Nutraceutical in Cardiovascular Primary Prevention
Condition: Hypercholesterolemia
MeSH terms: Hypercholesterolemia
Study type: Interventional
Phase: Phase 2

Summary: 
      Nutraceuticals have attracted interest as possible approach to be associated with lifestyle
      changes for lowering plasma cholesterol levels in patients with moderate
      hypercholesterolemia. Ruscica and colleagues showed that a 8-weeks treatment with a
      nutraceutical combination containing red yeast rice extract, berberine, policosanol,
      astaxanthin, coenzyme Q10, and folic acid was able to reduce significantly total cholesterol
      (-12.8%) and low-density lipoprotein-cholesterol (-21.1%) [11]. These nutraceutical compounds
      exert their lipid-lowering effect through different ways, like the inhibition of the
      hydroxymethylglutaryl coenzyme A (CoA) enzyme, increasing the hepatic expression of low
      density lipoprotein (LDL) receptor and the LDL degradation via enhanced hepatic binding and
      internalization. In addition, they up regulate the numbers and function of circulating
      endothelial progenitor cells increasing nitric oxide (NO) production. The purpose of the
      present study was to assess the effectiveness of CARDIOVIS COLESTEROLO 3 mg (containing red
      rice fermented with Monascus purpureus titrated with 3% monacolin K, hydrol mixture of olive
      fruit titrated with vitamin E, Coenzyme Q10 and polymethoxyflavones) in terms of cholesterol,
      endothelial and inflammatory parameters reduction.
    

Detailed description: 
      Epidemiology. Cardiovascular disease (CVD) is the most common cause of death globally: an
      estimated 17.5 million people died from CVD in 2012, representing 31% of all global deaths.
      Of these deaths, an estimated 7.4 million were due to coronary heart disease and 6.7 million
      were due to stroke. Consistent evidences suggest that a large proportion of CVD incidence
      could be prevented by lifestyle modifications.

      Atherosclerosis, hypercholesterolemia, inflammation and endothelial dysfunction
      Atherosclerosis covers a central rule in cardiovascular diseases. This process can be
      promoting by several risk factors, all related with endothelial dysfunction, as
      hypercholesterolemia, diabetes, cigarette smoking and arterial hypertension that acting as
      negative stimuli lead to a prothrombotic pathway by proinflammatory-induced cytokines and
      chemokine's production. Furthermore endothelial cells exposed to hypercholesterolemia are
      inhibited by the downregulation of extracellular nitric oxide synthase (eNOS) in the release
      of endothelium-derived relaxing factor, thus the benefits of lowering cholesterol are not
      only related to its primary implication in the atherosclerosis process, but also by the
      improvement of the endothelial function.

      Cardiovascular risk (systematic coronary risk evaluation, SCORE). Current guidelines
      recommend the cardiovascular risk estimation, using a risk estimation system such as SCORE,
      for adults >40 years of age, unless they are automatically categorized as being at high-risk
      or very high-risk based on documented cardiovascular disease, diabetes mellitus, or kidney
      disease. A patient is defined at low to moderate risk when the cardiovascular risk is below
      5%. Interventional strategies for hypercholesterolemia. The current guidelines
      recommendations for the management of hypercholesterolemia according cardiovascular risk are
      reported below in the Table. In addition to lifestyle advice, drugs may be considered in
      patients at low risk if LDL values are ≥ 190 mg/dl and in patients at moderate risk if LDL
      values are ≥ 100 mg/dl.

      Nutraceuticals Several studies have assessed the effect of dietary interventions on risk
      factors for CVDs, but there is often lack effectiveness in the long term, mainly due to poor
      compliance. Research has thus turned its attention to nutraceuticals, nutrients that have the
      ability to modulate physiological and pathophysiological molecular mechanisms, resulting in
      favorable health outcomes. Nutraceuticals enhance cardiovascular health through several
      metabolic pathways as via promoting vasodilatory, anti-atherogenic, antioxidant,
      antithrombotic and anti-inflammatory effects]. Of note the extracts of red yeast rice
      explicate a lowering lipid action through monacolins, a family of naturally occurring
      statins, especially monacolin K, that is an inhibitor of the hydroxymethylglutaryl-CoA
      enzyme. Several trials of its possible lipid-lowering effects have been conducted and a
      meta-analysis [10] assesses the effectiveness and safety of preparations on lipid
      modification. Nutraceuticals have attracted interest as possible approach to be associated
      with lifestyle changes for lowering plasma cholesterol levels in patients with moderate
      hypercholesterolemia. Ruscica and colleagues showed that a 8-weeks treatment with a
      nutraceutical combination containing red yeast rice extract, berberine, policosanol,
      astaxanthin, coenzyme Q10, and folic acid was able to reduce significantly total cholesterol
      (-12.8%) and low-density lipoprotein-cholesterol (-21.1%). These nutraceutical compounds
      exert their lipid-lowering effect through different ways, like the inhibition of the
      hydroxymethylglutaryl-CoA enzyme, increasing the hepatic expression of LDL receptor and the
      LDL degradation via enhanced hepatic binding and internalization. In addition, they up
      regulate the numbers and function of circulating endothelial progenitor cells increasing NO
      production. The purpose of the present study was to assess the effectiveness of CARDIOVIS
      COLESTEROLO 3 mg (containing red rice fermented with Monascus purpureus titrated with 3%
      monacolin K, hydrol mixture of olive fruit titrated with vitamin E, Coenzyme Q10 and
      polymethoxyflavones) in terms of cholesterol, endothelial and inflammatory parameters
      reduction.

      This is a prospective, single-center, and phase IIb study evaluating the effectiveness of
      CARDIOVIS COLESTEROLO 3 MG in improving cholesterol, endothelial and inflammatory parameters.
      Subjects that meet the inclusion criteria and have provided informed consent will be assigned
      to receive a daily oral dose of CARDIOVIS COLESTEROLO 3 mg. Before the treatment with
      CARDIOVIS COLESTEROLO 3 mg all subjects undergo a 4-week period of lifestyle advice and
      changes. If, after the 4 weeks, LDL values are confirmed above the established cutoffs, the
      subjects receive CARDIOVIS COLESTEROLO 3 mg. Finally, a last blood samples to assess a
      potential rebound effect after nutraceutical suspension is collected 4 weeks after the
      treatment stop.
    

Intervention name(s): nutraceutical
Intervention type(s): Drug
Intervention description(s): 8-week administration of nutraceutical compound
Intervention model: Single Group Assignment
Intervention model description: Subjects that meet the inclusion/exclusion criteria and have provided informed consent will undergo a 4-week period of lifestyle advice and changes. If, after the 4 weeks, LDL values are confirmed above the established cutoffs, the subjects receive CARDIOVIS COLESTEROLO 3 mg for 8 weeks. After the 8-week treatment period, all biological paprameters will be reassessed. Finally, a last blood samples to assess a potential rebound effect after nutraceutical suspension is collected 4 weeks after the treatment stop.
Masking: None (Open Label)
Primary purpose: Treatment