supplementation on flow-mediated dilation (FMD), systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) in adults. Web of Science, Scopus, Medline, Cochrane Library, and Google Scholar were searched up to May 24, 2021. Nineteen trials were included in this study. Weighted mean difference (WMD) and 95% confidence interval (CI) were calculated using a random-effects model. GSE supplementation significantly reduced DBP (WMD: -2.20 mmHg, 95% CI: -3.79 to -0.60, I2 = 88.8%) and HR (WMD: -1.25 bpm, 95% CI: -2.32 to -0.19, I2 = 59.5%) but had no significant effects on FMD (WMD: 1.02%, 95% CI: -0.62 to 2.66, I2 = 92.0%) and SBP (WMD: -3.55 mmHg, 95% CI: -7.59 to 0.49, I2 = 97.4%). Subgroup analysis revealed that the dose and duration of GSE administration and the characteristics of study participants could be sources of between-study heterogeneity. Significant non-linear relationships were found between DBP and the duration of GSE supplementation (P = 0.044) and its dose (P = 0.007). In conclusion, GSE may be beneficial for individuals with or at risk of cardiovascular disease because it may have hypotensive and HR-lowering properties.

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

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.

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.

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.

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).

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:

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: Th

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.

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 t

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.

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

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.

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

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.

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.

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.