Showing posts with label PUFAs. Show all posts
Showing posts with label PUFAs. Show all posts

Wednesday, 9 August 2017

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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Thursday, 26 February 2015

Carnitine and autism continued

The paper from everyone's favourite Saudi - Egyptian autism research tag-team that is Gehan Mostafa and Laila AL-Ayadhi [1] (open-access) on plasma polyunsaturated fatty acids and serum carnitine levels in a cohort of children diagnosed with autism / autism spectrum disorder (ASD) is served up for your reading delight today.

Regular readers of this blog might have heard me talk before about the pretty interesting research findings to come from this research partnership (see here and see here for example) covering all-manner of different sectors of the autism research environment.

This times around the name of the game was: "to investigate plasma levels of PUFAs [polyunsaturated fatty acids] and serum carnitine in relation to GI [gastrointestinal] manifestations in autistic children." The idea being that: "Carnitine and PUFAs are antiinflammatory molecules and their deficiency may result in GI inflammation and gut injury" following other work with autism in mind (see here).

A few pointers about the study might be in order:

  • "This cross-sectional study was conducted on 100 children with autism." Participants ranged in age between 3-10 years and importantly were not taking additional fatty acids or anticonvulsants. A control group of 100 age- and sex-matched children asymptomatic for autism were also studied: "not related to the children with autism, and demonstrated no clinical findings suggestive of immunological, GI or neuropsychiatric disorders."
  • Autism severity was assessed using the CARS and GI issues were examined "by an experienced pediatric gastroenterologist according to the Questionnaire on Pediatric Gastrointestinal Symptoms - Rome III Version used by previous studies that assessed gastrointestinal dysfunction in autism." Fasting blood samples were also provided and serum carnitine and plasma PUFAs examined.
  • Results: both biological measures were lower as a group for the children with autism compared to controls. Indeed: "Low serum carnitine and plasma DHA [Docosahexaenoic acid], AA [Arachidonic acid], linolenic and linoleic acids, below the 5th percentile of the control values, were found in 66%, 62%, 60%, 43% and 38%, respectively of autistic children."
  • Bearing in mind that PUFAs can exist in more than one form as per the old omega-3 / omega-6 issue (see here), authors also reported a group difference in the ratio of ω6/ω3 PUFAs: "ω6/w3 ratio (AA/DHA) was significantly higher in autistic patients" compared with controls. This is something also reported by the authors in other publications [2].
  • GI symptoms were reported to be present in about half of the autism group. An important sentence is included about GI issues: "They were recurrent, severe and the patients were attending the clinic because of these agonizing symptoms." Further: "Autistic patients with GI manifestations had significantly lower serum carnitine and plasma DHA than patients without such manifestations."

I know I tend to say this about nearly every study I blog about but this is interesting work. Carnitine and autism is an area which I've got quite a bit of time for on this blog and the growing consistency in results suggesting lower levels of this stuff in quite a few cases of autism (see here). Some of the genetics of carnitine metabolism might also be 'linked' to at least some autism too (see here) with a particular focus on the idea of inborn errors of metabolism. Certainly, autism research should know a thing or two about them (see here).

The relationship between fatty acids and autism reflects a slightly less clear picture in terms of results. In a post going back to 2011, I talked about some of the peer-reviewed research on the use of supplementary fatty acids for autism (see here) and how certain comorbidity present in quite a bit of autism (see here) might be the bigger target. More recent research has kinda corroborated that idea (see here).

"How GI factors are related to autism is not yet clear" is another important quote from the authors. Yes, we are now in an era where there is general acceptance that certain functional GI issues are over-represented among those with autism (see here) but the hows and whys are still the source of significant speculation. I'd be minded to suggest that it's likely to be complicated and probably without a universal factor for everyone with autism and GI issues. There are some areas emerging that may yield further information such as examination (not hype) of those trillions of wee beasties which call our gut home (see here) and a 'possible' relationship with more pathological bowel states (see here). The Mostafa/AL-Ayadhi findings suggest another possible correlate.

I leave you with a quote from the authors: "these data should be treated with caution until further investigations are performed, with a larger subject population, to determine whether the occurrence of GI manifestations is a mere association or a consequence to reduced plasma PUFAs and serum carnitine levels in autistic patients." I couldn't agree more.

Music then. The Strokes with New York City Cops.

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[1] Mostafa GA. & AL-Ayadhi LY. Reduced levels of plasma polyunsaturated fatty acids and serum carnitine in autistic children: relation to gastrointestinal manifestations. Behavioral and Brain Functions 2015, 11:4.

[2] 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 Neuroimmunology. 2015. Jan 27.

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ResearchBlogging.org Mostafa, G., & AL-Ayadhi, L. (2015). Reduced levels of plasma polyunsaturated fatty acids and serum carnitine in autistic children: relation to gastrointestinal manifestations Behavioral and Brain Functions, 11 (1) DOI: 10.1186/s12993-014-0048-2