Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2017

Open Access 01-12-2017 | Research

A red yeast rice-olive extract supplement reduces biomarkers of oxidative stress, OxLDL and Lp-PLA2, in subjects with metabolic syndrome: a randomised, double-blind, placebo-controlled trial

Authors: Nina Hermans, Anastasia Van der Auwera, Annelies Breynaert, Annelies Verlaet, Tess De Bruyne, Luc Van Gaal, Luc Pieters, Veronique Verhoeven

Published in: Trials | Issue 1/2017

Login to get access

Abstract

Background

Metabolic syndrome (MetS) refers to clustered cardiovascular risk factors (abdominal obesity, pre-diabetes, high blood pressure, dyslipidaemia). Therapies targeting oxidative stress may delay progression to atherosclerosis and diabetes. We investigated the anti-oxidative effect of a supplement combining red yeast rice and olive extract in patients with MetS.

Methods

A double-blind, placebo-controlled, randomised trial was conducted with 50 patients with MetS as defined by National Cholesterol Education Program Adult Treatment Panel III criteria. Forty-nine subjects randomly assigned to red yeast rice-olive extract (RYR-olive extract; 10.82 mg of monacolins and 9.32 mg of hydroxytyrosol per Cholesfytolplus capsule) or placebo completed the 8-week trial. Whereas effects on cardiovascular risk parameters of MetS have been reported recently, the observed significant 20% increase in oxidised low-density lipoprotein (OxLDL) prompted us to investigate other oxidative stress-related parameters: malondialdehyde (MDA), lipoprotein-associated phospholipase A2 (Lp-PLA2) and 8-hydroxy-2′-deoxyguanosine (8-OHdG). Statistical calculations included univariate quantitative analysis, multivariate linear regression and correlation analysis.

Results

The updated results indicate that an RYR-olive extract supplement significantly reduced Lp-PLA2 by 7% (p < 0.001), but it failed to show a significant decrease in plasma MDA and 8-OHdG (p > 0.05). Reductions in OxLDL (20%) and Lp-PLA2 (7%) were associated with each other (r = 0.740, p < 0.001).

Conclusions

RYR-olive extract significantly reduced Lp-PLA2 in correlation with the marked reduction in plasma OxLDL, which may lead to a reduced risk for cardiovascular disease in patients with MetS.

Trial registration

ClinicalTrials.gov identifier: NCT02065180. Registered on 13 February 2014.
Appendix
Available only for authorised users
Literature
1.
Duvnjak L, Duvnjak M. The metabolic syndrome - an ongoing story. J Physiol Pharmacol. 2009;60 Suppl 7:19–24.PubMed
2.
Li C, Ford ES. Is there a single underlying factor for the metabolic syndrome in adolescents? A confirmatory factor analysis. Diabetes Care. 2007;30(6):1556–61.CrossRefPubMed
3.
Pladevall M, Singal B, Williams LK, Brotons C, Guyer H, Sadurni J, et al. A single factor underlies the metabolic syndrome: a confirmatory factor analysis. Diabetes Care. 2006;29(1):113–22.CrossRefPubMed
4.
5.
Armutcu F, Ataymen M, Atmaca H, Gurel A. Oxidative stress markers, C-reactive protein and heat shock protein 70 levels in subjects with metabolic syndrome. Clin Chem Lab Med. 2008;46(6):785–90.CrossRefPubMed
6.
Palmieri VO, Grattagliano I, Portincasa P, Palasciano G. Systemic oxidative alterations are associated with visceral adiposity and liver steatosis in patients with metabolic syndrome. J Nutr. 2006;136(12):3022–6.PubMed
7.
Fujita K, Nishizawa H, Funahashi T, Shimomura I, Shimabukuro M. Systemic oxidative stress is associated with visceral fat accumulation and the metabolic syndrome. Circ J. 2006;70(11):1437–42.CrossRefPubMed
8.
Hansel B, Giral P, Nobecourt E, Chantepie S, Bruckert E, Chapman MJ, et al. Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense high-density lipoprotein particles displaying impaired antioxidative activity. J Clin Endocrinol Metab. 2004;89(10):4963–71.CrossRefPubMed
9.
Chae JS, Kim OY, Paik JK, Kang R, Seo WJ, Jeong TS, et al. Association of Lp-PLA2 activity and LDL size with interleukin-6, an inflammatory cytokine and oxidized LDL, a marker of oxidative stress, in women with metabolic syndrome. Atherosclerosis. 2011;218(2):499–506.CrossRefPubMed
10.
Persson M, Hedblad B, Nelson JJ, Berglund G. Elevated Lp-PLA2 levels add prognostic information to the metabolic syndrome on incidence of cardiovascular events among middle-aged nondiabetic subjects. Arterioscler Thromb Vasc Biol. 2007;27(6):1411–6.CrossRefPubMed
11.
Holvoet P, Lee DH, Steffes M, Gross M, Jacobs DRJ. Association between circulating oxidized low-density lipoprotein and incidence of the metabolic syndrome. JAMA. 2008;299(19):2287–93.CrossRefPubMedPubMedCentral
12.
Sigurdardottir V, Fagerberg B, Hulthe J. Circulating oxidized low-density lipoprotein (LDL) is associated with risk factors of the metabolic syndrome and LDL size in clinically healthy 58-year-old men (AIR study). J Intern Med. 2002;252(5):440–7.CrossRefPubMed
13.
Acevedo M, Varleta P, Kramer V, Valentino G, Quiroga T, Prieto C, et al. Comparison of lipoprotein-associated phospholipase A2 and high sensitive C-reactive protein as determinants of metabolic syndrome in subjects without coronary heart disease: in search of the best predictor. Int J Endocrinol. 2015;2015:934681.CrossRefPubMedPubMedCentral
14.
White HD, Simes J, Stewart RAH, Blankenberg S, Barnes EH, Marschner IC, et al. Changes in lipoprotein-associated phospholipase A2 activity predict coronary events and partly account for the treatment effect of pravastatin: results from the Long-Term Intervention with Pravastatin in Ischemic Disease study. J Am Heart Assoc. 2013;2(5), e000360.CrossRefPubMedPubMedCentral
15.
Lp-PLA2 Studies Collaboration. Lipoprotein-associated phospholipase A2 and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet. 2010;375(9725):1536–44.CrossRef
16.
Garg S, Madhu SV, Suneja S. Lipoprotein associated phospholipase A2 activity & its correlation with oxidized LDL & glycaemic status in early stages of type-2 diabetes mellitus. Indian J Med Res. 2015;141(1):107–14.CrossRefPubMedPubMedCentral
17.
Covas MI, de la Torre K, Farré-Albaladejo M, Kaikkonen J, Fitó M, López-Sabater C, et al. Postprandial LDL phenolic content and LDL oxidation are modulated by olive oil phenolic compounds in humans. Free Radic Biol Med. 2006;40(4):608–16.CrossRefPubMed
18.
Covas MI, Nyyssönen K, Poulsen HE, Kaikkonen J, Zunft HJF, Kiesewetter H, et al. The effect of polyphenols in olive oil on heart disease risk factors. Ann Intern Med. 2006;145(5):333–41.CrossRefPubMed
19.
de la Torre-Carbot K, Chávez-Servín JL, Jaúregui O, Castellote AI, Lamuela-Raventós RM, Nurmi T, et al. Elevated circulating LDL phenol levels in men who consumed virgin rather than refined olive oil are associated with less oxidation of plasma LDL. J Nutr. 2010;140(3):501–8.CrossRefPubMed
20.
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific opinion on the substantiation of health claims related to polyphenols in olive and protection of LDL particles from oxidative damage (ID 1333, 1638, 1639, 1696, 2865), maintenance of normal blood HDL-cholesterol concentrations (ID 1639), maintenance of normal blood pressure (ID 3781), “anti-inflammatory properties” (ID 1882), “contributes to the upper respiratory tract health” (ID 3468), “can help to maintain a normal function of gastrointestinal tract” (3779), and “contributes to body defences against external agents” (ID 3467) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J. 2011;9(4):2033.CrossRef
21.
Weinbrenner T, Fitó M, de la Torre R, Saez GT, Rijken P, Tormos C, et al. Olive oils high in phenolic compounds modulate oxidative/antioxidative status in men. J Nutr. 2004;134(9):2314–21.PubMed
22.
Heber D, Yip I, Ashley JM, Elashoff DA, Elashoff RM, Go VL. Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. Am J Clin Nutr. 1999;69(2):231–6.PubMed
23.
Klimek M, Wang S, Ogunkanmi A. Safety and efficacy of red yeast rice (Monascus purpureus) as an alternative therapy for hyperlipidemia. P T. 2009;34(6):313–27.PubMedPubMedCentral
24.
Li Y, Jiang L, Jia Z, Xin W, Yang S, Yang Q, et al. A meta-analysis of red yeast rice: an effective and relatively safe alternative approach for dyslipidemia. PLoS One. 2014;9(6), e98611.CrossRefPubMedPubMedCentral
25.
Lin CC, Li TC, Lai MM. Efficacy and safety of Monascus purpureus Went rice in subjects with hyperlipidemia. Eur J Endocrinol. 2005;153(5):679–86.CrossRefPubMed
26.
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), European Food Safety Authority (EFSA). Scientific opinion on the substantiation of health claims related to monacolin K from red yeast rice and maintenance of normal blood LDL-cholesterol concentrations (ID 1648, 1700) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J. 2011;9(4):2304.
27.
Verhoeven V, Van der Auwera A, Van Gaal L, Remmen R, Apers S, Stalpaert M, et al. Can red yeast rice and olive extract improve lipid profile and cardiovascular risk in metabolic syndrome? A double blind, placebo controlled randomized trial. BMC Complement Altern Med. 2015;15:52.CrossRefPubMedPubMedCentral
28.
Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640–5.CrossRefPubMed
29.
Hermans N, Cos P, Vanden Berghe D, Vlietinck AJ, de Bruyne T. Method development and validation for monitoring in vivo oxidative stress: evaluation of lipid peroxidation and fat-soluble vitamin status by HPLC in rat plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2005;822(1-2):33–9.CrossRefPubMed
30.
Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004;114(12):1752–61.CrossRefPubMedPubMedCentral
31.
Keaney Jr JF, Larson MG, Vasan RS, Wilson PW, Lipinska I, Corey D, et al. Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscler Thromb Vasc Biol. 2003;23(3):434–9.CrossRefPubMed
32.
Grattagliano I, Palmieri VO, Portincasa P, Moschetta A, Palasciano G. Oxidative stress-induced risk factors associated with the metabolic syndrome: a unifying hypothesis. J Nutr Biochem. 2008;19(8):491–504.CrossRefPubMed
33.
Wang WY, Li J, Yang D, Xu W, Zha RP, Wang YP. OxLDL stimulates lipoprotein-associated phospholipase A2 expression in THP-1 monocytes via PI3K and p38 MAPK pathways. Cardiovasc Res. 2010;85(4):845–52.CrossRefPubMed
34.
Moutzouri E, Liberopoulos EN, Tellis CC, Milionis HJ, Tselepis AD, Elisaf MS. Comparison of the effect of simvastatin versus simvastatin/ezetimibe versus rosuvastatin on markers of inflammation and oxidative stress in subjects with hypercholesterolemia. Atherosclerosis. 2013;231(1):8–14.CrossRefPubMed
35.
Silva IT, Mello APQ, Damasceno NRT. Antioxidant and inflammatory aspects of lipoprotein-associated phospholipase A2 (Lp-PLA2): a review. Lipids Health Dis. 2011;10:170.CrossRefPubMedPubMedCentral
36.
Hermans N, Cos P, De Meyer GRY, Maes L, Pieters L, vanden Berghe D, et al. Study of potential oxidative stress animal models for the evaluation of antioxidant activity: status of lipid peroxidation and fat-soluble antioxidants. J Pharm Pharmacol. 2007;59(1):131–6.CrossRefPubMed
37.
Black CN, Bot M, Scheffer PG, Penninx BWJH. Sociodemographic and lifestyle determinants of plasma oxidative stress markers 8-OHdG and F2-isoprostanes and associations with metabolic syndrome. Oxid Med Cell Longev. 2016;2016:7530820.CrossRefPubMedPubMedCentral
Metadata
Title
A red yeast rice-olive extract supplement reduces biomarkers of oxidative stress, OxLDL and Lp-PLA2, in subjects with metabolic syndrome: a randomised, double-blind, placebo-controlled trial
Authors
Nina Hermans
Anastasia Van der Auwera
Annelies Breynaert
Annelies Verlaet
Tess De Bruyne
Luc Van Gaal
Luc Pieters
Veronique Verhoeven
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Trials / Issue 1/2017
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-017-2058-5

Other articles of this Issue 1/2017

Trials 1/2017 Go to the issue

Study protocol

A mobile technology intervention to reduce sedentary behaviour in 2- to 4-year-old children (Mini Movers): study protocol for a randomised controlled trial

Study protocol

Community-based trial of annual versus biannual single-dose ivermectin plus albendazole against Wuchereria bancrofti infection in human and mosquito populations: study protocol for a cluster randomised controlled trial

Study protocol

High-speed resistance training and balance training for people with knee osteoarthritis to reduce falls risk: study protocol for a pilot randomized controlled trial

Study protocol

The effect of MElatonin on Depressive symptoms, Anxiety, CIrcadian and Sleep disturbances in patients after acute coronary syndrome (MEDACIS): study protocol for a randomized controlled trial

Study protocol

Saline versus balanced crystalloids for intravenous fluid therapy in the emergency department: study protocol for a cluster-randomized, multiple-crossover trial

Study protocol

A multicentre, randomised intervention study of the Paediatric Early Warning Score: study protocol for a randomised controlled trial