Fatty Acid Effective against Depression

A fatty acid found in fish oil can relieve the symptoms of depression in people who have failed to respond to antidepressant medication, according to a report in Archives of General Psychiatry (2002;59:913–9). The results of this study represent an important advance in the treatment of this common and often debilitating condition.

Seventy people with depression that had persisted despite treatment with standard antidepressants were randomly assigned to receive ethyl-eicosapentaenoate (E-EPA), in the amount of 1, 2, or 4 grams per day or a placebo for 12 weeks, in addition to their antidepressant medication. Compared with the placebo group, the group receiving 1 gram of E-EPA per day had a significantly better outcome on each of three different rating scales for depression. The difference between E-EPA and placebo was statistically significant on two of the three rating scales within 4 weeks of the start of treatment, and the advantage of E-EPA over placebo became even more pronounced after 8 and 12 weeks. Sixty-nine percent of the participants treated with 1 gram of E-EPA per day experienced a clinically significant improvement (at least a 50% reduction on the Hamilton Depression Rating Scale) whereas only 25% of those receiving the placebo had clinically significant improvement.

Surprisingly, no statistically significant improvements were seen in the groups treated with the larger amounts of E-EPA (2 and 4 grams per day). No serious side effects were seen, although some people taking 4 grams of E-EPA per day experienced gastrointestinal symptoms.

E-EPA is a chemically modified form of EPA, which occurs naturally in fish oils and which can be manufactured in the body from a precursor molecule found in certain oils such as flaxseed and soybean oil. For reasons that are not clear, depressed people often have subnormal levels of EPA. A deficiency of this fatty acid can impair the functioning of cell membranes, including the membranes of brain cells. EPA also appears to play a role in signal transmission in the brain, an effect that may influence mood. The presumed mechanism of action of E-EPA is fundamentally different than that of conventional antidepressants, which usually work by raising the levels of serotonin or other “chemical messengers.” Consequently, E-EPA therapy offers a new approach to the treatment of depression; one that has the potential to enhance the benefits of prescription drugs, or to be helpful when prescription medications are not.

In the new study, the best results were achieved with the smallest amount of E-EPA tested, whereas the larger amounts tested produced little or no benefit. The authors of the study speculated that taking too much E-EPA might cause an imbalance between the two major classes of essential fatty acids: the omega-3 class (which includes EPA) and the omega-6 class (which includes linoleic and arachidonic acids). Omega-3 and omega-6 fatty acids are both essential for normal brain function, and taking too much of either might lead to a relative deficiency of the other.

It is not known whether taking fish oil would produce the same benefits as those seen with E-EPA. Fish oil contains a mixture of fatty acids, some of which might conceivably interfere with the effect of the EPA. In addition, it is possible that the ethyl molecule, which is added to EPA to make E-EPA, somehow improves the transport or utilization of EPA. Unfortunately, E-EPA is not widely available at the present time. One gram of EPA is contained in approximately 5.5 grams of fish-oil concentrate or 10 grams (approximately 2 teaspoons) of cod liver oil.

Alan R. Gaby, MD, an expert in nutritional therapies, testified to the White House Commission on CAM upon request in December 2001. Dr. Gaby served as a member of the Ad-Hoc Advisory Panel of the National Institutes of Health Office of Alternative Medicine. He is the author of Preventing and Reversing Osteoporosis (Prima, 1994), and co-author of The Natural Pharmacy, 2nd Edition (Healthnotes, Prima, 1999), the A–Z Guide to Drug-Herb-Vitamin Interactions (Healthnotes, Prima, 1999), Clinical Essentials Volume 1 and 2 (Healthnotes, 2000), and The Patient’s Book of Natural Healing (Prima, 1999). A former professor at Bastyr University of Natural Health Sciences, in Kenmore, WA, where he served as the Endowed Professor of Nutrition, Dr. Gaby is the Chief Medical Editor for Healthnotes, Inc.

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