Introduction
Over the last few decades, multiple health benefits have been attributed to ingestion of fish oil. Eicosapentaenoic acid (EPA; 20:5 n-3) and docosa- hexaenoic acid (DHA; 22:6 n-3), found abundantly in fish oil, are its main functional components. Consumption of these fatty acids may be implicated in attenuation of blood lipids, reduction of inflammation, protection against various cancers of the breast, prostate and colon, and maintenance of blood glucose levels. The objective of the present review is to examine whether omega 3 fatty acids are effective in conferring these health benefits.
Omega-3 Fatty Acids from Fish Oil Decreases Risk of CHD and CHD-related Mortality
The beneficial effects of fish oil on coronary heart disease (CHD) are being recognized globally. Since 2000, dietary recommendations from the American Heart Association have acknowledged the cardioprotec- tive role of fish oil (1, 2 ). Currently, these guidelines recommend the consumption of fish, especially fatty fish, twice per week by all adults for primary prevention of CHD (2) . This would translate into an intake of 850- 1000 mg/d of EPA and DHA from fish oil(2) . Additionally, for patients with existing CHD, regular intake of 1g/d of EPA and DHA combined is suggested (2) . A round table discussion of experts at the Annual Scientific Meeting of European Society for Clinical Investigation associated reduced CHD mortality with consumption of 1-2 fish meals/week (3) . The discussion also concluded that “patients with dyslipidemia and/or postprandial hyperlipi- demia may reduce their coronary risk profile by administration of 1-4 g/d of marine n-3 PUFA” (3) .
One of the main effects by which fish oil prevents CHD related mortality is through its ability to lower triglyc- erides. Triglycerides have been shown to exist as an independent risk factor of CHD and its associated mortality (4) . A review of the literature shows that in patients with hypertriglyceridemia, low dose fish oil providing 850 mg-2.9 g/d of EPA + DHA can reduce plasma triglyceride levels by 6-8% per g consumed (1,5-7).
Other ways that fish oil may prevent CHD and CHD mortality are through its ability to reduce thrombotic tendency, prevent cardiac arrhythmia, and improve endothelial dysfunction (8-11) .
Many trials have confirmed the protective effect of fish and fish oil consumption on CHD mortality. A landmark study conducted over 3.5 years by the GISSI- Prevenzione investigators on 11 324 participants with previous history of myocardial infarction showed that supplementation of 850-882 mg/d of EPA and DHA resulted in a reduction in overall cardiovascular deaths and sudden cardiac deaths of about 45% (5) . A further meta-analysis of 10 studies on patients with recent or acute myocardial infarction (MI) or angina indicated that daily intake of fish oils for an average of 37 months resulted in decreased all-cause mortality by 16% and death due to MI by 24% (12) .
Thus, present evidence compellingly indicates that regular intake of fatty fish or fish oil should be recommended to prevent CHD event and mortality.
Omega-3 Fatty Acids from Fish Oil Helps to Reduce Inflammation
The inflammatory response is an important immune response that allows the body to deal with insult. Inflammation results from the production of various eicosanoids (prostaglandins (PG), leukotrienes (LT), and thromboxanes (TX)) by a cyclo-oxygenase enzyme (COX). Twenty carbon polyunsaturated fatty acids (PUFA), found in the phospholipids bilayer of cells, act as substrates for the COX enzyme. Since the membranes of most cells contain arachidonic acid (AA; 20:4 n-6), AA acts as the common precursor for eicosanoid synthesis. Liberation of AA by phospholi- pase A2 results in the formation of 2-series PG and 4- series LT. In turn, cytokines tumor necrosis factor a (TNF- a) interleukin 1b (IL-1b), and interleukin 6 (IL-6), are produced, resulting in inflammation (13) . Original Research Health Benefits of Consumption of Fish Oil Omega-3 Fatty Acids Sylvia Santosa, Peter JH Jones
Strong human evidence shows attenuated inflammation from increased consumption of EPA and DHA from fish oil (14-17) . This is because the inflammatory cell membrane incorporates EPA and DHA at the expense of AA. As a result, there is a decrease in availability of AA for the production of the potent inflammatory eicosanoids and cytokines (13,18,19) . Reduced inflamma- tion can also be explained through the increased presence of EPA, a 20C fatty acid which inhibits release of AA by phospholipase A2 and competes with AA for the COX enzyme (13,18,19 ). As a result, concentration increases of pro-inflammatory eicosanoids 3-series PG and 5-series LT that are less potent. Thus, a decrease in the production of TNF- a, IL-1b, and IL-6 ensues (19) . Though only in vitro evidence exists, EPA and DHA have also been shown to alter cytokine production through modifying gene expression (13) . Future in vivo evidence is needed to confirm the interaction of these omega 3 fatty acids with gene expression (13) .
Dietary supplementation of fish oil providing as little as 1.2 g of combined EPA and DHA, in conjunction with a low fat diet, has been shown to decrease production of TNF- a, IL-1b, and IL-6 (19) . Supplementation of more that 2.4 g/d of total EPA and DHA from fish oil has also been indicated in the reduction of these cytokines (19) . The decrease in TNF- a, IL-1b, and IL-6 production may have important implications in the treatment of chronic inflammatory conditions such as rheumatoid arthritis, asthma, and inflammatory bowel diseases. Omega-3 Fatty Acids from Fish Oil May Protect from Cancers of the Breast, Prostate, and Colon Cancers of the breast, colon and prostate are among the most common in North America (20) . Multiple epidemiological cohort and case control studies have found inverse correlations between incidence of breast and colon cancer, and omega 3 intake from fish (20,21) . Other papers report a similar association between prostate cancer incidence and fish oil (21-24) . Evidence from studies that supplemented tumor bearing rodents with EPA or DHA further supports the protective effect of these fatty acids on cancers of the breast, colon, and prostate (25-30) . Supplementation studies in rodents also show increased effectiveness of chemotherapy and radiation therapy (21) . However, this relationship does not seem to exist merely based on the amount of omega 3 fatty acids consumed, rather the ratio of n-3:n-6 found in the diet, with higher ratios being more protective (20,21,31) . Currently, a ratio of 1:2.3 of n-3:n-6 has been suggested as ideal (32) . Possible chemopreven- tative mechanisms through which fish oils act are suppression of neoplastic transformation, cell growth inhibition and enhanced apoptosis and antiangiogenicity (20,33) .
There is not as much evidence for the protective role of fish oil for the prevention of these cancers as there is for the prevention of CHD and inflammation because it is mainly based on epidemiological and experimental animal findings. Though no clinical trials have been conducted, the collective body of evidence indicates a possible protective effect of fish oil on these cancers
Omega-3 Fatty Acids from Fish Oil Has No Effect on Blood Glucose Control in Diabetics
The majority of the existing literature demonstrates that fish oil may be contraindicative or may have no effect on maintaining glucose control. High doses of 4-10 g/d of EPA and DHA from fish oil have been implicated in negatively affecting glycemic control (34) . A meta-analysis by Friedberg et al (35) showed no effect of fish oil on increased fasting glucose in type 1 and 2 diabetics. In general, doses of up to 3 g/d of omega 3s have been shown to have no negative impact on glycemic control (34,36-40) . Thus, lower doses may be considered safe for consumption. Consumption safety is especially noteworthy since diabetics are at high risk of dyslipi- demia and CHD and consumption of fish oil may reduce this risk.
Summary
Figure 1 shows the strength of evidence surrounding effects of EPA and DHA from fish oil on health. Low dose supplementation of up to 3.0 g/d of DHA and EPA from fish oil can be recommended to decrease risk of CHD and CHD associated mortality, and in treating disorders associated with inflammation. Though more human clinical trials are required, fish oil may play a role in cancer treatment and prevention. Studies indicate that low doses of fish oil have no effect on blood glucose control in diabetics. Therefore, this population may safely consume fish oil to decrease risk of dyslipidemia and CHD. However, clinicians should focus more on increasing the ratio of n-3:n-6 fatty acids to at least 1:2.3 in nutritional prevention and therapy of cancer.
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