The effect of olive leaf extract on cardiovascular health markers: a randomized placebo-controlled clinical trial

Yala Stevens, Bjorn Winkens, Daisy Jonkers, Adrian Masclee, Yala Stevens, Bjorn Winkens, Daisy Jonkers, Adrian Masclee

Abstract

Purpose: Overweight and obesity are associated with many health problems, including cardiovascular disease (CVD). Evidence from previous studies has shown that extracts from olive leaves rich in olive phenolics are able to positively affect CVD risk factors, such as high blood pressure and dyslipidemia. The aim of this study was to investigate the effect of 8-week olive leaf extract (OLE) administration on blood lipid profiles in overweight/obese subjects with mildly elevated cholesterol levels.

Methods: In this randomized, double-blind, placebo-controlled study, 77 healthy adult overweight/obese subjects (aged 56 ± 10 years and BMI 29.0 ± 2.7 kg/m2) with total cholesterol levels of 5.0-8.0 mmol/L (5.9 ± 0.7 mmol/L) were randomly assigned to receive 500 mg of OLE (n = 39) or placebo (n = 38) for 8 weeks. In total, 74 subjects completed the entire study protocol. At baseline, after 4 weeks, and after 8 weeks of supplementation, blood lipid profiles, oxidized low-density lipoprotein (oxLDL), blood pressure, glucose, and insulin levels were assessed. In addition, liver function parameters were measured at baseline and after 8 weeks.

Results: OLE supplementation did not significantly affect blood lipid levels after 4 weeks or after 8 weeks compared to placebo (all p > 0.05). For oxLDL, blood pressure, glucose, and insulin levels and liver function parameters, also no statistically significant differences were found between the two intervention groups (all p > 0.05).

Conclusions: Blood lipid profiles were not significantly affected by 8 weeks OLE supplementation in overweight/obese subjects with mildly elevated cholesterol levels.

Trial registered: The trial has been registered at ClinicalTrials.gov (NCT02990637).

Keywords: Blood lipid profiles; Cardiovascular disease; Olive leaf extract; Overweight.

Conflict of interest statement

YS is an employee of BioActor BV. DJ is involved in research projects as part of private–public partnership grants (i.e., TKI/Well on Wheat project and CCC NWO Carbokinetics).

References

    1. Collaborators GBDO, Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, et al. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 2017;377(1):13–27. doi: 10.1056/NEJMoa1614362.
    1. Kopelman P. Health risks associated with overweight and obesity. Obes Rev. 2007;8(Suppl 1):13–17. doi: 10.1111/j.1467-789X.2007.00311.x.
    1. Hurtubise J, McLellan K, Durr K, Onasanya O, Nwabuko D, Ndisang JF. The Different Facets of Dyslipidemia and Hypertension in Atherosclerosis. Curr Atheroscler Rep. 2016;18(12):82. doi: 10.1007/s11883-016-0632-z.
    1. Herrington W, Lacey B, Sherliker P, Armitage J, Lewington S. Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease. Circ Res. 2016;118(4):535–546. doi: 10.1161/CIRCRESAHA.115.307611.
    1. Nederlands Huisartsen Genootschap Cardiovasculair risicomanagement . Accessed 3 June 2020
    1. Martínez-González MA, Gea A, Ruiz-Canela M. The mediterranean diet and cardiovascular health. Circ Res. 2019;124(5):779–798. doi: 10.1161/circresaha.118.313348.
    1. Kouli GM, Panagiotakos DB, Kyrou I, Magriplis E, Georgousopoulou EN, Chrysohoou C, Tsigos C, Tousoulis D, Pitsavos C. Olive oil consumption and 10-year (2002–2012) cardiovascular disease incidence: the ATTICA study. Eur J Nutr. 2019;58(1):131–138. doi: 10.1007/s00394-017-1577-x.
    1. Guasch-Ferre M, Hu FB, Martinez-Gonzalez MA, Fito M, Bullo M, Estruch R, Ros E, Corella D, Recondo J, Gomez-Gracia E, Fiol M, Lapetra J, Serra-Majem L, Munoz MA, Pinto X, Lamuela-Raventos RM, Basora J, Buil-Cosiales P, Sorli JV, Ruiz-Gutierrez V, Martinez JA, Salas-Salvado J. Olive oil intake and risk of cardiovascular disease and mortality in the PREDIMED Study. BMC Med. 2014;12:78. doi: 10.1186/1741-7015-12-78.
    1. Estruch R, Ros E, Salas-Salvado J, Covas MI, Corella D, Aros F, Gomez-Gracia E, Ruiz-Gutierrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pinto X, Basora J, Munoz MA, Sorli JV, Martinez JA, Fito M, Gea A, Hernan MA, Martinez-Gonzalez MA, Investigators PS. Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med. 2018;378(25):e34. doi: 10.1056/NEJMoa1800389.
    1. Farras M, Canyelles M, Fito M, Escola-Gil JC. Effects of virgin olive oil and phenol-enriched virgin olive oils on lipoprotein atherogenicity. Nutrients. 2020;12(3):601. doi: 10.3390/nu12030601.
    1. Schwingshackl L, Krause M, Schmucker C, Hoffmann G, Rucker G, Meerpohl JJ. Impact of different types of olive oil on cardiovascular risk factors: a systematic review and network meta-analysis. Nutr Metab Cardiovasc Dis. 2019;29(10):1030–1039. doi: 10.1016/j.numecd.2019.07.001.
    1. Cicero AFG, Fogacci F, Colletti A. Food and plant bioactives for reducing cardiometabolic disease risk: an evidence based approach. Food Funct. 2017;8(6):2076–2088. doi: 10.1039/c7fo00178a.
    1. Lockyer S, Yaqoob P, Spencer JPE, Rowland I. Olive leaf phenolics and cardiovascular risk reduction: physiological effects and mechanisms of action. Nutrition Aging. 2012;1(2):125–140. doi: 10.3233/nua-2012-0011.
    1. Al-Azzawie HF, Alhamdani MS. Hypoglycemic and antioxidant effect of oleuropein in alloxan-diabetic rabbits. Life Sci. 2006;78(12):1371–1377. doi: 10.1016/j.lfs.2005.07.029.
    1. 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;57(19):8798–8804. doi: 10.1021/jf901280r.
    1. Eidi A, Eidi M, Darzi R. Antidiabetic effect of Olea europaea L. in normal and diabetic rats. Phytother Res. 2009;23(3):347–350. doi: 10.1002/ptr.2629.
    1. Jemai H, Bouaziz M, Fki I, El Feki A, Sayadi S. Hypolipidimic and antioxidant activities of oleuropein and its hydrolysis derivative-rich extracts from Chemlali olive leaves. Chem Biol Interact. 2008;176(2–3):88–98. doi: 10.1016/j.cbi.2008.08.014.
    1. Gonzalez M, Zarzuelo A, Gamez MJ, Utrilla MP, Jimenez J, Osuna I. Hypoglycemic activity of olive leaf. Planta Med. 1992;58(6):513–515. doi: 10.1055/s-2006-961538.
    1. Ivanov M, Vajic UJ, Mihailovic-Stanojevic N, Miloradovic Z, Jovovic D, Grujic-Milanovic J, Karanovic D, Dekanski D. Highly potent antioxidant Olea europaea L. leaf extract affects carotid and renal haemodynamics in experimental hypertension: the role of oleuropein. EXCLI J. 2018;17:29–44. doi: 10.17179/excli2017-1002.
    1. Wainstein J, Ganz T, Boaz M, Bar Dayan Y, Dolev E, Kerem Z, Madar Z. Olive leaf extract as a hypoglycemic agent in both human diabetic subjects and in rats. J Med Food. 2012;15(7):605–610. doi: 10.1089/jmf.2011.0243.
    1. Mohagheghi F, Bigdeli MR, Rasoulian B, Hashemi P, Pour MR. The neuroprotective effect of olive leaf extract is related to improved blood–brain barrier permeability and brain edema in rat with experimental focal cerebral ischemia. Phytomedicine. 2011;18(2–3):170–175. doi: 10.1016/j.phymed.2010.06.007.
    1. Wang L, Geng C, Jiang L, Gong D, Liu D, Yoshimura H, Zhong L. The anti-atherosclerotic effect of olive leaf extract is related to suppressed inflammatory response in rabbits with experimental atherosclerosis. Eur J Nutr. 2008;47(5):235–243. doi: 10.1007/s00394-008-0717-8.
    1. de Bock M, Derraik JG, Brennan CM, Biggs JB, Morgan PE, Hodgkinson SC, Hofman PL, Cutfield WS. 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. doi: 10.1371/journal.pone.0057622.
    1. Lockyer S, Rowland I, Spencer JPE, 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;56(4):1421–1432. doi: 10.1007/s00394-016-1188-y.
    1. Perrinjaquet-Moccetti T, Busjahn A, Schmidlin C, Schmidt A, Bradl B, Aydogan C. Food supplementation with an olive (Olea europaea L.) leaf extract reduces blood pressure in borderline hypertensive monozygotic twins. Phytother Res. 2008;22(9):1239–1242. doi: 10.1002/ptr.2455.
    1. Filip R, Possemiers S, Heyerick A, Pinheiro I, Raszewski G, Davicco MJ, Coxam V. Twelve-month consumption of a polyphenol extract from olive (Olea europaea) in a double blind, randomized trial increases serum total osteocalcin levels and improves serum lipid profiles in postmenopausal women with osteopenia. J Nutr Health Aging. 2015;19(1):77–86. doi: 10.1007/s12603-014-0480-x.
    1. Susalit E, Agus N, Effendi I, Tjandrawinata RR, Nofiarny D, Perrinjaquet-Moccetti T, Verbruggen M. Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: comparison with Captopril. Phytomedicine. 2011;18(4):251–258. doi: 10.1016/j.phymed.2010.08.016.
    1. Turck D, Bresson JL, Burlingame B, Dean T, Fairweather-Tait S, Heinonen M, et al. Guidance for the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health. EFSA J. 2018;16(1):05136. doi: 10.2903/j.efsa.2018.5136.
    1. Wilms E, Jonkers D, Savelkoul HFJ, Elizalde M, Tischmann L, de Vos P, Masclee AAM, Troost FJ. The impact of pectin supplementation on intestinal barrier function in healthy young adults and healthy elderly. Nutrients. 2019;11(7):1554. doi: 10.3390/nu11071554.
    1. Riegler G, Esposito I. Bristol scale stool form A still valid help in medical practice and clinical research. Tech Coloproctol. 2001;5(3):163–164. doi: 10.1007/s101510100019.
    1. Mahamuni SP, Khose RD, Menaa F, Badole SL. Therapeutic approaches to drug targets in hyperlipidemia. BioMedicine. 2012;2(4):137–146. doi: 10.1016/j.biomed.2012.08.002.
    1. Vega GL, Barlow CE, Grundy SM, Leonard D, DeFina LF. Triglyceride-to-high-density-lipoprotein-cholesterol ratio is an index of heart disease mortality and of incidence of type 2 diabetes mellitus in men. J Investig Med. 2014;62(2):345–349. doi: 10.2310/JIM.0000000000000044.
    1. Bittner V, Johnson BD, Zineh I, Rogers WJ, Vido D, Marroquin OC, Bairey-Merz CN, Sopko G. The triglyceride/high-density lipoprotein cholesterol ratio predicts all-cause mortality in women with suspected myocardial ischemia: a report from the Women’s Ischemia Syndrome Evaluation (WISE) Am Heart J. 2009;157(3):548–555. doi: 10.1016/j.ahj.2008.11.014.
    1. Hernaez A, Remaley AT, Farras M, Fernandez-Castillejo S, Subirana I, Schroder H, Fernandez-Mampel M, Munoz-Aguayo D, Sampson M, Sola R, Farre M, de la Torre R, Lopez-Sabater MC, Nyyssonen K, Zunft HJ, Covas MI, Fito M. Olive oil polyphenols decrease LDL concentrations and LDL atherogenicity in men in a randomized controlled trial. J Nutr. 2015;145(8):1692–1697. doi: 10.3945/jn.115.211557.
    1. Fernandez-Castillejo S, Valls RM, Castaner O, Rubio L, Catalan U, Pedret A, Macia A, Sampson ML, Covas MI, Fito M, Motilva MJ, Remaley AT, Sola R. Polyphenol rich olive oils improve lipoprotein particle atherogenic ratios and subclasses profile: a randomized, crossover, controlled trial. Mol Nutr Food Res. 2016;60(7):1544–1554. doi: 10.1002/mnfr.201501068.
    1. de Bock M, Thorstensen EB, Derraik JGB, 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;57(11):2079–2085. doi: 10.1002/mnfr.201200795.
    1. Redan BW, Buhman KK, Novotny JA, Ferruzzi MG. Altered transport and metabolism of phenolic compounds in obesity and diabetes: implications for functional food development and assessment. Adv Nutr. 2016;7(6):1090–1104. doi: 10.3945/an.116.013029.
    1. Burgess E, Hassmen P, Pumpa KL. Determinants of adherence to lifestyle intervention in adults with obesity: a systematic review. Clin Obes. 2017;7(3):123–135. doi: 10.1111/cob.12183.
    1. Mensink RP, Zock PL, Kester AD, Katan MB. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr. 2003;77(5):1146–1155. doi: 10.1093/ajcn/77.5.1146.
    1. Kastorini CM, Milionis HJ, Esposito K, Giugliano D, Goudevenos JA, Panagiotakos DB. The effect of Mediterranean diet on metabolic syndrome and its components: a meta-analysis of 50 studies and 534,906 individuals. J Am Coll Cardiol. 2011;57(11):1299–1313. doi: 10.1016/j.jacc.2010.09.073.
    1. Menaa F, Menaa A, Menaa B, Treton J. Trans-fatty acids, dangerous bonds for health? A background review paper of their use, consumption, health implications and regulation in France. Eur J Nutr. 2013;52(4):1289–1302. doi: 10.1007/s00394-012-0484-4.
    1. Gao S, Zhao D, Wang M, Zhao F, Han X, Qi Y, Liu J. Association between circulating oxidized LDL and atherosclerotic cardiovascular disease: a meta-analysis of observational studies. Can J Cardiol. 2017;33(12):1624–1632. doi: 10.1016/j.cjca.2017.07.015.
    1. Marchesini G, Moscatiello S, Di Domizio S, Forlani G. Obesity-associated liver disease. J Clin Endocrinol Metab. 2008;93(11 Suppl 1):S74–80. doi: 10.1210/jc.2008-1399.

Source: PubMed

Подписаться