Autism and altered levels of essential fatty acids

Brigandi et al. 2015. Int. J. Mol. Sci. 16: 10061-10076.

A quote to begin this post is taken from the paper by Sarah Brigandi and colleagues [1] (open-access available here): "Our study demonstrates an alteration in the PUFA [polyunsaturated fatty acids] profile and increased production of a PUFA-derived metabolite in autistic patients, supporting the hypothesis that abnormal lipid metabolism is implicated in autism."

The Brigandi results were based on the analysis of blood samples for fatty acid content for "121 autistic patients and 110 non-autistic, non-developmentally delayed controls, aged 3-17." Participants with autism met DSM-IV criteria and CARS scores for autism although did not include those "on the broader autism spectrum" diagnosed with Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) for example.

Using various analytical techniques including gas chromatography and liquid chromatography-mass spectrometry (LC-MS), authors assayed for various fatty acids (saturates, monosaturates and polyunstaurates) and also levels of that "PUFA-derived metabolite" prostaglandin E2 (PGE2) a "pro-inflammatory AA [arachidonic acid] metabolite" that "increases the risk of neuroinflammation which can lead to excessive production of reactive oxygen species (ROS)." For some further background you might wish to have a look at a previous occasion that PGE2 has been discussed on this blog (see here) and another occasion covering ROS (see here).

Results: "a number of PUFA, mainly AA and DHA [docosahexaenoic acid], were significantly lower in autistic individuals than controls." DHA, by the way, is known as an omega-3 fatty acid, so called because of the specific positioning of a chemical double bond in its chemical arrangement. Alongside another omega-3 fatty acid called eicosapentaenoic acid (EPA), this is the stuff that is usually listed as the active ingredient in the various fish oil supplements that you find dotted around these days.

When it came to levels of PGE2, Brigandi et al report some really quite interesting results albeit based on the analysis of considerably smaller participant groups (autism n=20 and controls n=20). So: "All control samples were under the detection limit for PGE2 detection of <0.71 ng/mL." The same however could not be said for the autism group where "PGE2 levels were detected in 9 of the 20 plasma samples from autistic individuals, ranging from 1.21 to 3.91 ng/mL." This was translated as a "marked difference" between the groups.

Just before I head into what these results *might* mean, it's worthwhile pointing out a few caveats surrounding the Brigandi study. As the authors report: "we did not conduct an age-matched nor gender-matched analysis between the autistic and control groups." Fair enough, so we can't rule out those factors impacting on the results obtained. Further: "Fasting was not a requirement prior to blood draws" and authors "did not collect dietary information from study participants." This last point in particular combines with a perhaps a too sweeping generalisation from the authors that they "do not expect dietary differences between the groups to be a primary explanation" for some of their results. Diets can and do differ when it comes to autism [2] and sometime in the most serious ways (see here). One needs to be very mindful of that fact more so when it comes to actual fat intake in cases of autism [3].

That all being said, I do think that these results invite much further study of fatty acids and autism (some autism) on top of quite a bit of other research in this area [4]. As per my previous posts in this area, the collected data so far on supplementing fatty acids in cases of autism is not exactly 'concrete' in terms of effectiveness (see here). Whereas an important comorbidity noted in quite a few cases of autism, ADHD (attention-deficit hyperactivity disorder) in whole or in part, is enjoying some rather more positive findings (see here and see here) indeed, even more generally [5], core autism does not seem to be benefiting as much from the supplementation side of things. It could be worthwhile focusing less on syndromes and more on symptoms [6] when it comes to supplementation as per the idea that fatty acids might be [partially] linked to things like reading ability (see here) or even with critical periods of requirement [7] in mind but I'd like to see a lot more science done on this first. That also includes looking at other potential biological correlates too [8]...

Maybe the VIDOMA study will provide a little more insight?

Music: Sheppard - Geronimo.

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[1] Brigandi SA. et al. Autistic Children Exhibit Decreased Levels of Essential Fatty Acids in Red Blood Cells. Int J Mol Sci. 2015 May 4;16(5):10061-10076.

[2] Kuschner ES. et al. A preliminary study of self-reported food selectivity in adolescents and young adults with autism spectrum disorder. Research in Autism Spectrum Disorders. 2015; 15-16: 53-59.

[3] Marí-Bauset S. et al. Fat intake in children with autism spectrum disorder in the Mediterranean region (Valencia, Spain). Nutr Neurosci. 2015 May 28.

[4] Bell JG. et al. Red blood cell fatty acid compositions in a patient with autistic spectrum disorder: a characteristic abnormality in neurodevelopmental disorders? Prostaglandins Leukot Essent Fatty Acids. 2000 Jul-Aug;63(1-2):21-5.

[5] Raine A. et al. Reduction in behavior problems with omega-3 supplementation in children aged 8–16 years: a randomized, double-blind, placebo-controlled, stratified, parallel-group trial. Journal of Child Psychology & Psychiatry. 2015; 56: 509-520.

[6] Bent S. et al. Internet-based, randomized, controlled trial of omega-3 fatty acids for hyperactivity in autism. J Am Acad Child Adolesc Psychiatry. 2014 Jun;53(6):658-66.

[7] van Elst K. et al. Food for thought: dietary changes in essential fatty acid ratios and the increase in autism spectrum disorders. Neurosci Biobehav Rev. 2014 Sep;45:369-78.

[8] Mostafa GA. et al. A possible association between elevated serum levels of brain-specific auto-antibodies and reduced plasma levels of docosahexaenoic acid in autistic children. J Neuroimmunol. 2015 Mar 15;280:16-20.

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Brigandi SA, Shao H, Qian SY, Shen Y, Wu BL, & Kang JX (2015). Autistic Children Exhibit Decreased Levels of Essential Fatty Acids in Red Blood Cells. International journal of molecular sciences, 16 (5), 10061-10076 PMID: 25946342