For many medical conditions, cigarettes are the main culprit – but when it comes to Parkinson’s, smoking might actually be beneficial. Here is why experts would still not recommend protective smoking.
Smoking is one of the most important preventable risk factors for morbidity and mortality worldwide. Smoking increases the risk of lung cancer, heart attack, stroke and many other diseases many times over. However, smoking does not lead to an increased risk for every disease. Exceptions confirm the rule here, too.
Smokers, for example, have a lower risk of developing ulcerative colitis than non-smokers – and if they stop smoking, the risk of a recurrent attack of colitis increases. Smoking also reduces the risk of endometrial cancer. This seems particularly counterintuitive, as for most other cancers the risk of developing the disease increases significantly with smoking. Cigarette smoke contains over 5,000 chemicals, some of which damage DNA, leading to mutations and ultimately to cancer. An anti-estrogenic effect of smoking could possibly explain the special situation with endometrial cancer, even though there is not yet sufficient evidence to support this theory.
Dwarfing the benefits in the diseases mentioned above the risk reduction from smoking is probably most relevant in Parkinson’s disease. Long-time smokers have an up to 70 % decreased risk of developing Parkinson’s disease compared to never-smokers. In former smokers, on the other hand, the risk increases continuously with the time of non-smoking. The large effect size, dose-dependent effect and repeated evidence of the association even after controlling for various possible confounding factors make it unlikely that this is just a coincidental association or one mediated by confounders. A genetic cause leading simultaneously to non-smoking (or a lower susceptibility to nicotine dependence) and to an increased risk of Parkinson’s disease seems unlikely as well, especially since the effect also exists in identical twins who share the same genetics.
The historically and culturally changing proportion of both sexes in the total number of smokers provides further evidence for a causal link between smoking and a risk reduction for Parkinson’s disease. The changing smoking habits of women and men over time and the differences in smoking habits between different countries can partly explain the changing incidence of Parkinson’s disease in the two sexes. Smoking as a protective factor for Parkinson is therefore well established.
The question remains which biological mechanism and which ingredient of cigarette smoke accounts for the protective effect. An obvious candidate is nicotine. Nicotine acts in the central nervous system and is responsible for the short-term stimulant effect of smoking. Animal models have shown a neuroprotective effect of nicotine in rats and primates; treatment with nicotine was able to slow down the degeneration of dopaminergic nigrostriatal neurons, which is causal for Parkinson symptoms. This ultimately led to the idea to try nicotine in the treatment of Parkinson patients. Even though the motor symptoms can often be treated relatively well with medication, there is still a lack of drugs that can stop or slow down the course of the disease.
Recently, the results of a study were published in which treatment with a nicotine patch was tested on patients in the early stages of Parkinson’s disease. For this double blind, placebo-controlled multicenter study, participating centers in the USA and Germany randomized 163 patients. Participants had received a Parkinson diagnosis in the 18 months prior to study entry, were in an early stage of the disease and did not yet have pronounced motor symptoms requiring dopaminergic therapy. The participants were therapy-naïve except for a MAO-B inhibitor medication (rasagiline, selegiline).
Patients in the intervention group received a nicotine patch at a dose of 7 mg/24 h from the start, this was then titrated up to the maximum tolerated dose (maximum 28 mg/24 h) and continued for one year. The primary endpoint was worsening in the UPDRS, an established scale for assessing the severity of PD symptoms. Neither the UPDRS nor the various secondary endpoints showed superiority of nicotine therapy over placebo. A weakness of the study was that a relatively large number of participants dropped out of both groups prematurely. The reason was mostly that motor symptoms worsened and patients started dopaminergic therapy, which in turn led to study exclusion. Nevertheless, the data clearly speaks against a therapeutic benefit of transdermal nicotine in the early stages of Parkinson’s disease.
Of course, even if smoking reduces the risk of Parkinson, all cigarette use must still be discouraged. Incidentally, another less problematic protective factor is caffeine. Coffee consumption also seems to reduce the risk, although not to the same extent as smoking. However, since most people tolerate caffeine and coffee well and there are few side effects, most doctors would recommend a cup of coffee instead of a cigarette.
Sources:
Transdermal Nicotine Treatment and Progression of Early Parkinson’s Disease; Oertel et al.; NEJM Evidence; Published August 22, 2023.
The epidemiology of Parkinson's disease: risk factors and prevention; Ascherio et al.; Lancet Neurology; Published November 15, 2016.
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