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04-02-2020, 08:13 PM | #1 | |||
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Grand Magnate
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I am curious about your views on the role of misfolded a-synuclein in the pathology of PD.
There is considerable evidence that this is significant; a PubMed search (Parkinson's Disease synuclein) returns more than 9000 papers. There does not seem to be any reported evidence, also from PubMed, of any interactions between synuclein and the low molecular weight compounds (homocysteine, glutathione, Vitamin B6, Vitamin E and Vitamin C) that you mentioned.
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"Thanks for this!" says: | parkinsons here-now (04-03-2020) |
04-03-2020, 10:40 AM | #2 | |||
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Junior Member
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I realized a few years ago that sometimes when studies don't appear in search engines like Pubmed (perhaps because there are few searches in that direction or because of the algorithms), books come to help us in those gaps. Magnesium in Parkinson’s disease: an update in clinical and basic aspects - Magnesium in the Central Nervous System - NCBI Bookshelf In one of them I found Oyanagi's 2010 study with magnesium and MPTP in mice. It was impossible for the group that received the highest dose of magnesium to provoke the experimental parkinsonism with MPTP. And I kept looking and found that in 2002, Golts had published a study on the ability of magnesium to inhibit alpha-synuclein aberration, both spontaneous and iron. Later, something similar happened to me with green tea and its main polyphenol, EGCG. Xu's 2016 study was the only one I knew of. Magnesium and green tea. But in recent years, many studies have come out that shed light on the whole world of Parkinson's: also vitamin C, astaxanthin, glutathione, vitamin K, vitamin B12, etc. Possibly the same cellular "environment" that produces neuronal death, is the one that damages the mitocondria and produces the "madness" or aberration of alpha-synuclein. Oxidation, inflammation, elevated homocysteine? All together? Green tea, magnesium or vitamin C act on all the possible mechanisms that produce degeneration in Parkinson's: oxidation, inflammation, homocysteine, alpha-synuclein, etc. And "curiously" they all prevent or reduce the risk of Parkinson's and delay or stop the disease from getting worse. 1) Magnesium: * Golts (2002). Magnesium inhibits spontaneous and iron-induced aggregation of alpha-synuclein. J Biol Chem. 2) Green Tea (EGCG polyphenol) -and also protects from damage produced by rotenone, paraquat...-. Lorenzen (2014). How Epigallocatechin Gallate Can Inhibit α-Synuclein Oligomer Toxicity in Vitro. J Biol Chem * Xu (2016). Epigallocatechin Gallate (EGCG) Inhibits Alpha-Synuclein Aggregation: A Potential Agent for Parkinson's Disease. Neurochem Res. * Roy (2017). Suppression, disaggregation, and modulation of γ-Synuclein fibrillation pathway by green tea polyphenol EGCG. Protein Sci. Yang (2017). EGCG-mediated Protection of the Membrane Disruption and Cytotoxicity Caused by the 'Active Oligomer' of α-Synuclein. Nature. Singh (2011). Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem. Pharmacol. * Bieschke (2010). EGCG remodels mature α-synuclein and amyloid-β fibrils and reduces cellular toxicity. Proc. Natl. Acad. Sci. USA. 3) Glutathione. * Seung (2003). Oxidized glutathione stimulated the amyloid formation of α-synuclein. FEBS Letters. Jewett (2018). Glutathione S-Transferase Alpha 4 Prevents Dopamine Neurodegeneration in a Rat Alpha-Synuclein Model of Parkinson's Disease. Front. Neurol Trinh (2008). Induction of the Phase II Detoxification Pathway Suppresses Neuron Loss in Drosophila Models of Parkinson's Disease. J Neurosci. * Koo (2013). α-Synuclein-mediated defense against oxidative stress via modulation of glutathione peroxidase. Biochim Biophys Acta. 4) Vitamin B6 and B2. Pyridoxine is key in the sense that glutathione and magnesium are, since it stimulates glutathione synthesis and improves magnesium assimilation (somewhere I read, but I have not been able to rescue the quote, that brings magnesium to the interior of the neuron). Wei (2020). Pyridoxine induces glutathione synthesis via PKM2-mediated Nrf2 transactivation and confers neuroprotection. Nature. Pouteau (2018). Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial. PLoS One. Abraham (1981). Effect of vitamin B-6 on plasma and red blood cell magnesium levels in premenopausal women. Ann Clin Lab Sci. Schuchardt (2017). Intestinal Absorption and Factors Influencing Bioavailability of Magnesium–An Update. Curr Nutr Food Sci. Riboflavin. And since vitamin B2 activates B6, I am not surprised by the results of studies on how riboflavin prevents Parkinson's by 50% (McCormick 1988) and improves motor skills by 44-71% (Coimbra 2003). 5) Vitamin B12. Jia (2019). Vitamin B12 inhibits α-synuclein fibrillogenesis and protects against amyloid-induced cytotoxicity. Food and Function. 6) Vitamin C. Khan (2012). Effect of L-ascorbic Acid on the climbing ability and protein levels in the brain of Drosophila model of Parkinson's disease. Int J Neurosci. Wang (2010). Redox reactions of the α-synuclein-Cu(2+) complex and their effects on neuronal cell viability. Biochemistry. 7) Possible link between Homocysteine and alpha-synuclein. Enomoto (2019). Alpha-synuclein phosphorylation by homocysteine. Alzheimer's and Dementia https://aanddjournal.net/article/S15...19)30853-2/pdf 8) Vitamin K: Silva (2013). Vitamins K interact with N-terminus α-synuclein and modulate the protein fibrillization in vitro. Exploring the interaction between quinones and α-synuclein. Neurochem Int. 9) Astaxanthin: Wang (2018). Reversal of homocysteine-induced neurotoxicity in rat hippocampal neurons by astaxanthin: evidences for mitochondrial dysfunction and signaling crosstalk. Cell Death Discov. 10) Baicalein (fungal flavonoid): Zhu (2004). The flavonoid baicalein inhibits fibrillation of a-synuclein and disaggregates existing fibrils. J. Biol. Chem. Numerous substances that function as antioxidants, anti-inflammatories, protectives of alpha-synuclein integrity, regulators of the neurotoxic homocysteine, are known to prevent or reduce the risk of Parkinson's, have anti-Parkinsonian epigenetic activity, improve motor and non-motor symptoms, slow down or stop the disease. Magnesium depends on B6, B6 on B2 and so on an endless chain of the fascinating mechanism of neuroprotection of the human body, which fails against the multiple degenerative factors in the disease. And it seems to me that they point to Parkinson's not only as multifactorial but also as multicarential (both obvious and subclinical deficiencies). Even if the recommended amount is consumed, as is the case with homocysteine, because the body "consumes" vitamin B9 (and B6 and B12) in an attempt to reduce its level. |
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04-08-2020, 04:58 PM | #3 | |||
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Member
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hello parkinsons here-now :
What is the best time of day to take vitamins (B 1, B3, B6, B9) so that they won't interfere with levadopa med? I take primarily mucuna bbeginning 9AM to 6 pm.. Kind Regards, MD
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"Thanks for this!" says: | parkinsons here-now (04-12-2020) |
04-12-2020, 09:50 AM | #4 | |||
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Junior Member
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Sorry for the delay in answering. My opinion comes from neurologists and from the experience of the participants of my forum, "Parkinson's Here and Now" (in Spanish). My father never dared to take any vitamins. In many ways, we are moving into uncharted territory. There is hardly any information. Some recommend taking them all away from the dose of synthetic or natural levodopa. Others divide them into three doses and take them with the main meals. If you take mucuna (without carbidopa), I think you should separate the B6 from the others and take it as far as possible from the Mucuna intake and increase the dose little by little. ---- As for the interference with levodopa: B1, no problem. Studies by Luong and Nguyen, Costantini, etc. B2, either. Coimbra in 2003 used 30 mg three times a day for months and achieved an improvement of 44-71 %. B3, no problem because it is recommended to improve the absorption and duration of the effect of levodopa. B6, there are neurologists who set the limit at 25 mg. This seems to me to be the safest, as it agrees with the comment in the levodopa leaflets (since carbidopa is added, 10-25 mg is not a problem). B9, I have not read any information about problems. B12, either. As for the caution with the vitamin itself: B3 with the dose, because it could cause flushing. B6, with caution because there are very sensitive people who perhaps with 5-10 mg already reach their maximum. B12, because some supplements have a lot of quantity and could produce headache. My reference is the neurologist Ahlskog, who has repeated the recommendation in successive editions of his book to control homocysteine: 25 mg of B6. 2.5 mg of B9. 2 mg or 2000 mcg of B12. Although it is always advisable to consult a specialist, I think it could be a good choice: - foods rich in the different B-group vitamins (nuts like pistachio or California nut); - natural supplements like brewer's yeast; - and some vitamin and mineral supplements with moderate amounts. For some more potent supplements I would be very careful. There are some that include 100 mg of vitamin B6. And as they say in my country: neither one nor the other. Neither prohibit even eating pistachios (as my father was told), nor take 100 mg (much higher amounts have been used in studies for dyskinesias by neuroleptics, but to use it along with levodopa I don't know). If I had Parkinson's, I wouldn't dare. Especially not with Mucuna. Kind Regards, |
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"Thanks for this!" says: | moondaughter (04-18-2020) |
01-17-2021, 11:38 PM | #5 | ||
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Newly Joined
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I've gone from 100/25 three times a day to (2) 250/25 x three times a day i get about 3 hours and then i drag my foot when i walk untill the next dose.
66 yrs old had this start 3 yrs ago . Dr just increases meds |
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