Fatty acid supplementation and autism (again)

The findings reported by Sarah Keim and colleagues [1] (open-access available here) provide the discussion fodder today, on a topic that has graced this blog a few times: fatty acid supplementation in the context of autism (see here).

Indeed, it was coincidental that at the same time as the Keim findings appeared on PubMed, so I also stumbled upon news headlines suggesting that maternal use of fish oil supplements (i.e. fatty acids) *might* reduce offspring risk of allergies (see here). This is also an interesting finding; particularly in light of some observations that, appearing alongside the presence of certain childhood allergies, risk(s) of certain neurodevelopmental disorders might be heightened (see here and see here). I might just be adding 2 and 2 together and coming up with 5, but it strikes me that there could be some potentially important connections to be further explored between fish oils, allergy and offspring behavioural diagnoses...

Anyhow, detailing some quite small-scale results - N=31 children "aged 18–38 mo born at ≤29 wk of gestation" - garnered as part of something called The Preemie Tots Trial, Keim et al observed results that "suggested improvements in core ASD [autism spectrum disorder] symptoms as measured by the BITSEA ASD [Brief Infant Toddler Social and Emotional Assessment] scale." I might add that other data from this trial has, I think, already seen the peer-reviewed science publication light of day [2] and on more than one occasion [3].

The actual aim of the Keim study was to "confirm the feasibility of a full-scale trial in toddlers born very preterm and exhibiting ASD symptoms." This is probably why the participant numbers were quite small on this occasion, and why the autism-related findings don't yet need to be trumpeted out loud too much.

To accomplish their research goals, authors conducted a 90-day trial employing the gold-standard research method - "randomized, fully blinded, placebo-controlled trial" - where preterm born children received either "Omega-3-6-9 Junior (Nordic Naturals, Inc.) treatment (including 338 mg eicosapentaenoic acid, 225 mg DHA, and 83 mg GLA)" or a placebo: "canola oil (124 mg palmitic acid, 39 mg stearic acid, 513 mg linoleic acid, 225 mg α-linolenic acid, and 1346 mg oleic acid)".

Outside of the results obtained suggesting some potential positive effect(s) for the fatty acid supplement on autistic signs and symptoms, researchers also confirmed that within the confines of their study period: "No safety concerns were noted." Given that such fatty acid supplements are widespread in their availability, and often sold as a food supplement rather than a preparation with some medicinal claims, I probably wouldn't have expected anything else. That being said, I have heard isolated reports of some children taking fatty acid supplements and things not necessarily being wholly positive in terms of behaviour, bearing in mind anecdote is not the singular of data. This might however also tally with other data reporting no effect from fatty acid supplementation in some instances of autism (see here).

I understand that there is more to come from Keim and colleagues now that this pilot data has been published. I'd like to think if the results are confirmed and some biochemistry added to the mix (i.e. measuring functional fatty acid levels before and after supplementation), this intervention approach could be rolled out much further, as well as things like potential best-responders (and non-responders) being more accurately identified...

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[1] Keim SA. et al. ω-3 and ω-6 Fatty Acid Supplementation May Reduce Autism Symptoms Based on Parent Report in Preterm Toddlers. J Nutr. 2018 Feb 1;148(2):227-235.

[2] Boone KM. et al. Omega-3 and -6 fatty acid supplementation and sensory processing in toddlers with ASD symptomology born preterm: A randomized controlled trial. Early Hum Dev. 2017 Dec;115:64-70.

[3] Sheppard KW. et al. Effect of Omega-3 and -6 Supplementation on Language in Preterm Toddlers Exhibiting Autism Spectrum Disorder Symptoms. J Autism Dev Disord. 2017 Nov;47(11):3358-3369.

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More evidence for the 'anti-aggression' effect of fish oils?

"In conclusion, this experiment indicates that Omega-3 administration has beneficial effects in reducing aggression among the general population."

So concluded the study by Laurent Bègue and colleagues [1] potentially adding to other research suggesting that fish oils - omega 3 fatty acids including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) - might have something of an interesting effect on aggression and violence in various contexts (see here).

Based on a "double-blind randomized trial" design, nearly 200 participants with seemingly no current clinical psychiatric issues were allocated to receive a daily omega-3 fish oil supplement or placebo ("copra oil") over a 6-week period. Self-reported aggression was measured before and after receipt of the active supplement or placebo. Bearing in mind that both researchers and participants were blinded to who was taking what, the self-reports for those taking the daily fish oil supplement suggested that they thought/reported themselves less aggressive at the end of the study compared with the beginning. Ergo, fish oils supplements might, in some part, *act* on self-reported aggression, bearing in mind that self-report may not be the only way to assess for something like aggression.

As per my previous blogging foray into this topic, there is a surprising amount of peer-reviewed research that has been done on the topic of fish oils and aggression [2]. Don't get me wrong, the science is not yet in any position to conclusively suggest that fish oils should be approved for reducing aggression and/or violence at a population level, but there are some glimmers that an effect may be present at least for some. Other, related investigations talking about a negative correlation between circulating blood omega-3 levels and various aspects of aggression [3] add to the 'correlative' evidence base in this area.

There are a myriad of reasons why people are aggressive that are probably going to be different in different occasions and in different environments. These range from the effect(s) of something like impulsiveness in reactive aggression to the often negative influence of things like drugs and/or alcohol or even as a possible manifestation of certain psychopathology. One also needs to understand that aggression is not always a negative thing as anyone who participates in combat sports for example, will testify.

There is likely no single 'quick fix' to such feelings and/or behaviours when undesirable, despite the strong need and want for such intervention(s) (although there are some glimmers of hope in the peer-reviewed domain). Bearing in mind however, that affecting aggression might be just one part of the fairly beneficial profile related to fatty acid supplement use, I'm fast approaching a position whereby the overall picture of fatty acid use is favouring 'beneficial' for many people over 'adverse'. If aggression is similarly [positively] affected, and given the relative in-expense and wide availability of such fatty acid supplements, the emphasis switches towards putting up logical arguments on why such supplements shouldn't be used rather than why they should...

To close, here's hoping...

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[1] Bègue L. et al. Omega-3 supplements reduce self-reported physical aggression in healthy adults. Psychiatry Research. 2018; 261: 307-311.

[2] Gajos JM. & Beaver KM. The effect of omega-3 fatty acids on aggression: A meta-analysis. Neurosci Biobehav Rev. 2016 Oct;69:147-58.

[3] Meyer BJ. et al. Baseline omega-3 index correlates with aggressive and attention deficit disorder behaviours in adult prisoners. PLoS One. 2015 Mar 20;10(3):e0120220.

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Mediterranean-style diet + fish oils = better diet quality and mental health in depression

"This is one of the first randomized controlled trials to show that healthy dietary changes are achievable and, supplemented with fish oil, can improve mental health in people with depression."

So said the findings reported by Natalie Parletta and colleagues [1] reporting results from a randomised-controlled trial investigating "the impacts of a Mediterranean-style diet intervention for mental health and quality of life (QoL) in people with depression."

Their study, called "HELFIMED (Healthy Eating for Life with a Mediterranean-style diet) Mood Study", drew on various data derived from a starting population of some 180 participants randomised to receive a Mediterranean diet plus fish oil (MedDiet) or a control social group who - "attended fortnightly social groups (e.g. sharing holiday stories, playing games, doing personality tests, watching a movie with discussion, book club)." The focus on 'social' noted in the control group was designed to "control for the social component of the cooking workshops that can help to improve depressive symptoms" used by the experimental (dietary) group. Having said that, I can't ever recall 'doing personality tests' as being something I've ever encountered in any social groups/outings down the years but hey-ho! We are also told that: "Assessments at baseline, 3 and 6 months included mental health, quality of life (QoL) and dietary questionnaires, and blood samples for erythrocyte fatty acid analysis" covering both groups over the intervention period.

Results: bearing in mind the numbers of completers at 3- and 6-months were quite a bit down on the starting numbers, a few important details were observed. So: "Compared to the social group, the MedDiet group reported significantly greater increase in their total Mediterranean diet score from baseline to 3 months... along with a significantly greater increase in consumption of vegetables, fruit, wholegrain foods, nuts and legumes, significantly lower consumption of unhealthy snacks and meat/chicken, and a greater diversity of vegetables." It appeared that quite a bit of 'nutrition education' and cooking classes et al seemed to do the trick in increasing the nutritional quality of participants food intake in this arm of the trial. Importantly too: "These dietary changes were maintained at 6 months" when intervention wasn't as intense as that given in the first 3-months.

Also: "Both the MedDiet and the social group reported significantly improved mental health on all outcome measures (DASS, PANAS, and AQoL-8D subscales) over 3 months (all P < 0.001) except for the AQoL-8D pain value." The authors speculate that this could be "attributed to the social component of the study as both groups were exposed to group workshops (either cooking or social group)." In other words, loneliness and/or lack of social support are important features when it comes to mental health in relation to depression (see here).

But... "Compared to the social group, the MedDiet group reported significantly greater improvement in their DASS depression score... and AQoL-8D mental health score over 3 months." The authors observed that transition to a Mediterranean diet plus fish oil supplement seemed to provide some value-added benefits when it came to self-reported depression scores. Whether it was the dietary change or the fish oil supplementation is not really clear from the data but the findings do invite further investigation.

Allowing for the fact that there were 'limitations' to this study (use of self-report, high attrition rate, single blind study design) I think it's fair to say that moves towards getting those with depression to eat healthier is a win-win situation on the basis of what the peer-reviewed evidence seems to point to [2]. Adding to the results of other similar trials in this area (see here) and there is a picture building up that alongside the physical health benefits a good diet (good insofar as containing fruit, vegetables, nuts, etc) can bring, there may be psychological benefits too [3]. It's not just about diet however, as the Parletta results show, but diet does seem to be quite a useful add-on.

The fish oil supplementing side of things is something else that requires some further investigation. I note that I've already covered other work by authors of this most recent study before on this blog with regards to their investigation on fatty acids and autism among other things (see here). In relation to depression (clinical depression), there is also evidence suggesting that certain types of fatty acid supplementation do seem to be able to act on presented symptoms (see here and see here) for some people at least. The problem, as I've mentioned in this study, is teasing apart fish oil/fatty acid supplements from the role played by the dietary changes.

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[1] Parletta N. et al. A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: A randomized controlled trial (HELFIMED). Nutr Neurosci. 2017 Dec 7:1-14.

[2] Fowles ER. et al. Stress, Depression, Social Support, and Eating Habits Reduce Diet Quality in the First Trimester in Low-Income Women: A Pilot Study. Journal of the Academy of Nutrition and Dietetics. 2012; 112: 1619-1625.

[3] Opie RS. et al. Dietary recommendations for the prevention of depression. Nutr Neurosci. 2017 Apr;20(3):161-171.

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Treating violence in schizophrenia with fish oils?

"Violent schizophrenia patients treated with fish oil (360mg DHA+540mg EPA) demonstrated a decrease in violence."

That was the primary conclusion arrived at in the study results by Yi Qiao and colleagues [1] suggesting that some aspects of nutrition may very well have implications for extremes of behaviour in the context of psychiatric diagnoses. The ClinicalTrials.gov entry for this study can be seen here.

DHA - Docosahexaenoic acid - and EPA - Eicosapentaenoic acid - are categorised as omega-3 fatty acids. In this research instance, Qiao et al divided up their "Fifty inpatients meeting ICD-10 criteria for schizophrenia" such that roughly half received a fish oil for 12 weeks and half received a placebo. I should add that this 'inpatient' group also scored significantly on the Modified Overt Aggression Scale (MOAS) at baseline.

Results: well, fish oil use did not seem to make any significant difference to some of the [positive and negative] signs and symptoms of schizophrenia compared with placebo use. But as per the opening sentence to this post, there did seem to be something significant to see when it came to follow-up of violent behaviour alongside the use of fish oils.

These are interesting findings. My first thoughts on reading the Qiao results harked back to previous work looking at the use of nutrition in the context of a prison population by Bernard Gesch and colleagues [2]. That research concluded that: "Antisocial behaviour in prisons, including violence, are reduced by vitamins, minerals and essential fatty acids" where EPA and DHA were part of the supplement provided under "double-blind, placebo-controlled, randomised trial" conditions; albeit in smaller doses that those used by Qiao and colleagues.

The Qiao results are also not the first time that fish oil use for violence in the context of schizophrenia have been talked about in the peer-reviewed science domain [3]. With the understanding that violence accompanying schizophrenia is probably going to be as complex as violence outside of schizophrenia, such promising results require some further replication and a little more data on possible hows-and-whys. The low cost, pretty favourable safety profile and reports of other potential health benefits associated with fish oil use however, suggest that such an intervention could easily be incorporated into treatment plan for many people fitting a similar profile to those described by Qiao and colleagues.

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[1] Qiao Y. et al. Effects of Omega-3 in the treatment of violent schizophrenia patients. Schizophr Res. 2017 Aug 19. pii: S0920-9964(17)30501-7.

[2] Gesch CB. et al. Influence of supplementary vitamins, minerals and essential fatty acids on the antisocial behaviour of young adult prisoners. Randomised, placebo-controlled trial. Br J Psychiatry. 2002 Jul;181:22-8.

[3] Légaré N. et al. Omega-3 and violence in schizophrenia. Schizophrenia Res. 2007; 96: 269.

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Omega-3 fatty acids and ADHD meta-analysed (again)

"In summary, there is evidence that n-3 PUFAs [polyunsaturated fatty acids] supplementation monotherapy improves clinical symptoms and cognitive performances in children and adolescents with ADHD [attention-deficit hyperactivity disorder], and that these youth have a deficiency in n-3 PUFAs levels."

So said the results of the systematic review and meta-analysis published by JanePei-Chen Chang and colleagues [1] taking in the collected peer-reviewed research literature on the topic of fatty acids and ADHD. This continues a research theme down the years suggesting that said compounds might be beneficial for at least some people diagnosed with ADHD (see here) and screening for signs of omega-3 fatty acid deficiency could be preferentially clinically indicated for those diagnosed or at risk of a diagnosis.

I don't want to dwell too much on the results because (a) they speak for themselves and (b) this is an area of science that has been a talking point for quite a few years. I know there has been a degree of 'over-hype' associated with fatty acids down the ages but as part of a larger scheme of work suggesting that food and nutrition are not so detached from some behavioural/developmental diagnoses (see here for another example) I'm minded to suggest that they are given their due credit. Certainly fatty acid supplements are quite inexpensive and also seemingly useful for various aspects of physical health too.

As to the mode of effect, well, we don't know all there is to know just yet. I note that some of the authors on the Chang paper are not adverse to the idea that something like psychiatry and immune functions are linked (see here). Whether at least some cases of ADHD might be accompanied by more 'inflammatory' issues is still the source of some debate; although I'd be quick to add in the quite voluminous research suggesting that allergy and ADHD might have more than a passing relationship (see here). Is is possible that supplementation with specific types of fatty acids typically labelled as 'anti-inflammatory' [2] could be working as anti-inflammatory agents? Well, possibly, but I daresay there may be other biological processes at work too. More research is indicated but the Chang results provide yet more [strong] evidence that at least some of those with ADHD may benefit from a fish oil or two a day.

And whilst on the topic of fatty acids, I might also direct you to an interesting piece of research recently published by Sheppard and colleagues [3]...

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[1] Chang JC. et al. Omega-3 Polyunsaturated Fatty Acids in Youths with Attention Deficit Hyperactivity Disorder (ADHD): A Systematic Review and Meta-Analysis of Clinical Trials and Biological Studies. Neuropsychopharmacology. 2017 Jul 25.

[2] Wall R. et al. Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev. 2010 May;68(5):280-9.

[3] Sheppard KW. et al. Effect of Omega-3 and -6 Supplementation on Language in Preterm Toddlers Exhibiting Autism Spectrum Disorder Symptoms. J Autism Dev Disord. 2017. July 26.

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Fatty acids and autism meta-analysed yet again (with a different result?)

OK I'm a little confused right now.

Not so long ago I talked about the paper from Horvath and colleagues [1] (see here) concluding that "the limited data currently available suggest that ω-3 FA [omega-3 fatty acid] supplementation does not enhance the performance of children with ASD [autism spectrum disorder]." Such a conclusion was based on the application of a systematic review and meta-analysis of the available peer-reviewed literature up to August 2016.

Now however, another systematic review and meta-analysis on the topic has emerged from Mazahery and colleagues [2] and reported something a little bit different: "Populations with ASD have lower n-3 LCPUFA status and n-3 LCPUFA supplementation can potentially improve some ASD symptoms." Don't you just love science!

OK, so what could be the reason(s) for the differing conclusions reached by the reviews on this topic? Well, Mazahery and colleagues (the most recent review) actually conducted two meta-analyses: "meta-analysis 1 compared blood levels of LCPUFA and their ratios arachidonic acid (ARA) to docosahexaenoic acid (DHA), ARA to eicosapentaenoic acid (EPA), or total n-6 to total n-3 LCPUFA in ASD to those of typically developing individuals (with no neurodevelopmental disorders), and meta-analysis 2 compared the effects of n-3 LCPUFA supplementation to placebo on symptoms of ASD." Horvath et al only conducted one meta-analysis in their study roughly equivalent to meta-analysis 2 presented by Mazahery looking at the effects of fatty acid supplementation on the presentation of autism. Mazahery and colleagues also surveyed the literature up to May 2016 and found four randomised-controlled trials (RCTs) (N=107) whereas Horvath et al (who published earlier!) surveyed the literature up to August 2016 and found five RCTs (N=183). Indeed, it appears that based on that last 'difference' one might see how the grand 'top of the scientific hierarchy' meta-analysis is yet again, only as good as the data it contains. And a certain celebrity in science circles seems to agree...

Where next I hear you ask? Well, I'd be tempted to follow the recommendations of Mazahery and colleagues when they suggest that: "Further research with large sample size and adequate study duration is warranted to confirm the efficacy of n-3 LCPUFA." Indeed, there are already studies to watch in this area. That and recognising that within the vast plurality that is the autisms it is not totally outside the realms of possibility that specific parts of the autism spectrum might be more vulnerable to fatty acid issues than others. Oh, and don't forget that outside of impacting autistic 'performance' (or not), fatty acid supplementation does seem to have other health-related properties too...

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[1] Horvath A. et al. ω-3 Fatty Acid Supplementation Does Not Affect Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis. J Nutr. 2017 Jan 11. pii: jn242354.

[2] Mazahery H. et al. Relationship between Long Chain n-3 Polyunsaturated Fatty Acids and Autism Spectrum Disorder: Systematic Review and Meta-Analysis of Case-Control and Randomised Controlled Trials. Nutrients. 2017 Feb 19;9(2). pii: E155.

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Mazahery H, Stonehouse W, Delshad M, Kruger MC, Conlon CA, Beck KL, & von Hurst PR (2017). Relationship between Long Chain n-3 Polyunsaturated Fatty Acids and Autism Spectrum Disorder: Systematic Review and Meta-Analysis of Case-Control and Randomised Controlled Trials. Nutrients, 9 (2) PMID: 28218722

Fish oils for schizophrenia?

Hot on the heels of the peer-reviewed research-based suggestion that fish oil supplementation (high in omega-3 PUFAs) might have some rather important effects pertinent to the transition to full-threshold psychotic disorder for 'young people with an at-risk mental state' (see here), are the results from Tomasz Pawełczyk and colleagues [1].

This time around it was a randomised, placebo-controlled trial "of either 2.2 g/day of n-3 PUFA, or olive oil placebo, with regard to symptom severity in first-episode schizophrenia patients." I might add that we have been expecting these results given the publication of the trial protocol not so long ago [2]. n-3 by the way, refers to omega-3 or rather the Greek lower case character ω or ωμέγα.

Seventy-one participants were randomly assigned to olive oil (placebo) or "1320 mg/day of EPA and 880 mg/day of DHA" and monitored over the course of the 26-week study period. "The primary outcome measure of the clinical evaluation was schizophrenia symptom severity change measured by the Positive and Negative Syndrome Scale (PANSS)."

Results: quite a few changes were noted as a consequence of the fish oil supplementation including that: "A fifty-percent improvement in symptom severity was achieved significantly more frequently in the n-3 PUFA group than in the placebo group." Also: "N-3 PUFA intervention was also associated with an improvement in general psychopathology, measured by means of PANSS... depressive symptoms..., the level of functioning... and clinical global impression." All-in-all, there was quite a bit to see from the use of a humble fish oil supplement in this cohort and hence quite a bit more research is indicated.

A quick survey of the other research literature in this area suggests that the Pawełczyk findings were probably not unexpected. A Cochrane Review ('Cochrane does...') a few years back [3] pointed out that whilst the available literature at that time was not all one-way when it comes to the use of polyunsaturated fatty acids (PUFAs) for people with schizophrenia, there were pockets of evidence suggesting some positive effects might be had from this quite simple intervention. Some but not all subsequent trials have hinted as possible positive effects for some on the schizophrenia spectrum.

If I had to quibble with the Pawełczyk study in any way I might suggest that one has to be slightly cautious about the use of olive oil as a placebo condition. Bearing in mind my not confusing a high fat diet with a ketogenic diet (high fat / low carbohydrate), one has to pause a little to take in the potentially interesting mouse results published by Ann Katrin Kraeuter and colleagues [4] that some media have headlined with "High fat/low carb diet could combat schizophrenia." I personally would like to see the fish oils pitted against a non-fat alternative in clinical study just to be sure.

Music: and what else but goodbye to a legend...

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[1] Pawełczyk T. et al. A randomized controlled study of the efficacy of six-month supplementation with concentrated fish oil rich in omega-3 polyunsaturated fatty acids in first episode schizophrenia. J Psychiatr Res. 2015 Nov 25;73:34-44.

[2] Pawełczyk T. et al. Omega-3 fatty acids in first-episode schizophrenia - a randomized controlled study of efficacy and relapse prevention (OFFER): rationale, design, and methods. BMC Psychiatry. 2015 May 2;15:97.

[3] Joy CB. et al. Polyunsaturated fatty acid supplementation for schizophrenia. Cochrane Database Syst Rev. 2003;(2):CD001257.

[4] Kraeuter AK. et al. Ketogenic diet reverses behavioral abnormalities in an acute NMDA receptor hypofunction model of schizophrenia. Schizophr Res. 2015 Dec;169(1-3):491-3.

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Pawełczyk, T., Grancow-Grabka, M., Kotlicka-Antczak, M., Trafalska, E., & Pawełczyk, A. (2016). A randomized controlled study of the efficacy of six-month supplementation with concentrated fish oil rich in omega-3 polyunsaturated fatty acids in first episode schizophrenia Journal of Psychiatric Research, 73, 34-44 DOI: 10.1016/j.jpsychires.2015.11.013

Fish oils preventing psychosis: long-term effects?

"This is the first study to show, to the best of our knowledge, that a 12-week intervention with omega-3 PUFAs [polyunsaturated fatty acids] prevented transition to full-threshold psychotic disorder and led to sustained symptomatic and functional improvements in young people with an at-risk mental state for 7 years (median)."

So said the quite remarkable findings reported by Paul Amminger and colleagues [1] (open-access available here) who followed up their previous research study [2] looking at the effects of a 12-week supplementation program consisting of either 1.2 grams per day of fish oil or placebo. On that previous occasion, said omega-3 PUFA supplement ("700 mg of eicosapentaenoic acid (20:5n3), 480 mg of docosahexaenoic acid (22:6n3), and 7.6 mg of mixed tocopherol (vitamin E)") reduced the risk of progression to psychotic disorder in individuals at ultra-high risk of psychosis for up to a year post-intervention baseline.

The latest results represent quite an impressive post-intervention follow-up to the original Amminger study. Looking at some of the original cohort of participants and drawing on several types of information including screening / questionnaire data and "rate of prescription of antipsychotic medication", the authors were able to quite confidently conclude that "omega-3 PUFAs may offer a viable longer-term prevention strategy with minimal associated risk in young people at ultrahigh risk of psychosis."

Insofar as the precise hows and whys of omega-3 PUFAs potentially affecting psychosis risk, well, we are left in quite a typical position of speculating. "Omega-3 PUFAs provide a range of neurochemical activities via modulation of neurotransmitter (noradrenaline, dopamine and serotonin) reuptake, degradation, synthesis and receptor binding, as well as anti-inflammatory and anti-apoptotic effects, and the enhancement of cell membrane fluidity and neurogenesis." Take yer pick, bearing in mind there may also be additive and interacting effects within this menu of potential modes of action.

If one assumes however that the possible connection between omega-3 PUFAs and various behavioural and psychiatric labels might have some commonalities (see here and see here for example), one might see a few additional ways and means that 'mode of action' might become a little clearer in the future. One factor, cognitive decline linked to cases of psychosis onset, might not however be the prime factor extrapolating from other recent results [3]...

Music: Felix Jaehn - Ain’t Nobody (Loves Me Better).

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[1] Amminger GP. et al. Longer-term outcome in the prevention of psychotic disorders by the Vienna omega-3 study. Nat Commun. 2015 Aug 11;6:7934.

[2] Amminger GP. et al. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2010 Feb;67(2):146-54.

[3] Chew EY. et al. Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function. JAMA. 2015; 314: 791-801.

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Amminger GP, Schäfer MR, Schlögelhofer M, Klier CM, & McGorry PD (2015). Longer-term outcome in the prevention of psychotic disorders by the Vienna omega-3 study. Nature communications, 6 PMID: 26263244

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

Omega-3 fatty acids and ADHD

With a title like that, this post could turn out to be quite a long winded blog entry. As it happens, I'm not going to subject you, dear reader, to such a literary onslaught but rather focus my attention on the paper by Elizabeth Hawkey & Joel Nigg [1] who undertook two meta-analyses and concluded that: "Omega-3 levels are reduced in children with ADHD [attention-deficit hyperactivity disorder]" and "Dietary supplementation appears to create modest improvements in symptoms".

"Maybe the 80s will be like radical or something"

Omega-3 fatty acids, including α-Linolenic acid (ALA), Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) sourced from things like fish have been the stuff of controversy and debate over the years, particularly focused on their potential link with various facets of child development. I don't want to get into all the nitty-gritty of discussions but suffice to say that this is an area which, for quite a few years, seemed to be cast into the scientific desert. In more recent times, science has started to more systematically examine the possibility of a link between omega-3 fatty acids and development and how supplementation might be indicated for some (see here).

Specifically with ADHD in mind, omega-3 fatty acids boasts quite a thriving research base. The one go-to article that many people have relied on in recent years was the Cochrane Review of PUFAs (polyunsaturated fatty acids) by Gillies and colleagues [2] that concluded: "Overall, there is little evidence that PUFA supplementation provides any benefit for the symptoms of ADHD in children and adolescents". Bearing in mind that review looked at research up to August 2011, the evidence base has moved on somewhat since then, with various controlled trials publishing results as per those from Milte and colleagues [3] and Richardson and colleagues [4] specifically based on analysis of the omega-3 fatty acids. Although not wholly positive [5], the combined results seem to imply that for some with ADHD, there may be certain benefits [6] to be had following certain supplementation.

There's little more for me to say on this topic aside from pointing out the need for further investigation on the hows and whys of fatty acid deficiency/supplementation with at least some diagnosed with ADHD and how this might also translate into other conditions where ADHD may be quite frequently comorbid (see here). As part of a wider body of peer-reviewed research suggestive that dietary variables may play some role for some with ADHD (see here and see here) I'm minded to suggest that food and nutrition should rank further up the research priorities hierarchy when it comes to intervention and ADHD.

So then, Urge Overkill? (if you don't recognise the band name, you'll probably recognise the song).

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[1] Hawkey E. & Nigg JT. Omega-3 fatty acid and ADHD: Blood level analysis and meta-analytic extension of supplementation trials. Clin Psychol Rev. 2014 Jun 2;34(6):496-505.

[2] Gillies D. et al. Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst Rev. 2012 Jul 11;7:CD007986.

[3] Milte CM. et al. Eicosapentaenoic and docosahexaenoic acids, cognition, and behavior in children with attention-deficit/hyperactivity disorder: a randomized controlled trial. Nutrition. 2012 Jun;28(6):670-7.

[4] Richardson AJ. et al. Docosahexaenoic acid for reading, cognition and behavior in children aged 7-9 years: a randomized, controlled trial (the DOLAB Study). PLoS One. 2012;7(9):e43909.

[5] Dubnov-Raz G. The effect of alpha-linolenic acid supplementation on ADHD symptoms in children: a randomized controlled double-blind study. Front. Hum. Neurosci. 2014; 8:780.

[6] Widenhorn-Müller K. et al. Effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on behavior and cognition in children with attention deficit/hyperactivity disorder (ADHD): a randomized placebo-controlled intervention trial. Prostaglandins Leukot Essent Fatty Acids. 2014 Jul-Aug;91(1-2):49-60.

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Hawkey E, & Nigg JT (2014). Omega-3 fatty acid and ADHD: Blood level analysis and meta-analytic extension of supplementation trials. Clinical psychology review, 34 (6), 496-505 PMID: 25181335