The connection between environmental factors and ALS

Over the years, researchers have been trying to determine the causes of amyotrophic lateral sclerosis (ALS), a disease that affects nerve cells in the brain and spinal cord. While genetics is thought to play a key role in influencing the condition, it’s not the only one.

Some studies have suggested that certain environmental, occupational, and lifestyle factors — including pesticide exposure, air pollution, and some workplace exposures — may also play a role in a person’s ALS risk.

Central to this research has been the concept of the ALS exposome. This refers to the lifetime accumulation of environmental and lifestyle exposures that may influence a person’s risk of developing ALS.

“You can think about it as everything that one is exposed to, whether it be toxicants, pollutants, medications, physical factors,” says Stephen Goutman, an associate professor of neurology at the University of Michigan in Ann Arbor, who co-authored a review of exposome research. “It’s one’s lifelong history of exposure.”

Examples of environmental exposures that have been studied in relation to ALS risk include:

• Pesticides: Research has consistently suggested a link between pesticide exposure and ALS risk. For example, some studies have linked occupational or residential pesticide exposure, living near areas with higher pesticide use, or storing pesticides at home with ALS risk. People with ALS have also been found in some studies to have higher levels of certain pesticides or related pollutants in their blood than people without ALS.
• Occupations and occupational exposures: Certain occupations, including production or manufacturing work, mechanics, construction, and agricultural work, as well as related exposures to pesticides, solvents, metals, particulate matter, and other pollutants, have been associated with increased ALS risk.
• Heavy metals: Exposure to heavy metals such as lead, mercury, cadmium, and zinc has also been studied in relation to ALS risk.
• Air pollution: Studies have suggested that long-term exposure to air pollution may contribute to ALS risk. Goutman and his co-authors noted in their review that levels of some pollutants studied in this context were below World Health Organization limits, suggesting that regulatory guidelines may need further review.
• Electromagnetic fields: Some research suggests a potential association between electromagnetic fields and ALS risk, particularly through occupational exposure. Evidence for residential exposure is inconsistent. 

Some lifestyle and personal-history factors that have been studied as part of the ALS exposome include:

• diet
• level of education
• history of head trauma
• alcohol consumption
• smoking
• exercise intensity

What the ALS exposome can and cannot tell us

Currently, scientists cannot pinpoint which specific factors determine whether a person develops ALS.

“I would say that right now we don’t know the exact causative factors in any single individual,” Goutman says. “So, I can’t look at any particular patient that I’m seeing and say that factor A, B, and C caused you to get ALS.”

And yet, the connections between some environmental factors and the overall risk of ALS are stronger than others.

“I think when we look at studies across the globe, when we summarize big populations of people with ALS and compare them to individuals without ALS,” he explains, “there are a number of factors that tend to rise to the top of this list of exposures or pollutants that we are most concerned about.”

According to Goutman, these include:

• pesticides
• heavy metals
• heavy manual labor, including jobs in production, construction, and extraction, such as those in mining, and in the extraction of heavy metals

Future research and potential for ALS prevention

Researchers hope that one day they’ll better understand what causes a person to develop ALS. Equally important, Goutman says, is understanding which people are most likely to develop ALS based on their prior exposure history, or their exposome.

“This really puts us in the position to be thinking about prevention,” he says.

However, more research is needed. For example, scientists would need to understand how to identify people who might be at higher risk because of certain exposures, which, in turn, may interact with genetic and other factors.

“And, then, what are our opportunities and capabilities for modifying how their exposures may go on to cause disease?” wonders Goutman.

Although at this time there aren’t any proven steps to prevent ALS, there are general recommendations to promote overall brain health. These are based largely on research into other neurodegenerative diseases.

“At this stage, I would say that we don’t have the scientific evidence that tells us that if one does A, B, C, and D, that their risk of ALS is going to be lessened,” Goutman says. “Having said that, we know that there are some studies out there looking at what are some of these modifiable risk factors of dementia, for example.”

Actions that support overall brain health in the general population include:

• avoiding smoking and secondhand smoke
• limiting alcohol
• eating a healthy diet
• staying physically active

Ultimately, when it comes to ALS risk, researchers are still working to understand the complex interactions between genetic and non-genetic factors, including those in the exposome.

The hope is to use this work as a foundation for future treatments and, one day, strategies that may help prevent the disease.