Grape Resveratrol Increases Serum Adiponectin and Downregulates Inflammatory Genes in Peripheral Blood Mononuclear Cells: A Triple-Blind, Placebo-Controlled, One-Year Clinical Trial in Patients with Stable Coronary Artery Disease

Triple-blind, randomized, placebo-controlled, monocenter, 1-year, 3-arm pilot trial in 75 stable CAD patients on guideline-based secondary prevention. Primary endpoint: change in hsCRP; Secondary endpoints: PAI-1, adiponectin, IL-6, IL-10, TNF-α, sCD40L, sVCAM. A PBMC microarray sub-study analyzed samples from 18 male patients with diabetes and hypertension (6 per group) across baseline, 6, and 12 months.

Placebo: maltodextrin capsules, 350 mg per capsule; 1 capsule daily in the morning for 6 months, then 2 capsules daily for the next 6 months. GE: conventional grape extract capsules, 350 mg per capsule; dosing the same as placebo (1 capsule daily for 6 months, then 2 daily for 6 months). GE-RES: resveratrol-containing grape extract capsules, 350 mg per capsule; dosing the same; each GE-RES capsule contains 8.1 mg resveratrol; daily intake: 1 capsule for 6 months, then 2 capsules for 6 months (total 16.2 mg/day of resveratrol in months 7–12).

In the GE-RES group, adiponectin increased by 9.6% at 12 months (p<0.01) and by 23% vs placebo at 12 months (p<0.05). PAI-1 decreased by 18.6% at 12 months (p=0.05). hsCRP declined in GE-RES but inter-group differences were not statistically significant (8% at 6 months, 18% at 12 months; p=0.09 and p=0.17 respectively). PBMC gene-expression analysis showed 6 inflammation-related transcription factors predicted to be activated or inhibited only in GE-RES after 12 months: KLF2 (activated); NF-κB and AP-1 (inhibited: JUN, ATF-2, CREBBP), with a downregulated subset of 27 extracellular-space inflammatory genes related to inflammation, cell movement, immune cell trafficking, and signaling. No adverse effects were detected. Conclusion: daily intake of a resveratrol-containing grape extract for 1 year could confer cardiovascular benefits in stable CAD by increasing adiponectin, reducing PAI-1, and dampening pro-inflammatory signaling in PBMCs; the presence of resveratrol appears essential. Findings are preliminary due to small sample size and exploratory endpoints; larger, longer trials are needed to confirm clinical impact.

Small sample size (n=75) and single-center; 1-year duration; PBMC microarray analysis in a small subpopulation (n=18; 6/group), limiting generalizability; High statin doses may confound hsCRP response; No detectable circulating resveratrol/metabolites, highlighting exposure-assessment limitations; Not powered for clinical outcomes; 13 cardiovascular events occurred, requiring larger follow-up for clinical relevance.