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Olive leaf in cardiometabolic disease – key benefits and evidence gaps

Olive leaf in cardiometabolic disease – key benefits and evidence gaps

Matthew Leach

Written by Matthew Leach and Ian Breakspear

One of the earliest scientific accounts of olive leaf as a medicine can be dated back to an 1854 issue of the Pharmaceutical Journal. In this issue, British botanist and pharmacognosist Daniel Hanbury quotes from a letter he received from a colleague, Sidney H. Maltass, who discusses the use of olive leaf decoction for fever, stating that “for many years I have found it more effective than quinine”.1 The use of olive leaf extract (OLE) for upper respiratory infections has since become popularised. In more recent years, there has been considerable interest in the role of OLE for cardiometabolic risk factors (such as hypertension [elevated blood pressure], dyslipidaemia [abnormal blood lipid levels] and dysglycaemia [abnormal blood glucose levels]; Figure 1).

Figure 1: Key activities of olive leaf extract for immune, infectious, cardiovascular and metabolic disease2-8

Hypertension & Dyslipidaemia

High-dose olive leaf extract (OLE) demonstrates promising antihypertensive and lipid lowering effects in humans. In a 2008 pilot randomised controlled trial, high doses of OLE (500 mg twice daily for 8 weeks, equivalent to 200 mg of oleuropein daily) administered to 40 monozygotic twins with borderline hypertension, was found to be superior to placebo in lowering blood pressure.9 By contrast, a 2021 randomised controlled trial of lower dose OLE (500 mg once daily for 8 weeks, equivalent to 83.5mg oleuropein per day) in 77 overweight individuals with borderline hypertension and mildly elevated cholesterol levels, was not found to be superior to placebo in lowering blood pressure or blood lipids.10

In a much larger clinical trial published in 2011, 232 patients with stage-1 hypertension were randomised to either OLE (500 mg twice daily for 8 weeks, equivalent to 200 mg of oleuropein daily) or the antihypertensive medication Captopril. The study found OLE to be comparable to Captopril in lowering both systolic and diastolic blood pressure. Patients in the OLE group also had a statistically significant reduction in serum triglyceride levels – a result not seen in the Captopril group.6

Glycaemic Regulation

Evidence from animal and mechanistic studies suggest a possible benefit in using olive leaf constituents for glycaemic regulation11; however, evidence from clinical studies is somewhat limited. In a small randomised controlled trial of 46 overweight middle-aged men, OLE (at a dose 4 capsules daily, equivalent to 51.1 mg of oleuropein and 9.7 mg of hydroxytyrosol daily) demonstrated a 15% improvement in insulin sensitivity, and a 28% improvement in pancreatic ß-cell responsiveness, when compared with placebo. Even though this study provides promising evidence of efficacy, and there were no adverse events reported in the OLE group, the study had several limitations: (a) the sample excluded women and those living with diabetes, (b) the OLE intervention was poorly described, and (c) the study did not use measures of glycaemic regulation commonly employed in clinical practice (such as HbA1c [a long-term measure of blood glucose control]).12

Some of the above study limitations were addressed in a 2011 randomised controlled trial, where 79 patients with type 2 diabetes were assigned to receive either 500 mg of OLE, or placebo, daily for 14 weeks. The study found a statistically significant difference in HbA1c levels between the OLE and placebo groups at 14 weeks (8.0% ± 1.5% vs. 8.9% ± 2.25%, respectively; P = 0.037). Fasting insulin levels were also significantly lower in the OLE group, although post-meal insulin levels were not significantly different to placebo.13 A major limitation of this study was that the authors did not analyse or declare the levels of key phytochemicals in the OLE preparation (such as oleuropein and hydroxytyrosol). The study also failed to report adverse events.

The study limitations previously mentioned, and the current uncertainty regarding the safety and effectiveness of OLE for diabetes, highlight the need for further research in this field. Responding to this call, the authors will be commencing a 24-week randomised controlled trial to investigate the impact of olive leaf extract (quantified for key phytochemicals including oleuropein and hydroxytyrosol), on HbA1c levels in patients with type 2 diabetes. The study will also assess the effect of OLE on insulin resistance, diabetes-related distress and health-related quality of life, as well as the safety of OLE. The trial is supported by a grant awarded by the Olive Wellness Institute (OWI).

Conclusion

Olive leaf extract shows promise as an intervention for modifying cardiometabolic risk factors. However, the lack of equivalence of OLE products on the Australian market14 makes clinical extrapolation from previous research somewhat problematic. Our research will establish whether a quantified Australian olive leaf extract can improve clinically relevant outcomes in patients with type 2 diabetes.

View article references

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