Omega-3 supplementation in ASD

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Omega-3 supplementation in ASD

Postby kulkulkan » Fri Mar 27, 2015 10:36 am

Mixed results.

This study found it very useful.

Eur J Clin Nutr. 2015 Mar 25. doi: 10.1038/ejcn.2015.28. [Epub ahead of print]
Omega-3 fatty acids in the management of autism spectrum disorders: findings from an open-label pilot study in Singapore.
Ooi YP1, Weng SJ2, Jang LY3, Low L3, Seah J3, Teo S3, Ang RP4, Lim CG2, Liew A3, Fung DS5, Sung M3.
Author information
The goal of this open-label trial was to examine the efficacy and safety of a 12-week omega-3 fatty acids supplementation among children suffering with Autism Spectrum Disorders (ASD). A total of 41 children and adolescents aged 7-18 years (36 boys, 5 girls; mean age=11.66, s.d.=3.05) diagnosed with ASD participated in the study. At post-treatment, participants showed significant improvements on all subscales of the Social Responsiveness Scale (P<0.01) and the Social and Attention Problems syndrome scales of the Child Behavior Checklist (P<0.05). Blood fatty acid levels were significantly correlated with changes in the core symptoms of ASD. Baseline levels of blood fatty acid levels were also predictive of response to the omega-3 treatment. Omega-3 fatty acids supplementation was well-tolerated and did not cause any serious side effects. Our findings lend some preliminary support for the use of omega-3 fatty acids supplementation in addressing ASD. Future randomized controlled trials of omega-3 fatty acids in ASD with blood fatty acid measurements with a larger sample and longer follow-up period is warranted.European Journal of Clinical Nutrition advance online publication, 25 March 2015; doi:10.1038/ejcn.2015.28

This randomized controlled study didn't find it all that helpful. It didn't appear to measure fatty acid levels before/after, just some cytokines.

Mol Autism. 2015 Mar 21;6:18. doi: 10.1186/s13229-015-0010-7. eCollection 2015.
A randomized, placebo controlled trial of omega-3 fatty acids in the treatment of young children with autism.
Mankad D1, Dupuis A2, Smile S3, Roberts W4, Brian J5, Lui T1, Genore L1, Zaghloul D1, Iaboni A1, Marcon PM6, Anagnostou E5.
Author information

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting more than 1% of children. It is characterized by social communication deficits and repetitive behaviors/restricted interests. In the absence of any medications known to improve core symptom domains, parents often use complementary alternative treatments, including omega-3 fatty acid supplements.

We conducted a 6-month, randomized, placebo controlled trial of omega-3 fatty acid supplements (1.5 g) vs placebo in children 2 to 5 years of age with ASD. Primary outcome measures included the autism composite score of the Pervasive Developmental Disorders Behavioral Inventory (PDDBI) and the externalizing problems score of the Behavior Assessment System for Children (BASC-2). Secondary outcome measures included clinical global improvement (Clinical Global Impression-Improvement (CGI-I)), adaptive function (Vineland Adaptive Behavior Scale (VABS-II)), and language gains (Preschool Language Scale (PLS-4)), as well as safety. Exploratory analysis investigated potential correlations between changes in cytokine profiles and treatment response.

Thirty-eight participants were randomized in a 1:1 fashion. There was no significant difference between groups on the 0- to 24-week change in PDDBI autism composite scores (p = 0.5). There was a significant group by week interaction on the BASC-2 externalizing problem score, with participants randomized to the treatment group demonstrating worsening scores (p = 0.02). There was no statistically significant week by group effect on either adaptive function (p = 0.09) or language (p = 0.6). Omega-3s were relatively well tolerated. Changes in cytokines during the study did not significantly correlate with treatment response.

This study does not support high dose supplementation of omega-3 fatty acids in young children with ASD.

TRIAL REGISTRATION: NCT01248728. Registered 22 November 2010.
Autism spectrum disorder; Complementary alternative treatment; Omega-3; Randomized controlled trial

This recent study also found low DHA for 70% of the kids and was correlated to anti-MBP auto-antibodies.

J Neuroimmunol. 2015 Mar 15;280:16-20. doi: 10.1016/j.jneuroim.2015.01.009. Epub 2015 Jan 28.
A possible association between elevated serum levels of brain-specific auto-antibodies and reduced plasma levels of docosahexaenoic acid in autistic children.
Mostafa GA1, El-Khashab HY2, Al-Ayadhi LY3.
Author information
Polyunsaturated fatty acids (PUFAs) are not only essential for energy production, but they also exhibit a range of immunomodulatory properties that progress through T cell mediated events. Autoimmunity may have a pathogenic role in a subgroup of autistic children. This study is the first to investigate the relationship between serum levels of anti-myelin basic protein (anti-MBP) brain-specific auto-antibodies and reduced plasma levels of PUFAs in autistic children. Plasma levels of PUFAs (including linoleic, alphalinolenic, arachidonic "AA" and docosahexaenoic "DHA" acids) and serum anti-MBP were measured in 80 autistic children, aged between 4 and 12 years, and 80 healthy-matched children. Autistic patients had significantly lower plasma levels of PUFAs than healthy children. On the other hand, ω6/ω3 ratio (AA/DHA) was significantly higher in autistic patients than healthy children. Low plasma DHA, AA, linolenic and linoleic acids were found in 67.5%, 50%, 40% and 35%, respectively of autistic children. On the other hand, 70% of autistic patients had elevated ω6/ω3 ratio. Autistic patients with increased serum levels of anti-MBP auto-antibodies (75%) had significantly lower plasma DHA (P<0.5) and significantly higher ω6/ω3 ratio (P<0.5) than patients who were seronegative for these antibodies. In conclusions, some autistic children have a significant positive association between reduced levels of plasma DHA and increased serum levels of anti-MBP brain-specific auto-antibodies. However, replication studies of larger samples are recommended to validate whether reduced levels of plasma PUFAs are a mere association or have a role in the induction of the production of anti-MBP in some autistic children.
Copyright © 2015 Elsevier B.V. All rights reserved.
Anti-myelin basic protein antibodies; Autism; Autoimmunity; Brain energy; Polyunsaturated fatty acids

María Luján
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Re: Omega-3 supplementation in ASD

Postby María Luján » Sun Mar 29, 2015 10:55 am

Hi kukulkan
What I honestly do not understand is the design of these studies. Without for example a careful investigation ( non.invasive) of potential GI issues, taking into account how fatty acids may have different roles depending on how the biochemistry may be impaired why is it expected results that are not affected by confounders?
My points
1- the need of taurine and glycine for bile salts. Without these aminoacids in proper amounts, the fatty acids can´t be properly handled.
2- the control of antioxidation system and the inflammation PATHWAYS
Mol Psychiatry. 2015 Mar 24. doi: 10.1038/mp.2015.22. [Epub ahead of print]
Inflammation as a predictive biomarker for response to omega-3 fatty acids in major depressive disorder: a proof-of-concept study.
Rapaport MH1, Nierenberg AA2, Schettler PJ1, Kinkead B1, Cardoos A2, Walker R2, Mischoulon D2.

This study explores whether inflammatory biomarkers act as moderators of clinical response to omega-3 (n-3) fatty acids in subjects with major depressive disorder (MDD). One hundred fifty-five subjects with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) MDD, a baseline 17-item Hamilton Depression Rating Scale (HAM-D-17) score ⩾15 and baseline biomarker data (interleukin (IL)-1ra, IL-6, high-sensitivity C-reactive protein (hs-CRP), leptin and adiponectin) were randomized between 18 May 2006 and 30 June 2011 to 8 weeks of double-blind treatment with eicosapentaenoic acid (EPA)-enriched n-3 1060 mg day-1, docosahexaenoic acid (DHA)-enriched n-3 900 mg day-1 or placebo. Outcomes were determined using mixed model repeated measures analysis for 'high' and 'low' inflammation groups based on individual and combined biomarkers. Results are presented in terms of standardized treatment effect size (ES) for change in HAM-D-17 from baseline to treatment week 8. Although overall treatment group differences were negligible (ES=-0.13 to +0.04), subjects with any 'high' inflammation improved more on EPA than placebo (ES=-0.39) or DHA (ES=-0.60) and less on DHA than placebo (ES=+0.21); furthermore, EPA-placebo separation increased with increasing numbers of markers of high inflammation. Subjects randomized to EPA with 'high' IL-1ra or hs-CRP or low adiponectin ('high' inflammation) had medium ES decreases in HAM-D-17 scores vs subjects 'low' on these biomarkers. Subjects with 'high' hs-CRP, IL-6 or leptin were less placebo-responsive than subjects with low levels of these biomarkers (medium to large ES differences). Employing multiple markers of inflammation facilitated identification of a more homogeneous cohort of subjects with MDD responding to EPA vs placebo in our cohort. Studies are needed to replicate and extend this proof-of-concept work

Why the design of the studies is done Without information about taurine and glycine status, inflammation (such as presented above) and autoimmunity?

Postaglandins Other Lipid Mediat. 2015 Feb 16. pii: S1098-8823(15)00006-4. doi: 10.1016/j.prostaglandins.2015.02.001. [Epub ahead of print]
Omega-3 fatty acids and inflammation: A perspective on the challenges of evaluating efficacy in clinical research.
Skulas-Ray AC1.

Chronic inflammation is a common underpinning of many diseases. There is a strong pre-clinical evidence base demonstrating the efficacy of omega-3 fatty acids for ameliorating inflammation and thereby reducing disease burden. Clinically, C-reactive protein (CRP) serves as both a reliable marker for monitoring inflammation and a modifiable endpoint for studies of anti-inflammatory pharmaceuticals. However, clinical omega-3 fatty acid supplementation trials have not replicated pre-clinical findings in terms of consistent CRP reductions. Methodological differences present numerous challenges in translating pre-clinical evidence to clinical results. It is crucial that future clinical nutrition research clearly distinguish between the reversal of established inflammation and preventing the development of inflammation. Future clinical studies evaluating the ability of omega-3 fatty acids to attenuate an excessive inflammatory response, may be advanced by employing new statistical approaches and utilizing models of induced inflammation, such as low-dose human endotoxemia.

Please look at

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Re: Omega-3 supplementation in ASD

Postby kulkulkan » Mon Mar 30, 2015 11:16 am

Good point Maria. Better to do more pilot studies to help investigate and identify potential biomarkers or possible confounders that may correlate to treatment response rather than jumping into double blind studies for all without any good correlating biomarkers.

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