This document discusses the health benefits of omega-3 fatty acids found in fish oil. It covers the main sources of omega-3s, their proposed mechanisms for reducing atherosclerosis like decreasing inflammation and triglyceride levels, safety concerns regarding fish oil supplements, and research showing correlations between fish oil consumption and reduced risk of heart disease. The marketing of fish oil as a supplement is also examined, noting both approved and less substantiated health claims made about omega-3s.

1. Title TBD Catherine Arnatt, Christina Keyser, Allison Kling, Truong An Le, Brendan Muoio, Baiden Opoku, Andrea Scott Class of 2013, School of Pharmacy, Virginia Commonwealth University, Richmond, VA Abstract n/a Introduction Fish oil consists of Omega-3 poly unsaturated fatty acids (PUFAs) which must be obtained from the diet because the body cannot synthesize them (1). The 2 PUFAs specifically from fish oil are EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). Fish store fat either in their livers or flesh, depending on the type of fish. The oil obtained from these fish is called fish oil. Salmon and trout have the highest amount of PUFAs per serving portion, 2.20 grams and 2.65 grams respectively (1). A study done by Chung, H. et al found that only eating non-fried fish, not shellfish or fish in mixed dishes, twice a week could increase concentrations of EPA and DHA in humans. This is an important point because the type, amount, and means of cooking affect the amount of PUFAs obtained from fish (2). Source There are several mechanisms in which it is believe that Omega-3 fatty acids work, though we are only highlighting those pertaining to atherosclerosis. One is that fatty acids affect production of plaques through various ways such as decreasing plasma triglyceride levels and possibly increasing plaque stability. Increased plasma levels of triglycerides have been associated with atherosclerosis (3). Omega-3 fatty acids are anti-inflammatory and thus decrease the activity of inflammatory cells, like macrophages and lymphocytes. Unstable plaques are characterized by increased amounts of inflammatory cells and a thin fibrous cap covering the plaque. Omega-3 fatty acids either block or decrease the amount of inflammatory cells in the plaque and by increasing the thickness of the fibrous cap (1). Both of these mechanisms demonstrate that Omega-3 fatty acids are beneficial in prevention and treatment of atherosclerosis. Mechanism Safety Omega-3 fish oil is safe for most people though it can cause some side effects such as belching, bad breath, heartburn, nausea, loose stools, rash, and nosebleeds. Taking them with meals and starting with low doses can often decrease these side effects. Another reported side effect is the reduction of blood pressure though it appears to be dependent on high doses (WebMD). Literature suggests that there are three main safety concerns that people historically are worried about when taking Omega-3 fish oils: the possibility of bleeding, over supplementation, and contamination. Though some fish meats are contaminated with industrial and environmental toxins like mercury, polychlorinated biphenyls, or dioxins, fish oil supplements typically have very low or negligible amounts.. Fish oil supplements undergo extensive purification processes to remove such environmental toxins. The relative safety of the product can be assessed by verifying the source as well as identifying US Pharmacopeia labeling (Bays, 2007). Pharmacokinetics Oral administration of 4g P-O3FA, in both healthy volunteers and patients with hypertriglyceridemia, EPA and DHA were found to be well absorbed. P-O3FA induced significant, dose-dependent increases in serum phospholipid EPA content, however, increases in DHA content were less marked and not dose dependent when administered as ethyl esters. The uptake of EPA and DHA into serum phospholipids in participant treated with P-O3FA was independent of age. Pharmacodynamics Studies showed that high fish consumption is associated with better cardiovascular health. The major benefit of fish oil is reduction of cardiac arrest which could lead to sudden death. The mechanisms involved in this process involve the antiarrhythmic activities, reduction of thrombotic and inflammatory processes and of serum triacylglycerol levels. Absorption of EPA, but not of DHA, from fish oil triacylglycerols was significantly improved from 69% to 90% by co-ingestion with the high-fat meal. Absorption of both EPA and DHA from fish oil ethyl esters was increased three-fold, to about 60%, by co-ingestion with the high-fat meal, indicating that absorption of fatty acid ethyl esters is highly dependent on the amount of co-ingested fat. Marketing In 2003, the FDA was petitioned to approve the claim, “Consumption of omega-3 fatty acids may reduce the risk of coronary heart disease.” This claim was rejected due to insufficient evidence; however, the qualified claim, “Supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease” has been approved. Despite the caution of these organizations, the average patient’s research will turn up extremely positive results for this product. Consumer health websites such as WebMD recommend Omega 3 Fish Oil for cholesterol, high blood pressure, depression, and a variety of other indications,6 and Wikipedia even reports that they may help prevent cancer, schizophrenia, Alzheimer’s, and Parkinson’s.7 While the FDA does police online retail sources of Omega-3 Fish Oil to regulate their health claims,8 consumers may still be subject to deceptively positive marketing regarding the benefits of Omega 3 Fish Oil. Results Risk factors for cardiovascular disease include abnormal serum lipid levels (mg/dL) through high levels of low density lipoprotein (LDL) and triglycerides (Tg) and low levels of high density lipoprotein (HDL). Research studying the effects of omega-3 fatty acids have shown that there may be a beneficial correlation between consumption of fish oil and decrease in triglycerides, though total cholesterol may increase slightly. Retrieved from: http://www.ahrq.gov/clinic/epcsums/o3cardrisksum.htm Figure 3.2 shows that the net decrease in Tg levels correlates to the amount of omega -3 consumed (g/day). The graph shows that the more omega-3 taken per dose, the greater the percent decrease in Tg levels. Discussion Literature suggests that an antithrombotic effect is possible (though not proven) and as a result fish oils could potentially increase the risk for bleeding. Though there is data suggesting that fish oils rich in omega-3 fatty acids inhibit thrombosis, data regarding the effects of fish oils on fibrinogen and clotting factors are more limited Most clinical trial evidence has shown that at high-dose omega-3 fatty acid intake, the increased risk of bleeding is very small and not of clinical significance even when combined with other agents that might also increase bleeding such as aspirin and warfarin. In fact, the antiatherothrombotic benefits far outweigh the unproved bleeding risks in patients at high risk for thrombosis (Bays, 2007). A second safety concern with these supplements is their susceptibility to undergo oxidation, contributing to patient intolerance and potential toxicities (Bays, 2007). One way to reduce fish oil oxidation and thus reduce fish oil rancidity, maintain freshness, and increase shelf life is to add the antioxidant Vitamin E. A second way to improve patient tolerance and reduce the fishy aftertaste is to refrigerate them. Often the fishy smell, patient intolerances, and potential toxicities of fish oil are removed during the manufacturer’s purification processes. It is suggested that omega-3 fish oil supplements that do have a strong, fishy smell and taste are poorly manufactured or are expired (Bays, 2007). Another potential, though highly rare toxicity, called hypervitaminosis could occur with excessive over consumption of fish oils containing high concentrations of fat-soluble vitamins D and A. References Acknowledgements Bays, H.E. (2007). Safety Considerations with Omega-3 Fatty Acid Therapy. Am J Cardiol 99; 35-43. Hubbard, William. (2004.) Letter Responding to Health Claim Petition dated June 23, 2003 (Wellness petition): Omega-3 Fatty Acids and Reduced Risk of Coronary Heart Disease (Docket No. 2003Q-0401). Retrieved 4/17/10 from http://www.fda.gov/Food/LabelingNutrition/LabelClaims/QualifiedHealthClaims/ucm072936.htm . National Library of Medicine. (2009.) Omega-3 fatty acids, fish oil, alpha-linoleic acid. Retrieved 4/17/10 from http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-fishoil.html#grade . Kris-Etherton, Penny M., William S. Harris, Lawrence Appel. (2002.) Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease. Circulation , 106 , 2747-2757. Yan Zhang