REVIEW PAPER
Hypolipaemic nutraceutics: red yeast rice and Armolipid, berberine and bergamot
 
More details
Hide details
1
National Institute of Public Health – National Institute of Hygiene, Warsaw, Poland
2
Institute of Rural Health, Lublin, Poland
CORRESPONDING AUTHOR
Longina Kłosiewicz-Latoszek   

Narodowy Instytut Zdrowia Publicznego - PZH, Powsińska 61/63, 02-903, Warszawa, Poland
 
 
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Increased serum cholesterol levels constitute one of the main risk factors for cardiovascular diseases. Statins are a major method for reducing the levels which also lower the risk of cardiovascular events. However, these valuable drugs cannot be used in all patients who need them due to contraindications and intolerance. In such cases, help can be sought from nutraceutics that reduce the serum cholesterol concentration. Since there are numerous products of this type available at drugstores, registered as supplements, there seems to be a need to demonstrate their effectiveness in preventing cardiovascular diseases induced by atherosclerosis. In literature, increasingly more attention is drawn to red yeast rice, Armolipid, berberine and bergamot.

Brief description:
This article presents knowledge about these nutraceutics based on clinical studies and expert statements relating to their use. The results of clinical studies and metaanalyses have shown that nutraceutics with cholesterol lowering properties, red yeast rice and Armolipid are the most favourable for reducing cardiovascular events. However, the evidence of benefits of berberine and bergamot is not so conclusive.

Conclusions:
Red yeast rice products and Armolipid may be used as an alternative treatment in statin intolerant patients, especially in combination with ezetimibe. These nutraceutics can be also considered, as an adjunct to diet therapy in primary prevention of cardiovascular diseases in patients with mild and moderate hypercholesterolaemia. The opinion of experts on berberine and bergamot is ambiguous.

Kłosiewicz-Latoszek L, Cybulska B, Stoś K, Tyszko P Hypolipaemic nutraceutics: red yeast rice and Armolipid, berberine and bergamot. Ann Agric Environ Med. doi: 10.26444/aaem/130629
 
REFERENCES (54)
1.
Mach F, Baigent C, Catapano AL, 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 the European Atherosclerosis Society (EAS). Eur Heart J. 2019; 41: 111–188. https:// doi: 10.1093/eurheartj/ehz455.
 
2.
Banach M, Patti AM, Giglio RV, et al. The role of nutraceuticals in statin intolerant patients. J Am Coll Cardiol. 2018 Jul 3; 72(1): 96–118. https:// doi: 10.1016/j.jacc.2018.04.040.
 
3.
Banach M, Bruckert E, Descamps OS, et al. The role of red yeast rice (RYR) supplementations in plasma cholesterol control: a review on expert opinion. Atheroscler Suppl. 2019 Dec; 39: e1-e8. doi: 10.1016/j.atherosclerosissup.2019.08.023.
 
4.
Cicero AFG, Colletti A, Bajrakti G, et al. Lipid lowering nutraceuticals in clinical practice: position paper from International Lipid Expert Panel (ILEP).Arch Med Sci. 2017 Aug; 13(5): 965–100.
 
5.
https://doi: 10.5114/aoms.2017.693265. Gerards MC, Terlou RJ, Yu H, et al. 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 Jun; 240(2): 415–23. https:// doi: 10.1016/j.atherosclerosis.2015.04.004.
 
6.
Chen CH, Uang YS, Wong ST, et al. Interaction between red yeast rice and CYP450/P-glicoprotein and its implications for the clinical pharmaco-kinetics of lovastatin. Evid Based Complement Alternat Med. 2012; 2012: 127043. https://doi: 10.1155/2012/127043.
 
7.
Farkouh A, Baumgärtel C. Mini-review: medication safety of red yeast rice. Int J Gen Med. 2019; 12: 167–171. doi: 10.2147/IJGM.S202446.
 
8.
Brouwers JR, Roeters van Lennep JE, Maais AH. Red yeast rice as a cholesterol lowering substance? Caution is warranted. Ned Tijdschr Geneeskd. 2016; 160: D99.
 
9.
Sahebkar A, Serban MC. Gluba-Brzoska A, et al. Lipid-modifing effects of nutraceuticals: an evidence based – approach. Nutrition. 2016; 32: 1179–1192. https://doi: 10.1016/j.nut.2016.04.007.
 
10.
Lu Z, Kou W, Du B, et al. Chinese Coronary Secondary Prevention Study. Effect of Xuezhikang, extract from red yeast Chinese rice on coronary events in Chinese population with previous myocardial infarction. Am J Cardiol. 2008; 101: 1689–1693. https://doi.org/10.1016/j.amjc....
 
11.
Ye P, Lu Zong-Liang, Du Bao-min, et al. Effect of xuezhikang on cardiovascular events and mortality in elderly patients with history of myocardial infarction. A subgroup analysis of elderly subjects from China Coronary Secondary Prevention Study. J Am Geriatr Sci. 2007; 55: 1015–1022. https://doi: 10.1111/j.1532-5415.2007.01230.
 
12.
Sungthong B, Yoothaekool C, Promphamorn S, et al. Efficacy of red yeast rice extract in myocardial infarction patients with bordeline hypercholesterolemia: a meta-analysis of randomized controlled trials. Sci Rep. 2020; 10: 2769. https://doi: 10.1038/541598-020-59796-6.
 
13.
Fogacci F, Banach M, Mikhailidis DP, et al. Lipid. Blood pressure Meta-analysis Collaboration International Lipid Expert Panel. Safety of red yeast rice supplementation: a systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 2019; 143: 1–16. https://doi: 10.1016/j.phrs.2019.02.028.
 
14.
Barrios V, Escobar C, Cicero AFG, et al. A nutraceutical approach (Armolipid Plus) to reduce total and LDL cholesterol in individuals with mild to moderate dyslipidemia: a review of clinical evidence. Atheroscler Suppl. 2017; 24: 1–15. https://doi: 10.1016/j.atherosclerosissup.2016.10.003.
 
15.
Marazzi G, Campolongo G, Pelliccia F, et al. Comparison of low-dose statin versus low dose statin + Armolipid Plus in high intensity statin intolerant patients with a previous coronary event and percutaneous coronary intervention (ADHERENCE trial). Am J Cardiol. 2017; 120: 893–897. https://doi: 10.1016/j.amjcard.2017.06.015.
 
16.
Marazzi G, Campolongo G, Pelliccia F, et al. Usefulness of low dose statin plus ezetymibe and/or nutraceuticals in patients with coronary artery disease intolerant to high dose statin treatment. Am J Cardiol. 2019; 123: 233–238. https://doi: 10.1016/j.amjcard.2018.09.041.
 
17.
Pirro M, Mannarino MR, Bianconi V, et al. The effects of nutraceutical combination on plasma lipids and glucose: a systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 2016; 110: 76 –88, https://doi: 10.1016/j.phrs.2016.04.021.
 
18.
Fulcher J, O’Connell R, Voysey M, et al. Efficacy and safety of LDL lowering therapy in men and women: a meta-analysis of individual data from 174000 participants in 26 randomised trials. Lancet. 2019; 385: 1397–1405. https://doi:10.1016/S0140-6736....
 
19.
Cholesterol Treatment Trialists’ Collaboration. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. Lancet. 2019; 393: 407–415. https://doi.org/10.1016/S0140-....
 
20.
Ustawa z dnia 25 sierpnia 2006 r. o bezpieczeństwie żywności i żywienia Dz. U. z 2006 r. Nr 171, poz. 1225 ze zmianami.
 
21.
Rozporządzenie (WE) nr 1924/2006 Parlamentu Europejskiego i Rady z dnia 20 grudnia 2006 r. w sprawie oświadczeń żywieniowych i zdrowotnych dotyczących żywności.
 
22.
Rozporządzenie Parlamentu Europejskiego i Rady (UE) NR 1169/2011 z dnia 25 października 2011 r. w sprawie przekazywania konsumentom informacji na temat żywności, zmiany rozporządzeń Parlamentu Europejskiego i Rady (WE) nr 1924/2006 i (WE) nr 1925/2006 oraz uchylenia dyrektywy Komisji 87/250/EWG, dyrektywy Rady 90/496/EWG, dyrektywy Komisji 1999/10/WE.
 
23.
Scientific Opinion on the substantiation of health claims related to monacolin K from red yeastrice and maintenance of normal blood LDL-cholesterol concentrations (ID 1648, 1700) pursuant to Article 13(1) of Regulation (EC) No 1924/2006, EFSA Journal 2011; 9(7): 2304.
 
24.
Rozporządzenie Komisji (UE) nr 432/2012 z dnia 16 maja 2012 r. ustanawiające wykaz dopuszczonych oświadczeń zdrowotnych dotyczących żywności, innych niż oświadczenia odnoszące się do zmniejszenia ryzyka choroby oraz rozwoju i zdrowia dzieci, z późniejszymi zmianami.
 
25.
Rozporządzenie Komisji (UE) nr 212/2014 z dnia 6 marca 2014 r. zmieniającego rozporządzenie (WE) nr 1881/2006 w odniesieniu do najwyższych dopuszczalnych poziomów zanieczyszczenia „cytrynina” w suplementach diety na bazie ryżu poddanego fermentacji grzybami Monascus purpureus.
 
26.
Scientific opinion on the safety of monacolins in red yeast rice. EFSA Journal 2018; 16(8): 5368.
 
27.
Song D, Hao J, Fan D. Biological properties and clinical application of berberine. Front Med. 2020, https:// doi: 10.1007/s11684-019-0724-6.
 
28.
Cheng Z, Liu S, Wu X, et al. Autologous erythrocytes delivery of berberine hydrochloride with long-acting effect for the hypolipidemia treatment. Drug Deliv. 2020; 27: 283–291. https:// doi: 10.1080/10717544.2020.1716880.
 
29.
Wu M, Wang J, Liu L-T. Advance of studies on anti-atherosclerosis mechanism of berberie. Chin J Integr Med. 2010; 16(2): 188–192.
 
30.
Xie X, Ma X, Zegn S, et al. Mechanisms of berberine for the treatment of atherosclerosis based on network pharmacology. Evid Based Complement Alter Med. 2020, Article ID 3568756, https://doi.org/10.1155/2020/3....
 
31.
Wei J, Jiang JD, Wu JD, et al. Research on the effective improvement of hyperlipidemia by berberine. Chin J Diabetes (Chin), 2005; 13: 49–51.
 
32.
Adorni MP, Zimetti F, Lupo MG, et al. Naturally occurring PCSK9 inhibitors. Nutrients. 2020 May 16; 12(5): https://doi: 10.3390/nu12051440.
 
33.
Brusq JM, Amcellin M, Grondin P, et al. Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine. J Lipid Res. 2006; 47: 1281–1288. doi: 10.1194/jlr.M600020-JLR200.
 
34.
Hsieh YS, Kuo WH, Lin TW, et al. Protective effects of berberine against low-density lipoprotein (LDL) oxidation and oxidized LDL-induced cytotoxicity on endothelial cells. J Agric Food Chem. 2007; 55: 10435–104.
 
35.
https://doi: 10.1021/jf071868c35.Pirillo A, Catapano AL. Berberine, a plant alkaloid with lipid – and glucose-lowering properties: from in vitro evidence to clinical studies. Atherosclerosis. 2015; 243(2): 449–61. https://doi: 10.1016/j.atherosclerosis.2015.09.032.
 
36.
Poli A, Visioli F. Pharmacology of nutraceuticals with lipid lowering properties: High Blood Press Cardiovasc Prev. 2019; 26: 113–118. https://doi: 10.1007/s40292-019-00311-x.
 
37.
Kong W, Wei J, Abidi P, et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med. 2004; 10: 1344–1351. https://doi: 10.1038/nm1135.
 
38.
Dong H, Wang N, Zhao L, Lu F. Berberine in the treatement of type 2 diabetes mellitus: A Systemic review and meta-analysis. Evid Base Complement Altern Med. 2012: 1–12. https://doi: 10.1155/2012/591654.
 
39.
Dong H, Zhao Y, Zhao L, Lu F. The effects of berberine on blood lipids: A systemic review and meta-analysis on randomized controlled trials. Planta Med. 2013; 79: 437–446, https://doi: 10.1055/s-0032-1328321.
 
40.
Lan J, Zhao Y, Dong F, et al. Meta-analysis of the effects and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. 2015; 161: 69–81, https://doi: 10.1016/jep2014.09.049.
 
41.
Leon-Martinez JM, Martinez-Abundis E, Gonzalez-Ortiz M, et al. Effect of berberine plus bezafibrate administration on the lipid profile of patients with mixed dyslipidemia. A pilot clinical trial. J Med Food. 2020 May 12, https://doi: 10.1089/jmf2020.0029.
 
42.
Mazza A, Nicoletti M, Lenti S, et al. Effectiveness and safety of novel nutraceutical formulation addend to ezetimibe in statin-intolerant hypercholesterolemic subjects with moderate-to-high cardiovascular risk. J Med Food. 2020 May 22, https://doi: 10.1089/jmf.2020.0019.
 
43.
Meng S, Wang LS, Huang ZQ, et al. Berberine ameliorates inflammation in patients with acute coronary syndrome following percutaneous coronary intervention. Clin Exp Pharmacol Physiol. 2012; 39: 406–11. https://doi: 10.1111/j.1440-1681.2012.05670.x.
 
44.
Mollace V, Sacco I, Janda E, et al. Hypolipaemic and hypoglycaemic activity of bergamot polyphenois: From animal models to human studies. Fitoterapia. 2011; 82: 309–316. https://doi: 10.1016/j.fitote.2010.10.014.
 
45.
Mannucci C, Navarra M, Calapai F, et al. Clinical pharmacology of citrus bergamia: A systematic review. Phytother Res. 2017; 31: 27–39. https://doi: 10.1002/ptr.5734.
 
46.
Giglio RV, Patti AM, Nikolic D, et al. The effect of bergamot on dyslipidemia. Phytomedicine. 2016; 23: 1175–1181. https://doi: 10.1016/j.phymed.2015.12.0054.
 
47.
Toth PP, Patti AM, Nikolic D, et al. Bergamot reduces plasma lipids, atherogenic small dense LDL and subclinical atherosclerosis in subjects with moderate hypercholesterolemia: A 6 months prospective study. Frontiers Pharmacol. 2016; 6: 299. https://doi: 10.3389/fphar.2015.002994.
 
48.
Ferlazzo N, Visalli G, Smerigio A, et al. Flavonoid fraction of orange and bergamot juices protect human lung epithelial cells from hydrogen peroxide-induced oxidative stress. Evid Based Complement Alternat Med. 2015; 957031. https://doi: 10.1155/2015/9570314.
 
49.
Impelizzeri D, Bruschetta G, Di Paola R, et al. The antinflammatory and antioxidant effects of bergamot ice extract (juBJe) in an experimental model of inflammatory bowel disease. Clin Nutr. 2015; 34: 1146–1154. https://doi: 10.1016/j.clnu.2014.11.012.
 
50.
Nauman MC, Johnson JJ. Clinical applicaton of bergamot (Citrus bergamia) for reducing high cholesterol and cardiovascular disease marker. Integr Food Nutr Metab. 2019 Mar 6(2). https://doi: 10.15761/FNM.10000249.
 
51.
Lamiquiz-Moneo I, Gine-Gonzalez J, Alisente S, et al. Effect of bergamot on lipid profile in humans: A systematic review. Crit Rev Food Sci Nutr. 2019 Oct 31: 1–11, https://doi: 10.1080/10408398.2019.1677554.
 
52.
Miceli N, Mondello MR, Monforte MT, et al. Hypolipidemic effect of Citrus BergamiRisso et Poileau juice in rats fed a hypercholesterolemic diet. J Agric Food Chem. 2007; 55: 10671–10677. https://doi: 10.1021/jf071772i.
 
53.
Di Donna L, Iacopetta D, Cappello AR, et al. Hypocholesterolaemic activity of 3-hydroxy-3-methyl-glutaryl flavanones enriched fraction from bergamot fruit (Citrus bergamia): “In vivo” studies. J Funct Food. 2014; 7: 558–568. https://doi.org/10.1016/j.jff.....
 
54.
Gliozzi MR, Walker S, Muscoli C, et al. Bergamot polyphenolic fraction enhances rosuwastatin-induced effect on LDL cholesterol, LOX-1expression and protein kinase B phophorylationin patients with hyperlipidemia. Intern J Cardiol. 2013; 170(2): 15. https://doi:10.1016/j.ijcard20....
 
eISSN:1898-2263
ISSN:1232-1966