Anyone looked into capsaicin for Parkinson’s? According to the following studies:
Capsaicin increases the number of dopaminergic neurons and the expression of the enzyme tyrosine hydroxylase (TH) in those neurons.
Increasing TH expression will increase the dopamine output despite reduced surviving neurons.
This in combination with the supposed increase in dopaminergic neurons which is quite miraculous this should be an effective treatment. I do have my doubts on how effective this would be but I think it would be a useful ancillary supplement for anyone with any condition of dopaminergic insufficiency. Though this study only confirms the increase in dopaminergic neuron amount and TH expression in the substantia nigra segment of the brain.
It also had impressive anti-inflammatory effects where it reduced certain ROS and key cytokines including TNF-α, IL-1β, IL-6.
It also seemed to increase glutathione production in the brain but this was in a cell culture not in an animal or human study.
Another study showed it reduced beta amyloid plaque production. There was an association between higher spicy food consumption and higher cognitive ability + lower beta amyloid plaque levels.
But then a follow up study that went on for 15 years that addressed the claims of the previous study showing the association of higher spicy food consumption and higher cognitive ability actually showed the opposite. So perhaps moderate chili intake is the answer.
“The main symptoms of Parkinson’s disease are tremor, rigidity, and bradykinesia, all of which are caused by the degeneration of tyrosine hydroxylase positive dopaminergic neurons in the substantia nigra. Consequently, there is less dopamine in the striatum because substantia nigra neurons project to the striatum. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and its active metabolite MPP+ (1-methyl-4-phenylpyridinium), are toxic chemical compounds that cause neurodegeneration of substantia nigra neurons. Therefore, MPTP and MPP+ treated animals are used as models of Parkinson’s disease [31,32].
Different interconnected mechanisms cause substantia nigra neurodegeneration in Parkinson’s disease, for example, alpha-synuclein aggregation, mitochondrial dysfunction, and microglial activation [31,32]. It was found that activated microglia contribute to the neurodegeneration process in the substantia nigra by producing oxidants and proinflammatory cytokines [31].
It was repeatedly found that capsaicin reduced neurodegeneration and motor impairment in animal models of Parkinson’s disease [12,31,33,34,35,36]. This compound exerted beneficial effects on Parkinson’s disease by decreasing microglial activation and reducing neuroinflammation [12,31,35,37]. These findings are summarized in Figure 3.
The beneficial effects of capsaicin in Parkinson’s disease are shown in simplified form. Capsaicin administration increases the number of dopaminergic neurons in the substantia nigra and the expression of tyrosine hydroxylase in these neurons. Consequently, there is more dopamine in the striatum. Moreover, after capsaicin treatment, microglial cells in the substantia nigra produce fewer oxidants and inflammatory cytokines. Left panel—before capsaicin treatment, right panel—after capsaicin treatment.
In an MPTP mouse model of Parkinson’s disease, it was found that intraperitoneal application of capsaicin (0.5 mg/kg) increased the number of dopaminergic (tyrosine hydroxylase positive) neurons in the substantia nigra. This effect was dependent on TRPV1 channels. The authors also found that capsaicin improved motor impairment and suggested that one of the mechanisms of these beneficial effects was that this compound decreased the production of reactive oxygen species and proinflammatory cytokines (TNF-α and IL-β) by activated microglia [31]. Similar results were obtained by a different laboratory in a lipopolysaccharide rat model of Parkinson’s disease. The authors found that intraperitoneal capsaicin (1 mg/kg) reduced neurodegeneration in the substantia nigra. In the presence of the tested compound, microglial cells shifted from a proinflammatory to an anti-inflammatory state and produced fewer oxidants and proinflammatory cytokines (IL-1β and IL-6). These neuroprotective effects were dependent on TRPV1 channels because they were reduced after administration of a selective TRPV1 inhibitor, capsazepine [35].
Not only microglial cells but also astrocytes (a different type of glial cell) are influenced by capsaicin in Parkinson’s disease [36]. It was found in an MPP+ animal model that capsaicin applied intraperitoneally (1 mg/kg; a single injection/day for 7 days) activated TRPV1 receptors on astrocytes in the substantia nigra. TRPV1 receptors activation enhanced the production of a ciliary neurotrophic factor by astrocytes which increased tyrosine hydroxylase activity in the substantia nigra and dopamine levels in the striatum [36]. Capsaicin also caused behavioral recovery in MPP+ animals. In a different study from the same laboratory, it was found in the same model of Parkinson’s disease that activated microglia produced fewer reactive oxygen species in the substantia nigra after intraperitoneal administration of capsaicin (1 mg/kg). Microglia-derived oxidative stress was reduced by a ciliary neurotrophic factor produced by capsaicin-stimulated astrocytes in the substantia nigra [12]. This effect of capsaicin reduced neurodegeneration and decreased motor impairment in MPP+ rats.
Alpha-synuclein deposition is an important feature of Parkinson’s disease [32]. A protective role of dietary capsaicin (20, 40, 80 and 100 μM for 24 days) against Parkinson’s disease was reported in flies expressing human alpha-synuclein. It was found that capsaicin increased dopamine content, reduced oxidative stress markers, and enhanced free radical scavenging potential in brains obtained from flies with Parkinson’s disease [38].
To summarize, capsaicin treatment reduces neurodegeneration and improves behavioral outcomes in different animal models of Parkinson’s disease. The important mechanism of this effect is that this compound reduces oxidants and proinflammatory cytokines production by activated microglia. This process is shown schematically in Figure 3.” - Beneficial Effects of Capsaicin in Disorders of the Central Nervous System Beneficial Effects of Capsaicin in Disorders of the Central Nervous System - PMC
“The present study aimed to identify the gene expression changes conferred by capsaicin in the cell model of 6-OHDA-induced Parkinson’s disease, to disclose the molecular mechanism of action of capsaicin. We used capsaicin-treated and paraffin-embedded wax blocks containing substantia nigra tissue from 6-OHDA-induced Parkinson’s disease rats to analyze transcriptional changes using Affymetrix GeneChip Whole Transcript Expression Arrays. A total of 108 genes were differentially expressed in response to capsaicin treatment, and seven of these genes were selected for further analysis: Olr724, COX1, Gsta2, Rab5a, Potef, Actg1, and Acadsb, of which Actg1 (actin gamma 1) was down-regulated and Gsta2 (Glutathione S-transferase alpha 2) was up-regulated. We successfully overexpressed Actg1 and Gsta2 in vitro. CCK-8 detection and flow cytometry demonstrated that overexpression of Actg1 and Gsta2 increased apoptosis in the 6-OHDA-induced Parkinson’s disease cell model. The imbalance between Actg1 and Gsta2 may be one of the mechanisms of cell damage in Parkinson’s disease (PD). Capsaicin can protect the cells and reduce the apoptosis rate by regulating Actg1 and Gsta2.” - Regulation of Actg1 and Gsta2 is possible mechanism by which capsaicin alleviates apoptosis in cell model of 6-OHDA-induced Parkinson’s disease https://portlandpress.com/bioscirep/article/40/6/BSR20191796/225257/Regulation-of-Actg1-and-Gsta2-is-possible
“Previous studies suggest that there is a geographic overlap between AD incidence and spicy food consumption. We previously reported that capsaicin-rich diet consumption was associated with better cognition and lower serum Amyloid-beta (Aβ) levels in people aged 40 years and over. In the present study, we found that intake of capsaicin, the pungent ingredient in chili peppers, reduced brain Aβ burden and rescued cognitive decline in APP/PS1 mice. Our in vivo and in vitro studies revealed that capsaicin shifted Amyloid precursor protein (APP) processing towards α-cleavage and precluded Aβ generation by promoting the maturation of a disintegrin and metalloproteinase 10 (ADAM10). We also found that capsaicin alleviated other AD-type pathologies, such as tau hyperphosphorylation, neuroinflammation and neurodegeneration. The present study suggests that capsaicin is a potential therapeutic candidate for AD and warrants clinical trials on chili peppers or capsaicin as dietary supplementation for the prevention and treatment of AD.” - Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer’s disease-type pathology and cognitive deficits in APP/PS1 mice Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer’s disease-type pathology and cognitive deficits in APP/PS1 mice - PMC
“We aimed to examine the association between chili intake and cognitive function in Chinese adults. This is a longitudinal study of 4852 adults (age 63.4 ± 7.7) attending the China Health and Nutrition Survey during 1991 and 2006. Cognitive function was assessed in 1997, 2000, 2004 and 2006. In total, 3302 completed cognitive screening tests in at least two surveys. Chili intake was assessed by a 3-day food record during home visits in each survey between 1991 and 2006. Multivariable mixed linear regression and logistic regression were used. Chili intake was inversely related to cognitive function. In fully adjusted models, including sociodemographic and lifestyle factors, compared with non-consumers, those whose cumulative average chili intake above 50 g/day had the regression coefficients (and 95% CI) for global cognitive function of −1.13 (−1.71–0.54). Compared with non-consumers, those with chili consumption above 50 g/day had the odds ratio (and 95% CI) of 2.12(1.63–2.77), 1.56(1.23–1.97) for self-reported poor memory and self-reported memory decline, respectively. The positive association between chili intake and cognitive decline was stronger among those with low BMI than those with high BMI. The longitudinal data indicate that higher chili intake is positively associated with cognitive decline in Chinese adults in both genders.” - High Chili Intake and Cognitive Function among 4582 Adults: An Open Cohort Study over 15 Years https://www.researchgate.net/publication/333413321_High_Chili_Intake_and_Cognitive_Function_among_4582_Adults_An_Open_Cohort_Study_over_15_Years
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