Efectos del tratamiento con un suplemento nutricional a base de monacolina K, berberina y coenzima Q10 (lipoK®) sobre el metabolismo lipídico en pacientes con hipercolesterolemia y riesgo cardiovascular moderado
DOI: 10.1016/j.semerg.2022.04.005
F Martinez-Martin 1, E Corbella 2, I Sarasa 3, F Trias 4, D Petitbò 5, M Licerán 6, R M Sánchez-Hernández 1, D Martin 7, A Sánchez 7, C Arnás 7, S de Dios 8, M Florido 9, X Pintó 10
1Endocrinology & Nutrition Dpt, University Hospital Dr. Negrin, Las Palmas de Gran Canaria, Spain. 2Lipid Unit and Vascular Risk. Internal Medicine Department Bellvitge University Hospital-IDIBELL, Spain; CIBEROBN, Spain. 3Lipid Unit and Vascular Risk. Internal Medicine Department Bellvitge University Hospital-IDIBELL, Spain. 4Lipid Unit and Vascular Risk. Internal Medicine Department Bellvitge University Hospital-IDIBELL, Spain; CAP Alhambra, L’Hospitalet de Llobregat, Spain. Electronic address: ftriaslipok@gmail.com. 5CAP Alhambra, L’Hospitalet de Llobregat, Spain. 6Lipid Unit and Vascular Risk. Internal Medicine Department Bellvitge University Hospital-IDIBELL, Spain; CAP Alhambra, L’Hospitalet de Llobregat, Spain. 7Endocrinology & Nutrition Unit Hospital San Roque, Las Palmas de Gran Canaria, Spain. 8Cardiooncology Unit Hospital Universitario la Zarzuela, Madrid, Spain. 9Bioksan Naturalmente Juntos S.L., Las Palmas De Gran Canaria, Spain. 10Lipid Unit and Vascular Risk. Internal Medicine Department Bellvitge University Hospital-IDIBELL, Spain; CIBEROBN, Spain; Universidad de Barcelona, Spain.
Abstract
Objective: The use of nutritional supplements to treat hypercholesterolemia is gradually increasing, however further studies on their efficacy and safety are required.
Patients and methods: The present clinical trial included patients with moderate hypercholesterolemia and cardiovascular risk who were treated either with a nutraceutical preparation containing 3.75mg of monacolin K, 515mg of berberine and 50mg of coenzyme Q10 per tablet (Lipok®) or with a placebo. The clinical and laboratory variables were analyzed at baseline and at three and six months. None of the patients was diabetic, and none was being treated with lipid-lowering drugs or with any other nutritional supplements affecting lipid metabolism.
Results: In patients of the intervention group and of the placebo group, baseline LDL-C was 134.7mg/dL (14.4) and 138.7mg/dL (15.2), respectively. At three months after treatment start, LDL-C had decreased by 26.1mg/dL (-32.4 to 19.7) and increased by 4.5mg/dL (-1.5 to 10.5) in the respective groups. In the intervention group, a similar decrease in non-HDL-C and total cholesterol was observed, while no significant changes were observed in either group for HDL-C, triglycerides and lipoprotein(a). A good tolerance and safety profile was observed.
Conclusion: In conclusion, this study demonstrates that the combination of monacolin K, berberine and coenzyme Q10 is effective and safe for treating hypercholesterolemia in patients with a moderate degree of excess LDL-C and cardiovascular risk.
Keywords: Hypercholesterolemia treatment; Nutraceuticals; Nutraceuticos; Nutritional supplements; Suplementos nutricionales; Tratamiento de la hipercolesterolemia.
Introduction
Hypercholesterolemia is a major cause of atherothrombotic cardiovascular disease (ACVD)1 and its detection and treatment in the general population is a fundamental preventive measure for controlling the growing epidemic of this disease.2 However, the control of hypercholesterolemia in the various degrees of cardiovascular risk (CVR) is still very poor.3 This is largely due to the inadequate use of lipid-lowering drugs, which is due to various factors among which therapeutic inertia by health professionals and lack of patient treatment adherence are notable.4, 5 Intolerance and concern about potential side effects are common causes of non-adherence to lipid-lowering drugs.6 Therefore, in recent years there has been a progressive increase in the use of dietary supplements that affect lipid metabolism, or nutraceuticals,7, 8 to treat hypercholesterolemia, particularly in subjects who are intolerant to statins and who, despite maintaining a healthy lifestyle, have a moderate CVR or a moderate degree of hypercholesterolemia. In fact, these products have been included in guidelines for the treatment of dyslipidaemia published by various scientific societies (European guidelines on dyslipidaemias)2, 9 in which red yeast rice (RYR) figures prominently. RYR is a nutraceutical obtained by fermenting rice (Oryza sativa) by the action of a yeast, Monascus purpureus,10 during which monacolins are produced, particularly monacolin K, whose structure is very similar to that of lovastatin and, like the latter, its main mechanism of action is decreasing intracellular synthesis of cholesterol by partial and reversible inhibition of the HMG-CoA reductase enzyme. To enhance its hypocholesterolemic action, RYR has been associated to other bioactive compounds, including products to inhibit cholesterol absorption, such as plant sterols, or enhancers for the hepatic uptake of cholesterol such as berberine, through increased LDL receptor activity.11 Berberine is an alkaloid contained in various species of plants of the Berberis genus (Berberis vulgaris, Berberis aquifolium, and Berberis aristata).12 It decreases LDL cholesterol (LDL-C) by increasing the activity of the LDL receptor by various mechanisms, among them the reduction of the protein PCSK9.13 Despite the progressive increase in the use of nutraceuticals to lower plasma cholesterol, the clinical evidence to justify their use is still limited. The present study analyzed the lipid effects of a combination of red yeast rice and berberine with coenzyme Q10 (ubiquinone), a molecule that has been used to prevent muscular symptoms related to statin use14 in a population with moderate hypercholesterolemia and CVR treated at lipids units.
Resumen
Objetivo: El uso de suplementos nutricionales para tratar la hipercolesterolemia está aumentando de forma progresiva; sin embargo son necesarios más estudios sobre su eficacia y seguridad.
Pacientes y métodos: En el presente ensayo clínico fueron incluidos pacientes con hipercolesterolemia y riesgo cardiovascular moderados que fueron tratados con un preparado nutracéutico que contenía 3,75 mg de monacolina K, 515 mg de berberina y 50 mg de coenzima Q10 por comprimido (Lipok®) o con placebo. Se analizaron las variables clínicas y de laboratorio en situación basal y a los 3 y 6 meses. Ningún paciente era diabético y ninguno seguía tratamiento con fármacos hipolipidemiantes u otros suplementos nutricionales con efectos sobre el metabolismo lipídico.
Resultados: En los pacientes del grupo de intervención y del grupo placebo, el c-LDL basal era de 134,7 mg/dL (14,4) y 138,7 mg/dL (15,2), respectivamente. A los 3 meses de tratamiento el c-LDL había disminuido 26,1 mg/dL (de –32,4 a 19,7) y aumentado 4,5 mg/dL (de –1,5 a 10,5) en ambos grupos, respectivamente. En el grupo de intervención se observó un descenso similar del c-no HDL y del colesterol total, mientras que no ocurrieron cambios significativos en ninguno de los 2 grupos en el c-HDL, los triglicéridos y la lipoproteína (a). Se observó un buen perfil de tolerancia y seguridad.
Conclusión. Este estudio demuestra que la combinación de monacolina K, berberina y coenzima Q10 es eficaz y segura para tratar la hipercolesterolemia en los pacientes con un grado de exceso de c-LDL y de riesgo cardiovascular moderados.