ALS Patients Have Higher Lead Levels in Blood, Review Study Finds

The link between lead and ALS does not prove causality, researchers caution

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A dropper squirts blood alongside several vials half-filled with blood.

People with amyotrophic lateral sclerosis (ALS) have significantly higher blood levels of lead, a toxic heavy metal, than those without the disease, a review study found.

While the findings strengthen accumulating evidence of a link between lead exposure and the risk of developing ALS, they do not definitively prove that lead exposure contributes to the disease, researchers noted.

Further studies are needed to clarify the mechanisms behind the link between lead levels and ALS.

The study, “Human tissue lead (Pb) levels and amyotrophic lateral sclerosis: a systematic review and meta-analysis of case-control studies,” was published in the journal Neurological Sciences.

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In people with ALS, motor neurons, the nerve cells in the brain and spinal cord that control voluntary movement, progressively stop working, impairing signal transmission to muscles. As a result, the muscles begin to waste away and become gradually weaker.

Environmental factors are thought to contribute to the risk of ALS development. Hobby or on-the-job exposure to lead, a naturally occurring metal known to be toxic to nerve cells, has been tied to ALS development and more severe disease progression.

Once it enters the body, lead may travel through the blood to other fluids and tissues, such as the brain and spinal cord, where it may accumulate to toxic levels.

While the damaging role of lead in ALS was systematically reviewed in a previous study, no study to date has reviewed data on the levels of lead in body fluids and tissues of ALS patients.

The study and its results

In the current study, a team of researchers at the University of Sassari in Italy systematically reviewed studies published up to February that reported lead levels in a range of body tissues and fluids in people with ALS versus those without the disease (who were used as controls).

A total of 14 studies were included in the meta-analysis, four of which investigated lead levels in more than one biological sample.

Overall, nine studies measured lead levels in the whole blood of a total of 409 people with ALS and 575 healthy controls. In five studies, lead levels were measured in the serum (the liquid, noncellular part of blood) of a total of 64 patients and 67 controls.

Finally, six studies measured lead levels in the cerebrospinal fluid (CSF; the fluid that surrounds the brain and spinal cord) in a total of 114 ALS patients and 130 controls.

A few other studies measured the levels of lead in urine and solid tissues, such as the bone, skeletal muscle, and nails. However, their number was too small to allow data to be combined in a meta-analysis, the team noted.

Results showed the levels of lead were significantly higher in the blood of ALS patients versus controls. While ALS patients also tended to have higher lead levels in serum and CSF than healthy individuals, these differences failed to reach statistical significance.

The absence of significant results for serum and CSF may be related to the smaller number of studies evaluating these samples, “highlighting the importance of further studies in the field,” the researchers wrote.

The team also noted lead’s known propensity to accumulate inside cells may also explain the results, as whole blood was the only biological sample that included cells.

These findings provide “further evidence of the association between [lead] bioaccumulation and ALS in body fluids,” the researchers wrote, and suggest the use of lead levels “in whole blood as a biomarker, probably in combination with other factors.”