GoDietary Treatments for Parkinson’s Disease

Suemin Yang Thomas Jefferson High School for Science and Technology

This article was originally included in the 2021 print publication of the Teknos Science Journal.

Snow glistened outside my window as I woke up to the chilled, dry air of my room. I got out of bed and walked over to my desk, where 14 cylindrical vials containing hundreds of Drosophila melanogaster -- the common fruit fly -- sat waiting for me to inspect. “The cold and dry air isn’t good for their reproduction,” I thought, hoping the weather hadn’t impacted them. I picked up a vial, and the flies began climbing the walls frantically in response. Many of them fell and struggled to climb to the top, as these were PARK8 mutant flies that had been genetically modified to present symptoms of Parkinson’s disease. Through the Neuroscience Research Lab, I was raising fruit flies in my house, in hopes of discovering a diet-based treatment for Parkinson’s disease. 

Parkinson’s disease (PD) is a neurodegenerative disorder that causes motor deficiencies such as rigid muscles, tremors, and weakness [2]. This disease is characterized by the dysfunction of dopaminergic neurons, which supply the brain with an important neurotransmitter: dopamine. Most common treatments focus on supplying the brain with forms of supplementary dopamine to reduce these symptoms [4]. Since these medications can be costly and complex, it is important to discover effective and accessible treatments that can improve the lives of the millions of patients struggling with this disease. Recently, dietary management has become a topic of interest for researchers looking into the treatment of Alzheimer’s disease, epilepsy, and traumatic brain injuries [3]. In particular, the ketogenic, or high fat diet, is a low-cost and non-invasive treatment that has also interested Parkinson’s researchers. 

A human pilot study by Phillips et al. put Parkinson’s patients on either ketogenic or low-fat diets for 8 weeks [4]. Intriguingly, both diet groups saw a statistically significant improvement in motor and non-motor functions, with the ketogenic group showing the most improvement. Although limited to only 38 patients, this study eluded to potential benefits of Parkinson’s patients maintaining these kinds of diets. The primary researcher, Matthew Phillips (personal communication, Jan. 22, 2021), explained that his interest in metabolic therapies was due to his aim of enhancing health, rather than just masking the disease as medications do. This study inspired an important development in my own project. Along with gathering evidence for the efficacy of different diets, my team and I also compared the effects of these diets to each other. For our experiment, we compared a ketogenic diet to a low-fat/high-carbohydrate diet, which had also proven to be effective in treating PD, and examined the impacts of these diets on the motor function of Parkinsonian D. melanogaster.   

In figuring out how to formulate a ketogenic diet for fruit flies, we looked at a study performed by Lee. et al. in 2019, in which the researchers were examining the use of a metabolite called beta-hydroxybutyrate in a ketogenic diet that was meant to ameliorate post-traumatic brain injury (post-TBI) aggression in D.melanogaster [3]. Beta-hydroxybutyrate is a ketone body produced by the metabolism of fatty acids [5]. Since mitochondrial dysfunction in the dopaminergic neurons is one underlying mechanism of Parkinson’s disease, supplying beta-hydroxybutyrate allows the citric acid cycle, a part of glucose metabolism which releases energy from carbohydrates, to occur seamlessly. Thus, this study supplemented a standard Drosophila diet with beta-hydroxybutyrate, creating a ketogenic diet. After using a high-impact trauma device to induce TBIs, the TBI flies that had been raised on the ketogenic diet containing beta-hydroxybutyrate were found to have markedly decreased aggression compared to the flies raised on a standard diet.

To explore the neurological basis for our low-fat/high carbohydrate diet, we examined a study performed by Kumar and Prashanth [1]. These researchers sought to observe the effects of a diet supplemented by chitosan on the neurological deficits of rotenone-induced D. melanogaster model of Parkinson’s disease. Chitosan is a complex carbohydrate found in the hard outer skeleton of shellfish such as lobsters and shrimp. Rotenone is a common pesticide that is used to elicit the neurodegenerative effects of Parkinson’s by inducing mitochondrial dysfunction. The flies that were put on a rotenone diet supplemented with chitosan had significantly less locomotor impairment and greater levels of dopamine than the standard rotenone diet flies. The researchers measured locomotor impairment by creating a climbing assay, in which the flies were put into a glass column, and then the percent of flies that climbed to the top was recorded.  

In my team’s study, we aimed to compare the efficacy of a ketogenic diet and a low-fat/high carbohydrate diet on the motor abilities of PARK8 mutant D. melanogaster. The ketogenic and low-fat/high carbohydrate diets were created by adding beta-hydroxybutyrate and sucrose respectively to the standard fly diet. We performed two different tests to assess motor function: the climbing assay and the Drosophila activity monitor. The first is a slightly modified version of the climbing assay used in the study performed by Kumar and Prashanth [1]. Rather than counting flies that reached the top of the glass column, we marked our column at a certain measurement and recorded the percentage of flies crossing that mark in a 2-minute time period, accounting for flies going both up and down the column. While the climbing assay is meant to assess climbing ability, the Drosophila activity monitor (DAM) assesses the individual movement levels of each fly. We placed individual flies into small tubes and, plugging each end, recorded the number of times each fly crossed the midline of the vial over a period of 20 minutes. We currently have preliminary data for the Drosophila activity monitor that shows a possibly statistically significant improvement in both diets, with the low-fat/high carbohydrate diet flies performing slightly better. However, more data is necessary before forming our final conclusions.  

Simple and effective dietary treatments, such as the ones studied through my research, are promising therapies for many neurological disorders. However, scientists are still working towards understanding the biological mechanisms that allow these diets to improve neural function. One major theory points to the gut-brain axis, which describes the way in which our gut microbes affect the function of our brains [6]. As more research is needed to delve into the specific workings of the connection between these seemingly unrelated parts of the human body, I will continue my own research into the efficacy of dietary management in treating neurological diseases. Even the flies raised in my own home contribute to the never ending search for solutions to human diseases and how they work.

References

[1] Kumar, P. P., & Prashanth, K. V. H. (2020). Diet with Low Molecular Weight Chitosan exerts neuromodulation in Rotenone induced Drosophila model of Parkinson's disease. Food and Chemical Toxicology, 146. https://doi.org/10.1016/j.fct.2020.111860

[2] Lange, K. W., Nakamura, Y., Chen, N., Guo, J., Kanaya, S., Lange, K. M., & Li, S. (2019). Diet and medical foods in Parkinson's disease. Food Science and Human Wellness, 8(2), 83-95. https://doi.org/10.1016/j.fshw.2019.03.

[3] Lee, D. C., Vali, K., Baldwin, S. R., Divino, J. N., Feliciano, J. L., Fequiere, J. R., Fernandez, M. A., Frageau, J. C., Longo, F. K., Madhoun, S. S., Mingione V, P., O'Toole, T. R., Ruiz, M. G., & Tanner, G. R. (2019). Dietary Supplementation With the Ketogenic Diet Metabolite Beta-Hydroxybutyrate Ameliorates Post-TBI Aggression in Young-Adult Male Drosophila. Frontiers in Neuroscience, 13, 1140. https://doi.org/10.3389%2Ffnins.2019.01140

[4] Phillips, M. C.L., Murtagh, D. K.J., Gilbertson, L. J., Asztely, F. J.S., & Lynch, C. D.P. (2018). Low-fat versus ketogenic diet in Parkinson's disease: A pilot randomized controlled trial. Movement Disorders, 33(8), 1306-1314. https://doi.org/10.1002%2Fmds.27390

[5] Simeone, T. A., Simeone, K. A., Stafstrom, C. E., & Rho, J. M. (2018). Do ketone bodies mediate the anti-seizure effects of the ketogenic diet? Neuropharmacology, 133, 233-241. https://doi.org/10.1016/j.neuropharm.2018.01.011

[6] Zimmer, C. (2019, January 29). Germs in your gut are talking to your brain. Scientists want to know what they're saying. The New York Times, 1. https://www.nytimes.com/2019/01/28/health/microbiome-brain-behavior-dementia.html