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Docosahexaenoic Acid

Also indexed as: DHA

Illustration

Docosahexaenoic acid (DHA), an omega-3 fatty acid, belongs to the class of nutrients called essential fatty acids.

Where is it found?

Cold-water fish, such as mackerel, salmon, herring, sardines, black cod, anchovies, and albacore tuna, are rich sources of DHA and EPA. Similarly, cod liver oil contains large amounts of DHA and EPA. Certain microalgae contain DHA and are used as a vegetarian source of this nutrient in some supplements. Most fish oil supplements contain 12% DHA.

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

Science Ratings Health Concerns
3Stars

Childhood intelligence

High blood pressure

High triglycerides

Peroxisomal disorders

Rheumatoid arthritis

Stress
2Stars

Depression

Epilepsy (given in combination with EPA)

Lupus

Psoriasis
1Star

Angina

Chronic obstructive pulmonary disease (COPD)

Dysmenorrhea (painful menstruation)

Migraine headaches

Osteoarthritis

Type 2 diabetes
3Stars Reliable and relatively consistent scientific data showing a substantial health benefit.
2Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1Star For an 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?

Premature infants who are not breast-fed are often DHA-deficient.1 A link has appeared between DHA deficiency and Alzheimer’s disease; however, no evidence at this time indicates that supplementation with DHA will help Alzheimer’s patients.2 Similarly, preliminary evidence shows that children with attention deficit disorder (ADD) have low DHA levels. However, no evidence demonstrates that DHA supplementation improves ADD.3 Preliminary evidence suggests that people with a variety of rare but related congenital diseases (Zellweger’s syndrome, neonatal adrenoleukodystrophy, and infantile Refsum’s disease) may be DHA-deficient, and may even benefit from DHA supplementation.4 Many doctors believe the diets of most people eating a Western diet do not provide optimal amounts of omega-3 fatty acids.

At least four studies have reported a reduced blood level of omega-3 fatty acids in people with depression.5 6 7 8

How much is usually taken?

Most healthy people do not supplement with fish oil containing DHA or vegetarian sources of DHA. The level of DHA given to premature infants who are not breast-fed should be determined by a pediatrician. Much of the research in adults has been based on 1–3 grams per day of DHA from fish oil, although higher levels have been taken when isolated DHA from microalgae sources is used.

Because cod liver oil contains large amounts of vitamin A and vitamin D, women who are or who could become pregnant should consult a doctor before taking cod liver oil. Adults should make sure the total amount of vitamin A and vitamin D from cod liver oil and other supplements does not exceed 25,000 IU (7,500 mcg) per day for vitamin A (15,000 IU per day for those over age 65) and 800 IU per day for vitamin D, unless they are being supervised by a doctor.

Are there any side effects or interactions?

While those with heart disease and diabetes often benefit from fish oil (the primary source of DHA in the diet),9 10 such people should check with their doctor before taking more than 3 or 4 grams of fish oil per day for several months. Elevations in blood sugar have sometimes been reported,11 though this may simply be due to small increases in weight resulting from high dietary fish oil.12 While DHA combined with EPA from fish oil consistently lowers triglycerides, it occasionally increases LDL cholesterol.13

Fish oil is easily damaged by oxygen, so small amounts of vitamin E are often included in fish oil supplements to prevent such oxidative damage.14 Doctors often recommend that people who supplement with fish oil or DHA take vitamin E supplements to protect EPA and DHA within the body from oxidative damage. Some evidence indicates that vitamin E may be protective against oxidative damage caused by fish oil.15 However, animal researchers have reported that the oxidative damage caused by DHA alone was not prevented with vitamin E supplementation.16 The level of oxidative damage caused by DHA has not been shown to result in significant health problems.

Some evidence suggests that adding vitamin E to EPA/DHA may prevent the fish oil-induced increase in serum glucose.17 Similarly, the impairment of glucose tolerance sometimes caused by the omega-3 fatty acid has been prevented by the addition of half an hour of moderate exercise three times a week.18 The effect of DHA by itself on glucose levels has not been adequately studied.

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.19 This suggests that pectin may overcome the occasional problem of increased LDL cholesterol from fish oil supplementation. The LDL cholesterol-raising effect of EPA and DHA may also be successfully prevented by taking garlic supplements (or presumably adding garlic to the diet) along with EPA and DHA.20 Adding pectin or garlic when people supplement with DHA by itself has yet to be studied.

According to a report in a Japanese medical journal, three people at high risk for colon cancer developed a variety of cancers after one to two years of supplementation with DHA.21 To date, this report has not been confirmed by other researchers. To the contrary, test tube studies report that DHA is toxic to cancer cells22 and may someday be considered as an adjunct to conventional treatment for cancer.23 Similarly, animal studies suggest that DHA may inhibit cancer.24

At the time of writing, there were no well-known drug interactions with docosahexaenoic acid.

References:

1. Crawford MA, Costeloe K, Ghebremeskel K, et al. Are deficits of arachidonic and docosahexaenoic acids responsible for the neural and vascular complications of preterm babies? Am J Clin Nutr 1997;66(4Suppl):1032S–41S [review].

2. Soderberg M, Edlund C, Kristensson K, et al. Fatty acid composition of brain phospholipids in aging and in Alzheimer’s disease. Lipids 1991;26:421–5.

3. Stevens LJ, Zentall SS, Deck JL, et al. Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder. Am J Clin Nutr 1995;62:761–8.

4. Martinez M, Vazquez E. MRI evidence that docosahexaenoic acid ethyl ester improves myelination in generalized peroxisomal disorders. Neurology 1998;51:26–32.

5. 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.

6. 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.

7. 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.

8. Maes M, Christophe A, Delanghe J, et al. Lowered omega3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Psychiatry Res 1999;85:275–91.

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

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

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

12. 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.

13. 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 [abstract].

14. 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.

15. Wander RC, Du S-H, Ketchum SO, Rowe KE. Effects of interaction of RRR-alpha-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.

16. Kubo K, Saito M, Tadokoro T, Maekawa A. Changes in susceptibility of tissues to lipid peroxidation after ingestion of various levels of docosahexaenoic acid and vitamin E. Br J Nutr 1997;78:655–69.

17. 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.

18. 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.

19. 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.

20. 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.

21. Akedo I, Ishikawa H, Nakamura T, et al. Three cases with familial adenomatous polyposis diagnosed as having malignant lesions in the course of a long-term trial using docosahexanoic acid (DHA)-concentrated fish oil capsules. Jpn J Clin Oncol 1998;28:762–5.

22. Kafrawy O, Zerouga M, Stillwell W, Jenski LJ. Docosahexaenoic acid in phosphatidylcholine mediates cytotoxicity more effectively than other omega-3 and omega-6 fatty acids. Cancer Lett 1998;132:23–9.

23. Bougnoux P, Germain E, Hubert B, et al. Cytotoxic drugs efficacy correlates with adiposte tissue docosahexanenoic level in locally advanced breast carcinoma. Br J Cancer 1999;79:1765–9.

24. de Bravo MG, de Antueno RJ, Toledo J, et al. Effects of an eicosapentaenoic and docosahexaenoic acid concentrate on a human lung carcinoma grown in nude mice. Lipids 1991;26:866–70.
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