Childhood dietary patterns and ADHD?

The findings of the systematic review and meta-analysis published by Bianca Del-Ponte and colleagues [1] provide the blogging fodder today, and the suggestion that: "a diet high in refined sugar and saturated fat can increase the risk, whereas a healthy diet, characterized by high consumption of fruits and vegetables, would protect against ADHD [attention-deficit hyperactivity disorder] or hyperactivity."

The starting point: "The diet during childhood has been investigated as a factor potentially involved in the ADHD etiology." Yes it has, and Del-Ponte et al managed to find 14 studies looking at this issue published in the peer-reviewed literature. The data were boiled down and results obtained suggesting that "healthy dietary patterns were protective against ADHD (OR: 0.65; 95% CI: 044 – 0.97), while unhealthy dietary patterns were found as risk to ADHD (OR: 1.41; 95% CI: 1.15–1.74)."

The authors admit that the science upon which they made their observation is "weak" insofar as cause and effect not being proved. This is an important point (see here) that follows other research in this area too (see here and see here) together with an understanding that many different variables *might* influence the risk of something like ADHD as a diagnosis or in behaviour (see here and see here for examples).

Still, if there is even the remotest possibility that diet might be something to consider in respect of ADHD, adding it to the intervention arsenal that already exists (see here) can only be a good thing...

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[1] Del-Ponte B. et al. Dietary patterns and attention deficit/hyperactivity disorder (ADHD): A systematic review and meta-analysis. Journal of Affective Disorders. 2019; 252: 160-173.

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A prenatal 'unhealthy' diet and offspring ADHD?

'Scientists study link between unhealthy pregnancy diet and ADHD' went one media headline covering the paper by Jolien Rijlaarsdam and colleagues [1].

The name of the research game was again to draw on data derived from ALSPAC (Avon Longitudinal Study of Parents and Children) (yes, again) to look-see "the degree to which prenatal high-fat and -sugar diet might relate to ADHD [attention-deficit hyperactivity disorder] symptoms via IGF2 DNA methylation for early-onset persistent (EOP) versus low CP [conduct problems] youth." In other words: "Experts examine how a diet high in fat and sugar could alter baby’s DNA in a way that might cause behavioural problems."

To do this meant looking at around 80 youth presenting with early-onset conduct problems compared with around 80 youths who didn't have the same magnitude of issues. Data on maternal nutrition captured for the two groups (ALSPAC did a lot of data collecting!) was cross-referenced with group status and also epigenetic - methylation - status of the insulin-like growth factor 2 gene (IGF2). IGF2 is a gene that seems to be pretty active during the nine months that made us but less so as we enter the big, wide world. As the name suggests it seems to have a 'growth' role which is probably why issues with this gene have also been associated with the development of a number of cancers.

Results: "Prenatal ‘unhealthy diet’ was positively associated with IGF2 methylation at birth for both the EOP and low CP youth." Minus any 'blame', such results suggest that maternal diet might be important for the developing child. I know this is it not exactly a shock, but in these days of more and more research and clinical focus on the special time called pregnancy, the idea that particular epigenetic changes might come from a chosen diet is a potentially important one.

Further: "For EOP only: (a) higher IGF2 methylation predicted ADHD symptoms; and (b) prenatal ‘unhealthy diet’ was associated with higher ADHD symptoms indirectly via higher IGF2 methylation." The higher IGF2 methylation - higher ADHD symptoms is an interesting association. Methylation - the addition of a methyl group - is normally taken to mean gene silencing suggesting that a malfunction of the the IGF2 gene and/or lower levels of its protein product might have some important implications. At this point I might add that whilst there is a bit of a research gap when it comes to IGF2 and behaviour specifically linked to ADHD, there is some interesting animal research looking at mice engineered to show low levels of the protein product in terms of behaviours such as anxiety [2] alongside "a role for the placenta in long-term programming of emotional behaviour." Cutting edge stuff to be sure.

"At present, this is not a study that would change my clinical practice, but if intervention studies resulting from this work show nutritional support in pregnancy can have an effect then we should take any opportunity we can to help." That was one comment from a physician discussing the results of the Rijlaarsdam study that I would agree with. The fact that the study focuses on just one gene in amongst the thousands potentially linked to conduct problems and ADHD is something to bear in mind.

Set however within the context that food can seemingly also affect behaviour and psychiatry as well as physiology (see here for example) I'd like to think that more studies on nutrition during pregnancy would be forthcoming and quickly on this important topic.

To close, thanks to Gene for the laughter...

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[1] Rijlaarsdam J. et al. Prenatal unhealthy diet, insulin-like growth factor 2 gene (IGF2) methylation, and attention deficit hyperactivity disorder symptoms in youth with early-onset conduct problems. J Child Psychol Psychiatry. 2016 Aug 18.

[2] Mikaelsson MA. et al. Placental programming of anxiety in adulthood revealed by Igf2-null models. Nat Commun. 2013;4:2311.

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Rijlaarsdam J, Cecil CA, Walton E, Mesirow MS, Relton CL, Gaunt TR, McArdle W, & Barker ED (2016). Prenatal unhealthy diet, insulin-like growth factor 2 gene (IGF2) methylation, and attention deficit hyperactivity disorder symptoms in youth with early-onset conduct problems. Journal of child psychology and psychiatry, and allied disciplines PMID: 27535767

Autism, the ketogenic diet and Dangermouse

I'm proud of my quite 'unusual' area of autism research interest focused primarily on whether diet might, in some way, shape or form, be linked to or impact on some cases of the autisms. It's not been a particularly popular area of research down the years it has to be said. Most of which I've put down to its links to areas far outside of the behavioural dyad (as its known these days). That and all the gastrointestinal (GI) baggage inevitably associated with diets like the gluten- and casein-free (GFCF) diet: leaky gut, gut bacteria, etc. which have been allied with other 'factors' leading to a sort of scientific death-by-association in some quarters.

Penfold  @Wikipedia  

Outside of the considerable politics, there is an evidence base to diet and autism. It's not a particularly strong scientific base it has to be said, but there are a few randomised controlled trials (RCTs) to be found, and in agreement with Tim Buie's latest take on gluten-free dietary intervention and autism* "There may be a subgroup of patients who might benefit from a gluten-free diet". Though we still don't know who.

Dr Buie, by the way, has also talked about things like lactose (the sugar in milk) intolerance and gut dysbiosis in cases of autism extending the potential of a dietary link. Assuming you adhere to the notion of the autisms - with all their heterogeneity and comorbidity - you might be inclined to also think that autism might not just be a condition of the grey-pink matter floating in the skull. Or maybe not....

Hopefully not being too 'me, me, me', I'm actually involved in writing a book about the area of diet and autism as we speak. It's been an interesting journey and allowed me to dig deep into the available science behind diet including some gems such as per this paper**. Outside of just GFCF diets, a variety of other food changes have also been on the research menu with autism in mind, including the ketogenic diet.

I've talked about the ketogenic diet before - what it is and how it is starting to enter mainstream medicine when it comes to managing certain types of epilepsy. Briefly, it's all about high fat (no, not that Hai Fat) and low carbohydrates and putting the body into a state known as ketosis. Indeed how this state seems to affect seizure patterns for some people. Yes, I know a similar sort of diet, sorry nutritional approach, has also been suggested as a weight loss measure but I'm not really that interested in that sort of thing on this blog.

With autism in mind and outside of any seizure-linked effect, there has been a suggestion, a small suggestion, that a ketogenic diet might also be able to affect certain behaviours linked to autism too as per the paper by Evangeliou and colleagues***. In a more case-study fashion, I'll also draw your attention to my fairly recent discussions on the paper by Martha Herbert and Julie Buckley (see here) on similar things. Other than that, we've got a bit of a scientific black hole when it comes to the question of whether such a very restrictive dietary intervention could 'help' where autism is present and who might be best responders.

The paper by David Ruskin and colleagues**** (open-access) which I'm finally getting to after quite a long-winded introduction, represents an addition to that autism-ketogenic diet literature and their observations of the BTBR 'Dangermouse' when on a ketogenic diet. OK I've exaggerated slightly. The BTBR mouse model of autism is not really Dangermouse; just a name I've assigned from my mis-spent youth watching far too much TV (see this post). But it is still quite a good mouse model of autism despite some recent criticism.

The Ruskin paper is open-access so I'm not going to go over the top with any description. It went something like: take several BTBR mice. House them with other mice (C57Bl/6). At 5 weeks of age, feed some of the mixed caged mice a ketogenic diet (KD) and others a control diet. Test mouse behaviour at 3-5 weeks of diet. Report results.

The results: well, the KD mice were certainly showing signs of ketosis as per some blood chemistry results including some much lower blood glucose levels (interesting!*****). There were also some interesting differences recorded to elements of mouse behaviour as a function of the use of the KD or not and mouse strain: "the KD did not affect behavior in C57Bl/6 mice". Importantly "the beneficial behavioral effects of the KD are not secondary to its well-known efficacy against epilepsy and seizure activity".

OK, it's another study of mouse behaviour and making the quite considerable leap from a proposed mouse model of autism to real-life autism. Mouse behaviour is not human behaviour (he says cleaning his whiskers). I'm no expert on how one goes about examining and testing mouse behaviour so I'll have to assume that the authors knew what they were doing and did it to the best of their abilities. I'm not necessarily expecting the Ruskin study to mark any substantial shift in opinion on how people view the research area of diet and autism it has to be said.

What this study does offer though, is another potentially fascinating glimpse into how diet might be related to some cases of autism. Indeed, whether the whole or facets of the intervention are worthy of much greater study. For example, I earlier mentioned Tim Buie's work on carbs and autism. The question is whether the lower carbohydrate load attached to a ketogenic diet might be the more important variable over and above fat, bearing in mind that there might be issues there too? Similarly, the authors ask whether the ketogenic diet might be something to consider where autism and certain types of epilepsy exist; as per another quote: "a KD could offer dual benefits in this difficult clinical population". Bear in mind however, I offer nothing like medical or clinical evidence by suggesting all this. Just speculating.

To close and paying homage to the era of Dangermouse (1980s), here's Neneh and Buffalo Stance.. ("know wot I mean?")

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* Buie T. The relationship of autism and gluten. Clin Ther. 2013; 35: 578-583.

** Asperger H. Psychopathology of children with coeliac disease. Ann Paediatr. 1961; 197: 346-351.

*** Evangeliou A. et al. Application of a ketogenic diet in children with autistic behavior: pilot study. J Child Neurol. 2003; 18: 113-118.

**** Ruskin DN. et al. Ketogenic diet improves core symptoms of autism in BTBR mice. PLoS ONE. 2013; 8: e65021.

***** Yancy WS. et al. A low-carbohydrate, ketogenic diet to treat type 2 diabetes. Nutrition & Metabolism. 2005; 2: 34.

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Ruskin, D., Svedova, J., Cote, J., Sandau, U., Rho, J., Kawamura, M., Boison, D., & Masino, S. (2013). Ketogenic Diet Improves Core Symptoms of Autism in BTBR Mice PLoS ONE, 8 (6) DOI: 10.1371/journal.pone.0065021

Chronic illness and healthcare for autism

Three articles caught my eye today in relation to some recurrent themes on this blog about autism not being protective of other chronic conditions and how some of the most 'disabling' aspects of autism are not necessarily due to the presentation of overt symptoms or comorbidities.

The first paper by Tyler and colleagues* examined risk for several chronic diseases including obesity, high blood pressure and high blood cholesterol levels in autism vs. matched controls. They suggested that hyperlipidemia in particular, set adults with autism aside from controls but importantly noted that anywhere from a fifth to a third of the autistic population surveyed presented with one of the chronic illnesses specified previously. I don't need to say much more about this paper aside from the words 'it's about time'. It has taken long enough for society to realise that conditions such as schizophrenia might place someone at greater risk of some of these issues. Now perhaps autism can benefit from similar health screening.

The next paper by Lai and colleagues ** perhaps ties into several things already discussed on this blog in relation to the effects of unmet health needs. Lai looked at dental health, finding that 12% of parents questioned said their child with autism had unmet dental needs. Even 1 in 10 children who had been to the dentist were reported still to have unmet dental needs. Whilst they suggested that behaviour was one 'barrier' to getting those needs met, they also suggested that unmet dental needs were present across the autism spectrum, implying ability and severity were not deciding factors in this health care 'hole' but possibly also other things like cost. Dental hygiene and health is fast becoming an important variable in several health-related matters. How about oral hygiene and your risk of cardiovascular disease? With autism in mind, I have previously touched upon the need for some sleuthing when trying to determine factors associated with self-injury and aggression.

The final paper by Parellada and colleagues *** is the more 'feel-good' paper reporting not on unmet health needs or risk factors but rather what can be done to make healthcare more accessible to people with autism. I need to find out more about this paper so as to make a more detailed post on it but first impressions are that they were doing a pretty good job in looking not just at autism as a triad (dyad?) of symptoms but rather a more rounded approach encompassing things like nutrition and gastroenterology. Indeed realising that you have a person first and a person 'with autism' second, is a key advancement to removing some of the barriers that a label of autism might bring about and therefore making healthcare accessible to all.

* Tyler CV. et al. Chronic disease risks in young adults with autism spectrum disorder: forewarned is forearmed. Am J Intellect Dev Disabil. September 2011

** Lai B. et al. Unmet dental needs and barriers to dental care among children with autism spectrum disorders. JADD. September 2011

*** Parellada M. et al. Specialty care programme for autism spectrum disorders in an urban population: a case-management model for healthcare delivery in an ASD population. Eur Psychiatry. September 2011

Diet determines gut bacteria

Continuing my interest/borderline obsession with all things gut bacterial, I offer this short post. It is a short post because this link to an entry in Science by Martin Enserink says just about everything I might want to say and probably better than I would say it. For those who want the slimmed down version.. for your consumption:

Enterotypes, that is categorised types of gut bacteria, seem to occur as a consequence of what form your diet takes according to this study by Gary Wu and colleagues*. So eat lots of meat and saturated fat and Bacteroides is the predominant species. If alcohol and polyunsaturated fats are among your primary dietary selections then Ruminococcus is your man/woman. Love your carbs? Then Prevotella predominates. Important also that whilst changes to fat and fibre content of your diet in the short term produce some detectable changes to gut bacteria, your enterotype seems to be a little more stable from meal to meal (at least in the 10 participants included in the trial over a period of 10 days).

There are so many more questions to be asked about this area of study. With my autism research hat on, I wonder what the bacterial consequences are when diets like a gluten- and casein-free diet are adopted, or when a specific carbohydrate diet (SCD) is followed over a course of months or years? Do the gut bacterial populations stay the same, or if not, could this conceivably tie into any behavioural effects noted from such dietary intervention the same way as happens when you 'shock and awe' gut bacteria with strong antimicrobials?

* Wu G. et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. September 2011. DOI: 10.1126/science.1208344

Edible colloids to reduce food fat content

A brief post. The August 2011 edition of Chemistry World carries an interesting article about the use of edible colloids as an alternative way of reducing the fat in foods (full-text here). I don't want to get into any debate about whether dietary fat is good or bad because (a) I don't know enough about it and (b) it is not the main aim of this post.

Being Chemistry World, the text is quite heavily chemistry-orientated but I was quite interested in some of the various ways that chemistry is approaching the issue of fat in food and our modern-day obsession with diet and fat reduction. The article lists a few interesting possibilities under investigation. Things like the incorporation of gel-coated air bubbles into foods behaving like fat droplets in the mouth, and the addition of emulsions to food which survive our stomach and areas of our gastrointestinal (GI) tract to make us feel fuller for longer. I know some people might gasp in horror as chemistry contemplates toying with our foods, and obviously a lot more research and investment needs to go into such areas. Having said that hands up if your diet solely consists of food which has not been manipulated in one way or another already?

All of these options must be better than the 'no food diet'?