Daily consumption of caper fruit along with atorvastatin has synergistic effects in hyperlipidemic patients: Randomized clinical trial
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.2014.07.048
PMid: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.2017.03.001
PMid:28416099
Laakso M, Kuusisto J. Diabetes Secondary to Treatment with Statins. Curr Diab Rep.2017; 17(2):10.
https://doi.org/10.1007/s11892-017-0837-8
PMid: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.2017.04.010
PMid: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.2005.01.053
PMid: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.2004.04.059
PMid: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/s12011-017-1059-2
PMid: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.2016.09.020
PMid: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.APPGL
PMid: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.S65
PMid: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/10.1097/00041433-200310000-00004
PMid: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/s12906-017-1569-7
PMid: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-x
PMid: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.2013.35620
PMid: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.2017.077
PMid: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/S0102-86502007000700010
PMid: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.i23.3534
PMid: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/s11739-017-1746-1
PMid: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.2016.02.071
PMid: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.2016.02.008
PMid: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/10.22374/1710-6222.24.1.1
PMid: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/NEJMoa050461
PMid: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.294.19.2437
PMid: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/NEJMoa040583
PMid:15007110
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