Vitamin-mineral mix for ADHD part 2

"Although direct benefit for core ADHD [attention-deficit hyperactivity disorder] symptoms was modest, with mixed findings across raters, the low rate of adverse effects and the benefits reported across multiple areas of functioning indicate micronutrients may be a favourable option for some children, particularly those with both ADHD and emotional dysregulation."

So said the findings reported by Julia Rucklidge and colleagues [1] posting results from their "fully blinded randomized controlled trial" of micronutrients in the context of childhood ADHD. Said study is similar to other research from this authorship group that has been previously covered on this blog (see here). The trial protocol (prospectively registered!) can be seen here and provides further details of the micronutrients in question, study design and various outcome measures employed.

Medication-free children diagnosed with ADHD were assigned to either the micronutrient formulation or placebo for 10 weeks. This was not a study for faint-hearted when it came to pill swallowing as up to 12 capsules a day were required to taken over the course of the study period. Then: "Data were collected from clinicians, parents, participants and teachers across a range of measures assessing ADHD symptoms, general functioning and impairment, mood, aggression and emotional regulation."

Results: well as per the opening sentence to this post, there were some important differences noted across the vitamin-mineral supplement group compared with the placebo arm of the trial. But: "No group differences were identified on clinician, parent and teacher ratings of overall ADHD symptoms." It appeared instead that specific aspects of ADHD presentation and more general issues such as aggression were seemingly affected by the micronutrient supplementation but effects were not necessarily just in universal terms of ADHD.

There are a few other important details to add to this post. First: "no group differences in adverse events and no serious adverse events identified" so taking a vitamin-mineral supplement in the context of paediatric ADHD over 10 weeks is a relatively safe affair we are told. I wouldn't have thought anything different to be honest. Bear also in mind that those diagnosed with ADHD may be at greater risk of vitamin deficiencies according to other research (see here) so there may have been a clinical need here also. Second, vitamin and mineral supplements are pretty widely available for many different age groups so getting hold of them is not likely to be a problem. Looking at the specific formulation used, it appears however that an important class of nutrient(s) are missing: essential fatty acids. I could be wrong, but given the quite large body of peer-reviewed research talking about specific fatty acid supplementation in the context of ADHD (see here) one might have expected to have seen this in the formulation used?

There is apparently more to come from this research initiative so I'll probably be posting a part 3 to complement this and the previous post on this topic. As part of the whole 'nutritional medicine as mainstream in psychiatry' ethos (see here) and bearing in mind the range of adverse outcomes over-represented when it comes to a diagnosis of ADHD (see here for example) I'd like to think that relatively simple and affordable moves to manage [some aspects of some] ADHD involving nutritional tools (see here also) are going to continue to be on the research agenda for some time yet.

----------

[1] Rucklidge JJ. et al. Vitamin-mineral treatment improves aggression and emotional regulation in children with ADHD: a fully blinded, randomized, placebo-controlled trial. J Child Psychol Psychiatry. 2017 Oct 2.

----------

Vitamin-mineral mix for ADHD?

The BBC quite recently ran with the headline: "Vitamins ‘effective in treating ADHD symptoms’" discussing an interesting paper by Julia Rucklidge and colleagues* reporting results from a controlled trial of a vitamin-mineral mix on 80 adults diagnosed with Attention-Deficit Hyperactivity Disorder (ADHD). The trial entry can be seen here and NHS Choices have also given the trial the research once-over.

Food n' medicine? @ Wikipedia 

The paper, by someone who is not an unfamiliar name to this blog based on some previous work looking at micronutrients for stress after earthquake (see here and see here), utilised the gold-standard of experimental design (double-blind randomised placebo-controlled trial). The authorship team looked at an all-in-one supplement containing things like "vitamin D, vitamin B12, folate, magnesium, ferritin, iron, calcium, zinc and copper" and compared use of it for 8 weeks against a placebo or dummy pill (see here). Their results, based on a protocol of intention-to-treat, "showed significant between-group differences favouring active treatment on self- and observer- but not clinician-ADHD rating scales". The authors conclude that their study "provides preliminary evidence of efficacy for micronutrients in the treatment of ADHD symptoms in adults, with a reassuring safety profile". I think we might have already seen a taster of these results in a publication** from late last year (2013) too.

Given my interest in Prof. Rucklidge's previous research and the potential effectiveness and ease of use of a simple vitamin-mineral supplement on anxiety and stress after a major natural disaster such as an earthquake, I was always going to be drawn to this paper. Indeed, with the current weather that we are enduring here in Blighty, I dare say that there may be some further applications from the previous Rucklidge results. That also similar findings, based on an equally rigorous methodological design, have been reported in cases of autism (see here) and the growing realisation of an overlap between autism and ADHD (see here) just adds to the interest. Dare I even mention the suggested link of food and nutrition between the two conditions too (see here)?

That's not to say that there isn't more to do in this area, particularly in light of the important issue of scientific replication. As Prof. Rucklidge talked about in another review paper*** preliminary support is all well and good****, but further well-controlled investigations are still required.  There is also the question of 'why'... why did supplementation with vitamins and minerals seem to 'work' on the presentation of ADHD? I can't offer a definitive answer on this, but as per some of the additional commentary on the BBC website about this work, the suggestion "that vitamins and minerals improved brain metabolism" is a front-runner explanation. Indeed, based on the study talking about treatment response** one finds a few potential starting points based on statements like: "higher baseline ferritin and lower baseline copper and vitamin D levels were associated with a better response to treatment for some but not all outcomes". Regular readers might already know about my interest in all things vitamin D, but one does wonder whether correcting this deficiency might have some interesting physiological effects not just directly related to the brain (see here) indeed harking back to that solar intensity - ADHD link posited not so long ago (see here). Indeed, other research has also turned up vitamin D deficiency as potentially being more frequent in [pediatric] ADHD***** too. I might add that I'm under no delusion that any effect is probably going to be synergistic across the various micronutrients and a lot more complicated that just a single effect on one physiological process.

Still the Rucklidge results offer some really interesting insights into both ADHD, or at least some types of ADHD (the ADHDs!) and how one might go about potentially improving quality of life for those diagnosed with the condition. That cases of adult ADHD seem to be increasing****** and as the authors noted about the issue of comorbidity - "[for] those with moderate/severe depression at baseline, there was a greater change in mood favouring active treatment over placebo" - one wonders whether a cheap and cost-effective nutritional supplement may indeed have an important role to play for at least some diagnosed with ADHD, bearing in mind my blogging caveat: no medical or clinical advice given or intended. Oh and such results might indeed be timely if the recent Nature news piece on the over-selling of medication strategies for ADHD is to be believed.

And to finish, treat your vitamin supplements as pharmaceutics...

Now something short and loud for your listening pleasure (and for all you lovers, er, rock lovers, out there).

----------

* Rucklidge JJ. et al. Vitamin-mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial. Br J Psychiatr. 2014: 30 Jan.

** Rucklidge JJ. et al. Moderators of treatment response in adults with ADHD treated with a vitamin-mineral supplement. Prog Neuropsychopharmacol Biol Psychiatry. 2013 Dec 26;50C:163-171.

*** Rucklidge JJ. & Kaplan BJ. Broad-spectrum micronutrient formulas for the treatment of psychiatric symptoms: a systematic review. Expert Rev Neurother. 2013 Jan;13(1):49-73.

**** Rucklidge JJ. et al. Can micronutrients improve neurocognitive functioning in adults with ADHD and severe mood dysregulation? A pilot study. J Altern Complement Med. 2011 Dec;17(12):1125-31.

***** Goksugur SB. et al. Vitamin D Status in Children with Attention Deficit Hyperactivity Disorder. Pediatr Int. 2014 Jan 13. doi: 10.1111/ped.12286.

****** Montejano L. et al. Adult ADHD: prevalence of diagnosis in a US population with employer health insurance. Curr Med Res Opin. 2011;27 Suppl 2:5-11.

----------

Julia J. Rucklidge, Chris M. Frampton, Brigette Gorman, & Anna Boggis (2014). Vitamin-mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial British Journal of Psychiatry Other: 10.1192/bjp.bp.113.132126

Complementary and Alternative Medicine (CAM) use and autism

I want to talk today about the paper by Roger Akins and colleagues [1] and their finding that: "Use of CAM [Complementary and Alternative Medicine] is common in families of young children with neurodevelopmental disorders". I know that this topic has a tendency to furrow brows and roll eyes in some quarters, particularly when written or spoken alongside the word 'autism', so I'm treading carefully with this quite long post. I will also make reference to my oft-cited caveat: no medical or clinical advice is given or intended on this blog.

elixir vitae @ Chemical Heritage Foundation

CAM - not to be mistaken for CAMHS - covers an awful lot of ground when it comes to the range of 'treatment' options available; as the NHS Choices website puts it "treatments that fall outside of mainstream healthcare". Under the CAM umbrella you have a range of procedures and interventions which cover everything from nutrition to mind-body interventions and seemingly everything in between. Views on CAM - the various ideas behind it and it's perceived effectiveness in general - tend to be split as a function of lots of different variables.

I found quite a good overview looking at the main reasons why people tend to use CAM from a cancer care perspective (see here) which I assume can be similarly applied to CAM use for other conditions or ailments too. Specifically with autism in mind, I dare say that the issues of 'feeling more in control' and 'natural and healing therapies' (bearing in mind the continued mis-representation of the word 'chemical') would probably rank high on the list of why CAM enjoys a following. Indeed, other autism research seems to back up some of these assertions [2].

I've been aware of CAM with autism in mind pretty much from the beginning of my research career, and this is certainly not the first time that it's been talked about in the peer-reviewed domain [3] (open-access) with some pretty good reviews of what CAM covers autism-wise [4] (open-access). The fact that I embarked on a research life examining the potential effectiveness of a gluten- and casein-free (GFCF) diet as an intervention for some of the signs and symptoms associated with autism (and possibly some of it's various comorbidities) might even put me in the CAM researcher box. If the truth be known however, I've never been particularly happy with giving the GFCF diet a place under the CAM umbrella, simply because more and more we are seeing peer-reviewed evidence emerging suggestive that food does seem to be implicated in some cases of autism (remembering the 'not quite coeliac disease paper' for example) and, in a similar vein to the condition called PKU, how food may for some people, have effects that go well beyond just a nutritional perspective. Just sayin'.

Anyhow, the Akins paper, which has received quite a bit of media attention (see here and see here and see here), looked at data derived from the CHARGE initiative (beincharge!) which on this occasion asked parents of young children with autism (n=453) or developmental delay (DD) (n=125) what kinds of interventions or therapies had been used to try and affect the presentation of autism, both conventional and falling under the CAM label. They reported that roughly a third of children in both their autism and DD groups were or had used intervention(s) described as CAM.

Some of the most popular interventions reported were those related to nutrition; be that the use of vitamin and mineral supplements or the implementation of a GFCF diet (or combinations thereof). Indeed to quote from one of the media sources on this paper: "Nearly 7 percent of children with autism were on the gluten-free/casein-free diet, particularly children with frequent gastrointestinal problems". Interestingly these interventions alongside the use of things like probiotics were generally considered 'safe' by researchers. Several other interventions were also reported including vitamin B12 injections and the use of chelating agents which have also been talked about on this blog (see here and see here).

One of the first things to pass through my mind upon reading the Akins paper was the parent survey results from the Autism Research Institute (ARI) which asked parents 'what worked for their child with autism' (see here). I know, I know, the ARI document is not peer-reviewed science and subject to all manner of biases including that of potentially bringing out more positive than negative responses for specific interventions, but that was where the Akins paper led me and indeed, how the CAM use results seem to map on to the ARI results.

I personally think autism research can learn a few lessons from the Akins paper from several different perspectives. So:

• When setting the research agenda for autism in terms of where money and resources might be needed, further examination of the safety and efficacy of some of the interventions reported as being used might be a wise move [5]. As I've talked about before on this blog, there is some preliminary evidence that for example, dietary intervention (see here) or the use of vitamin and mineral supplements (see here) might be helpful for some people on the autism spectrum (or for some of the autisms if you prefer), but more study [methodologically stronger and replicative] is required. And some investigators have been trying to get funding for such research [6] for quite a while now...

• Going back to that suggestion that CAM might reflect more 'natural' therapies, I know there is some continued chatter about where CAM fits into the evidence-based medicine (EBM) model which we subscribe to these days. I don't want to get into the quagmire of EBM vs. the power of personal experience, but rather that further study is also required into the possible interactions that such CAM therapies may have with more conventional medicine. Quite a while back I talked about the interaction between fish oil supplements and chemotherapeutics (that is medication used in the treatment of cancer). What this and other studies point out is that your vitamin or nutritional supplement might be currently classified as a food supplement but that does not mean it can't have often quite potent biological effects. And certainly with the medicines cabinet seemingly being used for quite a few people on the autism spectrum (see here), there is scope for lots of potential interactions.

• It was interesting to read that Akins and colleagues examined various correlates which potentially might explain CAM use as opposed to non-CAM use. So, they report that "Families who used >20 [greater than] hours per week of conventional services were more likely to use CAM" which could indicate an issue of either degree of parent involvement or severity of autistic symptoms [7] in the decision to use CAM or not. Interesting too was the focus on "immunization status" as a variable examined with CAM use or non-use in mind and their finding that "Underimmunized children were marginally more likely to use CAM but not more likely to have received potentially unsafe or disproven CAM". I probably don't need to point this out, but this perhaps again might be further evidence for that 'natural vs. synthetic or man-made' issue potentially at the core of CAM use. It also illustrates one possibility why CAM use in autism still resides on the edge of mainstream autism research insofar as the generalised association often [incorrectly] made between certain types of CAM and the issue of vaccination (or rather 'anti-vaccination') [8]. I'm not saying that there isn't alignment between some purveyors of CAM and specific views on issues like vaccination [9], merely that not everyone holds those views and this should not be a barrier to further research on CAM. A little bit like what happens when talking about certain gastrointestinal (GI) issues in relation to autism and the way that conversation sometimes goes....

• The relationship between parents of children with autism and their healthcare providers is also touched upon in the Akins paper and how: "Further research should address how health care providers can support families in making decisions about CAM use". Huang and colleagues [10] recorded a potentially important point when it came to CAM use and autism in their study when indicating: "In children with ASD (the diagnostic group with the highest use of and satisfaction with CAM), physician's perceived knowledge of CAM was lower (14% versus 38%; p<0.05), as was perceptions of the physician's interest in learning more (p<0.05)." It is of course slightly unreasonable to expect every physician to know everything there is to know about CAM, particularly when applied to a condition as complex as autism. But given the age of the Internet and Dr. Google where all kinds of information is available to all, there is perhaps an even greater need for physicians to inform themselves about the ins-and-outs of such interventions and strategies and be able to advise accordingly based on the available evidence. Indeed, some physicians seem to be doing just that [11].

The Akins paper is certainly an interesting one in terms of highlighting how frequent CAM use is when it comes to autism. More than that though, it opens up a variety of discussion points [12] on the medical model, use of EBM, the patient-physician relationship and some of the complexities and politics of autism. That being said, we shouldn't lose sight of the fact that there are probably lots of reasons why parents of children with autism use or don't use CAM; probably in all cases, such decisions arrived at as a consequence of many very individual factors.

What the Akins paper did not address however was the important issue of how effective CAM use was and just as important, how ineffective CAM use was and for whom. This I assume being the next step in the research agenda...?

To close, readers in the UK will probably have heard about the death of Roger Lloyd Pack a.k.a Trigger from Only Fools and Horses. So, here's a theme tune which should bring back a memory of two... Dave.

----------

[1] Akins RO. et al. Utilization Patterns of Conventional and Complementary/Alternative Treatments in Children with Autism Spectrum Disorders and Developmental Disabilities in a Population-Based Study. J Dev Behav Ped. 2014; 35: 1-10.

[2] Hanson E. et al. Use of complementary and alternative medicine among children diagnosed with autism spectrum disorder. J Autism Dev Disord. 2007 Apr;37(4):628-36.

[3] Levy SE. & Hyman SL. Complementary and Alternative Medicine Treatments for Children with Autism Spectrum Disorders. Child Adolesc Psychiatr Clin N Am. 2008 October; 17(4): 803–ix.

[4] Lofthouse N. et al. A Review of Complementary and Alternative Treatments for Autism Spectrum Disorders. Autism Res Treatment. 2012; 870391.

[5] Anagnostou E. & Hansen R. Medical treatment overview: traditional and novel psycho-pharmacological and complementary and alternative medications. Curr Opin Pediatr. 2011 Dec;23(6):621-7.

[6] Winburn E. et al. Parents' and Child Health Professionals' Attitudes Towards Dietary Interventions for Children with Autism Spectrum Disorders. J Autism Dev Disord. 2013 Sep 1.

[7] Perrin JM. et al. Complementary and alternative medicine use in a large pediatric autism sample. Pediatrics. 2012 Nov;130 Suppl 2:S77-82.

[8] Gupta VB. Communicating with parents of children with autism about vaccines and complementary and alternative approaches. J Dev Behav Pediatr. 2010 May;31(4):343-5.

[9] Ernst E. Rise in popularity of complementary and alternative medicine: reasons and consequences for vaccination. Vaccine. 2001 Oct 15;20 Suppl 1:S90-3

[10] Huang A. et al. Parental perspectives on use, benefits, and physician knowledge of complementary and alternative medicine in children with autistic disorder and attention-deficit/hyperactivity disorder. J Altern Complement Med. 2013 Sep;19(9):746-50.

[11] Golnik AE. & Ireland M. Complementary alternative medicine for children with autism: a physician survey. J Autism Dev Disord. 2009 Jul;39(7):996-1005.

[12] Committee on Children with Disabilities. American Academy of Pediatrics: Counseling families who choose complementary and alternative medicine for their child with chronic illness or disability. Committee on Children With Disabilities. Pediatrics. 2001 Mar;107(3):598-601.

----------

Akins, Roger S., Krakowiak, Paula, Angkustsiri, Kathleen, Hertz-Picciotto, Irva, & Hansen, Robin L. (2014). Utilization Patterns of Conventional and Complementary/Alternative Treatments in Children with Autism Spectrum Disorders and Developmental Disabilities in a Population-Based Study Journal of Developmental & Behavioral Pediatrics : http://journals.lww.com/jrnldbp/Abstract/2014/01000/Utilization_Patterns_of_Conventional_and.1.aspx

Iodine deficiency and autism

With all the recent-ish chatter about dietary quality for those on the spectrum (see here), coupled with a hint of something like the mechanisms of malabsorption being linked to specific cases (see here), the potential issue of 'nutritional deficiency' in relation to autism represents a pretty constant research topic these days.

 Iodine @ Wikipedia

I've talked before about research defining a deficiency in certain vitamins and minerals in relation to cases of autism on this blog; be it in relation to the vitamin-of-the-hour, vitamin D (see here) or vitamin B12 (see here) or something like zinc (see here).

The picture is a complicated one and not necessarily a universal one in terms of prevalence across the autism spectrum nor being solely due to poor eating patterns. But given the increasing understanding of the importance of nutrition to mental and physical health and wellbeing, one would expect quite a lot more to be said on this topic over the coming years.

The paper by Rasha Hamza and colleagues* detailing findings in relation to iodine in cases of autism and other family members adds to the interest. Based on a relatively small participant group, the authors reported that: "Of autistic children and their mothers, 54% and 58%, respectively, were iodine deficient". This contrasted with none of the 50 control group children or mothers presenting with iodine deficiency (ID).

Before progressing through the Hamza study further, I might point out that the British Dietetic Association (BDA) carries quite a detailed information sheet about iodine (see here) as does the US Office of Dietary Supplements (see here). Iodine is sourced mainly from food, and as you'll see from the links, outside of seafood and shellfish, milk and dairy products are one of the biggest dietary sources of iodine. Casein-free diet anyone?

A primary use for iodine in the body is for the production of thyroid hormones. Without going over previous ground, there is some research history when it comes to thyroid hormone and autism as per discussions on the measurement of thyroid hormone levels in autism (see here) and more recent research talking about maternal thyroid levels and offspring 'autistic symptoms' (see here). Dare I even mention the possible environmental variables which have been associated with thyroid function too?

Back to the Hamza paper. As well as measuring levels of urinary iodine (UI) - which apparently is quite a good way of measuring iodine intake** - the researchers also scored child participants with autism using the CARS so as to have some measure of the extent of their presented symptoms. That and examining levels of some of the various thyroid hormones, they were able to arrive at a few other preliminary, but potentially important conclusions.

"Childhood Autism Rating Scale (CARS) score correlated negatively with UI (r = -0.94, p <0.001)". I'm no statistician (add it to the long list of things for which I'm more amateur than professional) but a correlation (r) of -0.94 seems pretty good to me bearing in mind that (1) or (-1) indicates a perfect positive and negative correlation respectively. This data translates as a higher CARS score being generally associated with lower levels of urinary iodine. Further, when looking maternal and child UI output and other thyroid hormones, the authors reported some interesting positive correlations between child and mother values obtained.

It would be easy to say that the Hamza study has some methodological issues. Outside of the quite small participant group, and their exclusive focus on Egyptian families, this was very much a snapshot study in terms of looking at participants at a particular point in time. CARS, like many other autism screening and assessment instruments, is still quite a subjective measure also and who's to say that if this study was repeated a week or a month later, whether similar results would be had with the same group. And then there is that milk-free dietary issue to also consider...

But with all that in mind, this remains an interesting study. I note that other independent groups have also reported issues with iodine being related to cases of autism as per the findings by Blaurock-Busch and colleagues*** (open-access here) and a familiar name to this blog (see here) Jim Adams and his paper***. I was also drawn to an interesting communication on the topic of iodine deficiency as being related to autism from Sullivan & Maberly**** as food for thought, bearing in mind I'm less inclined to believe there is just one factor linked to the increasing numbers of cases of autism being reported.

So, perhaps on that collected basis, there is a little more research to do when it comes to iodine and autism? Oh, and with my blogging caveat about no medical or clinical advice given or intended, please take some proper medical advice if you're thinking about supplementing with iodine (see here).

To close, The Life of Riley by the Lightning Seeds (not to be confused with the life of Whiteley).

----------

* Hamza RT. et al. Iodine Deficiency in Egyptian Autistic Children and Their Mothers: Relation to Disease Severity. Arch Med Res. 2013 Oct 9. pii: S0188-4409(13)00222-1. doi: 10.1016/j.arcmed.2013.09.012.

** Delange F. et al. Determining median urinary iodine concentration that indicates adequate iodine intake at population level. Bulletin of the World Health Organization. 2002; 80: 633-636.

*** Blaurock-Busch E. et al. Toxic Metals and Essential Elements in Hair and Severity of Symptoms among Children with Autism. Maedica (Buchar). 2012 Jan;7(1):38-48.

**** Adams JB. et al. Analyses of toxic metals and essential minerals in the hair of Arizona children with autism and associated conditions, and their mothers. Biol Trace Elem Res. 2006 Jun;110(3):193-209.

***** Sullivan KM. & Maberly GF. Iodine deficiency as a cause of autism? BMJ. Rapid Response. 13 October 2004.

----------

Hamza RT, Hewedi DH, & Sallam MT (2013). Iodine Deficiency in Egyptian Autistic Children and Their Mothers: Relation to Disease Severity. Archives of medical research PMID: 24120386

Vitamins and autism: double-blind, placebo-controlled RCT

It is the gold-standard of experimental trial designs, second only to the meta-analysis on the hierarchy of evidence-based practice: the double-blind, placebo-controlled, randomised controlled trial. To you and me it means that neither participants nor investigators knew who was taking what during the trial, the 'what' experimental treatment was compared against a placebo or sham treatment option, and when it came to deciding who got 'what' or placebo, it was a very random affair.

So it was with a new study by Jim Adams and colleagues* looking at the effects of an individually titrated vitamin and mineral supplement for children and adults with autism spectrum conditions. Regular readers will know that Jim Adams has cropped up more than once on this blog with his various research into the more nutritional aspects to autism, or at least linked to some cases of autism. Indeed the current paper rounds off quite a research publication intensive year for him.

The study. Well it is the best kind of study (open-access) with results which are difficult to ignore or put down purely to methodological issues given the study design and participant group size. To summarise:

• The trial was registered with the NIH Clinical Trials directory (here). Recruited participants diagnosed with an autism spectrum condition formed either an Arizona or National group reflecting geographic status but also whether or not a series of medical exams looking at nutrition and metabolism were carried out. 72 participants split between the Arizona and National groups were allocated to a vitamin-mineral supplement group and compared with 69 participants receiving a placebo designed to look and taste the same as the active supplement.
• The supplement itself contained quite a bit including things like MSM. Most vitamins and minerals were within current RDA guidelines where data on the typical and upper-limit values were available. A few exceptions were things like vitamin D[3], biotin, chromium, iodine, molybdenum, manganese and zinc which were all at the upper ranges in terms of concentration.
• The study analysed data from baseline upto 12 weeks on supplement (or placebo) based on a variety of psychometric and biological parameters. The ATEC is mentioned (and its growing popularity). I've talked about the relative lack of good measures to analyse behavioural 'change' in autism before and it looks like the authors used more than one source schedule for their measurements to perhaps compensate for this void in the research literature.
• The findings. Well there are quite a few of them and it is slightly difficult to say what individual component did what, but here goes: (a) quite a few of the levels of vitamins, the 'b vitamins' in particular, were increased in the experimental group who underwent nutritional testing when assayed for in blood or urine, (b) a general 'normalisation' of minerals compared to control values was observed; most interesting that physiological levels of lithium (+485%) and calcium (+43%) went up alongside levels of iodine (+54%) and molybdenum (+48%), whereas iron levels seemed to drop (-9%), (c) levels of sulphate (total and free), that dusty compound under the bed compound, increased (+83% & +17% respectively) as did levels of glutathione (reduced) (+17%), (d) levels of ATP, NADH and coenzyme Q10 all increased, (e) levels of methylmalonic acid seemed to show improvement (-41%), and homocysteine levels also dropped (-34%), (f) behaviourally, positive effects were noted in areas of hyperactivity, number of tantrums, receptive language and play compared to the placebo.
• The attrition rates were slightly unexpected in that more participants dropped out of the placebo group (n=11) than the experimental group (n=8) even when comparing drop-outs due to adverse effects (n=5, n=3 respectively). Temporary adverse effects were also reported during the early days of getting the dosages right but these seemed to be short-lived for the majority of participants.

I have already made a few active links in the above summary to posts previously made on this blog in relation to the current findings. Without trying to repeat myself, the interesting things from my point of view were that glutathione and sulphate (sulfate) levels went up, homocysteine and methylmalonic acid levels went down; that and an overall 'normalisation' of various vitamin and mineral levels so important for lots of things including being co-factors for various enzymes. The accompanying behavioural changes also reported for supplemented participants reiterates the fact that participants physical health might just tie into behavioural presentation.

This is a big paper both in terms of content and results and also in terms of potential implications to autism. I know some people might look at the competing interests statement at the end of the paper and see that there are various connections between the supplement suppliers, testing companies and some of the authors. I have to say that this does not worry me so much knowing what it means to register a trial with the NIH and the requirement to publish your results whatever they show. That and the gold-standard trial design instills quite a bit of faith that the results are accurate, at least in the group examined. The next questions: finding out which people with autism might be 'best' responders to such a supplement and looking at the longer term profile of supplementation with regards to safety and outcome. A definite watch this space.

* Adams JB. et al. Effect of a vitamin/mineral supplement on children and adults with autism. BMC Pediatrics. December 2011.