Omega-3 Fatty Acids

Epidemiological and observational studies have suggested that consumption of fish and omega-3 fatty acids has a protective role against several illnesses, including depression. Some clinical data support the hypothesis that omega-3 fatty acids are a potential treatment option for mood disorders. Cold-water fish, including cod, salmon, and mackerel, contain the essential omega-3 fatty acids Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA). Flaxseed, canola oil, and walnuts are also potential dietary sources of these omega-3 fatty acids. Dietary supplements containing fish oil are also widely available. Omega-3 fatty acids help regulate everyday cellular functions in the body that are necessary for good health. DHA is important as a major structural component of cell membranes, while EPA is thought to play an important role in neuronal signal transduction. DHA and EPA are not produced in the body and people can only get these fatty acids through their diet or from nutritional supplements.

Published studies indicate that EPA has some efficacy as an adjunct treatment for mood disorders, particularly for the control of symptoms of depression. However, large-scale, randomized clinical trials are lacking. Several recent review articles and meta-analyses agree that adjunctive treatment with omega-3 fatty acids carries a low risk of side effects and has a beneficial effect on physical health. However, the efficacy on treating mood disorders is not conclusive.

Two clinical trials showed positive outcomes as adjunct treatment for patients with depression that had been refractory to treatment. One study showed longer duration in remission in patients with bipolar disorder. Whether omega-3 fatty acid will prove more useful for acute, long-term or prophylactic purposes has yet to be determined. The mechanism by which omega-3 fatty acids can exert a positive effect on mental health is unknown. Hypotheses include an anti-inflammation effect, by enhancing cell membrane integrity, or by altering signal transduction in nerve cells. The dosage of omega-3 fatty acids used in clinical trials varied widely, from 1 gram to 9.6 grams combined EPA and DHA daily. These studies show that omega-3 fatty acid supplements are generally well-tolerated even at higher doses without significant adverse effects. Trials using pure DHA or EPA alone produced conflicting results.

One study, using pure DHA (2 grams daily) alone, produced no effect. Another study suggested that 1 to 2 grams daily of EPA was equally effective as higher dosages. The optimal doses of EPA and DHA have not yet been determined through clinical trials. Although omega-3 fatty acids are generally well-tolerated, they do have potential side-effects. Omega-3 fatty acids exert a dose-related effect on bleeding time, which may cause a risk of bleeding. Other potential side effects of omega-3 fatty acids include a fishy aftertaste and gastrointestinal disturbances, all of which appear to be mild and dose-dependent. Some fish contain high levels of heavy metals such as mercury, nickel, lead and other toxins when not processed properly. The FDA and the U.S. Environmental Protection Agency (EPA) have issued statements advising women who may become pregnant, women who are pregnant, breastfeeding mothers, and young children to avoid eating some types of fish. However, fish oil supplements satisfy safety standards for potential contaminants, e.g., heavy metals or other toxins. The United States Food and Drug Administration (FDA) recommends consumption of 3 grams of EPA and DHA omega-3 fatty acids each day, with no more than 2 grams per day coming from dietary supplements. Thus, a daily dosage of 1 to 2 grams EPA is considered safe and possibly beneficial as an adjunct treatment in mood disorders, particular in unipolar or bipolar depression.

As with any treatment, this therapy should be monitored by a physician. Many products are available over-the-counter or from the internet in a wide range of prices, from as low as 10 dollars to 50 dollars a bottle, usually for a one-month supply. Variation in prices is mainly due to differences in the distillation process (concentration, purity), higher ratio EPA/DHA (from 1.5:1 to 7:1), and efforts to reduce oxidation (adding small amount of Vitamin E, packaging in an oxygen free environment). Three grades exist: health food grade, pharmaceutical grade, and International Fish Oils Standard (IFOS). The products with 5-star IFOS ratings are the most expensive. However, no existing data suggest that differences in grade correspond to differences in efficacy. In general, people should choose a product from a known or reputable source, such as a trusted brand, with at least 60% combined EPA and DHA per capsule. Capsules with an added antioxidant to reduce lipid peroxidation are recommended. Besides being active oxidation products, peroxidation leads to a fishy after taste, a side effect which becomes particularly intolerable for some people.

Potential Risks

  • May cause prolonged bleeding time and increased bleeding risk especially in patients on anticoagulation therapy, use of NSAID; possibility of increase the risk of GI bleeding when used in combination with SSRI’s.
  • Oxidation of omega-3 FA forming biologically active oxidation products.
  • Possible alters glucose metabolism in diabetics, requires close monitoring and possible adjusting diabetic medications.
  • One case report of hypomania associated with omega-3 fatty acid. B. Question of Heavy Metals and Contaminants
  • Accumulation of traces of heavy metals (mercury, head, nickel, arsenic and cadmium) and other contaminants (PCBs) in the food chains; potentially might be found in less-refined fish oil supplement.
  • From, an independent test in 2006 of fish oils on the US market found that all of the products satisfy safety standards for potential contaminants.
  • IFOS, International Fish Oils Standard, the most stringent current standard fish oils that are molecularly distilled under vacuum, virtually no measurable level of contaminants could be found. C. Other Considerations
  • Some patients unable to tolerate fishy aftertaste.
  • Not acceptable to people who follow vegetarian diet (unfortunately, omega-3 fatty acids from vegetable source convert inefficiently, about 5 to 15%, to EPA and DHA).