Allergic disease and ADHD yet again...

Although words like 'first' and 'largest' were used in the paper by Chia-Feng Yang and colleagues [1] (open-access available here) observing that "AD [atopic dermatitis] and asthma with allergic sensitization are associated with ADHD [attention-deficit hyperactivity disorder] in children", I'm minded to be a little cautious with such 'we're the first/best' assertions.

Cautious because, on quite a few peer-reviewed research occasions (see here for example), a possible *link* between various allergic disease and ADHD has already been noted; even potentially extending to studies talking about how treatment for allergic disease might on some occasions also impact on presented ADHD symptoms (see here) (with no medical advice given or intended).

Yang et al relied on data from a research favourite country, Taiwan, derived from an initiative called the Childhood Environment and Allergic diseases Study (CEAS). The clue is in the name of the initiative in terms of what they were looking for/at, as per other publications derived from the initiative [2]. From the 3200-odd participants eligible for participation, researchers relied on data from over 2700 children. Questions about allergic disease history were asked to parents of said participants, alongside other 'environmental' factors such as family income, tobacco exposure and breastfeeding history. I note also a question about 'incensing at home' is also included relating to the use of burning incense typically linked to religious practices in certain cultures.

When it came to a diagnosis of ADHD, it's not entirely clear about how this was ascertained but it looks like diagnosis was given by a clinician: "The conditions of disease in children were confirmed by board-certified child psychiatrists or pediatric neurologists, according to the clinical evaluation." I should also mention that participants also received skin prick tests (SPTs) covering a range of potential allergens: "house dust mites (HDMs mix, including Der p, Der f, Der m, and Blot allergens), cockroaches, dog dander, milk, egg, and crab allergens" as way of defining allergic sensitisation.

Results: there was a "strong positive association between ADHD and allergic sensitization as diagnosed by positive SPTs." In other words, despite finding a fairly low level of ADHD in their sample (1%), those who 'reacted' to one or more of the allergens tested for via the skin prick test seemed to be at some increased risk of ADHD. Such an enhanced risk spanned both those presenting with "AD with allergic sensitization and asthma with allergic sensitization."

The authors provide some further results and details on the possible hows-and-whys of their results. Obviously the immune system figures quite strongly given what for example, they were testing for with the SPT and their focus on AD and asthma. The word 'inflammation' also figures quite heavily. I note too that the authors reiterate previous suggestions that: "Control of allergens exposure might be a critical factor influencing the development of ADHD."

There is a further scheme of work to follow in this area, not just dealing with mechanisms but also in relation to 'treating' allergies also potentially 'treating' [some] ADHD. I say this on the basis that other independent research has observed that before reaching for the antihistamine as a potential ADHD-modifier, there may actually be a connection between early antihistamine exposure and the development of ADHD [3] (albeit with potential confounders) to keep in mind. Other work also supporting a link between ADHD and atopic disease [4] provides some other 'clues' that may require further investigation; not least "cow's milk intolerance", which ties into similar findings (see here) and could also be one route from which ADHD heightens the risk of subsequent future psychiatric disorder (see here) in light of other 'milk' associations (see here).

----------

[1] Yang CF. et al. Association between allergic diseases, allergic sensitization and attention-deficit/hyperactivity disorder in children: A large-scale, population-based study. J Chin Med Assoc. 2017 Nov 24. pii: S1726-4901(17)30304-0.

[2] Wang IJ. et al. Allergens, air pollutants, and childhood allergic diseases. Int J Hyg Environ Health. 2016 Jan;219(1):66-71.

[3] Schmitt J. et al. Increased attention-deficit/hyperactivity symptoms in atopic dermatitis are associated with history of antihistamine use. Allergy. 2017 Oct 4.

[4] Hak E. et al. Association of childhood attention-deficit/hyperactivity disorder with atopic diseases and skin infections? A matched case-control study using the General Practice Research Database. Ann Allergy Asthma Immunol. 2013 Aug;111(2):102-106.e2.

----------

On dietary and nutritional therapies for ME/CFS

ME/CFS in case you don't already know refers to Myalgic Encephalomyelitis / Chronic Fatigue Syndrome and, according to the findings reported by Nadia Campagnolo and colleagues [1], is in need of quite a bit more scientific investigation when it comes to the application of dietary changes and nutritional supplements to potentially alter the course of the condition(s).

Surveying the peer-reviewed literature "from 1994 to May 2016" the authors looked for peer-reviewed studies where "CFS/ME patients modified their diet or supplemented their habitual diet on patient-centred outcomes (fatigue, quality of life, physical activity and/or psychological wellbeing)." They found 17 studies that included 14 different interventions. Unfortunately they concluded that: "Many studies did not show therapeutic benefit on CFS/ME" alongside the observation that the methodological quality of the research in this areas 'could do better'.

But it was not all research doom-and-gloom as some approaches seemed to show promise: "Improvements in fatigue were observed for nicotinamide adenine dinucleotide hydride (NADH), probiotics, high cocoa polyphenol rich chocolate, and a combination of NADH and coenzyme Q10." Without wishing to toot my blogging trumpet, some of these approaches have been discussed before on this blog (Coenzyme Q10 and NADH supplementation for Chronic Fatigue Syndrome? and Coenzyme Q10 and NADH supplementation for Chronic Fatigue Syndrome continued) and beyond that, the target organ of something like the use of probiotics for CFS has made an appearance more than once too (see here for example). I might also add that just outside of the search dates used by Campagnolo et al was the suggestion that issues with a staple foodstuff - cows milk - might be over-represented in cases of CFS (see here) and that a milk-free diet could be useful [2] for some at least. By saying all that, I'm not giving any medical or clinical advice...

As science starts to move further away from the the biopsychosocial (BPS) model of CFS/ME (see here) and starts looking at genetics, biology and somatic disease processes with regards to the various presentations included under the banner of ME/CFS (see here) I foresee some interesting developments further down the line. Granted, dietary and nutritional approaches to CFS/ME are probably not considered 'mainstream' in terms of management strategies but that does not mean they aren't important or at least important in the context of a diagnosis of ME/CFS seemingly being protective of nothing. Central to any future studies in this or any related area is the idea that there may be lots going on under the 'plural' diagnostic umbrella of ME/CFS (see here). Indeed, something that even the PACE trial is starting to take on board [3].

----------

[1] Campagnolo N. et al. Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review. J Hum Nutr Diet. 2017 Jan 22.

[2] Rowe PC. et al. Cow's milk protein intolerance in adolescents and young adults with chronic fatigue syndrome. Acta Paediatr. 2016 Sep;105(9):e412-8.

[3] Williams TE. et al. Heterogeneity in chronic fatigue syndrome - empirically defined subgroups from the PACE trial. Psychol Med. 2017 Jan 23:1-12.

----------

Campagnolo N, Johnston S, Collatz A, Staines D, & Marshall-Gradisnik S (2017). Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review. Journal of human nutrition and dietetics : the official journal of the British Dietetic Association PMID: 28111818

Cows milk protein intolerance and chronic fatigue syndrome

"Cow's milk protein intolerance is a common problem in young people with chronic fatigue syndrome, and is a treatable contributor to their symptoms."

So said the paper by Peter Rowe and colleagues [1] who looked prospectively for signs of cow's milk protein intolerance (CMPI) in "55 adolescents and young adults with chronic fatigue syndrome" over the course of 2 years. Defining CMPI using 4 factors: "(1) no evidence of immediate or anaphylactic reactions to milk, (2) at least 2 of the following 3 chronic symptoms: gastroesophageal reflux, early satiety, and epigastric/abdominal pain, (3) improvement in upper gastrointestinal symptoms on a milk protein elimination diet, and (4) at least 2 recurrences of upper gastrointestinal symptoms > 2 hours following open re-exposure to milk protein" researchers set about on this fairly unusual study course to ascertain some preliminary prevalence data and to see what impact such food issues might have on self-reported quality of life.

Nearly a third of their quite small participant group (17/55) hit their thresholds for CMPI and we are told that in comparison to non-CMPI participants, those with milk issues "had significantly worse health-related quality of life at baseline but not at 6 months (after institution of the milk-free diet)." As per that opening quote, prevalence of CMPI might be common in cases of CFS and might play some not insignificant role on quality of life.

Wearing my 'diet and behaviour' hat (see here for example) the Rowe results make for interesting reading. The fact that some of the authors have quite a lot of research standing when it comes to chronic fatigue syndrome (CFS) adds to my interest in these results; specifically with another of their papers in mind on orthostatic intolerance and gastrointestinal (GI) symptoms [2] for example (orthostatic intolerance = development of symptoms when standing upright, and is thought to be linked to quite a few cases of CFS).

Quality of life (health-related) when applied to CFS is something else that has already been covered on this blog (see here) and the observation that its presentation can be about as bad as it gets for some people in comparison to various other diagnostic labels. Anything therefore that can improve [elements of] such an important measure has to be taken seriously, particularly when it is something as 'treatable' as potentially eliminating milk from ones diet (I say this with no medical or clinical advice given or intended).

But just before anyone decides to embark of a milk-free diet solely on the basis of Rowe results, a bit of a research 'to-do' list to think about in this area: (a) The sample size was quite small and we need to know more with larger sample sizes and perhaps more strenuous research methodologies. (b) The measures used to assess CMPI didn't appear to include anything 'biological'. I know this is still a bit of a grey area in terms of 'intolerance vs' allergy' but I'd like to think that more could be attempted during future study including that related to those bowel symptoms [3] given previous discussions in this area (see here). (c) Given that this was a study of CFS I think most people would like to know whether CFS symptoms were impacted by a milk-free diet as well as quality of life measures. Again, measuring CFS is not the easiest of tasks given the number of definitions (see here) but it's not impossible. (d) Acknowledging that not all milk is the same (see here and see here) and that protein is but one element of milk, I have to wonder whether it might be worthwhile doing some further study on this too. Given also that institution of a milk-free diet is not without potential complications, the question is once again: is there more science to be done?

But that doesn't mean that the Rowe results are not interesting...

----------

[1] Rowe PC. et al. Cow's Milk Protein Intolerance in Adolescents and Young Adults with Chronic Fatigue Syndrome. Acta Paediatr. 2016 May 13.

[2] Sullivan SD. et al. Gastrointestinal symptoms associated with orthostatic intolerance. J Pediatr Gastroenterol Nutr. 2005 Apr;40(4):425-8.

[3] Frissora CL. & Koch KL. Symptom overlap and comorbidity of irritable bowel syndrome with other conditions. Curr Gastroenterol Rep. 2005 Aug;7(4):264-71.

----------

Rowe, P., Marden, C., Jasion, S., Cranston, E., Flaherty, M., & Kelly, K. (2016). Cow's Milk Protein Intolerance in Adolescents and Young Adults with Chronic Fatigue Syndrome Acta Paediatrica DOI: 10.1111/apa.13476