Daily consumption of caper fruit along with atorvastatin has synergistic effects in hyperlipidemic patients: Randomized clinical trial

Authors

  • Seied Saeid Esmaeili Department of Iranian Traditional Medicine, Faculty of Medicine, Shahed University, Tehran, Iran
  • Saeed Sardari 1. Department of Iranian Traditional Medicine, Faculty of Medicine, Shahed University, Tehran, Iran 2. Department of Persian Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
  • Faramarz Fallahi Department of Cardiology Mostafa Khomeini Hospital, Faculty of Medicine, Shahed University, Tehran, Iran
  • Ali Davati Department of Iranian Traditional Medicine, Faculty of Medicine, Shahed University, Tehran, Iran
  • Fatemeh Emadi Department of Iranian Traditional Medicine, Faculty of Medicine, Shahed University, Tehran, Iran
  • Mohammad Gholamifesharaki Department of Biostatistics, Faculty of Medical sciences, Tarbiat Modares University, Tehran, Iran
  • Narjes Khavasi Department of Persian Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

DOI:

https://doi.org/10.31661/gmj.v8i.1345

Keywords:

Caper, Atorvastatin, Lipid Profile

Abstract

Background: Dyslipidemia leads to micro- and macro-vascular complications. Atorvastatin is the main therapeutic drug used for dyslipidemia, but it causes side effects such as new type 2 diabetes mellitus onset and elevation of liver enzymes. Herbs may be useful in reducing atorvastatin doses. Caper fruit, an herbal drug in Iranian traditional medicine, has hypolipidemic effects. Hence, the effect of atorvastatin therapy with and without daily caper fruit pickle (CFP) consumption was assessed on hyperlipidemia. Materials and Methods: In this single-blinded, randomized, controlled trial, 60 hyperlipidemic patients were allocated in two groups and treated with 10 mg atorvastatin plus 40-50 g CFP (A10+CFP) or atorvastatin alone (A10) for eight weeks. Biochemical parameters were measured at baseline, 4, and eight weeks of the intervention. One-way repeated measure ANOVA and mixed ANOVA were used to measure the effect of the two treatments and the interaction between the type of treatment and time on lipid profile. Results: Serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) were significantly decreased in the A10+CFP group compared with the A10 group (P<0.001 and P<0.001, respectively) from baseline up to the week 8. At week 4, mean changes of LDL-C was significantly higher in the A10+CFP compared with the A10 (P=.01). Adjusting for the baseline variables, the mean difference of alanine aminotransferase (P<0.01) and triglyceride (P=.003) were significantly higher in the A10+CFP group at the end. Conclusion: This study reports that the intake of CFP along with atorvastatin daily may have synergistic effects which improve the lipid profile in hyperlipidemic patients. [GMJ.2019;8:e1345]

References

Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2012; 125(1): e2-e220. PMid:22179539 Tiwari V, Khokhar M. Mechanism of action of anti-hypercholesterolemia drugs and their resistance. Eur J Pharmacol. 2014; 741: 156-70. https://doi.org/10.1016/j.ejphar.2014.07.048PMid:25151024 Casula M, Mozzanica F, Scotti L, Tragni E, Pirillo A, Corrao G, et al. Statin use and risk of new-onset diabetes: A meta-analysis of observational studies. Nutr Metab Cardiovasc Dis. 2017; 27(5): 396-406. https://doi.org/10.1016/j.numecd.2017.03.001PMid:28416099 Laakso M, Kuusisto J. Diabetes Secondary to Treatment with Statins. Curr Diab Rep.2017; 17(2):10. https://doi.org/10.1007/s11892-017-0837-8PMid:28155189 Nazem Jahan MA. Eksir -e- Aazam [Great Elixir]: (Diseases). Tehran: Sarir -e- Ardehal 2008. [In Persian]. Kalantari H, Foruozandeh H, Khodayar MJ, Siahpoosh A, Saki N, Kheradmand P. Antioxidant and hepatoprotective effects of Capparis spinosa L. ntfractions and Quercetin on tert-butyl hydroperoxide- induced acute liver damage in mice. J Tradit Complement Med. 2018; 8(1): 120-127. https://doi.org/10.1016/j.jtcme.2017.04.010PMid:29321999 PMCid:PMC5755993 Eddouks M, Lemhadri A, Michel J.B. Hypolipidemic activity of aqueous extract of Capparis spinosa L. in normal and diabetic rats. J Ethnopharmacol. 2005; 98(3): 345-50. https://doi.org/10.1016/j.jep.2005.01.053PMid:15814271 Goodman E, Daniels SR, Morrison JA, Huang B, Dolan LM. Contrasting prevalence of and demographic disparities in the World Health Organization and National Cholesterol Education Program Adult Treatment Panel III definitions of metabolic syndrome among adolescents. J Pediatr. 2004; 145(4):445-51. https://doi.org/10.1016/j.jpeds.2004.04.059PMid:15480365 Mousavi SN, Faghihi A, Motaghinejad M, Shiasi M, Imanparast F, Amiri HL, et al. Zinc and Selenium Co-supplementation Reduces Some Lipid Peroxidation and Angiogenesis Markers in a Rat Model of NAFLD-Fed High Fat Diet. Biol Trace Elem Res. 2018; 181(2): 288-295. https://doi.org/10.1007/s12011-017-1059-2PMid:28577233 Lorvand Amiri H, Agah S, Tolouei Azar J, Hosseini S, Shidfar F, Mousavi SN. Effect of daily calcitriol supplementation with and without calcium on disease regression in non-alcoholic fatty liver patients following an energy-restricted diet: Randomized, controlled, Single-blind trial. Clin Nutr. 2017; 36(6):1490-1497. https://doi.org/10.1016/j.clnu.2016.09.020PMid:27720403 Khavasi N, Khadem E, Ayati MH, Torbati MA, Fazljou SMB. Daily Consumption of the Capparis spinosa Reduces Some Atherogenic Indices in Patients with Non-alcoholic Fatty Liver Disease: A Randomized, Single-blind, Clinical Trial. Iran Red Cres Med J. 2018(In Press). https://doi.org/10.5812/ircmj.63446 Jellinger PS, Handelsman Y, Rosenblit PD, Bloomgarden ZT, Fonseca VA, Garber AJ, et al. American association of clinical endocrinologists and american colledge of endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract. 2017; 23(Suppl 2): 1-87. https://doi.org/10.4158/EP171764.APPGLPMid:28437620 Emtiazy M, Keshavarz M, Khodadoost M, Kamalinejad M, Gooshahgir S. A, Shahrad Bajestani H, et al. Relation between Body Humors and Hypercholesterolemia: An Iranian Traditional Medicine Perspective Based on the Teaching of Avicenna. Iran Red Crescent Med J. 2012; 14(3): 133-8. PMid:22737569 PMCid:PMC3372029 Kritchevsky D. Fiber, lipids, and atherosclerosis. Am J Clin Nutr. 1978; 31(10 Suppl): S65-s74. https://doi.org/10.1093/ajcn/31.10.S65PMid:101075 Miller YI, Chang MK, Binder CJ, Shaw PX, Witztum JL. Oxidized low density lipoprotein and innate immune receptors. Curr Opin Lipidol. 2003; 14(5): 437-45. https://doi.org/10.1097/00041433-200310000-00004PMid:14501582 El Azhary K, Tahiri Jouti N, El Khachibi M, Moutia M, Tabyaoui I, El Hou A, et al., Anti-inflammatory potential of Capparis spinosa L. in vivo in mice through inhibition of cell infiltration and cytokine gene expression. BMC Complement Altern Med. 2017; 17(1): 81. https://doi.org/10.1186/s12906-017-1569-7PMid:28143472 PMCid:PMC5282892 Moutia M, El Azhary K, Elouaddari A, Al Jahid A, Jamal Eddine J, Seghrouchni F, et al. Capparis Spinosa L. promotes anti-inflammatory response in vitro through the control of cytokine gene expression in human peripheral blood mononuclear cells. BMC Immunol. 2016; 17(1): 26. https://doi.org/10.1186/s12865-016-0164-xPMid:27483999 PMCid:PMC4969972 Dawid-Pac R. Medicinal plants used in treatment of inflammatory skin diseases. Postepy Dermatol Alergol. 2013; 30(3): 170-7. https://doi.org/10.5114/pdia.2013.35620PMid:24278070 PMCid:PMC3834722 Khavasi N, Somi MH, Khadem E, Faramarzi E, Ayati MH, Fazljou SMB, et al. Effect of Daily Caper Fruit Pickle Consumption on Disease Regression in Patients with Non-Alcoholic Fatty Liver Disease: a Single-Blinded Randomized Clinical Trial. Adv Pharm Bull. 2017; 7(4): 645-650. https://doi.org/10.15171/apb.2017.077PMid:29399555 PMCid:PMC5788220 Simões F.C, Marques RG, Diestel CF, Caetano CE, Dinis A, Horst NL, et al. Lipidic profile among rats submitted to total splenectomy isolated or combined with splenic autotransplant. Acta Cirúrgica Brasileira. 2007; 22: 46-51. https://doi.org/10.1590/S0102-86502007000700010PMid:17505655 Tarantino G, Scalera A, Finelli C. Liver-spleen axis: intersection between immunity, infections and metabolism. World journal of gastroenterology: World J Gasteroenetrol. 2013; 19(23): 3534. https://doi.org/10.3748/wjg.v19.i23.3534PMid:23801854 PMCid:PMC3691032 Polimeni L, Pastori D, Baratta F, Tozzi G, Novo M, Vicinanza R, et al. Spleen dimensions are inversely associated with lysosomal acid lipase activity in patients with non-alcoholic fatty liver disease. Intern Emerg Med 2017; 12(8): 1159-1165. https://doi.org/10.1007/s11739-017-1746-1PMid:28900817 Thompson PD, Panza G, Zaleski A, Taylor B. Statin-Associated Side Effects. J Am Coll Cardiol. 2016; 67(20): 2395-2410. https://doi.org/10.1016/j.jacc.2016.02.071PMid:27199064 Sahebkar A, Beccuti G, Simental-Mendía LE, Nobili V, Bo S. Nigella sativa (black seed) effects on plasma lipid concentrations in humans: A systematic review and meta-analysis of randomized placebo-controlled trials. Pharmacol Res. 2016; 106: 37-50. https://doi.org/10.1016/j.phrs.2016.02.008PMid:26875640 Guertin J.R, Rahme E, LeLorierJ. Use of Continuous Exposure Variables when Examining Dose-Dependent Pharmacological Effects - Application to the Association between Exposure to Higher Statin Doses and the Incidence of Diabetes. J Popul Ther Clin Pharmacol. 2017; 24(1): 5-15. https://doi.org/10.22374/1710-6222.24.1.1PMid:28186711 LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005; 352(14): 1425-35. https://doi.org/10.1056/NEJMoa050461PMid:15755765 Pedersen TR, Faergeman O, Kastelein JJ, Olsson AG, Tikkanen MJ, Holme I, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005; 294(19): 2437-45. https://doi.org/10.1001/jama.294.19.2437PMid:16287954 Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004; 350(15):1495-504. https://doi.org/10.1056/NEJMoa040583PMid:15007110

Published

2019-05-27

Issue

Section

Original Article