Learn how non-nicotine and non-caffeine compounds in tobacco and coffee may shield the brain from Parkinson's disease, paving the way for innovative therapies.
Study: Smoking, coffee intake, and Parkinson’s disease: Potential protective mechanisms and components. Image Credit: New Africa / Shutterstock.com
A recent review published in the journal NeuroToxicology highlights how specific components found in tobacco and coffee may offer protective benefits against Parkinson’s disease (PD).
Current treatments for PD
PD is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra. Some of the most common medications used to treat PD include L-DOPA, dopamine agonists, as well as dopamine degradation inhibitors such as monoamine oxidase B (MAO B) inhibitors and catechol-O-methyl transferase (COMT) inhibitors.
Although effective in reducing symptom intensity, these medications are limited in their ability to mitigate disease progression. Additional strategies for PD treatment primarily address oxidative stress, mitochondrial dysfunction, excitotoxicity, the Wnt/β-catenin signaling pathway, and non-dopaminergic neurotransmitter systems.
How do tobacco and coffee affect PD risk?
The most significant risk factor of PD is advanced age; however, various genetic, environmental, and lifestyle risk factors can also increase the risk of PD.
Interestingly, smoking and coffee consumption have been reported to reduce the risk of PD, which has been attributed to bioactive, non-nicotine and non-caffeine components in cigarettes and coffee, respectively. Other factors negatively associated with PD development include serum uric acid levels, physical activity, moderate alcohol intake, non-steroidal anti-inflammatory drugs (NSAIDs), calcium channel blockers, and welding.
Many candidate molecules and molecular mechanisms associated with these lifestyle factors have been identified. Among these molecules, clinical trials of nicotine, caffeine, and urate have been conducted; however, none of these trials have found therapeutic benefits in PD, indicating the need for further research into alternative compounds.
MAO B inhibitors in tobacco and coffee
Several neurodegenerative diseases, including PD, are associated with increased MAO B levels in the brain. Notably, previous studies investigating different brain regions in smokers and non-smokers have reported lower MAO B levels in the brains of smokers.
Reversible and selective MAO B inhibitors present in tobacco include trans, trans-farnesol, menadione (2-methyl-1,4-naphthoquinone), 1,4-naphthoquinone, scopoletin, and diosmetin. Furthermore, norharman and harman are robust MAO inhibitors present in cigarette smoke and coffee.
Recent studies have identified six novel MAO inhibitors in tobacco smoke, including α-linolenic acid, a polyunsaturated fatty acid with anti-inflammatory, antioxidative, and neuroprotective properties. These compounds can inhibit both human MAO A and MAO B isoenzymes. Similarly, green coffee contains numerous bioactive flavonoids such as quercetin, myricetin, and rutin with MAO B inhibitory activity.
Inhibition of α-synuclein fibrillation by tobacco and coffee compounds
The aggregation of α-synuclein, a presynaptic neuronal protein, is a hallmark of PD and other synucleinopathies. Nicotine and hydroquinone in cigarette smoke can inhibit α-synuclein fibrillation in a dose-dependent manner. Similarly, caffeine present in coffee reduces the toxicity of α-synuclein aggregates.
Eicosanoyl-5-hydroxytryptamide, a coffee component, has shown beneficial effects in reducing α-synuclein aggregation and phosphorylation in experimental models. Likewise, catechol-containing compounds and antioxidant compounds from tobacco smoke and coffee exhibit α-synuclein fibrillation inhibitory effects.
COMT inhibition by tobacco and coffee compounds
COMT catalyzes the O-methylation metabolism of dopamine and prevents its synthesis. Inhibiting COMT increases L-DOPA levels and its transportation to the brain.
Among numerous catechol-containing compounds from tobacco smoke or coffee, quercetin is the most potent inhibitor of COMT. Other potential COMT inhibitors present in tobacco and coffee include chlorogenic acid, caffeic acid, rutin, and myricitrin, which also contribute to their anti-PD effects.
Suppression of neuroinflammation by tobacco and coffee compounds
Neuroinflammation in the brain significantly contributes to the degeneration of dopaminergic neurons, thereby leading to the development and progression of PD. Several alkaloids, phenols, phenolic acids, and flavonoids found in tobacco and coffee have shown potent neuroprotective and anti-inflammatory activities in both in vitro and in vivo models of PD.
Gut microbiota alteration by tobacco and coffee compounds
Changes in gut microbiota composition may also contribute to PD pathogenesis by increasing the transportation of α-synuclein aggregates from the gut to the brain. Smoking and coffee drinking have been found to reduce PD risk by altering the gut microbiota composition, which improves intestinal barrier integrity by increasing beneficial microorganisms and decreasing harmful ones.
Nuclear factor erythroid 2-related 2 (Nrf2) pathway activation by tobacco and coffee compounds
Several compounds from tobacco and coffee reduced PD risk by activating the Nrf2 pathway and subsequently protecting against oxidative or electrophilic stress. Natural Nrf2 activators found in tobacco and coffee include catechol, 4-methylcatechol, hydroquinone, and 4-vinylcatechol.
Journal reference:
- Hong, S. W., Page, R., & Truman, P. (2025). Smoking, coffee intake, and Parkinson’s disease: Potential protective mechanisms and components. NeuroToxicology. doi:10.1016/j.neuro.2024.12.003