The Evolving Omega-3 Fatty Acid Story: The Icing on the Cake (And Why It Shouldn’t Be Eaten)

October 3, 2011 · Posted in Current Treatments 

sources of omega-3 fatty acidsOmega-3 fatty acids are important for brain development and function and are essential to the human diet since they cannot be synthesized by the body. Omega-3 fatty acids are derived from canola oil, walnuts, flax seed oil, leafy vegetables, and especially fish. The main omega-3 fatty acids include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). They have anti-inflammatory effects, unlike omega-6 fatty acids, which are pro-inflammatory. The omega-6 fatty acids come from soy, peanuts, corn oil, and meats, and are associated with increases in obesity, myocardial infarction, and stroke.

In a recent review of the literature, John Davis and Joe Hiblen found that diets that include high levels of omega-3 fatty acids are associated with decreased incidence of depression, suicide, and cardiovascular disease. The researchers performed a meta-analysis of all the prospective depression treatment studies of omega-3 fatty acids compared to placebo. They found that EPA had antidepressant effects in humans, with moderate effect size and a high degree of statistical significance. DHA, however, did not appear to have an antidepressant effect, and pure DHA was even associated with some worsening of depression.

Editor’s note: This meta-analysis helps clarify some of the ambiguities in the literature about the antidepressant efficacy of the omega-3 fatty acids, clarifying that EPA alone is an effective antidepressant. The one study that did not find antidepressant effects with EPA was carried out by the Bipolar Collaborative Network, in which I am an investigator. Our study, published in an article by Keck et al., showed that 6g of EPA was not significantly more effective than placebo in bipolar depression or in rapid cyclers. However, there is some indication that 6g may be too high a dose of EPA, and most of the recommendations now suggest using 1-2g of either EPA or an EPA/DHA combination.

There have been some positive studies of omega-3 fatty acids in schizophrenia including, most impressively, an article published in Australia last year that indicated that omega-3 fatty acids compared with placebo decreased the rate of conversion from prodromal psychotic symptoms to full-blown schizophrenia.

Further support for the role of omega-3 fatty acids in brain development has been found by Jing X. Kang, who studied an animal model in which some animals were genetically engineered to be deficient in DHA. Kang found that the non-engineered control animals had more production of new neurons and more robust neurons (with more neurite formation, greater spine density, and more myelin) and, most importantly, these animals had better spatial memory than the DHA-deficient animals.

In a recent talk about omega-3s, John Davis cited similar evidence from a family study of young offenders. The study showed that low amounts of omega-3 fatty acids in a mother’s diet were associated with decreased coordination and decreased IQ levels in her children, particularly in male offspring.

These findings are consistent with a report by Staci Bilbo et al. in the Journal of the Federation of American Societies for Experimental Biology last year that showed that maternal diet and in utero transfer of nutrient substances can have long-term effects on brain development and inflammation in rodents. Bilbo reported that adult offspring of mothers who had high-fat diets while pregnant had increased brain inflammation and behavioral abnormalities compared with those whose mothers had normal diets. This occurred despite the animals beginning normal diets after weaning.

Editor’s Note: Together, these studies suggest a variation on the old saw “you are what you eat.” You may instead be “what your mother ate,” because apparently early dietary influences can have long-term effects on the set point of brain inflammation, depressed and anxious behavior, and obesity in adults.

The ratio of pro-inflammatory omega-6 fatty acids to anti-inflammatory omega-3 fatty acids has dramatically changed with the history of civilized humans. Early in the agricultural revolution there appears to have been a 1:1 ratio of omega-6 to omega-3 fatty acids in the general diet. However, in the 1950s this became a 10:1 ratio and in the 1980s to 1990s it became a 20:1 ratio. This marked change in dietary intake may be one of the factors leading to the current pandemic of obesity, particularly in the U.S. and in other developed countries in which high fat diets predominate.

Since there is a close link between depression and obesity, it appears prudent for those at high risk for depression and bipolar disorder (who may be at even greater risk for obesity than the general population) to attempt to limit dietary intake of fats and proinflammatory omega-6 fatty acids.

There appears to be a progression of influences combining to bring about obesity in those with bipolar disorder. This might start with initial dietary habits (and as noted above, even the maternal diet conveyed to the fetus in utero). Then depression and weight gain often co-occur (potentially because of both increased appetite and decreased activity in those with atypical depression). Finally, weight gain can result from the number of psychotropic medications with weight gain vulnerability. In the studies of Susan McElroy and colleagues, one of the risk factors for overweight and obesity in outpatients with bipolar disorder was the number of prior exposures to psychotropic medications that increase the risk of weight gain.

As reviewed at right, not all treatments for bipolar illness increase risk of weight gain, so choosing drugs with less weight gain potential is beneficial for those patients at high risk for overweight and obesity.

Another option to limit weight gain from medications is the use of drugs with weight loss side effects to counteract those with weight gain effects. Drugs with weight loss side effects include the anticonvulsants topiramate (Topamax) and zonisamide (Zonegran), both of which are associated with weight loss in patients with seizure disorders and affective disorders. The anti-diabetic drug metformin also helps limit weight gain when used in conjunction with atypical antipsychotics while helping to sensitize insulin receptors and treat insulin resistance in type II diabetes.


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