Written by Tabish Mehraj, PhD Science Writer, Grape seed extract (GSE) supplementation over two months showed great effectiveness as compared to placebo, the GSE group showed significant improvements in lipid profile (p < 0.05), blood pressure parameters (p < 0.001), insulin resistance markers (p < 0.05), and insulin sensitivity (p < 0.05). Additionally, liver enzyme levels and hepatic steatosis severity were significantly reduced (p < 0.05; p = 0.002). Overall, GSE supplementation showed beneficial metabolic and hepatic effects.

Non-alcoholic fatty liver disease (NAFLD) is a condition affecting most of the global population and is characterized by the accumulation of fat around hepatic tissues, which exceeds the liver weight by 5-10%. It is a common issue in women with little or no alcohol consumption. It progresses from nonalcoholic steatohepatitis (NASH) to fibrosis and ultimately to cirrhosis, causing advanced damage. Most people have it at stage 1, which could be reversed by certain lifestyle modifications. NAFLD is widely regarded as a liver-related condition associated with abnormal lipid metabolism, insulin resistance, and hypertension. NAFLD is manageable in early stages, as weight loss of 4-5% can significantly reduce liver fat.

Grape seed extract (GSE) is an excellent source of proanthocyanidins and polyphenols, both of which have strong anti-inflammatory and antioxidant properties. While many reports suggest that grape seed extract (GSE) could improve metabolic parameters and has certain effects in patients with non-alcoholic fatty liver disease (NAFLD), particularly on insulin sensitivity indices and blood pressure, these effects have not been fully explored. Hence, this study, done by Parisa Ghanbari and team, aimed to assess the effects of GSE supplementation on liver enzyme levels, glycemic status, lipid profile, blood pressure, and the severity of hepatic steatosis in patients with NAFLD.

This double-blind, placebo-controlled, randomized clinical trial enrolled 50 patients with NAFLD aged 20 to 60 years and with a BMI of 25 to 35 kg/m². Participants were randomized into two groups: the GSE group (n=25) and the placebo group (n=25). The intervention group received 520 mg of GSE daily (two 260 mg tablets), and the control group received matching placebo tablets (consisting of cellulose, silicon dioxide, magnesium stearate and starch) for two months. The study’s outcomes were assessed at baseline and after 8 weeks of intervention. The outcomes included glycemic status, lipid profile, liver function, and hepatic steatosis using ultrasound. Statistical analysis was performed using paired t-tests for intragroup comparisons and ANCOVA to assess between-group differences after adjusting baseline values.

The study was accomplished with a higher participant compliance. Followed by taking the two months of GSE supplement, considerable improvements were observed compared to the placebo group. The results are as follows:

• Improved lipid profile: Significant reductions in, triglycerides (TG) from 173.24 ± 34.36 to 158.84 ± 34.26 mg/dL (−14.10 mg/dL) total cholesterol (TC) reduced from 191.14 ± 23.70 to 182.58 ± 21.59 mg/dL and Low-Density Lipoprotein (LDL-c), with a significant increase in High Density Lipoprotein (HDL-c) from 43.28 ± 8.34 to 48.91 ± 7.32 mg/dL, reflecting an increase of 5.63 mg/dL.in the GSE group compared with placebo.
• Better cardiovascular parameters: Significant decreases in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) in the intervention group 108.40 ± 11.06 vs. 95.60 ± 7.37;132.80 ± 13.39 vs. 118.00 ± 9.12, 97.60 ± 9.25 vs.84.40 ± 8.20.
• Enhanced insulin regulation: Significant reductions in insulin levels and HOMA-IR indicated improved insulin resistance. Our investigation observed a mean difference in HOMA-IR of -0.52 ± 0.97 post-intervention.
• Increased insulin sensitivity: Significant increase in the QUICKI index, reflecting improved insulin sensitivity 14.26 ± 3.26 vs. 12.29 ± 2.26; 3.35 ± 0.88 vs. 2.83 ± 0.60, 0.32 ± 0.01 vs. 0.33 ± 0.01, p = 0.002.
• Improved liver health: Significant reductions in liver enzyme levels and hepatic steatosis severity compared with the placebo group 34.87 ± 8.70 vs. 24.28 ± 8.61; 21.40 ± 3.80 vs. 18.75 ± 4.08.

The study suggests that GSE improves NAFLD by acting through multiple pathways. The reduction in oxidative stress is due to its high proanthocyanidin content, thereby inhibiting adipogenesis and stimulating lipolysis. The improvement in insulin sensitivity is particularly important, as insulin resistance is a major driver of fat accumulation around the liver. Its effect on hypertension could be due to the reduced endothelin-1 expression and nitric oxide production, improving vascular function. GSE enhances biochemical markers, leading to improvements in liver structure.

Key Strengths and Limitations of Grape Seed Extract in NAFLD Study

The study comprises of a detailed comprehensive examination of the therapeutic potential of GSE for the management of NAFLD. The randomized, double-blind, placebo-controlled design establishes an association between GSE and improvements in hepatic, cardiovascular, and metabolic health. The study offered a robust clinical trial design, minimizing observation and selection biases thus allowing accurate assessment of GSE supplementation efficacy. For the statistical analysis, use of ANCOVA strengthens the results, ensuring improvements in the GSE group were significant when compared to the placebo. Participant compliance report suggests the GSE to be well tolerated. The study limitations include the small sample size, the need for additional imaging techniques to better assess hepatic steatosis, and the short intervention duration. Future studies including a larger and more diverse subject group and longer intervention period, with various imaging diagnostic tools to properly detect steatosis, are needed to better comprehend the potential benefits of GSE supplementation for cardiovascular and hepatic parameters in NAFLD subjects.

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Posted March 13, 2026.

Dr. Tabish Mehraj is a pharmaceutical scientist with expertise in pharmaceutics, drug delivery, and formulation development. She earned her PhD in Pharmaceutical Sciences from the University of Mississippi, where her research focused on the formulation, optimization, and characterization of lipid-based nanocarriers for targeted liver delivery of antimalarial therapeutics. Dr. Mehraj has also served as an ORISE Fellow at the U.S. Food and Drug Administration (FDA), where she evaluated the effects of formulation and process design on the quality and performance of intravaginal drug delivery systems and developed bio-relevant in vitro drug release testing methods. She has teaching experience in pharmaceutical and life sciences courses and has authored peer-reviewed publications, book chapters, and conference presentations. Dr. Mehraj is an active member of the American Association of Pharmaceutical Scientists and has been recognized by honor societies including Rho Chi and Gamma Beta Phi.

References:

1. Ghanbari, P., Raiesi, D., Alboebadi, R., Zarejavid, A., Dianati, M., Razmi, H., & Bazyar, H. (2024). 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 randomized, double-blind, placebo-controlled study. BMC Complementary Medicine and Therapies, 24(1), 192.