Though I am still changing the odd typo and adjusting certain audio levels I am basically done with my documentary about Parkinson's disease. The section which is undergoing the most activity is the credits because hundreds of studies were used and I have transcribed only a fraction of them. As I update the credits, or any other file for that matter, I will upload/replace the existing video. I disabled the comment section for each video because internet chatter is cheap, often thoughtless (and pointless). In no way is this the final word on the subject and due to continuing scientific developments I will update the doc with relevant information when possible. My intention in making this project was to raise more questions than provide answers. This especially true for the second half starting with the Causation video. I hope you find this informative and it is intended as a resource to come back to.
Cheers,
Rich
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The studies saying that levodopa intolerance is caused by levodopa-induced DNA methylation seem to be in conflict with academic.oup.com/brain/arti..., which concludes: " We conclude that motor fluctuations and dyskinesias are not associated with the duration of levodopa therapy, but rather with longer disease duration and higher levodopa daily dose. Hence, the practice to withhold levodopa therapy with the objective of delaying the occurrence of motor complications is not justified."
"Chronic treatment with levodopa (LD) in Parkinson's disease (PD) can cause drug induced dyskinesias. Mucuna pruriens endocarp powder (MPEP) contains several compounds including natural LD and has been reported to not cause drug-induced dyskinesias. We evaluated the effects of Mucuna pruriens to determine if its underlying mechanistic actions are exclusively due to LD. We first compared MPEP with and without carbidopa (CD), and LD+CD in hemiparkinsonian (HP) monkeys. Each treatment ameliorated parkinsonism. We then compared the neuronal firing properties of the substantia nigra reticulata (SNR) and subthalamic nucleus (STN) in HP monkeys with MPEP + CD and LD + CD to evaluate basal ganglia circuitry alterations. Both treatments decreased SNR firing rate compared to HP state. However, LD+CD treatments significantly increased SNR bursting firing patterns that were not seen with MPEP+CD treatments. No significant changes were seen in STN firing properties. We then evaluated the effects of a water extract of MPEP. Oral MPWE ameliorated parkinsonism without causing drug-induced dyskinesias. The distinctive neurophysiological findings in the basal ganglia and the ability to ameliorate parkinsonism without causing dyskinesias strongly suggest that Mucuna pruriens acts through a novel mechanism that is different from that of LD."
I believe this article is included in the second chapter about the Hinz protocol (Amino Acid Management of Parkinson's Disease).
I have been taking 800 mg - 1,000 mg/per day of 100% pure levodopa from MP for about 4 years (with other components) and have 0 side effects. Part of the problem with any form of levodopa (synthetic or natural) is they can cause niacin deficiency. Carbidopa/benserazide cause pyridoxine deficiency. These facts were known in the 1970's and both of these deficiencies are also part of the problem.
GPR109a (the iodine chapter):
Low-dose niacin supplementation modulates GPR109A, niacin index and ameliorates Parkinson's disease symptoms without side effects
PS. I designed this documentary like a combination of an onion and a puzzle. There is different and additional information about the same subject as it progresses.
My name is Jim, 66 yrs young, diagnosed Aug 2001 with PD. I' ve noticed a big change in the last year. I followed the GU study, and realized that even with FDA fast tracking, Tasigna approval is 10 years down the road. It took several months, but I located a Dr who prescribed Tasigna, 200 mg off label. I have noticed a couple of changes and will report on them after 4 months, today is 62 days on Tasigna. Luckily so far I have tolerated the drug with no problems.
I take sinemet oral dissolving tablet, usually 2 tabs every 3 hours starting at 5 am. I am sometimes able to skip the 8 pm and nighttime dose (11 pm -1 am). I take 5 mg selegiline twice daily 5 am and 2 pm). Diskenesia is apparent most of the day. My neuro prescribed Amantadine which controlled the diskenesia, but gave me problematic hypotension. I'm off the Amantadine.
I have a wedding to attend late Oct 2017. Spoke to my neuro's nurse about mucuna purines. She advised me not to make any changes with my current meds until I meet with the Dr at my next appointment in Sept.
I understand mucuna purines does not produce the side effects of sinemet. Or side effects are greatly diminished. . Do you think mucuna purines would reduce my diskenesia so that it is unnoticeable. It looks like my cause and effect window is roughly 45 days.
I have to do this fast because my computer died and I am at the library...
I will answer your question about dyskinesia and mucuna p. later in this response but first I will not what basic supplements can be taken with sinemet/madopar to make it work better.
250 mg/day of niacin (slow release is fine) because any form of levodopa (synthetic/natural) can cause a sub-clinical niacin deficiency:
Low-dose niacin supplementation modulates GPR109A, niacin index and ameliorates Parkinson’s disease symptoms without side effects
"The aromatic amino acid decarboxylase inhibitor carbidopa (typically prescribed as a part of carbidopa/levodopa) was shown to deplete niacin levels in the body in PD patients."
Mind you it has to be niacin which causes flushing and not either niacinamide or no-flush niacin.
Secondly, anyone taking carbidopa (sinemet) or benserazide causes a pyridoxine deficiency (vitamin B6), and the best form of B6 is P5P/pyridoxyl 5 phosphate.
Herb, Nutrient, and Drug Interactions: Clinical Implications and Therapeutic Strategies
"A DDI such as carbidopa or benserazide can neutralize the interactions between pyridoxine and levodopa but may also deplete vitamin B6."
The levodopa/pyridoxine interaction referenced in the book is if you are taking mucuna pruriens (or synthetic levodopa alone) derived levodopa (minus a carbidopa/benserazide) it will increase the conversion of levodopa to dopamine in the body and will diminish the effectiveness of levodopa. Without if you are not taking a decarboxylase inhibitor B6/P5P/pyridoxine is unnecessary.
Also, a pyridoxine deficiency is associated with Parkinson's disease neuropathy.
Levodopa/carbidopa intestinal gel, neuropathy, and B-vitamins – Is there an association?
Results: "Compared to the oral group, LICG patients had a longer disease duration and higher LDD (daily levodopa doses). All individuals of the LCIG (levodopa/carbidopa intestinal gel) group and most of the oral group had electrophysiologically sensorimotor axonal neuropathy, which was more, but not significantly pronounced, in the LCIG Group."
"Conclusions: Axonal sensory neuropathy is frequent in advanced IPD treated with levodopa irrespective of the route of application. LDD correlates with pyridoxine deficiency and homocysteine elevation, but not with cobalamine or folate. The data set is too small to prove or rule out an association of pyridoxine deficiency and hyperhomocysteinemia with neuropathy, but the results deserve further investigations."
Vitamin B12 (cobalamin) is essential for Parkinson's disease therapy:
Low Levels of Vitamin B12 in Parkinson's Contributes to Disability
"Low levels of vitamin B12 are known to be linked to neuropathy and cognitive impairment in advanced Parkinson's disease, however it's not clear how B12 status in early Parkinson's affects disease progression and disability."
The best form of B12 is methylcobalamin and, unfortunately, it is not what your doctor injects you with when you get an injection. Methyl B12 is a potent, bio-active form of B12 and it is perfectly safe to take in larger than proscribed doses. Most doctors recommend 1 mg/day and methylcobalamin has been safely used up to doses as large as 50 mg/day intravenous:
Treatment with high dose vitamin B12 been shown to be safe for more than 50 years
I have been taking 5 mg/day sublingual methylcobalamin for at least 6 years with no side effects and the lowest dose I took was 2.5 mg/day. The good news about oral B12 is it is as effective as B12 injections:
As for any mucuna pruriens/natural (no carbidopa/benserazide) form of levodopa its associated side effects are nausea and vomiting. In the book about PD therapies I recently posted a researcher gave himself a dose of 2 1/2 grams (yikes) of levodopa, felt nauseous and immediately vomited multiple times. This symptom and not dyskinesia is the major side effect of pure levodopa. In days prior to carbidopa doctors administered doses as large as 2 - 6 grams a day!
Fortunately doses of this magnitude are not required for a positive response. Here is the most recent article about mucuna P. and PD (as of 2017):
Mucuna pruriens in Parkinson disease
A double-blind, randomized, controlled, crossover study
"Conclusion: Single-dose MP intake met all noninferiority efficacy and safety outcome measures in comparison to dispersible levodopa/benserazide. Clinical effects of high-dose MP were similar to levodopa alone at the same dose, with a more favorable tolerability profile."
You are currently taking a sublingual dose of sinemet and this, along with a liquidized form of levodopa, is the most effective form of (natural/synthetic) levodopa. I previously wrote an thread about liquefying your levodopa and interestingly enough, Zandopa is a powder which is mixed with water, dissolved then drank.
In the above thread 200 mg of vitamin C helps to better stabilize levodopa and make it more effective so it is of benefit to use vitamin C.
Getting back to B12 for a second. For swallowed levodopa to be more effectively used you should limit consumption of meat to dinner time and avoid it at lunch and breakfast. Proteins directly interfere with the absorption of levodopa because the amino acids which compose protein compete with levodopa in the stomach and thus it will lose effectiveness. If you go veggie or have a reduced meat diet there is an unintended side effect. The major source of B12 in the diet is meat and vegetable products contain very little B12. So by increasing the effectiveness of levodopa by liquefying it you will decrease your intake of B12 - not a good idea. This makes B12 supplementation doubly important.
Well I have thrown enough at you for the moment and my library computer time is coming to an end. Now I have to go and start looking for a new computer - not what I planned.
Best wishes and if you have any more questions or uncertainties send them this way.
Thanks for getting back to me Rich. I've got some reading to do before trying MP. I try my best to take carb-levo one hour before meals because of the interaction with proteins. When my meds don't get me to the "on" time, it's almost always because of meals. If we have plans for dinner out, I'll take my sinemet early,as much as an hour before. Otherwise I stay on schedule.
Firstly R congratulations on your dedication and work in completing this project. I look forward to watching, i am imagining It will take a while and the effect on my brain may mean i am excused from suduko for the duration. Nice to see you around again.
Subject change:
Im not convinced that the reference above answers park bears query.
The Brain Article (July 2014) is a large human study.
"In this 4-year multicentre study, we investigated a large cohort of patients with Parkinson’s disease in a sub-Saharan African country (Ghana), where access to medication is limited and the initiation of levodopa therapy often occurs many years after onset. The primary objective was to investigate whether the occurrence of motor complications is primarily related to the duration of levodopa therapy or to disease-related factors. "
Your article (2012) is about 16 moneys treated with Mucuna.
I previously read the article quoted by PB. My issue is synthetic levodopa treatment causes dyskinesia, either now or later, and natural levodopa does not. One thing to consider is from the article I quoted the researchers used 'endocarp powder', which contains only 5.5% levodopa. Zandopa, HP-200, contains only 3.3 percent levodopa and yet both of these supplements have been shown to relieve PD symptoms in patients who previously used synthetic levodopa. Additionally, a small, random, double blind cross over trial of 8 patients and the results showed the 8 PWP had a better response while taking 40% levodopa/MP than an equivalent amount of synthetic levodopa. It is my opinion Sinemet is not a good drug and hence all the new alternative forms being made available. If Sinemet worked effectively Rytary, inhaled, melevodopa (the methyl ester of L-dopa), subcutaneous L-dopa......would not be needed. It is the elephant in the room for PD therapeutics. Additionally, those of you who use Sinemet if you can get your hands on Madopar - levodopa/benserazide, you should do so because Madopar is a better drug than Sinemet. Lower doses of Madopar are required to produce an equal amount of dopamine with a larger dose of Sinemet. My father used 25/250 Sinemet 4 times a day and it did not go well.
Congratulations and many thanks, Rich! We are so lucky to have you in our HU group! I can tell from watching the segment on drinking coffee and smoking that I definitely need a fresh brain for all this info, so will watch bit by bit and I look forward to all the informed comments and questions that will surely arise in our forum here.
Well, I did watch it and I for one am glad that you still have to pay the bills. It is complex but simple. I thought it was a little slow but soon came to find that the length of the presentation, which is extremely comprehensive, was just right for the length.
I narrated almost everything considering that some people may not have proper eye sight. Yes it is long but focussed on it's content. There were multiple times I was in a state of disbelief over some of the information I uncovered. My favorite quote was from 1902 in regards to the 'uric acid diathesis'. I almost fell out of my chair when I first read the quotation.
As for paying the bills, I did so but with no financing I had to gut it out and finish the job. I thought about using kickstarter but they stated that 'no dietary supplements' could be included....that was a killer for me.
I have found my time on this site a little confusing, kind of a fish out of water sort of thing. I don't know if I am slow or just naive. I understand that I have a difficult time explaining things clearly now but I will use the best clips of movies to get my point across.
I watched three parts of your videos.....very interesting. have to think more about it, but I can feel it brewing already.
the bird's eye view tells me, that gov't types would have an interest in deciphering dopamine, and not for the common good only. obviously I don't trust this acadamia.
long narrative, but if you consider orwell's book, and note hitler's hand tremors;(they were eating amphetamines like manna from heaven....) apparently, kennedy was prescribed something similar for his back by a german doctor; who had a hole cluch of them hooked on this, marylin included, throw into that (I don't know if it was shopped but) I think I spyed with my little eye tat putin betrayed a weakness of one of his arms, and you might have a chemical warfare of a kind that lets you targrt individuals and not armies.
for another, it's become imperative or been made imperitive that movement disorders be understood because of the cost of medicare or Obamacare.
all for now. good work, going a ways to understand the environment's contribution to this scourge.
a drooling zombie kim what ever is not so scary, eh?
Congratulations are in order. Very enjoyable to sit and listen to your presentation, a plethora of ideas.
I will be reinstituting some of the suggestions. What you have given to all is a porthole that we can revisit again and take what we feel is beneficial to us.
You sounded relieved that it was done however next step would be writing a book and expending all the ideas. I have not seen anything out there that came even close to your format
The credits are not finished and only 5 of the 16 sections are complete so I still have a lot of work to go.
I made the doc as a resource to be revisited hence the information overload. As for a book?? I need some R & R (some fun too) because lacking any financial backing I had to make the minimal amount of money to pay the bills to maximize the amount of time I had to work on it. Consequently it drained my finances. To add insult to injury, kickstarter said 'no dietary supplements' in a project so I lost this possible source of income.
All in all it was a great experience and I learned so much working on the doc.
"Kickstarter is an American public-benefit corporation[2] based in Brooklyn, New York, that maintains a global crowdfunding platform focused on creativity.[3] The company's stated mission is to "help bring creative projects to life".[4] Kickstarter has reportedly received more than $1.9 billion in pledges from 9.4 million backers to fund 257,000 creative projects, such as films, music, stage shows, comics, journalism, video games, technology and food-related projects.[5]"
Hey my friend. The cardiologist that is mentioned within the segment about COQ-10 is my cardiologist, Peter Langstroen of Ty;er Texas. What a coincidence.
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