New Insights into Parkinson's Disease: Exploring Risk Factors, Management Strategies, and Emerging Treatments

The Alarming Rise in Parkinson’s Disease with Dr. Ray Dorsey (YouTube link)

Recent advancements in Parkinson’s Disease (PD) research have provided new insights into its progression and potential treatments:

• COVID-19 Linked to Parkinson's Risk: Some studies indicate that COVID-19 may increase the risk of Parkinson's disease. This is supported by a rise in cases of parkinsonism, a group of symptoms including tremors, slow movement, stiffness, and balance problems, following COVID-19 infections.^[29]
• Gut Microbiota Link to Parkinson’s Disease: Researchers found that reduced bacterial genes related to vitamins B2 and B7 synthesis in the gut microbiota are linked to Parkinson’s disease. This deficiency affects intestinal short-chain fatty acids and polyamines, which maintain the intestinal barrier. B vitamin therapy could potentially restore the barrier and treat Parkinson’s disease.^[27]
• Potential link between air pollution and Parkinson's disease: The prevalence of Parkinson's seems to rise alongside increasing air pollution levels, with higher rates in polluted areas and developing countries with poor air quality. While the link isn't yet conclusive, this research offers a promising new direction.^[28]
• Smartwatch Technology: Research has shown that consumer devices like smartwatches can monitor PD symptoms over time, offering a window into the disease’s progression. This technology could accelerate therapy approvals as it provides objective, real-world measures of disease progression.^[1]

• Resting Tremor: A study by Murdoch University’s Center for Healthy Aging is focusing on interventions to treat resting tremor, a symptom unique to PD as it primarily occurs when the person is at rest.^[2]

• Molecular Switch: Scientists from the University of Dundee have discovered a molecular switch in the brain that may protect against PD, offering a potential new target for treatment.^[3]

• CHCHD2 Gene Mutation: Tokyo Medical and Dental University researchers have identified a pathological mechanism for familial PD caused by a mutation in the CHCHD2 gene. Inhibiting the associated protein Csnk1e/d may slow or halt PD development in patients with this mutation.^[4]

These insights represent significant steps forward in understanding and potentially treating Parkinson’s Disease.

Awakenings (1990) Trailer #1 (YouTube link)

Parkinson's Disease (PD): An Overview

Parkinson’s Disease is the second most common neurodegenerative disorder, primarily affecting people over 85. It's characterized by the buildup of α-synuclein protein in brain cells, leading to cell death. Symptoms include both motor (tremors, stiffness) and non-motor (smell changes, mood swings) issues, which can appear together or separately.

Risk Factors for PD

• Genetics
• Environmental toxins
• Head injuries
• Gut bacteria composition

Progression of PD

α-synuclein clumps disrupt cellular functions and cause the loss of dopamine-producing neurons in the midbrain, crucial for movement control. These clumps may spread between neurons like prions.

Other Research Advancements

• The TMAO pathway's role in PD patients
• Link between smell dysfunction and neurodegenerative diseases
• Association between pesticide exposure and increased PD risk
• Autophagy (cellular cleanup) decline as a potential contributor to PD, especially with age (research by Nobel laureate Yoshinori Ohsumi)

Impact and Current Treatments

Globally, around six million people have PD, experiencing nerve cell loss and Lewy body deposits (α-synuclein clumps). While there's no cure or treatment to slow PD progression, medications like levodopa (L-DOPA) manage symptoms by boosting dopamine levels. Genetic research is identifying mutations linked to PD, such as those in the TMEM230 gene affecting dopamine packaging in neurons.

L-DOPA, a medication that can cross the blood-brain barrier, is used to increase brain dopamine levels for treating PD and dopamine-responsive dystonia. Oliver Sacks' book "Awakenings" details his experiences using L-DOPA to treat patients in the late 1960s.

Exploring New Approaches

Lifestyle changes like ketogenic diets have shown promise in reducing PD symptoms, highlighting the need for further research on diverse treatment options and preventative measures.

Ketogenic Diets and Parkinson's Disease

A small study showed that five out of seven PD patients experienced significant symptom improvement after following a ketogenic diet for 28 days.

Side Effects of Ketogenic Diets

While generally safe, long-term keto diets may cause constipation, dehydration, and electrolyte/micronutrient deficiencies. Potential risks include increased chance of kidney stones, gallbladder problems, and bone fractures (especially in children). Women may experience menstrual irregularities and potential fertility issues. Nutritional ketosis doesn't typically reach ketone levels that cause ketoacidosis (blood acidification), but long-term safety requires further study.

Environmental Risks

Exposure to trichloroethylene (TCE), particularly in workplaces, has been linked to an increased risk of developing parkinsonism. Studies show workplace TCE exposure can significantly raise the chances of developing Parkinson's disease.

How to Improve Motivation & Focus By Leveraging Dopamine (YouTube link)

References

1. Smartwatches offer window into Parkinson's disease progression
2. Resting tremor in focus in new Parkinson's study
3. Doctors say they are getting closer to understanding Parkinson’s Disease
4. New insights into the development of Parkinson's disease in the brain
5. A New Gene Has Been Linked to Parkinson's Disease
6. A New Model for Discerning Parkinson’s
7. Parkinson's Disease Infographic
8. Parkinson's Disease Linked to Microbiome
9. New Parkinson's Drug May Combat Movement Difficulties
10. Increased Intestinal Permeability Correlates with Sigmoid Mucosa alpha-Synuclein Staining and Endotoxin Exposure Markers in Early Parkinson's Disease
11. Alpha-synuclein and Parkinson's Disease
12. Could Parkinson's disease start in the gut?
13. We’ve Got a Lot of Nerves (Michael Greger, M.D. FACLM)
14. Low-Level Pesticide Exposure Linked to Parkinson's Disease
15. The fat-fueled brain: unnatural or advantageous?
16. Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study
17. New Genetic Associations for Parkinson’s Disease Identified
18. A gut-brain link for Parkinson’s gets a closer look (good)
19. L-DOPA
20. How your sense of smell predicts your overall health
21. Rates of Parkinson’s disease are exploding. A common chemical may be to blame
22. Nucleolar Disruption in Dopaminergic Neurons Leads to Oxidative Damage and Parkinsonism through Repression of Mammalian Target of Rapamycin Signaling
23. Does Data-Independent Acquisition Data Contain Hidden Gems? A Case Study Related to Alzheimer's Disease
24. Neuroprotective Effect of Melatonin on Sleep Disorders Associated with Parkinson’s Disease
25. The Role of Intestinal Microbiota and Diet as Modulating Factors in the Course of Alzheimer’s and Parkinson’s Diseases
26. Voigt, R.M.; Wang, Z.; Brown, J.M.; Engen, P.A.; Naqib, A.; Goetz, C.G.; Hall, D.A.; Metman, L.V.; Shaikh, M.; Forsyth, C.B.; et al. Gut microbial metabolites in Parkinson’s disease: Association with lifestyle, disease characteristics, and treatment status. Neurobiol. Dis. 2022, 170, 105780. [Google Scholar] [CrossRef]
27. Treating the gut-brain connection with B vitamins to treat Parkinson's Disease
28. Bad Air and Parkinson Disease-The Fog May Be Lifting
29. What We Know About Covid’s Impact on Your Brain

Inflammatory Bowel Disease—Knowing the Basics

Inflammatory bowel disease (IBD) is a complicated chronic inflammatory disease that involves various genetic and environmental driving factors.^[1]

Video 1.  The Best Diet for Crohn’s Disease Treatment (YouTube link)

Types of IBD?

Inflammatory bowel disease (IBD) is an umbrella term used to describe disorders that involve chronic inflammation of your digestive tract. Types of IBD include:

• Ulcerative colitis
• Which involves inflammation and sores (ulcers) along the superficial lining of your large intestine (colon) and rectum
• Crohn's disease
• Which is characterized by inflammation of the lining of your digestive tract, which often can involve the deeper layers of the digestive tract

Both ulcerative colitis and Crohn's disease usually are characterized by diarrhea, rectal bleeding, abdominal pain, fatigue and weight loss.

Image via: AHealthBlog

Diets and IBD

IBD can be debilitating and sometimes leads to life-threatening complications.  Although its pathogenesis is poorly understood, an increasing number of studies have highlighted that dietary intake plays a key role in disease occurrence due to its underlying effects on gut microbiota, barrier function, and mucosal immunity.^[2] For instance, 

• Westernized diet (WD)
• In [7], it shows the implications of the WD in the onset and progression of IBD
• WD is very different from the traditional diet of previous generations when the prevalence of IBD was considerably lower
• The most radical change has been the switch from a plant-based to an animal-sourced diet
• Another important change brought about by the Western diet is an overall higher calorie intake, especially from sugar, refined carbohydrates, animal proteins and ultra-processed foods.
• High-salt diet
• Can exacerbate intestinal inflammation by reducing Lactobacillus abundance and butyrate metabolism^[3]
• High-fat diet
• Can contribute toward IBD progression by activating proinflammatory signaling and disrupting barrier systems^[4]
• Ketogenic diet (KD)
• KD is characterized by high-fat and low-carbohydrate, is a dietary therapy that was initially used to treat drug-resistant epilepsy.^[5]
• In a study, it has shown that KD significantly reduced inflammatory responses, protected intestinal barrier function, and reduced ILC3 production and the expression of related inflammatory cytokines (IL-17α, IL-18, IL-22, Ccl4), whereas the opposite effects were observed for the low-carbohydrate diet (LCD).^[6]

More Readings

• Gut microbiota
• The Importance of Microbiota in Healthy Aging
• Barrier function
• Leaky Gut Syndrome and Autoimmune Disease
• Mucosal immunity
• Mucosal Immunity in COVID-19: A Neglected but Critical Aspect of SARS-CoV-2 Infection

References

1. Digby-Bell, J. L., Atreya, R., Monteleone, G. & Powell, N. Interrogating host immunity to predict treatment response in inflammatory bowel disease. Nat. Rev. Gastroenterol. Hepatol. 17, 9–20 (2020).
2. Keshteli, A. H., Madsen, K. L. & Dieleman, L. A. Diet in the pathogenesis and management of ulcerative colitis; a review of randomized controlled dietary interventions. Nutrients 11, 1498 (2019).
3. Miranda, P. M. et al. High salt diet exacerbates colitis in mice by decreasing Lactobacillus levels and butyrate production. Microbiome 6, 57 (2018).
4. Rohr, M. W., Narasimhulu, C. A., Rudeski-Rohr, T. A. & Parthasarathy, S. Negative effects of a high-fat diet on intestinal permeability: a review. Adv. Nutr. 11, 77–91 (2020).
5. Ulamek-Koziol, M., Czuczwar, S. J., Januszewski, S. & Pluta, R. Ketogenic diet and epilepsy. Nutrients 11, 2510 (2019).
6. Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome
7. Implications of the Westernized Diet in the Onset and Progression of IBD
8. Diet and nutrition in the management of inflammatory bowel disease
9. Walnuts may help protect against ulcerative colitis

Important Health Effects of Dietary Fiber

Dietary fiber consists of non-starch polysaccharides (NSP) and many other plant components such as resistant starch, resistant dextrins, inulin, lignin, chitins, pectins, beta-glucans, and oligosaccharides.

Video 1.  Is the Fiber Theory Wrong? (YouTube link)

Dietary fiber can contribute to your overall good health and longevity, and can have a positive impact on lowering risk of diseases related to Western diets, which include:^[1]

• Cancers^[25,26]
• Diabetes^[27]
• Tumor formation
• Disordered laxation
• Autoimmune diseases
• Coronary heart disease^[28]
• Inflammatory bowel disease
• Mineral related abnormalities

by feeding and promoting healthy gut bacteria.

In this article, we will cover the health effects of fiber from two prospectives:

• Traditional wisdom 
• Mostly from digestive system perspective
• Gut Microbiota 
• Mostly from immune system perspective

Traditional Wisdom

Proven benefits of dietary fiber include fewer colon polyps and thus less risk of colon cancer.  Dietary fiber is also thought to help prevent iron overload, which could promote inflammation in the colon that leads to mucosal damage, since fiber binds to iron and helps the metal pass out of the body through the digestive tract.^[5]

• Insoluble fiber
• Insoluble fiber you consume is passed through your gut undigested and sweeps out it like a broom
• Benefits
• It is an effective laxative to relieve your constipation or irregular stools
• Soluble fiber
• Soluble fiber attracts fluid in your gut, creating a slow-moving gel
• Benefits
• It slows digestion, which allows vitamins and minerals to absorb through intestinal walls
• For example, daily consumption of dietary fiber significantly increases calcium absorption and enhances bone mineralization during pubertal growth^[11]
• It can help lower plasma cholesterol levels and help to normalize blood glucose and insulin levels

Gut Microbiota

Intestinal epithelial barrier

The total surface area of the gastrointestinal system is approximately 300 to 400 sq. m.  However, only a single epithelial layer separates you from enormous amounts of antigens of both dietary and microbial origin.

Sitting on top of this cell lining is a layer of mucus that is also an important part of the intestinal epithelial barrier. This barrier's job is to regulate everything that passes between your intestine and the rest of your body.

Together with the immune cells located in your gut, which represents almost 70% of the entire immune system, the barrier helps control how your immune system reacts to anything foreign. When the barrier is weak or comprised, you have a condition called leaky gut syndrome which can potentially increase your risk of autoimmune diseases.

Short-chain fatty acids

Dietary fiber can be fermented into short chain fatty acids (SCFAs) in your guts. SCFAs have a number of health promoting effects:^[1,14]

• Lowering the pH of the colon
• Inhibiting growth of pathogenic organism
• Increasing mineral absorption
• Serving as a vital fuel source for the colonic epithelium and key regulators of immune homeostasis
• Which serves as the prototypical example of the symbiotic nature between the microbiome and the host in terms of diet and metabolism

Of the SCFAs, butyrate is considered to be the preferred fuel of cells of colon (i.e. colonocytes).  Without butyrates for energy, colon cells can undergo autophagy (self digestion) and die.^[18]

Video 2.  How The Gut Microbiota Affects Our Health with Dr. Erica & Dr. Justin Sonnenburg (YouTube link)

Beneficial gut bacteria
Most gut bacteria reside only in the colon (which has a volume of 0.4 liters). SCFAs are produced by these beneficial colonic bacteria (probiotics) that feed on, or ferment prebiotics, which are plant products that contain adequate amounts of dietary fiber. 
In the video above, Dr. Sonnenburg found that microbes in the guts of Americans make more enzymes that degrade mucins, compared with those in the Hadza who still lead a historic hunter-gatherer way of life in Tanzania. These enzymes allow bacteria to harvest carbohydrates from the mucosal lining of the gut, rather than from plant fiber.^[20]
In other words,

“If you’re not feeding your gut microbiome with dietary fiber,” Dr. Sonnenburg said, “your gut microbiome is literally feeding on you,” 

which may result in changes in microbiota localization and barrier disruption in the distal gut. Interactions between resident microbes and host leading to immune dysregulation may explain several diseases that share inflammation as a common basis. 
Besides serving as foods to colonic bacteria, scientists have also found that polyphenols bound to the fiber may have a significant physiological impact within the large intestine, affecting microflora development and intestinal antioxidant status by producing metabolites that can be absorbed through the mucosa.^[13]

Sources of Dietary Fiber 

In recent years, it become clear that in order to be truly healthy, you need a healthy gut. Dietary fiber is used as food for your beneficial bacteria, and a healthy microbiome is essential to optimizing your health. For example, they produce compounds that help regulate your immune function and even improve brain health.
Dietary fiber can be found from the following food sources:

• Insoluble fiber 
• Blackberry seeds, celery, dark-green leafy vegetables, green beans, skins of onions, and whole grains
• Soluble fiber
• Apples, barley, beans, berries, citrus fruits, cucumbers, oats, nuts, peas and psyllium.

Note that many whole foods contain both soluble and insoluble fiber.  Dr. Mercola recommend consuming a minimum of 35 grams of fiber and ideally > 50 grams from whole foods per day.^[12] Also, be warned that your gut may not be used to these amounts of fiber, you will want to gradually increase to those levels, as they can cause gas and bloating and even constipation until your microbiome readjusts.

References

1. V Kumar, A K Sinha, H P Makkar, G de Boeck, K Becker. Dietary roles of non-starch polysaccharides in human nutrition: a review. Crit Rev Food Sci Nutr. 2012;52(10):899-935
2. How The Gut Microbiota Affects Our Health with Dr. Erica & Dr. Justin Sonnenburg
3. Gut Bacteria Can Fluctuate With the Seasons
4. Paleopoo: What We Can Learn from Fossilized Feces
5. Why You Should Always Use Organic Red Onions
6. J. I. Wurzelmann et al., "Iron Intake and the Risk of Colorectal Cancer," Cancer Epidemiology, Biomarkers and Prevention, 5, no. 7 (July 1, 1996): 503-7.  PMID: 8827353.
7. Justin Sonnenburg on "The Good Gut"
8. Mucins in the mucosal barrier to infection
9. Scientists bust myth that our bodies have more bacteria than human cells
10. Dr Greger on dietary fibers
11. S A Abrams, I J Griffin, K M Hawthorne, L Liang, S K Gunn, G Darlington, K J Ellis. A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents. Am J Clin Nutr. 2005 Aug;82(2):471-6.
12. Fat for Fuel (Dr. Mercola)
13. F Saura-Calixto. Concept and health-related properties of nonextractable polyphenols: the missing dietary polyphenols. J Agric Food Chem. 2012 Nov 14;60(45):11195-200.
14. J R Goldsmith, R B Sartor. The role of diet on intestinal microbiota metabolism: downstream impacts on host immune function and health, and therapeutic implications. J Gastroenterol. 2014 May;49(5):785-98.
15. The Good Gut: Taking Control of Your Weight, Your Mood, and Your Long-term Health
16. Justin Sonnenburg and Erica Sonnenburg Publications
17. Starving our microbial self: the deleterious consequences of a diet deficient in microbiota-accessible carbohydrates
18. Donohoe, Dallas R.; Garge, Nikhil; Zhang, Xinxin; Sun, Wei; O'Connell, Thomas M.; Bunger, Maureen K.; Bultman, Scott J. (2011). "The Microbiome and Butyrate Regulate Energy Metabolism and Autophagy in the Mammalian Colon". Cell Metabolism. 13 (5): 517–26. 
19. Lupton, Joanne R. (February 1, 2004). Microbial Degradation Products Influence Colon Cancer Risk: the Butyrate Controversy. vol. 134 no. 2: J. Nutr. pp. 479–482.
20. Sonnenburg JL, Xu J, Leip DD, Chen CH, Westover BP, Weatherford J, Buhler JD, Gordon JI. Glycan foraging in vivo by an intestine-adapted bacterial symbiont. Science. 2005;307:1955–1959.
21. ‘Ridiculously Healthy’ Elderly Have the Same Gut Microbiome as Healthy 30 Year-Olds
22. Gut microbes could help trigger multiple sclerosis
23. Constipation and Its Remedies (Travel and Health)
24. Which Food Fights Cancer Better? (Travel to Health)
25. Aune D, Chan DS, Lau R, et al. Dietary fibre, whole grains, and risk of  colorectal cancer; systematic review and dose-response meta-analysis of prospective studies.  BMJ. 2011;343:d6617.
26. Aune D, Chan DS, Greenwood DC, et al.  Dietary fiber and breast cancer risk: a systematic review and meta-analysis of prospective studies.  Ann Oncol. 2012;23(6):1394-402.
27. Yao B, Fang H, Xu W, et al.  Dietary fiber intake and risk of type 2 diabetes: a dose-response analysis of prospective studies, Eur J Epidemiol. 2014;29(2):79-88.
28. Threapleton DE, Greenwood DC, Evans CE, et al. Dietary fibre intake and risk of cardiovascular disease: systematic review and meta-analysis. BMJ. 2013;347:f6879.
29. The Effects of Nutritional Yeast for Cancer
• A clinical study demonstrated improved wound healing using oral beta-glucans 
• In Japan, there have been 22 randomized controlled studies on the use of beta-glucans as an adjunct cancer treatment. Researchers found that “yeast beta-glucan can enhance the effect of anticancer chemotherapy or radiation therapy and have a positive effect on the survival and quality of life of cancer patients.” 
30. Bouhnik Y et al. Effects of Bifidobacterium sp fermented milk ingested with or without inulin on colonic bifidobacteria and enzymatic activities in healthy humans. European Journal of Clinical Nutrition 1996 Apr; 50(4):269-73.
31. Gyawali R et al. The role of prebiotics in disease prevention and health promotion. Chapter 12 in Dietary Interventions in Gastrointestinal Diseases, 2019. Pages 151-67.
32. Mahboobi S et al. Effects of prebiotic and synbiotic supplementation on glycaemia and lipid profile in type 2 diabetes: A meta-analysis of randomized controlled trials. Advanced Pharmaceutical Bulletin 2018 Nov; 8(4):565-74.
33. Nowak A et al. Antigenotoxic activity of lactic acid bacteria, prebiotics, and products of their fermentation against selected mutagens. Regulatory Toxicology and Pharmacology 2015 Dec; 73(3):938-46.