Olive (Olea europaea L.) Leaf Polyphenols Improve Insulin Sensitivity in Middle-Aged Overweight Men: A Randomized, Placebo-Controlled, Crossover Trial

Randomized, double-blind, placebo-controlled crossover trial in overweight middle-aged men at risk of metabolic syndrome in the Auckland region of New Zealand. For the olive leaf extract arm, 46 participants were randomized and 45 were included in the intention-to-treat analysis.

Olive leaf extract was given orally as four capsules once daily for 12 weeks, providing 51.1 mg oleuropein and 9.7 mg hydroxytyrosol per day. The active capsules contained olive leaf extract suspended in safflower oil; the placebo contained safflower oil only.

Olive leaf polyphenol supplementation improved insulin sensitivity and pancreatic beta-cell secretory capacity, but it did not produce consistent benefits for other cardiovascular risk factors. The Matsuda index improved to 5.46 with olive leaf extract versus 4.73 with placebo after 12 weeks, a 15% improvement, p = 0.024. Disposition index improved to 5.45 versus 4.26, a 28% improvement, p = 0.013. Glucose AUC decreased 6% (p = 0.008) and insulin AUC decreased 14% (p = 0.041), with reductions in glucose at 30 minutes and 60 minutes and insulin at 60 minutes. No significant changes were seen in lipids, ambulatory blood pressure, body composition, or carotid intima-media thickness; interleukin-6 increased by 32%, and IGFBP-1 and IGFBP-2 also increased significantly.

The trial was small, short term, and limited to overweight middle-aged men, which restricts generalizability. It used a crossover design with 45 participants in the intention-to-treat analysis, and several outcomes were unchanged despite the favorable glycemic findings. Some participants were also taking lipid-lowering or antihypertensive medications, which may complicate interpretation of subgroup findings.