Red yeast rice (RYR or red Koji) is an ingredient in dietary supplements often used for people with dyslipidemia or with statin-intolerance. These supplements contain monacolin K (lovastatin). This 2017 study published by NCBI made a case-by-case assessment highlighting myopathies and liver injury as potential safety issues, thus suggesting that the safety profile of RYR is similar to statins. RYR is used in Chinese medicine as a natural statin to improves blood circulation by decreasing cholesterol and triglyceride levels. Certain studies have shown that statin use and a higher risk of PD are related and that PD symptoms appear to be stronger following use of statins. These findings raise the hypothesis that the safety profile of RYR is highly similar to that of synthetic statins and warrants further investigation to finally characterize the safety profile of RYR. The conclusion of this report is that the safety profile of RYR is similar to that of statins and the risk profile of these supplements needs to be examined and regulated.
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
Prebiotics to prevent and treat constipation
This 2020 NCBI meta-analysis takes a close look at prebiotics which play a role in augmenting the presence of gut microbiota such as Bifidobacterium, Clostridium, Bacteroidetes, and Lactobacilli which have been demonstrated in functional gastrointestinal disorders. There are only a few studies of the efficacy of prebiotics for chronic constipation and the utility of different commercially available prebiotics in patients with functional and chronic idiopathic constipation. 21 randomized controlled trials were reviewed showing prebiotics to be effective treatments for chronic idiopathic constipation; improvement in stool consistency; the number of bowel moments, and bloating.
Source: Therapeutic Effects of Prebiotics in Constipation: A Review – PubMed
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.
Could Coenzyme Q10 be Used as a Supplement for PD Patients?
A paper by Robert Alan Bonakdar, MD, and Erminia Guarneri MD, published by aafp.org in 2005 looks at coenzyme Q10 and its use in the treatment of a variety of disorders including PD, plus cardiac, immunologic, and oncologic conditions. Coenzyme Q10 appears to be a safe supplement with minimal side effects and low drug interaction potential. As yet, coenzyme Q10 has not been approved for the treatment of specific diseases in the USA. A randomized, double-blind, placebo-controlled, multicenter study of 80 patients found that 1,200 mg per day of coenzyme Q10 was associated with up to 44 percent less functional decline in patients with Parkinson’s disease, including activities of daily living. A study of 28 patients with Parkinson’s disease also demonstrated mild symptom improvement with daily oral dosing of 360 mg of coenzyme Q10. These results are awaiting confirmation.
Initial Pramipexole vs. Initial Levodopa in Early PD – Which is Better?
A study published on the JAMA Network focused on the long-term effect of initiating pramipexole vs levodopa in early PD. The subjects were followed for up to two years and after six years. Disability was assessed using the modified Shwab and England Activities of Daily Living Scale. Other factors that were assessed included daytime sleepiness; disease severity; dopaminergic events; edema; depression; cognitive impairment and quality of life. Self-reported results were similar. Dopaminergic motor complications were more common in the initial levodopa group (68.4%) although disabling dyskinesias were uncommon in both groups. The mean (SD) Epworth Sleepiness Scale score was significantly higher in the initial pramipexole group. Mean (SD) changes from baseline in the total Unified Parkinson’s Disease Rating Scale score did not significantly differ. The study concluded that persistent differences favoring initial pramipexole were seen in the rates of dopaminergic motor complications, with less severe somnolence favoring initial levodopa.
Should Pramipexole be Used in PD Treatment?
A 2003 study published on Springer.com looked at pramipexole in comparison with I-dopa. The study subjects were twenty right-handed patients with early or mild PD. They were evaluated using neuropsychological and clinical assessments during three treatment modalities. 1. When in the off treatment condition; 2. When on pramipexole and 3. When on i-dopa. In comparison to the off treatment condition, the DA-agonist pramipexole produced a significant impairment of short term verbal memory, attentional-executive functions, and verbal fluency, while l-dopa did not. Pramipexole opposite to l-dopa, failed to improve FAS and Stroop tests. Pramipexole may worsen cognitive functions although not exceeding normative values.
Source: Pramipexole in comparison to l-dopa: a neuropsychological study | SpringerLink
Potential PD Treatment with Repurposed Drugs
A 2018 Springer article examines drug repurposing in PD due to the ever-increasing costs and lengthy processes for drug development. Existing compounds are being approved for other indications as novel treatments in PD. Advances in rational and systemic drug repurposing have identified a number of drugs with potential benefits for PD pathology and offer a potentially quicker route to drug discovery. Among the drugs being considered for repurposing for PD are ambroxol; isradipine; Inosine; ursodeoxycholic acid; deferiprone; exenatide; Nilotinib and Simvastatin. Despite the potential advantages offered by drug repurposing, as a strategy, it offers unique challenges, including the unavoidable need for expensive and risky clinical trials to demonstrate safety and efficacy in a new population while the limited patent protection often means a lack of commercial interest or incentive for further investment.
The Potential of Ambroxol for PD Treatment
Dr. Stephen Mullin of the University of Plymouth talks for The Cure Parkinson’s Trust about the research into GBA Parkinson’s and the current convergent studies which all seem to be pointing towards GBA. In terms of the prospects to develop drugs to slow the development of PD, GBA is the most advanced. The next phase will be identifying PD patients who are carriers of the mutations in the GBA gene and beginning clinical human trials. Simultaneously there needs to be research into how GBA causes PD in humans. The prospects for ambroxol as a disease modifying agent in GBA PD are strong. Ambroxol has already been used by many patients and may be able to reverse some of the effects that lead to PD.
Source: The Ambroxol Trial – The facts | The Cure Parkinson’s Trust
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.
Health Solutions Library for Critical Diseases Including PD
If you’re dealing with a chronic disease or you know someone who is then Chris Kresser’s Health Solutions Library can provide you with resources. Among the resources are books and ebooks that cover preventing and reversing chronic illness and guides for living a healthier life. There are also courses you can take in health care and articles focused on health written by leading specialists. Kresser offers an easy-to-use index to help you find the resources for your particular ailment.
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.
Metallothionein
Metallothionein (MT) is a family of cysteine-rich proteins localized in the membrane of the Golgi apparatus (an organelle in eukaryotic cells). MT can bind with most physiological and xenobiotic heavy metals and MT plays a role in protecting against metal toxicity and oxidative stress. MT also plays a part in transcription factor regulation, and so defects in MT function may lead to malignant transformation of cells and ultimately cancer. Metallothionein also has a part in controlling oxidative stress, metal storage, transportation, binding, and detoxification.
Source: Metallothionein – Wikipedia
www.walshinstitute.org/uploads/1/7/9/9/17997321/metallothionein-pp.pdf
Recommended MT-Promotion Formulation
Glutathione 200.0 mg
Alanine 16.8 mg
Asparagine 5.5 mg
Aspartic Acid 8.5 mg
Glutamic Acid 12.0 mg
Glutamine 4.4 mg
Glycine 11.6 mg
Isoleucine 4.0 mg
Lysine 35.7 mg
Methionine 6.3 mg
Proline 7.0 mg
Serine 27.4 mg
Threonine 8.6 mg
Valine 2.2 mg
Selenium** 200.0 mcg (as selenomethionine)
book: www.amazon.com/Nutrient-Power-Heal-Biochemistry-Brain-ebook/dp/B00J75IQUA
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
New Research on NIACIN vs NMN
A 2020 trial looks at the anti-aging effects of niacin. The key is to promote not only a longer life but a healthier life. As we age our NAD molecules decrease so that there is not enough fuel for Sirtuins enzymes that can help reverse DNA damage and signs of aging. One of the main reasons our NAD+ decreases is the enzyme CD38. CD38 is also involved in the degradation of the precursor to NAD, nicotinamide mononucleotide (NMN). As we age our CD38 levels increase and NAD+ go down. The less we activate our Sirtuins the more CD38 we have, so NAMPT suppresses CD38 expression via SIRT1. We can break this vicious circle by taking niacin which can create NAD+ so Sirtuins will have the fuel they need. The study notes that increased NAD+ levels remarkably improved disease hallmarks and mitochondrial mass. This is interesting for treating high cholesterol cases and chronic disease.
Here are the links to the research papers referenced in the video: www.ncbi.nlm.nih.gov/pmc/arti… www.ncbi.nlm.nih.gov/pubmed/3… www.ncbi.nlm.nih.gov/pubmed/3… www.ncbi.nlm.nih.gov/pubmed/1… www.ncbi.nlm.nih.gov/pmc/arti… www.ncbi.nlm.nih.gov/books/NB… www.ncbi.nlm.nih.gov/pmc/arti… www.ncbi.nlm.nih.gov/pmc/arti…
Some notes about niacin safety depending on HDL/LDL cholesterol levels:
abcnews.go.com/blogs/health/2011/11/15/niacin-statin-combo-offers-no-clinical-benefit-says-study/
pennstatehershey.adam.com/content.aspx?productid=107&pid=33&gid=000335#Possible%20Interactions
Big study showing the risk of high dose niacin + some cholesterol-lowering medication
www.cardiosmart.org/News-and-Events/2013/03/In-High-Doses-Niacin-Causes-More-Harm-than-Good#:~:text=After%20tracking%20patients%20for%20years,skin%20issues%2C%20and%20gastrointestinal%20problems.
High dose for treating cholesterol is normally 1-2 grams but may be as high as 12 grams
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)
Interview with Dale E. Bredesen, md on Reversing Cognitive Decline
In 2015 Dale E. Bredesen md was interviewed by IMCJ about reversing cognitive decline. Dr. Bredesen is an expert in mechanisms of neurodegenerative diseases. About the monotherapeutic approach to degenerative diseases, the doctor said that a cocktail of therapies can be more successful. We now are recognizing multiple subtypes of Alzheimer’s disease. Dr. Bredesen sees the underlying molecular mechanistics of what we refer to as Alzheimer’s disease, as 3 subtypes, two of which are not illnesses. If you look at the molecular mechanistics, what you see is that this is actually a well-orchestrated, non-disease, strategic downsizing based on many different inputs and a mismatch of those with what is actually required to maintain those synapses and to continue with the remodeling that goes on throughout life. Bredesen approaches this with a systematic protocol of lifestyle and nutritional interventions which was published in 2014 in the journal Aging. Dr. Bredesen: “You need to look at a number of critical features such as things like metal homeostasis and proteostasis and insulin resistance, which have been the subject of a tremendous amount of research and, of course, specific inflammatory pathways.”
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)