Usefulness of Nutraceuticals (Armolipid Plus) Versus Ezetimibe and Combination in Statin-Intolerant Patients With Dyslipidemia With Coronary Heart Disease

doi:10.1016/j.amjcard.2015.09.023

The American Journal of Cardiology

Volume 116, Issue 12, 15 December 2015, Pages 1798-1801

https://doi.org/10.1016/j.amjcard.2015.09.023 Get rights and content

Statins are extensively used to treat dyslipidemia, but, because of their low tolerability profile, they are discontinued in a significant proportion of patients. Ezetimibe and nutraceuticals have been introduced as alternative therapies and have proved to be effective and well tolerated. A single-blind, single-center, randomized, prospective, and parallel group trial comparing a combination of nutraceuticals (red yeast rice, policosanol, berberine, folic acid, coenzyme Q10 and astaxanthin), called Armolipid Plus, and ezetimibe for 3 months in terms of efficacy and tolerability. Patients who did not achieve their therapeutic target (low-density lipoprotein cholesterol <100 mg/dl) could add the alternative treatment on top of randomized treatment for another 12 months: 100 patients who are dyslipidemic with ischemic heart disease treated with percutaneous coronary intervention were enrolled (ezetimibe n = 50, nutraceutical n = 50). Efficacy (lipid profile) and tolerability (adverse events, transaminases, and creatine kinase) were assessed after 3 and 12 months. After 3 months, 14 patients in the nutraceutical group achieved their therapeutic target, whereas none of the patients in the ezetimibe group did. At 1-year follow-up, 58 patients (72.5%) of the combined therapy group (n = 86) and 14 (100%) of the nutraceutical group reached the therapeutic goal. No patients experienced important undesirable effects. In conclusion, nutraceuticals alone or in combination with ezetimibe are well tolerated and improve the lipid profile in statin-intolerant patients with coronary heart disease. Further studies are needed to assess long-term effects of nutraceuticals on mortality.

Section snippets

Methods

In this single-blind, single center, randomized, prospective, and parallel group trial we compared a nutraceutical combination with ezetimibe in terms of efficacy and tolerability, in statin-intolerant patients who are dyslipidemic treated with PCI (Clinicaltrials.gov identifier: NCT01490229). The composition of the nutraceutical combination was as follows: berberine 500 mg, policosanol 10 mg, red yeast rice 200 mg, folic acid 0.2 mg, coenzyme Q10 2.0 mg, and astaxanthin 0.5 mg (Armolipid Plus;

Results

One hundred patients were enrolled consecutively. Of this study population, 64% subjects had stable angina and 36% subjects had unstable angina. Fifty patients were randomized to receive ezetimibe and 50 patients to receive the nutraceutical combination.

Baseline clinical features and lipid profiles were similar between groups (Table 1).

At 3-month visit, the 2 groups differed for LDL-C, TC, and triglycerides, with lower levels in the nutraceutical combination group than in the ezetimibe group

Discussion

In the present study, we assessed the effects of 2 alternative treatments to statins, ezetimibe, and a combination of nutraceuticals (Armolipid Plus) in patients with CHD and previous PCI. We found that the combination of nutraceuticals was significantly more effective than ezetimibe, as there were significantly greater reductions in TC, LDL-C, and triglycerides with Armolipid Plus than ezetimibe. This is consistent with the outcome of a previous trial¹¹ and was expected because the

Disclosures

The authors have no conflicts of interest to disclose.

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Hypercholesterolemia is a risk factor of cardiovascular diseases, which have been managed using statin drugs. Red yeast rice (RYR) as a traditional food in the Eastern Asia countries has anti-hyperlipidemia activity. Recently, a variety of food supplement products containing RYR have been developed to lower blood cholesterol, which is attributed to the presence of monacolins, especially monacolin K (lovastatin, a statin drug). This review was aimed to summarize the clinical trials using RYR products to investigate their effects on lipid profiles in humans. Relevant articles of human clinical trials were retrieved from PubMed and discussed here. Results showed that RYR and its extracts have been included in commercially available products alone and in combinations with various other materials, which include bioactive compounds such as coenzyme Q10 and berberine, vitamins, extracts from other plants such as phytosterols, polyunsaturated fatty acids or even probiotics. The durations of the trials ranged from 4 weeks to 60 months. The content of monacolin K ranged from 0.32 mg/pack to 10 mg/pack. The data of these human clinical trials demonstrated that these RYR supplement products were sufficient to reduce blood cholesterol in different populations. However, the inclusions of certain materials might not have additive effect. Additionally, studies including a lovastatin only positive control group with the equivalent dose as that of monacolin K in the RYR products remain to be done. Furthermore, variations of monacolin K contents and presence of toxic citrinin are still concerns. Last, bioactivities of other components in RYR should be investigated as well. More future studies will certainly help to fully explore the potentials of this traditional food in the combat against cardiovascular and other metabolic diseases.
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Para el tratamiento de la hipercolesterolemia, además de aconsejar una alimentación saludable, puede ser conveniente recomendar alimentos funcionales o nutracéuticos con efecto hipolipemiante. Dado el progresivo incremento en el número de estos productos y su creciente utilización por la población, la Sociedad Española de Arteriosclerosis (SEA) ha creído conveniente revisar la información disponible, seleccionar los resultados de los estudios científicamente más sólidos y posicionarse sobre la utilidad de los mismos, para recomendar a los profesionales sanitarios y a la población general su potencial utilidad en términos de eficacia y sus posibles beneficios y limitaciones. Se han identificado los siguientes escenarios clínicos en los que se podrían utilizar estos productos y que se analizarán con más detalle en este documento: 1. Tratamiento hipolipemiante en sujetos con intolerancia a estatinas. 2. Tratamiento hipolipemiante «a la carta» en personas en prevención primaria. 3. Prevención cardiovascular a largo plazo en personas sin indicación de tratamiento hipolipemiante. 4. Pacientes con tratamiento hipolipemiante optimizado que no alcanzan objetivos terapéuticos.
In the management of hypercholesterolemia, besides advising a healthy, plant-based diet, it may be useful to recommend functional foods or nutraceutical with cholesterol-lowering properties. Given the progressive increase in the number of these products and their rising use by the population, the Spanish Society of Arteriosclerosis (SEA) has considered it appropriate to review the available information, select the results of the scientifically more robust studies and take a position on their usefulness, to recommend to health professionals and the general population their potential utility in terms of efficacy and their possible benefits and limitations. The following clinical scenarios have been identified in which these products could be used and will be analyzed in more detail in this document: (1) Hypolipidemic treatment in subjects with statin intolerance. (2) Hypolipidemic treatment «a la carte» in individuals in primary prevention. (3) Long-term cardiovascular prevention in individuals with no indication for lipid-lowering therapy. (4) Patients with optimized lipid-lowering treatment who do not achieve therapeutic objectives.
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Citation Excerpt :
Furthermore, policosanol can increase HDL-C and reduce TC levels in hyperlipidemic zebrafish, improve the symptoms of fatty liver, promote the proliferation and tissue regeneration ability of microglial BV-2 cells, and inhibit the function of cholesterol ester transfer protein (CETP) (Lee et al., 2016). Recently, researchers discovered that Armolipid Plus, a nutrient mixture containing policosanol, can lower blood pressure, decrease the concentrations of TC and LDL-C, promote glucose metabolism, and reduce Apo-B/Apo A-I function without obvious side effects (Marazzi et al., 2015; Mazza et al., 2015). It has been well documented that policosanol has a better adjuvant treatment effect on hyperlipidemia.
Octacosanol is a widely distributed natural higher aliphatic alcohol that can be isolated and purified from rice bran, sugarcane, beeswax, insect wax, etc. Octacosanol exerts various biological effects, including anti-fatigue, anti-hypoxia, antioxidant, anti-inflammatory, antitumor, etc. Meanwhile, it has the effects of regulating the body's immune function and energy metabolism and has potential benefits for cardiovascular disease, cerebrovascular disorders, diabetes, Parkinson's disease, and others. Octacosanol is primarily responsible for regulating multiple signaling pathways, such as AMPK, PI3K/Akt, and MAPK/NF-κB, to achieve different physiological functions. This review systemically summarized the progress in characterization, extraction and purification, biological functions, molecular mechanisms, and bioavailability of octacosanol. This study will provide a reference for many investigators to further explore the physiological functions of higher aliphatic alcohols and apply them as supplements in functional foods.
Red Yeast Rice for Hypercholesterolemia: JACC Focus Seminar
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The extracts of red yeast rice (RYR) are currently the most effective cholesterol-lowering nutraceuticals. This activity is mainly due to monacolin K, a weak reversible inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, whose daily consumption causes a reduction in low-density lipoprotein (LDL)-cholesterol plasma levels up to 15% to 25% within 6 to 8 weeks. The decrease in LDL-cholesterol is accompanied by a proportional decrease in total and non–high-density lipoprotein cholesterol, plasma apolipoprotein B, and high-sensitivity C-reactive protein. Some trials suggest that RYR use is associated with improvement in endothelial function and arterial stiffness, whereas a long-term study supports its role in the prevention of cardiovascular events. Despite the statin-like mechanism of action, the risk related to 3 to 10 mg monacolin K taken per day is minimal (mild myalgia in previously severely statin-intolerant subjects). RYR could represent a therapeutic tool to support lifestyle improvement in managing mild to moderate hypercholesterolemia in low-risk patients, including those who cannot be treated with statins or other LDL-cholesterol–lowering therapies.

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Coronary Artery DiseaseUsefulness of Nutraceuticals (Armolipid Plus) Versus Ezetimibe and Combination in Statin-Intolerant Patients With Dyslipidemia With Coronary Heart Disease

Section snippets

Methods

Results

Discussion

Disclosures

Atheroscler Suppl

Am J Cardiol

J Clin Lipidol

Nutr Res

J Clin Lipidol

Arch Med Res

Atherosclerosis

Nutr Metab Cardiovasc Dis

Nutraceutical-definition and introduction

AAPS Pharm Sci

Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized trial

Ann Intern Med

HypoCol (red yeast rice) lowers plasma cholesterol- a randomized placebo controlled study

Scand Cardiovasc J

Cardiovascular and metabolic effects of Berberine

World J Cardiol

Coronary Artery Disease
Usefulness of Nutraceuticals (Armolipid Plus) Versus Ezetimibe and Combination in Statin-Intolerant Patients With Dyslipidemia With Coronary Heart Disease