Background: Olive tree (Olea europaea, Oleaceae) leaves have been widely used in traditional herbal medicine to prevent and treat various diseases especially in Mediterranean countries. They contain several potentially bioactive compounds that may have hypoglycemic and hypolipidemic properties. Summary: The literature has recently been attempting to define the relationship between olive leaf (Olea europaea L. folium) polyphenols and a number of health problems. Oleuropein, the basic phenolic compound of olive leaf and its extract, is responsible for the characteristic bitter taste and unique aroma of olive fruits. Furthermore, it is shown that oleuropein and its hydrolyzed products have many beneficial effects on human health because of its antioxidant characters. A number of studies report that olive leaf has potentially positive effects on the parameters related to diabetes and cardiovascular diseases by various mechanisms. Besides, toxicity studies suggest that olive leaf is generally safe even at high doses. Key messages: Although current results obtained until today seem promising, the studies in this subject are usually on cell culture and animal trials. Moreover, mostly the extract forms of olive leaves are used in the studies. More randomized controlled human clinical trials with extensive toxicity studies are needed to evaluate potential health effects and safety.

1.
Boss A, Bishop KS, Marlow G, Barnett MP, Ferguson LR. Evidence to Support the Anti-Cancer Effect of Olive Leaf Extract and Future Directions.
Nutrients
. 2016 Aug;8(8):E513.
2.
Hassen I, Casabianca H, Hosni K. Biological activities of the natural antioxidant oleuropein: exceeding the expectation – A mini-review.
J Funct Foods
. 2015;18:926–40.
3.
Salah MB, Hafedh A, Manef A. Anti-diabetic activity and oxidative stress improvement of Tunisian Gerboui olive leaves extract on alloxan induced diabetic rats.
J Mater
. 2017;8:1359–64.
4.
Servili M, Baldioli M, Selvaggini R, Macchioni A, Montedoro G. Phenolic compounds of olive fruit: one- and two-dimensional nuclear magnetic resonance characterization of Nüzhenide and its distribution in the constitutive parts of fruit.
J Agric Food Chem
. 1999 Jan;47(1):12–8.
5.
Lins PG, Marina Piccoli Pugine S, Scatolini AM, de Melo MP. In vitro antioxidant activity of olive leaf extract (Olea europaea L.) and its protective effect on oxidative damage in human erythrocytes.
Heliyon
. 2018 Sep;4(9):e00805.
6.
Castellano JM, Delgado Hervás T, Guinda Garín MÁ, Gutiérrez-Adánez P, Rada M, Sántos-Lozano JM. Determination of major bioactive compounds from olive leaf.
Food Science and Technology – Zurich
. 2015;64(1):431–8.
7.
Servili M, Esposto S, Fabiani R, Urbani S, Taticchi A, Mariucci F, et al. Phenolic compounds in olive oil: antioxidant, health and organoleptic activities according to their chemical structure.
Inflammopharmacology
. 2009 Apr;17(2):76–84.
8.
El SN, Karakaya S. Olive tree (Olea europaea) leaves: potential beneficial effects on human health.
Nutr Rev
. 2009 Nov;67(11):632–8.
9.
Khan Y, Panchal S, Vyas N, Butani A, Kumar V. Olea europaea: a phyto-pharmacological review.
Pharmacogn Rev
. 2007;1(1):114–8.
10.
Al-Azzawie HF, Alhamdani MS. Hypoglycemic and antioxidant effect of oleuropein in alloxan-diabetic rabbits.
Life Sci
. 2006 Feb;78(12):1371–7.
11.
Rafferty EP, Wylie AR, Elliott CT, Chevallier OP, Grieve DJ, Green BD. In vitro and in vivo effects of natural putative secretagogues of glucagon-like peptide-1 (GLP-1).
Sci Pharm
. 2011 Jul-Sep;79(3):615–21.
12.
Jemai H, Fki I, Bouaziz M, Bouallagui Z, El Feki A, Isoda H, et al. Lipid-lowering and antioxidant effects of hydroxytyrosol and its triacetylated derivative recovered from olive tree leaves in cholesterol-fed rats.
J Agric Food Chem
. 2008 Apr;56(8):2630–6.
13.
Bali EB, Ergin V, Rackova L, Bayraktar O, Küçükboyaci N, Karasu Ç. Olive leaf extracts protect cardiomyocytes against 4-hydroxynonenal-induced toxicity in vitro: comparison with oleuropein, hydroxytyrosol, and quercetin.
Planta Med
. 2014 Aug;80(12):984–92.
14.
de Bock M, Thorstensen EB, Derraik JG, Henderson HV, Hofman PL, Cutfield WS. Human absorption and metabolism of oleuropein and hydroxytyrosol ingested as olive (Olea europaea L.) leaf extract.
Mol Nutr Food Res
. 2013 Nov;57(11):2079–85.
15.
Guinda Á, Castellano JM, Santos-Lozano JM, Delgado-Hervás T, Gutiérrez-Adánez P, Rada M. Determination of major bioactive compounds from olive leaf.
Lebensm Wiss Technol
. 2015;64(1):431–8.
16.
EMA. Assessment report on Olea europaea L., folium. United Kingdom: Committee on Herbal Medicinal Products (HMPC); 2012. Report No.: EMA/HMPC/430506/2009.
17.
Gariboldi P, Jommi G, Verotta L. Secoiridoids from Olea europaea.
Phytochemistry
. 1986;25(4):865–9.
18.
Soler-Rivas C, Espín JC, Wichers HJ. Oleuropein and related compounds.
J Sci Food Agric
. 2000;80(7):1013–23.
19.
Omar SH. Oleuropein in olive and its pharmacological effects.
Sci Pharm
. 2010 Apr-Jun;78(2):133–54.
20.
Echeverría F, Ortiz M, Valenzuela R, Videla LA. Hydroxytyrosol and Cytoprotection: A Projection for Clinical Interventions.
Int J Mol Sci
. 2017 Apr;18(5):930.
21.
Le Tutour B, Guedon D. Antioxidative activities of Olea europaea leaves and related phenolic compounds.
Phytochemistry
. 1992;31(4):1173–8.
22.
Charoenprasert S, Mitchell A. Factors influencing phenolic compounds in table olives (Olea europaea).
J Agric Food Chem
. 2012 Jul;60(29):7081–95.
23.
Şahin S, Bilgin M, Dramur MU. Investigation of Oleuropein Content in Olive Leaf Extract Obtained by Supercritical Fluid Extraction and Soxhlet Methods.
Sep Sci Technol
. 2011;46(11):1829–37.
24.
Yateem HA, Al-Rimawi F. Optimum Conditions for Oleuropein Extraction from Olive Leaves.
Int J Appl Sci Technol
. 2014;4(5):153–7.
25.
Visioli F, Galli C, Bornet F, Mattei A, Patelli R, Galli G, et al. Olive oil phenolics are dose-dependently absorbed in humans.
FEBS Lett
. 2000 Feb;468(2-3):159–60.
26.
Hashmi MA, Khan A, Hanif M, Farooq U, Perveen S. Traditional Uses, Phytochemistry, and Pharmacology of Olea europaea (Olive).
Evid Based Complement Alternat Med
. 2015;2015:541591.
27.
Wainstein J, Ganz T, Boaz M, Bar Dayan Y, Dolev E, Kerem Z, et al. Olive leaf extract as a hypoglycemic agent in both human diabetic subjects and in rats.
J Med Food
. 2012 Jul;15(7):605–10.
28.
Ghosian Moghaddam M, Masomi Y, Razavian M. The effect of oral consumption of olive leaves on serum glucose level and lipid profile of diabetic rats.
J Basic Clin Pathophysiol
. 2013;1(2):39–44.
29.
Abunab H, Dator WL, Hawamdeh S. Effect of olive leaf extract on glucose levels in diabetes-induced rats: A systematic review and meta-analysis.
J Diabetes
. 2017 Oct;9(10):947–57.
30.
Cao K, Xu J, Zou X, Li Y, Chen C, Zheng A, et al. Hydroxytyrosol prevents diet-induced metabolic syndrome and attenuates mitochondrial abnormalities in obese mice.
Free Radic Biol Med
. 2014 Feb;67:396–407.
31.
Hamden K, Allouche N, Damak M, Elfeki A. Hypoglycemic and antioxidant effects of phenolic extracts and purified hydroxytyrosol from olive mill waste in vitro and in rats.
Chem Biol Interact
. 2009 Aug;180(3):421–32.
32.
Tabernero M, Sarriá B, Largo C, Martínez-López S, Madrona A, Espartero JL, et al. Comparative evaluation of the metabolic effects of hydroxytyrosol and its lipophilic derivatives (hydroxytyrosyl acetate and ethyl hydroxytyrosyl ether) in hypercholesterolemic rats.
Food Funct
. 2014 Jul;5(7):1556–63.
33.
Pirozzi C, Lama A, Simeoli R, Paciello O, Pagano TB, Mollica MP, et al. Hydroxytyrosol prevents metabolic impairment reducing hepatic inflammation and restoring duodenal integrity in a rat model of NAFLD.
J Nutr Biochem
. 2016 Apr;30:108–15.
34.
Jemai H, El Feki A, Sayadi S. Antidiabetic and antioxidant effects of hydroxytyrosol and oleuropein from olive leaves in alloxan-diabetic rats.
J Agric Food Chem
. 2009 Oct;57(19):8798–804.
35.
Peyrol J, Riva C, Amiot MJ. Hydroxytyrosol in the Prevention of the Metabolic Syndrome and Related Disorders.
Nutrients
. 2017 Mar;9(3):306.
36.
de Bock M, Derraik JG, Brennan CM, Biggs JB, Morgan PE, Hodgkinson SC, et al. Olive (Olea europaea L.) leaf polyphenols improve insulin sensitivity in middle-aged overweight men: a randomized, placebo-controlled, crossover trial.
PLoS One
. 2013;8(3):e57622.
37.
Kontogianni VG, Charisiadis P, Margianni E, Lamari FN, Gerothanassis IP, Tzakos AG. Olive leaf extracts are a natural source of advanced glycation end product inhibitors.
J Med Food
. 2013 Sep;16(9):817–22.
38.
Salah MB, Abdelmelek H, Abderraba M. Effects of olive leave extract on metabolic disorders and oxidative stress induced by 2.45 GHz WIFI signals.
Environ Toxicol Pharmacol
. 2013 Nov;36(3):826–34.
39.
Cumaoğlu A, Ari N, Kartal M, Karasu Ç. Polyphenolic extracts from Olea europea L. protect against cytokine-induced β-cell damage through maintenance of redox homeostasis.
Rejuvenation Res
. 2011 Jun;14(3):325–34.
40.
Kaeidi A, Esmaeili-Mahani S, Sheibani V, Abbasnejad M, Rasoulian B, Hajializadeh Z, et al. Olive (Olea europaea L.) leaf extract attenuates early diabetic neuropathic pain through prevention of high glucose-induced apoptosis: in vitro and in vivo studies.
J Ethnopharmacol
. 2011 Jun;136(1):188–96.
41.
Mapanga RF, Tufts MA, Shode FO, Musabayane CT. Renal effects of plant-derived oleanolic acid in streptozotocin-induced diabetic rats.
Ren Fail
. 2009;31(6):481–91.
42.
Kiraz A, Simsek T, Tekin SZ, Elmas S, Tekin M, Sahin H, et al. Investigation of the effects of oleuropein rich diet on rat enteric bacterial flora.
Bratisl Lek Listy
. 2016;117(12):734–7.
43.
Liehr M, Mereu A, Pastor JJ, Quintela JC, Staats S, Rimbach G, et al. Olive oil bioactives protect pigs against experimentally-induced chronic inflammation independently of alterations in gut microbiota.
PLoS One
. 2017 Mar;12(3):e0174239.
44.
Lockyer S, Rowland I, Spencer JP, Yaqoob P, Stonehouse W. Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: a randomised controlled trial.
Eur J Nutr
. 2017 Jun;56(4):1421–32.
45.
Olmez E, Vural K, Gok S, Ozturk Z, Kayalar H, Ayhan S, et al. Olive Leaf Extract Improves the Atherogenic Lipid Profile in Rats Fed a High Cholesterol Diet.
Phytother Res
. 2015 Oct;29(10):1652–7.
46.
Poudyal H, Campbell F, Brown L. Olive leaf extract attenuates cardiac, hepatic, and metabolic changes in high carbohydrate-, high fat-fed rats.
J Nutr
. 2010 May;140(5):946–53.
47.
Boss A, Kao CH, Murray PM, Marlow G, Barnett MP, Ferguson LR. Human intervention study to assess the effects of supplementation with olive leaf extract on peripheral blood mononuclear cell gene expression.
Int J Mol Sci
. 2016 Dec;17(12):2019.
48.
Yoon L, Liu YN, Park H, Kim HS. Olive Leaf Extract Elevates Hepatic PPAR α mRNA Expression and Improves Serum Lipid Profiles in Ovariectomized Rats.
J Med Food
. 2015 Jul;18(7):738–44.
49.
Efentakis P, Iliodromitis EK, Mikros E, Papachristodoulou A, Dagres N, Skaltsounis AL, et al. Effects of the olive tree leaf constituents on myocardial oxidative damage and atherosclerosis.
Planta Med
. 2015 Jun;81(8):648–54.
50.
Visioli F, Bellosta S, Galli C. Oleuropein, the bitter principle of olives, enhances nitric oxide production by mouse macrophages.
Life Sci
. 1998;62(6):541–6.
51.
Wu LX, Xu YY, Yang ZJ, Feng Q. Hydroxytyrosol and olive leaf extract exert cardioprotective effects by inhibiting GRP78 and CHOP expression.
J Biomed Res
. 2018 Sep;32(5):371–9.
52.
Xu Y, Wu L, Chen A, Xu C, Feng Q. Protective effects of olive leaf extract on acrolein-exacerbated myocardial infarction via an endoplasmic reticulum stress pathway.
Int J Mol Sci
. 2018 Feb;19(2):493.
53.
Clewell AE, Béres E, Vértesi A, Glávits R, Hirka G, Endres JR, et al. A comprehensive toxicological safety assessment of an extract of Olea Europaea L. leaves (BonoliveTM).
Int J Toxicol
. 2016 Mar-Apr;35(2):208–21.
54.
Guex CG, Reginato FZ, Figueredo KC, da Silva AR, Pires FB, Jesus RD, et al. Safety assessment of ethanolic extract of Olea europaea L. leaves after acute and subacute administration to Wistar rats.
Regul Toxicol Pharmacol
. 2018 Jun;95:395–9.
55.
Kendall M, Batterham M, Obied H, Prenzler PD, Ryan D, Robards K. Zero effect of multiple dosage of olive leaf supplements on urinary biomarkers of oxidative stress in healthy humans.
Nutrition
. 2009 Mar;25(3):270–80.
56.
Omer SA, Elobeid MA, Elamin MH, Hassan ZK, Virk P, Daghestani MH, et al. Toxicity of olive leaves (Olea europaea L.) in Wistar albino rats.
Asian J Anim Vet Adv
. 2012;7(11):1175–82.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.