Docosahexaenoic acid (DHA) is a 22-carbon omega-3 fatty acid (22:6n-3) that is highly concentrated in the brain, retina, and spermatozoa (Gerster 1998). Some DHA is derived from its parent compound alpha-linolenic acid (ALA) but the biotransformation process is slow, unreliable, and does not increase levels of DHA sufficiently to allow for normal biochemical functioning (Gerster 1998; Gerster 1995; Uauy-Dagach and Valenzuela 1992). Therefore, preformed DHA must be consumed in the diet.

DHA is essential for neural and visual development during the first six months of life (Cunnane et al. 2000; Horrocks and Yeo 1999). Low DHA levels during this critical phase can affect cognitive and visual functioning in children (Birch et al. 2000). Deficiency of this long-chain fatty acid has also been associated with attention-deficit hyperactivity disorder (ADHD) in children (Burgess et al. 2000; Stevens et al. 1995). Adults also require DHA for normal brain function; insufficient levels of DHA have been associated with depression and Alzheimer's disease (Edwards et al. 1998; Horrocks and Yeo 1999; Peet et al. 1998).

• Cold water fatty fish: wild salmon (not farm raised), tuna (bluefin tuna have up to five times more DHA than other tuna variants), mackerel, sardines, shellfish, herring (Broadhurst et al. 1998; Gamez-Meza et al. 1999; Horrocks and Yeo 1999; Rice 1996) 
• Some organ meats: liver and brain (USDA 1999) 
• Lower levels of DHA found in eggs (USDA 1999) 

DHA is a 22-carbon omega-3 fatty acid (22:6n-3 fatty acid).

Commercial products include (Ringer et al. 1998):

• Fish oil capsules that contain DHA plus EPA
• DHA extracted from microalgae (contains no EPA) 

Some products may also contain vitamin E to prevent oxidation of the oil in the capsule to maintain freshness through the expiration date. Follow the directions on product labels for both dosage information and storage requirements. Some products may require refrigeration. Do not use products beyond their expiration date.

Attention-Deficit Hyperactivity Disorder (ADHD): In one study, it was observed that 53 children with ADHD had significantly lower n-3 fatty acid concentrations, particularly DHA, compared to 43 healthy controls; the reason for this lower concentration is unknown (Stevens et al. 1995). In addition, researchers have found that lower concentrations of n-3 fatty acids may also be associated with significantly more learning, health, and sleep problems in children (Burgess et al. 2000)

Depression: Epidemiological studies suggest that low n-3 fatty acid intake, particularly of DHA, may correlate with increasing rates of depression (Hibbeln and Salem 1995). Studies have shown that depressed patients have lower serum and platelet levels of DHA compared to healthy controls (Conquer and Holub 1996). More research is needed to confirm whether there is an association between low DHA levels and depression. In addition, studies should investigate whether DHA supplementation alleviates symptoms of depression.

Heart Disease: DHA supplementation significantly enhanced the DHA status of vegetarian subjects in addition to lowering both total cholesterol:HDL-cholesterol and LDL-cholesterol:HDL-cholesterol ratios (Conquer and Holub 1996). Additional carefully controlled clinical trials may be warranted.

Infant Development: DHA plays a crucial role in the growth and development of both the central nervous system and retinal function in infants (Xiang et al. 2000). Supplementation with DHA may offer benefits to both preterm and healthy full-term infants (Birch et al. 2000; Carlson 1996; Simopoulos 1991; Uauy and Hoffman 2000). Breast milk contains DHA, but because most infant formulas available in the U.S. are lacking DHA, some researchers suggest that DHA should be provided to formula-fed infants (Birch et al. 2000). For this reason, a group of nutrition experts, under the auspices of the International Society for the Study of Fatty Acids and Lipids (Issfal), have issued recommendations for adequate intakes of n-3 fatty acids in infant formulas and diets (Simopoulos et al. 1999). According to these recommendations, pregnant and lactating women should consume 300 mg/day of DHA. Adequate intakes for infants on formula diets should be 0.35% DHA.

Dietary recommendations: 2 to 3 servings of fatty fish per week, which corresponds to 1.25 g EPA and DHA per day (Gerster 1998)

Fish oil supplements: 3 to 4 g standardized fish oils per day, which is the equivalent of 2 to 3 servings of fatty fish per week (Gerster 1995)

Algal-derived DHA supplements: 200 mg per day (Ringer et al. 1998)

Side effects observed in clinical trials using fish oil capsules include loose stools, abdominal discomfort, and unpleasant eructation (Robinson et al. 1994). Although it does not appear to pose a clinical concern, fish oil supplements may also cause a slight prolongation of bleeding time (Robinson et al. 1994; Simopoulos 1991). These effects may be avoided by using DHA supplements derived from algae sources (Conquer and Holub 1996).

Some sources say that supplements containing eicosapentaenoic acid (EPA) are not recommended for infants or small children because they offset the balance between DHA and EPA during this phase of development (Schmidt 1997). By inference, it would be wise to exercise caution in pregnant women as well.

Consumption of fish oils may increase antioxidant requirements in the body; some recommend that individuals taking fish oil supplements should take extra vitamin E (Meydani 1992). Caution should likely be exercised, though, when using this combination in patients with bleeding disorders as well as in patients on anticoagulant or antiplatelet medications.

In a double-blind, randomized, crossover study, six healthy volunteers were given aspirin (40 mg/day) combined with omega-3 fatty acids (5.3 g) (Iacoviello et al. 1992). The combination lowered the fibrinolytic response to venous occlusion and could be helpful in the treatment of some forms of coronary artery disease.

In a double-blind, randomized, placebo-controlled study, 28 cardiac transplant patients received an immunosuppressive regimen consisting of cyclosporine (6 mg/kg body weight), azathioprine (2mg/kg/day), and prednisolone (0.2 mg/kg/day) with either omega-3 fatty acids (4 g/day: 46.5% eicosapentaenoic acid (EPA) and 37.8% DHA) or placebo (Andreassen et al. 1997). Both treatment groups also received alpha-tocopherol (3.7 mg). Treatment commenced 4 days postoperatively and continued for 6 months, with blood levels of cyclosporine remaining stable for both groups. After 6 months, systolic blood pressure decreased in the omega-3 group and increased in the control group. Diastolic blood pressure increased in both groups; this increase was statistically significant in the control group. An earlier study in 20 cardiac transplant patients receiving omega-3 fatty acids (3 g/day: EPA and DHA) in conjunction with cyclosporine and antihypertensive medications for 12 weeks supports these findings (Ventura et al. 1993). The mechanism of action may be due to decreasing systemic vascular resistance. The combination of omega-3 fatty acids with cyclosporine may show promise as effective hypertension prophylaxis in cardiac transplant patients.

Another placebo-controlled, prospective, double-blind, randomized study involving 26 patients was conducted to evaluate the effects of omega-3 fatty acids on cyclosporine-induced nephrotoxicity (Badalamenti et al. 1995). Liver transplant patients were given omega-3 fatty acids (12 g/day: 18% EPA and 12% DHA) or placebo while on cyclosporine therapy. After 2 months, renal plasma flow increased by 22%, the glomerular filtration rate (GFR) increased by 33%, renal blood flow increased by 17%, and renal vascular resistance decreased by 20% for patients receiving omega-3 fatty acids. No changes were noted in the control group.

Kidney transplant recipients also benefited from supplementation with omega-3 fatty acids (6 g: 30% EPA and 20% DHA) during cyclosporine therapy in a double-blind, placebo-controlled, prospective, randomized clinical trial involving 21 subjects (Homan van der Heide et al. 1990). After 3 months, blood pressure decreased in the omega-3 group, and GFR and renal plasma flow increased by 20.3% and 16.4%, respectively. However, another double-blind, randomized, controlled study with 25 renal transplant patients did not demonstrate any clinically significant benefits derived from one year of treatment with omega-3 fatty acids (6 g: 30% EPA, 20% DHA) (Kooijmans-Coutinho et al. 1996).

Omega-3 fatty acids (5 and 10 mL/kg body weight) significantly protected the gastric mucosa against ulcers induced by NSAIDs, reserpine, and necrotizing agents in rats (Al-Harbi et al. 1995).

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