Advertisement

Berberis aristata combined with Silybum marianum on lipid profile in patients not tolerating statins at high doses

  • Giuseppe Derosa
    Correspondence
    Corresponding author. Department of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS Policlinico S. Matteo, Pavia, P.le C. Golgi, 2 – 27100, Pavia, Italy.
    Affiliations
    Department of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS, Policlinico S. Matteo, Pavia, Italy

    Center for the Study of Endocrine-Metabolic Pathophysiology and Clinical Research, University of Pavia, Pavia, Italy
    Search for articles by this author
  • Davide Romano
    Affiliations
    Department of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS, Policlinico S. Matteo, Pavia, Italy
    Search for articles by this author
  • Angela D'Angelo
    Affiliations
    Department of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS, Policlinico S. Matteo, Pavia, Italy
    Search for articles by this author
  • Pamela Maffioli
    Affiliations
    Department of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS, Policlinico S. Matteo, Pavia, Italy

    PhD School in Experimental Medicine, University of Pavia, Pavia, Italy
    Search for articles by this author

      Highlights

      • Adverse events are more common at higher doses of statins, and often contribute to patients low adherence to treatment.
      • To reduce the risk of statin-induced adverse events, we can use a lower dose of statin combined with nonstatin drugs.
      • Berberis aristata/Silybum marianum reduced fasting plasma glucose, insulin and HOMA-index compared to baseline and also to placebo.
      • Lipid profile did not change with statin at half dose and B. aristata/S. marianum, while it worsened with placebo.
      • B. aristata/S. marianum can be used in addition to statins in patients not tolerating high dose of these drugs.

      Abstract

      Aim

      To evaluate the effects of Berberis aristata combined with Silybum marianum in dyslipidemic patients intolerant to statins at high doses.

      Methods

      137 euglycemic, dyslipidemic subjects, with previous adverse events to statins at high doses, were enrolled. Statins were stopped for 1 month (run-in), then they were re-introduced at the half of the previously taken dose. At randomization, patients tolerating the half dose of statin, were assigned to add placebo or B. aristata/S. marianum 588/105 mg, 1 tablet during the lunch and 1 tablet during the dinner, for six months. We evaluated lipid profile and safety parameters variation at randomization, and after 3, and 6 months.

      Results

      B. aristata/S. marianum reduced fasting plasma glucose (−9 mg/dl), insulin (−0.7 μU/ml), and HOMA-index (−0.35) levels compared to baseline and also to placebo. Lipid profile did not significantly change after 6 months since the reduction of statin dosage and the introduction of B. aristata/S. marianum, while it worsened in the placebo group both compared to placebo and with active treatment (+23.4 mg/dl for total cholesterol, +19.6 mg/dl for LDL-cholesterol, +23.1 mg/dl for triglycerides with placebo compared to B. aristata/S. marianum). We did not record any variations of safety parameters in nether of groups.

      Conclusions

      B. aristata/S. marianum can be considered as addition to statins in patients not tolerating high dose of these drugs.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Wilt T.J.
        • Bloomfield H.E.
        • MacDonald R.
        • et al.
        Effectiveness of statin therapy in adults with coronary heart disease.
        Arch. Intern. Med. 2004; 164: 1427-1436
        • Guyton J.R.
        • Bays H.E.
        • Grundy S.M.
        • Jacobson T.A.
        An assessment by the statin intolerance panel: 2014 update.
        J. Clin. Lipidol. 2014; 8: S72-81
        • Derosa G.
        • Maffioli P.
        Nutraceuticals for the treatment of metabolic diseases: evidence from clinical practice.
        Expert Rev. Endocr. Metab. 2014; https://doi.org/10.1586/17446651.2015.995630
        • Derosa G.
        • Maffioli P.
        • Cicero A.F.
        Berberine on metabolic and cardiovascular risk factors: an analysis from preclinical evidences to clinical trials.
        Expert Opin. Biol. Ther. 2012; 12: 1113-1124
        • Derosa G.
        • D'Angelo A.
        • Bonaventura A.
        • et al.
        Effects of berberine on lipid profile in subjects with low cardiovascular risk.
        Expert Opin. Biol. Ther. 2013; 13: 475-482
        • Derosa G.
        • Bonaventura A.
        • Bianchi L.
        • et al.
        Effects of berberis aristata/silybum marianum association on metabolic parameters and adipocytokines in overweight dyslipidemic patients.
        J. Biol. Regul. Homeost. Agents. 2013; 27: 709-720
        • Derosa G.
        • Bonaventura A.
        • Bianchi L.
        • et al.
        Berberis aristata/silybum marianum fixed combination on lipid profile and insulin secretion in dyslipidemic patients.
        Expert Opin. Biol. Ther. 2013; 13: 1495-1506
        • Kong W.
        • Wei J.
        • Abidi P.
        • Lin M.
        • et al.
        Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins.
        Nat. Med. 2004; 10: 1344-1351
        • Chen W.
        • Miao Y.Q.
        • Fan D.J.
        • et al.
        Bioavailability study of berberine and the enhancing effects of TPGS on intestinal absorption in rats.
        AAPS PharmSciTech. 2011; 12: 705-711
        • Pan G.Y.
        • Wang G.J.
        • Liu X.D.
        • et al.
        The involvement of P-glycoprotein in berberine absorption.
        Pharmacol. Toxicol. 2002; 91: 193-197
        • Chae H.W.
        • Kim I.W.
        • Jin H.E.
        • et al.
        Effect of ion-pair formation with bile salts on the in vitro cellular transport of berberine.
        Arch. Pharm. Res. 2008; 31: 103-110
        • Luper S.
        A review of plants used in the treatment of liver disease: part 1.
        Altern. Med. Rev. 1998; 3: 410-421
        • Zhou S.
        • Lim L.Y.
        • Chowbay B.
        Herbal modulation of P-glycoprotein.
        Drug Metab. Rev. 2004; 36: 57-104
        • Kidd P.
        • Head K.
        A review of the bioavailability and clinical efficacy of milk thistle phytosome: a silybin-phosphatidylcholine complex (Siliphos).
        Altern. Med. Rev. 2005; 10: 193-203
        • Proposed International Guidelines for Biomedical Research Involving Human Subjects
        The Council for International Organisation of Medical Sciences.
        1982 (Geneva)
        • Expert Panel on Detection
        Evaluation, and treatment of high blood cholesterol in Adults. Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult treatment panel III).
        JAMA. 2001; 285: 2486-2497
        • World Health Organization
        Obesity: Preventing and Managing the Global Epidemic.
        (Report of WHO Consultation on Obesity) WHO, GenevaJune 1997
      1. 1999 world health organization-international society of hypertension guidelines for the management of hypertension. guidelines subcommittee.
        J. Hypertens. 1999; 17: 151-183
        • NCEP
        Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult treatment panel III) final report.
        Circulation. 2002; 106: 3143-4216
        • Derosa G.
        • Ferrari I.
        • D'Angelo A.
        • Salvadeo S.A.
        • Fogari E.
        • Gravina A.
        • Mereu R.
        • Palumbo I.
        • Maffioli P.
        • Randazzo S.
        • Cicero A.F.
        Oral fat load effects on inflammation and endothelial stress markers in healthy subjects.
        Heart Vessels. 2009; 24: 204-210
        • Derosa G.
        • Ferrari I.
        • D'Angelo A.
        • Salvadeo S.A.
        • Fogari E.
        • Gravina A.
        • Mereu R.
        • Palumbo I.
        • Maffioli P.
        • Randazzo S.
        • Cicero A.F.
        Effects of a standardized oral fat load on vascular remodelling markers in healthy subjects.
        Microvasc. Res. 2010; 80: 110-115
        • Winer B.J.
        Statistical Principles in Experimental Design.
        second ed. McGraw-Hill, New York (USA)1971
        • Kong W.J.
        • Wei J.
        • Zuo Z.Y.
        • et al.
        Combination of simvastatin with berberine improves the lipid-lowering efficacy.
        Metabolism. 2008; 57: 1029-1037
        • Di Pierro F.
        • Villanova N.
        • Agostini F.
        • et al.
        Pilot study on the additive effects of berberine and oral type 2 diabetes agents for patients with suboptimal glycemic control.
        Diabetes Metab. Syndr. Obes. 2012; 5: 213-217
        • Wang Z.S.
        • Lu F.E.
        • Chen G.
        • et al.
        Effect of berberine on insulin secretion and glucokinase activity of NIT-1 cells.
        Yao Xue Xue Bao. 2007; 42: 1045-1049
        • Cheng Z.
        • Pang T.
        • Gu M.
        • et al.
        Berberine-stimulated glucose uptake in L6 myotubes involves both AMPK and p38 MAPK.
        Biochim. Biophys. Acta. 2006; 1760: 1682-1689
        • Huseini H.F.
        • Larijani B.
        • Heshmat R.
        • et al.
        The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial.
        Phytother. Res. 2006; 20: 1036-1039