Few illnesses have symptoms as visible, and as disconcerting, as Parkinson’s disease.  Celebrities such as Michael J. Fox, Muhammad Ali, Alan Alda, the Reverend Jesse Jackson, and many others, have raised public awareness of this neurodegenerative disease.  The resting tremors, distinctive shuffling gait, and rigid posture of a person with Parkinson’s have led to the disease being popularly seen as a movement disorder.  While it’s certainly true that Parkinson’s disease (PD) affects parts of the brain that control movement, PD can also be seen more broadly, as a metabolic health condition which stems partly from inflammation, and from issues relating to cellular energy production.  Here we’ll take that important perspective, assessing the role of metabolism and cellular energy dysfunction in the progression of Parkinson’s disease.  

Parkinson’s Disease Basics: Definition and Risk Factors 

Recognized in ancient India but described in the west only in 1817 by English pharmacist James Parkinson, the disease was known as ‘the shaking palsy’ and was misunderstood for many decades.  It wasn’t until the 1870s that the disease was thoroughly studied by Jean-Martin Charcot, the ‘father of modern neurology’, who identified its characteristics: 

• Tremor:  shaking affecting the feet, jaw, and hands 
• Bradykinesia:  unusually slow movements, even during familiar tasks 
• Rigidity:  stiffness in the muscles, which remain almost permanently tensed up 
• Postural Instability:  impaired balance and visible changes in posture.¹ 

PD is most prominently caused by the death of brain cells that produce dopamine, a key neurotransmitter which helps our brain cells communicate, governing our responses to events, foods, and experiences.  PD has motor (movement) aspects, triggered by imbalances in dopamine and the other neurotransmitters.  There are also non-motor symptoms, including gut dysfunction, dysregulated sleep, depression, and cognitive decline.  An important biological marker of PD is the presence of Lewy bodies, which are spherical protein clumps (primarily made up of a protein called alpha-synuclein) which displace healthy cell components.  They are strongly linked to Lewy body dementia, a neurodegenerative disorder which is often discussed alongside PD.  

It is theorized that problems leading to PD begin with neurons that link to the gut and the sense of smell.  The damage then spreads to the lower brainstem (resulting in sleep problems and constipation), then to an area of the brain called the substantia nigra.  Among other tasks, this crucial region helps control movement and produces dopamine, so pharmaceutical treatments for PD focus on increasing the dopamine supply.² 

Eventually, neuronal damage spreads to other parts of the brain, causing ongoing cognitive problems.  It’s important to note that this damage is not instantaneous; the cells show defective metabolism for many years before they eventually die.  But why would one person suffer from these effects, and not others?  And why have incidences of PD been increasing? 

The Recent Rise in PD Cases: A Medical Puzzle 

Incidences of PD have been rising significantly in the last 15-20 years.  Researchers from The Parkinson’s Foundation estimate that 90,000 people became ill with PD in 2022, a 50% increase compared to just 10 years before.³  A similar increase was found in New Zealand, where cases increased by about 50% in only 14 years.⁴  Here are risk factors that could contribute to PD:  

• Genetics plays a role, and the children of PD sufferers are at increased risk. However, genetics is an important factor in only 10-20% of PD cases, leaving the remainder to be “idiopathic” (of unknown cause).⁵ 
• Exposure to pesticides and herbicides increases the risk of developing PD by up to 60%.^{6, 7, 4}  The pesticide rotenone has been found to affect dopamine-producing cells.⁸  
• PD risk increases with age, with the average age of onset being 62.5  Our increased longevity, however, does not account for all of the recent increase.⁴ 
• Head trauma resulting from contact sports, such as football, increases PD risk according to research.⁹  Muhammed Ali suffered from early-onset Parkinson’s disease, diagnosed three years after he retired.¹⁰  Head injuries result in neuroinflammation, production of free radicals, and the disruption of mitochondrial function, which are heavily implicated with PD.¹¹ 
• Finally, modern lifestyle factors contribute to risk, including sedentary habits (which involve little movement or exercise).  And research is revealing the key role of dietary choices, as we’ll see shortly.^{12, 13, 14}

Lifestyle may be the biggest threat.  Out of all these factors, lifestyle may carry the biggest impact across the population because we are all exposed to some extent to a “bad diet” or “not working out enough.”  This affects the metabolic health of cells in our brain and body.  Simply put, our metabolism is the collection of chemical processes that convert food into energy.  When a patient’s lifestyle is damaging to metabolic health, the results can be obesity, hyperglycemia (elevated blood sugar), hypertension (high blood pressure), and hyperlipidemia (high triglycerides and low “good” cholesterol), all of which are implicated in PD.^{15, 16, 17, 18} 

Poor metabolic health can give rise to Metabolic Syndrome, which drives oxidative stress and inflammation, and is a known risk factor for the brain aging found in PD.  Therefore, improving our metabolic health can affect the rate of brain aging by controlling neuroinflammation, reducing mitochondrial dysfunction, and mitigating protein-folding errors:¹⁹ 

Metabolic linkages to Parkinson’s Disease: (Reactive Oxygen Species (ROS) describes oxidative stress; the Ubiquitin-Proteosome Pathway (UPS) governs protein behaviors within a cell).²⁰  

A New View of Parkinson’s Disease 

Well-known neurologist-researcher Dr. Matthew Phillips advocates a new view for PD.  That is, to gain a more complete picture of PD, we need to step away from the traditional perception of the disease as a neurodegenerative disorder which is focal (i.e., mainly affecting just one part of the brain: the substantia nigra) and simply causes motor issues.  These visible symptoms are just a small part of it.  Research has found that non-motor symptoms are both hugely important and much more difficult to track: 

• Gut dysfunction (bloating and constipation) is seen in 80% of cases and can appear years or decades before motor symptoms.²¹ 
• Sleep disturbances are also common, including insomnia, and REM sleep disorders, where the sufferer talks or kicks out while deeply asleep.  
• Mood problems, which at least 60% of people with PD exhibit, including depression, anxiety, or both. 
• Pain syndromes, such as ‘frozen shoulder’ or sciatica (pain, weakness or tingling in the leg) are common in PD patients. 
• Autonomic dysfunctions, including hypotension (a drop in blood pressure when standing up or sitting down), urinary dysfunction (incontinence, pain, etc.), and profuse sweating. 
• Cognitive problems and impairment, such as apathy and hallucinations.   

Just as much as motor problems, and perhaps more so, this collection of non-motor symptoms is Parkinson’s disease, and each is linked to metabolic factors.⁴ 

And to understand how metabolic health connects to brain health, let’s look at one of the smallest components in the body: the energy-producing organelles within our cells known as mitochondria.  

Understanding Mitochondria and Parkinson’s Disease  

These tiny, bean-shaped structures are crucial for cell health.  They do much of the metabolic work within a cell by coordinating cell metabolism (energy creation and distribution).  Neurons need plenty of mitochondria because they have high energy requirements, but in the brains of PD sufferers, the mitochondria do not function properly.  Their numbers are reduced, and they have abnormal shapes.  They don’t fuse or divide as they should, and most importantly, they don’t produce enough energy for the neuron.  

Three of the PD risks we discussed (genetics, environmental toxicants, and head trauma) can damage neuronal mitochondria. 

That’s not all.  Modern dietary habits also damage mitochondria.  Our bodies evolved thousands of years ago in one set of dietary circumstances, but now, after decades of rapid change in agriculture and the food industry, we are in a very different place.  We have very different food patterns from our ancestors.  Continuously eating meals or snacks creates an imbalance in two opposing but complementary processes:  anabolism (which builds up the body) and catabolism (which breaks down cells).  In a balanced system, there is sufficient time for catabolism, but the Standard American Diet (SAD) keeps the body in an anabolic state, partly through the plentiful glucose available from processed carbohydrates.  Overly abundant glucose reaches our mitochondria, and free radicals are produced, damaging those organelles.  

Our mitochondria need time for catabolism, when they can rest and heal.  Without it, our mitochondria are overwhelmed, deluged, and sickened by our dietary choices.  Some researchers now believe that mitochondrial dysfunction resulting from diet is a key player in the recent growth in PD cases.⁴ 

Understanding the Metabolic Link to the Gut-Brain Axis in Parkinson’s Disease 

Recent studies have shown that gut dysfunction is an early contributor to the risk of PD, with constipation as one of the earliest clues.^{22, 23}  Changes in the gut microbiome and increased permeability in the intestinal barrier (i.e. “leaky gut”) are common.  These problems can be addressed in part by changes in diet, which has proved more important than anticipated in preventing PD and addressing its effects.  Increased intake of fiber and polyphenols can re-balance the gut microbiome by providing food for ‘good’ gut bacteria and balancing the excess sugar intake of the SAD which feeds ‘bad’ bacteria.²⁴  As a result, the ‘good’ bacteria contribute to better metabolism in the microbiome, releasing beneficial metabolites called short-chain fatty acids (SCFAs), which research is increasingly showing are important factors in PD.²⁵ 

Managing Metabolic Health to Reduce Parkinson’s Risk and Progression 

The advice for maintaining healthy metabolism and vibrant mitochondria is just what you’d expect: 

• Regular Exercise can help improve insulin sensitivity and regulate blood sugar levels. 
• Quality Sleep is essential for metabolic health and brain function, so consider sleep hygiene and habits. 
• Regular Health Check-ups with your healthcare provider to monitor metabolic health markers, such as blood pressure, blood sugar and cholesterol levels, and body weight – to avoid metabolic syndrome. 
• Healthy Diet: Adopting a balanced and nutritious diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats can help improve metabolic health and lower the risk of Parkinson’s disease.²⁶  In particular, the Mediterranean diet and diets like it have been recommended for people concerned about Parkinson’s.²⁷  
• Implementing ketogenic-type (or lower carbohydrate, higher healthy fat) approaches into the diet.  Ketogenic approaches involve elevating the levels of ketones in the body.  Ketones are energy-rich molecules that can provide neurons with an alternative fuel (other than glucose sugar).  Ketones produce more energy per unit of oxygen, generate fewer free radicals, and can bypass brain insulin resistance.  All in all, raising ketone levels gives our mitochondria a well-deserved break to restore, heal, and regenerate.  Two common ways increase ketone levels are: 
• Time-restricted eating, which typically involves no eating for a period of at least 12 hours or more (such as 14 or 16 hours of no eating).  This process leads the body to a “fasted” state, switching from glucose to ketones for energy. 
• Changing the composition of the diet by decreasing carbohydrate intake and increasing intake of healthy fats. 

The habits and practices necessary for maintaining a healthy brain and metabolism are better understood now than ever before.  Despite the increased availability of information, many of us struggle to fulfill the obligations to our bodies without some amount of help.  Some people may choose to follow certain diets, and fill in their gaps with supplementation tools where they fall short.  Our brain health supplement RELEVATE has become a preferable choice for many.  Designed with 17 nutrients from the brain protective and supportive Mediterranean and MIND diets, RELEVATE provides a daily dose of important brain nutrients.  In fact, studies have found that adhering to the MIND diet is associated with up to 42% lower risk of incident Parkinsonism (symptoms related to Parkinson’s) and also slower progression.³⁰ 

Just like physical fitness, strengthening your brain health is a process that evolves over time with persistent effort. 

In honor of Parkinson's Awareness Month, when you sign up for a RELEVATE subscription, you'll also get extra support to guide you on your journey to improved nutritional brain health: 

• Enjoy a 3-month MIND Meal Planning Pad, designed to simplify the process of incorporating brain-boosting foods into your diet.  
• Plus, receive a 6-Day MIND Diet Inspiration Sheet, complete with examples of meals and snacks to conveniently integrate into your schedule.  
• You'll also receive a Colorful MIND Diet Food Wheel Magnet, featuring weekly serving reminders for the 8 core food groups recommended by the Mediterranean-MIND diet.  
• Pair this with our Vitamin Organizer, labeled with the days of the week, to ensure you stay consistent with your daily brain-supportive nutrition. 

Commit to your metabolic and neurological well-being this Parkinson's Awareness Month by subscribing to RELEVATE here, use code APRILMIND at checkout. 

Takeaways: 

Some aspects of Parkinson’s disease are beyond our control, but our lifestyle choices can greatly affect our risk.  The relationship between metabolic health and Parkinson’s disease underscores the importance of lifestyle management – particularly our dietary choices.  Metabolic factors such as insulin resistance, dyslipidemia, obesity, and chronic inflammation could contribute to the pathogenesis and progression of Parkinson's.  By prioritizing healthy eating, regular exercise, weight management, stress reduction, adequate sleep, and medical monitoring, individuals can mitigate metabolic risk factors and potentially reduce the risk of developing Parkinson's or slow its progression. 

References

1. Parkinson’s Disease | National Institute of Neurological Disorders and Stroke. (n.d.). Retrieved April 7, 2024, from https://www.ninds.nih.gov/health-information/disorders/parkinsons-disease 
2. Parkinson’s Disease – Symptoms, Diagnosis and Treatment. (n.d.). Retrieved April 7, 2024, from https://www.aans.org/en/Patients/Neurosurgical-Conditions-and-Treatments/Parkinsons-Disease 
3. New Study Shows the Incidence of Parkinson’s Disease in the U.S. is 50% Higher than Previous Estimates | Parkinson’s Foundation. (n.d.). Retrieved April 7, 2024 from https://www.parkinson.org/about-us/news/incidence-2022 
4. Parkinson’s Disease- Dr Matthew Phillips: Fasting & Dietary Strategies as Parkinson’s Therapies - YouTube. (n.d.). Retrieved April 7, 2024, from https://www.youtube.com/watch?v=iBNNIIDBIYU 
5. Parkinson’s Disease Risk Factors and Causes | Johns Hopkins Medicine. (n.d.). Retrieved April 7, 2024, from https://www.hopkinsmedicine.org/health/conditions-and-diseases/parkinsons-disease/parkinsons-disease-risk-factors-and-causes 
6. Tanner, C. M., et al.  (2011). Rotenone, paraquat, and Parkinson’s disease. Environmental Health Perspectives, 119(6), 866–872. https://doi.org/10.1289/EHP.1002839 
7. The Relationship Between Pesticides and Parkinson’s | American Parkinson Disease Association. (n.d.). Retrieved April 7, 2024, from https://www.apdaparkinson.org/article/the-relationship-between-pesticides-and-parkinsons/ 
8. Pamies, D., et al. (2018). Rotenone exerts developmental neurotoxicity in a human brain spheroid model. Toxicology and Applied Pharmacology, 354, 101–114. https://doi.org/10.1016/J.TAAP.2018.02.003 
9. Bruce, H. J., et al. (2023). American Football Play and Parkinson Disease Among Men. JAMA Network Open, 6(8), e2328644–e2328644. https://doi.org/10.1001/JAMANETWORKOPEN.2023.28644 
10. Okun, M. S., Mayberg, H. S., & Delong, M. R. (2023). Muhammad Ali and Young-Onset Idiopathic Parkinson Disease—The Missing Evidence. JAMA Neurology, 80(1), 5–6. https://doi.org/10.1001/JAMANEUROL.2022.3584 
11. Kenborg, L., Rugbjerg, K., Lee, P. C., Ravnskjær, L., Christensen, J., Ritz, B., & Lassen, C. F. (2015). Head injury and risk for Parkinson disease: Results from a Danish case-control study. Neurology, 84(11), 1098. https://doi.org/10.1212/WNL.0000000000001362 
12. Chahine, L. M., & Darweesh, S. K. L. (2023). Physical Activity and the Risk of Parkinson Disease: Moving in the Right Direction. Neurology, 101(4), 151–152. https://doi.org/10.1212/WNL.0000000000207527 
13. Jones, J. D., et al (2022). Physical inactivity is associated with Parkinson’s disease mild cognitive impairment and dementia. Mental Health and Physical Activity, 23, 100461. https://doi.org/10.1016/J.MHPA.2022.100461 
14. Gao, X., Chen, H., Fung, T. T., Logroscino, G., Schwarzschild, M. A., Hu, F. B., & Ascherio, A. (2007). Prospective study of dietary pattern and risk of Parkinson disease. The American Journal of Clinical Nutrition, 86(5), 1486–1494. https://doi.org/10.1093/AJCN/86.5.1486 
15. Chen, J., Guan, Z., Wang, L., Song, G., Ma, B., & Wang, Y. (2014). Meta-Analysis: Overweight, Obesity, and Parkinson’s Disease. International Journal of Endocrinology, 2014. https://doi.org/10.1155/2014/203930 
16. Dai, C., Tan, C., Zhao, L., Liang, Y., Liu, G., Liu, H., Zhong, Y., Liu, Z., Mo, L., Liu, X., & Chen, L. (2023). Glucose metabolism impairment in Parkinson’s disease. Brain Research Bulletin, 199, 110672. https://doi.org/10.1016/J.BRAINRESBULL.2023.110672 
17. Hou, L., Li, Q., Jiang, L., Qiu, H., Geng, C., Hong, J. S., Li, H., & Wang, Q. (2018). Hypertension and Diagnosis of Parkinson’s Disease: A Meta-Analysis of Cohort Studies. Frontiers in Neurology, 9(MAR). https://doi.org/10.3389/FNEUR.2018.00162 
18. Hu, G. (2010). Total Cholesterol and the Risk of Parkinson’s Disease: A Review for Some New Findings. Parkinson’s Disease, 2010. https://doi.org/10.4061/2010/836962 
19. Soni, R., & Shah, J. (2022). Deciphering Intertwined Molecular Pathways Underlying Metabolic Syndrome Leading to Parkinson’s Disease. ACS Chemical Neuroscience, 13(15), 2240–2251. https://doi.org/10.1021/ACSCHEMNEURO.2C00165/ASSET/IMAGES/MEDIUM/CN2C00165_0004.GIF 
20. Shen, Y. F., Tang, Y., Zhang, X. J., Huang, K. X., & Le, W. D. (2013). Adaptive changes in autophagy after UPS impairment in Parkinson’s disease. Acta Pharmacologica Sinica, 34(5), 667–673. https://doi.org/10.1038/APS.2012.203 
21. Yang, D., Zhao, et al. (2019). The Role of the Gut Microbiota in the Pathogenesis of Parkinson’s Disease. Frontiers in Neurology, 10, 1155. https://doi.org/10.3389/FNEUR.2019.01155 
22. Cirstea, M. S., Yu, A. C., Golz, E., Sundvick, K., Kliger, D., Radisavljevic, N., Foulger, L. H., Mackenzie, M., Huan, T., Finlay, B. B., & Appel-Cresswell, S. (2020). Microbiota Composition and Metabolism Are Associated With Gut Function in Parkinson’s Disease. Movement Disorders, 35(7), 1208–1217. https://doi.org/10.1002/MDS.28052 
23. New Evidence Suggests Link Between Gut Health and Parkinson’s Disease | Duke Health. (n.d.). Retrieved April 7, 2024, from https://corporate.dukehealth.org/news/new-evidence-suggests-link-between-gut-health-and-parkinsons-disease 
24. Skjærbæk, C., Knudsen, K., Horsager, J., & Borghammer, P. (2021). Gastrointestinal Dysfunction in Parkinson’s Disease. Journal of Clinical Medicine, 10(3), 1–17. https://doi.org/10.3390/JCM10030493 
25. Unger, M. M., Spiegel, J., Dillmann, K. U., Grundmann, D., Philippeit, H., Bürmann, J., Faßbender, K., Schwiertz, A., & Schäfer, K. H. (2016). Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. Parkinsonism & Related Disorders, 32, 66–72. https://doi.org/10.1016/J.PARKRELDIS.2016.08.019 
26. Seidl, S. E., Santiago, J. A., Bilyk, H., & Potashkin, J. A. (2014). The emerging role of nutrition in Parkinson’s disease. Frontiers in Aging Neuroscience, 6(MAR). https://doi.org/10.3389/FNAGI.2014.00036/ABSTRACT 
27. A complete Parkinson’s diet guide. - parkinsonfoundation.org. (n.d.). Retrieved April 7, 2024, from https://parkinsonfoundation.org/blog/a-complete-parkinsons-diet-guide 
28. Gandhi, K. R., & Saadabadi, A. (2023). Levodopa (L-Dopa). PNDR: Psychologists’ Neuropsychotropic Drug Reference, 185–189. https://doi.org/10.4324/9781315825748-35 
29. 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/MDS.27390 
30. Agarwal, P., Wang, Y., Buchman, A. S., Holland, T. M., Bennett, D. A., & Morris, M. C. (2018). MIND DIET ASSOCIATED WITH REDUCED INCIDENCE AND DELAYED PROGRESSION OF PARKINSONISM IN OLD AGE. The Journal of Nutrition, Health & Aging, 22(10), 1211. https://doi.org/10.1007/S12603-018-1094-5