The main objective of the article is to determine the role of antioxidant and marine n-3 fatty acids in improving the endothelial function in hypercholesterolemic people. The marine n-3 fatty acids associate to the vascular functions making its mechanism be linked to improving the endothelial functions. Most of the studies have shown that the supplementation the diet with marine fish helps in preventing some of the coronary diseases. It is hard to ignore the role of the antioxidants in complementing the action of marine omega-3 fatty acids. The fish oil rich diet normally contains some amount of antioxidant in the form of vitamin E. The antioxidant vitamin serves in complementing the action of the fish oil rich diet by reducing the oxidative stress consequently resulting to improved endothelial functions.
Role of Omega-3 Fatty Acids on Endothelial Functions
Role of fatty acid on endothelial functions
Antioxidants and Marine N-3 Fatty Acids Improves Endothelial Function in Hypercholesterolemic People
The hypercholesterolemic people refer to the individuals who suffer from the high concentration of cholesterol in their bodies. These hypercholesterolemic people normally needs the improvement of their endothelial functions in order accommodate the high levels of cholesterol in their bodies. The individuals normally witness a change in their aortic consequently altering their endothelial functions. Hypercholesterolemia is responsible for alteration of dilatation function of the endothelium in the small blood vessels. Further, the alteration of the aortic functioning also makes the patients be susceptible to higher blood pressure. Studies show that the patients normally witness abnormality in the endothelium-dependent dilator function in the human circulation (Goodfellow et al., 2002). The extent of impairment (endothelium-dependent dilator) depends on the level of hypercholesterolemia. From this, it is true that any factor, which will help in restoring the endothelium functions, will help in counteracting some of the effects resulting from hypercholesterolemia.
The marine n-3 fatty acids always associate to the vascular functions making its mechanism is linked to improving the endothelial functions. Most of the studies have shown that the supplementation the diet with marine fish helps in preventing some of the coronary diseases. The mechanism for the action of n-3 fatty acids associates with its action in improving the profile of the serum lipid and decreasing the blood pressure. Further, the n-3 fatty acids also act in preventing the aggregation of platelet while also generating vasodilator prostaglandins. The production of vasodilator prostaglandins makes the omega-3 fatty acids to be essential in improving the vascular functions. The antioxidant vitamin serves in complementing the action of the fish oil rich diet by reducing the oxidative stress consequently resulting to improved endothelial functions. The antioxidants also prove important in improving the endothelial function in its action of acting against the oxidative stress. However, the antioxidants can only work in the presence of the omega-3 fatty acids because of the recognized effects of hypercholesterolemia on the endothelial functions (vascular relaxation).
Many studies carried out on the influence of fish on the health of individuals have established that people who ate at least two fish meals diet in a week had less association to coronary heart disease. This helps in explaining the effect of fish oil diet on improving the endothelial functions. People who associate with coronary diseases, such as high blood pressure normally exhibit endothelial dysfunctions. Considering that one of the major causes of coronary diseases is high amount of cholesterol (hypercholesterolemia) it is true that the inclusion of fish oil diet is significant in improving the health of the hypercholesterolmic people. Evidences that are more recent associated to the death of individuals, resulting from coronary heart diseases shows that there were less deaths associated to the individuals eating at least 35 g of fish. Men who consumed 35 g or more of fish daily compared with those who consumed none had a relative risk of death from CHD of 0.62 and a relative risk of no sudden death from MI of 0.33 (Khan et al., 2002).
Study carried on the influence of omega 3 fatty acid on hypercholesterolmic individuals shows that there is a similarity in all the groups concerning the changes witnessed in blood flow associated with the brachial artery. The test was carried immediately after the wrist cuff release (peak flow, 1 min after cuff release and 3 min after sublingual GTN) (Loscalzo, 2003). The treatment with omega-3 fatty acids showed a higher influence in increasing significantly the flow-mediated dilation as compared to treatment with placebo. However, the table shows that omega-3 fatty acids treatment resulted to reduction for triglyceride. Further, the fatty acids did not present any influence on the serum concentration of the total cholesterol (VLDL, LDL or HDL cholesterol). The treatment with placebo did not exhibit any significant influence on the level of lipid. Consequently, the figures also shows that the reduction for triglycerides do not have correlation to the improvement in the endothelium-dependent FMD. Further, there was similarity in the dilation caused by the glyceryl trinitrate in both groups.
Influence of the omega-3 fatty acids
Dietary supplementation with n-3 fatty acids causes an improvement in the endothelium-dependent FMD associated to the brachial artery. The brachial arteries have similar characteristics to the coronary artery, with studies showing that brachial responses have a close correlation to the response related to the coronary circulation. Further, the treatment with the marine omega-3 fatty acids results to a significant reduction for triglycerides, as always reported in the existing studies. Existing studies shows that there is no significant relation between the improvement in endothelial functions and level triglyceride. The hypercholesterolemia subjects used in the study exhibited higher total LDL cholesterol with a slightly elevated triglyceride levels (Fahs et al., 2012). This situation means that the improvement in the endothelial functions cannot have correlation to the reduction in the triglycerides. The disease, hypertriglyceridemia normally have lesser relation to atherosclerosis than elevated LDL cholesterol. Consequently, the use of multivariate analysis in the LDL and HDL cholesterol contributes to disappearance of their association to the hypertriglyceridemia.
The antioxidants in the presence of the omega-3 fatty acids reduce the oxygen-derived free radical created in neutrophils and monocytes. The two, antioxidants and the omega-3 fatty acids, undergo a mechanism involving reduction in the oxygen radical formation and the increase in the subsequent increase in the availability of nitric oxide, in the endothelial cells. Many studies carried out on the influence of fish on the health of individuals have established that people who ate at least two fish meals diet in a week had less association to coronary heart disease. This helps in explaining the effect of fish oil diet on improving the endothelial functions. People who associate with coronary diseases, such as high blood pressure normally exhibit endothelial dysfunctions. Considering that one of the major causes of coronary diseases is high amount of cholesterol (hypercholesterolemia), it is true that the inclusion of fish oil diet is significant in improving the health of the hypercholesterolmic people (Khan et al., 2002).
The double blind method used for the study, with the placebo group acting as the control, showed that the n-3 fatty acids have a correlation to the endothelial functions. The study shows that the n-3 fatty acids, contained in fish oils improves the endothelial functions in the hypercholesterolemia patients especially those having large systemic arteries. Further, the study also presents an incidence of FMD loss in the brachial artery. The FMD loss always impairs the activity of the endothelium-derived nitric oxide (NO) in hypercholesterolemia patients (Hamazaki, 2001). The response of the normal dilator to GTN shows that there is preservation of the ability of the vascular smooth muscle dilator to respond to nitric oxide. The inclusion of 4 IU vitamins also help in illustrating the role played by the antioxidant in improving endothelial functions.
Mechanism for action of omega-3 fatty acids
Possible mechanism for the action of omega-3 fatty acids in improving endothelial function associates to the bilipid layer composition with multiple potential effects on endothelial functions. The fish oil rich diet, containing the omega-3 fatty acids, has both the EPA and DHA. The increase in the size of the membrane associated with the two substances (EPA and DHA) has direct relation to the improvement in the endothelial functions. This is true considering the effects of increasing the amount of the acids in the membrane of the red cells. According to the influence associated with the EPA and DHA, it is true that the supplementation by the n-3 fatty acids acts in altering the membrane fluidity of the endothelial cells (Goodfellow et al., 2002).
Action of the antioxidants
The improved fluidity helps in triggering an increased synthesis for nitric oxide. It is hard to ignore the role of the antioxidants in complementing the action of marine omega-3 fatty acids. The fish oil rich diet normally contains some amount of antioxidant in the form of vitamin E The antioxidant vitamin serves in complementing the action of the fish oil rich diet by reducing the oxidative stress consequently resulting to improved endothelial functions. The antioxidants in the presence of the omega-3 fatty acids reduce the oxygen derived free radical formation in neutrophils and monocytes (Khan et al., 2002). The reduction process results to enhancement of nitric oxide production in the endothelial cells. Consequently, the basic mechanism involves the process of reduction in the oxygen radical formation and the increase in the subsequent increase in the availability of nitric oxide, in the endothelial cells.
Serum triglyceride
The intake of omega-3 fatty acid arising from fish diet has a correlation to the level of serum triglyceride in the body. Research carried shows that 4 g/d of omega-3 fatty acids from fish oil decreased the concentration of serum triglyceride by 25% to 30% (Kris-Etherton et al., 2002). In the process of reducing the concentration of serum triglyceride, the omega-3 fatty acids also increase the level of LDL cholesterol and the HDL cholesterol. The higher levels of triglyceride in the hypercholesterolmic people normally lead to endothelial dysfunction. The EPA and DHA, contained in the omega-3 fatty acids, have properties responsible for lowering the levels of triglyceride in the body. The increase of the HDL cholesterol is significant for the improved endothelial functions in the individuals with hypercholesterolemia. Low levels of HDL cholesterol normally results to impaired functions of endothelium thereby prompting for the need of a process which can increase the levels. The intake of omega-3 fatty acids comes in handy, since its impact on the triglyceride helps in increasing the levels of the HDL cholesterol. Further, there is also a need to maintain higher levels of LDL cholesterol in the hypercholesterolmic people. This is because decreasing the levels of LDL cholesterol always decreases the cardiac morbidity and mortality hence its relation to the endothelial functions (Kris-Etherton et al., 2002).
Blood pressure
There is a relation between blood pressure and the endothelial functions, with a lowered blood pressure resulting to improved endothelial functions. There are higher chances that the hypercholesteromic patients can associate with high blood pressure thereby lowering the endothelial functions. The inclusion of omega-3 fatty acids in the diet, in turn, has an influence in lowering the blood pressures. The already existing studies indicate that hypertensive subjects who consumed 5.6 g/d of omega-3 fatty acids are likely to decrease their blood pressure -5.5/-3.3 mmHg (Kris-Etherton et al., 2002). This implies that there is a significant reduction of blood pressure for the individuals who included fish oil diet in their meals. Both DHA and EPA functions in lowering the blood pressure even though the former is always effective. However, this mechanism may fall short in exclusive management of high blood pressure because of the higher doses required for lowering the blood pressure.
Thrombosis and hemostasis
The primary functions of endothelium is to control the blood vessel wall permeability besides its function in providing a blood -- compatible lining surface (Kris-Etherton et al., 2002). This action is important in preventing thrombosis and hemostasis in individuals. Consequently, endothelial dysfunction, occurring in the hypercholesterolmic people, will exhibit thrombosis. The omega-3 fatty acids help in restoring these basic functions of endothelium since they help in preventing the thrombosis and hemostasis. The omega-3 fatty acids prevent thrombosis through reducing aggregation of the platelets. The reduction in aggregation helps in prolonging the bleeding time. Further, the omega-3 fatty acids also help in enhancing the occurrence of fibrinolysis, which is important in prolonging the bleeding time. The EPA and DHA influence the actions of collagen in the hypercholesterolmic individuals thereby resulting to platelet aggregation, which then affect hemostasis. A study carried on coronary patients taking 5.1 g/d of omega-3 fatty acid for 6 months showed that they experience a reduction in thrombomodulin (Kris-Etherton et al., 2002).
Clinical implication
This study helps in confirming the importance of dietary supplementation to the health of an individual. Considering the role of endothelial dysfunction in the hypercholesterolemia people, it is true that fish oil diets are has associated clinical benefits. Its action in improving the endothelial functions cannot be disregarded among the clinical benefits. The clinical evidence shows that the use of fish oil diet in improving the endothelial functions has no proved adverse effects on the health of the individuals. Consequently, the success of this study gives support for a future clinical role of omega-3 fatty acids. The study also explains why the individuals consuming fish-oil diet normally have clinical benefits as compared to others.
Safety of omega-3 fatty acids
There is need for carrying a research on the safety of omega-3 fatty acids especially for consumption to give assurance of its importance on the hypercholesterolmic individuals. Considering that omega-3 fatty acids has been part of human diet for the last centuries is one o the evidences that it is safety. Estimates show that the ratio for consumption of omega-6 to that of omega-3 is 1:1 meaning that it is safe. Further, FDA ruled that inclusion of up to 3 g/d of omega-3 fatty acids is Generalized Recognized as Safe (GRAS). The ruling came after the realization that the omega-3 fatty acids had an influence in glycemic control especially on patients with bleeding tendencies. The FDA has also presented their approval for using omega-3 fatty acids as dietary supplements. The approval by the FDA is enough proof that EPA and DHA omega-3 fatty acids are a better recommendation for the hypercholesterolmic individuals (Kris-Etherton et al., 2002).
Apart from studying the safety, there is also need to consider the reasons why some individuals may end up avoiding the inclusion of omega-3 fatty acids in their diets. Among the common reason for avoiding consumption is fish aftertaste. Study shows that some patients are likely to avoid consumptions because of the related gastrointestinal disturbances and nausea, which causes intolerance to the fatty acids.
Risk of side effects from ingestion of omega-3 fatty acids
Gastrointestinal upset
Clinical bleeding
Fishy aftertaste
Worsening glycemia
Rise in LDC-c+
Up to 1 g/d
Very low
Very low
Low
Very low
Very low
1 to 3 g/d
Moderate
Very low
Moderate
Low
Moderate
>3 g/d
Moderate
Low
Likely
Moderate
likely
It is also important to consider the risks, which may arise from consumption of fish since it, may act in deteriorating the health of the subjects. Some fish species normally contains significant levels of poisonous chemicals such as mercury and dioxins. These chemicals normally enter into the system of the fish due to the pollution of water surfaces by the chemicals. The fish get these chemicals into their system through intake of the polluted water and food. This means, that through the fish, the chemicals have the ability to bioconcentrate in the man food chain consequently leading to high levels of the substances (Kris-Etherton et al., 2002). This implies that there is need for regulating the quality of fish consumed by a responsible authority to ensure that there is reduced concentration of the chemicals in the aquatic food chain. The FDA helps in regulating all the types of commercial fish taken for consumption ensuring that they are fit for consumption. Further, the Environmental Protection agency regulates the sport-caught fish. Due to these adverse effects arising, there is need for the hypercholesterolmic individuals to consume a wide variety of species within the guidelines (Kris-Etherton et al., 2002). Considering the guidelines given by FDA, is essential in reducing the level of mercury exposure while increasing the intake of omega-3 fatty acid intake.
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