Fish Oil and Cod Liver Oil (EPA & DHA)

Also indexed as: Eicosapentaenoic Acid, Omega-3 Fatty Acids

What is it?

Oil from fish contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); both are omega-3 fatty acids.

Most fish oil supplements are 18% EPA and 12% DHA, or a total of 30% omega-3. These omega-3 fatty acids, unlike the omega-3 fatty acid found in linseed oiland other vegetable oils (such as alpha linolenic acid), keep blood triglycerides in check (high triglycerides are generally linked with increased risk of heart disease) and may inhibit the progression of atherosclerosis.¹ EPA and DHA keep blood from clotting too quickly.

EPA and DHA also have anti-inflammatory activity. As a result, fish oil is used to help people with various inflammatory conditions, such as Crohn’s disease² and rheumatoid arthritis.³ The anti-inflammatory effects of EPA and DHA may also account for the findings of some reports that show fish oil supplementation helps some people with kidney diseases⁴ ⁵ ⁶ and may help protect against chronic obstructive pulmonary disease.⁷

The omega-3 fatty acids in fish oil help to balance the omega-6 fatty acids, which are found mostly in vegetable oils. When these two groups of fatty acids are out of balance, the body releases chemicals that promote inflammation. People appear to produce more of these inflammatory chemicals when experiencing psychological stress (e.g., academic examinations). With a fatty acid imbalance, inflammatory response to stress appears to be amplified.⁸

Prostaglandins are hormone-like substances produced within the body that regulate dilation of blood vessels, inflammatory response, and other critical processes. Omega-3 fatty acids are needed for prostaglandin formation. Probably as a result of their effect on prostaglandins responsible for blood vessel dilation, a double-blind trial found that omega-3 fatty acids from fish oil helped to treat people with Raynaud’s disease.⁹

Schizophrenia is linked with abnormalities in fatty acid metabolism, and preliminary research suggests that fish oil supplementation may be helpful to people with schizophrenia.¹⁰ However, a double-blind study that used 3 grams per day of eicosapentaenoic acid failed to demonstrate any benefit for patients with chronic schizophrenia.¹¹

DHA is essential for vision in infants. Researchers are now studying this relationship to better understand how much DHA is needed.

EPA and DHA also modulate immune function,¹² probably as a result of their effect on prostaglandin production. Perhaps as a result of this effect, fish oil has helped prevent some types of cancer in animals¹³ ¹⁴ ¹⁵ and humans,¹⁶ although this evidence remains preliminary.

Preliminary evidence also shows that omega-3 fatty acids from fish oil may help regulate the rhythm of the heart. EPA and DHA have been reported to help prevent cardiac arrhythmias.¹⁷

Where is it found?

EPA and DHA are found in mackerel, salmon, herring, sardines, sablefish (black cod), anchovies, albacore tuna, and wild game. Cod liver oil contains large amounts of EPA and DHA. Fish oil supplements typically contain 18% EPA and 12% DHA, though more purified (i.e., higher in EPA and DHA) fish oil supplements are sometimes available. In addition, DHA is available in a supplement that does not contain significant amounts of EPA.

Fish oil has been used in connection with the following conditions (refer to the individual health concern for complete information):

Science Ratings	Health Concerns
	Crohn’s disease (enteric-coated, free-fatty-acid form of fish oil) High blood pressure High triglycerides Rheumatoid arthritis
	Macular degeneration (in combination with acetyl-L-carnitine and coenzyme Q10) Asthma Atherosclerosis Bipolar disorder Breast-feeding support Cardiac arrhythmia (do not take, or take only with a doctor's supervision, if there is a history of sustained ventricular tachycardia or ventricular fibrillation) Cystic fibrosis (EPA) Depression Eczema Heart attack Immune function (omega-3 fatty acids for critically ill and post surgery patients only) Intermittent claudication (in combination with vitamin B6, folic acid, vitamin E, oleic acid, and alpha-linolenic acid) Kidney disease Lupus Multiple sclerosis Osteoporosis (in combination with evening primrose oil) Phenylketonuria (if deficient in polyunsaturated fatty acids) Pre- and post-surgery health Pregnancy and postpartum support (to prevent premature delivery) Psoriasis Raynaud’s disease Schizophrenia Sickle cell anaemia Ulcerative colitis
	Angina Chronic fatigue syndrome Chronic obstructive pulmonary disease (COPD) Colon cancer (reduces risk) Dysmenorrhoea (painful menstruation) Endometriosis Glaucoma Migraine headaches Osteoarthritis Osteoporosis Photosensitivity Preeclampsia Type 1 diabetes Type 2 diabetes
Reliable and relatively consistent scientific data showing a substantial health benefit. Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit. For a herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support and/or minimal health benefit.

Who is likely to be deficient?

So-called “primitive” diets have much higher levels of EPA and DHA than modern diets. As a result, some researchers and doctors believe that most people who eat a typical western diet are likely to be consuming less-than-optimal amounts of EPA and DHA. To a very limited extent, omega-3 fatty acids from vegetable sources, such as linseed oil, can convert to EPA.

At least four studies have reported a reduced blood level of omega-3 fatty acids in people with depression.¹⁸ ¹⁹ ²⁰ ²¹

People with rheumatoid arthritis have been found to have decreased levels of omega-3 fatty acids, such as are found in fish oil, in their joint fluid and blood.²²

How much is usually taken?

Presumably, healthy people who frequently eat fatty fish (several times per week) have no need to supplement with fish oil. How much EPA and DHA, if any, should be supplemented by healthy people who do not eat much fatty fish, remains unclear.

Most researchers studying the effects of EPA and DHA in humans who have a variety of health conditions have given those people at least 3 grams of the total of EPA plus DHA—an amount that may require 10 grams of fish oil, because most fish oil contains only 18% EPA and 12% DHA.

The health benefits for people with Crohn’s disease have been reported with a special, enteric-coated preparation of purified EPA/DHA manufactured from fish oil. This preparation of purified fatty acids has also been reported to not cause the gastrointestinal symptoms that often result from taking regular fish oil supplements, again suggesting unique benefit.²³

In one trial, the maximum amount of fish oil tolerated by people being treated for cancer-related weight loss was reported to be approximately 21 grams per day.²⁴ However, in people who do not have cancer, the maximum tolerated amount may be different.

Are there any side effects or interactions?

While those with heart disease and diabetes have often been reported to benefit from supplementation with fish oil,²⁵ ²⁶ both groups should check with their doctor before taking more than 3 grams of fish oil per day for several months. Elevations in blood sugar and cholesterol levels may occur in some people who take fish oil.²⁷

The increase in blood sugar appears to be related in part to the amount of fish oil used.²⁸ Some evidence suggests that adding vitamin E to fish oil may prevent the fish oil-induced increase in blood sugar levels.²⁹ In other research, the impairment of sugar metabolism sometimes caused by supplementation with fish oil has been prevented by the addition of half an hour of moderate exercise three times a week.³⁰

While supplementation with fish oil consistently lowers triglycerides, the effect of fish oil on LDL (“bad”) cholesterol varies, and in some people, fish oil supplementation has been reported to increase LDL levels.³¹ People who took fish oil and who also took 15 grams of pectin per day were reported to have reductions in LDL cholesterol.³² This suggests that pectin may overcome the occasional problem of increased LDL cholesterol reported in people who supplement with fish oil. The LDL-cholesterol raising effect of EPA and DHA has also been reported to be prevented by taking garlic supplements (or presumably including garlic in the diet) along with EPA and DHA.³³

Are there any drug interactions?
Certain medicines may interact with Fish Oil and Cod Liver Oil. Refer to drug interactions for a list of those medicines.

References
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1. von Schacky C, Angerer P, Kothny W, et al. The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1999;130:554-62.

2. Mate J, Castanos R, Garcia-Samaniego J, Pajares JM. Does dietary fish oil maintain the remission of Crohn’s disease: a case control study. Gastroenterology 1991;100:A228 [abstract].

3. Kremer JM, Lawrence DA, Petrillow GF, et al. Effects of highdose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Arthritis Rheum 1995;38:1107-14.

4. Donadio JV Jr, Bergstrahl EJ, Offord KP, et al. A controlled trial of fish oil in IgA nephropathy. N Engl J Med 1994;331:1194-9.

5. Peck LW. Essential fatty acid deficiency in renal failure: can supplements really help? J Am Diet Assoc 1997;97:5150-3.

6. Donadio JV Jr, Grande JP, Bergstralh EJ, et al. The long-term outcome of patients with IgA nephropathy treated with fish oil in a controlled trial. Mayo Nephrology Collaborative Group. J Am Soc Nephrol 1999;10:1772-7.

7. Shahar E, Folsom AR, Melnick SL, et al. Dietary n-3 polyunsaturated fatty acids and smoking-related chronic obstructive pulmonary disease. Atherosclerosis Risk in Communities Study Investigators. N Engl J Med 1994;331:228-33.

8. Maes M, Christophe A, Bosmans E, et al. In humans, serum polyunsaturated fatty acid levels predict the response of proinflammatory cytokines to psychological stress. Biol Psychiatry 2000;47:910-20.

9. DiGiacoma RA, Kremer JM, Shah DM. Fish-oil dietary supplementation in patients with Raynaud’s phenomenon: a double-blind, controlled, prospective study. Am J Med 1989;86:158-64.

10. Laugharne JDE, Mellor JE, Peet M. Fatty acids and schizophrenia.Lipids 1996;31:S163-5.

11. Fenton WS, Dickerson F, Boronow J, et al. A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Am J Psychiatry 2001;158:2071-4.

12. Alexander JW. Immunonutrition: the role of omega-3 fatty acids.Nutr 1998;14:627-33.

13. Braden LM, Carroll KK. Dietary polyunsaturated fat in relation to mammary carcinogenesis in rats. Lipids 1986;21(4):285.

14. O’Connor TP, Roebuck BD, Peterson F, et al. Effect of dietary intake of fish oil and fish protein on the development of L-azaserine-induced preneoplastic lesions in the rat pancreas. J Natl Cancer Inst 1985;75:959-62.

15. Gonzalez MJ. Fish oil, lipid peroxidation and mammary tumor growth. J Am Coll Nutr 1995;14:325.

16. Zhu ZR, Mannisto JAS, Pietinene P, et al. Fatty acid composition of breast adipose tissue in breast cancer patients and patients with benign breast disease. Nutr Cancer 1995;24:151-60.

17. Nair SSD, Leitch JW, Falconer J, Garg ML. Prevention of cardiac arrhythmia by dietary (n-3) polyunsaturated fatty acids and their mechanism of action. J Nutr 1997;127:383-93.

18. Maes M, Smith R, Christophe A, et al. Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids. J Affect Disord 1996;38:35–46.

19. Edwards R, Peet M, Shay J, Horrobin D. Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients. J Affect Disord 1998;48:149–55.

20. Peet M, Murphy B, Shay J, Horrobin D. Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients. Biol Psychiatry 1998;43:315–9.

21. Maes M, Christophe A, Delanghe J, et al. Lowered omega 3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Psychiatry Res 1999;85:275–91.

22. Navarro E, Esteve M, Olivé A, et al. Abnormal fatty acid pattern in rheumatoid arthritis. A rationale for treatment with marine and botanical lipids. J Rheumatol 2000;27:298–303.

23. Belluzzi A, Brignola C, Campieri M, et al. Effects of new fish oil derivative on fatty acid phospholipid-membrane pattern in a group of Crohn’s disease patients. Dig Dis Sci 1994;39:2589–94.

24. Burns CP, Halabi S, Clamon GH, et al. Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia: cancer and leukemia group B study 9473. Clin Cancer Res 1999;5:3942–7.

25. Leaf A, Weber PC. Cardiovascular effects of n-3 fatty acids. N Engl J Med 1988;318:549–57.

26. Malasanos TH, Stacpoole PW. Biological effects of omega-3 fatty acids in diabetes mellitus. Diabetes Care 1991;14:1160–79.

27. Schectman G, Kaul S, Kassebah AH. Effect of fish oil concentrate on lipoprotein composition in NIDDM. Diabetes 1988; 37:1567–73.

28. Toft I, Bonaa KH, Ingebretsen OC, et al. Effects of n-3 polyunsaturated fatty acids on glucose homeostasis and blood pressure in essential hypertension. Ann Intern Med 1995;123:911–8.

29. Luostarinen R, Wallin R, Wibell L, et al. Vitamin E supplementation counteracts the fish oil-induced increase of blood glucose in humans. Nutr Res 1995; 15:953–68.

30. Dunstan DW, Burke V, Mori TA, et al. The independent and combined effects of aerobic exercise and dietary fish intake on serum lipids and glycemic control in NIDDM. Diabetes Care 1997; 20:913–21.

31. Harris WS, Zucker ML, Dujovne CA. Omega-3 fatty acids in type IV hyperlipidemia: fish oils vs methyl esters. Am J Clin Nutr 1987;45:858 [abstr].

32. Sheehan JP, Wei IW, Ulchaker M, Tserng KY. Effect of high fiber intake in fish oil-treated patients with non-insulin-dependent diabetes mellitus Am J Clin Nutr 1997; 66:1183–7.

33. Adler AJ, Holub BJ. Effect of garlic and fish-oil supplementation on serum lipid and lipoprotein concentrations in hypercholesterolemic men. Am J Clin Nutr 1997; 65:445–50.

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The information presented in Healthnotes is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or chemist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires March 2007.

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