Higher levels of exhaled carbon monoxide were associated with a lower risk of developing Parkinson’s disease, even among people who had never smoked. In an accompanying JAMA Neurology editorial, Radboudumc researcher Sirwan Darweesh and colleagues discuss what the findings could mean for future prevention research.
People who smoke have consistently been found to have a lower risk of developing Parkinson’s disease. Studies suggest that this risk may be around 50% lower, with heavier smoking generally associated with a greater reduction. This puzzling observation has raised an important question: which component of smoking might be responsible for the apparent protective effect?
New research published in JAMA Neurology points to carbon monoxide as one possible explanation. In a study of more than 500,000 adults followed for an average of 12 years, higher levels of exhaled carbon monoxide were associated with a lower risk of developing Parkinson’s disease among people who had never smoked. In an accompanying editorial, Radboudumc neurologist and research group leader Sirwan Darweesh and colleagues place the findings in the broader context of Parkinson’s prevention.
“The lower risk of Parkinson’s among smokers has intrigued researchers for decades, but smoking itself can obviously never be a prevention strategy,” says Darweesh. “The important question is whether we can identify the underlying biological mechanism and eventually translate that into a safe intervention.”
Searching for the protective factor
Parkinson’s disease is a progressive neurological disorder affecting more than 11 million people worldwide. Identifying factors that could reduce the risk of developing the disease is therefore an important area of research.
Carbon monoxide, or CO, is one possible candidate. At high concentrations, such as those caused by smoke inhalation or air pollution, carbon monoxide is toxic. But the human body also produces very small amounts of CO naturally. At low levels, it acts as a signaling molecule and is involved in processes related to oxidative stress, immune responses, and cell survival. Previous laboratory and animal studies have suggested that low concentrations of CO may have neuroprotective effects.
Lower risk among never-smokers
The researchers examined exhaled carbon monoxide levels measured at the start of the study and compared these with participants’ subsequent risk of developing Parkinson’s disease.
Among people who had never smoked, those with the highest levels of exhaled CO had a 39% lower risk of developing Parkinson’s disease than those with the lowest levels. The association became stronger as CO levels increased.
Because this association was also seen in never-smokers, smoking itself cannot explain the finding. Carbon monoxide can originate from other environmental sources and is also produced naturally by the body. The results remained consistent across a range of additional analyses.
However, the study was observational. It therefore cannot establish that carbon monoxide itself prevents Parkinson’s disease.
From association to intervention
Darweesh and colleagues argue in their editorial that the next step is to move from observational evidence toward experimental research.
“These findings are an important clue, but they do not yet show that carbon monoxide has a protective effect,” says Darweesh. “The crucial next step is to test whether carefully controlled low-dose CO can actually influence the disease process. Randomized trials will be essential to answer that question.”
The first randomized clinical trial investigating low-dose carbon monoxide in relation to Parkinson’s disease has recently started at Harvard, and similar studies are expected to follow.
Together with other lines of research into Parkinson’s prevention, such studies could eventually show whether biological pathways involving carbon monoxide can be targeted safely.
The findings do not suggest that smoking protects health. Instead, they offer a possible explanation for a long-standing observation and point toward a new direction for research into preventing Parkinson’s disease.