Effects of A Food Supplement Containing Oleuropein, Elenolic Acid, Rutin, Hydroxytyrosol and Tyrosol in Patients with Hepatic Steatosis

Giuseppe Derosa^{1, 2,} , Angela D’Angelo^{3, 4}, Giovanni V. Gaudio⁵ and Luigina Guasti⁶

¹Centre of Diabetes and Metabolic Diseases, University of Pavia, and IRCCS Policlinico San Matteo Foundation, PAVIA, Italy

²Laboratory of Molecular Medicine, University of Pavia, PAVIA, Italy;Department of Internal Medicine and Therapeutics, University of Pavia, PAVIA, Italy

³Laboratory of Molecular Medicine, University of Pavia, PAVIA, Italy

⁴Department of Internal Medicine and Therapeutics, University of Pavia, PAVIA, Italy

⁵Internal Medicine Division, Angelo Bellini Hospital, Somma Lombardo, VARESE, Italy

⁶Geriatric Division, ASST dei Sette Laghi, University of Insubria, VARESE, Italy

Cite this paper:
Giuseppe Derosa, Angela D’Angelo, Giovanni V. Gaudio and Luigina Guasti. Effects of A Food Supplement Containing Oleuropein, Elenolic Acid, Rutin, Hydroxytyrosol and Tyrosol in Patients with Hepatic Steatosis. American Journal of Medical Sciences and Medicine. 2025; 13(1):8-14. doi: 10.12691/ajmsm-13-1-2

Abstract

Non-alcoholic fatty liver disease (NAFLD) represents the leading cause of liver disease and is characterized by obesity, hyperglycemia, insulin-resistance, dyslipidemia and hypertension. The aim of this study was to evaluate if Olife® consumption in patients with NAFLD could improve fatty liver grade and related metabolic and inflammatory parameters. Eighty-two Caucasian patients aged ≥ 18 of both sexes diagnosed with NAFLD, according to practice guidelines, were enrolled in a single-center, double-blind, open label, randomized, controlled study. Patients were randomized to follow a standardized Diet or a standardized Diet + Olife® for 3 months. No changes in BMI, circumference, FPG, TC, LDL-C, HDL-C and Tg were observed with either treatment. In the group of patients receiving Diet + Olife®, a significant decrease in hs-CRP and TNF-α as well as an increase in ADN (p < 0.05 compared to Baseline and Diet) was observed, respectively. Transaminases and γ-GT were significantly reduced (p < 0.05 vs Baseline and Diet) in Diet + Olife® group compared to Diet group, respectively. In addition, AST/ALT ratio and HIS were significantly lower (p < 0.05 vs Baseline and Diet) in the Diet + Olife® group compared to Diet group, respectively. All patients showed signs of hepatic steatosis improvement or disappearance. In conclusion Olife® added to Diet ameliorates hepatic parameters and echography grading, and manages to reduce inflammatory parameters during the 3 months of study.

Keywords:
food supplement oleuropein elenolic acid rutin hydroxytyrosol tyrosol hepatic steatosis

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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References:

[1]	Lonardo, A., Ballestri, S., Marchesini, G., Angulo, P. and Loria, P, “Nonalcoholic fatty liver disease: a precursor of the metabolic syndrome”, Dig Liver Dis, 47 (3), 181-190, 2015.
[2]	Rinella, M.E, “Nonalcoholic Fatty Liver Disease: A Systematic Review”, JAMA, 313 (22), 2263-2273, 2015.
[3]	Koppe, S.W, “Obesity and the liver: nonalcoholic fatty liver disease”, Transl Res, 164, 312-322, 2014.
[4]	Kontogianni, M.D., Tileli, N., Margariti, A., Georgoulis, M., Deutsch, M., Tiniakos, D., Fragopoulou, E., Zafiropoulou, R., Manios, Y. and Papatheodoridis, G, “Adherence to the Mediterranean diet is associated with the severity of non-alcoholic fatty liver disease”, Clin Nutr, 33 (4), 678-683, 2014.
[5]	Ryan, M.C., Itsiopoulos, C., Thodis, T., Ward, G., Trost, N., Hofferberth, S., O'Dea, K., Desmond, P.V., Johnson, N.A. and Wilson, A.M, “The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease”, J Hepatol, 59 (1), 138-143, .2013
[6]	Trovato, F.M., Catalano, D., Martines, G.F., Pace, P. and Trovato, G.M, “Mediterranean diet and non-alcoholic fatty liver disease: the need of extended and comprehensive interventions”, Clin Nutr 34 (1), 86-88, 2015.
[7]	Hernandez-Rodas, M.C., Valenzuela, R. and Videla, L.A, “Relevant Aspects of Nutritional and Dietary Interventions in Non-Alcoholic Fatty Liver Disease”, Int J Mol Sci, 16 (10), 25168-25198, 2015.
[8]	Derosa, G., Guasti, L., D'Angelo, A., Martinotti, C., Valentino, M.C., Di Matteo, S., Bruno, G.M., Maresca, A.M., Gaudio, G.V. and Maffioli, P, “Probiotic Therapy With VSL#3® in Patients With NAFLD: A Randomized Clinical Trial”, Front Nutr, 9, 846873, 2022.
[9]	El, S.N. and Karakaya, S, “Olive tree (Olea europaea) leaves: potential beneficial effects on human health”, Nutr Rev, 67 (11), 632-638, 2009.
[10]	Servili, M., Baldioli, M., Selvaggini, R., Macchioni, A. and 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, 47 (1), 12-18, 1999.
[11]	Al-Azzawie, H.F and Alhamdani, M.S, “Hypoglycemic and antioxidant effect of oleuropein in alloxan-diabetic rabbits”, Life Sci, 78 (12), 1371-1377, 2006.
[12]	Rafferty, E.P., Wylie, A.R., Elliott, C.T., Chevallier, O.P., Grieve, D.J. and Green, B.D, “In vitro and in vivo effects of natural putative secretagogues of Glucagon-Like Peptide-1 (GLP-1)”, Sci Pharm, 79 (3), 615-621, 2011.
[13]	Acar-Tek, N. and Ağagündüz, D, “Olive leaf (Olea Europaea L. folium): potential effects on glycemia and lipidemia”, Ann Nutr Metab, 76 (1), 10-15, 2000.
[14]	Abenavoli, L., Milanović, M., Milić, N., Luzza, F. and Giuffrè, A.M, “Olive oil antioxidants and non-alcoholic fatty liver disease”, Expert Rev Gastroenterol Hepatol, 13 (8), 739-749, 2019.
[15]	Rezaei, S., Akhlaghi, M., Sasani, M.R. and Barati Boldaji, R, “Olive oil lessened fatty liver severity independent of cardiometabolic correction in patients with non-alcoholic fatty liver disease: A randomized clinical trial”, Nutrition, 57, 154-161, 2019.
[16]	Shidfar, F., Bahrololumi, S.S., Doaei, S., Mohammadzadeh, A., Gholamalizadeh, M. and Mohammadimanesh, A, “The Effects of Extra Virgin Olive Oil on Alanine Aminotransferase, Aspartate Aminotransferase, and Ultrasonographic Indices of Hepatic Steatosis in Nonalcoholic Fatty Liver Disease Patients Undergoing Low Calorie Diet”, Can J Gastroenterol Hepatol 2018, 1053710, 2018.
[17]	Nigam, P., Bhatt, S., Misra, A., Chadha, D.S., Vaidya, M., Dasgupta, J. and Pasha, Q.M, “Effect of a 6-month intervention with cooking oils containing a high concentration of monounsaturated fatty acids (olive and canola oils) compared with control oil in male Asian Indians with nonalcoholic fatty liver disease”, Diabetes Technol Ther, 16 (4), 255-261, 2014.
[18]	Cueto-Galán, R., Barón, F.J., Valdivielso, P., Pintó, X., Corbella, E., Gómez-Gracia, E., Wärnberg, J. and los investigadores del Estudio PREDIMED, “Changes in fatty liver index after consuming a Mediterranean diet: 6-year follow-up of the PREDIMED-Malaga trial”, Med Clin (Barc), 148 (10), 435-443, 2017.
[19]	Derosa,G., D’Angelo, A. and Maffioli, P, “Olea Europaea Effects on Glyco-Metabolic Parameters and on Glycemic Status in Patients with Impaired Fasting Glucose”, J Food Nutr Res, 10 (10), 674-680, 2022.
[20]	Proposed International Guidelines for Biomedical Research Involving Human Subjects, “The Council for International Organisation of Medical Sciences”, Geneva, 1982.
[21]	Chalasani, N., Younossi, Z., Lavine, J.E., Charlton, M., Cusi, K., Rinella, M., Harrison, S.A., Brunt, E.M. and Sanyal, A.J, “The Diagnosis and Management of Nonalcoholic Fatty Liver Disease: Practice Guidance From the American Association for the Study of Liver Diseases”, Hepatology, 67, 328-357, 2018.
[22]	Lee, J.H., Kim, D., Kim, H.J., Lee, C.H., Yang, J.I., Kim, W., Kim, Y.J., Yoon, J.H., Cho, S.H., Sung, M.W. and Lee, H.S, “Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease”, Dig Liver Dis, 42 (7), 503-508, 2010.
[23]	Lichtenstein, A.H., Appel, L.J., Brands, M., Carnethon, M., Daniels, S., Franch, H.A., Franklin, B., Kris-Etherton, P., Harris, W.S., Howard, B., Karanja, N., Lefevre, M., Rudel, L., Sacks, F., Van Horn, L., Winston, M. and Wylie-Rosett, J, “Summary of American Heart Association Diet and Lifestyle Recommendations Revision 2006”, Arterioscler Thromb Vasc Biol, 26, 2186-2191, 2006.
[24]	European Diabetes Policy Group 1999, “A desktop guide to type 2 diabetes mellitus”, Diabet Med, 16, 716-730, 1999.
[25]	Klose, S. and Borner, K, “Enzymatische Bestimmung des Gesamtcholesterins mit dem [Enzymatic dosage of total cholesterolemia by Greiner Selective Analyzer (GSA II)]”, J Clin Chem Clin Biochem, 15, 121-130, 1978.
[26]	Wahlefeld, A.W, “Triglycerides determination after enzymatic hydrolysis”, in: Bergmeyer, H.U, ed., Methods of Enzymatic Analysis, 2nd English ed., Academic Press, New York, 1974, 18-31.
[27]	Havel, R.J., Eder, H.A. and Bragdon, J.H, “The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum”, J Clin Invest, 34, 1345-1353, 1955.
[28]	Friedewald, W.T., Levy, R.I. and Fredrickson, D.S, “Estimation of the concentration of low density lipoprotein in plasma, without use of the preparative ultracentrifuge”, Clin Chem, 18, 499-502, 1972.
[29]	Rifai, N., Tracy, R.P. and Ridker, P.M, “Clinical efficacy of an automated high-sensitivity C-reactive protein assay”, Clin Chem, 45, 2136-2141, 1999.
[30]	Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., Ezaki, O., Akanuma, Y., Gavrilova, O., Vinson, C., Reitman, M.L., Kagechika, H., Shudo, K., Yoda, M., Nakano, Y., Tobe, K., Nagai, R., Kimura, S., Tomita, M., Froguel, P. and Kadowaki, T, “The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity”, Nature Med, 7, 941-946, 2001.
[31]	Zhang, M. and Tracey, K, The Cytokine Handbook, 3rd ed, Academic Press, San Diego, 1988.
[32]	Strauss, S., Gavish, E., Gottlieb, P. and Katsnelson, L, “Interobserver and intraobserver variability in the sonographic assessment of fatty liver”, AJR, 189 (6), W320-323, 2007.
[33]	Hashimoto, E., Tanjgi, M. and Tokusghige, K, “Characteristics and diagnosis of NAFLD/NASH”, J Gastroenterol Hepatol, 28 (4), 64-70, 2013.
[34]	Winer, B.J, Statistical Principles in Experimental Design, 2nd ed., McGraw-Hill, New York (USA), 1971.
[35]	Echeverría, F., Ortiz, M., Valenzuela, R. and Videla, L.A, “Hydroxytyrosol and cytoprotection: a projection for clinical interventions”, Int J Mol Sci, 18, E930, 2017.
[36]	Serreli, G. and Deiana, M, “Biological relevance of extra virgin olive oil polyphenols metabolites”, Antioxidants (Basel), 7 (12), pii: E17, 2018.
[37]	Carrasco-Pancorbo, A., Cerretani, L., Bendini, A., Segura-Carretero, A., Del Carlo, M., Gallina-Toschi, T., Lercker, G., Compagnone, D. and Fernández-Gutiérrez, A, “Evaluation of the antioxidant capacity of individual phenolic compounds in virgin olive oil”, J Agric Food Chem, 3 (23), 8918-8925, 2005.
[38]	Faine, L.A., Diniz, Y.S., Galhardi, C.M., Rodrigues, H.G., Burneiko, R.C., Santana, L.S., Cicogna, A.C. and Novelli, E.L, “Synergistic action of olive oil supplementation and dietary restriction on serum lipids and cardiac antioxidant defences”, Can J Physiol Pharmacol, 82 (11), 969-975, 2004.
[39]	Fong, D.G., Nehra, V., Lindor, K.D. and Buchman, A.L, “Metabolic and nutritional considerations in nonalcoholic fatty liver”, Hepatology, 32, 3-10, 2000.
[40]	Vazquez-Roncero, A., Maestro-Duran, R. and Graciani-Constante, E, “Phenolic compounds in olive fruits. II: Polyphenols in vegetation water”, Grasas Aceites, 25, 341-345, 1974.
[41]	Servili, M., Baldioli, M., Selvaggini, R., Miniati, E., Macchioni, A. and Montedoro, G, “High-performance liquid chromatography evaluation of phenols in olive fruit, virgin olive oil, vegetation waters, and pomace and 1D- and 2D-nuclear magnetic resonance characterization”, J Am Oil Chem Soc, 76, 873-882, 1999.
[42]	Mulinacci, N., Romani, A., Galardi, C., Pinelli, P., Giaccherini, C. and Vincieri, F.F, “Polyphenolic content in olive oil waste waters and related olive samples”, J Agric Food Chem, 49, 3509-3514, 2001.
[43]	Santini, S.J., Porcu, C., Tarantino, G., Amicarelli, F. and Balsano, C, “Oleuropein overrides liver damage in steatotic mice”, T J Funct Food, 65, 103756, 2020.
[44]	Porcu, C., Sideri, S., Martini, M., Cocomazzi, A., Galli, A., Tarantino, G. and Balsano, C, “Oleuropein Induces AMPK-Dependent Autophagy in NAFLD Mice, Regardless of the Gender”, Int J Mol Sci, 19, 3948, 2018.
[45]	Domitrović, R., Jakovac, H., Marchesi, V.V., Šain, I., Romić, Ž. and Rahelić, D, “Preventive andtherapeutic effects of oleuropein against carbon tetrachloride-induced liver damage in mice”, Pharmacol Res, 65, 451-464, 2012.
[46]	Park, S., Choi, Y., Um, S.J., Yoon, S.K. and Park, T, “Oleuropein attenuates hepatic steatosis induced by high-fat diet in mice”, J Hepatol, 54, 984-993, 2011.
[47]	Kim, S.W., Hur, W., Li, T.Z., Lee, Y.K., Choi, J.E., Hong, S.W., Lyoo, K.S., You, C.R., Jung, E.S., Jung, C.K., Park, T., Um, S.J. and Yoon, S.K, “Oleuropein prevents the progression of steatohepatitis to hepatic fibrosis induced by a high-fat diet in mice”, Exp Mol Med, 46 (4), e92, 2014.
[48]	Barbaro, B., Toietta, G., Maggio, R., Arciello, M., Tarocchi, M., Galli, A. and Balsano. C, “Effects of the Olive-Derived Polyphenol Oleuropein on Human Health”, Int J Mol Sci, 15, 18508-18524, 2014.