Olive Leaf Extract: The Oleuropein Blood Pressure Trials and the Captopril Head-to-Head

Olive leaf extract is sold widely as a blood pressure and immune support supplement. Its principal bioactive is oleuropein, a secoiridoid compound also found in extra virgin olive oil but at much lower concentrations. The leaf extract trial record is modest in size but unusually direct, including a head-to-head trial against the prescription ACE inhibitor captopril.

The Susalit captopril head-to-head

The most-cited olive leaf trial is Susalit and colleagues 2011, an Indonesian double-blind randomized study of 232 adults with stage 1 hypertension. Participants received 1,000 mg per day of olive leaf extract standardized to 20 percent oleuropein, or captopril 25 mg twice daily for 8 weeks. Both arms produced clinically meaningful and statistically similar blood pressure reductions — systolic fell by 11.5 mmHg in the olive leaf arm versus 13.7 mmHg with captopril [1]. The trial has been criticized for the relatively low captopril dose, but the finding that olive leaf reached the same effect range is striking.

Pre-hypertensive twins

Perrinjaquet-Moccetti and colleagues 2008 randomized 40 pre-hypertensive monozygotic twins to 500 or 1,000 mg per day of olive leaf extract or placebo for 8 weeks. Systolic pressure fell by approximately 11 mmHg in the higher-dose arm versus baseline, with smaller effects at the lower dose [2]. The within-pair design controls for genetics and most environmental exposures, strengthening the inference.

The lipid signal

Several trials have reported small reductions in LDL cholesterol (5 to 10 mg/dL) with olive leaf extract over 8 to 12 weeks [3]. The 2019 systematic review by Lockyer and colleagues found that the LDL effect was less robust than the blood pressure effect [4]. Mechanism likely involves antioxidant inhibition of LDL oxidation and modest stimulation of LDL receptor expression.

Glycemic and inflammatory effects

A 2013 trial in middle-aged overweight men by de Bock and colleagues found that 51.1 mg per day of oleuropein for 12 weeks improved insulin sensitivity by 15 percent measured with hyperinsulinemic euglycemic clamp [5]. Inflammatory markers were modestly reduced but the effect size was small. The clinical relevance for non-diabetic adults is uncertain.

Mechanism and pharmacology

Oleuropein and its hydrolysis product hydroxytyrosol scavenge superoxide and peroxyl radicals, inhibit angiotensin-converting enzyme in vitro, and improve endothelial NO bioavailability in human aortic endothelial cells. Oral bioavailability of oleuropein is moderate, with rapid first-pass metabolism to hydroxytyrosol metabolites in plasma. Extracts standardized to 16 to 20 percent oleuropein at 500 to 1,000 mg per day approach the doses used in positive trials.

Interactions and cautions

Additive hypotensive effects with prescription antihypertensives are plausible and have been reported anecdotally. Olive leaf inhibits CYP2C9 in vitro, raising theoretical concerns for warfarin and certain NSAIDs. Hypoglycemic episodes have been reported in patients on sulfonylureas. People should not substitute olive leaf for prescribed antihypertensive therapy in stage 2 hypertension; the magnitude of effect is similar to a low-dose ACE inhibitor and unlikely to control more severe blood pressure elevation.