"This is a very thorough systematic review that links pesticide exposure to motor neurone disease (MND, amyotrophic lateral sclerosis). The underlying cause(s) of MND have been researched for decades. The general feeling is that it is multifactorial: i.e., there are probably many risk factors which determine the likelihood of contracting the disease. The authors of this paper have identified another risk factor. The paper makes no attempt to explore the mechanisms by which pesticides might initiate MND – this is a pity. However, they do identify groups of pesticides with particular associations with MND.

"My work in NZ pointed to links between exposure to methyl bromide (a fumigant pesticide used in wood exporting ports) and MND in Nelson. This all points to the need for pesticides to be handled carefully to reduce agricultural workers’ exposure. This is very important in an agricultural country like NZ. In my opinion, it is unlikely that pesticide residues in food will be a relevant exposure route because doses are incredibly low."

"ALS is a difficult disease to study due to its relative rareness. Hence, the use of case-control studies makes sense. But these are usually seen as weaker, as they rely on memory (or occupational type) as a proxy for exposure. This makes it difficult to assess exposures, as farming and military practices vary between individuals and countries, as does chemical use.

Also, being rare, an increase in risk has to be taken in the context of it being very unlikely. A 70% increase in risk may sound like a lot, but the absolute risk of moving from 1:200,000 to 1.7 in 200,000 will not see many more people affected.

Self-reported exposure to pesticide may bias towards those having the disease reporting more, if they believe a particular exposure to be the cause of their disease. The relationship with agrochemicals has been purported as a risk factor for some time now.

When examining the exposure, a mix of toxins is lumped together in many studies, meaning no clear linkage between exposure to a single chemical and disease outcome is possible.

Familial cases were included in some studies, and these generally make up around 5-10% of cases and are thought to have a stronger genetic component.

All in all, I find the links between agrochemicals and ALS still at a point of equipoise, but further studies of more rigorous design will provide better data to make decisions.

Small numbers of Australians have high exposure to agrochemicals, suggesting a range of exposures may lead to ALS in this country. An aging population in Australia may see more cases here in the future."

"I can see this paper potentially generating some scary-sounding headlines, but it is important to take a step back and look at what was done - and what was not done. 

This paper contains no new experimental data. Instead, the authors performed a meta-analysis. This is an approach where the results of different studies on the same topic are combined to try and find an overall effect. In this case, they found a statistical association between exposure to some types of pesticides and one type of motor neuron disease (MND). They are not the first to report such an association, but association is not causation. It merely indicates what might be interesting to look at further.

The problem with any meta-analysis is that it is only as good as the underlying studies it is based on. In this case, as the authors themselves admit, many of the underlying studies have issues, not least of which is that pesticide exposure was generally only based on answers to survey questions; it wasn’t measured directly. This means the authors have no idea how much pesticides people were actually exposed to, nor what other risk factors, such as age or lifestyle, might have had an effect. The effect was also only seen in men and not women, and although MND is more common in men than women, if pesticide exposure were a causal factor, we would expect to see some form of effect in both.

It’s unlikely that any single factor will cause MND. So, while reducing exposure to pesticides is a sensible general precaution, the paper is not a eureka moment about the risks of pesticide exposure, and people don’t need to panic.”

"This new analysis combined data from eight case-control studies conducted in the United States (x5), Canada/France (x1), Italy (x1) and Australia (x1). It found that people who had ever been exposed to pesticides at any point during their working lives were at a higher risk of developing ALS (amyotrophic lateral sclerosis) compared to those who had never been occupationally exposed. 

This study's focus on occupational exposure was a clear strength, and the overall increased risk seen when pooling eight diverse studies strengthens confidence in the findings. 

However, differences in each study’s design also introduced heterogeneity that's hard to fully account for. For instance, one of the studies included military veterans exposed to Agent Orange, a wartime exposure likely quite different from typical occupational exposure. Other studies found an increased risk of ALS linked to separate risk factors such as head trauma, which couldn't be fully disentangled from pesticide exposure in this analysis. 

Most of the included studies also relied on self-reported exposure, and these tended to show larger associations between pesticides and ALS than studies using expert assessment. As the study's authors noted, this raises the possibility that recall bias played a role – people who already have ALS, or who already suspect a link between pesticides and the disease, may be more likely to remember and report past pesticide exposure.

Despite these considerations, these findings support the case that occupational pesticide exposure is linked to a higher risk of ALS and sets the stage for further research into which specific chemicals or pesticide components may be responsible, whether risk increases with higher doses or longer exposure (a dose-response relationship), and whether protective equipment or exposure limits can meaningfully reduce risk so we can better protect workers today and future generations from this devastating disease, which so often strikes individuals in the prime of life."

"Amyotrophic lateral sclerosis (ALS) is a devastating, incurable and progressive neurodegenerative disease involving the nerves of the motor system in the brain and spinal cord. Despite several years of research, we still do not understand the cause of ALS. However, it is most likely a combination of genetic background, lifestyle, environmental or other risk factors (head injury being a leading risk factor). There are two general forms of ALS: hereditary, with mutations in key genes, and sporadic, where the mutations in the genes associated with hereditary ALS are largely absent. Sporadic ALS is the most common form.

Environmental exposures that could trigger ALS have been widely studied; these include heavy metal exposure, air pollution, solvents and pesticides. However, while some studies of pesticides have shown an association of pesticides with ALS, most studies have shown no association.

This new study adds to our understanding by examining eight case-control studies from 1990 and performing a meta-analysis. A meta-analysis is a statistical measure used on pooled data that can combine the results of multiple independent studies and provide a stronger conclusion than the single studies alone. The study looked at control studies of confirmed ALS where occupational exposure to pesticides (fungicides, herbicides and insecticides) could be defined. These studies also attempted to control for other confounding variables (age, smoking, exposure to other chemicals).

The major finding was that, compared with no exposure, any workplace exposure to pesticides was associated with a 60% heightened risk of ALS, with evidence that high exposures had a higher risk than low exposures. Since ALS is very rare, this means only a small number of extra cases, though. While there was a significant association with the overall class, neither fungicides nor herbicides were significantly different.

Insecticides as a class were associated; however, no specific pesticides were indicated. Furthermore, as these are case-control studies, finding an association cannot confirm a causal relationship. As well, the conclusions are limited by the small number of studies involved, and factors such as recall bias in assessment of pesticide exposure.

Nonetheless, this study adds important data to the evidence that occupational exposure to pesticides may increase the risk of ALS and guide future exploration and understanding of this terrible disease.