Does Dietary Nicotine Protect Against Parkinson's Disease?
Abstract & Commentary
By Claire Henchcliffe, MD
Associate Professor of Neurology and Neuroscience, Weill Cornell Medical College
Dr. Henchcliffe reports she is on the speakers bureau and advisory board for Allergan and Teva; speakers bureau for Boehringer-Ingelheim, GlaxoSmithKline, and Novartis; advisory board for Merz; and is a consultant for Gerson Lehman Group and Guidepoint Global. This article originally appeared in the December 2013 issue of Neurology Alert.
Synopsis: This population-based, case-control study suggests that dietary intake of peppers and related species may be associated with decreased risk of Parkinson's disease. These plants are related to tobacco, raising the possibility that nicotine may be the underlying link.
Source: Searles Nielsen S, et al. 2013 nicotine from edible Solanaceae and risk of Parkinson disease. Ann Neurol 2013; 74:472-477.
This case-control study evaluated risk of parkinson's disease (PD) associated with dietary nicotine intake from edible plants of the Solanaceae family. A total of 490 newly diagnosed PD cases were compared with 644 controls. Of these participants, 63% of cases and 64% of controls were men, and mean age at the time of assessment was 66 years old (cases) and 68 years old (controls). Half of the PD cases and 62% of controls were classified as having significant history of smoking. PD cases were diagnosed by a movement disorders expert or by chart review by a team of neurologists at two centers in the Pacific Northwest. Edible Solanaceae family members studied were peppers, tomatoes including tomato juice, and potatoes (baked or mashed only), and nicotine intake associated with these was estimated based upon standard values for dry weight. A number of other non-Solanaceae vegetables also were evaluated. Logistic regression was used to calculate odds ratios with adjustments made for age, sex, race/ethnicity, non-Solanaceae vegetable intake, tobacco, and caffeine. Other potential confounders excluded were education, family history of PD, estimated alternative Mediterranean diet score, body mass index, and secondary smoking. The odds ratio (OR) for Parkinson's disease related to Solanaceae intake was 0.81 (95% confidence interval [CI], 0.65-1.01; P-trend = 0.07). However, by breaking down into different Solanaceae family members, this value was driven by intake of peppers (OR, 0.43; 95% CI, 0.24-0.78; P-trend = 0.005). For tomatoes, the OR was 0.83 (95% CI, 0.56-1.24) and for potatoes was 1.12 (95% CI, 0.73-1.7). Nicotine from eggplant intake was insufficient to meet the limit of quantitation. Not only were peppers associated with a lower risk of Parkinson's disease, an inverse association of PD risk with increasing pepper consumption was identified. For all participants, eating peppers 2-4 times weekly was associated with an OR of 0.7 (95% CI, 0.50-1.00), whereas the OR for daily intake was 0.5 (95% CI, 0.22-1.15). This inverse association was more pronounced in those who were not tobacco users.
Tobacco smoking has been associated with decreased PD risk in multiple studies, and nicotine has been suggested as the tobacco component responsible. This study addresses whether dietary intake of nicotine may have a similar association, and provides support for a link between risk of PD and dietary intake of edible plants of the Solanaceae family, which include peppers, tomatoes, potatoes, and eggplants, as well as tobacco. Not only does the study supports an association with dietary nicotine intake, but also a potential dose response, since the greatest risk reduction was associated pepper intake (highest nicotine content per kilogram of all the vegetables assessed here). Additionally results were more compelling in the subgroup of subjects who were not tobacco users vs those who were. All of this, therefore, supports a role for nicotine as at least one of the chemical compounds responsible for the inverse association of Solanaceae ingestion with PD risk. Moreover, nicotine possesses neuroprotective properties in the rotenone and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine animal models of PD. However, caution should be used in interpreting these results. Dietary data collection relies on subject self-report. Certain foodstuffs were not included, for example salsa or French fries. There is also first-pass metabolism in the liver that cannot be accounted for in such a study design. It is always challenging to discern which of an array of chemical constituents is/are relevant to risk modification. Peppers, in addition to containing nicotine, are excellent sources of nutrients previously found to be associated with lower PD risk, such as carotenoids, and also provide multiples of the B vitamins and trace elements. Nonetheless, this study now provides independent support for a potential role of nicotine as neuroprotectant, and should stimulate further study as a potentially modifiable risk factor. It is, therefore, timely that an international clinical trial is now underway to examine the effect of transdermal nicotine administered in early PD.