On glyphosate and autism (without scaremongering)

Glyphosate use and autism rates - should I blog about it?

Well, after some deliberation I decided it was a topic worthy of an entry. There is some peer-reviewed science discussions behind it and, as per other areas of controversy on the autism research landscape, the idea that 'science is about debate' (why else does everyone keep going on about open-access and transparency) should always prevail.

I'm assuming most people have heard of the organophosphonate (that's phosphonate not phosphate) herbicide glyphosate - N-phosphonomethylglycine - over the course of its discovery and use under the trade name Roundup. First patented as a chelating agent (another area of 'discussion' with autism in mind) glyphosate has been successfully killing weeds for quite a few years by interfering with some of the chemistry of the aromatic amino acids tryptophan, tyrosine and phenylalanine via its actions on the shikimate pathway. As per many other herbicides, such formulations always require a degree of care in their use given the possibility of side-effects following accidental over-exposure. Indeed, government agencies are cottoning on to this fact (see here).

The debate on glyphosate and its potential effects on human and animal health has been a hot one in recent times. Partly overlapping with the introduction of genetically modified (GM) crops that are glyphosate-tolerant (Roundup Ready) by the company who initially brought glyphosate to the market, the safety angle of glyphosate has been scrutinised and debated. Only this year (2015), an arm of the World Health Organisation (WHO) described glyphosate (and several organophosphate pesticides I might add) as "probably carcinogenic to humans". Following such an announcement, quite a few media column inches were produced as one might expect.

Set within that context, discussions have turned to whether there may be other 'effects' following the fairly widespread use of glyphosate. Perhaps inevitably, autism, and particularly the quite phenomenal increase in cases of autism, has been suggested to be 'linked' to the use of glyphosate. One might say that in this respect, glyphosate is a victim of its own success insofar as how widely it has been and is currently used.

The paper that seems to have started the ball rolling suggesting a link between glyphosate and autism is that from Anthony Samsel and Stephanie Seneff [1]. A review paper focussing specifically on the proposed inhibitory actions of glyphosate on CYP enzymes, mention of autism in the text and particularly that "glyphosate may be the most significant environmental toxin contributing to autism" was bound to stir up debate. With added soundbites about how half of children will be born with autism in the United States by 2025 and graphs correlating autism prevalence and glyphosate use, such observations were ripe for speculation and discussion.

Further papers from Samsel & Seneff [2] have continued the theme that autism may be one of many conditions/labels where glyphosate might be implicated. Drawing on animal and plant studies implicating glyphosate use with specific depletion of manganese (Mn), a whirlwind of research studies and references have been used to link such depletions to autism (and associated aspects such as anxiety) among various other conditions. To quote: "Many diseases and conditions are currently on the rise in step with glyphosate usage in agriculture, particularly on GM crops of corn and soy. These include autism, AD [Alzheimer's disease], PD [Parkinson's disease], anxiety disorder, osteoporosis, inflammatory bowel disease, renal lithiasis, osteomalacia, cholestasis, thyroid dysfunction, and infertility. All of these conditions can be substantially explained by the dysregulation of Mn utilization in the body due to glyphosate." Just in case you thought that Samsel / Seneff are the sole research team talking about glyphosate use and autism rates, I'll also refer you to the paper by Cynthia Nevison [3] that has been previously discussed on this blog (see here).

As other commentators have noted, there are a few considerations to mention about the discussions so far on any relationship between glyphosate use and autism. That 'correlation is not the same as causation' is perhaps the most important element to the data as they currently stand given that, to my knowledge, no-one has actually published any peer-reviewed results on levels of glyphosate and/or metabolites in people with autism and/or other family members compared to asymptomatic controls for example. It's not as if such a feat is too complicated given the various means and methods already published on this topic [4].

'Correlation is not the same as causation' is one of the themes also discussed in the review paper by Miguel Faria [5] who provides an important discussion to some of the points raised by Samsel & Seneff. I don't want to head too much into this quite long commentary on the Samsel / Seneff paper (complete with author replies) but it does strike me as providing something of a counter-balance to the very hypothesis-based writings of the original authors. That glyphosate is one of a multitude of herbicides and insecticides in use is an important point made in terms of the difficulties in disentangling it from the 'chemical soup' (not to demonise) that we live our lives in these days. The only other thing that I might mention is my much-used notion about the continued pluralisation of autism (see here) and its varied comorbidity as being something to bear in mind when it comes to any discussions about aetiology.

Where next, or is there even 'a next' for looking at any possible relationship between glyphosate use and autism rates? Well, I'd like to think that autism research can learn a lesson or two about not throwing out baby and bathwater when it comes to theories about [some] autism as per what seems to have happened to something like methylmalonic acid (MMA) and autism (see here) for example. It's not beyond the realms of possibility that certain chemicals or mixtures might be linked to autism risk and/or onset as per preliminary research talk about dioxin exposure being potentially linked to [some] autism or autistic traits (see here) albeit with a lot more follow-up research required.

But such research needs to be done with care and assiduity; mindful that this is a topic that will inevitably garner significant attention (as per the editorial sentence on the original Samsel / Seneff paper: "Note added by the Publisher: This paper attracts great attention.") and knowing what can happen sometimes when science and media mix (see here).

Perhaps a little less focus on soundbites and more on cold, objective science is the best way forward in this area?

Music: Fleetwood Mac- Dreams.

----------

[1] Samsel A. & Seneff S. Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases. Entropy 2013. 15; 1416-1463.

[2] Samsel A. & Seneff S. Glyphosate, pathways to modern diseases III: Manganese, neurological diseases, and associated pathologies. Surgical Neurology International. 2015;6:45.

[3] Nevison CD. A comparison of temporal trends in United States autism prevalence to trends in suspected environmental factors. Environ Health. 2014 Sep 5;13:73.

[4] Yoshioka N. et al. Rapid determination of glyphosate, glufosinate, bialaphos, and their major metabolites in serum by liquid chromatography-tandem mass spectrometry using hydrophilic interaction chromatography. J Chromatogr A. 2011 Jun 10;1218(23):3675-80.

[5] Faria MA. Glyphosate, neurological diseases – and the scientific method. Surgical Neurology International. 2015;6:132. doi:10.4103/2152-7806.162550.

----------

Faria MA (2015). Glyphosate, neurological diseases - and the scientific method. Surgical neurology international, 6 PMID: 26322242

Estimating parental occupational exposures and autism

Under pressure @ Paul Whiteley

I've spent quite a bit of time ducking in and out of an analytical chemistry lab down the years. Aside from a surprising lack of bubbling test tubes - cue the media representation of a scientist complete with white lab coat and safety specs holding up a funny coloured liquid to the light whilst looking inquisitively - there are a few things that you pick up quickly while at the bench. So interesting acronyms like COSHH (Control of Substances Hazardous to Health) and MSDS (Materials Safety Data Sheet) become watchwords, all in the name of 'elf and safety.

Reading MSDS-s in particular, can give you quite a wake-up call about how even routinely used chemicals can hide some pretty damaging effects as per this example for the solvent methanol. Don't even ask me about the commonly used solvent acetonitrile, also called methyl cyanide - that's cyanide but not the sparkling variety. Even good old dihydrogen oxide - 'water' to you and me - has its own MSDS. You and fire brigades across the globe will be glad to know that it's non-flammable.

Regular readers of this blog will probably have seen a few common threads running through the various posts with particular emphasis on how our modern-day physical environment may potentially impact on various facets of human (and animal) biology and functioning. I have tried not to fall too far into the 'synthetic is bad' pothole simply because such sweeping generalisations about all the various 'chemicals' making up our environment are not supported by the available evidence base. That however does not mean that certain compounds may not be able to potentially exert an effect on health and wellbeing, either at an individual or group level, in the short- or long-term, and even impact on our future generations. Sounds suspiciously like epigenetics again to me...

With this in mind, a recent paper by McCanlies and colleagues* was always going to be of interest and the suggestion that parental occupational exposure to certain chemical compounds might be more common to parents of children with autism compared to controls. Admittedly based on quite a small participant group (N=174) derived from the CHARGE study, the authors who included Irva Hertz-Picciotto, reported that "... exposures to lacquer, varnish, and xylene occurred more often in the parents of children with ASD". With sentences like that you can see how headlines can be made. There is however some 'devil in the detail' about such statements which becomes apparent from the full-text paper:

• Of the 174 families included in this study (based on an original cohort of 249 children), 93 families had a child with an autism spectrum condition and 81 had 'unaffected' children.
• Both parents were quizzed via a structured telephone interview about their jobs and likely exposure to chemicals found in the workplace before, during and shortly after pregnancy. So questions relating to the place of employment, what the company did/made and respective work duties were amongst the data collected.
• One of three industrial hygienists also independently assessed potential occupational exposures initially based on a list of 49 agents supplied by the study authors. Industrial hygienists did not have access to participant grouping (autism or control) nor access to identifiable parental responses. They were however provided with some data relating to things like job history, tasks and responsibilities. Exposure level based on the 49 agents was then estimated and coded on a 0-3 scale where 0 = none and 3 = high estimated level of exposure.
• Results: several possible exposures were identified. The most common exposures identified by industrial hygienists in the autism group were toluene (30.4%), metals (30.4%) and nickel (30.4%). The least common exposures were carbon disulfide (1.1%) and perchlorate (1.1%). For the control group, top of the pops were metals (32.5%) and aluminium (30%).
• Parental self-reports suggested that disinfectant exposure was most frequently cited in the autism group (42.5%) same also with control parents (37.2%) during the index (pre-pregnancy) and pregnancy time frames.
• When it came to assigning odds ratios (OR) (based on forest plots), lacquer exposure, varnish and xylene showed the strongest differences between the autism vs. control group from the industrial hygienists results. Parent self-reported OR data suggested that solvent and asphalt exposure were the better differentiators between the groups but when adjusted, no association was significantly so. 
• Interestingly when it came to pesticide exposure, the industrial hygienists actually suggested that a slightly greater percentage of parents in the control group were exposed to things like insecticides and herbicides than the autism group parents, although overall the numbers were quite small.

I've thought quite a bit about this study and what the results might mean. Granted it was a pilot study and all in all no significant group differences were noted between the autism and control groups, so no smoking gun for all cases. Having said that nothing rules out a possible effect from individual level exposures as perhaps showing some relationship - remembering the recent post on HPPE and cognitive functions - and as yet the cumulative impact of more than one exposure cannot be forgotten. Bear in mind also that no specific biological measures of exposure were included in this trial; so even though exposure patterns were estimated, in reality, no real evidence of effect (or not) can be truly gained from this study as it stands.

Genes and environment is a relationship also worth bearing in mind when reading such studies, as per the recent data looking at the Rett syndrome MECP2 issue combined with PBDE exposure (in mice). The genetics of autism is, er, complicated, very complicated (2193 genes, etc, etc. so far). I would perhaps be interested to see if at an individual level, there is any relationship between exposure pattern and genes. The primary question being: where do you start to look?

As discussed in previous posts, we all live in a very different 'chemical' world these days compared with only a couple of hundred years ago. Granted, quite a bit of the progress made in terms of industrialisation is as a direct result of that new synthetic chemical world and so we should be cautious about forming too many sweeping prejudices about how bad the chemical soup is that we live in (ever wondered what chemical components are present in your PC/laptop/tablet/phone that allow you to read this post?).

To quote that wise old sage Darth Vader "don't be too proud of this technological terror you've constructed..".  Wise words indeed. It could be argued that we have been playing with fire for quite a few years now in terms of not keeping up with the potential individual and importantly, cumulative effects of the compounds we have ingeniously invented. In particular what effect they may / may not have on the developing infant.

More research please.

To end, if I had to have one, this would be my favourite Fleetwood Mac song: Go your own way.

* McCanlies EC. et al. Parental Occupational Exposures and Autism Spectrum Disorder. JADD. March 2012.
DOI: 10.1007/s10803-012-1468-1

Edible colloids to reduce food fat content

A brief post. The August 2011 edition of Chemistry World carries an interesting article about the use of edible colloids as an alternative way of reducing the fat in foods (full-text here). I don't want to get into any debate about whether dietary fat is good or bad because (a) I don't know enough about it and (b) it is not the main aim of this post.

Being Chemistry World, the text is quite heavily chemistry-orientated but I was quite interested in some of the various ways that chemistry is approaching the issue of fat in food and our modern-day obsession with diet and fat reduction. The article lists a few interesting possibilities under investigation. Things like the incorporation of gel-coated air bubbles into foods behaving like fat droplets in the mouth, and the addition of emulsions to food which survive our stomach and areas of our gastrointestinal (GI) tract to make us feel fuller for longer. I know some people might gasp in horror as chemistry contemplates toying with our foods, and obviously a lot more research and investment needs to go into such areas. Having said that hands up if your diet solely consists of food which has not been manipulated in one way or another already?

All of these options must be better than the 'no food diet'?