Omega-3 in the Prevention of Cardiovascular Diseases

In the last years, Mexico has experimented changes in the epidemiological and nutritional transition. There is a decrease of communicable diseases and an increase of chronic diseases, becoming the main causes of death, mainly cardiovascular diseases. Experimental, epidemiological and interventional studies have demonstrated the beneficial cardiovascular effects of eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA), which have antiatherosclerotic, antithrombotic, antiarrhythmic and anti-inflammatory effects. The American Dietetic Association recommend an ingestion of 250 to 1000 mg/day of omega 3. This paper mentions the functional characteristics, biosynthesis and mechanisms of omega-3 fatty acids. This paper also reviews the clinical evidence that support their role as a cardioprotective factor. Derived from the analysis of the reviewed studies, it is concluded that taking into account the benefits of omega-3 fatty acids in the prevention and treatment of cardiovascular diseases, it is necessary to increase the consumption of foods rich in these fatty acids.

INTRODUCTION

Fatty acids belong to the group of fats, and their nature determines the chemical, biological and physiological characteristics of the different fatty acids¹. Some of these characteristics that distinguish one fatty acid from another are the number of carbon atoms found in their chain and the absence or presence of double bonds, in this way they can be saturated or unsaturated fatty acids (monounsaturated and polyunsaturated) respectively.² In this sense, the functions of the fatty acids are diverse. In addition to their energetic value, they are also part of the phospholipids found in the membranes of the body's cells and determine in a greater or lesser extent the structure and functionality of the cell. Such functionality refers to aspects like fluidity and permeability, lipid peroxidation, etc.³ Today, polyunsaturated fatty acids, especially omega-6 and omega-3, are considered the most relevant ones because they can generate bioactive components with several physiological actions.^4,5

Food contains omega-3 fatty acids in three main active forms: eicosapentaenoic acid (20: 5 omega 3, EPA), docosahexaenoic acid (22: 6 omega 3, DHA) and alpha-linolenic acid (18: 3 omega 3, a-ALA).⁶ EPA and DHA forms can be found in fish oils, fish that mainly live in cold waters such as salmon, tuna, sardines, among other varieties. EPA, DHA and ALA are essential fatty acids, they need to be ingested in the diet, since the body cannot synthesize them.⁷ Dietary habits are factors that predispose the population to present certain pathologies such as cardiovascular diseases (CVD). They are among the main causes of death in developed countries and their incidence has been increasing in developing countries.⁸

During the last 20 years, Mexico has been through an epidemiological transition, reducing infectious diseases as the main causes of death and giving way to chronic non-communicable diseases.⁹ These last ones caused the reduction of the healthy years of life, generating important costs to health systems and to those who suffer from them.9 Several studies have shown that increasing the consumption of omega-3 fatty acids in the diet helps preventing cardiovascular diseases.¹⁰ Therefore, the objective of this review is to present recent evidence on the effects of omega-3 fatty acids in the prevention of CVD.

BIOSYNTHESIS

Chemically, omega-3 fatty acids are long chains of carbon atoms (18-22) with 3 to 6 double bonds in the chain. They are considered omega-3 fatty acids because the first double bond is on the third carbon atom from the end of the molecule. They are also known as n-3 fatty acids where n refers to the place where the double bond is in the chain.¹¹

The metabolism of omega-3 long chain polyunsaturated fatty acids (PUFAs) is synthesized from precursor molecules and is separated into two families: the one that derives from linoleic acid and the one that derives from alpha-linolenic acid. Because the body is unable to synthesize these two PUFAs, they are indispensable in the diet.¹² In both cases they are metabolized by the desaturation and elongation sequence, with the help of partial beta-oxidation (lipid metabolism), in this way the 24-carbon PUFA can donate two carbons without losing double bonds and give rise to 22-carbon PUFAs, which are transformed after passing through multiple oxidation enzymatic processes.⁸ Thus, linoleic acid is metabolized to arachidonic acid (AA), and α-linolenic acid (ALA) is converted to eicosapentaenoic acid (EPA) and subsequently to docosahexaenoic acid (DHA).¹³ These metabolic conversions are performed by the elongases and desaturases enzymes in charge of elongation and desaturation. They are used for both families of PUFA so that there can be a competition for the enzymes¹⁴, as can be seen in Figure 1. This competition will depend on the diet, if you eat food rich in linoleic acid and low α-linolenic acid, the way by which desaturases and elongases lean will be the series of omega 6, or viceversa.¹⁵ In literature, the daily recommended intake of omega-3 fatty acids vary from 250 mg to 1 g of EPA and DHA. Recent evidence shows that the intake of EPA and DHA is inversely related to cardiovascular risk in a dose dependent manner up to about 250 mg/day in healthy populations, and the intake of 1 g/day is associated with a marked protection from a sudden cardiac death.¹⁶ The α-linolenic acid is considered an essential nutrient since it is not synthesized by the human organism and it is obtained from foods, where the main sources are fish like salmon that provides 1,238 mg, herring 1,712 mg, tuna 1,279 mg, mackerel 1,046 mg, sardine 835 mg, and rainbow 744 mg (the portion of reference is 85 g of fish).¹⁷

Figure 1: Biosynthesis of long chain polyunsaturated fatty acids.⁸

MECHANISMS OF ACTION

Omega-3 fatty acids are incorporated as structural components in the phospholipids of the cell membrane, which increases membrane fluidity. Besides, omega-3 fatty acids work as natural substrates which intervene in the synthesis of other molecular compounds such as cyclooxygenases, lipoxygenase, and they also act to synthesize prostaglandins, leukotrienes and resolvins. These molecules produce favorable changes in cell membranes in cardiovascular diseases. (For example: vasodilation and vasoconstriction, adhesion process, inflammatory responses and the formation of platelet aggregation).¹⁸

Eicosanoids, which are molecules resulting from the synthesis of omega-3 fatty acids, work as ligands for nuclear transcription receptors that control genes. These mechanisms influence several important factors in the development of coronary disease, this reduces serum triglyceride levels, blood pressure, platelet aggregation, heart rate and plaque vulnerability, as well as a better endothelial function.¹⁹ There are two ways of action: in the first one, cyclooxygenases that convert arachidonic acid (AA) into thromboxane and prostaglandins, act as a powerful mediator of inflammation, pain, fever and increased vascular permeability; in the second AA pathway, lipoxygenase is involved and produces different leukotrienes, which are powerful pro-inflammatory agents that increase vascular permeability, immune cell activity, and stimulate the release of inflammatory cytokines.⁸

CARDIOVASCULAR EFFECT

CVDs are the main cause of death worldwide: more people die annually from CDVs than from any other cause. An estimated 17.5 million people died of CVD in 2012, representing 31% of all global deaths and this figure is expected to grow up to 23.6 million by 2030. As the magnitude of CVD continues to accelerate globally, there is an urgent need to raise awareness and develop stricter strategies to reduce those diseases.²⁰ Early studies indicate a low incidence of atherosclerotic heart disease among Eskimos, attributed to a diet rich in fish oil from marine vertebrates. Subsequently, several controlled trials provided evidence that consumption of omega-3 PUFAs from fish oils was responsible for protective effects against CVD.^19-21 A recent study researched the CVD preventive effect of administering omega-3 fatty acids to patients with existing CVD (that is, in the secondary prevention of CV outcomes), through supplements (without dietary counselling) with doses sufﬁciently high, and for a long time to manifest their preventive action.²² In the final analyses, the authors considered 11 randomized, double-blind, placebo controlled trials that complied with the inclusion criteria, 15,348 patients in total with a history of CVD. No statistically significant association was observed for all-cause mortality (RR, 0.89; 95% CI, 0.78 to 1.02) and cerebrovascular accident (RR, 1.31; 95% CI, 0.90 to 1.90). On the contrary, statistically significant protective effects were observed for cardiac death (RR, 0.68; 95% CI, 0.56 to 0.83), sudden death (RR, 0.67; 95% CI, 0.52 to 0.87), and myocardial infarction (RR, 0.75; 95% CI, 0.63 to 0.88).²² The authors summarized that the effect of omega-3 supplementation on major cardiovascular events decreases mortality in patients with a coronary heart disease.^20,21

Recent studies have reported that omega-3 fatty acids help lower serum triglyceride levels by reducing liver synthesis of very low density lipoprotein and increasing fatty acid degradation and accelerating the elimination of triglycerides of plasma.^23-25 Carl et al. state that convincing evidence from extensive research over the last three decades points out the potential beneficial effects of omega-3 PUFA in primary prevention of the coronary artery calcification and post-myocardial infarction, sudden cardiac death, heart failure, atherosclerosis, and atrial fibrillation.²⁶ According to the evidence reported by De Caterine, omega-3 fatty acids continue to attract attention for their possible incorporation into healthy lifestyles and into drugs to prevent CVDs, but important gaps in knowledge persist. Clinical and mechanistic studies of the putative benefits of omega-3 fatty acids for primary and secondary prevention are still ongoing studies. ²⁷

CONCLUSION

According to the reported data, it is necessary to consume omega-3 fatty acids in our diet, from sources rich in omega-3 like fish, fish oil, vegetables and seeds that contain them. The consumption of omega-3 is usually of utmost importance as it has a protective cardiovascular effect. Therefore, it is considered useful during the preventive phase and even as an alternative treatment.

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^[a] Department of Medicine, School of Health Sciences, Universidad Autónoma del Estado de Hidalgo. Ex Hacienda la Concepción s/n, Carr. Pachuca – Tilcuautla, C.P. 42060, Tilcuautla, Hgo., México.

Corresponding Author: Martha Izbeth Cerón Sandoval. E-mail: izbetceron@gmail.com