A Combination of Lactoplantibacillus plantarum Strains CECT7527, CECT7528, and CECT7529 Plus Monacolin K Reduces Blood Cholesterol: Results from a Randomized, Double-Blind, Placebo-Controlled Study

Rafael Guerrero-Bonmatty, Guadalupe Gil-Fernández, Francisco José Rodríguez-Velasco, Jordi Espadaler-Mazo, Rafael Guerrero-Bonmatty, Guadalupe Gil-Fernández, Francisco José Rodríguez-Velasco, Jordi Espadaler-Mazo

Abstract

Background: Dietary supplements have been proposed to help manage blood cholesterol, including red yeast rice (RYR) extracts, plant sterols and stanols, beta-glucans, and some probiotics. This study was conducted to evaluate the efficacy of RYR (containing 10 mg of monacolin K) combined with 109 CFU of three Lactoplantibacillus plantarum strains (CECT7527, CECT7528, and CECT7529).

Methods: A 12-week randomized, double-blinded, placebo-controlled clinical trial was conducted. In total, 39 adult patients were enrolled, having total cholesterol (TC) ≥200 mg/dL, and being statin-naïve or having recently stopped statin treatment because of intolerance. Active product or placebo were taken once daily, and subjects were evaluated at baseline, 6, and 12 weeks.

Results: Study groups were comparable at baseline, except for history of recent hypercholesterolemia treatment (81% in active vs. 22% in placebo). Changes in LDL cholesterol and TC became significant compared to placebo (mean difference between groups and standard error of the mean = 23.6 ± 1.5 mg/dL, p = 0.023 and 31.4 ± 1.9 mg/dL, p = 0.011, respectively) upon adjusting for the baseline imbalance in hypercholesterolemia treatment. No adverse effects were noted during the study.

Conclusion: This combination of 10 mg of monacolin K and L. plantarum strains was well tolerated and achieved a statistically significant greater reduction in LDL-C and TC in the intervention group compared to the placebo, once adjusting for recent history of hypercholesterolemia treatment.

Keywords: LDL-cholesterol; Lactoplantibacillus plantarum; bile-salt hydrolases; monacolin K; probiotic bacteria; statins.

Conflict of interest statement

J.E.-M. is a full-time employee of AB-BIOTICS SA, the company manufacturing the nutraceutical product used in this study. All other authors (R.G.-B., G.G.-F., F.J.R.-V.) report no conflicts of interest.

Figures

Figure 1
Figure 1
CONSORT flowchart of recruited patients.
Figure 2
Figure 2
Mean blood levels of LDL-C (a) and TC (b) in the placebo (dashed line) and active (continuous line) groups, adjusted for history of recent hypercholesterolemia treatment. Error bars indicate standard errors of the adjusted means. In repeated measures general linear model analysis (GLM), the effect of treatment was statistically significant both in LDL-C (p = 0.023) and TC (p = 0.011), as well as the effect of history of recent hypercholesterolemia treatment (p < 0.001 for both).

References

    1. World Health Organization WHO Media Centre: Cardiovascular Diseases. [(accessed on 6 March 2021)]; Available online: .
    1. Ference B.A., Ginsberg H.N., Graham I., Ray K.K., Packard C.J., Bruckert E., Hegele R.A., Krauss R.M., Raal F.J., Schunkert H., et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur. Heart J. 2017;38:2459–2472. doi: 10.1093/eurheartj/ehx144.
    1. Silverman M.G., Ference B.A., Im K., Wiviott S.D., Giugliano R.P., Grundy S.M., Braunwald E., Sabatine M.S. Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis. JAMA. 2016;316:1289–1297. doi: 10.1001/jama.2016.13985.
    1. Grundy S.M., Stone N.J., Bailey A.L., Beam C., Birtcher K.K., Blumenthal R.S., Braun L.T., de Ferranti S., Faiella-Tommasino J., Forman D.E., et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J. Am. Coll Cardiol. 2019;73:e285–e350. doi: 10.1016/j.jacc.2018.11.003.
    1. Mach F., Baigent C., Catapano A., Koskinas K., Casula M., Badimon L., Chapman M., De Backer G., Delgado V., Ference B., et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Eur. Heart J. 2019;41:111–188. doi: 10.1093/eurheartj/ehz455.
    1. Mills E.J., Rachlis B., Wu P., Devereaux P.J., Arora P., Perri D. Primary prevention of cardiovascular mortality and events with statin treatments: A network meta-analysis involving more than 65,000 patients. J. Am. Coll Cardiol. 2008;52:1769–1781. doi: 10.1016/j.jacc.2008.08.039.
    1. Yebyo H.G., Aschmann H.E., Puhan M.A. Finding the Balance Between Benefits and Harms When Using Statins for Primary Prevention of Cardiovascular Disease: A Modeling Study. Ann. Intern. Med. 2019;170:1–10. doi: 10.7326/M18-1279.
    1. Nissen S.E., Stroes E., Dent-Acosta R.E., Rosenson R.S., Lehman S.J., Sattar N., Preiss D., Bruckert E., Ceska R., Lepor N., et al. Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance: The GAUSS-3 Randomized Clinical Trial. JAMA. 2016;315:1580–1590. doi: 10.1001/jama.2016.3608.
    1. Zhang H., Plutzky J., Skentzos S., Morrison F., Mar P., Shubina M., Turchin A. Discontinuation of statins in routine care settings: A cohort study. Ann. Intern. Med. 2013;158:526–534. doi: 10.7326/0003-4819-158-7-201304020-00004.
    1. Yebyo H.G., Aschmann H.E., Kaufmann M., Puhan M.A. Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta-analysis, and network meta-analysis of randomized trials with 94,283 participants. Am. Heart J. 2019;210:18–28. doi: 10.1016/j.ahj.2018.12.007.
    1. Cai R., Yuan Y., Sun J., Xia W., Huang R., Tian S., Dong X., Shen Y., Wang S. Statins worsen glycemic control of T2DM in target LDL-c level and LDL-c reduction dependent manners: A meta-analysis. Expert Opin. Pharmacother. 2016;17:1839–1849. doi: 10.1080/14656566.2016.1220539.
    1. Saeed K.M.I. Prevalence of Risk Factors for Non-Communicable Diseases in the Adult Population of Urban Areas in Kabul City, Afghanistan. Cent. Asian J. Glob. Health. 2013;2:69. doi: 10.5195/CAJGH.2013.69.
    1. Zhang H., Plutzky J., Shubina M., Turchin A. Continued Statin Prescriptions After Adverse Reactions and Patient Outcomes: A Cohort Study. Ann. Intern. Med. 2017;167:221–227. doi: 10.7326/M16-0838.
    1. Ward N.C., Pang J., Ryan J.D.M., Watts G.F. Nutraceuticals in the management of patients with statin-associated muscle symptoms, with a note on real-world experience. Clin. Cardiol. 2018;41:159–165. doi: 10.1002/clc.22862.
    1. Bianconi V., Mannarino M.R., Sahebkar A., Cosentino T., Pirro M. Cholesterol-Lowering Nutraceuticals Affecting Vascular Function and Cardiovascular Disease Risk. Curr. Cardiol. Rep. 2018;20:53. doi: 10.1007/s11886-018-0994-7.
    1. Le Roy T., Lecuyer E., Chassaing B., Rhimi M., Lhomme M., Boudebbouze S., Ichou F., Haro Barcelo J., Huby T., Guerin M., et al. The intestinal microbiota regulates host cholesterol homeostasis. BMC Biol. 2019;17:94. doi: 10.1186/s12915-019-0715-8.
    1. Molinero N., Ruiz L., Sanchez B., Margolles A., Delgado S. Intestinal Bacteria Interplay With Bile and Cholesterol Metabolism: Implications on Host Physiology. Front. Physiol. 2019;10:185. doi: 10.3389/fphys.2019.00185.
    1. Hill C., Guarner F., Reid G., Gibson G.R., Merenstein D.J., Pot B., Morelli L., Canani R.B., Flint H.J., Salminen S., et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 2014;11:506–514. doi: 10.1038/nrgastro.2014.66.
    1. Wu Y., Zhang Q., Ren Y., Ruan Z. Effect of probiotic Lactobacillus on lipid profile: A systematic review and meta-analysis of randomized, controlled trials. PLoS ONE. 2017;12:e0178868. doi: 10.1371/journal.pone.0178868.
    1. Zheng J., Wittouck S., Salvetti E., Franz C., Harris H.M.B., Mattarelli P., O’Toole P.W., Pot B., Vandamme P., Walter J., et al. A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. Int. J. Syst. Evol. Microbiol. 2020;70:2782–2858. doi: 10.1099/ijsem.0.004107.
    1. Ruscica M., Pavanello C., Gandini S., Macchi C., Botta M., Dall’Orto D., Del Puppo M., Bertolotti M., Bosisio R., Mombelli G., et al. Nutraceutical approach for the management of cardiovascular risk—A combination containing the probiotic Bifidobacterium longum BB536 and red yeast rice extract: Results from a randomized, double-blind, placebo-controlled study. Nutr. J. 2019;18:13. doi: 10.1186/s12937-019-0438-2.
    1. Mazza A., Schiavon L., Rigatelli G., Torin G., Montanaro F., Lenti S. The short-term supplementation of monacolin K improves the lipid and metabolic patterns of hypertensive and hypercholesterolemic subjects at low cardiovascular risk. Food Funct. 2018;9:3845–3852. doi: 10.1039/C8FO00415C.
    1. Derosa G., D’Angelo A., Maffioli P. Coenzyme q10 liquid supplementation in dyslipidemic subjects with statin-related clinical symptoms: A double-blind, randomized, placebo-controlled study. Drug Des. Dev. Ther. 2019;13:3647–3655. doi: 10.2147/DDDT.S223153.
    1. Fuentes M.C., Lajo T., Carrion J.M., Cune J. Cholesterol-lowering efficacy of Lactobacillus plantarum CECT 7527, 7528 and 7529 in hypercholesterolaemic adults. Br. J. Nutr. 2013;109:1866–1872. doi: 10.1017/S000711451200373X.
    1. Seong S.J., Ohk B., Kang W.Y., Gwon M.R., Kim B.K., Cho S., Yang D.H., Lee H.W., Yoon Y.R. Pharmacokinetic Drug Interactions Between Amlodipine, Valsartan, and Rosuvastatin in Healthy Volunteers. Adv. Ther. 2019;36:1642–1656. doi: 10.1007/s12325-019-00976-9.
    1. Gude D. Angiotensin-converting enzyme inhibitors in lipid metabolism and atherosclerosis: An ace up the sleeve? J. Sci. Soc. 2014;41:59–60. doi: 10.4103/0974-5009.126762.
    1. Faul F., Erdfelder E., Buchner A., Lang A.G. Statistical power analyses using G*Power 3.1: Tests for correlation and regression analyses. Behav. Res. Methods. 2009;41:1149–1160. doi: 10.3758/BRM.41.4.1149.
    1. Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd ed. Lawrence Erlbaum Associates; Hillsdale, NJ, USA: 1988.
    1. Committee for Medicinal Products for Human Use . Guideline on Adjustment for Baseline Covariates in Clinical Trials. European Medicines Agency; London, UK: 2015. Technical report, EMA/CHMP/295050/2013.
    1. Guardia Serecigni J., Jiménez Arriero M., Pascual Pastor F., Flórez Menéndez G., Contel Guillamón M. In: Guías Clinicas SOCIDROGALCOHOL Basadas en la EVIDENCIA CIENTÍFICA. 2nd ed. Socidrogalcohol, editor. Socidrogalcohol; Valencia, Spain: 2008. p. 165.
    1. Fuentes M.C., Lajo T., Carrión J.M., Cuñé J. A randomized clinical trial evaluating a proprietary mixture of Lactobacillus plantarum strains for lowering cholesterol. Mediterranean J. Nutr. Metab. 2016;9:125–135. doi: 10.3233/MNM-160065.
    1. Bosch M., Fuentes M.C., Audivert S., Bonachera M.A., Peiro S., Cune J. Lactobacillus plantarum CECT 7527, 7528 and 7529: Probiotic candidates to reduce cholesterol levels. J. Sci. Food Agric. 2014;94:803–809. doi: 10.1002/jsfa.6467.
    1. Mukerji P., Roper J.M., Stahl B., Smith A.B., Burns F., Rae J.C., Yeung N., Lyra A., Svard L., Saarinen M.T., et al. Safety evaluation of AB-LIFE((R)) (Lactobacillus plantarum CECT 7527, 7528 and 7529): Antibiotic resistance and 90-day repeated-dose study in rats. Food Chem. Toxicol. 2016;92:117–128. doi: 10.1016/j.fct.2016.03.018.
    1. Endo A. The discovery and development of HMG-CoA reductase inhibitors. J. Lipid Res. 1992;33:1569–1582. doi: 10.1016/S0022-2275(20)41379-3.
    1. Gerards M.C., Terlou R.J., Yu H., Koks C.H., Gerdes V.E. Traditional Chinese lipid-lowering agent red yeast rice results in significant LDL reduction but safety is uncertain—A systematic review and meta-analysis. Atherosclerosis. 2015;240:415–423. doi: 10.1016/j.atherosclerosis.2015.04.004.
    1. Liu J., Zhang J., Shi Y., Grimsgaard S., Alraek T., Fonnebo V. Chinese red yeast rice (Monascus purpureus) for primary hyperlipidemia: A meta-analysis of randomized controlled trials. Chin. Med. 2006;1:4. doi: 10.1186/1749-8546-1-4.
    1. Dujovne C.A. Red Yeast Rice Preparations: Are They Suitable Substitutions for Statins? Am. J. Med. 2017;130:1148–1150. doi: 10.1016/j.amjmed.2017.05.013.
    1. Fogacci F., Banach M., Mikhailidis D.P., Bruckert E., Toth P.P., Watts G.F., Reiner Z., Mancini J., Rizzo M., Mitchenko O., et al. Safety of red yeast rice supplementation: A systematic review and meta-analysis of randomized controlled trials. Pharmacol. Res. 2019;143:1–16. doi: 10.1016/j.phrs.2019.02.028.
    1. Xiao L., Pan G. An important intestinal transporter that regulates the enterohepatic circulation of bile acids and cholesterol homeostasis: The apical sodium-dependent bile acid transporter (SLC10A2/ASBT) Clin. Res. Hepatol. Gastroenterol. 2017;41:509–515. doi: 10.1016/j.clinre.2017.02.001.
    1. Joyce S.A., MacSharry J., Casey P.G., Kinsella M., Murphy E.F., Shanahan F., Hill C., Gahan C.G. Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut. Proc. Natl. Acad. Sci. USA. 2014;111:7421–7426. doi: 10.1073/pnas.1323599111.
    1. Long S.L., Gahan C.G.M., Joyce S.A. Interactions between gut bacteria and bile in health and disease. Mol. Aspects Med. 2017;56:54–65. doi: 10.1016/j.mam.2017.06.002.
    1. Espadaler J., Audivert S., Navarro-Tapia E., Buj D. Demographic and Clinical Charactersitics Influencing the Effects of a Cholesterol-Lowering Probiotic; Proceedings of the 10th Workshop on Probiotics and Prebiotics; Las Palmas de Gran Canaria, Spain. 6–8 February 2019; p. 6.
    1. Kullisaar T., Zilmer K., Salum T., Rehema A., Zilmer M. The use of probiotic L. fermentum ME-3 containing Reg’Activ Cholesterol supplement for 4 weeks has a positive influence on blood lipoprotein profiles and inflammatory cytokines: An open-label preliminary study. Nutr. J. 2016;15:93. doi: 10.1186/s12937-016-0213-6.
    1. Gupta S., Wang Z. Treatment satisfaction with different weight loss methods among respondents with obesity. Clin. Obes. 2016;6:161–170. doi: 10.1111/cob.12140.
    1. Calugi S., Marchesini G., El Ghoch M., Gavasso I., Dalle Grave R. The association between weight maintenance and session-by-session diet adherence, weight loss and weight-loss satisfaction. Eat. Weight Disord. 2020;25:127–133. doi: 10.1007/s40519-018-0528-8.
    1. Talbert R.L. New therapeutic options in the National Cholesterol Education Program Adult Treatment Panel III. Am. J. Manag. Care. 2002;8:S301–S307.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere