Friday, 20 July 2018

A short-term aquatic exercise intervention for (some) individuals with CFS/ME?

I have to say that I did um-and-ah about whether or not to make this blog entry on the results published by Suzanne Broadbent and colleagues [1]. In it, researchers talked about the use of "a short-term aquatic exercise programme" with a small group of women diagnosed with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

My 'in two minds' state was because the words 'exercise as intervention' and 'CFS/ME' have a rather poor history both in research and clinical terms; as proposals like 'graded exercise therapy' (GET) have the ability to invoke some rather adverse memories and reports for some/many people (see here and see here). As you can see, I did in the end decide that science should be seen and heard, even if it might be a tad uncomfortable. As hopefully you'll see, the Broadbent results might even provide some much needed focus in the area of activity and exercise with CFS/ME in mind minus any sweeping generalisations and psychobabble explanations which have typically followed such research.

Before progressing through their paper, it is worth mentioning that some of the authors on this most recent paper have some 'research form' when it comes to looking at exercise in the context of CFS/ME. Yes, there is mention of the words 'graded exercise' [2] in previous publications, but interestingly this is wrapped in the context of "immune system dysfunction in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)" and their looking at various biological aspects of exercise [3] with an immune system slant to it. This is not your regular 'de-conditioning' thinking...

Aquatic exercise was the name of the research game on this most recent occasion, and an open trial detailing various physiological and behavioural measures pre- and post-use of "an initial 20-min aquatic exercise session then two self-paced 20-min sessions per week for 4 weeks" with 11 women. As you can already see, this was not a controlled trial and there was no comparison group used; just an initial research foray looking at whether their fairly brief water-based exercise program might produce some meaningful results or not. I assume that the authors were conscious that water-based exercise has some advantages over er, not water-based activity, in relation to impact (aquatic exercise is typically termed 'low impact) and also strength-building (water resistance is much greater than air resistance). I might also add that others have been following the development of this trial with some interest (see here).

'First, do no harm' is a primary tenet in all of medicine, and on the basis of "no reports of symptom exacerbation" in their small participant cohort, the authors can tick an important item of their research checklist on this occasion. Alongside, authors detail results based on various physiological parameters: "6 min Walk Test (6MWT), perceived exertion (RPE), hand grip strength, Sit-to-Stand, Sit-Reach test, Apley's shoulder test" as well as monitoring heart rate after each session. There's even mention of "24- and 48-h post-session tiredness/pain scores" which, I assume, could be stretched to mean looking at aspects of an important symptom: post-extertional malaise (PEM). And on that basis the authors reported that many of those physiological parameters did show changes between pre- and post-intervention in relation to things like grip strength, the 6MWT and also pain ("24-h post-test tiredness and pain decreased"). Ergo, aquatic exercise was seemingly well-tolerated in their small participant group and further - more scientifically 'stronger' - investigations are perhaps indicated to substantiate this finding.

When I first tweeted about the Broadbent article, it did create some discussion (see here). I wasn't surprised by this given the nature of the trial and some of the references to other peer-reviewed research made by authors. It's not easy to put into words how much damage has been done by the widespread (universal?) advocacy of something like GET when it comes to ME/CFS. Suffice to say that for many people with CFS/ME, any study that mentions 'exercise' as an intervention is likely to be met with a degree of scepticism. Once bitten and all that. And I also note the words "raising the possibility that there could be future lawsuits from ME patients whose condition has worsened from the treatment" have recently been mentioned in relation to GET...

But I do think there is more research to be done in this area on the back of the Broadbent results. Minus hype, sweeping generalisation and again importantly without any 'psychological theory' input, further analysis of the physiological effects of exercise on those with ME/CFS is a must, particularly with something like PEM in mind. No, I'm not advocating research practices that unethically put people with CFS/ME onto exercise regimes, but rather smaller research steps starting, for example, with the greater use of actigraphy on a day-to-day basis. It's been a real point of contention that actigraphy - the (objective) study of rest and activity cycles - has not been more incorporated into CFS/ME research (see here). Particularly, when discussions about 'recovery' from ME/CFS have been prominent in many quarters (see here) seemingly without mention of objective ways and means of establishing parameters of such recovery. I'd also suggest that the authors' previous work on immune function following exercise could also be applied to further aquatic exercise research too...

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[1] Broadbent S. et al. Effects of a short-term aquatic exercise intervention on symptoms and exercise capacity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis: a pilot study. Eur J Appl Physiol. 2018 Jun 19.

[2] Broadbent S. & Coutts R. Intermittent and graded exercise effects on NK cell degranulation markers LAMP-1/LAMP-2 and CD8+CD38+ in chronic fatigue syndrome/myalgic encephalomyelitis. Physiol Rep. 2017 Mar;5(5). pii: e13091.

[3] Broadbent S. & Coutts R. Graded versus Intermittent Exercise Effects on Lymphocytes in Chronic Fatigue Syndrome. Med Sci Sports Exerc. 2016 Sep;48(9):1655-63.

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Thursday, 19 July 2018

Probiotics for anxiety: fine if you're a (diseased) rodent, but not yet ready for mass roll-out for humans

"While probiotic administration reduces anxiety-like behavior in rodents, the current state of clinical research does not (yet) support probiotics as an efficacious treatment for anxiety."

That was the research bottom-line reported by Daniel Reis and colleagues [1] who scoured the various peer-reviewed science databases looking "to evaluate the clinical and preclinical (animal model) evidence regarding the effect of probiotic administration on anxiety."

Probiotics, in case you don't already know, describe a range of bacteria and yeasts that are touted "as having various health benefits." Most probiotics are taken orally and are thought to be acting on the multitude of wee beasties that in particular, call our gut home (gut microbiota). Anxiety represents a 'state' that manifests as various physical and psychological symptoms. I've talked a lot about anxiety on this blog in the specific context of autism (see here for example) and how absolutely disabling it can be. Mentioning anxiety in the same sentence as probiotics provides a clue that something called the 'gut-brain axis' might be important for some...

Reis et al undertook a systematic review and meta-analysis of the pertinent research literature, having previously published their intention to do so (see here). Randomised-controlled trials matching their inclusion criteria were examined up to November 2017 including both pre-clinical (animal) and clinical (human) studies. The various results were collated, examined and boiled down to a consensus on the basis of the currently available data.

Bearing in mind that the word 'probiotic' covers a lot of ground in terms of what bacteria/yeasts and what preparations are included, the results were a bit of a mixed bag. As mentioned in the opening line to this post, if you're a rodent, the chances are favourable that taking a probiotic might *reduce* anxiety-like behaviour(s). One has to be a little careful about how one defines 'animal anxiety' but compared to placebo, probiotics - specifically including Lactobacillus (L.) rhamnosus - might be something to consider. Even better if you are a 'diseased' rodent...

When it came to the research on anxiety and probiotics in humans, the current status of the research is a little more 'complicated'. So: "Combining standardized mean differences (SMDs) for the 14 included studies revealed a pooled SMD of -0.12, indicating that probiotic administration did not result in a significant reduction of anxiety." The results did not alter where dose and duration were taken into account or whether 'healthy' or 'clinical' participants were observed. Ergo, the current state of the research (up to November 2017) does not generally suggest an action for probiotics in the treatment/management of anxiety in humans.

Of course that does not mean that every study on animals and humans found the same direction (or lack) of effect. We are told that: "At the level of individual trials, 12 of the 22 included animal studies found that probiotics significantly reduced anxiety-like behavior on at least one outcome measure" and "3 of the 14 included clinical studies (encompassing 1527 individuals) found that probiotics significantly reduced symptoms of anxiety." I might also direct your attention to earlier meta-analyses that found that probiotics did seem to affect psychological symptoms in people including anxiety (see here). One therefore needs to be mindful of the limitations of such systematic reviews and meta-analyses and the sweeping generalisations that are made as a result.

But... the results, as they currently stand, suggest that more investigation and perhaps less 'hype' is required around the topic of probiotics for anxiety.

And speaking of meta-analyses over-turning other meta-analyses, I'm not sure I would describe fish oils for a healthy heart as 'nonsense' as one media report did on the basis of a new review. Particularly when other reviews not-so-long ago along similar lines, came to a slightly different opinion with regards to some groups of people...

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[1] Reis DJ. et al. The anxiolytic effect of probiotics: A systematic review and meta-analysis of the clinical and preclinical literature. PLoS ONE. 2018; 13(6): e0199041.

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Wednesday, 18 July 2018

Another blood test for autism?

"These results form the foundation for the development of a biochemical test for ASD [autism spectrum disorder] which promises to aid diagnosis of ASD and provide biochemical understanding of the disease, applicable to at least a subset of the ASD population."

OK, use of the word 'disease' in the context of autism is really, really not OK in this day and age. Researchers, peer reviewers and their publishing journals should be doing something about this kind of language. There are however some potentially important aspects to the work published by Daniel Howsmon and colleagues [1] worth talking about. Not least is their observation on how "folate‐dependent one carbon metabolism (FOCM) and transsulfuration (TS) pathways" that have been quite readily *associated* with autism might be linked to quite a bit more than just uncovering the biochemistry of at least some autism (see here for example).

Before progressing further into these findings, I note there has already been some media interest in them (see here) with a byline reading: "First physiological test for autism proves high accuracy in second trial." We'll see about that...

So, after quite a long introduction about 'biomarkers for autism' and how they "come with their own set of challenges before they reach clinical translation", authors report further results building on some of their previous work in this area [2] that I've already covered on this blog (see here). On that previous research occasion, the suggestion was that between 5 and 7 metabolites linked to folate and/or transsulfuration pathways provided a 'best fit' when it came to picking out children diagnosed with autism from those not diagnosed with autism.

This time around, there was an 'extension' to that work: "(a) By comparing univariate analysis with four different multivariate methods on FOCM/TS data for ASD biomarker development to ensure that the identified results are not restricted to FDA [Fisher Discriminant Analysis] and (b) to test and validate multivariate FOCM/TS biomarkers on data collected from a new cohort of ASD participants." The words 'training data' and 'validation data' are used quite a bit throughout the Howsmon article, illustrating how different statistical classification methods were initially applied to training data from the cohort used in their first paper, which were then tested on a new cohort of participants (n=154) diagnosed with an ASD. Given some of the names included on the authorship list, it's no surprise that participant data with regards to the metabolites being looked at were drawn from other studies looking at the possible clinical value of preparations like folinic acid (see here) and sapropterin (see here) with autism in mind.

When those different statistical classification methods were applied and data was crunched, a few observations were made. The headline result was that one model/method produced the best 'potential' biomarker results and it was the same/similar method to that previously discussed by the authors. To quote: "An FDA model using five variables was shown to slightly outperform the other models on this new validation data set." That being said, the accuracy rates (including false positive and false negative rates) hovering around the high 80%s have to take into account that two of the metabolites thought to be important on the last research occasion - % DNA methylation and 8‐OHG - "were not present in the validation set" on this research occasion. This is a pity and a weakness of the current study.

So, do we at last have a 'physiological test' with 'high accuracy' for picking out autism from not-autism? Erm, not quite yet. With all due respect to the authors, their data is interesting and does partially back up their original findings, but we're not quite there yet with regards to rolling out any sort of biological test for autism. Indeed, in these days of the plural 'autisms' (see here) and acknowledging that the diagnosis of autism rarely presents in some sort of diagnostic vacuum (see here) it could be worthwhile re-evaluating whether we're ever likely to see a 'one biological test to diagnose them all' situation.

Further investigations are however indicated and of course, this more recent information does add to the quite rich data already generated suggesting that quite a bit more focus on things like methionine, homocysteine, cysteine and glutathione in relation to autism could be an important research path to follow. I'm also minded to suggest that different research teams taking on a 'possible biomarker for autism' type research perhaps need to talk more to each other (see here) pooling findings, resources and perhaps participant groups too...

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[1] Howsmon DP. et al. Multivariate techniques enable a biochemical classification of children with autism spectrum disorder versus typically‐developing peers: A comparison and validation study. Bioengineering & Translational Medicine. 2018. May 14.

[2] Howsmon DP. et al. Classification and adaptive behavior prediction of children with autism spectrum disorder based upon multivariate data analysis of markers of oxidative stress and DNA methylation. PLoS Comput Biol. 2017 Mar 16;13(3):e1005385.

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Tuesday, 17 July 2018

The prevalence of autism in China meta-analysed

"Based on diagnostic criteria the pooled prevalence of ASDs [autism spectrum disorder] was 39.23 per 10,000... specifically, the prevalence of autism was 10.18 per 10,000."

That was the conclusion reached by Fei Wang and colleagues [1] following their "comprehensive meta-analysis of the pooled prevalence of ASDs in China" based on data from 44 studies comprising about 2.3 million people aged below 18 years of age. Relying on data published from database inception up to February 2017, authors trawled the peer-reviewed scientific domain  - "PubMed, EMBASE, PsycINFO, China National Knowledge Infrastructure, Chinese biomedical literature service system (SinoMed) and Wan Fang" - looking for pertinent articles regarding the epidemiology of autism in China. Their results covered "30 provinces/ municipalities/ autonomous regions in China" and were in the most part conducted in the 21st century. A few studies (n=7) were rated as being of 'high methodological quality' with the remaining meeting guidance for 'moderate quality'.

Accepting that diagnosis via DSM or ICD was not the only inclusion criteria - also including "screening tools [such as the Clancy Autism Behavior Scale (CABS), Children Autism Spectrum Test (CAST) and Checklist for Autism in Toddlers (CHAT)]" - the collected figures arrived at 0.39% and 0.01% for ASD and autism are quite a bit lower than we're typically used to seeing. Take for examples, the most recent stats from the US CDC on [estimated] ASD prevalence (see here) talking about 1.7% of 8-year olds diagnosed with autism or the data from Northern Ireland (see here) (2.9% of school-aged children), and you can see quite a stark difference. Only when Wang took into account the prevalence of ASD solely based on those studies utilising screening tools does the figure of 429.07 per 10,000 equating to 4.29% look anything like the data from those other countries.

What could all this mean? Well, we do have to be a little careful not to read too much into these collected statistics. As per another paper [2] published at roughly the same time as the Wang paper, there may be various factors - 'challenges' - influencing the particular status of autism screening and case ascertainment in China that might need consideration. As far as I can see, there is for example, no national screening guidance for autism covering all of China, so "inconsistencies in screening and diagnostic procedures... and discrepancies between diagnostic criteria" are going to be potentially significant variables. Indeed, other studies have pointed to a 'high prevalence rate of suspected autism' in some parts of China (see here) which is directly contrary to the Wang findings. Alongside other potentially important factors such as 'willingness' to screen for autism and socioeconomic factors influencing 'ability' to screen for autism, and the picture that emerges is a complicated one.

But... one also has to entertain the possibility that the prevalence of autism in China *might* be different to other countries around the globe. I've kinda touched upon this quite recently (see here). I don't want to speculate too much about why this might be at this point, but some combination of genes and elements of environment could be relevant (see here) with lots more science to be done...

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[1] Wang F. et al. The prevalence of autism spectrum disorders in China: a comprehensive meta-analysis. Int J Biol Sci. 2018 May 12;14(7):717-725.

[2] Pang Y. et al. Challenges of case identification and diagnosis of Autism Spectrum Disorders in China: A critical review of procedures, assessment, and diagnostic criteria. Research in Autism Spectrum Disorders. 2018; 53: 53-66.

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Monday, 16 July 2018

"A strict and lifelong gluten-free diet can help recover vitamin D level without any supplementation"

The quote titling this post - "A strict and lifelong gluten-free diet can help recover vitamin D level without any supplementation" - comes from the results published by Fabiana Zingone & Carolina Ciacci [1].

These authors inspected the peer-reviewed literature looking at vitamin D levels in relation to the archetypal 'diet can affect health' autoimmune condition that is coeliac (celiac) disease. They looked at both something called calcifediol, otherwise known as 25-hydroxyvitamin D (25(OH)D), and also something called calcitriol, also known as 1,25-dihydroxyvitamin D3. The difference between the two 'forms' of vitamin D is that one represents the 'pre-hormone' version  - (25(OH)D) - that is typically quantified to give a 'where you're at' measurement of biological vitamin D levels, and the other - 1,25-dihydroxyvitamin D3 - is the 'active' metabolite. Through the wonders of something called mass spectrometry, these and other 'forms' of vitamin D are able to be quite accurately measured [2] in various biological fluids.

Zingone & Ciacci reported that "most of the studies on vitamin D in adult CeD [coeliac disease] report a 25 (OH) vitamin D deficiency at diagnosis that disappears when the patient goes on a gluten-free diet, independently of any supplementation." This finding really intrigued me. It got me thinking of a few things; notably about mechanisms and biological relationships and indeed, how applicable such a finding could be to the general 'not coeliac' population or those 'around the diagnostic edges' of CeD.

OK, it should be noted that part-and-parcel of CeD is an issue with malabsorption, where 'the body does not fully absorb nutrients' (see here). The inflammatory processes at work in CeD do some pretty awful things to the structure and functioning of the mucosal lining of the bowel which aren't really conducive to optimal absorption of nutrients from food. The implementation of a gluten-free diet does help matters; and so logic dictates that absorption of something like vitamin D from food sources will be improved when a gluten-free diet is implemented. I've also blogged about how this process *may* also be part of the effect noted in relation to [some] autism and the use of similar dietary intervention strategies (see here). Alongside, I'll mention that, done right, a gluten-free diet is actually not the most unhealthiest diet in the world either.

Having already sort-of mentioned something like non-coeliac gluten/wheat sensitivity in the contest of the 'diagnostic edges' of CeD, I do wonder if there could be a further plan of research there too. Y'know to look at questions like whether such not-quite-coeliac-disease conditions also (a) manifest as having low levels of vitamin D when not diet treated and (b) whether the use of a gluten-free or other diet (see here) might similarly positively effect vitamin D levels in those circumstances?

There's also another potentially important explanation to consider which was tweeted by Dr Emily Deans (she of the fabulous Evolutionary Psychiatry blogs): could vitamin D deficiency be a marker of something more general? To quote from Dr Deans' tweet (shown pictured above): "Because it’s [vitamin D] an inverse acute phase reactant and goes down with illness and up with health." There is some sound logic behind such an observation insofar as vitamin D insufficiency/deficiency being associated with all manner of physical and behavioural/psychiatric diagnoses/conditions/states (see here and see here for examples). Correction of vitamin D deficiency is all well and good when it comes to correcting biological measures, but outside of treating something like rickets, the evidence for extra-skeletal effects from such supplementation is currently not that great.

Finally, I'll draw your attention back to some work suggesting that vitamin D might itself have some interesting effects on gut barrier function (at least in mice) (see here). One wonders what this could also mean for CeD and the spectrum of gluten-related issues?

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[1] Zingone F. & Ciacci C. The value and significance of 25(OH) and 1,25(OH) vitamin D serum levels in adult coeliac patients: A review of the literature. Dig Liver Dis. 2018 Apr 13. pii: S1590-8658(18)30702-3.

[2] van den Ouweland JM. et al. Vitamin D and metabolites measurement by tandem mass spectrometry. Rev Endocr Metab Disord. 2013 Jun;14(2):159-84.

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Saturday, 14 July 2018

Shocker alert: gut problems in autism impact on sleep (again)

"Increased odds of sleep problems were most frequently associated with gastrointestinal distress (GID) and non-verbal IQ (NVIQ), followed by male sex and age."

That was one of the findings reported by Ann Johansson and colleagues [1] who set out to examine "the relationship between sleep problems and characteristics of children with ASD [autism spectrum disorder] in a large, nationwide sample." Mention of the words 'Simons Simplex Collection' in the Johansson article provides a clue as to the source population examined in this study and some of the hows-and-whys of the research. From what I also understand, this paper is part of a doctoral thesis by Johansson looking at some of the possible genetics of sleep with autism in mind (see here). Indeed, if one scrolls to page 70 of the thesis, one finds the study in question...

The Simons Simplex Collection Sleep Interview (SSCSI) was the instrument of choice for assessing sleep issues. This is a short parent-report questionnaire that includes both a composite score for total sleep issues and subscale scores for things like 'sleep duration issues'. Alongside, GID was classified "if they were reported (yes/no) to have bloating/excess gas, celiac disease, constipation, diarrhea, ulcers, gastroesophageal reflux disease, inflammatory bowel disease (Crohn’s disease, ulcerative colitis), irritable bowel syndrome, abdominal pain, unusual stools, vomiting, and/or other GID." Throw in scores on the ADOS "used to measure ASD severity" and crunch the data...

I've inserted the word 'again' into the title of this post because this is not the first time that functional gastrointestinal issues 'over-represented' in autism have been connected to sleep issues (see here). This time around, researchers mention that over 40% of their cohort (2000+ children) "were categorized as having mild or moderate/severe sleep problems" according to their SSCSI composite score. 'Difficulty falling asleep' seemed to be one of the more frequently reported issues. GID - gastrointestinal distress - was the strongest factor linked to sleep issues (odds ratio = 2.79), again based on the SSCSI composite score for sleep issues. There were other combinations of symptoms potentially linking to sleep noted by the authors but I'm minded to put them to one side for now.

Caveats? Well, one big caveat sticks out: the reliance on parent-reported responses to a questionnaire about sleep without any reference to objective measures of sleep. I've gone on and on (and on) about the use of actigraphy when it comes to sleep research relating to various diagnostic labels (see here and see here for examples) and well, keep coming to the same conclusion about a strong requirement for such objective measures on sleep-wake cycles. I appreciate that there may be some 'consumer resistance' to wearing a wristband for example, to measure activity and rest cycles (see here), but surely someone, somewhere can engineer something when kids don't want to wear such gadgets? Insofar as the classification of GID also relying on parental report, I'm a little kinder to this because the evidence is pretty good for suggesting that parents might be tuned into what is typical and what is not typical from a functional bowel habits perspective in their offspring (see here)...

No mind, the results do accord with other independent data on how gut issues present in autism can seemingly have some far-reaching effects. As to 'how', well, I would always start with the obvious explanation: pain and discomfort caused by bowel issues affecting sleep, and then work back from there. Indeed, as if I need to say it again, bowel issues (both functional and more pathological) are truly 'over-represented' when it comes to a diagnosis of autism (see here) and science and clinical practice really need to do a lot more to tackle such issues as and when they are reported/detected...

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[1] Johansson AEE. et al. Characteristics of sleep in children with autism spectrum disorders from the Simons Simplex Collection. Research in Autism Spectrum Disorders. 2018; 53: 18-30.

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Friday, 13 July 2018

"little evidence for the involvement of Mg2+ in the mood disorders"?

Mg2+ described in the title of this post refers to magnesium, a mineral that participates in quite a few important biological reactions in the human body. Outside of its proposed involvement in a variety of somatic conditions and diagnoses, a deficiency in magnesium has also been *linked* to various psychiatric and behavioural issues too (see here). The findings reported by Danny Phelan and colleagues [1] however, stress caution in making too many sweeping generalisations on the basis of the currently available peer-reviewed data, albeit with hints that magnesium might have some role to play for some...

The name of the research game for Phelan et al was 'systematic review and meta-analysis', which basically means identifying, collating and 'boiling down' the [currently available] relevant research into some sort of coherent whole. Some 58 research articles including over 45,000 participants were used for 'quantitative synthesis' across a variety of different effects: the prevalence/incidence of depression as a function of magnesium intake, magnesium levels as a function of mood disorder status, magnesium concentration according to mood disorder severity and mood disorder status as a function of magnesium treatment. The results were interesting...

"Adherence to a diet high in Mg2+ was associated with a lower prevalence of depression in cross-sectional studies... but not in longitudinal cohorts that assessed the incidence of new-onset depression." Taking into account the difference in study design, this finding translates as a suggestion that "dietary Mg2+ intake may play a part in the pathology of depression" with the caveat that cause-and-effect was not proven. Accepting also that 'depression' as an umbrella term covers quite a bit of diagnostic ground, authors observed that: "There were no studies which reported on the effects of dietary Mg2+ on symptoms of bipolar disorder" so no conclusions can be currently formed either way.

Next: "Against expectations, we found higher Mg2+ levels in bodily fluids in patients with a mood disorder relative to healthy control subjects." This is a peculiar finding and one that needs further explanation beyond possibly just reflecting "the hypothesis that an increase in Mg2+ may underlie the clinical efficacy of (fast-acting) antidepressants" or dehydration *caused by* the use of pharmacotherapy indicated for mood disorders. I might add that such a findings could just be indicative of magnesium showing a epiphenomenal relationship with mood disorder too.

Finally: "In line with expectations, we found that treatment with Mg2+ supplements was associated with a decline in depressive symptoms." The authors yet again mention that study design/type may have something to do with the results observed; in particular, that a such an effect seemed to be confined to those studies with no placebo condition.

I was initially a little unsure about the 'cautiousness' expressed by Phelan et al on a possible role for magnesium in [some] mood disorders. Statements like: "Our results provide little evidence for the involvement of Mg2+ in the mood disorders" didn't seemingly really reflect the findings being reported on, but with a bit of further critical thinking I've changed my tune a bit. I would still perhaps argue that it would have been more accurate to say something along the lines of 'there is evidence out there for an effect on dietary magnesium potentially being associated with a lower instance of depression but that evidence is not as methodologically strong as one would hope'. But oh-um. Certainly I think we can conclude that there is an additional scheme of research to follow to aid in future position statements on this topic.

And then there is the question of 'why?'. Why should magnesium affect mental health? And what about any effects from various 'different types' of magnesium available?

To close, I've linked to this before but here it is again: possibly the best opening to a film ever...

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[1] Phelan D. et al. Magnesium and mood disorders: systematic review and meta-analysis. BJPsych Open. 2018 Jul;4(4):167-179.

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