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Eicosapentaenoic Acid, Omega-3 Fatty Acids

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• Drug interactions

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

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.

Health Concerns

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

Rating	Health Concerns
	Crohn's disease (enteric-coated, free-fatty-acid form of fish oil) High blood pressure High triglycerides Rheumatoid arthritis
	Anxiety related to substance abuse 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 High cholesterol (krill oil) 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) Lupus Macular degeneration (in combination with acetyl-L-carnitine and coenzyme Q10) 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) Premenstrual syndrome (krill oil) Psoriasis Raynaud's disease Schizophrenia Sickle cell anemia Ulcerative colitis Kidney disease
	Alzheimer's disease (very mild cases only) Angina Chronic fatigue syndrome Chronic obstructive pulmonary disease (COPD) Colon cancer (reduces risk) Dysmenorrhea (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. An herb is primarily supported by traditional use, or the herb or supplement has little scientific support and/or minimal health benefit.

Deficiency Symptoms

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 flaxseed oil, can convert to EPA.

At least four studies have reported a reduced blood level of omega-3 fatty acids in people with depression.^{1, 2, 3, 4}

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.⁵

Dosage

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.⁶

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.⁷ However, in people who do not have cancer, the maximum tolerated amount may be different.

Side Effects

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,^{8, 9} 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.¹⁰

The increase in blood sugar appears to be related in part to the amount of fish oil used.¹¹ Some evidence suggests that adding vitamin E to fish oil may prevent the fish oil-induced increase in blood sugar levels.¹² 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.¹³

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.¹⁴ People who took fish oil and who also took 15 grams of pectin per day were reported to have reductions in LDL cholesterol.¹⁵ 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.¹⁶

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

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. Leaf A, Weber PC. Cardiovascular effects of n-3 fatty acids. N Engl J Med 1988;318:549-57.
9. Malasanos TH, Stacpoole PW. Biological effects of omega-3 fatty acids in diabetes mellitus. Diabetes Care 1991;14:1160-79.
10. Schectman G, Kaul S, Kassebah AH. Effect of fish oil concentrate on lipoprotein composition in NIDDM. Diabetes 1988; 37:1567-73.
11. 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.
12. 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.
13. 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.
14. 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].
15. 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.
16. 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.

Last Review: 09-01-2007

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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 pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires June 2009.