Health Benefits of Fish Oil

HEALTH BENEFITS OF FISH OIL

Fish oil is a rich source of long chain omega-3 fatty acids which are polyunsaturated fats that primarily include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Initially, these compounds were suggested as a daily omega-3 fatty acid supplement for the prevention of cardiovascular disease (CVD). Consequently, fish oil supplements are widely used in the United Kingdom and other developed countries ^[1].

The American Heart Association’s 2006 Diet and Lifestyle Recommendations advise that patients without established coronary artery disease (CAD) consume at least 2 servings of fish per week, preferably fatty fish high in EPA and DHA. For secondary prevention of CAD, the guidelines propose a daily fish consumption equivalent to 1 g/day of EPA and DHA ^[2].

EPA and DHA are found in numerous regions of the body, including cell membranes, and are involved in anti-inflammatory actions as well as cell membrane viscosity. EPA and DHA are essential for proper fetal development and healthy aging. DHA is a crucial component of cell membranes and is abundant in the brain and retina. EPA and DHA are also precursors to many metabolites that are potent lipid mediators, considered by many investigators to be beneficial in the prevention or treatment of several diseases ^[3].

Effects on Cardiovascular disease

The potential for EPA and DHA to play a role in lowering the risk of CVD was initially discovered in Greenland Inuit studies, where a low rate of mortality from myocardial infarction (MI) and ischemic heart disease was associated to a high dietary intake of EPA and DHA ^[4]. Cardiovascular disease is the cause of 38% of all deaths in the United States, many of which are preventable. Many chronic diseases, including CVD, are thought to be caused by chronic inflammation. EPA and DHA are believed to have anti-inflammatory effects, play a role in oxidative stress, and improve cellular function through gene expression alterations. In a study that used human blood samples, EPA+DHA intake changed the expression of 1040 genes and resulted in a decreased expression of genes involved in inflammatory and atherogenesis related pathways, such as nuclear transcription factor kB signaling, eicosanoid synthesis, scavenger receptor activity, adipogenesis, and hypoxia signaling. Circulating markers of inflammation, such as C-reactive protein (CRP), TNF a, and some ILs (IL-6, IL-1), correlate with an increased probability of experiencing a cardiovascular event. CRP is synthesized by the liver in response to inflammatory signals such as IL-6, and high levels of CRP are associated with an increased risk of CVD. In a trial of 89 patients, those given EPA+DHA had a significantly lower level of high-sensitivity CRP (66.7 %, P 0.01). The same study also found a significant reduction in heat shock protein 27 antibody titers (57.69%, P < 0.05), which has been demonstrated to be overexpressed in heart muscle cells after a period of ischemia (ischemia-reperfusion injury) and may have a cardioprotective impact ^[3].

The myocardium has been shown to have a direct electrophysiological effect from omega-3 fatty acids. Initial experience with animal ischemia models demonstrated that the ventricular fibrillation threshold was increased in animals fed with omega-3 fatty acid. This progressed to a demonstration, on a cellular and ion channel level, that omega-3 fatty acid reduce both sodium currents and L-type calcium currents. It is hypothesized that during ischemia, a reduction in the sodium ion current protects hyperexcitable tissue, and a reduction in the calcium ion current reduces arrhythmogenic depolarizing currents ^[2].

In addition, omega-3 fatty acids have been found to play a role in atherosclerosis and peripheral arterial disease (PAD). Both EPA and DHA are expected to increase plaque stability, decrease endothelial activity, and improve vascular permeability, lowering the risk of a cardiovascular event ^[3].

Effects on plasma lipid and lipoprotein metabolism

Dyslipidaemia, particularly hypertriglyceridemia, hypercholesterolemia, and/or a low high density lipoprotein (HDL) cholesterol level, is a major risk factor for atherosclerosis and CVD development. The cardioprotective effects of fish oils are partially attributed to their triglyceride (TG)-lowering action, while their effect on cholesterol levels appears weak or inexistent. Both EPA and DHA reduce TG levels in normolipidaemic and hyperlipidaemic patients by 15 to 30% when given individually for 6 weeks or longer ^[5].

Fish oils generally have no effect on total cholesterol but their impact on low density lipoprotein (LDL) and HDL cholesterol varies depending on dose, form, and population ^[5].

Effects on blood pressure

Hypertension is a powerful predictor of cardiovascular risk, and there is convincing evidence that reducing blood pressure (BP) decreases the risk of total mortality, cardiovascular mortality and stroke. Although the clinical effect of doses lower than 0.5 g/d, equivalent to one portion of oily fish per week, could not be established, a meta-analysis of 36 intervention trials confirmed the hypotensive role of fish oils on both systolic and diastolic BP, especially in elderly and hypertensive patients ^[5].

Several mechanisms could explain the benefits of fish oil supplementation in terms of clinical outcomes. Firstly, the results of several studies have indicated that omega-3 fatty acid supplementation has beneficial effects on blood pressure, plasma triglycerides, and heart rate, all of which are protective against the development of CVD. Secondly, omega-3 fatty acids have been demonstrated in several trials to improve flow mediated arterial dilatation, which is a measure of endothelial function and health. Thirdly, omega-3 fatty acids have been demonstrated to have antiarrhythmic properties that could be clinically beneficial. Finally, studies have reported that fish oil can reduce thrombosis. Additionally, studies have reported that the anti-inflammatory properties of fish oil could have a preventive role in the pathophysiology of CVD outcomes. Other mechanisms could also be involved to explain the effect of fish oil on CVD outcomes ^[1].

In 2010, the European Food Safety Authority (EFSA) concluded that EPA and DHA aid in the maintenance of normal cardiac function, blood pressure, and triglyceride levels in the general population. As part of a healthy diet, EFSA recommends an intake of 250 mg/day of EPA+DHA to maintain normal cardiac function, 3 g/d to maintain normal blood pressure, and 2 g/d to maintain normal blood triglyceride concentrations ^[4].

Effects on Attention-Deficit Hyperactivity Disorder (ADHD)

The review mentioned had a focus on attention-deficit hyperactivity disorder (ADHD), and reported that half of the 12 intervention trials reported positive results but did not clearly recommend EPA and DHA for improvement of aspects of ADHD. ADHD was associated with low blood levels of EPA and DHA in a meta-analysis of nine epidemiology studies. DHA was found to have a positive correlation with attention and a negative correlation with the severity of ADHD in an epidemiology investigation. Although a Cochrane meta-analysis of 2016 did not recommend EPA and DHA in the treatment of ADHD, other systematic reviews and meta-analyses reached more positive conclusions ^[6].

Effects on Cognition and Dementia

DHA is quantitatively the most important omega-3 polyunsaturated fatty acid in the brain and has consistently been shown to have unique and indispensable roles in the neuronal membrane ^[7]. Omega-3 fatty acids were found to be beneficial at the early stages of Alzheimer’s disease, but not later stages, according to a comprehensive evaluation of intervention trials. When intervention trials on cognition parameters published up to 2015 were broken down according to dose of DHA used, it became apparent that trials using more than 600 mg DHA per day had positive results in terms of memory, executive function, or learning, while those using lower doses largely had neutral results. However, more recently, both neutral and positive results were published with doses >600 mg DHA per day. Thus, cognitive decline can be slowed, and Alzheimer’s disease can be prevented or improved in its early, but not in later stages of Alzheimer’s disease ^[6].

Adverse effects of fish oil

The FDA warns of potential bleeding complications with the coadministration of anticoagulants. This warning is based on observational studies that suggested a prolonged bleeding time in populations ingesting high levels of fish oil and on in vitro studies that demonstrated an effect on pro-thrombotic mediators such as a reduction in thromboxane A2 production and platelet activation factor. The same trend, however, has not been clearly demonstrated in measurements of clotting times or in factors of fibrinolysis. And there is very little evidence that a lower target INR is necessary in patients receiving chronic warfarin therapy and fish oil ^[2].

REFERENCES

1. Li Z, Zhong W, Liu S, Kraus V, Zhang Y, Gao X, et al. Associations of habitual fish oil supplementation with cardiovascular outcomes and all cause mortality: evidence from a large population based cohort study. BMJ. [Internet]. 2020 [cited 2022 Mar 4]; 368: 1-9. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249244/
2. Weitz D, Weintraub H, Fisher E, Schwartzbard A. Fish oil for the treatment of cardiovascular disease. Cardiology in Review. [Internet]. 2010 [cited 2022 Mar 4]; 18: 258-63. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217043/
3. Swanson D, Block R, Mousa S. Omega-3 fatty acids EPA and DHA: health benefits throughout life. Advance in Nutrition. [Internet]. 2012 [cited 2022 Mar 4]; 3: 1-7. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262608/
4. Innes J, Calder P. Marine Omega-3 (N-3) Fatty Acids for Cardiovascular Health: An Update for 2020. International Journal of Molecular Sciences. [Internet]. 2020 [cited 2022 Mar 4]; 21: 1-21. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072971/
5. Cottin S, Sanders T, Hall W. The differential effects of EPA and DHA on cardiovascular risk factors. Proceeding of the Nutrition Society. [Internet]. 2011 [cited 2022 Mar 4]; 70: 215-31. Available form: http://www.cambridge.org/core/journals/proceedings-of-the-nutrition-society/article/differential-effects-of-epa-and-dha-on-cardiovascular-risk-factors/63DCD0AB997CFFA16862B21470853E53
6. Schacky C. Importance of EPA and DHA Blood Levels in Brain Structure and Function. Nutrients. [Internet]. 2021 [cited 2022 Mar 4]; 13: 1-18. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066148/
7. Dyall S. Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Frontiers in Aging Neuroscience. [Internet]. 2015 [cited 2022 Mar 4]; 7: 1-15. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404917/