Rakhad Alrawi1 and Rafal Al-Rawi2
1Grand Canyon University, Arizona, USA.
2Hawler Medical University, Kurdistan, Iraq.
DOI: https://doi.org/10.5897/PP2018/0002
Copyright © 2018 Author(s) retain the copyright of this article.
This article is published under the terms of the Creative Commons Attribution License 4.0.
Abstract
Cardiovascular diseases (coronary heart disease, heart failure, and cardiac arrhythmias) are considered as the major cause of morbidity and mortality world wide. Triglycerides and cholesterol are lipids that circulate in the blood, cab be stored as fat cells and/or build up a plaque inside the coronary arteries causing cardiovascular diseases. Omega-3 and omega- 6 are bioactive lipids. Omega-3 fatty acids are nutrients, which can be used in the prevention and/or treatment of many diseases.
Polyunsaturated fatty acids (PUFAs);
Generally, fatty acids can be divided into three types according to their degree of saturation (number of double bonds between carbon atoms): Saturated fatty acids: They are found most commonly in animal products and in palm oil. They are key contributors to cardiovascular diseases, a major health threat worldwide (Mozaffarian et al., 2010); Monounsaturated fatty acids (MUFA): Vegetable oils such as olive oil and sesame oil, and sunflower oil are a good source of MUFA, like oleic acid (Mozaffarian et al., 2010); and polyunsaturated fatty acids (PUFAs): are fatty acids with more than one carbon-carbon double bond, including omega-3 and omega- 6. They are the bioactive lipids. Omega-3 consists of three major fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from marine sources, and alpha-linolenic acid (ALA) which is from plant sources (Harris et al., 2008). On other hand, omega-6 fatty acids include linoleic, gamma-linolenic, and arachidonic acids (Bradberry and Hilleman, 2013).
Pathological aspects:
It has been reported that cardiovascular diseases (coronary heart disease, heart failure, and cardiac arrhythmias) are considered as the major cause of morbidity and mortality in the world. The overall death rate for all cardiovascular diseases in USA is 236.1 per 100 000 persons. Pharmacologic drugs therapy has some limitations, as many patients are still left with significant morbidity despite those therapies. New treatment modality, such as the development of gene transfer vectors has given researchers the tool to target specific genes that play a role in cardiovascular diseases. The main problem facing disease prevention is lack of precise approach for early detection and prevention strategies of the disease. Results of research indicated that the polyunsaturated fatty acids (mainly omega-3) have an excellent way of preventing and curing many diseases including cardiovascular diseases as well as cancer considered as the highest number of diseases killing millions of people in the world (Mozaffarian et al., 2010; Rawi and AlRawi, 2017). It is well known that coronary heart disease is a disease in which a plaque (mainly cholesterol) builds up inside the coronary arteries. Plaque narrows the coronary arteries and reduces the flow of oxygen-rich blood to the heart muscle. A large blood clot can completely block blood flow through a coronary artery leading to heart attack. Sometimes partial block of coronary artery may cause angina (chest pain) especially with activity or stress. Without quick treatment, a heart attack can lead to death. Changing lifestyle, diets and medicines can help prevent coronary artery disease (NIH, 2017). It was reported that risk factors of CHD included high blood pressure, smoking, obesity, diabetes, lack of exercise, poor diet, high blood triglycerides, lipoprotein and cholesterol (serum LDL, low density lipoprotein, ), family history, hypertension and depression. It was estimated that 31 percent of the U.S population has high triglycerides, a major risk factor for cardiovascular disease (Alrawi and Alrawi, 2017). Furthermore, highdensity lipoprotein (HDL, hyperalphalipoproteinemia) has a protective effect over development of coronary artery disease. High levels of lipoprotein, a compound is formed when LDL cholesterol combines with a protein known as apolipoprotein. High-density lipoprotein (HDL) is positively associated with a decreased risk of coronary heart disease (CHD). Randomized, controlled clinical trials have demonstrated that interventions to raise HDL cholesterol levels are associated with reduced CHD events. Furthermore, researches showed that blood triglyceride levels predict cardiovascular disease, a principal cause of mortality in Western society.
Conventional and non- Conventional Drugs used for High Triglycerides:
The two most common conventional treatments for high triglycerides are statins and fibrates, with both having their own side effects. Statins is a drug used by people who have low HDL cholesterol and high LDL cholesterol. Statins are effective in treating high triglycerides but only in patients with hypertriglyceridemia. Fibrates are used to lower triglyceride levels. Studies show that in patients with cardiovascular disease, modestly elevated triglyceride levels and low HDL cholesterol levels, fibrates have been shown to decrease the risk of cardiovascular events. Moreover, research results showed that there are several ways to lower cholesterol and triglyceride levels naturally. Among these ways are: diet (long-chain omega-3 fatty acids are effective for reducing plasma triglyceride levels), cut back on calories; reduce alcohol, lifestyle, and exercise regularly. According to researchers, niacin (vitamin B3) can significantly reduce LDL cholesterol, triglyceride and lipoprotein levels, while increasing HDL cholesterol levels, lipoic acid, garlic, essential oils, lavender, holy basil. Nevertheless, omega-3 fatty acids are nutrients used in the management of many diseases; they are considered as nutraceuticals. Nutraceutical refers to a nutrient that has characteristics of a drug (Boothe, 1997).
Nevertheless, triglycerides and cholesterol are different types of lipids that circulate in the blood. Any calories not needed by the body are converted into triglycerides and stored as fat cells. This becomes a problem when the body has more calories than is being used for energy, which leads to high triglycerides (hypertriglyceridemia). Cholesterol is used to build cells and produce certain hormones. High-density lipoprotein (HDL) helps remove fat from the body by binding with it in the bloodstream and carrying it back to the liver for disposal. Low-density lipoprotein (LDL) carries mostly fats and only a small amount of protein from the liver to other parts of the body. Elevated LDL cholesterol is well-established as a major predictor of coronary heart disease. Most researchers now consider triglycerides a third important risk factor for plaque buildup in the arteries. Plasma lipoprotein–lipid levels modulate the risk for atherosclerosis and cardiovascular disease (CVD). In studies where LDL cholesterol levels were significantly reduced with the use of statin medications, many patients still had elevated triglyceride levels, putting them at continued risk of developing cardiovascular disease. This proves that in addition to the critical role that LDL cholesterol plays in the buildup of plaque inside the arteries, which is called atherosclerosis, high triglycerides also play a significant role. LDL cholesterol and HDL cholesterol are key factors in pathogenesis of atherosclerosis and coronary heart disease. Increased LDL cholesterol levels and decreased HDL cholesterol levels are associated with increased risk for coronary heart disease.Increased levels of triglycerides are not a risk factor on their own. However, there is evidence that the triglyceride is a synergistic coronary artery disease risk factor. High triglyceride levels along with high LDL levels and low HDL levels suggest some underlying pathologic process, which indicates a high risk for coronary artery disease. It has been reported that using of supplement likes fish oil, garlic, niacin and lipoic acid in combination with diet and lifestyle reduces high triglycerides. Essential oils, such as lavender, holy basil and lemongrass, can also be used to help treat hypertriglyceridemia. Furthermore, it was reported that omega-3-rich triglycerides (found in fish oil) are increasingly recognized as having modulating roles in many physiological and pathological conditions. The catabolism of lipid emulsions would be improved after enrichment with fish oil (Josh, 2017).
Furthermore, biologists and clinicians have studied lipoprotein lipase (LPL) for a long time. LPL is an enzyme that hydrolyzes triglyceride (TG) into free fatty acids and glycerol. High LPL activity is associated with lower TG and higher high-density lipoprotein cholesterol (HDL-C) levels, so basically it is the main enzyme that removes triglyceride from the bloodstream. It also determines blood plasma levels of high-density lipoprotein. A high omega-6/omega-3 ratio promotes the pathogenesis of many chronic diseases, including cardiovascular disease. Increased dietary intake of linoleic acid (LA) leads to oxidation of LDL, platelet aggregation, and interferes with the incorporation of essential fatty acids (EFA) in cell membrane phospholipids.
LPL is found in heart, muscle, and adipose tissue. It functions as a triglyceride hydrolysis. It was also reported that lipoprotein lipase hydrolyzes chylomicron and very low density lipoprotein triglycerides to provide fatty acids to tissues. Recent studies also indicate that LPL stimulates selective uptake of lipids from high density lipoprotein (HDL) and very low density lipoprotein. Results of research indicated that plasma lipid–lipoprotein levels are under genetic control (Alrawi and Alrawi, 2017). Many studies have shown that plasma lipoprotein concentrations are significant predictors of CHD risk. Genes with key roles in lipoprotein metabolism are excellent candidates for interindividual variation in susceptibility to CHD. Among these candidate genes is LPL, which hydrolyzes triglyceride-rich lipoproteins generating free fatty acids and glycerol for energy utilization and storage. Several common variants, or polymorphisms, have been identified in the LPLgene. The majority of these are synonymous polymorphisms that do not affect the protein sequence of LPL (Josh, 2017).
Health benefits of omega-3 fatty acids:
Omega-3 exhibits strong antimicrobial activity against various pathogens (Huang et al., 2011), and is also an important part of cell membranes where they modulate membrane protein function, cellular signaling, and gene expression (Jenabian et al., 2012). Common dietary sources of omega-3 fatty acid are cod liver oil, fish oil, and marine animals with a high amount of fat, such as, tuna, sardines, herring mackerel, salmon, and menhaden (Harris et al., 2008). Oily fishes contain higher amount of omega-3 fatty acids. Flaxseed oil and nuts, especially walnuts, are also rich in omega-3 fatty acids (Feldman, 2002; Moghadasian, 2008). Omega-3 is extremely important for brain development in babies. PUFAs are important structural elements of cell membranes and essential in the formation of new tissue, including neurons and glia cells. They are also involved in axonal myelination, they are key components in synaptic functions and serve as second messengers (Hornstra, 2000). The intake of long-chain Omega-3 causes a positive influence on brain functioning, reduces depression development, delays the beginning of Alzheimer’s disease and prevents psychotic disorders (Van Gelder et al., 2007; Amminger et al., 2010). Strong evidences for reduced risks of coronary heart disease, hypertension and atherosclerosis have been found from increased amounts of omega-3 in the diet, by lowering blood viscosity, reducing plasma fibrinogen, reducing fasting serum triglyceride levels, and decreasing blood pressure. It also has been shown that omega-3 supplementation can reduce total cholesterol in the body (Simopoulos, 2008). It was found that EPA and DHA can reduce the risk of cardiovascular disease by reducing the total serum cholesterol and serum triglycerides (Wang et al., 2006). Other studies have shown that the inclusion of EPA and DHA at 3g/day reduces the risk of cardiovascular diseases by decreasing plasma triacylglycerols, blood pressure and platelet aggregation (Breslow, 2006; Dasgupta and Bhattacharyya, 2007). Intake of EPA and DHA was also found to lower the risk of ischemic heart disease (Lemaitre et al., 2003) and cardiac arrest in humans (Bhatnagar and Durrington, 2003). Moreover, National Institute of Health (NIH, 2017) documented a strong scientific evidence that fish oil supplementation can help lower high blood pressure, reduce blood triglyceride levels, and help to prevent secondary cardiovascular disease risks. Results of research indicated that omega-3 treatment has many other benefits among them are: gastrointestinal tracts health, especially a significant reduction in number of ulcers, duration of ulcers, and level of pain in patients with recurrent aphthous stomatitis (Khouli and Gendy, 2014), reducing obesity (Gunnarsdottir et al., 2008), growth inhibition of cancer (Nikolakopoulou et al., 2013), fighting inflammation in rheumatoid arthritis (Simopoulos, 2008), wound healing (Diegelman and Evans, 2004), preventative of diabetes (Peter et al., 2004), increase visual acuity (Eileen et al., 2005; Joseph and Faraone, 2005), promoting bone health (Wan, 2010), and preventing periodontal disease (Serhan, 2008).
Dietary Recommendations to avoid CHD:
The American Heart Association suggests two servings of fatty fish per week, along with plant-derived omega-3 fatty acids, from soybean products, walnuts, flaxseed oil, and canola oil (Gebauer et al., 2006). The American Heart Association has suggested that 0.5 to 1.8 gm/day of EPA/DHA is regarded as safe in healthy people. The World Health Organization (WHO/FAO, 2003) recommended eating 1-2 servings of fish with each serving supplying 200-500 mg of DHA and EPA per week. The level of supplementation differs based on the benefits desired; a higher intake is necessary for some health improvements such as those already suffering from coronary heart disease or inflammatory diseases, but these recommended values are contested (Hibbeln et al., 2006). Omega-3 to Omega-6 ratio has become a model for gauging the proper balance of these fats in oils and the diet. Diets with greater than a 1:10 ratio of omega-3 to omega-6 are not recommended, whereas a 1:1 ratio is considered perfect. Very unhealthy ratios of 1:25 and 1:50 are common, especially with the consumption of fast food, high amounts of fried food, and low intake of fresh whole foods. Results of research indicated that Omega-3-rich (n-3) triglycerides (TG) are increasingly recognized as having modulating roles in many physiological and pathological conditions. Biochemists, molecular biologists and clinicians have many standards for CHD biochemical risk factors as well as molecular markers to predict CHD. Most previous investigations have successfully predicted CHD. Several studies support the benefits of lowering cholesterol and triglyceride levels to decrease the risk for developing cardiovascular disease. LDL cholesterol and HDL cholesterol are key factors in the pathogenesis of atherosclerosis and coronary artery disease. Increased LDL cholesterol levels and decreased HDL cholesterol levels are associated with increased risk for coronary heart disease. Increased levels of triglycerides are not a risk factor on their own. However, there is evidence that the triglyceride is a synergistic coronary artery disease risk factor. High triglyceride levels along with high LDL levels and low HDL levels suggest some underlying pathologic process, which indicates a high risk for coronary artery disease (Josh, 2017; Shukla et al., 2011; Artemis and Simopoulos, 2002; Kwak et al., 2012; Schreiner et al., 1993).
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