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Long-chain Omega-3 Fatty acids from Fish: Health Benefits, Potential Mechanisms

Long-chain Omega-3 Fatty acids from Fish: Health Benefits, Potential Mechanisms, and Associated Risks

This week we want to introduce you to Philip A. Wood, DVM, PhD. His specialty is fatty acid metabolism and genetics and he has published more than 75 peer reviewed papers about the impact of genetics, diet, physical activity and drugs on diseases of excess fat. He has recently published the book How Fat Works and is now joining our featured writers group. His first article Long-chain Omega-3 Fatty acids from Fish: Health Benefits, Potential Mechanisms, and Associated Risks delivers timely info you can use to help your patients.

Long-chain Omega-3 Fatty acids from Fish:
Health Benefits, Potential Mechanisms, and Associated Risks

Philip A. Wood, DVM, PhD

Healthful benefits are associated with eating oily fish or taking fish oil supplements, both of which are rich in long-chain omega-3 fatty acids. The most dramatic benefit is a reduction in death from coronary heart disease or fatal arrhythmia (1, 3). Patients affected by insulin resistance, metabolic syndrome, and type 2 diabetes commonly experience hypertriglyceridemia, proinflammatory and prothrombotic states, abnormally low high-density lipoprotein-cholesterol (HDL-C), and hypertension, all of which increase the risk for cardiovascular disease. Consuming long-chain omega-3 fatty acids may assist in reversing these risk factors (1-4).

All omega-3 fatty acids contain multiple double bonds in their structures (polyunsaturated). The first double bond—three carbons from the methyl end of the fatty acid—is considered the omega-3 bond, the signature feature of these fatty acids (45). Even so, linolenic acid, an omega-3 fatty acid that has 18 carbons and is concentrated in flaxseed and walnuts, does not share the properties of 20- and 22-carbon acids; therefore, it is not considered here. The focus here is on two long-chain fatty acids that are also called n-3 fatty acids: the 20-carbon eicosapentaenoic acid (EPA) and the 22-carbon docosahexaenoic acid (DHA).

Eating oily fish or taking fish oil capsules containing EPA and DHA provides various benefits (Table 1). The most extensively documented benefit is a reduction in acute myocardial events such as ventricular arrhythmia, fibrillation or flutter resulting in sudden death (1-3). Hyperinsulinemia is often associated with increased hepatic fatty acid and triglyceride synthesis, with reduction in mitochondrial fatty acid oxidation, or fat burning. Conversely, omega-3 fatty acids promote the opposite effects, reducing production of excess fat and increasing mitochondrial and peroxisomal oxidation of fatty acids (45-67).

Table 1. Healthful properties associated with long-chain omega-3 fatty acids

Beneficial Effect
Disease Reduction Effect
Potential Mechanism
Hypotriglyceridemic (i.e., improves dyslipidemia) Reduces blood triglyceride concentrations and lowers the risk for pancreatitis.Reduces total blood non-HDL-C (predominately VLDL-C).Slightly increases HDL-C.May increase LDL-C. Increases lipoprotein lipase-mediated clearance of VLDL-triglyceride.Reduces fatty acid and triglyceride synthesis. Increases fatty acid oxidation in liver.
Anti-inflammatory Reduces inflammatory mediators such as interleukins and tumor necrosis factor-a.Reduces adhesion molecule expression. Increases the synthesis of anti-inflammatory omega-3 fatty acid-derived eicosanoids such as 3-series prostenoids and 5-series leukotrienes.
Antithrombotic Reduces platelet aggregation. May increase fibrinolysis. Mechanism unclear.
Antiarrhythmia Reduces heart rate, ventricular arrhythmia and fibrillation, and sudden death Unknown mechanism directly affectss heart.
Antihypertensive May lower blood pressure Enhances nitric oxide production.

Note. Note. Summarized from refs. HDL-C, high-density lipoprotein-cholesterol; ; VLDL-C, very low-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol.

Many of the benefits summarized in Table 1 are dose dependent. Furthermore, some results have been reproducibly demonstrated in clinical trials, whereas others remain circumstantial. Mozaffarian and Rimm (1) summarized these benefits and the intake amounts of EPA and DHA that corresponded with prevention or modification of different disease processes. The most clearly documented benefit of omega-3 fatty acids that they found was reduced mortality from either myocardial infarction (as a result of coronoary heart disease) or fatal arrhythmia among people with a modest daily intake of 250 mg (EPA+DHA)/day (1). The reduction in both causes of mortality appears to reach a plateau of benefit at ~750 mg (EPA+DHA)/day intake (1). Although the hypotriglyceridemic and antithrombotic benefits of EPA and DHA appear to increase with increasing doses (1), the overall effect of reducing risk of nonfatal coronary heart disease is of modest benefit and the studies that have been reported are equivocal (1).

The American Heart Association and American Diabetes Association recommends consuming two-three servings of oily fish per week (4) to provide the desired quantity of EPA and DHA. However, the amount of EPA and DHA that we obtain from eating fish varies depending on the type of fish we consume. For example, as shown generally (1), the highest content of EPA+DHA in a 3.5-oz. serving comes from salmon (1043 mg [wild] to 2648 mg [farmed]), Atlantic Herring (2014 mg), and Atlantic Mackerel (1203 mg). In contrast, lower EPA+DHA content is common in fish such as snapper (321 mg), albacore tuna (862 mg) and light tuna (270 mg). Fish do not synthesize substantial amounts of these fatty acids but, like humans, obtain them from their diet; thus, the concentrations of omega-3 fatty acids can vary even within types of fish. For other types of fish and their representative concentrations of omega-3 fatty acids, see refs. Many fish oil capsules contain 200-800 mg EPA+DHA per capsule providing an alternative to eating fish.

Alongside recommendations to consume more fish have come increased concerns about the presence in fish of methylmercury, PCBs, dioxins, and other environmental contaminants. Fish are often highlighted as containing these contaminants, but other common foods such as beef, pork, dairy, and vegetables contain concentrations of PCBs and dioxins similar to those found in many fish (1). Furthermore, many of the types of fish we eat to obtain omega-3 fatty acids have the lowest concentrations of environmental contaminants, and the concentrations found are well below the established FDA levels of concern (1). On the other hand, fish that are predatory and long-lived, such as sharks and swordfish, do tend to accumulate these toxins. Thus, the greatest risk of contaminants, especially methylmercury, is for women of child-bearing age, nursing mothers, and young children (1) who eat predatory fish.

Consuming fish for the long-chain omega-3 fatty acids EPA and DHA that they provide offers many benefits. Pregnant or nursing women and young children may be warranted in limiting their consumption of fish species known to contain more environmental contaminants. Nevertheless, the benefits of consuming fish clearly outweigh the risks.

To learn more about Dr. Woods click here, and go to the bottom of the page

1. Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health. Evaluating the risks and the benefits. JAMA 296: 1885-1899, 2006.
2. McKenney JM. Omega-3 fatty acids in the management of hypertriglyceridemia: New findings and formulations. http://princetoncme.com/public/2005-134/report2.php.
3. Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 106:2747-2757, 2002.
4. Nettleton JA, Katz R. n-3 long-chain polyunsaturated fatty acids in type 2 diabetes: A review. J Am Diet Assoc 105:428-440, 2005.
4.5. Wood PA. How Fat Works. Harvard University Press, Cambridge, MA, pp. 30, 155-157, 2006.
5.6. Clarke SD. Polyunsaturated fatty acid regulation of gene transcription: A molecular mechanism to improve metabolic syndrome. J Nutr 131:1129-1132, 2001.
6.7. Neschen S, Moore I, Regittnig W, Yu CL, Wang Y, Pypaert M, Petersen KF, Shulman GI. Contrasting effects of fish oil and safflower oil on hepatic peroxisomal and tissue lipid content. Am J Physiol Endocrinol Metab 282:E395-E401, 2002.