Skip to main content Accessibility help

Extra-virgin olive oil consumption reduces the age-related decrease in HDL and paraoxonase 1 anti-inflammatory activities

  • Soumaya Loued (a1), Hicham Berrougui (a1), Pamela Componova (a1), Souad Ikhlef (a1), Olfa Helal (a1) and Abdelouahed Khalil (a1) (a2)...


Paraoxonase 1 (PON1) is associated with HDL and modulates the antioxidant and anti-inflammatory role of HDL. The goals of the present study were to investigate the effect of ageing and the role of PON1 on the anti-inflammatory activity of HDL, and to determine whether extra-virgin olive oil (EVOO) consumption could improve the atheroprotective activity of HDL. HDL and PON1 were isolated from the plasma of ten young (Y-HDL and Y-PON1) and ten elderly (E-HDL and E-PON1) healthy volunteers before and after 12 weeks of EVOO consumption. Inflammation was assessed by measuring intracellular adhesion molecule 1 (ICAM-1) expression. THP-1 (human acute monocytic leukaemia cell line) monocyte chemotaxis was measured using a Boyden chamber. Oxidative damage to HDL was assessed by measuring conjugated diene formation and changes in electrophoretic migration. Y-HDL had more anti-inflammatory activity than E-HDL. The conjugated diene content and the electrophoretic mobility of E-HDL were higher than those of Y-HDL. Y-PON1 had significant anti-inflammatory activity, reducing ICAM-1 expression by 32·64 (sd 2·63) %, while E-PON1 had no significant effect. THP-1 chemotaxis measurements confirmed the ICAM-1 expression results. The 12 weeks of EVOO consumption significantly increased the anti-inflammatory activities of both HDL and PON1. The anti-inflammatory activity of HDL was modulated by PON1 and was lower in the elderly volunteers. EVOO consumption increased the anti-inflammatory effect of HDL and reduced the age-related decrease in anti-atherogenic activity.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Extra-virgin olive oil consumption reduces the age-related decrease in HDL and paraoxonase 1 anti-inflammatory activities
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Extra-virgin olive oil consumption reduces the age-related decrease in HDL and paraoxonase 1 anti-inflammatory activities
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Extra-virgin olive oil consumption reduces the age-related decrease in HDL and paraoxonase 1 anti-inflammatory activities
      Available formats


Corresponding author

*Corresponding author: A. Khalil, fax +1 819 564 5320, email


Hide All
1Schwenke, DC (1998) Aging, menopause, and free radicals. Semin Reprod Endocrinol 16, 281308.
2Geelen, P, Lorga Filho, A, Primo, J, et al. (1997) Experience with implantable cardioverter defibrillator therapy in elderly patients. Eur Heart J 18, 13391342.
3Reaven, PD, Napoli, C, Merat, S, et al. (1999) Lipoprotein modification and atherosclerosis in aging. Exp Gerontol 34, 527537.
4Khalil, A, Jay-Gerin, JP, Fulop, T, et al. (1998) Age-related increased susceptibility of high-density lipoproteins (HDL) to in vitro oxidation induced by gamma-radiolysis of water. FEBS Lett 435, 153158.
5Khalil, A, Wagner, JR, Lacombe, G, et al. (1996) Increased susceptibility of low-density lipoprotein (LDL) to oxidation by gamma-radiolysis with age. FEBS Lett 392, 4548.
6Gowri, MS, Van der Westhuyzen, DR, Bridges, SR, et al. (1999) Decreased protection by HDL from poorly controlled type 2 diabetic subjects against LDL oxidation may be due to the abnormal composition of HDL. Arterioscler Thromb Vasc Biol 19, 22262233.
7Zago, V, Sanguinetti, S, Brites, F, et al. (2004) Impaired high density lipoprotein antioxidant activity in healthy postmenopausal women. Atherosclerosis 177, 203210.
8deGoma, EM, deGoma, RL & Rader, DJ (2008) Beyond high-density lipoprotein cholesterol levels evaluating high-density lipoprotein function as influenced by novel therapeutic approaches. J Am Coll Cardiol 51, 21992211.
9Camont, L, Chapman, MJ & Kontush, A (2011) Biological activities of HDL subpopulations and their relevance to cardiovascular disease. Trends Mol Med 17, 594603.
10Barter, PJ, Nicholls, S, Rye, KA, et al. (2004) Antiinflammatory properties of HDL. Circ Res 95, 764772.
11Seres, I, Paragh, G, Deschene, E, et al. (2004) Study of factors influencing the decreased HDL associated PON1 activity with aging. Exp Gerontol 39, 5966.
12Berrougui, H, Isabelle, M, Cloutier, M, et al. (2007) Age-related impairment of HDL-mediated cholesterol efflux. J Lipid Res 48, 328336.
13Baker, PW, Rye, KA, Gamble, JR, et al. (1999) Ability of reconstituted high density lipoproteins to inhibit cytokine-induced expression of vascular cell adhesion molecule-1 in human umbilical vein endothelial cells. J Lipid Res 40, 345353.
14Recalde, D, Ostos, MA, Badell, E, et al. (2004) Human apolipoprotein A-IV reduces secretion of proinflammatory cytokines and atherosclerotic effects of a chronic infection mimicked by lipopolysaccharide. Arterioscler Thromb Vasc Biol 24, 756761.
15Loued, S, Isabelle, M, Berrougui, H, et al. (2012) The anti-inflammatory effect of paraoxonase 1 against oxidized lipids depends on its association with high density lipoproteins. Life Sci 90, 8288.
16Shih, DM, Gu, L, Xia, YR, et al. (1998) Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 394, 284287.
17Deakin, S, Leviev, I, Gomaraschi, M, et al. (2002) Enzymatically active paraoxonase-1 is located at the external membrane of producing cells and released by a high affinity, saturable, desorption mechanism. J Biol Chem 277, 43014308.
18Mackness, MI, Mackness, B, Durrington, PN, et al. (1996) Paraoxonase: biochemistry, genetics and relationship to plasma lipoproteins. Curr Opin Lipidol 7, 6976.
19Mackness, MI, Durrington, PN, Ayub, A, et al. (1999) Low serum paraoxonase: a risk factor for atherosclerotic disease? Chem Biol Interact 119–120, 389397.
20Durrington, PN, Mackness, B & Mackness, MI (2001) Paraoxonase and atherosclerosis. Arterioscler Thromb Vasc Biol 21, 473480.
21Mackness, B, Hine, D, Liu, Y, et al. (2004) Paraoxonase-1 inhibits oxidised LDL-induced MCP-1 production by endothelial cells. Biochem Biophys Res Commun 318, 680683.
22Marsillach, J, Camps, J, Ferre, N, et al. (2009) Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in experimental liver disease. BMC Gastroenterol 9, 3.
23Watson, AD, Navab, M, Hama, SY, et al. (1995) Effect of platelet activating factor-acetylhydrolase on the formation and action of minimally oxidized low density lipoprotein. J Clin Invest 95, 774782.
24Mackness, B, Durrington, P, McElduff, P, et al. (2003) Low paraoxonase activity predicts coronary events in the Caerphilly Prospective Study. Circulation 107, 27752779.
25Robertson, KS, Hawe, E, Miller, GJ, et al. (2003) Human paraoxonase gene cluster polymorphisms as predictors of coronary heart disease risk in the prospective Northwick Park Heart Study II. Biochim Biophys Acta 1639, 203212.
26Deakin, SP & James, RW (2004) Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1. Clin Sci (Lond) 107, 435447.
27MacKness, B, Mackness, MI, Durrington, PN, et al. (2000) Paraoxonase activity in two healthy populations with differing rates of coronary heart disease. Eur J Clin Invest 30, 410.
28Senti, M, Tomas, M, Anglada, R, et al. (2003) Interrelationship of smoking, paraoxonase activity, and leisure time physical activity: a population-based study. Eur J Intern Med 14, 178184.
29Yu, R, Yekta, B, Vakili, L, et al. (2008) Proatherogenic high-density lipoprotein, vascular inflammation, and mimetic peptides. Curr Atheroscler Rep 10, 171176.
30Perona, JS, Cabello-Moruno, R & Ruiz-Gutierrez, V (2006) The role of virgin olive oil components in the modulation of endothelial function. J Nutr Biochem 17, 429445.
31Perez-Jimenez, F, Alvarez de Cienfuegos, G, Badimon, L, et al. (2005) International conference on the healthy effect of virgin olive oil. Eur J Clin Invest 35, 421424.
32Mata, P, Alvarez-Sala, LA, Rubio, MJ, et al. (1992) Effects of long-term monounsaturated- vs polyunsaturated-enriched diets on lipoproteins in healthy men and women. Am J Clin Nutr 55, 846850.
33Stock, J (2011) Importance of HDL functionality to cardiovascular risk. Atherosclerosis 218, 1920.
34Sattler, W, Mohr, D & Stocker, R (1994) Rapid isolation of lipoproteins and assessment of their peroxidation by high-performance liquid chromatography postcolumn chemiluminescence. Methods Enzymol 233, 469489.
35Khalil, A & Fulop, T (2001) A comparison of the kinetics of low-density lipoprotein oxidation induced by copper or by gamma-rays: influence of radiation dose-rate and copper concentration. Can J Physiol Pharmacol 79, 114121.
36Pryor, WA & Castle, L (1984) Chemical methods for the detection of lipid hydroperoxides. Methods Enzymol 105, 293299.
37Levine, RL, Garland, D, Oliver, CN, et al. (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186, 464478.
38Gan, KN, Smolen, A, Eckerson, HW, et al. (1991) Purification of human serum paraoxonase/arylesterase. Evidence for one esterase catalyzing both activities. Drug Metab Dispos 19, 100106.
39Valiyaveettil, M, Alamneh, Y, Biggemann, L, et al. (2011) In vitro efficacy of paraoxonase 1 from multiple sources against various organophosphates. Toxicol In vitro 25, 905913.
40Rodrigo, L, Mackness, B, Durrington, PN, et al. (2001) Hydrolysis of platelet-activating factor by human serum paraoxonase. Biochem J 354, 17.
41Mackness, B, Mackness, MI, Arrol, S, et al. (1998) Effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification. FEBS Lett 423, 5760.
42Lidington, EA, Moyes, DL, McCormack, AM, et al. (1999) A comparison of primary endothelial cells and endothelial cell lines for studies of immune interactions. Transpl Immunol 7, 239246.
43Sofi, F, Cesari, F, Abbate, R, et al. (2008) Adherence to Mediterranean diet and health status: meta-analysis. BMJ 337, a1344.
44Gjonca, A & Bobak, M (1997) Albanian paradox, another example of protective effect of Mediterranean lifestyle? Lancet 350, 18151817.
45Papageorgiou, N, Tousoulis, D, Psaltopoulou, T, et al. (2011) Divergent anti-inflammatory effects of different oil acute consumption on healthy individuals. Eur J Clin Nutr 65, 514519.
46Cockerill, GW, Rye, KA, Gamble, JR, et al. (1995) High-density lipoproteins inhibit cytokine-induced expression of endothelial cell adhesion molecules. Arterioscler Thromb Vasc Biol 15, 19871994.
47Cockerill, GW, Huehns, TY, Weerasinghe, A, et al. (2001) Elevation of plasma high-density lipoprotein concentration reduces interleukin-1-induced expression of E-selectin in an in vivo model of acute inflammation. Circulation 103, 108112.
48Morgantini, C, Natali, A, Boldrini, B, et al. (2011) Anti-inflammatory and antioxidant properties of HDLs are impaired in type 2 diabetes. Diabetes 60, 26172623.
49Kimura, T, Tomura, H, Mogi, C, et al. (2006) Role of scavenger receptor class B type I and sphingosine 1-phosphate receptors in high density lipoprotein-induced inhibition of adhesion molecule expression in endothelial cells. J Biol Chem 281, 3745737467.
50Ng, DS, Chu, T, Esposito, B, et al. (2008) Paraoxonase-1 deficiency in mice predisposes to vascular inflammation, oxidative stress, and thrombogenicity in the absence of hyperlipidemia. Cardiovasc Pathol 17, 226232.
51Rasic-Milutinovic, Z, Popovic, T, Perunicic-Pekovic, G, et al. (2012) Lower serum paraoxonase-1 activity is related to linoleic and docosahexanoic fatty acids in type 2 diabetic patients. Arch Med Res 43, 7582.
52James, RW, Leviev, I & Righetti, A (2000) Smoking is associated with reduced serum paraoxonase activity and concentration in patients with coronary artery disease. Circulation 101, 22522257.
53Abbott, CA, Mackness, MI, Kumar, S, et al. (1995) Serum paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins. Arterioscler Thromb Vasc Biol 15, 18121818.
54Ikeda, Y, Suehiro, T, Inoue, M, et al. (1998) Serum paraoxonase activity and its relationship to diabetic complications in patients with non-insulin-dependent diabetes mellitus. Metabolism 47, 598602.
55Tomas, M, Senti, M, Garcia-Faria, F, et al. (2000) Effect of simvastatin therapy on paraoxonase activity and related lipoproteins in familial hypercholesterolemic patients. Arterioscler Thromb Vasc Biol 20, 21132119.
56Jaouad, L, Milochevitch, C & Khalil, A (2003) PON1 paraoxonase activity is reduced during HDL oxidation and is an indicator of HDL antioxidant capacity. Free Radic Res 37, 7783.
57Ahmed, Z, Ravandi, A, Maguire, GF, et al. (2002) Multiple substrates for paraoxonase-1 during oxidation of phosphatidylcholine by peroxynitrite. Biochem Biophys Res Commun 290, 391396.
58Jaouad, L, de Guise, C, Berrougui, H, et al. (2006) Age-related decrease in high-density lipoproteins antioxidant activity is due to an alteration in the PON1's free sulfhydyl groups. Atherosclerosis 185, 191200.
59Garin, MC, Kalix, B, Morabia, A, et al. (2005) Small, dense lipoprotein particles and reduced paraoxonase-1 in patients with the metabolic syndrome. J Clin Endocrinol Metab 90, 22642269.
60Van Lenten, BJ, Hama, SY, de Beer, FC, et al. (1995) Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures. J Clin Invest 96, 27582767.
61Mehdi, MM & Rizvi, SI (2012) Human plasma paraoxonase 1 (PON1) arylesterase activity during aging: correlation with susceptibility of LDL oxidation. Arch Med Res 43, 438443.
62Bogani, P, Galli, C, Villa, M, et al. (2007) Postprandial anti-inflammatory and antioxidant effects of extra virgin olive oil. Atherosclerosis 190, 181186.
63Konstantinidou, V, Covas, MI, Munoz-Aguayo, D, et al. (2010) In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: a randomized controlled trial. FASEB J 24, 25462557.
64Cabello-Moruno, R, Perona, JS, Osada, J, et al. (2007) Modifications in postprandial triglyceride-rich lipoprotein composition and size after the intake of pomace olive oil. J Am Coll Nutr 26, 2431.
65Covas, MI, de la Torre, K, Farre-Albaladejo, M, et al. (2006) Postprandial LDL phenolic content and LDL oxidation are modulated by olive oil phenolic compounds in humans. Free Radic Biol Med 40, 608616.
66Berrougui, H, Cloutier, M, Isabelle, M, et al. (2006) Phenolic-extract from argan oil (Argania spinosa L.) inhibits human low-density lipoprotein (LDL) oxidation and enhances cholesterol efflux from human THP-1 macrophages. Atherosclerosis 184, 389396.
67Connelly, PW, Maguire, GF, Picardo, CM, et al. (2008) Development of an immunoblot assay with infrared fluorescence to quantify paraoxonase 1 in serum and plasma. J Lipid Res 49, 245250.
68Fuhrman, B & Aviram, M (2002) Preservation of paraoxonase activity by wine flavonoids: possible role in protection of LDL from lipid peroxidation. Ann N Y Acad Sci 957, 321324.
69Noll, C, Hamelet, J, Matulewicz, E, et al. (2009) Effects of red wine polyphenolic compounds on paraoxonase-1 and lectin-like oxidized low-density lipoprotein receptor-1 in hyperhomocysteinemic mice. J Nutr Biochem 20, 586596.
70Sviridov, D, Mukhamedova, N, Remaley, AT, et al. (2008) Antiatherogenic functionality of high density lipoprotein: how much versus how good. J Atheroscler Thromb 15, 5262.
71Lahoz, C, Alonso, R, Ordovas, JM, et al. (1997) Effects of dietary fat saturation on eicosanoid production, platelet aggregation and blood pressure. Eur J Clin Invest 27, 780787.
72Ruiz-Gutierrez, V, Muriana, FJ, Guerrero, A, et al. (1996) Plasma lipids, erythrocyte membrane lipids and blood pressure of hypertensive women after ingestion of dietary oleic acid from two different sources. J Hypertens 14, 14831490.
73Alonso, A, Ruiz-Gutierrez, V & Martinez-Gonzalez, MA (2006) Monounsaturated fatty acids, olive oil and blood pressure: epidemiological, clinical and experimental evidence. Public Health Nutr 9, 251257.



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed