"Vitamin D and omega-3 reduced irritability symptoms in children with ASD"

The title heading this post - "Vitamin D and omega-3 reduced irritability symptoms in children with ASD [autism spectrum disorder]" - comes from the findings reported by Hajar Mazahery and colleagues [1] discussing the results of their clinical trial. I have already mentioned the Mazahery trial before on this blog (see here) as a 'study to watch' based on the publication of their study protocol [2]. It looks like the wait is finally over...

So, as researchers previously reported, there were four arms to this clinical trial: supplementation with vitamin D alone ("2000 IU/day, VID"), supplementation with an omega-3 fatty acid ("722 mg/day DHA, OM"), vitamin D plus fatty acid supplementation together ("2000 IU/day vitamin D + 722 mg/day DHA, VIDOM") and a placebo group (olive oil). Results are reported for over 70 children diagnosed with an autism spectrum disorder (ASD) - "VID = 19, OM = 23, VIDOM = 15, placebo = 16" - over a 12-month period, with the primary outcome being "the Aberrant Behaviour Checklist (ABC) domains of irritability and hyperactivity."

Aside from the main finding - "vitamin D and omega-3 LCPUFA [long chain polyunsaturated fatty acid] reduced irritability symptoms in children with ASD" (compared against placebo) - a few other observations are noteworthy: "Compared to placebo, children on VID [vitamin D] also had greater reduction in hyperactivity." All this bearing in mind that the biological testing to examine for vitamin D and fatty levels reported "a good compliance rate" indicating that supplements were routinely being taken as required by the study.

Implications? Well, strike up more peer-reviewed evidence that nutrition is important not just for physiological health but also for psychological/behavioural health and wellbeing too (see here). Add this research also to other peer-reviewed science that suggests that at least 'some autism' might be particularly 'sensitive' to elements of such nutritional medicine (see here).

I could go on about how vitamin D in particular seems to be something important to autism (see here and see here for examples). I could also go on about how fatty acids have some important evidence-based history with autism in mind (see here). But do I really need to? Minus any medical or clinical advice given or intended, the Mazahery results really speak for themselves.

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[1] Mazahery H. et al. A randomised controlled trial of vitamin D and omega-3 long chain polyunsaturated fatty acids in the treatment of irritability and hyperactivity among children with Autism Spectrum Disorder. The Journal of Steroid Biochemistry and Molecular Biology. 2018. Oct 26.

[2] Mazahery H. et al. Vitamin D and omega-3 fatty acid supplements in children with autism spectrum disorder: a study protocol for a factorial randomised, double-blind, placebo-controlled trial. Trials 2016; 17:295.

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"Omega-3 polyunsaturated fatty acid treatment for anxiety might be effective in clinical settings"

Today I present the findings of yet another systematic review and meta-analysis as per the publication from Kuan-Pin Su and colleagues [1] that concluded: "omega-3 PUFAs [polyunsaturated fatty acids] might help to reduce the symptoms of clinical anxiety." A finding that may have some quite profound implications for lots and lots of different diagnoses/conditions/labels where anxiety seems to be particularly over-represented and life-draining (see here and see here for examples).

So, the starting hypothesis was that "omega-3 PUFAs might have anxiolytic effects in patients with significant anxiety- and fear-related symptoms." Various studies, both in animals and humans, have implicated fatty acids in 'emotional states', particularly the so-called 'good fatty acids' including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The authors reported that "there have been no systematic reviews of this topic to date" so decided to remedy the situation.

Trawling through various repositories and databases of peer-reviewed science, they searched for relevant science on the topic of fatty acid supplementation and anxiety measurement. From little over a hundred possible science articles, they whittled the numbers down to 19 studies including over 1200 participants "with omega-3 PUFA treatment (mean age, 43.7 years; mean female proportion, 55.0%; mean omega-3 PUFA dosage, 1605.7 mg/d)" and "1037 participants without omega-3 PUFA treatment (mean age, 40.6 years; mean female proportion, 55.0%)." Taking into account that some studies (most) included a placebo element to their design, different dosages and formulations of PUFAs were used and that various different tools and schedules were used to 'measure anxiety', there were some boiled-down messages to emerge.

First: "The overall findings revealed modest anxiolytic effects of omega-3 PUFAs in individuals with various neuropsychiatric or major physical illnesses." That's not to say that every study was 'positive' in terms of PUFA effects on anxiety, but generally speaking the evidence tended to side more with an effect rather than no effect. Second, dose and formulation seemed to matter: "Participants treated with a daily dose of 2000 mg or more of omega-3 PUFAs showed a significantly greater association of treatment with reduced anxiety symptoms." Third: "the association of omega-3 PUFA treatment with reduced anxiety symptoms was significantly stronger in subgroups with specific clinical diagnoses than in subgroups without specific clinical conditions." So the effect of PUFA supplementation was stronger in those with a clinical diagnosis of something like anxiety than those who didn't have one.

Downsides? Well, there are of course limitations to the data included in the Su study; for example, "the significant heterogeneity among the included studies... with potential influence by some outlier studies" and these should not be underestimated. I'm also minded to bring in the [still emerging] issue that meta-analyses are only as good as the data that they are based on (see here and see here for examples). And I'd also mention that side-effects are something not discussed too heavily in the Su study but one shouldn't assume that just because we're talking about a fish oil so this is somehow side-effect free for everyone...

Given the low cost of fatty acid supplements and their wide, very wide, availability, the Su results provide some pretty good support to suggest that 'giving it a go' could be an option for at least some people diagnosed with an anxiety disorder. Please don't however take that as me giving anyone medical or clinical advice; I'm merely following what the results say and the media coverage that has followed (see here).

And since we're on the topic of food and mood, I note the recent meta-analysis from Camille Lassale and colleagues [2] suggesting that "adhering to a healthy diet, in particular a traditional Mediterranean diet, or avoiding a pro-inflammatory diet appears to confer some protection against depression in observational studies" has been garnering news headlines (see here). These studies combined suggest that diet might have an important effect of mood and well being. Now, where have I heard that before (see here)...?

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[1] Su K-P. et al. Association of Use of Omega-3 Polyunsaturated Fatty Acids With Changes in Severity of Anxiety Symptoms. JAMA Network Open. 2018;1(5):e182327.

[2] Lassale C. et al. Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Molecular Psychiatry. 2018. Sept 26.

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ALSPAC does... prenatal mercury exposure and autism or autistic traits

The ALSPAC - Avon Longitudinal Study of Parents and Children - mentioned in the title of this post is something of quite a regular feature on this blog (see here and see here for examples).

On this particular blogging occasion I'm heading into the findings reported by Jean Golding and colleagues [1] who utilised this fabulous research resource to examine whether "prenatal exposure from total maternal blood Hg [mercury] in the first half of pregnancy is associated with the risk of autism or of extreme levels of autistic traits." They concluded that there were "no adverse effect of prenatal total blood Hg on autism or autistic traits provided the mother ate fish."

OK, mention of the heavy metal mercury in the context of autism and/or autistic traits can be a touchy subject for some. I'm talking about the various 'discussions' that have taken place both in the lay and peer-reviewed science arenas concerned with the exposure patterns relevant to mercury in the context of autism (see here and see here). This, on the basis that mercury exists in several 'forms', and those different forms have different potential exposure routes.

Golding et al relied on some of the gold-standard analytical methods for the analysis of whole blood Hg collected in the most part "at < 18 weeks gestation": "inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS)." Variations on this method - ICP mass spectrometry - have been previously reported on in the context of mercury and autism research (see here and see here). Alongside, they looked at measured levels of mercury in relation to various behavioural and other variable groupings: "(1) direct comparison of 45 pregnancies resulting in children with diagnosed autism from a population of 3840, (2) comparison of high scores on each of the four autistic traits within the population at risk (n~2800), and (3) indirect measures of association of these outcomes with proxies for increased Hg levels such as frequency of fish consumption and exposure to dental amalgam (n > 8000)." They however cautioned that: "Although we accounted for several important confounders which are relevant to Hg levels and autism, the possibility of unmeasured confounding cannot be ruled out." I can think of one potential confounder that was not seemingly included in their list outside of fish consumption and dental amalgams but ho-hum...

Alongside their overall 'no relationship' results, a few other details are noteworthy. First: "all correlations indicated that with increasing levels of [maternal] mercury, the signs of autism [in offspring] were slightly less, but none were statistically significant." Interesting idea - higher maternal levels of mercury during pregnancy 'correlates' with 'less' autistic traits in offspring in childhood - but to reiterate, not statistically significant. Second was that 'provided the mother ate fish' detail attached to the main findings. So: "we have shown a differential relationship between the social cognition trait and prenatal Hg exposure, such that there was a significant difference in apparently protective effects contingent upon whether the mother ate fish." The authors opine as to what it is about fish consumption that might "counteract any possible adverse cognitive and behavioral differences that may be caused by prenatal exposure to Hg" including "the beneficial components of fish such as the omega-3 fatty acids, iodine, and vitamins D and B2." This in the context that omega-3 fatty acids have some research form in relation to autism (see here) as does the sunshine vitamin/hormone that is vitamin D (see here).

One has to be slightly careful with the Golding results given the focus on prenatal exposure, and prenatal exposure at only one early point in pregnancy, as well as also not actually looking at mercury levels in the children themselves. The current results say nothing for example, about any possible direct or acquired role for mercury in relation to autism as per other findings published during the same period [2]. Neither do they offer any additional information on the idea that exposure issues to such heavy metals may be only one part of the story, and that the biological processes involved in removing such heavy metals may be somehow perturbed in relation to some autism (see here).

But... set within the idea that prenatal mercury exposure may be linked to the 'etiology' of at least some autism, the Golding findings represent pretty strong evidence suggestive of no connection.

Music to close, and could I recommend the soundtrack to Sonic 3 while you work?

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[1] Golding J. et al. Prenatal mercury exposure and features of autism: a prospective population study. Molecular Autism. 2018; 9: 30.

[2] Qin YY. et al. A comparison of blood metal levels in autism spectrum disorder and unaffected children in Shenzhen of China and factors involved in bioaccumulation of metals. Environ Sci Pollut Res Int. 2018 Apr 22.

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"Comprehensive Nutritional and Dietary Intervention for Autism Spectrum Disorder"

It's been a while coming but the paper by Jim Adams and colleagues [1] detailing the effects of a "comprehensive nutritional and dietary intervention for autism spectrum disorder" has finally seen the peer-reviewed light of day. I say 'a while coming' because as per the ClinicalTrials.gov entry for this research (see here), it was seemingly scheduled to start back in 2011 and be completed by 2013, I assume, without taking 5 years to write up and be published. But better late than never I suppose.

Anyhow, the nutritional and dietary intervention scheduled adopted by Adams et al was rather a complicated affair as per the study description. So: "Day 0: Vitamin/Mineral supplementation begins. Day 30: Essential Fatty Acid supplementation begins. Day 60: Epsom salt baths begin. Day 90: Carnitine Supplementation begins. Day 180: Digestive Enzyme supplementation begins. Day 210: Healthy, casein-free, gluten-free diet [HGCSF] begins." Quite a few of those individual intervention elements have been fodder for this blog before (see here and see here for examples); also reflecting other research interests from Adams and colleagues (see here). Talk about a gluten- and casein-free diet is also music to my [research] ears (see here), as is the welcome inclusion of sulfate / sulphate back into autism research proceedings (see here).

Results of that nutritional and dietary schedule are reported for a starting pool of 67 children diagnosed with an autism spectrum disorder (ASD), where 28 participants completed the 'treatment' arm and some 27 participants completed a non-treatment arm (where no new intervention(s) were reported for the 12 months of the study). Additional findings for 50 not-autism controls (I don't like the word 'neurotypical' and its rather sweeping connotations) are also reported. The study duration was a year, and the sorts of measures examined over the course of the intervention were quite comprehensive, covering both behaviour and cognition and also physiological parameters.

Results: it's always refreshing to see a study first and foremost reports any adverse effects based on the tenet 'first, do no harm'. Authors note that: "A few adverse effects were reported for some treatments" and go on to list what happened over the course of each element of the intervention. They talk for example, how: "One parent reported that implementation of the diet [healthy, gluten- and casein-free diet] in a strict manner resulted in increased aggression towards peers, inability to problem solve, and increased spinning behavior, probably due to frustration in regards to removal of favorite foods." Thankfully, most of the adverse effects noted over the study period were relatively minor and certainly not life threatening. Once again, first, do no harm.

With levels of compliance regarding the various study elements also reported as being quite high, the authors report that across the various behavioural assessments - including the CARS, SRS, VABS, and ATEC - significant effects in favour of intervention were found. Based on blinded evaluations using something called the Reynolds Intellectual Assessment Scales (RIAS), authors reported "a significant improvement in nonverbal intellectual ability in the treatment group compared to the non-treatment group." By contrast, blinded use of the gold-standard assessment instrument known as ADOS revealed "no significant change on the ADOS scores for either treatment or non-treatment group." Interestingly, when parents were asked to rate the effectiveness of each part of the intervention, results revealed that: "The highest rated treatments were the vitamin/mineral supplement and the essential fatty acids, followed by the Healthy HGCSF diets, followed by the carnitine, digestive enzymes, and Epsom salt baths."

Adams and colleagues also provide further details on "3 exceptional cases of improvement during the study, all of which occurred in the treatment group." For one participant it appears that the introduction of a carnitine supplement was associated with some quite remarkable improvements in relation to strength and energy levels in particular. The authors note that: "low carnitine seems likely to have contributed to her challenges, and carnitine supplementation seems to have helped." There could be some interesting tie-ups there with regards to previous peer-reviewed results too (see here for example). For another participant it seemed that the introduction of a HGCSF diet *correlated* with the resolution of urination problems, where a dairy-free diet removed the need for "intermittent catheterization" and resolution of associated problems. OK, these examples don't so much focus on the core issues associated with autism, but I'm pretty sure that they were factors that would have influenced quality of life.

There is quite a bit more to see in the Adams paper and I would encourage readers to take the time to read it in its entirety. Despite the fact that not every measure showed significant effects from such an intervention regime, I like the idea that authors didn't just focus on one intervention but rather, in a systematic way, looked at a whole suite of interventions focused on nutritional and dietary factors. I believe this is more 'naturalistic' in terms of what parents/caregivers tend to report. Indeed the authors themselves discuss how: "A limitation of this study is that all participants received all treatments, whereas probably only a subset are likely to benefit from any single intervention (for example, only participants with low carnitine are likely to benefit from carnitine supplementation)." Yup.

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[1] Adams JB. et al. Comprehensive Nutritional and Dietary Intervention for Autism Spectrum Disorder—A Randomized, Controlled 12-Month Trial. Nutrients. 2018; 10(3): 369.

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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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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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Fatty acids and autism meta-analysed again (yet again)

"Our preliminary meta-analysis suggests that supplementation of omega 3 fatty acids may improve hyperactivity, lethargy, and stereotypy in ASD [autism spectrum disorder] patients."

So said the results of the meta-analysis of randomized controlled trials undertaken by Yu-Shian Cheng and colleagues [1] adding further to this interesting area of nutrition with autism in mind. Before venturing through the results, I'll draw your attention to two other occasions this year when fatty acids use and autism have been given the meta-analysis treatment (see here and see here) albeit coming to slightly different conclusions.

This time around six studies made the grade for inclusion in the meta-analysis covering nearly 200 participants. All pitted an omega-3 fatty supplement against placebo and discussed study periods ranging from 6 weeks to 24 weeks. Various schedules were used to measure the impact (if any) of supplementation and/or placebo but the Autism Behavior Checklist (ABC) seemed to be one of the more frequently used assessment scales.

Results: bearing in mind "the average Jadad score was 4.67 with a standard deviation of 0.52" denoting that the methodological quality of the collected literature was pretty good, authors reported a general skewing trend towards 'better response by omega 3' over that of response to the placebos used by the various studies. This covered various areas of both core autistic behaviour(s) such as stereotypy and other, quality of life affecting parameters such as hyperactivity.

But... the clinical picture was not so clear-cut when it came to other autism-related measures such as the SRS - Social Responsiveness Scale - where "there was only borderline improved response by placebo in SRS total scores than those by omega 3." Taking into account the collected results, I do wonder whether use of something like an omega-3 supplement with autism in mind might actually be more relevant to the presence of co-occurring attention-deficit hyperactivity disorder (ADHD) given that (a) ADHD is very much over-represented in relation to autism (see here) and (b) the evidence base on the use of fatty acid supplements for ADHD seems to show a much more 'clear' positive relationship (see here).

There is another point raised in the Cheng paper that is worth noting: "Meta-analysis demonstrated no significant difference in the rate of discontinuation due to side effects between children receiving omega 3 and those treated by placebo." Although this does not mean that fatty acid supplements are universally 'side-effect' free, it does provide some good evidence that such supplementation was generally well-tolerated by the cohorts included for study. I say this bearing in mind that: "Gastrointestinal discomfort and irritability were most commonly reported side effects in the omega 3 groups" understanding that gastrointestinal (GI) issues are already over-represented when it comes to autism (see here).

Minus sweeping generalisations and keeping in mind the prime directive of this blog - no medical or clinical advice is given or intended - I have to say that the peer-reviewed science base for using omega-3 fatty acid supplements in the context of autism (or autism+ADHD?) is looking rather favourable. I say that in connection to the behavioural data that has so far been produced following supplementation but also more generally, with population evidence that omega-3 supplement seems to be good for aspects of physical health and wellbeing too. Certainly, the risk-benefit profile of fatty acid supplementation seems to favour benefit over risk...

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[1] Cheng Y-S. et al. Supplementation of omega 3 fatty acids may improve hyperactivity, lethargy, and stereotypy in children with autism spectrum disorders: a meta-analysis of randomized controlled trials. Neuropsychiatric Disease and Treatment 2017: 13  2531–2543.

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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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Methylphenidate + fatty acids for ADHD? Erm, we need more science...

I don't mind telling you that I was left a bit baffled by the results published by Mahbobeh Firouzkouhi Moghaddam and colleagues [1] (open-access available here) talking about the use of specific polyunsaturated fatty acids (PUFAs) as a sort of add-on to more traditional pharmacotherapy indicated for cases of attention-deficit hyperactivity disorder (ADHD). Baffled because science is supposed to be presented in such a way that methods and results are easy to read and intepret and hence replicate, and appropriate conclusions are supposed to be based on those results. Read on and I hope you'll see what I mean...

Based on the use of a randomised, placebo-controlled trial design, some 40 children (6-12 years of age) who obtained "the least score in an ADHD rating scale questionnaire, responding to the treatment based on least reduction of 25% of symptoms relative to the base state in ADHD scaling" were allocated to either a methylphenidate (MPH) + PUFA ("capsules containing 180mg EPA and 120 mg DHA") group or a MPH + placebo group. Participants were monitored quite regularly over 8 weeks of intervention via the ADHD rating scale adopted and "filled by the resident of psychiatry for patients of both groups." I say all that bearing in mind that I'm not exactly sure what specific ADHD rating scale was actually used during the study.

No mind, the results: "mean severity of symptoms before treatment in both groups of methylphenidate plus PUFA and placebo was the same, and severity of symptoms after treatment in the group under methylphenidate plus PUFA treatment had reduced much more compared to the placebo group, and major changes were observed in the subscale of predominantly attention deficit type." The authors were able to describe the types of symptom patterns presenting by participants in relation to ADHD type. Indeed, quite impressively: "Response to treatment (a reduction of at least 25% in the signs) in the group taking methylphenidate plus PUFA was 90% (18 patients) and in methylphenidate plus placebo group, it was 60% (12 patients)." They did also note side-effects in both groups; the most common in both groups (taking MPH) were sleep disorders and anorexia. For the PUFA group "just one case of burping" was recorded. Researchers concluded that further trials are needed to confirm/refute their findings.

Appreciating that these study results are presented in English but English is perhaps not the mother tongue of researchers, I can get past the slightly odd tone of the article text in places. I do still have an issue with not being able to find out which ADHD scale was used during the study; something that is important if someone wanted to try and independently replicate this study.

More than that, I have to say that I am also a little hesitant when it comes to the way the statistics and findings have been presented in this paper. My first reading of the results was that MPH + PUFA supplementation was superior to MPH + placebo based on the text presented in the article. A more detailed look at the findings revealed that this was not necessarily the case based on (a) looking at the comparisons across the various types of ADHD pre- and post-intervention groups (see Table 1 of the paper) and (b) comparing 'mean severity of symptoms after treatment' between the PUFA and placebo groups (Table 2). You will see that assuming a drop in ADHD scores denotes improvement in behaviour(s), Table 1 suggests that only those with the mixed/combined type of ADHD as a group showed a reduction in scores (9.4±8.39 vs. 0.6±1.20) between pre- and post-intervention with MPH + PUFAs. This was compared with two groups in the MPH + placebo arm of the trial: predominantly attention deficit and mixed type, where a reduction was noted. In all other scenarios, the group values actually increased. Bearing in mind the authors don't actually tell us how many people were included in those ADHD groups, I was a little surprised to see that the p-values remained highly significant for all ADHD types across both study arms. One can only deduce from these findings - those presented in Table 1 - that MPH + PUFA supplementation is at best, as good as MPH + placebo for a specific type of ADHD but at worst, potentially making MPH less effective in other types of ADHD.

Then to the data showing "comparison between the mean severity of symptoms in the intervention and control groups after the treatment" (Table 2). Here again, the picture is one of no real [statistical] difference between MPH alone and MPH + PUFA supplementation after 8 weeks of intervention based on the group scores and the p-values produced. Yes, you could say that MPH + PUFA seems to show some equivalence to MPH + placebo, but then the question 'why take a PUFA supplement?' comes to the surface. And please also, none of that 'almost significant' stuff based on a p-value of 0.18 for example particularly in light of other discussions...

"This study shows that PUFA is an efficient nutrient to treat ADHD and it can be used to treat patients." I'm not so sure that this sentence is completely compatible with the study findings as they are presented; both in the text of the results and the table data. Don't get me wrong, more than most I would love to see fatty acids finding their place with at least some people presenting either with a diagnosis of ADHD or significant features of ADHD (see here and see here for examples) also on the back of some very recent peer-reviewed findings [2]. The trouble is that I don't think these are necessarily the results to show that...

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[1] Moghaddam MF. et al. Effectiveness of methylphenidate and PUFA for the treatment of patients with ADHD: A double-blinded randomized clinical trial. Electron Physician. 2017 May 25;9(5):4412-4418.

[2] 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.

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The pharmacological and non-pharmacological treatment of paediatric ADHD

The findings - "systematic review with network meta-analyses" - reported by Ferrán Catalá-López and colleagues [1] (open-access available here) on the topic of treating attention-deficit hyperactivity disorder (ADHD) were expected [2].

Looking at the available peer-reviewed science comparing "the efficacy and safety of pharmacological, psychological and complementary and alternative medicine interventions for the treatment of ADHD in children and adolescents" authors identified nearly 200 randomised trials looking at various intervention options. With data from over 26,000 people diagnosed with ADHD to examine, they applied some nifty statistical analyses leading to various conclusions on the basis of their categorisations of the various interventions analysed: "pharmacological (stimulants, non-stimulants, antidepressants, antipsychotics, and other unlicensed drugs), psychological (behavioural, cognitive training and neurofeedback) and complementary and alternative medicine (dietary therapy, fatty acids, amino acids, minerals, herbal therapy, homeopathy, and physical activity)."

First: "behavioural therapy (alone or in combination with stimulants), stimulants, and non-stimulant seemed significantly more efficacious than placebo." I don't think this is a particularly novel finding given the intervention options typically indicated for ADHD (see here).

Then: "Behavioural therapy in combination with stimulants seemed superior to stimulants or non-stimulants." This is important insofar as any notion that use of pharmacotherapy alone is going to 'tackle' ADHD. It also suggests that parents, teachers and significant others have a role to play in managing the symptoms of childhood ADHD as per various examples (see here).

Also: "Most of the efficacious pharmacological treatments were associated with harms (anorexia, weight loss and insomnia), but an increased risk of serious adverse events was not observed." It should be no surprise to anyone that there is a cost-benefit balance to be struck when it comes to pharmacotherapy for ADHD or anything else. Medicines always have the potential for side-effects. The lack however, of 'serious adverse events' noted by Catalá-López et al is reassuring and adds to other reviews (see here) highlighting a role for regular monitoring and good medicines management with specific regards to medicines indicated for ADHD.

Finally: "There is lack of evidence for cognitive training, neurofeedback, antidepressants, antipsychotics, dietary therapy, fatty acids, and other complementary and alternative medicine." I don't disagree with these findings but do find it a little 'odd' that other systematic reviews/meta-analyses of something like dietary interventions and/or use of fatty acids for ADHD have come to slightly different conclusions (see here and see here respectively). I don't doubt that there are going to be some subtle differences in what studies were included for further analysis and the interpretation of findings, but 'lack of evidence' is, in my mind at least, perhaps not an entirely accurate viewpoint. Indeed, a more recent paper is a further case in point [3].

"An open and honest discussion with parents and older children about uncertainties of available treatments and the balance between benefits, costs, and potential harms should be established before starting treatment." I think a sentence like this should be added to every article trying to arrive at a coherent statement for many different behavioural and psychiatric labels. It tells us that whilst scientific progress is being made when it comes to the important management of ADHD (see here), there typically is no one-size-fits-all 'silver bullet' that will vanquish all of the challenging symptoms of ADHD and onward improve current and future quality of life. Added to the idea that a multi-pronged approach to managing ADHD is typically better than any one single intervention option, and the Catalá-López article might turn out to be something rather important for many different people with various degrees of interest in ADHD and beyond.

Music: and when Mars Attacks...

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[1] Catalá-López F. et al. The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review with network meta-analyses of randomised trials. PLoS One. 2017 Jul 12;12(7):e0180355.

[2] Catalá-López F. et al. The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: protocol for a systematic review and network meta-analysis of randomized controlled trials. Systematic Reviews. 2015;4:19.

[3] 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.

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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

Mitochondria support for mitochondrial activity in [some] autism

"This study examined the effect of common mitochondrial treatments on specific mitochondrial components in a group of children diagnosed with ASD [autism spectrum disorder], some of which also were diagnosed with co-morbid mitochondrial disease."

That was the premise of the study results published by Leanna Delhey and colleagues [1] (open-access available here) and follows previous discussions suggesting that mitochondrial disease might not be totally unfamiliar to at least some autism (see here). Including some notable names on the authorship list previously linked to the area of mitochondrial functions in relation to autism (see here), the authors provide some important information about how specific mitochondrial function might be 'supported' by various interventions.

I'm not on this occasion going to venture into all the details discussed by Delhey but I do want to pick out some interesting titbits. First, of the 127 children diagnosed with an autism spectrum disorder (ASD), we are told that "15% of the sample was clinically diagnosed with mitochondrial disease." Bearing in mind this particular cohort might not be totally representative of the autistic population at large, 15% is not an insignificant figure. What this tells us is that as and when a diagnosis of autism is received, screening for a possible mitochondrial disorder should be initiated (yes, an autism diagnosis is a starting point not the finishing line and the diagnosis rarely exists in a diagnostic vacuum).

Next, various supplements were taken by participants, some of which have recognised effects on mitochondrial functions. Of particular note was the use of coenzyme Q10 (CoQ10) and carnitine; both of which have been discussed on this blog previously (see here and see here respectively) with the word 'mitochondrial' also being mentioned. Interestingly, a couple of other supplements are also included in the Delhey paper including fatty acids and folate; some of which I have to say, didn't immediately pop into my mind as being primarily mitochondrial-related (folate is though, still a hot topic when it comes to autism). The authors head into how said supplements might affect specific facets of mitochondrial function. It also reminded me that I really need to brush up on my knowledge of mitochondrial functions...

"This study provides empirical support for common mitochondrial treatments and demonstrates that the relationship between activities of mitochondrial components might be a marker to follow in addition to absolute activities." I'd agree that there is the beginnings of a roadmap for further study based on the Delhey results. That and including important parameters related to the presentation of autism and how it may/may not be affected by treating underlying mitochondrial disorder, and the scene is set for further recognition of how indeed, autism rarely exists in a diagnostic vacuum...

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[1] Delhey LM. et al. The Effect of Mitochondrial Supplements on Mitochondrial Activity in Children with Autism Spectrum Disorder. J Clin Med. 2017 Feb 13;6(2). pii: E18.

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Delhey LM, Nur Kilinc E, Yin L, Slattery JC, Tippett ML, Rose S, Bennuri SC, Kahler SG, Damle S, Legido A, Goldenthal MJ, & Frye RE (2017). The Effect of Mitochondrial Supplements on Mitochondrial Activity in Children with Autism Spectrum Disorder. Journal of clinical medicine, 6 (2) PMID: 28208802

A few-foods diet for ADHD: a systematic review of meta-analyses of double-blind, placebo-controlled trials

"... the effect sizes of a few-foods diet are medium to large, justifying implementation of a diagnostic FFD [few-foods diet] in subgroups of children with ADHD [attention-deficit hyperactivity disorder], thus offering innovative treatment opportunities for ADHD."

So said the "Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials" published by Lidy Pelsser and colleagues [1] (open-access available here) looking at various dietary interventions that have been studied with ADHD in mind. Pelsser, I might add, is a name not completely unfamiliar to this area of investigation as per other research on elimination diets and ADHD (see here).

The few-foods diet mentioned in the opening sentence of this post, could include a few things but Pelsser et al make specific reference to it consisting of "lamb, chicken, potatoes, rice, banana, apple and brassica: foods chosen as they were unlikely to produce an adverse response." You'll perhaps note that there are a few food groups missing from that list of foods, not least the grains (including the gluten protein), dairy products (containing the casein protein) and those processed foods that we all like to enjoy.

The Pelsser paper is an interesting one insofar as their systematically reviewing meta-analyses that were already conducted on dietary intervention(s) for ADHD. Said meta-analyses included in their paper were only allowed in if they meta-analysed double-blind placebo-controlled trials (the gold-standard of clinical trial design). If one assumes that a meta-analysis - where data from different trials is analysed and condensed into a sort of position statement - sits at the top of the evidence-based science hierarchy, the Pelsser study design perhaps sits on top of the top!

Although the FFD receives some welcome scientific backing in the review paper, it was not the only dietary intervention looked at the Pelsser and colleagues. To quote: "six supplement meta-analyses—all investigating the effects of poly-unsaturated fatty acids (PUFA)... —and eight elimination meta-analyses, examining respectively the effects of sugar..., AFC [artificial food colour elimination]..., the Feingold diet..., and the FFD... on ADHD" were reported on. The other interventions did not - for various possible reasons - match up to the research success reported with regards to the current standing of the few-foods diet for ADHD. This included the story on fatty acids for ADHD which has been mentioned previously on this blog (see here for example).

I do not make recommendations on this blog when it comes to intervention and the like for anything. I will however, once again quote Pelsser et al based on their very thorough analysis of the peer-reviewed science in the area of dietary intervention for ADHD: "the effect sizes of a few-foods diet are medium to large, justifying implementation of a diagnostic FFD in subgroups of children with ADHD, thus offering innovative treatment opportunities for ADHD". Also: "FFD research should focus on the mechanism of food in children with ADHD." Their words not mine, and based on some rather credible evidence. I might also add that appropriate dietetic input is a must before anyone heads into the FFD willy-nilly and no, this is not about 'clean eating' or any related fad...

And just before you go, how about casting your eye over the observations made by Alejandra Ríos-Hernández and colleagues [2] and their raising the question of "whether low adherence to a Mediterranean diet might play a role in ADHD development"? Food for thought in the context of the Pelsser data, although perhaps minus the [pregnancy] licorice?

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[1] Pelsser LM. et al. Diet and ADHD, Reviewing the Evidence: A Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials Evaluating the Efficacy of Diet Interventions on the Behavior of Children with ADHD. PLoS One. 2017 Jan 25;12(1):e0169277.

[2] Ríos-Hernández A. et al. The Mediterranean Diet and ADHD in Children and Adolescents. Pediatrics. 2017. Jan 30.

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Pelsser LM, Frankena K, Toorman J, & Rodrigues Pereira R (2017). Diet and ADHD, Reviewing the Evidence: A Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials Evaluating the Efficacy of Diet Interventions on the Behavior of Children with ADHD. PloS one, 12 (1) PMID: 28121994

Fatty acids 'for autism'? Meta-analysis says probably not but...

"Because of the limited number of included studies and small sample sizes, no firm conclusions can be drawn. However, the limited data currently available suggest that ω-3 FA [fatty acid] supplementation does not enhance the performance of children with ASD [autism spectrum disorder]."

Those were the conclusions reached in the systematic review and meta-analysis paper published by Andrea Horvath and colleagues [1] looking at the collected peer-reviewed literature on the topic up to August 2016. Specifically focused on randomised-controlled trials (RCTs), where participants are randomly allocated to receive a treatment - in this case ω-3 (omega-3) FA supplementation - or no treatment/placebo, researchers identified 5 studies where ω-3 supplements had been delivered to children diagnosed as being on the autism spectrum. The authors add: "With 4 exceptions, there were no statistically significant differences in ASD symptoms between groups measured by validated scales."

I'm not too surprised by these findings given some previous discussion on this topic (see here). I would however point out a few relevant issues that should be considered when it comes to fatty acids and autism: (i) Despite core symptoms not necessarily showing any general 'improvement' following fatty acid supplementation, this does not mean that other non-core features might not be affected by such supplements. Take for example, the collected data on what fatty acid supplementation might do for [some] attention-deficit hyperactivity disorder (ADHD) for example (see here), allied to the idea that ADHD might be 'over-represented' when it comes to autism (see here). Same goes for fatty acids and reading ability (see here) and indeed, into adulthood, the possibility of a connection between fatty acids and conditions such as bipolar disorder (see here) or psychosis (see here) (bearing in mind some recent discussions on the psychosis 'association'). Both bipolar disorder and psychosis have cropped up in relation to autism (see here and see here respectively). (ii) Horvath and colleagues report that: "Adverse effects were similar in both groups" meaning that fatty acid supplementation is probably not any more 'dangerous' than the placebos or 'no supplementation' used in the reviewed studies when it comes to autism. Given the growing literature suggesting that everyone should be eating a little more fish for heart health for example, supplementing those who don't like fish or who don't seem to eat enough fish is not ruled out. This is particularly relevant when one talks about autism and some peculiar eating habits (see here). (iii) There is a sizeable peer-reviewed literature talking about alterations in the levels of essential fatty acids in cases of autism (see here). Allied to the idea that there is no 'one-size-fits-all' intervention for 'the autisms', it is conceivable that selected supplementation on the basis of those presenting with deficiency could be considered advantageous. Much like when another nutrient of the hour - vitamin D - is shown to be deficient in relation to autism (see here), the onus should surely be to correct the deficiency when found, albeit under appropriate medical supervision (see here).

I don't disagree with the findings reported by Horvath and colleagues and, as I've said a few times before, vitamins and other supplements should be treated in the same way as other 'medicines' in terms of their use and safety (even if they don't typically come as a prescription). But I'd hate to think that the message 'fish oils generally don't benefit autism' gets translated into those on the autism spectrum potentially ignoring what are some potentially important nutrients for general health and wellbeing [2]...

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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] Alexander DD. et al. A Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies of Eicosapentaenoic and Docosahexaenoic Long-Chain Omega-3 Fatty Acids and Coronary Heart Disease Risk. Mayo Clinic Proceedings. 2017; 92: 15-29.

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Horvath A, Łukasik J, & Szajewska H (2017). ω-3 Fatty Acid Supplementation Does Not Affect Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis. The Journal of nutrition PMID: 28077731