Magnesium and ADHD meta-analysed

The study results published by Mohammad Effatpanah and colleagues [1] provided some food for thought recently on the topic of whether there may be an *association* between "serum magnesium levels and the diagnosis of attention deficit hyperactivity disorder (ADHD)."

The name of the research game was meta-analysis, that well used 'boiling down' of the published (hopefully peer-reviewed) science literature into something like a coherent 'conclusion'. The starting point for Effatpanah was that: "Current research suggests conflicting evidence surrounding the association between serum magnesium levels and the diagnosis of attention deficit hyperactivity disorder (ADHD)." It's interesting that this isn't the first time that magnesium and ADHD has been put under the meta-analysis microscope [2] and that particular meta-analysis didn't suggest such conflict.

Never mind. Seven studies made the grade for Effatpanah, together revealing that "subjects with ADHD had 0.105 mmol/l (95% CI: -0.188, -0.022; P < 0.013) lower serum magnesium levels compared with to their healthy controls." Researchers did also talk about 'high heterogeneity' across the studies analysed. This indicates that whilst there may well be "an inverse relationship between serum magnesium deficiency and ADHD" overall, the individual studies included in their meta-analysis weren't always in agreement with one and another.

So what conclusions can we take from the Effatpanah and other (meta-analysis) studies in this area? Well, more investigation is required on the suggestion of a *link* between magnesium and ADHD. We need to know more about the biology of why reduced biological levels of magnesium might be important to ADHD or ADHD-type behaviours [3] and whether something as simple as supplementing with magnesium *might* make a difference for some people [4] (minus any medical or clinical advice from me on this or any other topic). Indeed, on that last issue, I might refer you back to some other occasions where magnesium has been mentioned in the context of nutritional intervention for ADHD (see here). I'm also inclined to mention that there may be other 'labels' where magnesium might require a little more study (see here), some of which might 'overlap' with a diagnosis of ADHD. And of course, we should remember that magnesium 'issues' in the context of autism might not be the end of the story when it comes to trace metals and ADHD (see here)...

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[1] Effatpanah M. et al. Magnesium status and attention deficit hyperactivity disorder (ADHD): A meta-analysis. Psychiatry Res. 2019 Feb 19;274:228-234.

[2] Huang YH. et al. Significantly lower serum and hair magnesium levels in children with attention deficit hyperactivity disorder than controls: A systematic review and meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Mar 2;90:134-141.

[3] Black LJ. et al. Low dietary intake of magnesium is associated with increased externalising behaviours in adolescents. Public Health Nutr. 2015 Jul;18(10):1824-30.

[4] Ghanizadeh A. A systematic review of magnesium therapy for treating attention deficit hyperactivity disorder. Arch Iran Med. 2013 Jul;16(7):412-7.

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"Hypovitaminosis D is frequent and associated with depressive symptoms and anxiety disorders in schizophrenia"

The paper published by Guillaume Fond and colleagues [1] concluding that: "Hypovitaminosis D is frequent and associated with depressive symptoms and anxiety disorders in schizophrenia" provides the blogging fodder today. Hypovitaminosis D is just another way of saying vitamin D deficiency (or perhaps insufficiency) and follows a number of previous research findings (see here) concluding that schizophrenia seems to be one of a number of conditions/diagnosis/labels where tested vitamin D levels show sub-optimality.

Fond report results based on their examination of the "national FondaMental Expert Center (FACE-SZ) Cohort", something that has been talked about on this blog before (see here). So: "A comprehensive 2 daylong clinical and neuropsychological battery was administered in 140 SZ subjects included between 2015 and 2017" including vitamin D testing and analyses looking for the signs and symptoms of depression and anxiety.

Results: about one in five of the study participants were in a state of hypovitaminosis D. Looking at the accumulated behavioural data - "Depressive symptoms were assessed by the Positive and Negative Syndrome Scale depressive subscore and current anxiety disorder by the Structured Clinical Interview for Mental Disorders" - I was particularly struck by the *link* between vitamin D deficiency and 'current anxiety disorder' ("aOR = 6.18 [2.15-17.75], p = 0.001"). Further: "Vitamin D supplementation has been administered during the previous 12 months in only 8.5% of the subjects but was associated with lower depressive symptoms... and lower rate of current anxiety disorder... compared to patients with hypovitaminosis D."

These are interesting results. They reiterate that a diagnosis of schizophrenia does not seem to be protective against the development of vitamin D deficiency/insufficiency. They also highlight that schizophrenia perhaps should not be considered as a stand-alone diagnosis; something that is beginning to be realised across various different behavioural labels (see here). The suggestion of an *association* between anxiety and/or depression in the context of vitamin D is also important (perhaps even relevant to other studies that have suggested a direct link between vitamin D and schizophrenia). And then there is the 'already supplemented' finding that seems to fly in the face of quite a lot of other evidence suggesting that correcting vitamin D deficiency in the context of something like depression might not be directly applicable to improvement in depressive symptoms (see here). Research questions remain but the Fond results look interesting...

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[1] Fond G. et al. Hypovitaminosis D is associated with depression and anxiety in schizophrenia: Results from the national FACE-SZ cohort. Psychiatry Res. 2018 Sep 13;270:104-110.

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Vitamin D deficiency in adult patients admitted to a psychiatric ward: same as before

The 'same as before' part of the title of this post refers to the observation that vitamin D deficiency is not an uncommon feature for those admitted to psychiatric hospitals (see here and see here).

This time around I present the results published by Dipen Patel & Manjunath Minajagi [1] who reported that: "49% (N = 51) of participants were vitamin D deficient (serum 25(OH)D <30 nmol/L), and a further 42% (N = 44) were vitamin D insufficient (<50 nmol/L); 8.7% (N = 9) of participants were vitamin D sufficient (>50 nmol/L)."

'Participants' mentioned by Patel & Minajagi, referred to 104 adults (average age of 40) admitted to a psychiatric hospital who provided written consent to participate in their study and were diagnosed with a range of psychiatric disorders including "depressive episode", "bipolar affective disorder", "schizophrenia" and/or "personality disorder". We are told that: "Vitamin D levels were requested alongside standard admission blood tests on serum samples collected by venepuncture." Sounds like a good call by all accounts.

Alongside noting those quite important numbers/percentages of vitamin D deficiency and insufficiency (see here for more information about the distinction), authors also reported that: "There were no statistically significant differences noted in mean serum 25(OH)D associated with gender, age or primary diagnosis." They did however mention that: "Mean serum 25(OH)D was higher in participants of White British ethnicity compared with those of other ethnic backgrounds" indicating that skin colour probably plays a role in vitamin D production/levels. A shocker indeed [2].

"At the current time, there is insufficient evidence to draw any firm conclusions regarding an association between vitamin D deficiency and non-musculoskeletal health outcomes, including mental illness. More research in the form of larger epidemiological and intervention studies are needed to investigate the association between vitamin D and mental health outcomes; indeed, randomised controlled trials are planned that will hopefully shed more light on this intriguing area in the future." Sorry about the large text grab noted in that last sentence, but the authors said it better than I ever could in terms of (a) being cautious about making any specific connections between vitamin D deficiency/insufficiency and 'mental illness' and (b) the value of supplementation (see here and see here) outside of just restoring vitamin D levels to where they should be.

That being said, there is a further scheme of work to look at drawing on data from other labels (see here for example). Remembering also that, minus too many sweeping generalisations, some of the other health issues that seem to follow a psychiatric label *might* also show some involvement with vitamin D [3] too...

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[1] Patel D. & Minajagi M. Prevalence of vitamin D deficiency in adult patients admitted to a psychiatric hospital. BJPsych Bull. 2018 May 2:1-4.

[2] Bonilla C. et al. Skin pigmentation, sun exposure and vitamin D levels in children of the Avon Longitudinal Study of Parents and Children. BMC Public Health. 2014;14:597.

[3] Lu L. et al. Association of vitamin D with risk of type 2 diabetes: A Mendelian randomisation study in European and Chinese adults. PLoS Med. 2018 May 2;15(5):e1002566.

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On iron and vitamin D and autism

"This study suggests that deficiency of iron and Vitamin D as well as anemia were more common in autistic compared to control children."

'This study' refers to the findings reported by Abdulbari Bener and colleagues [1] (open-access available here) who set out to "investigate iron deficiency anemia and Vitamin D deficiency among autism children" in Qatar, a part of the world not renowned for its 'lack of sunshine' (a source material for the production of vitamin D).

Looking at some 300 children diagnosed with an autism spectrum disorder (ASD) and an equal number of controls, not-autism controls "who visited the primary health-care centers", researchers concluded that as a group, those with autism were more likely to present with low serum iron levels (and various related measures) and further that: "Vitamin D deficiency was considerably more common among autistic children." The authors provide some background details on what constitutes vitamin D deficiency and other 'levels': "Participants were classified into four categories: (1) severe Vitamin D deficiency, 25OHD <10 ng/ml; (2) moderate deficiency, 25OHD 10–19 ng/ml; (3) mild deficiency, 25OHD 20–29 ng/ml; and normal/optimal level is between 30 and 80 ng/ml."

When attempting to ascertain what factors might be important to the autism vs. not-autism participants, researchers reported that: "serum iron deficiency, serum calcium levels, serum Vitamin D levels; ferritin, reduced physical activity; child order, body mass index percentiles, and parental consanguinity can all be considered strong predictors and major factors associated with autism spectrum disorders." I might add that consanguinity defined as "unions between couples who share at least one common ancestor" is perhaps something more 'culturally-relevant' to autism in certain countries and societies [2] but not necessarily widely applicable...

What's more to say about the Bener findings? Well, given that issues with iron (see here) and issues with vitamin D (see here) are no strangers to the autism research landscape, there is little novelty in the conclusions reached even if being "the first report on an establishing level of iron deficiency in children with autism in Qatar and in Arabian Gulf Countries." The implication is again that preferential screening and treatment of such issues should be offered when a diagnosis of autism is received, save any further health inequalities arising. Whether or not treating something like iron deficiency and/or vitamin D issues will impact on behavioural presentation (see here) is perhaps an issue for another day. I say this bearing in mind the sentiments expressed in the recent paper by Philippe Autier and colleagues [3] examining the collected data on vitamin D supplementation "on non-skeletal disorders" and results seemingly "strengthening the hypothesis that low vitamin D status is a consequence of ill health, rather than its cause."

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[1] Bener A. et al. Iron and vitamin D levels among autism spectrum disorders children. Ann Afr Med. 2017 Oct-Dec;16(4):186-191.

[2] Mahajnah M. et al. Clinical characteristics of autism spectrum disorder in Israel: impact of ethnic and social diversities. Biomed Res Int. 2015;2015:962093.

[3] Autier P. et al. Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials. Lancet Diabetes Endocrinol. 2017 Oct 25. pii: S2213-8587(17)30357-1.

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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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Vitamin D deficiency is rife in an in-patient psychiatric unit for young people

"Adolescents within tier 4 adolescent mental health services may be at higher risk of vitamin D deficiency and so assessment of vitamin D levels should be considered as part of a standard physical health review for this group of young people."

So said the results reported by Neil Stewart & Simon Lewis [1] (open-access) who surveyed blood test results of patients admitted to a tier 4 psychiatric unit for vitamin D levels. Such a study was conducted on the basis that "it is plausible that vitamin D and/or vitamin D deficiency have a role in the pathogenesis of mental illness." Yes, indeed I might agree (see here and see here for examples).

Authors identified some 27 individuals who were tested for vitamin D deficiency between 2012 and 2014 from a population of 56. Over 80% (22/27) had vitamin D levels falling into the deficient or severely deficient range, and none of them had vitamin D levels reaching the bottom end of the typical range (75–250 nmol/L). A few other points are worthwhile noting: "In individuals from BME [black and minority ethnic] groups, who were potentially at higher risk of vitamin D deficiency due to increased skin pigmentation, 52.9% (9/17) were tested for vitamin D levels and 100% were deficient or severely deficient."

I was rather happy to see that authors have very much stuck to their findings minus too much speculation about their meaning. They, for example, suggest that all patients entering their particular service should "be considered at high risk of vitamin D deficiency" for whatever reason(s). They emphasise that vitamin D testing should be part and parcel of the routine physical examination normally provided to patients. They even talk about correcting any deficiency/insufficiency whilst monitoring vitamin D levels for any adverse effects or toxicity. In short, treat the physical health of their patients/service users despite the focus of their service being psychiatric. Lessons I'm sure that could be applied to many different labels/diagnoses with a behavioural or psychiatric element to them.

Going back to the idea that vitamin D deficiency might play a role in various conditions/states outside of those linked to bone health, the authors add to other voices suggesting that more investigation is needed to confirm/refute links between vitamin D status and behavioural or psychiatric issues. They note: "If an association between depression and vitamin D deficiency were to be confirmed through future study, vitamin D supplementation could potentially be a cost-effective treatment adjunct with minimal adverse effects." Again, I can't argue with the logic.

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[1] Stewart NF. & Lewis SN. Vitamin D deficiency in adolescents in a tier 4 psychiatric unit. BJPsych Bull. 2017 Jun;41(3):133-136.

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On the "increasing evidence for an association between vitamin D insufficiency and depression"

The quote titling this brief post - "increasing evidence for an association between vitamin D insufficiency and depression" - comes from the review by Parker and colleagues [1] who seem to be no strangers to reviewing evidence on a possible link between the sunshine vitamin/hormone and depression [2].

Affiliated to the Black Dog Institute in Oz ('black dog' being used as a metaphor for depression for quite a few years), the authors surveyed the quite voluminous peer-reviewed research literature on the topic of vitamin D and depression and concluded that there is 'adequate' evidence linking vitamin D levels and depression and also that: "Vitamin D supplementation/augmentation can be an effective treatment."

With no medical or clinical advice given or intended, regular readers of this blog won't perhaps be too surprised by this latest review offering. I've covered the topic again and again and again on this blog and quite frankly it's getting to the point where I'm getting sick of hearing myself talk/type about it. That being said, there are still questions that need answering on this issue: (1) given that 'depression' is quite a nebulous term, are there specific 'types' of depression that vitamin D levels/supplementation seem to be more associated with? (2) what is/are the mode(s) of action? bearing in mind there may be some clues in other literature linked to the possible extra-skeletal actions of vitamin D and (3) how and where do the genetics of vitamin D metabolism fit into all this?

I think it's also important to point out that depression is generally not something that just 'evaporates' when a vitamin D pill or any other pill is taken; more research needs to be done on the timing of supplementation and optimal dosage too as well as the potential use of vitamin D as an adjuvant to more traditional pharmacotherapy. There is a scheme of work to be followed but yet again, research on the possible link between vitamin D and depression continues at a pace.

And as if to further prove the point [3]...

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[1] Parker GB. et al. Vitamin D and depression. J Affect Disord. 2016 Oct 11;208:56-61.

[2] Parker G. & Brotchie H. 'D' for depression: any role for vitamin D? 'Food for Thought' II. Acta Psychiatr Scand. 2011 Oct;124(4):243-9

[3] Shin YC. et al. The associations among vitamin D deficiency, C-reactive protein, and depressive symptoms. J Psychosom Res. 2016 Nov;90:98-104.

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Parker GB, Brotchie H, & Graham RK (2016). Vitamin D and depression. Journal of affective disorders, 208, 56-61 PMID: 27750060

Vitamin D and autism: the story so far...

I don't want to keep you too long today aside from directing you to the literature review by Hajar Mazahery and colleagues [1] (open-access available here) discussing the collected peer-review literature on the topic of vitamin D and autism to date.


Anyone that stops by this blog might already know about my interest in the science around this issue (see here and see here for example) and how quite a few more resources really should be directed into this 'sunshine' research area. The Mazahery review pulls in the major themes included in the research literature including what has been published so far on levels of vitamin D and autism (and insufficiency/deficiency percentages), a possible role for ethnicity and migration, and use of vitamin D as a possible intervention option. They do also make mention of some of the genetics of vitamin D metabolism (see here) (and there is even more recent research on this [2]) and the potentially important link to areas such as autoimmunity with autism in mind (see here).

I'll leave you with their closing remarks: "Conclusions are not yet possible due to the inconsistent results, different methodological approaches employed, and very few trials in the current literature. However, there are some indications that early exposure to inadequate vitamin D may interact with other factors and contribute to the aetiology of autism, low vitamin D status might be highly prevalent in populations with ASD, and intervention with vitamin D might be beneficial in reducing autism symptoms among those who have ASD." That combined with what NICE here in England have already proposed more generally (see here) and you can perhaps see that vitamin D and the 'English Disease' (rickets) [3] might be but one connection for this important vitamin/hormone.

Oh, and as part of a wider group of variables 'linked' to autism, vitamin D is also discussed in the recent mini-review paper by Takeo Fujiwara and colleagues [4]. Thick and fast people, thick and fast...

And completely unrelated to today's post, IMFAR 2016 starts today.

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[1] Mazahery H. et al. Vitamin D and Autism Spectrum Disorder: A Literature Review. Nutrients. 2016 Apr 21;8(4). pii: E236.

[2] Coşkun S. et al. Association of polymorphisms in the vitamin D receptor gene and serum 25-hydroxyvitamin D levels in children with autism spectrum disorder. Gene. 2016 May 4. pii: S0378-1119(16)30361-4.

[3] Belton NR. Rickets--not only the "English disease". Acta Paediatr Scand Suppl. 1986;323:68-75.

[4] Fujiwara T. et al. Chemicals, Nutrition, and Autism Spectrum Disorder: A Mini-Review. Front. Neurosci. 2016; April 20.

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Mazahery H, Camargo CA, Conlon C, Beck KL, Kruger MC, & von Hurst PR (2016). Vitamin D and Autism Spectrum Disorder: A Literature Review. Nutrients, 8 (4) PMID: 27110819

Iodine and autism (again)

Welcome back to Questioning Answers in 2016.

Let's continue our travels down the autism peer-reviewed research path by starting with some brief discussion of the findings reported by Anna Błażewicz and colleagues [1] talking about iodine and autism.

With the aim of assessing "the iodine status of Polish boys with severe autism compared to their healthy peers" (authors words not mine), researchers reported results for various iodine and related measures (including metabolites related to thyroid function). They concluded that: "Thyroid hormones were within normal reference ranges in both groups while urinary iodine was significantly lower in autistic boys suggesting that further studies into the nonhormonal role of iodine in autism are required."

I've previously covered the topic of iodine and autism on this blog (see here). That time as this, we are talking about quite a few participants with autism presenting with iodine deficiency keeping in mind that the measurement of iodine in urine is actually quite a good way of ascertaining nutritional iodine status [2]. Błażewicz et al also suggested that various presented symptoms pertinent to autism might 'correlate' with iodine status; something again suggested in previous, independent results [3].

Insofar as the 'nonhormonal' uses of iodine and what deficiency in [some] autism might mean, I'd be minded to point other areas of interest outside of just cognitive effects [4]. The intersection between iodine, selenium and iron is worthwhile mentioning in light of the various co-dependencies of these nutrients in maintaining health and wellbeing. Other research has noted deficiencies in these three nutrients as part of a pattern in some autism [5]. Together with a suite of peer-reviewed literature suggesting that there maybe much more to see when it comes to micronutrient levels in at least some cases of autism, the onus once again is on screening followed by evidence-guided decisions on possible intervention(s).

Music, and as always at this time of year, think Vienna and An der schönen blauen Donau...

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[1] Błażewicz A. et al. Iodine in autism spectrum disorders. Journal of Trace Elements in Medicine and Biology. 2015. Dec 4.

[2] 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.

[3] 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.

[4] Redman K. et al. Iodine Deficiency and the Brain: Effects and Mechanisms. Crit Rev Food Sci Nutr. 2015 Apr 16:0.

[5] 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.

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Błażewicz, A., Makarewicz, A., Korona-Glowniak, I., Dolliver, W., & Kocjan, R. (2015). Iodine in autism spectrum disorders Journal of Trace Elements in Medicine and Biology DOI: 10.1016/j.jtemb.2015.12.002

Scurvy and autism continued

"Scurvy as a Manifestation of Food Selectivity in Children with Autism" read the title of the paper by Nina Ma and colleagues [1] continuing a topic of some interest to this blog regarding the need for more research and practical focus on nutritional insufficiency and deficiency when it comes to the label of autism (see here for example).

As per other occasions when scurvy - a condition linked to a deficiency of vitamin C - has been talked about in the context of autism (see here), the Ma paper continues an all-too familiar theme of how "a long-standing history of food selectivity" when it comes to at least some autism, can have some pretty serious onward health implications (see here). Alongside reporting on how "an elaborate panel of tests and procedures were undertaken before the diagnosis of scurvy was made" in seven children, all of whom had a developmental disorder, Ma et al highlight how vitamin C treatment "led to rapid recovery of symptoms." Without doing a Linus Pauling special on the wonders of vitamin C (accepting that in some respects he might not have been too far off the mark) I would draw your attention to some very preliminary work looking at vitamin C supplementation (sorry, ascorbic acid) with autism in mind [2].

That none of the children included in the Ma study "were supplemented with a multivitamin" at the time of their clinical evaluation is also relevant, especially in light of some rather sweeping generalisations made about other autism research on the use of dietary/nutritional supplementation and autism (see here). Certainly, what this and other related research suggests is that (a) a diagnosis of autism may indeed place someone at risk of certain dietary or nutritional issues and (b) appropriate screening should be in place to mitigate any potential health effects from such dietary-related problems. Oh, and just in case you were wondering, the horror that is a gluten- and casein-free (GFCF) diet when done correctly, is probably not to blame for cases of scurvy in relation to autism (see here)...

Music: Nothing But Thieves - Trip Switch.

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[1] Ma NS. et al. Brief Report: Scurvy as a Manifestation of Food Selectivity in Children with Autism. J Autism Dev Disord. 2015 Nov 21.

[2] Dolske MC. et al. A preliminary trial of ascorbic acid as supplemental therapy for autism. Prog Neuropsychopharmacol Biol Psychiatry. 1993 Sep;17(5):765-74.

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Ma NS, Thompson C, & Weston S (2015). Brief Report: Scurvy as a Manifestation of Food Selectivity in Children with Autism. Journal of autism and developmental disorders PMID: 26590972

Reduced zinc levels in schizophrenia: study AND meta-analysis

"Single element analysis indicated that the concentrations of cesium, zinc, and selenium were significantly reduced in patients with schizophrenia in both the training and test groups."

Those were some of the findings reported by Lei Cai and colleagues [1] (open-access available here) as part of their study "to quantify the levels of 35 elements in the sera of 111 Schizophrenia patients and 110 healthy participants, which consisted of a training (61/61 for cases/controls included) and a test group including remaining participants."

Following some increasing interest in the field of metallomics (see here) focused on "the detection, mapping, and quantification of essential trace elements in body fluids, tissues, and organs", Cai et al employed the powerful analytical tool of inductively coupled plasma-mass spectrometry (ICP-MS) to such metals analysis with schizophrenia in mind.

"Serum samples were collected from the patients at baseline before initiation of anti-psychotic treatment" we are told. Alongside the analysis of samples from asymptomatic controls, authors reported that zinc in particular, might be something to watch for in schizophrenia given that: "Zn [zinc] tended to affect Schizophrenia in an individual way, Se [selenium] in combination with other elements, and Cs [caesium] in both an independent- and network-based manners."

Not content with just doing their own science, Cai and colleagues also decided to conduct a meta-analysis on some of the previous research that has been done on metals and schizophrenia with a specific focus on "Zn or Zinc or Se or Selenium or Cs or Cesium or Phosphorus or P or Lead or Pb or Ytterbium or Yb and Schizophrenia." They reported that the previous research looking at zinc levels in schizophrenia were a little mixed depending on where geographically the study was based but: "The meta-analysis including 522 cases and 360 controls supported that Zinc was significantly associated with Schizophrenia." This 'my study + meta-analyse your studies' model has been discussed before on this blog, and with schizophrenia similarly in mind (see here).

"It is worth noting that the current study did not address the causes of the trace element deficiencies and was not designed to establish a cause and effect relationship with Schizophrenia. Although nutritional deficiencies of Zn, Cs, and Se may increase the risk for Schizophrenia, it is equally plausible that Schizophrenia may lead to altered metabolism." This is an important point to the Cai study insofar as the questions that remain about 'cause-and-effect' in relation to something like zinc and schizophrenia. The fact that zinc levels, like other nutrients, seem to be related to quite an array of conditions (autism, attention-deficit hyperactivity disorder (ADHD), depression) likewise means that one has to be cautious about putting forward any exclusive relationship between zinc and schizophrenia. That is unless one accepts that all these conditions might have some commonalities? I might also put the study by Liu and colleagues [2] to you at this stage, and their findings suggesting that there wasn't too much to see when it came to zinc and schizophrenia in their cohort as a balance.

With no clinical advice given or intended, I suppose the next stage of this work is the question of whether supplementing with something like zinc [3] might do anything further than correct a nutritional deficiency?

Music: 'Alive' by Sia and some impressive renditions of the Empi kata and Kanku Dai kata among others (although one of my brood says the young karateka in the video needs to work more on her kicks).

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[1] Cai L. et al. Serum trace element differences between Schizophrenia patients and controls in the Han Chinese population. Sci Rep. 2015 Oct 12;5:15013.

[2] Liu T. et al. Comparative Study on Serum Levels of 10 Trace Elements in Schizophrenia. PLoS One. 2015 Jul 17;10(7):e0133622.

[3] Grabrucker AM. et al. Brain-Delivery of Zinc-Ions as Potential Treatment for Neurological Diseases: Mini Review. Drug Deliv Lett. 2011 Sep;1(1):13-23.

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Cai, L., Chen, T., Yang, J., Zhou, K., Yan, X., Chen, W., Sun, L., Li, L., Qin, S., Wang, P., Yang, P., Cui, D., Burmeister, M., He, L., Jia, W., & Wan, C. (2015). Serum trace element differences between Schizophrenia patients and controls in the Han Chinese population Scientific Reports, 5 DOI: 10.1038/srep15013