www.ncbi.nlm.nih.gov/pmc/articles/PMC6741661/pdf/CNS-8-70.pdf
used fir AD
Supplements
Stemregen ingredients review:
Sea buckthorn berry 500 mg per day, increase risk of bleeding
available on iherb or bulk supplements at Amazon
research on the release of stem cells induced by Sea buckthorn berry
Blue-grean algae – Aphanizomenon flos-aquae – may slow blood clotting
אצה כחולה ירוקה מאגם קלמאת' – 90 כמוסות – טינק
Fucus vesiculosus – has some risk, see >>
Phlorotannin – not directly related to stem cells, some health benefits >>
Panax notoginseng – has a blood thinner effect
Aloe Macroclada – increase number of circulating stem cells >>
β-glucans – interacts with Warfarin
Highly fractionated colostrum (cow pre-milk) – good for preventing gut permeability
Piper nigrum – black paper
levodopa magnesium oxide
Applies to: Dopar (levodopa), magnesium oxide
Antacids and some oral aluminum, calcium, or magnesium containing preparations may increase the absorption of levodopa. The mechanisms may be related to increased gastric pH and/or decreased gastric emptying time, resulting in less gastric degradation of levodopa and more levodopa absorption from the small intestine. This effect may be beneficial in some patients, but also difficult to predict and monitor. For most patients, this interaction is not clinically significant and no specific intervention would be required. Dosing intervals could be spaced by at least 2 hours if it is preferred to avoid this interaction.
References
Rivera-Calimlin L, Dujovne CA, Morgan JP, Lasagna L, Bianchine JR (1970) “L-dopa treatment failure: explanation and correction.” Br Med J, 4, p. 93-4
Rivera-Calimlim L, Dujovne CA, Morgan JP, Lasagna L, Bianchine JR (1971) “Absorption and metabolism of L-dopa by the human stomach.” Eur J Clin Invest, 1, p. 313-20
Fermaglich J, O’Dougherty DS (1972) “Effect of gastric motility on levodopa.” Dis Nerv Syst, 33, p. 624-5
Huberman:
Peter Attia:
David Syncair
David Sinclair Supplements List – 15 He Takes in 2024 & Doses
Rhonda Patrick:
Joe Rogan:
Creatine monohydrate
boost ATP production (mitochondria booster)
neuroprotective for PD
dose: 3-5 grams per day
We studied 10 regular exercising men with Parkinson’s disease on levodopa (LD) under two conditions–no exercise and vigorous exercise started 1 hour after LD ingestion. We compared LD levels and motor scores on the Unified Parkinson’s Disease Rating Scale (UPDRS). There was a high degree of agreeme …
Misfolded Alpha synuclein protein accumulate into aggregates (oligomers) and damage host cell. PD patients brain cells tend to express alpha synuclein in large amounts, Alpha-synucleinis assumed to have a role in the disease process, reducing Alpha-synuclein level may prevent neuron death and delay or reverse the disease process More information >> [20]
The goal here is to normalize Alpha-synuclein level by using a simple protocol
Some notes:
The protocol:
1 – Sweating – 3 liters/day or so, research show that Alpha-synuclein accumulate around sweat glands, it seems safe to assume that Alpha-synuclein is secreted via the sweat glands [18], [1]
2 – Alpha-synuclein is also secreted in the urine, so you can detox by drinking a lot and using mild diuretics e.g. parsley [2]
3 – Probiotics Bacillus Subtillis PXN21, “eats” Alpha-synuclein in the gut, this probiotics is in the market for a number of years, it’s probably safe Successful experiment in animal model(worms) [3].
Note: several bacteria species ( Lactobacillus and Enterococcus) interact with Levodopa ,and so , limit production of dopamine in the brain
4 – Optimise detox at the cell level (from the cell, out), raise glutathione level ( intravenous or suppository glutatyon or eat the precursors e.g sulfur found in eggs and cruciferous vegetables).
Glutathione has other benefits( master detoxifier, master anti oxidant), so it’s a good idea to boost it anyway [19].
How to increase glutathione by Mark Hayman [17]
More ways to increase glutathione [4].
5 –
Sleep issues may have an adverse effect on brain detox processes, in particular on alpha synuclein clearance [6].
Most of the brain detox is done by the Glymphatic System during sleep, give it time, 7-8 hours of sleep, don’t go to sleep to late. More information [7].
6 – Improve autophagy by intermittent fasting, preferably keto-fast – meaning a ketogenic diet in a 12 hours or less, daily eating window Ketogenic diet induced autophagy [8].
7- Alpha synuclein is found in Vertebras e.g cow, pig, chicken. Those molecules are almost identical to the human Alpha-synuclein, but not 100% identical, and may have a role in creating a pathology, much like in prion infection, more information >>[9].
Consider avoiding vertebrates, especially brain, bone merrow, bone broth.
Eggs – OK, as far as I checked.
8 – Mannitol
Mannitol was shown to inhibit formation of Alpha-synuclein oligomers[10], and there are anecdotal improvement reports of PD patients.
A clinical experiment (n=36) did not show significant improvement
You can add Mannitol to your diet in the dosage used in the experiment – start with 2.5 gram 2 times a day, gradually increase to 9 grams 2 times a day.
Why use Mannitol if the experiment showed no improvement ?
If, for example, subjects have existing damage(accumulated before the experiment), but new damage build up is slowed by say 50%, that’s very good, but the subjects will not experience any improvement. Maybe after a long time, difference relative to the control group will begin to show
9 – HSP – Heat shock proteins
Heat shock proteins – are listed here as they slow down or inhibit the formation of Alpha-synuclein oligomers.
The level of HSP in the body rise in response to adverse conditions (ice bath, sauna…intense exercise)
Sulforaphane- a compound found mostly in broccoli sprouts, also increase level of HSP. Sulforaphane is available in supplement form
Sulforaphaneis also beneficial to brain health as it reduces inflammation, increase anti oxidant activity and more [13], so it’s a good idea to use it anyway.
Mannitol also increase HSP level, this is one of the suggested mechanisms of action that explain why it inhibits creation of Alpha-synuclein oligomers, and generally improves PD [11].
More information on Sulforaphane >>
[13]
HSP27 binds Alpha synuclein >>[14]
and
Sulforaphane increase level of HSP27 >> [15]
also Sulforaphane increase level of HSP70 >>
[16]
10 – High intensity exercise
Irisin, a hormone secreted into the blood during high endurance and aerobic exercise, reduces levels of alpha-synuclein and restores movement in mouse models of PD [22]
Clinical research showing beneficial effect of high intensity exercise in PD patients [23]
11 – Ambroxol – an over-the-counter cough syrup
One of the major genetic risk factors believed to contribute to the development of PD is having a mutation in the gene called GBA1 (glucocerebrosidase). Unable to do its job correctly, this damaged gene leads to the build-up of unhealthy, misfolded clumps of alpha-synuclein in the brain. These clumps, called Lewy bodies, impact dopamine production and are the hallmark of PD.
A 2020 study published in JAMA Neurology, titled, “Ambroxol for the Treatment of Patients with Parkinson Disease with and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial” (Mullin et al., 2020), investigated whether an over-the-counter cough syrup, called Ambroxol, may be the key. [24]
12 – Mega dose, Vitamin B1 (Thiamine),
Vitamin B1, especially in high dose, improve PD status according to a number of studies, one mechanism of action is reduction of Alpha-synuclein [24]
What to expect ?
If there is existing damage, and the protocol manage to stop/delay/reduce further damage, e.g. by 100%, this would be a significant achievement, but will not show as reduced symptoms (assuming n=1, meaning you tried it on yourself and you don’t have a control group etc).
A healthy person loose about 1% of its dopaminergic neurons every adult year, this will not present symptoms as symptoms start showing when 80% or more of the dopaminergic capacity is gone
Not saying this to discourage, I believe the protocol worth the effort, and can by you time. I believe solutions based on gene therapy and stem cell technology will be available soon.
Measuring Alpha-synuclein level require biopsy, we don’t have this technology available, but based on what we know from animal models, the protocol should work, at list some of it.
Besides it’s effect on Alpha-synuclein, the protocol is expected to improve brain health through several mechanisms including reduced inflammation, normalizing heavy metals and other toxins, reduce oxidative stress, improved insulin sensitivity… So…good idea to try it anyway.
One more thing, a quote from coacher Tony Robins –
Take Massive Action
What do you think ? feedback welcome, please comment below
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Want to try it ? good luck ! ( needless to say, it’s your responsibility )
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Guy
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Note:
This TED talk ___ suggests that misfolded alpha-synuclein aggregates are not a problem as long as normal alpha-synuclein is abundant, is this claim is correct, the above protocol should be avoided
I collected the above set of tools, as they directly affect alpha-synuclein. Nevertheless, most those are very popular general health tools e.g IM fasting, Keto, detox, sleep cycle compatible with circadian rhythm, Glutathione, Heat shock protein…
So, since they are popular, they seem to be safe.
[1] –
Gibbons, C. H., J. Garcia, N. Wang, L. C. Shih, and R. Freeman, 2016, The diagnostic discrimination of cutaneous α-synuclein deposition in Parkinson disease: Neurology, v. 87, no. 5, p. 505–512, doi:10.1212/wnl.0000000000002919.
[2] –
Giri, B., M. Seamon, A. Banerjee, S. Chauhan, S. Purohit, J. Morgan, B. Baban, and C. Wakade, 2021, Emerging urinary alpha-synuclein and miRNA biomarkers in Parkinson’s disease: Metabolic Brain Disease, v. 37, no. 6, p. 1687–1696, doi:10.1007/s11011-021-00735-2.
[3] –
Probiotic Bacillus subtilis Protects against α-Synuclein Aggregation -, 2022: <healthlinks.cc/probiotic-bacillus-subtilis-protects-against-%ce%b1-synuclein-aggregation/> (accessed October 6, 2022).
[4] –
Berkheiser, K., 2018, 10 Natural Ways to Increase Your Glutathione Levels: Healthline Media: <www.healthline.com/nutrition/how-to-increase-glutathione#TOC_TITLE_HDR_4> (accessed October 6, 2022).
[5] –
Perfeito, R., M. Ribeiro, and A. C. Rego, 2016, Alpha-synuclein-induced oxidative stress correlates with altered superoxide dismutase and glutathione synthesis in human neuroblastoma SH-SY5Y cells: Archives of Toxicology, v. 91, no. 3, p. 1245–1259, doi:10.1007/s00204-016-1788-6.
[6] –
Sundaram, S., R. L. Hughes, E. Peterson, E. M. Müller-Oehring, H. M. Brontë-Stewart, K. L. Poston, A. Faerman, C. Bhowmick, and T. Schulte, 2019, Establishing a framework for neuropathological correlates and glymphatic system functioning in Parkinson’s disease: Neuroscience & Biobehavioral Reviews, v. 103, p. 305–315, doi:10.1016/j.neubiorev.2019.05.016.
[7] –
Raypole, C., 2020, How to “Detox” Your Brain (Hint: It’s Easier Than You Think): Healthline Media: <www.healthline.com/health/brain-detox> (accessed October 6, 2022).
[8] –
Lindberg, S., 2018, Autophagy: What You Need to Know: Healthline Media: <www.healthline.com/health/autophagy#diet:~:text=In%20response%20to%20this%20restriction%2C%20your%20body%20will%20begin%20to%20start%20producing%20ketone%20bodies%20that%20have%20many%20protective%20effects.%20Khorana%20says%20studies%20suggest%20that%20ketosis%20can%20also%20cause%20starvation%2Dinduced%20autophagy%2C%20which%20has%20neuroprotective%20functions.> (accessed October 6, 2022).
[9] –
[10] –
Linetsky, E., S. Abd Elhadi, M. Bauer, A. Gallant, M. Namnah, S. Weiss, D. Segal, R. Sharon, and D. Arkadir, 2022, Safety and Tolerability, Dose-Escalating, Double-Blind Trial of Oral Mannitol in Parkinson’s Disease: Frontiers in Neurology, v. 12, doi:10.3389/fneur.2021.716126.
[11] –
Linetsky, E., S. Abd Elhadi, M. Bauer, A. Gallant, M. Namnah, S. Weiss, D. Segal, R. Sharon, and D. Arkadir, 2022, Safety and Tolerability, Dose-Escalating, Double-Blind Trial of Oral Mannitol in Parkinson’s Disease: Frontiers in Neurology, v. 12, doi:10.3389/fneur.2021.716126.
[12] –
[13] –
Sulforaphane, which is high in broccoli sprouts, clears away brain amyloid plaques and tau tangles and ameliorated memory defects in mice., 2019: <www.foundmyfitness.com/news/s/emuzn7/sulforaphane_which_is_high_in_broccoli_sprouts_clears_away_brain_amyloid_plaques_and_tau_tangles_and_ameliorated_memory_defects_in_mice/comments/gsmrq4#:~:text=To%20learn%20more,jed%2Dw%2Dfahey> (accessed October 6, 2022).
[14] –
Cox, D., D. R. Whiten, J. W. P. Brown, M. H. Horrocks, R. San Gil, C. M. Dobson, D. Klenerman, A. M. van Oijen, and H. Ecroyd, 2018, The small heat shock protein Hsp27 binds α-synuclein fibrils, preventing elongation and cytotoxicity: Journal of Biological Chemistry, v. 293, no. 12, p. 4486–4497, doi:10.1074/jbc.m117.813865.
[15] –
Gan, N., Y.-C. Wu, M. Brunet, C. Garrido, F.-L. Chung, C. Dai, and L. Mi, 2010, Sulforaphane Activates Heat Shock Response and Enhances Proteasome Activity through Up-regulation of Hsp27: Journal of Biological Chemistry, v. 285, no. 46, p. 35528–35536, doi:10.1074/jbc.m110.152686.
[16] –
Schepici, G., P. Bramanti, and E. Mazzon, 2020, Efficacy of Sulforaphane in Neurodegenerative Diseases: International Journal of Molecular Sciences, v. 21, no. 22, p. 8637, doi:10.3390/ijms21228637.
17-
Hyman, M., 2010, What is Glutathione and How Do I Get More of It? – Dr. Mark Hyman: <drhyman.com/blog/2010/05/12/what-is-glutathione-and-how-do-i-get-more-of-it/> (accessed October 9, 2022).
18-
Wang, N., C. H. Gibbons, J. Lafo, and R. Freeman, 2013, -Synuclein in cutaneous autonomic nerves: Neurology, v. 81, no. 18, p. 1604–1610, doi:10.1212/wnl.0b013e3182a9f449.
19-
Dringen, R., 2000, Metabolism and functions of glutathione in brain: Progress in Neurobiology, v. 62, no. 6, p. 649–671, doi:10.1016/s0301-0082(99)00060-x.
20-
Fields, C. R., N. Bengoa-Vergniory, and R. Wade-Martins, 2019, Targeting Alpha-Synuclein as a Therapy for Parkinson’s Disease: Frontiers in Molecular Neuroscience, v. 12, doi:10.3389/fnmol.2019.00299.
21-
Peters, R., 2006, Ageing and the brain: Postgraduate Medical Journal, v. 82, no. 964, p. 84–88, doi:10.1136/pgmj.2005.036665.
22-
23 –
Forced exercise 35% improvement, motor learning ? upregulate dopamine
24 – Ambroxol
www.parkinson.org/blog/science-news/ambroxol
25 – Vitamin B1
https://youtube.com/RpMEMX-c7VU?t=7
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