Fish Oil (EPA and DHA) and Cod Liver Oil

Physiology and Clinical Effects
Fish oil contains EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid); both are omega-3 oils. Most fish oil supplements are 18% EPA and 12% DHA, or a total of 30% omega-3. These special omega-3 oils, unlike other omega-3 oils, keep blood triglycerides in check (high triglycerides are generally linked with increased risk of heart disease). EPA and DHA keep blood from clotting too quickly. They also have anti-inflammatory activity. As a result, fish oil is used to help people with various inflammatory conditions, including Crohn’s disease.¹ Fish oil may help people with a wide variety of disorders, including chronic kidney diseases.^{2 3} Chronic obstructive pulmonary disease may be less likely to develop in those with a greater intake of omega-3 fatty acids.⁴

Due to its effects on prostaglandin metabolism, fish oil has helped some people with Raynaud’s phenomenon in double-blind research.⁵ Schizophrenia is linked with abnormalities in fatty acid metabolism, and preliminary research has found fish oil helpful in people with schizophrenia.⁶

DHA is essential for vision in infants. Fish oil may also help prevent some types of cancer in animals^{7 8 9} and humans,¹⁰ but this evidence remains preliminary. Preliminary evidence shows that fish oil may help prevent cardiac arrhythmias.¹¹ Finally, fish oil modulates immune function,¹² though details remain unclear.

Food Sources
EPA and DHA are found in mackerel, salmon, herring, sardines, sable fish (black cod), anchovies, albacore tuna, and wild game. Cod liver oil contains large amounts of EPA and DHA.

Deficiency Risk and Symptoms
To a very limited extent, omega-3 oil from vegetable sources, such as flaxseed oil, can convert to EPA. Most doctors believe most people do not eat enough EPA and DHA. So-called primitive diets have much higher levels than modern diets.

Recommended Dosage
Most of the research with fish oil has given people with a variety of health conditions at least 3 grams 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. A lesser, ideal amount for healthy people has not been determined.

The health benefits for individuals with Crohn’s disease have been reported with a special enteric-coated, “free fatty acid” form of EPA/DHA taken from fish oil. The enteric coated free fatty acid form has also been reported to not cause gastrointestinal symptoms often resulting from taking regular fish oil supplements, again suggesting unique benefit.¹³

Contraindications
While those with heart disease and diabetes often benefit from fish oil,^{14 15} both groups should check with their doctor before taking more than 3 or 4 grams of fish oil for several months. Elevations in blood sugar and cholesterol levels may occur in some individuals who take fish oil.¹⁶ The increase in blood sugar appears to be related in part to the amount of fish oil used.¹⁷ While supplementation with fish oil consistently lowers triglycerides, the effect of fish oil on LDL cholesterol varies, and sometimes the levels actually increase.¹⁸ Also, because EPA and DHA reduce blood clotting, people taking them sometimes get nose bleeds.¹⁹ Some people who supplement several grams of fish oil will experience gastrointestinal upset and burp up a “fishy” smell.

Due to its very high levels of vitamin A and vitamin D, cod liver oil should not be taken by women who are or who could become pregnant before consulting a doctor. Other adults should consult with a doctor before taking cod liver oil (or other supplements) containing more than 25,000 (7,500 mcg) of vitamin A per day or 800 IU of vitamin D per day.

Fish oil is easily damaged by oxygen, so a few milligrams or IUs of vitamin E should be included in all fish oil supplements.²⁰ In addition, people who supplement with fish oil should take additional vitamin E supplements (several hundred IUs) to protect EPA and DHA within the body from oxidative damage.²¹

Some evidence suggests that adding vitamin E to EPA/DHA may prevent the fish oil-induced increase in serum glucose.²² Similarly, the impairment of glucose tolerance sometimes caused by the omega-3 oil has been prevented by the addition of half an hour of moderate exercise three times a week.²³

People who take fish oil containing EPA and DHA and who also take 15 grams of pectin per day have been reported to have reductions in LDL cholesterol.²⁴ This suggests that pectin may overcome the occasional problem of increased LDL cholesterol from fish oil supplementation. The LDL-C raising effect of EPA and DHA may also be successfully prevented by taking garlic supplements (or presumably including garlic in the diet) along with EPA and DHA.²⁵

References:

1. 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].
2. Donadio JV Jr, Bergstralh EJ, Offord KP, et al. A controlled trial of fish oil in IgA nephropathy. N Engl J Med 1994;331:1194–9.
3. Peck LW. Essential fatty acid deficiency in renal failure: can supplements really help? J Am Dietet Assoc 1997;97:5150–3.
4. 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.
5. 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.
6. Laugharne JDE, Mellor JE, Peet M. Fatty acids and schizophrenia. Lipids 1996;31:S-163–5.
7. Braden LM, Carroll KK. Dietary polyunsaturated fat in relation to mammary carcinogenesis in rats. Lipids 1986;21(4):285.
8. O’Connor TP, 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(5):959–62.
9. Gonzalez MJ. Fish oil, lipid peroxidation and mammary tumor growth. J Am Coll Nutr 1995;14:325.
10. 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.
11. 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.
12. Alexander JW. Immunonutrition: the role of omega-3 fatty acids. Nutr 1998;14:627–33.
13. 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. 
14. Leaf A, Weber PC. Cardiovascular effects of n-3 fatty acids. N Engl J Med 1988;318:549–57.
15. Malasanos TH, Stacpoole PW. Biological effects of omega-3 fatty acids in diabetes mellitus. Diabetes Care 1991;14:1160–79.
16. Schectman G, Kaul S, Kassebah AH. Effect of fish oil concentrate on lipoprotein composition in NIDDM. Diabetes 1988; 37:1567–73.
17. 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.
18. 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(4):858 [abstr].
19. Clarke JTR, Cullen-Dean G, Reglink E, et al. Increased incidence of epistaxis in adolescents with familial hypercholesterolemia treated with fish oil. J Pediatr 1990;116:139–41.
20. Piche LA, Draper HH, Cole PD. Malondialdehyde excretion by subjects consuming cod liver oil vs a concentrate of n-3 fatty acids. Lipids 1988;23:370–1.
21. Wander RC, Du S-H, Ketchum SO, Rowe KE. Effects of interaction of RRR-”-tocopheryl acetate and fish oil on low-density-lipoprotein oxidation in postmenopausal women with and without hormone-replacement therapy. Am J Clin Nutr 1996;63:184–93.
22. 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.
23. 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.
24. Sheehan JP, Wei IW, Ulchaker M, Tserng K-Y. Effect of high fiber intake in fish oil-treated patients with non-insulin-dependent diabetes mellitus Am J Clin Nutr 1997; 66:1183–7.
25. 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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