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).

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* 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.

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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

Micronutrients for stress and anxiety after earthquake

Lycosthènes @ Wikipedia

The junction between stress, anxiety and environment is of particular interest to this blog. I don't pretend to be an expert on the various mechanisms at work in such a relationship but, based on quite a thorough reading of some of the autism research literature in this area, I am beginning to understand how anxiety, chronic anxiety in particular, is a debilitating condition and plays a primary role in the reduction in quality of life for many, many people.

Moving slightly away from the autism link, I've talked before about some interesting research by Julia Rucklidge and colleagues at the University of Canterbury, New Zealand and their studies following the 2011 earthquake described at the time as " New Zealand's darkest day".

The main premise of that research was that supplementation with various micronutrients - vitamins, minerals and other compounds - may increase 'resiliance' to stress and anxiety associated with highly stressful events like earthquake in individuals diagnosed with ADHD and asymptomatic groups. Quite a bold claim I'm sure you would agree.

Today I'm following up that earlier post as a result of the fairly recent publication of this paper by Dr Rucklidge and colleagues* looking at different micronutrient formulations and their impact on stress and emotions linked to the 2011 earthquake (see trial database entry here). I apologise that I cannot post a link to the full-text paper but hope a short summary from me will suffice:

• Two formulations were evaluated which, to save any commercial advertising issues, I will refer to as B and C, dispensed to 91 participants exhibiting heightened anxiety or stress a few months after the earthquake (B: n =30; C low dose: n=31; C high dose: n=30) based on a random allocation. A separate group of 25 people who either initially declined to participate or did not meet inclusion criteria acted as a non-randomised control group.
• Various measures of anxiety and stress were delivered and completed at baseline and 4-weeks (study end). Measures included: the Depression Anxiety & Stress Scale (DASS), the Traumatic Exposure Severity Scale (TESS) and the Impact of Event Scale (IES) alongside other measures.
• Results: all three treatment groups showed a significant decrease in measures of anxiety and stress following supplementation (based on change in scores between baseline and 4-weeks active treatment). Comparisons with the non-supplemented control group also revealed significant improvements in "stress, anxiety, avoidance, and arousal after 4 weeks of consumption of micronutrients".
• Across the two preparations and different dosages, there were a few differences related to mood, anxiety and energy which have been put down the slightly broader spectrum of nutrients included in formulation C over formulation B. 

Appreciating that there are a number of potential forms of bias to be had in this type of research including a lack of blinding and no placebo as a control, I have to say that I am quite impressed with the reported findings. The authors have gone to some lengths to control for as many factors as possible (being free of psychotropic medication, exclusion of various conditions/states including neurological disorders) and looked at various angles including SES, alcohol/caffeine/smoking/drug use, mental health history, etc as potential influencing variables. Also importantly reporting potential adverse effects from supplementation.

I kinda like the suggestion that the stress and anxiety of being involved in such a horrific natural act might to some degree be abated by simple supplementation with an off-the-shelf micronutrient supplement. Even if it is purely a placebo action - 'take this pill it will help with your anxiety and stress' - giving a daily vitamin-mineral supplement after a disaster like that knocking out infrastructure and interfering with access to food for example, is probably not such a bad idea also in light of the increased risk for disease following such natural disasters (see the Haiti earthquake for a good example). It has to be slightly less expensive and more easy to administer than a few sessions of behavioural therapy or a course of more traditional pharmacotherapy even just as an emergency measure?

The authors do discuss some of the research on how certain components of the micronutrient preparations used might potentially be able to affect symptoms like stress. I'm taken back to the work of David Kennedy and colleagues at Northumbria University and their reports on high-dose vitamin B and vitamin C supplementation on perceived stress in healthy volunteers** (under placebo-controlled, double-blind conditions). There are several hundred more references on this topic also.

Finally, one has to wonder how deep the rabbit hole goes with regards to micronutrient supplementation and stress and anxiety. Outside of the natural disaster bit, could this work imply that nutritional supplementation might be an alternative route to treating anxiety and stress in the general population? (or at least some cases of anxiety and stress). Physiologically what are the mechanisms of effect, acknowledging snippets of research of interest to me on things like gut hyperpermeability and stress (see here)? What about those trillion or so bacteria which reside in our deepest, darkest bowels; how do they respond to stress and what action can they exert? (I note that this same team are going to be looking at a probiotic formulation in a subsequent trial). Even the possibility of trauma being transmitted across generations as per this interesting post on pregnant 9/11 survivors and the emerging field of epigenetics? Lots and lots of questions to answer.

To finish, how about a little piano genius from Ben Folds Five (and Fraggle Rock?).

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* Rucklidge JJ. et al. Shaken but unstirred? Effects of micronutrients on stress and trauma after an earthquake: RCT evidence comparing formulas and doses. Human Psychopharmacology. July 2012.

** Kennedy DO. et al. Effects of high-dose B vitamin complex with vitamin C and minerals on subjective mood and performance in healthy males. Psychopharmacology. 2010; 211: 55-68.

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Rucklidge JJ, Andridge R, Gorman B, Blampied N, Gordon H, & Boggis A (2012). Shaken but unstirred? Effects of micronutrients on stress and trauma after an earthquake: RCT evidence comparing formulas and doses. Human psychopharmacology PMID: 22782571

On stress, earthquakes and vitamins

There are a few things that will eventually make 2011 memorable for some people. For the people of New Zealand one of the core memories will be the earthquake which struck Christchurch in February this year.

The 6.3-magnitude quake which struck only 10km from the city caused so many fatalities and so much damage because of how shallow its depth was. Indeed combined with the catastrophe which struck Japan a month later, the world will never forget the earthquakes of 2011.

It is difficult to see if any good can come from such disasters. Yes, we can improve building design, flood defences and such like, but the human cost will extend for generations for those directly affected by the quakes. At the risk of sounding cold and callous, science has however started to learn other lessons from these sad events, particularly on the ways and means support can be offered to those people who witnessed the events and lived to tell the tale.

I have previously blogged about post-traumatic stress disorder (PTSD) in relation to autism, and the changes proposed to the diagnosis in the new DSM-5 schedule. Living through an earthquake which might have robbed you of loved ones, your home and all the personal possessions inside would, I think, perhaps leave someone susceptible to problems like PTSD, alongside other psychiatric correlates such as anxiety and stress. The usual routes to tackling such problems would fall to either the talking therapies or in more extreme cases, pharmacotherapy. Recent reports including in the Mail on Sunday a few days back suggest another potential 'treatment' option for such scenarios: the use of vitamins and minerals.

The trial in question looking at micronutrient use on anxiety and stress after the earthquake period was carried out by a team at Canterbury University lead by Julia Rucklidge. A quick email chat confirms that the results at the moment are still under analysis so I cannot offer any link to the finished article. Dr Rucklidge has already stated that ".. people taking the micronutrients are less stressed and anxious than people we followed who did not take the micronutrients" so one can imagine what the results will show. I can't tell you more than that; I can't tell you how the trial was carried out, what precisely micronutrients constitutes, nothing very much. In any other circumstance I would perhaps be making some wry comments about jumping the gun (apologies Usain) something similar to the suggestion that TV viewing causes autism. In this case I won't, simply because Dr Rucklidge and colleagues do have some good history of publishing studies in this area, most notably their earlier study* on micronutrient effects to ADHD following the 7.1-magnitude earthquake which struck in September 2010. I am currently reading this paper so may post a part two sometime soon focusing also on whether vitamins increase psychological resilience and just how that might come about.

* Rucklidge J. et al. Micronutrients reduce stress and anxiety in adults with Attention-Deficit/Hyperactivity Disorder following a 7.1 earthquake. Psychiatry Research. July 2011