Exploring the Potential Health Benefits of Olive Leaf Extracts

Olive oil, nearly 75% of which originates in Spain, is widely recognized as a source of healthy fats, but the light gray foliage of olive trees may also represent a treasure trove of substances that afford potential health benefits.

Like most plants, olive leaves contain an array of phytochemicals. Extracts of olive leaves (OLE) contain secoiridoids (primarily, oleuropein, oleosid, and oleurosid) and polyphenols, including 3-hydroxytyrosol (HT) and its derivatives. The profile of these and other phenolics is dynamic and dependent on cultivar, time of harvest, tree maturation, and even extraction technology (Wani, Masoodi, Gani, et al. 2018).

A careful examination of OLE safety, particularly genotoxicity of HT and classic toxicokinetics and metabolism in rodents, indicates that a 15% or 35% pure HT preparation was not mutagenic based on Ames tests, although cytotoxicity was observed in human lymphocytes at high concentrations (Auñon-Calles, Canut, and Visioli 2013). Like many xenobiotic substances, HT and its derivatives appear to be sulfated and undergo other metabolic processes prior to urinary elimination (D’Angelo, Manna, Migliardi, et al. 2001). These investigations indicate that these olive leaf phenolics are safe at studied doses and routes of administration.

Understanding the bioavailability of these phenolics, particularly HT and oleuropein, is essential if the scientific community is to evaluate their safety and potential health benefits. Several years ago, a group of investigators evaluated the bioavailability of these phenolics among 16 healthy women with normal BMIs and living in the Netherlands (García-Villalba, Larrosa, Possemiers, et al. 2014). The pre- and postmenopausal subjects consumed 250 mg of oleuropein-rich OLE, which produced 15 dominant metabolites, which peaked in plasma and urine samples at 30 and 60 min post oral administration.

Earlier assessments of oleuropein absorption using a rodent model estimated an intestinal bioavailability at ~12% to ~41%, depending on the osmotic tone of the perfused gastrointestinal lumen (Edgecombe, Stretch, and Hayball 2000). Two later absorption studies among humans or a human cell line provided different results. In one study among ileostomy patients, apparent absorption ranged from 55% to 66% of the administered dose (Vissers, Zock, Roodenburg, et al. 2002). Another study using human Caco-2 cells and other in vitro intestinal models indicated some of the OLE phenolics are stable under gastric acid conditions in the stomach and duodenum, whereas some are hydrolyzed in the jejunum and ileum. It also appears that some of the conjugated forms, particularly that of oleuropein, reach the colon where subsequent fermentation by colonic microflora may contribute to further biotransformations (Corona, Tzounis, Dessl, et al. 2006).

A short-term study that introduced OLE (~140 mg HT, ~6 mg oleuropein per day) administered to 61 humans indicated systolic and diastolic blood pressures may be reduced sufficiently to reduce the risk of coronary heart disease and possibly stroke by 14%–22% (Lockyer, Rowland, Spencer, et al. 2017). An earlier study by the same group indicated the consumption of an OLE with ~51 mg of oleuropein and ~10 mg of HT by 18 humans over a 4-week period may decrease vascular stiffness, perhaps as a result of a decline in inflammatory cytokine IL-8 production (Lockyer, Corona, Yaqoob, et al. 2015). Another 8-week study among 72 subjects diagnosed with stage 1 hypertension that evaluated a commercial OLE (composition undisclosed) indicated that the administration of 500 mg of the extract twice daily was as effective (statistically) in lowering blood pressure as a 12.5 mg dose of a common anti-hypertensive medication also administered twice daily (Susalit, Agus, Effendi, et al. 2011).

A European Food Safety Authority panel concluded that OLE, standardized for its polyphenol content (e.g., HT and its derivatives), was sufficiently characterized and supported for a number of health claims, such as a contribution to the health and normal function of the gastrointestinal tract and upper respiratory tract (EFSA 2011). More recently, the U.S. Food and Drug Administration accepted a GRAS notification for a phenolic preparation from olive fruit that advanced 5 mg to 10 mg of HT per serving in an array of baked goods, beverages, snacks, and related products intended for the general population was safe (FDA 2018).

The emerging evidence thus underscores the possibility of a novel added value from the olive oil industry. Understanding the physical and physiological complexities of future value-added food ingredients is essential.