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Olive Leaf Extract and Bioavailability

Olive Leaf Extract and Bioavailability

We know that olive leaves are an important source of bioactive compounds. Importantly, olive leaves offer environmental benefits because of the exploitation of residues of olive oil.

Many research objectives have been initiated to assess the antioxidant, antimicrobial and anticancer effects of olive leaf aqueous extract before and after in vitro gastrointestinal processes. (1)

The bioavailability of a substance is described as the extent and rate at which the active compound (the original form, or a metabolite) enters the systemic circulation and accesses its site of action in the body. In simple terms, bioavailability tells us how much of the active form of a supplement or drug reaches the area of action in the body. Without the substance entering the circulation, and reaching the site of action, there will typically be little or no therapeutic effects.


In Spanish research, optimal phenolic extraction processes were used. Individual bioactive molecules such as oleuropein, hydroxytyrosol, luteolin, apigenin and vebascoside were found at high concentration in the aqueous extract while others like vanillin, p-cumaric acid and caffeic acid were minor compounds.

Concerning the in vitro digestion processing, most of the phenolic acids present in the olive leaf aqueous extract, except for caffeic acid, were found in both the simulated gastric fluid and the simulated intestinal fluid in their free form, which is rather unstable during gastric digestion. More importantly, the remaining amount of phenolic compounds after gastric and duodenal digestion was very significant, especially the concentration of oleuropein, which is the most abundant phenol in olive leaves. This is of interest bearing in mind the protective effects of oleuropein against oxidative damage.

In this research, it was found that the digested extract maintained high antioxidant activity, which may be positively correlated to the amount of hydroxityrosol, tyrosol and especially oleuropein found after gastric and intestinal digestion because they are known to possess high antioxidant activity.

Knowledge of phenolics bioavailability is essential to understand their conjugation and bioavailability in the organism.

There is evidence (2) that when phenolics are absorbed in their free form, their absorption and conjugation follow the same pathways as that of flavonoids. In addition, phenolic metabolites can retain a strong antioxidant activity and might exert a strong antioxidant activity in vivo.(2)

In the assay of antimicrobial activity, the entire extracts were used because they may be more beneficial than isolated constituents –a  bioactive individual component can change its properties in the presence of other compounds in the extracts. (3)


Overall, results suggest that the olive leaf aqueous extract, which possessed high content of phenolic compounds, could be absorbed by the gastrointestinal tract, and its regular consumption may be helpful in the management and prevention of oxidative stress-related chronic diseases, bacterial infection, or cancer. In fact, even after simulated digestion, the olive leaf extract depicted in vitro antioxidant, antimicrobial and anti-tumour activities. (1)



Previous research in New Zealand (4) supports efficient bioavailability. Compared to capsules, olive leaf extract in liquid formulation led to greater oleuropein peak levels in plasma.

Previous literature on the bioavailability of olive phenols has focused on hydroxytyrosol and oleuropein. Conjugated metabolites of hydroxytyrosol are the main olive phenolic metabolites found in biological fluids in vivo. However,there is further emerging literature on bioactivity of these metabolites. For example, glucuronidated hydroxysterol is a free-radical scavenger five times more potent than the parent hydroxytyrosol. (5) Although glucuronidated hydroxytyrosol is inactive against LDL-cholesterol oxidation, it protected renal tubular cells against oxidative damage in vivo. (6)


An explanation for olive phenol bioactivity has been proposed, with downregulation of proatherogenic genes after olive oil consumption. (7) There is also in vitro evidence of nutrigenomic interaction on several cell lines covering cancer (8) and insulin sensitivity. (9)

In summary of this New Zealand research, conjugated (sulphated and glucuronidated) metabolites of hydroxytyrosol are the primary oleuropein metabolites recovered in plasma and urine following olive leaf extract consumption.

Further Spanish research strengthens the antioxidant benefits of olive phenolics. It was concluded that oleuropein is extensively metabolized to yield many other metabolites which have specific biological properties many of which are yet to be explored. In this study, the intake of 250mg of an oleuropein-rich olive leaf extract decreased plasma MDA levels in post-menopausal women, which was related to higher plasma levels of metabolites derived from oleuropein.


Malondialdehyde (MDA) is one of the final products of polyunsaturated fatty acids peroxidation in the cells. An increase in free radicals causes overproduction of MDA. Malondialdehyde level is commonly known as a marker of oxidative stress and the antioxidant status in cancerous patients.


Where does this research leave us?

We now can feel confident in using high quality olive leaf extract where reduced oxidative stress is a primary consideration. Anti-microbial and anti-viral activity, insulin sensitivity, cardiovascular protection and oral health are areas in which olive leaf extract has potential benefits.

View article references

  1. Bioavailability of Bioactive Molecules from Olive Leaf Extracts and its Functional Value Daniel Martin-Vertedor, Maria Garrido, Jose Antonio Pariente, Javier Espino, Jonathan Delgado-Adamez Phytother.Res 30:1172-1179 (2016)
  2. Heleno SA et al., 2015 Bioactivity of phenolic acids; metabolites versus parent compounds, a review. Food Chem 173, 501-513
  3. Borchers AT et at 2004. Mushrooms, tumours, and immunity, an update. Exp Biol Med 229, 393-406 Lee and Lee 2010. The microencapsulared ascorbic acid release in vivo and its effect on iron bioavailability. Arch Pharm Res 26. 874-87
  4. Human Absorption and metabolism of oleuropein and hydroxytyrosol ingested as olive (Olea europaea L.) leaf extract. Martin de Bock et al. Mol. Nutr. Food Res. 2013 2079-2085
  5. Tuck KL et al. Structural characterization of the metabolites of hydroxytyrosol, the principle phenolic component in olive oil, in rats. J.Agric, Food Chem. 2002, 50, 2404-2409
  6. Deiana M et al. Hydroxytyrosol glucuronides protect renal tubular epithelial cells against H2O2 induced oxidative damage. Chem. Biol. Interact. 2011, 193. 232-239
  7. Konstantinidou, V et al. In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Meditarranean diet: a randomized controlled trial. FASEB J. 2010, 24.2546-2557
  8. Khymenets O et al. Mononuclear cell transcriptome response after sustained virgin olive oil consumption in humans: an exploratory nutrigenomics study. OMICS 2009, 13, 7-19
  9. Konstantinidou V et al. Time course of changes in the expression of insulin sensitivity-related genes after an acute load of virgin olive oil. OMICS 20099, 13, 431-438