Other dietary considerations

It is important to consider the nutrients which can ultimately influence omega-3 status. Among them, four important dietary factors also relate to MDD: zinc, selenium, folic acid and dietary antioxidants. A number of studies have shown that zinc levels are lower among patients with depression and a recent study found that 25 mg zinc supplementation may improve depressive symptoms [57]. Interestingly, 25 mg of zinc supplemented for two months has also been shown to significantly increase omega-3 status in the plasma phospholipids at the expense of saturated fat [58]. Lowered levels of selenium have been associated with negative mood scores in at least 5 studies [59]. Selenium plays a significant role in the human antioxidant defense system. In addition, selenium deficiency can interfere with the normal conversion of ALA into EPA and DHA, and results in an increase in the omega-6:omega-3 ratio [60].

Regarding folic acid, a growing body of research has documented the low levels of folic acid among patients with depression [61]. In addition, there are small clinical trials showing a beneficial effect of folic acid in depression, and its ability to enhance the effectiveness of antidepressant medications at just 500 mcg [61,62]. It is of relevance here because folic acid has been shown to increase omega-3 status when supplemented, and decrease omega-3 status when it is in deficiency in the animal model [63]. In addition, a folic acid deficient diet can enhance lipid peroxidation [64].

In patients with MDD there are in fact signs of oxidative stress and lipid peroxidation, and antidepressant medications may reverse the severity of oxidative stress in depressed patients [65]. A recent human study found that depressive symptoms are independently correlated with lipid peroxidation [66]. Patients with obsessive compulsive disorder (OCD) and co-morbid depression have higher levels of lipid peroxidation than those with OCD alone [67]. Dietary antioxidants are known to influence the antioxidant defense system, and new research suggests that dietary antioxidants can influence omega-3 status. Specifically, a diet devoid of antioxidants lowered essential fatty acid levels in the plasma of trained athletes, even though the amount and types of fats were not altered [68]. Omega-3 fatty acids have been shown to decrease lipid peroxidation in vivo [69], and antioxidant supplementation can prevent the negative influence of saturated fat on BDNF levels and cognitive function in animals [70].

Conclusion

While far from robust, there is enough epidemiological, laboratory and clinical evidence to suggest that omega-3 fatty acids may play a role in certain cases of depression. Fish oil supplements are well tolerated, and have been shown to be without significant side effects over large scale, 3-year research [71]. Generally, omega-3 supplements are inexpensive, which makes them an attractive option as an adjuvant to standard care. At this time, however, the routine use of omega-3 fatty acids for the treatment of MDD cannot be recommended.

The research reviewed here shows that the data is far from unequivocal. Large trials are warranted to truly determine efficacy, appropriate dosing and the potentially active components – EPA, DHA, or both. It is also clear that omega-3 intake occurs in dietary context, one that includes other important nutrients. Future research should consider the influence of zinc, selenium, folic acid and dietary antioxidant status to determine who may be a successful candidate for omega-3 supplementation.

In the meantime, given the current excess intake of omega-6 rich oils, and the emerging research on omega-3 fatty acids and MDD, all mental health professionals should at least ensure adequate intake of omega-3 fatty acids among patients with MDD. The current average North American intake of EPA and DHA is approximately 130 mg per day, well short of the minimum 650 mg recommended by the international panel of lipid experts [6]. While it is not necessary for mental health professionals to become clinical nutritionists, consideration of a patient's dietary quality may be worthwhile. Hopefully future research will determine if dietary modifications or supplementation can influence the outcome of standard care.

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Lipids in Health and Disease 2004, 3:25doi:10.1186/1476-511X-3-25

The electronic version of this article is the complete one and can be found online at: http://www.lipidworld.com/content/3/1/25

© 2004 Logan; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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