More than 50 years after the discovery of reduced mortality rates in patients with Parkinson’s disease (PD) who smoke cigarettes, researchers may be on the cusp of opening the door to nicotine-based treatments that could help ease symptoms of the disease.

The problem, of course, lies with decades of clinical investigations that have definitively linked tobacco use with cancer, stroke, and other serious ailments. The confounding results present a fairly unique ethical issue to the global medical community: Do we prevent the debilitating symptoms of PD with nicotine use, all while knowing that the patient may very well die from lung cancer?

While the risks of tobacco use are well-illustrated, can we continue to turn a blind eye to the compelling data that suggests nicotine is neuroprotective?

An Undeniable Connection

A paper published in Public Health Reports in 1959 describes findings1 from a collaborative study by the United States Public Health Service and the Veterans Administration (VA) that investigated the link between tobacco use and various causes of death. Approximately 200,000 policyholders of life insurance issued by the U.S. government had previously answered questionnaires indicating their tobacco use status and frequency. Upon their deaths, the VA sent the policyholder’s death notice to the Public Health Service, which obtained additional needed details from the doctor who signed the death certificate or from the hospital where the patient died. From the long list of diseases included in the study, majority of them were associated with a higher risk of mortality among smokers as compared to non-smokers and occasional smokers. However, there were some diseases for which smoking was not associated with elevated risk of death, most notably PD (the study author refers to it as paralysis agitans). Smokers had a dramatically lower risk of PD, with those who smoked 10 or more cigarettes daily having the lowest risk.

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CLINICAL CHART: Parkinsonism Treatments

Subsequent research has firmly established this perplexing connection, generally showing that active smokers have the lowest PD risk, followed by former smokers, while people who have never smoked have the highest risk. Indeed, a study published in the May 2015 issue of the American Journal of Epidemiology reported that people with a history of smoking had a 45% lower risk of developing PD. Other research has shown a similar level of risk, including a large National Institutes of Health study3 reported in Neurology in 2010, which found that current smokers had a 44% lower risk of PD than people who had never smoked. The findings further showed that past smokers had a reduced PD risk that was inversely related to the number of years they had smoked: Compared with people who had never smoked, former smokers who had smoked for 30 years or more had a 41% lower risk, while those who had smoked for 20 to 29 years had a 36% lower risk, and those who smoked for 10 to 19 years had a 22% lower risk.

“It is possible that the potential biological effect of nicotine or other active components in cigarettes against Parkinson’s may be saturated at low concentrations,” study co-author Honglei Chen, MD, PhD, a senior researcher at the National Institute of Environmental Health Sciences, told Neurology Advisor. “Also, Parkinson’s disease may take decades to develop. Sustained effects may be needed to lower the risk.”

The protective effect of smoking appears to also apply to second-hand smoke. In a study published in 20124, researchers at the University of Washington in Seattle confirmed that rates of smoking were much lower among PD patients than non-PD controls. Additionally, they observed that even among people who had never smoked, those who had been exposed to second-hand smoke had a decreased risk level similar to that of active smokers, and the same type of inverse dose-response relationship was found: The longer participants had lived with an active smoker, the lower their PD risk was.