Cardiovascular prevention and omega-3

The synergy of specific components, including omega 3 and monacolin K, reduces blood cholesterol and triglyceride levels and improves endothelial function for effective cardiovascular prevention.

Primary cardiovascular prevention today represents one of the best strategies to prevent cardiovascular diseases such as myocardial infarction. One of the most effective preventive approaches is the constant administration of specific supplements to reduce LDL cholesterol levels in the blood. These are typically based on substances that help, among other things, to maintain healthy blood vessels and heart. Cardiol Forte, the supplement that combines omega-3, monacolin K, coenzyme Q10, hydroxytyrosol, folic acid, vitamins B12 and E, and piperine, thanks to its components with efficacy demonstrated by clinical study, offers the possibility to significantly reduce LDL cholesterol levels when combined with an active lifestyle and a controlled diet.

Index

1. Cardiovascular diseases

1.1 Atherosclerosis

1.2 Oxidative stress, lipids and plaque formation

2. The ingredients of Cardiol Forte

2.1 Omega-3

2.2 Red yeast rice

2.3 Coenzyme Q10

2.4 Hydroxytyrosol

2.5 Other components

3. Clinical study on Cardiol Forte

3.1 Results of the clinical study

4. Sources

Cardiovascular diseases

Cardiovascular diseases are the leading cause of morbidity, comorbidity, and mortality worldwide. The origin of most cardiovascular diseases is atherosclerosis, which is directly related to altered lipid status parameters (total cholesterol, LDL or "bad" cholesterol, and triglycerides). Current guidelines for cardiovascular prevention and treatment of these diseases are based on the systematic coronary risk evaluation system (SCORE), which can assess the 10-year risk of fatal cardiovascular diseases and whose value is estimated based on age, sex, systolic blood pressure, smoking habits, and total cholesterol concentration. The latter mainly depends on cholesterol synthesis and absorption capacity. The balance between these processes is responsible for maintaining cholesterol homeostasis. Besides total cholesterol, a high LDL cholesterol value is also a well-known risk factor for cardiovascular diseases. Therefore, both factors, along with oxidative stress and inflammation—conditions often associated with obesity—predispose to the onset of a very important risk factor for cardiovascular diseases: atherosclerosis.

Atherosclerosis

Atherosclerosis is a chronic disease of complex etiology that involves early local arterial injury, followed by lipid deposition, fibrous tissue proliferation, local arterial thickening, and finally plaque formation. When an atheromatous plaque forms, a narrowing (stenosis) occurs in the artery, causing insufficient arterial blood supply. Additionally, atheromatous plaques are highly unstable and may rupture, leading to thrombus formation that occludes the artery and causes cardiovascular diseases such as myocardial infarction. The pathogenesis of atherosclerosis is not fully understood but is associated with lipid metabolism disorders, endothelial cell damage, inflammation, and immune dysfunction involving macrophages, endothelial cells, vascular smooth muscle cells, and platelets. Among the triggering factors, two are particularly important: oxidative stress and high blood lipid levels.

Oxidative stress, lipids and plaque formation

Oxidative stress is the main cause of atheromatous plaque formation, along with high LDL cholesterol levels. The production of reactive oxygen species (ROS) in response to inflammatory stimuli causes LDL cholesterol oxidation, a phenomenon known as lipid peroxidation. When oxidized, LDL cholesterol tends to form plaques that deposit in the arteries, causing damage to endothelial cells and inducing the expression of pro-inflammatory factors in these cells. The mechanism by which oxidized LDL cholesterol forms plaques involves macrophages. This type of cholesterol has a strong affinity for a particular type of receptor (scavenger) present on mononuclear macrophages. Binding of oxidized LDL cholesterol to these receptors causes activation, proliferation, aggregation, and degeneration of macrophages. At the end of this process, macrophages undergo cell death and become foam cells, which aggregate to form lipid plaques.

The ingredients of Cardiol Forte

For effective cardiovascular prevention that counters oxidative stress and blood lipid levels, specific nutraceutical supplements can be used to treat these conditions. Cardiol Forte is a dietary supplement based on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), monacolin K (10 mg) from red yeast rice (RYR), whose components have demonstrated lipid-lowering and/or endothelial protective action, hydroxytyrosol (a polyphenol extracted from the olive fruit), coenzyme Q10, folic acid (vitamin B9), vitamin B12 and vitamin E, and piperine.

Omega 3

The omega-3 fatty acids are long-chain polyunsaturated fatty acids (PUFAs) including alpha-linolenic acid (ALA; 18:3), eicosapentaenoic acid (EPA; 20:5), and docosahexaenoic acid (DHA; 22:6). EPA and DHA mainly derive from the consumption of fish or fish oil. ALA is mainly obtained from flax seeds, chia seeds, and walnuts. EPA and DHA can be synthesized in the human body using ALA as a precursor. However, this conversion accounts for only 6% of EPA and less than 4% of DHA. Interest in omega-3 fatty acids arose from epidemiological observations of populations on the west coast of Greenland, where a reduced incidence of dyslipidemias and myocardial infarction mortality was observed compared to other European populations. This phenomenon is explained by the fact that such populations consume large amounts of fish, and consequently omega 3 and EPA in particular, from which a molecule called TXA3 is formed. TXA3 is a non-aggregating substance, meaning it reduces platelet aggregation efficiency, leading to a lower tendency for thrombus formation and, consequently, a lower incidence of atherosclerosis. Therefore, omega 3 administration can reduce the progression of atherosclerotic lesions and improve the hemodynamic and physical properties of large arteries. Furthermore, omega-3s contribute to cardiovascular prevention through the following effects:

• anti-inflammatory and antiarrhythmic effect;
• reduction of plasma triglycerides;
• vasodilation and reduction of blood pressure;
• improvement of arterial and endothelial function.

Red yeast rice

The nutraceutical red yeast rice is obtained from the fermentation of rice (Oryza sativa) by yeasts (M. pilosus, M.floridanus, M. ruber and Pleurotus ostreatus). In Cardiol Forte, the yeast used is Monascus purpureus. The typical red color is due to pigments produced by secondary fermentation. The fermentation of yeast and rice produces a complex of substances called monacolins, which have recognized cholesterol-lowering properties supporting cardiovascular prevention. The most commonly used monacolin concentration is usually around 1.9%, and there are different types of monacolins depending on the yeast strain used and fermentation conditions. One of these subtypes is monacolin K, an analogue of lovastatin that has the same cholesterol-lowering effects as the drug but without the typical side effects of statins. Its main mechanism of action is to inhibit the enzyme controlling the rate of cholesterol synthesis. According to the latest European guidelines from cardiology and atherosclerosis societies for the management and treatment of dyslipidemia, the use of monacolin K can be considered in patients with elevated total cholesterol levels who do not qualify for statin treatment based on the overall cardiovascular risk assessment. Specifically, the guidelines recommend the use of 5-10 mg/day of monacolin K in these subjects.

Coenzyme Q10

Coenzyme Q10, also known as ubiquinone, is a compound naturally synthesized in the human body and used by cells for several cellular processes including:

• aerobic respiration and aerobic metabolism;
• cellular respiration;
• oxidative metabolism.

Besides participating in various cellular processes, coenzyme Q10 has antioxidant properties, protecting cells from the action of free radicals, substances capable of damaging different cellular structures including membranes, membrane lipids, and DNA. For this reason, blood levels of coenzyme Q10 are often used in studies as a measure of oxidative stress. The antioxidant properties confer to coenzyme Q10 an important role in cardiovascular prevention and in the treatment of certain heart diseases. For example, supplementation with CoQ10 in patients with moderate to severe heart failure is associated with symptom reduction and reduction of major adverse cardiovascular events. Moreover, it has been observed that three out of four patients with heart diseases have low levels of coenzyme Q10 and that plasma levels in patients with ischemic heart disease and dilated cardiomyopathy are much lower compared to controls.

Coenzyme Q10 and statins

Coenzyme Q10 is also very useful in preventing and improving muscle symptoms related to the use of statins or statin-like drugs. Statins or statin-like drugs are commonly used medications to lower cholesterol. Their side effects on muscles, such as cramps and myopathies, are well known. For this reason, several clinical studies have shown that coenzyme Q10 supplementation improved muscle symptoms associated with statins, implying that coenzyme Q10 supplementation can be a complementary approach to managing statin- or statin-like induced myopathy. Specifically, coenzyme Q10 improved (compared to placebo) muscle pain, muscle weakness, muscle cramps, and muscle fatigue, regardless of the doses administered (100-600 mg/day) or the duration of supplementation (from 30 days to 3 months).

Hydroxytyrosol

Hydroxytyrosol is an amphipathic phenol extracted from the olive fruit and, according to the EFSA opinion of 2011 and EU Regulation 432/2012, is the only "food" officially recognized to have a clear health effect if consumed regularly (for oils containing at least 5 mg of hydroxytyrosol per 20 g of oil). In this regard, the European Food Safety Authority (EFSA) published the following statement about its role in protecting LDL cholesterol from oxidation: "A daily intake of 20 g of olive oil, containing at least 5 mg of hydroxytyrosol, provides the expected beneficial effects." Hydroxytyrosol exhibits many bioactive properties, including antioxidant, anti-inflammatory, cardioprotective, cytoprotective, and endothelial and vascular regulatory effects. Regarding cardiovascular disease prevention, besides its antioxidant capacity, hydroxytyrosol has been shown to inhibit platelet aggregation, chronic cardiac toxicity, the expression of aging-related proteins, as well as attenuate metabolic alterations of glucose, triglycerides, and total cholesterol. In particular, its beneficial effects are linked to its antioxidant capacity, which results in:

• the ability to reduce LDL cholesterol oxidation, thus preventing atherosclerotic plaque formation;
• a beneficial effect on high-density lipoproteins (HDL), which play a central role in reverse cholesterol transport by removing excess cholesterol from peripheral cells (cholesterol efflux capacity). It has been observed that hydroxytyrosol supplementation provides local antioxidant protection to HDL, improving their functionality;
• a potential mitochondria-targeted antioxidant effect in inflamed endothelium. Treatment of endothelial cells with hydroxytyrosol suppresses inflammatory angiogenesis, reduces oxidant production, and increases the activity of antioxidant enzymes such as superoxide dismutase.

Other components

Other components of Cardiol Forte include piperine and vitamins B9 (folic acid), B12, and E.

Piperine

Piperine (PIP) is an alkaloid found in various species of pepper, mainly Linn. and P. longum, in concentrations ranging from 5 to 8%. In Cardiol Forte, piperine is derived from Piper nigrum. It presents several properties including:

• ability to protect blood vessels in cases of hypertension;
• protection of cells from oxidative stress;
• ability to inhibit some molecules responsible for triggering inflammatory processes.

Several studies have also shown that piperine can protect cardiomyocytes from damage caused by ischemia/reperfusion, reducing cellular damage and the programmed cell death process (apoptosis). Furthermore, piperine, thanks to its ability to increase salivary and gastric secretion, stimulates digestion, improving intestinal absorption of many nutrients such as coenzyme Q10.

Vitamins B9 and B12

Vitamin B9 (folic acid) and vitamin B12 (cobalamin) belong to the B complex vitamins, which are involved in numerous cellular processes and functions including correct red blood cell synthesis and antioxidant functions. Vitamin B12 in particular has antioxidant properties including direct neutralization of reactive oxygen species (ROS), indirect stimulation of ROS elimination through glutathione preservation, modulation of cytokine and growth factor production to offer protection from oxidative stress induced by immune response, and reduction of oxidative stress induced by homocysteine. Homocysteine is a substance that, if present in high amounts (a condition known as hyperhomocysteinemia), causes several problems and is a risk factor for cardiovascular issues. Vitamins B9 and B12 participate in numerous processes involved in homocysteine metabolism, such as preventing its accumulation in the body. Such accumulation is harmful because it may increase the likelihood of cortical inflammation, oxidative stress, and consequent damage to mitochondria and DNA strands. This means that a reduction in vitamin B9 and B12 levels could lead to an increase in plasma homocysteine.

Vitamin E

Vitamin E (alpha-tocopherol) is an important fat-soluble antioxidant that eliminates some antioxidant substances (peroxyl radicals) and thus interrupts the oxidation process of polyunsaturated fatty acids and other cellular structures. In the presence of vitamin E, peroxyl radicals react and combine with it rather than cellular structures. In this way, the chain reaction of peroxyl radical production is interrupted and further oxidation of membrane lipids is prevented. The antioxidant activity of vitamin E may be responsible for regulating several enzymes involved in signal propagation. Vitamin E can directly bind to enzymes involved in generating lipid mediators or to transport proteins involved in signal transduction and it has also been shown that vitamin E supplementation improves cell-mediated and humoral immune responses with increased lymphocyte proliferation, immunoglobulin levels, antibody responses, natural killer cell activity, and interleukin production. Additionally, vitamin E has anti-inflammatory effects. This has been demonstrated by the results of a randomized controlled clinical trial in which vitamin E supplementation significantly reduced biomarkers of vascular and systemic inflammation.

Clinical study on Cardiol Forte

The synergy of Cardiol Forte components was investigated in a single-center, double-blind, placebo-controlled study published in April 2020 and conducted at 4 Italian institutions:

• Cardiovascular prevention unit, Anesthesia and Intensive Care Unit, and Cardiology and Intensive Cardiology Therapy Unit at the Hospital Department of ASL Frosinone;
• Department of Medical and Surgical Sciences at Alma Mater Studiorum University of Bologna;
• Pulmonology Unit at the Department of Internal Medicine of the University of L’Aquila;
• Policlinico Umberto I of the "La Sapienza" University of Rome.

Of the 80 patients enrolled, 75 completed the study (37 in the Cardiol Forte group and 38 in the placebo control group). The study lasted a total of 18 weeks (8 weeks treatment + 2 weeks washout + 8 weeks treatment). The following parameters were evaluated:

• Total cholesterol, LDL cholesterol and HDL cholesterol
• Triglycerides
• Endothelial function (measured by flow-mediated dilation).

Results of the clinical study

After 8 weeks of treatment, LDL cholesterol levels were reduced by 17% in the Cardiol Forte group and by 6.4% in the control group, compared to baseline (visit 1). These changes persisted until the end of the washout period (visit 2), with a further reduction of 23.5% in the Cardiol Forte group and 14.1% in the control group. At the end of the study (visit 3), LDL cholesterol in the group that used Cardiol Forte was reduced by 34.3%, while in the control group it was reduced by 22.6%. Total cholesterol and triglyceride levels were significantly reduced during the study in the group that used Cardiol Forte, while in the control group total cholesterol was reduced by 8.5 ± 5.18% and no change was observed in triglyceride levels. HDL-C cholesterol did not change in either group. In the group that used Cardiol Forte, flow-mediated dilation (FMD) improved significantly compared to placebo. Endothelial function and the vasodilatory capacity of the arterial circulation increased by 18.8 ± 3.2% after 8 weeks of treatment, with a further increase observed at visit 2 of 22.9 ± 4.4% and at visit 3 of 39.3 ± 5.2%. In the control group, FMD increased by 10.9 ± 4.2% at visit 1 and by 17.1 ± 5.2% at visit 3. This data is particularly interesting because a meta-analysis of 35 studies (17,280 patients total) indicated that each 1% increase in FMD is associated with a 12% reduction in expected cardiovascular events (relative risk = 0.88, 95% CI: 0.84–0.91, p < 0.001). In conclusion, a dietary supplement like Cardiol Forte, containing lipid-lowering and antioxidant components, in association with lifestyle changes and a controlled diet, can significantly reduce cholesterol levels and improve endothelial function, thereby reducing cardiovascular risk in patients with mild to moderate hypercholesterolemia.

Sources

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