ncbi.nlm.nih.gov/pmc/articl...
The inverse relationship between PD incidence and any form of nicotine intake such as cigarette smoking (Hernán et al. 2002; Ritz et al. 2007; Li et al. 2015), smokeless tobacco (O’Reilly et al. 2005; Liu et al. 2017b; Yang et al. 2017), exposure to environmental tobacco smoke (Searles Nielsen et al. 2012; Han et al. 2020a; Liu et al. 2020), or even from a dietary source such as peppers (Ma et al. 2020) suggests a therapeutic potential for nicotine in PD.
Dietary nicotine intake was calculated based on consumption of peppers, tomatoes, processed tomatoes, potatoes, and tea. ncbi.nlm.nih.gov/pmc/articl...
What naturally contains nicotine?
Nicotine is an alkaloid found in the nightshade family of plants (Solanaceae), predominantly in tobacco, and in lower quantities in tomato, potato, eggplant (aubergine), and green pepper. Nicotine alkaloids are also found in the leaves of the coca plant.
It is of relevance to note that a recent clinical study using oral administration of nicotine, reported positive effects of nicotine on falls and freezing gait in PD (Lieberman et al. 2019). Furthermore, pulsatile nicotine preparations in forms of inhalers or nasal spray are available and approved by FDA for smoking cessation and could be re-purposed for PD pending evaluation of their effectiveness in clinical trials. In addition, as alluded to earlier, potential usefulness of a pulsatile nicotine administration in improving nonmotor symptoms (e.g., depression or cognitive decline) that are commonly associated with PD (Quik et al. 2015; Tizabi and Getachew 2017; Tizabi et al. 2019), could be an added advantage of nicotinic therapy (Fig. 1).
Butyrate:
Butyrate is a short-chain fatty acid (SCFA) that is produced by gut microbiota and acts primarily as an energy source for colonic epithelial cells and has been shown to have anti-inflammatory, enteroendocrine and epigenetic effects that not only influences colonic and systemic health but can also affect the brain function (Cantu-Jungles et al., 2019). Recent advances in our understanding of the gut-brain axis has resulted in new insights and potential novel targets for therapeutic intervention in PD (Baizabal-Carvallo and Alonso-Juarez, 2020; Cirstea et al. 2020; Cryan et al. 2020). Indeed, it has been suggested that the initiation and progression of PD may be impeded through manipulation of the gut microbiota.