Widely used chemical strongly linked to Parkinson’s disease

A groundbreaking epidemiological study has produced the most compelling evidence yet that exposure to the chemical solvent trichloroethylene (TCE)—common in soil and groundwater—increases the risk of developing Parkinson's disease. The movement disorder afflicts about 1 million Americans, and is likely the fastest growing neurodegenerative disease in the world; its global prevalence has doubled in the past 25 years.

The report, published today in JAMA Neurology, involved examining the medical records of tens of thousands of Marine Corps and Navy veterans who trained at Marine Corps Base Camp Lejeune in North Carolina from 1975 to 1985. Those exposed there to water heavily contaminated with TCE had a 70% higher risk of developing Parkinson's disease decades later compared with similar veterans who trained elsewhere. The Camp Lejeune contingent also had higher rates of symptoms such as erectile dysfunction and loss of smell that are early harbingers of Parkinson's, which causes tremors; problems with moving, speaking, and balance; and in many cases dementia. Swallowing difficulties often lead to death from pneumonia.

About 90% of Parkinson's cases can't be explained by genetics, but there have been hints that exposure to TCE may trigger it. The new study, led by researchers at the University of California, San Francisco (UCSF), represents by far the strongest environmental link between TCE and the disease. Until now, the entire epidemiological literature included fewer than 20 people who developed Parkinson's after TCE exposure.

The Camp Lejeune analysis "is exceptionally important," says Briana De Miranda, a neurotoxicologist at the University of Alabama at Birmingham who studies TCE's pathological impacts in the brains of rats. "It gives us an extremely large population to assess a risk factor in a very carefully designed epidemiological study."

"We had suspicions, but this is the evidence," agrees Gary Miller, a neurotoxicologist who studies Parkinson's disease at Columbia University. "It's very compelling."

TCE is a colorless liquid that readily crosses biological membranes. It turns into vapor quickly and can be absorbed by ingestion, through skin or by inhalation. It's used today mainly in producing refrigerants and as a degreaser in heavy industry.

But in the 20th century, TCE was used for many purposes, including making decaffeinated coffee, dry cleaning, carpet cleaning, and as an inhaled surgical anesthetic for children and women in labor. TCE is highly persistent in soil and groundwater; inhalation through vapor from these hidden sources is likely the prime route of exposure today. However, it's detectable in many foods, in up to one-third of U.S. drinking water, and in breast milk, blood, and urine.

To conduct the study, the UCSF team and colleagues elsewhere scoured Department of Veterans Affairs and Medicare health records of nearly 85,000 Marine Corps and Navy personnel who were stationed for at least 3 months at Camp Lejeune decades ago. At the time, wells on the base were contaminated from leaking underground storage tanks, industrial spills, and waste disposal sites. Water used on the base contained TCE levels more than 70 times the level allowed by the U.S. Environmental Protection Agency (EPA). Recruits could have ingested TCE in food or water, been exposed through their skin when bathing or showering, or inhaled the highly volatile compound, which was also used by the military for degreasing and cleaning metal machinery.

The researchers calculated the rate of Parkinson's disease in the veterans and compared it with the rate in more than 72,000 veterans who lived at Marine Corps Base Camp Pendleton, a similar training ground in California where there were not high levels of TCE. By 2021, 279 of the Camp Lejeune veterans, or 0.33%, had developed Parkinson's versus 151 of those at Camp Pendleton, or 0.21%. After adjusting for differences in age, sex, race, and ethnicity, the scientists found veterans from Camp Lejeune had a 70% higher rate of Parkinson's disease than the Camp Pendleton group.

In the Camp Lejeune veterans, the researchers also found higher rates of symptoms known to precede the onset of the movement disorder. Because the recruits were so young—an average age of 20—while at the training camp, the mostly male cohorts had an average age just shy of 60 when the analysis of their health records ended in 2021. That means that more Parkinson's diagnoses may occur as most people develop the disease after age 60.

Animal studies have shown that TCE acts in an area of the midbrain responsible for movement control. It inhibits complex 1, the leading enzyme in a chain of reactions that convert food to energy in cellular organelles called mitochondria. In rodents exposed to TCE, the dopamine-generating neurons in the midbrain's substantia nigra are destroyed, as happens in human Parkinson's disease. Pesticides such as paraquat and rotenone that have been associated with Parkinson's disease also leave that pathological signature in rodents.

The Camp Lejeune study's lead author, UCSF epidemiologist Sam Goldman, conducted a small twin study published in 2012 showing that TCE exposure increased the risk of the disease in humans. That work, he says, was prompted by a published report of a cluster of Parkinson's cases in a factory where workers were chronically and heavily exposed to TCE, which was used as a metal degreaser.

Goldman was motivated to undertake the current study in 2017. That year, the U.S. government declared that any veteran who served at Camp Lejeune in the contaminated water era and had Parkinson's disease would be presumed to have developed it because of TCE exposure at the base, despite the scant epidemiological evidence. "I just felt … we really need to have greater certainty about this," Goldman says.

The study did have weaknesses. For instance, just because a Marine was stationed Camp Lejeune did not guarantee that they were exposed to TCE; if that was the case, the study may actually be underestimating the link between TCE and Parkinson's. On the other hand, it's possible that Camp Lejeune trainees with Parkinson's were overrepresented in the study because—thanks to the new government policy—they were increasingly seeking care through VA beginning in 2017. Indeed, when the investigators looked only at cases ascertained before that year, the increased risk of Parkinson's was lower: 28%. However, the recruits were also younger before 2017 and less likely to have developed the disease, for which age is the leading risk factor.

In January, EPA declared that TCE presents an "unreasonable risk of injury to human health" and said it will develop a rule regulating its use. (The chemical is also a known carcinogen.) But that "really means nothing for what's already in the environment," De Miranda says. Mitigating against exposure is tricky, she adds, because, unlike with pesticides, underground TCE locations aren't always documented.

"Alarmingly, TCE vapor intrusion is widespread today and ranges from an elementary school situated on top of a former chemical facility in Shanghai, China, to multimillion-dollar homes built on a previous aerospace plant in Newport Beach, California," the authors of an accompanying editorial in JAMA Neurology write.

The new study will likely add ammunition to class action lawsuits that were launched after Congress last year enabled veterans from Camp Lejeune to sue the government for health damage they suffered from exposure to the contaminated water there decades ago. "This is increasing evidence that environmental factors are important causes of Parkinson's disease," Miller says. "But we are just scratching the surface. We need to continue studying this."