Action items that may improve PD status

  • evidence-based
  • Root causes may play a role in many conditions, in all causes listed below, a link to PD was found
  • Key items in the list include: Keto, Fasting, Intermittent fasting, FMD, mitochondria support,  micronutrient optimization/supplementation, macro’s, pathogens, poisons, mind-body, motor learning, masticking, vibration therapy, diet, exercise, EMF radiation dysbiosis & licky gut. cold/ heat exposure,   hormetic stressors, sleep optimization.
  • The goal of the list is to map causes and available treatments relevant to the condition.
  • This is a work in progress, adding new items all the time (sign up for updates)
  • Visit https://healthlinks.cc/list/meds/pd-meds/ for the meds related

 

Could Intermittent Fasting/ Caloric Restriction/ Exercise Improve PD Status

This review was written by Dr. Mark P. Mattson of the John Hopkins University School of Medicine and published in the 2014 Journal of Parkinson’s Disease. It examines whether lifestyle changes that increase insulin sensitivity such as increased exercise and intermittent energy restriction (intermittent fasting)  could counteract neurodegenerative processes and improve functionality. Various studies on animal models seem to indicate that peripheral insulin resistance and midlife diabetes may increase the risk of PD. This review examines whether improved peripheral and brain energy metabolism, exercise, GLP-1 analogs, and intermittent energy restrictions (IER) could boost neuronal adaptive stress response pathways and ultimately enhance neurotrophic signaling, DNA repair, mitochondrial biogenesis, and proteostasis.

Interventions that Improve Body and Brain Bioenergetics for Parkinson’s Disease Risk Reduction and Therapy by Dr Mark Mattson
Mark Mattson in TED: fasting/caloric restriction/ intermittent fasting…help against neurodegenerative conditions

In Development: Neuralink’s Brain Implants , to Treat PD

The latest invention from Neuralink is ultra-thin “threads” that could be injected into the brain to examine neuron activity. These brain-chip interfaces could hopefully be used to treat chronic conditions like PD. One of the goals of this new technology is to allow humans to keep up with the constant leaps and bounds of AI tech. So far there have only been animal trials of Neuralink’s new technology but with astounding results. Neuralink president, Max Hodak said that the company is close to clinical trials in neurological disorders.

The first human trials will focus on paralysis patients and will involve installing four of the new devices into the patient’s brains. If successful, Neuralink will probably release some developer API. The new technology has the potential for use on PD patients and could be used to improve deep brain stimulation therapy. Deep brain technology already exists but not at the level that Neuralink will hopefully be offering.

Source: Musk’s Neuralink close to clinical trials of “brain interface” device –

The Link Between Helicobacter Pylori and PD?

This 2018 report from the Journal of Parkinson’s Disease examines the association between the gut bacteria Helicobacter pylori and PD. H. pylori is a common gut bacterium that causes ulcers, gastritis, and can lead to stomach cancer. The majority of PD cases are caused by unknown environmental factors, and bacterial infections could be one of them. This has led doctors to look at the link between H. pylori and PD. After reviewing past studies on the subject four important points were noted: H. pylori-infected PD patients experience worse motor function issues than those not infected; people with PD are more prone to be infected by H. pylori and eradication of H. pylori could improve motor function and levodopa absorption in people with PD.

Source: Eradicating Helicobacter pylori Infections May Be a Key Treatment for Parkinson’s Disease

Keto for PD: The William Curtis Story

Mike Mutzel from High-Intensity Health (author of Belly Fat Effect) talks to William Curtis about his PD journey and how a ketogenic diet changed his life. Curtis suffered from PD for over 17 years before he started exercising, fasting, and following a low-carb, ketogenic diet that remarkably improved his PD symptoms. Through trial and error, Curtis found the right balance in his diet. The William Curtis’ program for easing PD symptoms is not appropriate for everyone. For example, PD patients that have balance problems could do more harm to themselves if they followed Curtis’ diet. After 12 hours of fasting through the night, Curtis has a bulletproof coffee in the morning prepared with butter, heavy cream, coconut oil, and Stevia. This helps his PD symptoms and increases the ketone D-betahydroxybutyrate (BHB).

good results in rats
www.ncbi.nlm.nih.gov/pmc/articles/PMC4912670/

keto vs low fat
8 weeks
both diets had good results, keto was better
pubmed.ncbi.nlm.nih.gov/30098269/

some ways Keto help are not well understood
www.ncbi.nlm.nih.gov/pmc/articles/PMC5790787/

Curtis has a website
ketonesforparkinsons.com/

Could Fasting Help Control PD Symptoms?

This 2019 report in the National Library of Medicine (National Center for Biotechnology Information) looks at lifestyles and dietary habits associated with PD. A fasting mimicking diet (FMD), fasting 3 days followed by 4 days of refeeding for three 1-week cycles, which accelerated the retention of motor function and attenuated the loss of dopaminergic neurons in the substantia nigra in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mice. Levels of brain-derived neurotrophic factor (BDNF), known to promote the survival of dopaminergic neurons, were increased in PD mice after FMD, suggesting the involvement of BDNF in FMD-mediated neuroprotection. The findings showed that FMD also inhibited neuroinflammation and modulated the shifts in gut microbiota composition.

Source: Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson’s Disease Mice via Gut Microbiota and Metabolites – PubMed

Interaction of Mitochondria, a-Syn, and the Endo-lysosomal System

A 2019 study published in the International Journal of Molecular Sciences looked at the interaction of mitochondria, a-synuclein and the endo-lysosomal system. PD is characterized by dopaminergic neuronal loss and the alpha-synuclein-containing Lewy body inclusions in the substantia nigra. Genetic investigations have revealed evidence of the involvement of mitochondrial function, alpha-synuclein (α-syn) aggregation, and the endo-lysosomal system, in disease pathogenesis. Although familial parkinsonism makes up less than 10% of adult parkinsonism, the findings generated from genetic studies have enhanced the understanding of the neuron degeneration processes. These include mitochondrial dysfunction, disruption of network integrity, and α-syn accumulation; the functions of the proteasome and endo-lysosomal pathways in cellular degradation. Mitochondrial dysfunctions, endo-lysosomal disruptions, and α-syn aggregation mutually interact within neurons, while α-syn prion-like propagation may also be associated with PD in an inter-neuronal manner. Both mitochondria and endo-lysosomal dysfunction contribute to the development of α-syn pathology, however, the specific organelle playing the most important role might be decided by genetic and environmental factors. Most likely, a vicious cycle may develop once one system becomes dysfunctional. Further elucidation of the precise molecular mechanisms involved in the pathogenesis of PD may lead to the development of future therapeutic targets to treat PD.

Source: The Overcrowded Crossroads: Mitochondria, Alpha-Synuclein, and the Endo-Lysosomal System Interaction in Parkinson’s Disease

Could α-Synuclein Inhibition be a Treatment for PD?

A 2020 publication in the MDPI journal, Biomolecules looks at targeting a-syn for PD therapeutics. PD is characterized by the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy Bodies (cytoplasmic inclusions). The Lewy Bodies are clumps of protein that can build up and create problems in the brain. The Lewy Bodies contain the aggregated a-synuclein protein that can propagate throughout the brain. Many PD studies have looked at ways of inhibiting a-synuclein accumulation to ease PD symptoms. There are various approaches to a-syn inhibition and multiple clinical trials that examine the link between PD and a-syn, with the hope that a treatment may be found for PD using a-syn. Given the central role of α-syn in PD pathology and progression, α-syn met the criteria to be a tantalizing and evident therapeutic target for PD. Promising strategies include predominantly immunization, anti-aggregative molecules, and an increase in α-syn clearance.

Source: Targeting α-Synuclein for PD Therapeutics: A Pursuit on All Fronts

Ridding Cells of Harmful Protein Aggregates by Inducing Autophagy

This short, enlightening video clip is an extract from a FoundMyFitness interview with Dr. Guido Kroemer. PD is characterized by protein aggregation of a-synuclein and mitochondrial dysfunction, partly due to mitophagy failure. A recently proposed strategy in preventing (or perhaps treating) neurodegenerative diseases like PD is to starve the cells or use biochemical methods to induce general autophagy and thus help the cell rid itself of protein aggregates. Here Dr. Kroemer describes how mitophagy contributes to the pathophysiology of neurodegenerative diseases like PD and Alzheimer’s and how autophagy might mitigate these processes.

Neuronal Autophagy and the Predisposition for PD

A study by Dr. Yue published by the Michal J. Fox Foundation tested the hypothesis that neuronal autophagy is critical for the regulation of alpha-synuclein protein levels and protective against neuronal death; dysfunction of autophagy predisposes to the pathogenesis of PD in dopamine neurons. This was done by establishing conditional knock-out mice in which an essential autophagy gene, Atg7, is deleted specifically in dopamine neurons. These pre-clinical models were used to investigate whether alpha-synuclein wildtype or PD-mutant A53T will be accumulated and deposited into Lewy body-like inclusions in the mutant dopamine neurons. In addition, they studied the effect of inactivation of autophagy on oxidative stress level, striatal dopamine content, and dopamine neuron degeneration. results suggest that neuronal autophagy is critical for the regulation of alpha-synuclein protein levels and protective against neuronal death; dysfunction of autophagy may predispose dopamine neuron to PD-like pathology.

Source: Autophagy in Dopamine Neurons: Clearance of Alpha-synuclein and Neuroprotection

PD and Autophagy Impairment in Synucleinopathy

A 2019 study published by NCBI discusses the active participation of autophagy impairment in alpha-synuclein accumulation and propagation, as well as alpha-synuclein-independent neurodegenerative processes in the field of synucleinopathy. There is genetic and post-mortem evidence suggesting that autophagy is involved in synucleinopathies. Also, studies demonstrate the role of autophagy in the pathology of synucleinopathy. α-syn is mainly degraded by both macroautophagy and chaperone-mediated autophagy. Thus, autophagy defects induce intracellular α-syn accumulation, participating in its aggregative state towards the formation of α-syn-positive intracytoplasmic inclusions. Plus, autophagy defects also increase the α-syn secretion by the non-autophagic exosomal pathway, leading to increased cell-to-cell transmission of the protein, and thus the propagation of the α-syn-linked pathology in different brain regions of the CNS. However, autophagy defects also cause detriment effects in cellular homeostasis: (i) lysosomal impairment through structural or functional defects leads to accumulation of non-degraded products and increased production of ROS; (ii) decreased mitophagy leads to neuronal bioenergetic imbalance, and (iii) defective cargo trafficking impairs the addressing of vesicles to lysosomal clearance. There is increasing evidence that inducing the autophagy pathways (by natural, chemical, or genetic approaches), has become a relevant therapeutic approach to counteract the deleterious effects of autophagy impairment in synucleinopathy.

Source: Autophagy in Synucleinopathy: The Overwhelmed and Defective Machinery

What is the Potential of Stem Cell Treatment for PD? (YouTube Webinar)

This webinar is a recording of a live broadcast that took place in June 2019 and consisted of a panel discussion on cell-based therapy for PD. Chairing the panel is Professor Patrik Brundin. The panel of experts includes Gaynor Edwards, a person affected by PD; Parkinson’s neurologist, Clair Henchcliffe and Dr. Roger Barker, consultant neurologist. The panel discusses what kind of stem-cells exist; the source of stem-cells; the uses of stem-cells, and specifically dopamine stem-cells. The panel talks about current trials and the timeline for when stem-cells will be a viable treatment for PD. One of the issues raised is whether we will be able to produce stem-cells in large enough quantities. The panel of experts takes questions from viewers and gives answers on subjects like stem-cell tourist and the cost of treatment. The final word on the subject is that despite the cost of potential stem-cell treatment it will save money spent on the medical care of untreated patients in the long term.

Low‐Fat vs Ketogenic Diet for PD?

A 2018 study published in NCBI  aimed to compare the plausibility, safety, and efficacy of a low‐fat, high‐carbohydrate diet versus a ketogenic diet in PD patients. Primary outcomes were within‐ and between‐group changes in MDS‐UPDRS Parts 1 to 4 over 8 weeks. 47 patients were randomized, of which 44 commenced the diets and 38 completed the study (86% completion rate for patients commencing the diets). The ketogenic diet group maintained physiological ketosis. Both groups significantly decreased their MDS‐UPDRS scores, but the ketogenic group decreased more in Part 1 (−4.58 ± 2.17 points, representing a 41% improvement in baseline Part 1 scores) compared to the low‐fat group (−0.99 ± 3.63 points, representing an 11% improvement) (P < 0.001), with the largest between‐group decreases observed for urinary problems, pain and other sensations, fatigue, daytime sleepiness, and cognitive impairment. The trial found that It is plausible and safe for PD patients to maintain a low‐fat or ketogenic diet for 8 weeks. Both diet groups significantly improved in motor and nonmotor symptoms; however, the ketogenic group showed greater improvements in nonmotor symptoms.

Source: Low‐fat versus ketogenic diet in Parkinson’s disease: A pilot randomized controlled trial (© 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.)

 

Could Creating a Healthy Gut Using FMD Prevent or Treat PD?

A 2018 study published by the NIH looked at neuroprotection of the fasting mimicking diet (FMD) on MPTP-induced PD mice via gut microbiota and metabolites. During the study the mice were put on a diet of fasting 3 days followed by 4 days of refeeding for three 1-week cycles. This accelerated the retention of motor function and attenuated the loss of dopaminergic neurons in the substantia nigra in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mice. The findings demonstrated that FMD can be a new means of preventing and treating PD through promoting a favorable gut microbiota composition and metabolites.

Source: Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson’s Disease Mice via Gut Microbiota and Metabolites – PubMed

ApoE4 Information for Alzheimer’s, and Chronic Diseases Including PD

The Wiki page, Apoe4 offers a collection of resources and information that can help you prevent and address health problems related to APOE -ε4 allele. APOE, short for Apolipoprotein E, is both a protein and a gene. As a protein, ApoE is involved in the metabolism of fats (lipids) in the body and comes in different isoforms. In our modern environment, the ε4 allele of the gene confers a higher risk for Alzheimer’s disease and other medical conditions. It is possible to be tested to see if you carry the E4 gene which would mean you are more likely to develop Alzheimer’s, although many other factors also determine vulnerability to Alzheimer’s. E4 is also associated with other chronic diseases including dementia, brain disorders, high cholesterol, infectious diseases susceptibility, gallstones, and cardiovascular disease.

Source: ApoE4.Info Wiki

Review of Possible Use of a Keto Diet in PD Treatment

A review focused on the role of ketogenic diets in neurodegenerative diseases (including PD) was published in the MDPI journal Nutrient in 2019. The goal of the review was to assess the effectiveness of ketogenic diets as part of therapy for neurodegenerative diseases. In PD, dopaminergic neurons in the substantia nigra are affected by a degeneration process leading to motor and non-motor disturbances. The available results of research projects dealing with the use of the KD and ketone bodies in neurodegenerative diseases are fairly promising. At the same time, the majority of studies reviewed were employed in vitro or by using animal models. The number of studies with human participation is rather small, and those that exist feature relatively short therapy duration periods.

Source: Role of Ketogenic Diets in Neurodegenerative Diseases (Alzheimer’s Disease and Parkinson’s Disease)

Fact Sheet: Dietary Supplements for Primary Mitochodrial Disorders

NIH publishes a fact sheet for health professionals on dietary supplements for primary mitochondrial disorders. The fact sheet summarizes published scientific trials, other studies, and reports on the use of dietary supplements to treat primary mitochondrial disorders. The most common ingredients in dietary supplements used in PMD therapy include vitamin C, vitamin E, and alpha-lipoic acid; electron donors and acceptors, such as CoQ10and riboflavin; compounds that can be used as alternative energy sources, such as creatine; and compounds that can conjugate or bind mitochondrial toxins, such as carnitine. A combination of these products is commonly called a mitochondrial cocktail. However, there are many combinations and dosages so the term is nonspecific and nondescriptive. Drug interaction needs to be taken into consideration as well as the level of evidence of efficiency, quality of ingredients, and dosage.

Source: Dietary Supplements for Primary Mitochondrial Disorders – Health Professional Fact Sheet

Review: The Role of Dietary Fat in Treatment of Brain Diseases

A review published in the Current Neuropharmacology journal in 2018 looked at the impact of dietary fats on brain function. It also examined gut-brain communication through microbiota; the impact of probiotics and prebiotics on brain functions; SCFA’s, microbiota, and neuroinflammation. It reviewed lipid sensing, satiety, and processing of hedonic food; the impact of diet on the hypo-thalamic control of reproduction; neuroprotective effects of N-3 PUFAs; dietary PUFAs, brain PUFAs and the role of PUFAs. The results of this review revealed that dietary fats are both friends and foes for brain functions. However, dietary manipulation for the treatment of brain disorders is not just a promise for the future, but a reality. In fact, the clinical relevance of the manipulation of dietary lipids, as for KDs, is well-known and currently in use for the treatment of brain diseases.

Source: Impact of Dietary Fats on Brain Functions
LGIT safe (see 305)

2020 Clinical Trial: Mannitol for PD

The NIH Clinical Trial published information on a study provided by Arkadir David of the Hadassah Medical Organization. The study took 60 participants and ran a phase II single center, randomized, double blind and placebo controlled study assessing the safety, tolerability, and effects of progressively increased dose of oral mannitol in PD. The study began in November 2018 and will end in December 2020. There were 60 Participants of both genders and aged 40 to 75 years. The study assessed the safety of mannitol by the number of treatment-related adverse events and significant changes in vital signs. Tolerability was tested by the level of discomfort. Other changes in participants that were monitored included changes in constipation assessment; Montreal Cognitive Assessment; Brief Smell Identification; change in levodopa-equivalent dose units; change in non-motor symptoms of PD scale and the change in the ratio of total-to-proteinase K-resistant a-syn in red blood cells measured by enzyme-linked immunosorbent assay. Results of this study have not yet been posted.

Source: Safety, Tolerability and Effects of Mannitol in Parkinson’s Disease – Full Text View – ClinicalTrials.gov

 

Vitamin D | Linus Pauling Institute | Oregon State University

n a randomized, double-blind, placebo-controlled study, 112 PD patients (mean age, 72 years) on standard PD treatment were supplemented with 1,200 IU/day of vitamin D or a placebo for 12 months. Vitamin D supplementation nearly doubled serum 25-hydroxyvitamin D concentration (from mean of 22.5 ng/mL to 41.7 ng/mL) in supplemented subjects and limited the progression of PD, as indicated by a greater proportion of patients who showed no worsening (as assessed by the Hoehn and Yahr stage and the United Parkinson Disease Rating Scale part II) in the supplemented group compared to the placebo group (243). It is not known whether vitamin D insufficiency has a role in the pathogenesis of the disease, but the repletion of vitamin D may provide health benefits that go beyond the prevention and/or the treatment of PD. For example, vitamin D deficiency may contribute to the increased risk of osteoporosis and bone fracture in individuals with neurologic disorders, including PD and multiple sclerosis (244-246). Interestingly, sunlight exposure was found to be associated with improved vitamin D status, higher bone mineral density of the second metacarpal bone, and lower incidence of hip fracture in a prospective study conducted in 324 elderly people with PD (247).

Source: Vitamin D | Linus Pauling Institute | Oregon State University

All About mTOR, mTOR Inhibitors and mTOR Activators

SelfHacked published an article by Puya Yazdi, MD in September 2020 about mTOR and natural mTOR inhibitors and activators. mTOR responds to signals from nutrients, growth factors and cellular energy status and controls cell growth and proliferation based on regulating protein syntheses. mTOR is one of those things that’s good to have cycled. Sometimes we want to increase it to grow muscle and improve certain aspects of cognition, while the rest of the time we want to have low levels to increase longevity, decrease the risk of cancer, and reduce inflammation. Too much mTOR activation is associated with many diseases including neurodegeneration. There are mTOR inhibitors mainly used as immunosuppressants to prevent transplant rejection and in anticancer therapy and strategies such as ketogenic diets. mTOR activators include a variety of amino acids and the hormone insulin as well as proteins, excess carbs, Orexin, and more. For health and longevity, we’d want systemic mTOR levels to be low most of the time, with occasional periods of activation. Research suggests it’s preferable to have mTOR more active in your brain and muscles rather than in your fat cells and liver. Exercise is ideal because it does exactly this.

Source: All About mTOR + Natural mTOR Inhibitors & Activators – SelfHacked