Blood lead levels tied to ALS risk

NEW YORK (Reuters Health) - A new study strengthens evidence linking long-term lead exposure to the risk of developing the fatal neurological condition amyotrophic lateral sclerosis (ALS).

A health worker collects blood from patient in Hai Phong City, Vietnam in this October 15, 2005 file photo. REUTERS/Nguyen Huy Kham

The findings do not definitively prove that lead exposure contributes to ALS, also known as Lou Gehrig’s disease. And even if lead does contribute, the risk of any one person developing the relatively uncommon disease due to lead exposure would be quite low, researchers say.

Still, the results strengthen the case that lifelong lead exposure may play a role in ALS, according to senior researcher Dr. Freya Kamel, a staff scientist at the U.S. National Institute of Environmental Health Sciences, in Research Triangle Park, North Carolina.

ALS is an invariably fatal disease in which the nerve cells that control movement progressively degenerate, leading to paralysis and death from respiratory failure. It is diagnosed in about 5,000 Americans each year.

Up to 10 percent of ALS cases are an inherited form of the disease. In most cases, though, ALS occurs for no known reason.

A number of studies have suggested that lead exposure may be a risk factor for ALS, showing associations between higher blood lead levels and an increased risk of ALS.

Such correlations are not, however, proof of cause-and-effect. One alternative explanation is that ALS itself causes people to have higher blood lead levels; lead is stored in the bones, and as ALS progresses, bone mass may break down and release lead into the bloodstream.

In the new study, however, researchers found that even when they accounted for markers of such “bone turnover,” blood lead levels were still associated with ALS risk.

The study, published in the American Journal of Epidemiology, involved 184 U.S. male veterans with ALS and 194 vets without the disease. All of the men were white and the average age in each group was 63 and 64, respectively.

Analyzing blood samples from the men, the researchers found that a doubling in the blood lead level was associated with a doubling in the risk of ALS. That was true even when the investigators accounted for markers of bone breakdown -- suggesting that it was not the ALS causing the higher lead levels.

“It’s important to rule that out,” Kamel said in an interview, noting that the findings “tighten up” the evidence that higher lead exposure may contribute to ALS in some people.

That said, even if lead exposure is a factor in ALS, that alone would not be enough. Scientists believe that ALS arises from a combination of genetic susceptibility and certain environmental exposures, Kamel explained.

But exactly what those genes or environmental exposures are remains “very much up in the air,” she said. The best evidence so far, as far as environmental factors, is for lead exposure, according to Kamel. It is biologically plausible, she said, since lead is known to have toxic effects on the central nervous system.

Blood lead levels are generally thought to reflect recent exposure to the metal. But Kamel said that in people with no obvious source of current lead exposure, stored lead released from the bones may be the main driver of blood lead levels -- particularly in older adults, whose bones mass may be breaking down faster.

The blood lead levels in these study participants, therefore, may be reflective of their lifelong exposure. The findings, Kamel said, highlight the possibility that long-term, relatively low-level lead exposure may have important health effects.

On average, ALS patients in the study had higher blood lead levels than the comparison group, but both groups had fairly low levels. ALS patients averaged 2.4 micrograms of lead per deciliter of blood (mcg/dL), with a range of 0.7 to 7.6 mcg/dL, while the comparison group’s lead levels averaged 1.7 mcg/dL, with a range of 0.3 to 6.9 mcg/dL.

Lead is present in the air, soil and water, but public health efforts in recent decades to reduce environmental levels -- by taking lead out of gasoline and paints, for example -- have cut Americans’ lead exposure.

SOURCE: American Journal of Epidemiology, online April 20, 2010.