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Systematic Review/Meta-analysis Shows that Grape Seed Extract May Improve Fasting Plasma Glucose, Total Cholesterol, Low-Density Lipoprotein Cholesterol, Triglycerides, and C-reactive Protein Levels
Date 01-15-2021
HC# 052015-656
Grape (Vitis vinifera, Vitaceae)
Glycemic Control 
Systematic Review/Meta-analysis

Asbaghi O, Nazarian B, Reiner Z, et al. The effects of grape seed extract on glycemic control, serum lipoproteins, inflammation, and body weight: A systematic review and meta-analysis of randomized controlled trials. Phytother Res. February 2020;34(2):239-253. doi: 10.1002/ptr.6518.

Metabolic syndrome (MetS) is a risk factor for cardiovascular disease (CVD). MetS is characterized by the presence of several metabolic disorders, including abdominal obesity, hypertension, hyperglycemia, and atherogenic dyslipidemia. Etiopathogenic mechanisms include insulin resistance, oxidative stress, and low-grade chronic inflammation. More than 20% of adults worldwide are affected by MetS. Grape (Vitis vinifera, Vitaceae) seed extract (GSE) has been demonstrated to have beneficial effects on metabolic abnormalities in patients with and without MetS. GSE has been shown to improve lipoprotein metabolism, restrict adipogenesis, mimic insulin action, and reduce inflammation. However, studies show conflicting results on biochemical markers including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and C-reactive protein (CRP). The purpose of this systematic review and meta-analysis was to evaluate the efficacy of GSE on glycemic control, serum lipoproteins, CRP levels, and anthropometric parameters.

A keyword search was performed using EMBASE, Cochrane Library, Web of Science, and PubMed through May 30, 2019. Randomized controlled trials with either parallel designs or crossover studies that evaluated the effects of GSE on glycemic control, serum lipoproteins, CRP, and anthropometric measurements were included. Animal studies, in vitro studies, case reports, observational studies, trials without a control group, and studies that did not achieve the least quality score were excluded. A total of 724 articles were identified; 694 were excluded due to duplicate articles and not meeting inclusion criteria. Thirty articles were screened by title and abstract. Eleven were excluded as non-relevant. Nineteen full text articles were assessed for eligibility. Three were excluded for not having the desired data, and one was excluded for the use of grape seed oil as intervention. Fifteen studies were included in this systematic review and meta-analysis. Studies were conducted in Italy (n = 1), Australia (n = 2), Japan (n = 2), UK (n = 1), US (n = 3), Iran (n = 5), and Tunisia (n = 1) and published between 2003 and 2017. Ten studies used a parallel design and five were crossover studies. One study included only male participants and two, only female. The remaining 12 included both male and female participants. The pooled sample size was 825 with 451 assigned to intervention and 374 to control groups. Mean age ranged from 19.8 to 63.6 years and body mass index (BMI) from 21.3 to 37.0 kg/m2. Trial periods ranged between four and 25 weeks and used GSE doses between 100 and 2000 mg/day. Four trials were conducted using healthy participants. The remaining trials included participants diagnosed with type 2 diabetes mellitus (T2DM), high cholesterol, prehypertension and hypertension, MetS, CVD, hyperlipidemia, chronic kidney disease, and patients receiving hemodialysis. Three studies used two intervention groups with two different doses of GSE supplementation and, thus, have two effect sizes each.

GSE effects on glycemic control showed a significant decrease in fasting plasma glucose (FPG) (P = 0.001) in seven studies with eight effect sizes. Subgroup analysis was significant for all parameters except for studies where participants had a baseline FPG < 100 mg/dL, duration > 6 wks, GSE dose < 300 mg/day, performed on healthy participants, crossover design studies, and participants with normal BMI. Pooled data from three studies with four effect sizes showed no significant effect of GSE on hemoglobin A1c (HbA1c) levels. Subgroup analysis was subsequently not conducted due to small effect sizes.

The effects of GSE on lipoproteins showed a significant reduction in TC (P = 0.001) in 13 studies with 15 effect sizes; however, conflicting results were observed in studies with participants having TC levels < 200 mg/dL, duration ≤ 6 weeks, GSE doses ≥ 300 mg/day, studies using healthy participants, crossover design studies, participants with normal BMI, and overweight and obese participants. LDL-C was significantly lower in a meta-analysis of 11 studies with 13 effect sizes (P = 0.004). In subgroup analysis, results were similar except that no significant differences were observed in studies where participants had LDL-C levels < 100 mg/dL, duration ≤ 6 weeks, GSE dosage ≥ 300 mg/day, studies on healthy participants, crossover design studies, participants with normal BMI, and overweight participants. Thirteen studies with 15 effect sizes showed a significant reduction in triglycerides (P < 0.001). Subgroup analysis was significant for all parameters except where participants had triglycerides levels < 150 mg/dL, healthy participants, and obese participants. No significant differences were observed in meta-analysis or subgroup analysis for HDL-C.

Pooled analysis from six studies showed a significant reduction in CRP concentration (P < 0.001). A subgroup analysis was not performed due to a limited number of studies. No significant differences were observed for body weight in five studies with seven effect sizes or BMI in four studies with five effect sizes. In both instances, subgroup analysis was not performed due to limited data.

The authors conclude that this "meta-analysis demonstrated that GSE intake significantly reduced FPG, TC, LDL-C, triglycerides, and CRP level." However, GSE does not appear to have an effect on HbA1c, HDL-C, or anthropometric measurements.

The authors declare no conflict of interest.

Samaara Robbins