High levels of metals in body raise ALS risk, affect patient survival
Levels of copper, selenium, and zinc elevated in patients' blood and urine
People with higher levels of certain metals in their blood and urine are more likely to develop amyotrophic lateral sclerosis (ALS), a U.S. study reports.
Findings also suggest that, among ALS patients, higher metal levels linked with significantly poorer long-term survival.
“By measuring [blood] and urine metal levels, we confirmed that individual metals, such as copper, selenium and zinc, were associated with greater ALS risk and shorter survival,” researchers wrote in the study, “Multiple metal exposures associate with higher amyotrophic lateral sclerosis risk and mortality independent of genetic risk and correlate to self-reported exposures: a case-control study,” published in the Journal of Neurology, Neurosurgery and Psychiatry.
Levels of various metals analyzed in blood, urine of 454 ALS patients
The causes of ALS aren’t fully understood. Genetics are thought to play a role, but environmental exposures have also been linked with the disease.
Some research has suggested that exposure to metals may increase the risk of ALS, but most studies in this area have been relatively small, making it difficult to draw sweeping conclusions. Additionally, studies of metal exposure and ALS risk generally have not accounted for the role of genetics in influencing ALS risk.
“Strengthening our understanding of the importance of exposure to metals as a risk factor for ALS is essential for future targeted prevention of the disease and improved therapeutic strategies,” Stephen Goutman, MD, the senior study’s author and director of the Pranger ALS Clinic at the University of Michigan, said in a university news release.
To get a better idea of how metal exposure impacts ALS risk, scientists analyzed blood and/or urine samples collected from 454 ALS patients seen at that clinic, as well as 294 people without the disease for comparison. Notably, their analyses also accounted for genetic variations known to affect both ALS risk and the accumulation of metals in the body.
“We conducted a large cohort study to investigate the association between metal exposures and ALS, as well as the potential influence of gene-metal interactions on ALS,” the scientists wrote.
Results indicated that some metals, particularly copper, selenium, and zinc, tended to be found at higher levels in ALS patients. Patients who had worked in professions associated with metal exposure, such as construction, generally tended to have higher levels of these metals, the researchers noted.
Still, “exposure to these metals can occur through diet, drinking water, supplements and environmental pollutants,” they wrote.
Higher metal levels collectively seen to raise ALS risk about three times
In statistical analyses that accounted for multiple metals collectively, higher levels associated with a roughly threefold higher likelihood of developing ALS. Among the ALS patients, higher metal levels also associated with poorer survival.
Statistical models showed that taking ALS-related genetics into account had minimal effect on these associations, which implies that the effects of metal exposure on ALS risk are largely independent from those of genetics.
“Despite its influence on ALS susceptibility, genetic background did not significantly alter the relationship between metal exposure and ALS risk or survival,” the scientists wrote.
Researchers highlighted that analyses accounting for multiple metals in combination showed stronger associations with ALS risk and survival than similar analyses looking at any one type of metal individually. In fact, while metal exposure overall was linked with a higher ALS risk, higher levels of a few specific metals — such as nickel — linked with a lower ALS risk when assessed alone.
“This variability highlights the complex nature of metal exposures and their measurements,” the researchers wrote. “Given this variability, further research is needed to better understand these associations and their implications for ALS pathogenesis [disease development].”
Still, as study results indicate a link between high metal exposure and a higher ALS risk and worse survival outcomes, its findings imply that taking steps to reduce metal exposure might help lower the likelihood of developing ALS and improve outcomes for patients.
“These findings emphasize the necessity of accounting for occupational and environmental factors when evaluating a person’s overall exposure risk,” said Dae Gyu Jang, PhD, the study’s first author and a postdoctoral fellow in the university’s neurology department. “Our future research will further focus on what exposures have the strongest associations and their implications on the disease.”
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