Docosahexaenoic AcidWhat does it do? Omega-3 fatty acids, such as docosahexaenoic acid (DHA), belong to the class of nutrients called essential fatty acids. DHA has been shown to reduce levels of blood triglycerides. High triglycerides are linked with heart disease in most, but not all, research. DHA alone appears to be just as effective as fish oils (which contain both DHA and EPA) in beneficially lowering triglyceride levels in people at risk for heart disease.1 In part, this may be because some DHA is converted to EPA in the body.2 Unlike EPA, however, DHA may not reduce excessive blood clotting.3 DHA appears to be essential for normal visual and neurological (nervous system) development in infants.4 5 However, DHA supplementation did not affect the development of visual acuity in formula-fed infants in a double-blind trial.6 Nevertheless, other double-blind research links DHA supplementation in premature infants to better brain functioning.7 The effects of DHA on the nervous system may well extend beyond infancy. Young adults given 1.5–1.8 grams DHA per day showed less evidence of aggression in response to mental stress, compared with people in the control group in a double-blind trial.8
DHA supplementation in healthy young men has been shown to decrease the activity of immune cells, such as natural killer (NK) cells and the cells that regulate inflammation responses in the body.9 The anti-inflammatory effects of DHA may be useful in the management of autoimmune disorders; however, such benefits need to be balanced with the potential for increased risk of infections.DHA deficiency plays an important role in a group of congenital diseases called peroxisomal disorders, which damage the protective covering (myelin) around nerves. Although rare, the worst of these disorders (i.e., Zellweger’s syndrome) is life-threatening within the first year of life. Daily oral supplementation of 100–600 mg of DHA has been shown to increase blood levels of DHA, to protect myelin, and to improve the signs and symptoms of these potentially devastating disorders.10 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):Who is likely to be deficient? Premature infants who are not breast-fed are often DHA-deficient.11 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.12 Similarly, preliminary evidence shows that children with attention deficit disorder (ADD) have low DHA levels. However, no evidence demonstrates that DHA supplementation improves ADD.13 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.14 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.15 16 17 18How 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),19 20 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,21 though this may simply be due to small increases in weight resulting from high dietary fish oil.22 While DHA combined with EPA from fish oil consistently lowers triglycerides, it occasionally increases LDL cholesterol.23 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.24 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.25 However, animal researchers have reported that the oxidative damage caused by DHA alone was not prevented with vitamin E supplementation.26 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.27 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.28 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.29 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.30 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.31 To date, this report has not been confirmed by other researchers. To the contrary, test tube studies report that DHA is toxic to cancer cells32 and may someday be considered as an adjunct to conventional treatment for cancer.33 Similarly, animal studies suggest that DHA may inhibit cancer.34
At the time of writing, there were no well-known drug interactions with docosahexaenoic acid.
1. Davidson MH, Maki KC, Kalkowski J, et al. Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: A randomized, double-blind, placebo-controlled trial. J Am Coll Nutr 1997;16:236–43.
2. Conquer JA, Holub BJ. Supplementation with an algae source of docosahexaenoic acid increases (n-3) fatty acid status and alters selected risk factors for heart disease in vegetarian subjects. J Nutr 1996;126:3032–9.
3. Nelson GJ, Schmidt PS, Bartolini GL, et al. The effect of dietary docosahexaenoic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans. Lipids 1997;32:1129–36.
4. Gibson RA, Neumann MA, Makrides M. Effect of dietary docosahexaenoic acid on brain composition and neural function in term infants. Lipids 1996;31:177S–81S.
5. Makrides M, Neumann MA, Gibson RA. Is dietary docosahexaenoic acid essential for term infants? Lipids 1996;31:115–9.
6. Makrides M, Neumann MA, Simmer K, Gibson RA. A critical appraisal of the role of dietary long-chain polyunsaturated fatty acids on neural indices of term infants: a randomized, controlled trial. Pediatrics 2000;105:32–8.
7. Werkman SH, Carlson SE. A randomized trial of visual attention of preterm infants fed docosahexaenoic acid until nine months. Lipids 1996;31:91–7.
8. Hamazaki T, Sawazaki S, Itomura M, et al. The effect of docosahexaenoic acid on aggression in young adults. A placebo-controlled double-blind study. J Clin Invest 1996;97:1129–33.
9. Kelley DS, Taylor PC, Nelson GJ, et al. Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men. Lipids 1999;34:317–24.
10. Martinez M, Vazquez E. MRI evidence that docosahexaenoic acid ethyl ester improves myelination in generalized peroxisomal disorders. Neurology 1998;51:26–32.
11. 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].
12. 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.
13. 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.
14. Martinez M, Vazquez E. MRI evidence that docosahexaenoic acid ethyl ester improves myelination in generalized peroxisomal disorders. Neurology 1998;51:26–32.
15. 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.
16. 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.
17. 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.
18. 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.
19. Leaf A, Weber PC. Cardiovascular effects of n-3 fatty acids. N Engl J Med 1988;318:549–57.
20. Malasanos TH, Stacpoole PW. Biological effects of omega-3 fatty acids in diabetes mellitus. Diabetes Care 1991;14:1160–79.
21. Schectman G, Kaul S, Kassebah AH. Effect of fish oil concentrate on lipoprotein composition in NIDDM. Diabetes 1988;37:1567–73.
22. 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.
23. 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].
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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.
31. 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.
32. 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.
33. 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.
34. 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.