Some feedbacks from the International Society of Nutritional Psychiatry Research (ISNPR) about safety concerns of DHA...

Any impression about any research paper showing possible negative effects related to high dose of DHA (Kuan-Pin, Taichung)?

From Felice (Australia): There seems to be a U-shaped relationship between DHA and depression (Jacka et al. BJN in press & Freeman at the PUFA newsletter - http://www.fatsoflife.com/pufa-december-2012/nutrition-omega-3-fatty-acids-and-depression/)

From Joe (Maryland): Be aware that for major depression the recent metanalyses indicate that preparations too less EPA (less than 60%) are not effective for reducing depressive symptoms while there is a dose response for EPA (Lin et al. Molecular Psychiatry 2012; Martins et al. Molecular Psychiatry 2012 - http://www.ncbi.nlm.nih.gov/pubmed/22824812). This may not however apply to reduction of ADHD or disruptive symptoms. Refer to a nice reference for safety of n-3 HUFAs from the Norwegian Food Safety Committee (2011).

From David (Boston): There is a concern about bleeding from doses greater than 3g/day but this is mostly theoretical.

From Chih-Chiang (Taipei): No impression that higher DHA will have severe adverse effects in reviewing the omega 3 papers in cognition. However, some suggest the ratio of ALA/LA is 1:4 will have better effects on learning in animal study (Yehuda et al, Neurobiol Aging 2002; Jadoon & Chiu J Affect Dis 2012).

From Vicent (Valencia): There is some recent, preclinical evidence for harmful effects of high-dose DHA on the brain (Pan et al Brain Research 2011). And they speculated that these bidirectional actions of DHA on cognition might be explained by the effects of DHA on endocannabinoid and CB1 receptor levels. Also refer to an interesting expert discussion raising several controversies I guess somehow related to your question (Watkins et al J Mol Neuroscience 2007). Lastly, there is the Eritsland´s review on safety of PUFAs, which includes the theoretical risk of bleeding (pp 198-9) mentioned by David.

From Gene (Ohio): One thing is that you need enough antioxidants on board to handle the omega-3 load. Polyunsaturated fatty acids are “drying oils” formerly used to make paint and varnish because on exposure to oxygen they harden into a film. So potential toxicity could come from a high dose without adequate vitamin E or other antioxidant.

From Michael (Bangkok): Why fish oils may not always be adequate treatments for depression or other inflammatory illnesses: DHA, an omega-3 polyunsaturated fatty acid, induces a Th-1-like immune response (Maes et al Neuroendocrinol Letters 2007). 

From Bronwyn (Australia): DHA-rich supplements appear to be less effective than EPA-rich supplements for the treatment of depression.  As far as I know,  there are no RCTs that report adverse effects of DHA.  However there is a proposition that DHA may oppose the beneficial actions of EPA -  It would be worthwhile looking more closely at the arguments presented by Sublette et al (2011) in their meta-analysis and also Maes et al (Neuroendocrinology Letters, 2007) propose that DHA can induce inflammatory markers.

From Natalie (Australia): Ours published last year that compared high DHA and high EPA supplements, finding benefits with both combined although superior for DHA. Although high EPA or ethyl-EPA has been reportedly effective in some studies with depression, we cannot rule out the effect of DHA. I also discuss this in our discussion (Sinn et al BJN 2012).

From Kuan-Pin (Taichung): I like to follow Natalie's comments and the paper. I also agree that it might be to early to give up DHA. Our meta-analyses on depression and dementia also showed DHA deficits (Lin et al Biol Psychiatry 2010; Lin et al JCP 2012). In addition, we found that DHA, but not EPA, deficit is associated with IFN-induced depression (Su et al Biol Psychiatry). I think it is worthy to investigate if DHA and EPA could target different dimensions of symptoms. 

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