Sinemet MG Conversion to Zandopa MG Conversion to Madopar. Synergy between Mucuna Pruriens & Withania somnifera. B12/thiamne thoughts...

[silvestrov]

The first link is to an article about a woman who combined Zandopa with Madopar and cups of green tea for her PD symptoms. The article has to be downloaded to read the complete article (which I cut the Sinemet = Mucuna Powder = Madopar image).

researchgate.net/publicatio...

Secondly, the following study shows that when Mucuna pruriens is combined with Withania somnifera there is therapeutic synergy. The most important sentence I read is as follows (the complete study can be downloaded as a pdf file:

"Furthermore, it was found that the use of Mp and Ws considerably improved the tyrosine hydroxylase expression in the substantianigra region of the brain."

scirp.org/journal/PaperInfo...

Many of you take high dose thiamine and should give high dose B12 per day (which is also higher than doctor recommended). Let's look at the specifics.

Daily high dose thiamine equals 4,000 mg/day (4 grams).

100 mg of thiamine equals 8,333 % of the daily allowance

4,000 mg of thiamine equals 333,320 % of the daily allowance

A doctor will give you a 1 mg/month injection of B12 which equals 41,666.6% of your daily allowance.

When confronted with smoke inhalation patients, people with potentially lethal cyanide exposure, they may receive 5 to 10 grams of hydroxocobalamin in one day.

5,000 mg/5 grams equals 208,333,000 % to 416,666,000 % in one day. You read that right, that's two hundred eight million, three hundred thirty three thousand to four hundred sixteen million, six hundred sixty six thousand percent of your daily allowance of B12 (with transient side effects). Here is the B12 safety article:

stichtingb12tekort.nl/weten...

I have often recommended people to take 5 mg/per day of (oral/sublingual) methylcobalamin (as a prophylactic measure to prevent peripheral neuropathy and the rise of homocysteine and methylmelanic levels caused by L-dopa therapy.

5 mg/day methylcobalamin = 208,333 % daily allowance

4,000 mg/day thiamine = 333,320 % daily allowance

What is a few percentage points between friends?

I recommend larger dose of B12 for many reasons and this one is central to my thoughts:

Modest increase in plasma homocysteine follows levodopa initiation in Parkinson's disease.

"Levodopa elevates tHcy and lowers vitamin B12 concentration to modest degrees."

ncbi.nlm.nih.gov/pubmed/153...

Low Levels of Vitamin B12 May Worsen Walking, Cognition in Parkinson’s Patients

Supplement May Boost Balance, Memory, But Impact on Disease Trajectory Unknown

ucsf.edu/news/2018/03/40999...

[Greenday]

Rich do you think that along with high doses of B12, maintaining optimum blood levels of both Folate & B6, but within the safe limits, could synergistically lower homocysteine levels?

There are few studies that suggest this approach

ncbi.nlm.nih.gov/pubmed/979...

However some studies appear contradictory for high levels of Folic acid / B-Complex

ncbi.nlm.nih.gov/pubmed/226...

Also NAC appears to potentially normalize homocysteine levels

ncbi.nlm.nih.gov/pubmed/257...

ncbi.nlm.nih.gov/pubmed/892...

[silvestrov in reply to Greenday]

I take 400 mcg of folate (methyltetrahydrofolic acid) and 25 mg P5P - pyridoxyl 5 phosphate along with 100 mg thiamine, 100 mg riboflavin with the 5 mg of Methyl B12 to form a potent B complex vitamin. I have taken this protocol for years with the only side effect of having good energy levels. B vitamins work together and yes taking folate and pyridoxine with B12 is a good way to keep homocysteine levels in check.

From all the different supplements I have taken Methyl B12 has been one of the most helpful (and I tried it long before taking NAC, and for me, it has helped me more than NAC.) I was apparently deficient in B12 and reacted like I was shot out of a cannon with the first dose. After 4 days of higher than normal energy levels my energy plateaued and I had no fatigue with better energy than when I started taking B12. It has been 5 (maybe 6) years of taking B12 at this dose. I tried 6 mg of swallowed cyanocobalamin and it was underwhelming to say the least. It is difficult to have side effects from taking B vitamins because they are water soluble. As noted B12 has been used at staggering doses and also intravenously in ALS, etc... patients.

I tried adding biotin and pantothenic acid to the above B complex but pantothenic acid made me feel like I was a car running 'rich' - with too much gasoline and not enough air. I chugged around and then just passed out. I could feel no difference in any way for biotin so I use the above supplements.

EDIT: I forgot to note I also take 250 mg/day of niacin and 1,500 mg/day of niacinamide/nicotinamide. Each has different neuroprotective properties and the niacinamide is good for joint health and has helped me keep osteoarthritis at bay.

[faridaro in reply to silvestrov]

Just a quick question - do you supplement with Lithium (low dose) which is supposed to enhance B12 transport into cells according to some studies?

nancymullanmd.com/big-deal-...

[silvestrov in reply to faridaro]

Thanks for asking this question because I have not considered the B12 lithium relationship. I do not take low dose lithium (LDL) though I considered it. At the time I read Dr Laura Mischley's masters thesis on LDL and she stated that it had a chemical similarity with magnesium so it might interfere with Mg absorption and it was bad for hypothyroid conditions. Here is her thesis:

digital.lib.washington.edu/...

"..lithium definitely affects thyroid function as repeatedly shown by studies on cell cultures, experimental animals, volunteers, and patients; b) inhibition of thyroid hormone release is the critical mechanism in the development of hypothyroidism, goitre, and, perhaps, changes in the texture of the gland which are detected by ultrasonic scanning."

ncbi.nlm.nih.gov/pmc/articl...

"...Thus, the chemistry of Li has similarities to that of Mg,"

en.m.wikipedia.org/wiki/Dia...

It is an interesting relationship between B12 and she advocates taking lithium prior to taking B12.

"When lithium is low and/or serum B12 is particularly high, use lithium supplementation prior to adding more B12."

"Increasing B12 in the absence of lithium may further deplete lithium levels due to the use of lithium to aid in the transport of the added B12. Ideally, lithium should be in balance prior to adding excess B12 so as not to create lithium depletion."

But what about taking lithium without B12?

Vitamin B12 and folate levels and lithium administration in patients with affective disorders

"Conclusions: Our data may represent a lithium-associated decrease in serum B12 concentration. The clinical significance of these findings is not yet clear."

sciencedirect.com/science/a...

B12 & bipolar disorder:

"A February 1984 study published in the “American Journal of Psychiatry” related the case of mania that manifested in a patient that vitamin B-12 supplementation immediately resolved. A December 2000 study conducted by University of the West Indies researchers and published in the “West Indian Medical Journal” found the symptoms in a diagnosed type 1 bipolar disorder patient improved dramatically following vitamin B-12 supplementation. More recently, a September 2009 study conducted by Medical University of South Carolina researchers and published in the “Journal of Psychiatric Practice” partially attributed a patient’s psychosis to vitamin B-12 deficiency, and subsequent supplementation alleviated some symptoms significantly."

livestrong.com/article/5070...

Vitamin B12 deficiency common in primary hypothyroidism.

ncbi.nlm.nih.gov/pubmed/186...

"We hypothesize that the central biochemical event in thyroid disease is that of an acquired, altered mitochondrial function due to deficiency of magnesium, selenium, and coenzyme Q10."

sciencedirect.com/science/a...

And where I found the above study:

thyroidpharmacist.com/artic...

So B12 can lower lithium levels and lithium can lower B12 levels and low B12 levels makes bipolar symptoms worse (which lithium is used to treat). Lithium can cause hypothyroid problems and both B12 and magnesium can help resolve thyroid problems.

Lithium levels are reduced in psychiatric and people who commit suicide:

"These findings suggest that even very low levels of lithium in drinking water may play a role in reducing suicide risk within the general population."

msrc.fsu.edu/system/files/O...

"Patients who had made suicide attempts (by using either violent or nonviolent means) had significantly lower mean CSF magnesium level irrespective of the diagnosis."

ncbi.nlm.nih.gov/pubmed/257...

"In conclusion, active suicidal or death ideation occurs in up to one-third of PD patients. Comorbid psychiatric disorders, more than PD-related disease variables, are associated with this ideation, highlighting the need for a comprehensive approach to the clinical care of PD patients."

ncbi.nlm.nih.gov/pmc/articl...

"We rarely see patients so depressed with Parkinson's that they commit suicide. I don't think his suicide had anything to do with his diagnosis. Williams had a mood disorder and was struggling mostly with mood issues."

nydailynews.com/life-style/...

After reviewing this information I concluded that the people who are on HU who need to be checked for their lithium levels are those who have a mood disorder separate from PD. Plus, the mood disorder may be mitigated/reduced by B12, magnesium and selenium.

"Ebselen is a organoselenium compound with anti-inflammatory, anti-oxidant and cytoprotective activity."

pubchem.ncbi.nlm.nih.gov/co...

A safe lithium mimetic for bipolar disorder

ncbi.nlm.nih.gov/pmc/articl...

The Antioxidant Ebselen Prevents Neurotoxicity and Clinical Symptoms in a Primate Model of Parkinson's Disease

sciencedirect.com/science/a...

Both lithium and magnesium have been shown to be neuroprotective in PD models.

Your question and link are good because they opened up the relationship between hypothyroidism, depression and suicide with magnesium, B12, selenium, lithium and PD.

[999---666 in reply to silvestrov]

got the atlas of natural cures" by glenn s, rothfield, excellent info. therein he (has pd himself) says that lithium does not cure but stops progression of disease, even alzhiemera. he is a practising healer, naturepath. I think.

[silvestrov in reply to 999---666]

Several years ago I investigated low dose lithium and after reading the following article I decided I did not need to take lithium.

"Persons with any type of neurologic injury often have

deficiencies in neuroprotective nutrients such as magnesium, zinc, selenium, vitamin B12, folate, and lithium."

Prior to investigating lithium I was already taking magnesium chloride & threonate, zinc piccolinate, selenomethionine, methycobalamin and methyltetrahydrofolic acid. Plus, the article mentions....

"....increase of the anti-inflammatory metabolite and

docosanoid precursor, 17-hydroxy-DHA"

And I had also been taking DHA omega three supplements prior to investigating lithium.

But for those of you intetested in low cost, safe and non-toxic PD therapeutic, low dose lithium is worth looking into. Of the articles I read on the nutrient the following study is the best:

jpands.org/vol20no4/marshal...

[999---666 in reply to silvestrov]

conventional docs don't offer this treatment. time proven, no casualties. inexplicable!

[999---666 in reply to silvestrov]

excellent article. how is your health? are you mobile? speech? how long have you hod this pd? i'm not happy with my neuro, thinking of switching to pruriens canua is it? because supplement i'm dependent on has 18 mg iron and it 's not compatible with levodopa. what your opinion?

[silvestrov in reply to 999---666]

I will have to get back to you in a couple/three days because my work load during this time is rough.

[999---666 in reply to silvestrov]

you can work. good for you, later.

[Hmop in reply to 999---666]

Where could I find it? Thanks

[Hmop in reply to 999---666]

Where I could find it? Thanks

[Hmop in reply to 999---666]

Where could I find it? Thanks

[Greenday in reply to silvestrov]

Thank you for your quick response. Great to pinpoint the importance of methyl B12, which often overlooked. Methylocobalamin appears to replete my energy levels as well and within short time I feel the difference. However my blood exams showed 10% increase in homocysteine levels, but well within the safe limits, even though my vitamins B were slightly higher. I did stop NAC for a couple of months before taking blood exams, which might have an impact on my homocystein levels.

Also, I'd really like to have your opinion about the use of high doses of Thiamine HCI (2x2g/daily) as passionately suggested by some forum members. The most noticeable effect mentioned by most is the increase in energy levels. However the use of highly biovailable thiamine derivatives is often dismissed: for example, Sulbutiamine, a lipid soluble synthetic thiamine, which effectively increases thiamine levels in the brain, it is long used for chronic fatigue, fibromyalgia and as nootropic, but at much lower dosage (2x200mg), with some studies to back up its efficacy. ncbi.nlm.nih.gov/pubmed/287...

[silvestrov in reply to Greenday]

I will get back to you in a couple days. Work is picking up and I will be read busy....

[Greenday in reply to silvestrov]

No worries, take your time, your work on this forum has been remarkable! I really value your opinion, I keep reading 2-3 years old post of yours and always informative.

[silvestrov in reply to Greenday]

First of all, everyone taking thiamine should not be 'downing' it with either coffee or tea. The following is from wikipedia:

"Plant thiamine antagonists are heat-stable and occur as both the ortho- and para-hydroxyphenols. Some examples of these antagonists are caffeic acid, chlorogenic acid, and tannic acid. These compounds interact with the thiamine to oxidize the thiazole ring, thus rendering it unable to be absorbed. Two flavonoids, quercetin and rutin, have also been implicated as thiamine antagonists."

Caffeic acid is found in tea and coffee. Chlorogenic acid is in both coffee and green tea. Tannic acid is in coffee and black tea. Quercetin is in coffee and green tea. Rutin is in green tea, coffee and black tea.

As for why thiamine would improve PD symptoms? I think this paragraph nails it:

"Pyruvate dehydrogenase is the first component enzyme of pyruvate dehydrogenase complex (PDC). The pyruvate dehydrogenase complex contributes to transforming pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration, so pyruvate dehydrogenase contributes to linking the glycolysis metabolic pathway to the citric acid cycle and releasing energy via NADH."

NADH has been shown to be good for PwP as its precursors, niacin, nicotinamide/niacinamide, NADr/Niagen.

Pyruvate dehydrogenase is the major enzyme which thiamine stimulates:

"Cofactor supplementation with thiamine, carnitine, and lipoic acid is the standard of care. The cases of pyruvate dehydrogenase complex deficiency (PDCD) that are responsive to these cofactors respond to supplementation, especially thiamine."

emedicine.medscape.com/arti...

I have been quite interested in sodium pyruvate supplementation because of its importance in energy production and here is a study which shows synergy between sodium pyruvate and luteolin:

Additive Protective Effects of Luteolin and Pyruvate against 6-Hydroxydopamine and 3-Hydroxykynurenine Induced Neurotoxicity in SH-SY5Y Cells

"Moreover, luteolin and sodium pyruvate, administered together, acted additively, so to achieve the same effect, lower concentrations were needed."

What other supplements did luteolin out perform in the study? Luteolin outperformed:

"One day after plating, amentoflavone, apigenin, chrysine, epigallocatechin 3-gallate, isorhamnetin, kaempferol, luteolin, luteolin-7-glucosid, saponarin, sinensetin, naringenin, myricetin, quercetin, rosmarinic acid, rutin and sodium pyruvate were added at various concentrations to the cells for 24 hours."

Apigenin, EGCG, kaempferol, myricetin, quercetin, rosmarinic acid and rutin have all been shown to be neuroprotective in PD studies. Perhaps others on the list...and luteolin out performed them all.

file.scirp.org/pdf/PP_20130...

Swanson sells a triple pyruvate complex which is used by weightlifters, I lifted weights years ago as a young man, and it contains:

"Calcium (from calcium pyruvate) 75 mg 8%,Sodium (from sodium pyruvate) 30 mg <1%, Potassium (from potassium pyruvate) 20 mg."

amazon.com/Swanson-Triple-P...

And I had to quit taking the complex. Realizing mitochondrial dysfunction is a consequence to being exposed to chemicals I combined various supplements to make a huge multi-vitamin mitochondrial supplement featuring large doses of Coq10, fish oil, NAC, lipoic acid, magnesium..... and I decided to add the triple pyruvate complex to the mix. I had enough energy to run through a brick wall. I was shaking, not from parkinsonian symptoms, from having too much energy. It only took 3 days for the effect to happen.

Luteolin (and rutin) has been used to treat ALS with good results:

tandfonline.com/doi/full/10...

Thiamine and biotin are the only 2 B vitamins in which has a sulfur component so it may effect glutathione levels:

researchgate.net/publicatio...

As for combining sulbutiamine with other forms of thiamine that is an interesting proposition. Sulbutiamine has been tested on PwP and improved executive function:

Effects of Sulbutiamine on Cognitive Slowing, Objective and Subjective, and on the Feeling of Fatigue of Parkinson's Patients

"In Parkinson's patients, treated with sulbutiamine, an improvement in the cognitive, executive and mnesic functions was observed, with diminution of the sensation of fatigue."

patents.google.com/patent/U...

They do not mention any motor improvement or motor deterioration so perhaps its effect is mainly on non-motor symptoms of PD. So the combination of sulbutiamine with any other form of thiamine is an open question. Sulbutiamine is a nootropic so seeing it improve PD executive function is not that much of a surprise.

[faridaro in reply to Greenday]

It's good to add TMG to lower homocysteine.

[sunvox in reply to silvestrov]

Your statements about vitamin B3 are wrong. Niacin and niacinamide are both NAD+ prescursors and have the exact same effect molecularly within the body.

hvmn.com/biohacker-guide/me...

[silvestrov in reply to sunvox]

Thanks for replying to my posting because upon reviewing the article, "Upregulation of GPR109A in Parkinson’s

Disease", I discovered important information. But first things first. In the discussion of the aforementioned article, the authors stated:

"The neuroprotective role of niacinamide is documented in

MPTP and other models of PD in mice [54,55]. The role of NAD, decreased apoptosis (by blocking PARP pathway), decreased

oxidative stress and inhibition of NOS have been implicated as possible mechanisms involved in neuroprotection by niacinamide."

"Niacin has been shown to be neuroprotective in animal stroke models [56]. Niacin was thought to be involved in vascular and axonal remodeling of the animals. However, there is no published data that demonstrates the neuroprotection of niacin in any PD animal model. Both niacin and niacinamide are sources of NAD. Niacin but not niacinamide acts as an agonist of GPR109A."

researchgate.net/publicatio...

And that is why I take both niacin and nicotinamide. It took me a while to remember, but years ago I simultaneously took NADH & resveratrol/pterostilbene for 3 months and it did nothing for me. For my biology I had the greatest benefit from combining coq10 with high DHA fish oil.

The important info (that I previously missed) is as follows,

"Butyrates (GPR109A agonists) are also known to inhibit Inflammation through inhibiting NFkB in Crohn’s disease [57]. Butyrates decrease pro-inflammatory cytokine (TNFa, IL-6 and IwL-1b) expression via inhibition of NFkB activation and IkB degradation [58]. Butyrates also inhibit NFkB activation via GPR109A and increases IkB levels in-vitro in intestinal epithelialcell lines [59]."

Mannitol is (rightly) taken by many on this site but I think either microencapsulated butyric acid, sodium butyrate or phenylbutyrate is better than mannitol because it is a product of colonic bacteria. And butyrates also reduce inflammation by being GPR109a agonists.

This is good stuff!

Thanks again.

Rich

[Gioc in reply to silvestrov]

A beautiful intuition and beautiful research. Surely the niacin (niacin acid) will give us PwP many satisfactions in the future in practical use, that it is very different from niacinamide.

thank you.

[Farooqji]

Good research. Thanks for sharing

[Farooqji]

I am copying and pasting an excerpt from the book "A History of the Chemical Therapy of Parkinsonism" which is in line with the post

"Nagashayana and associates (Department of Kayachikitsa, Government Ayurveda College, Thiruvananthapuram) recently reported that administration of an Ayurvedic “concoction in cow’s milk of powdered Mucuna pruriens and Hyoscyamus reticulatusseeds and Withania somnifera and Sida cordifolia roots” to thirteen clinically diagnosed parkinsonian patients for fifty-six days following ‘Ayurvedic cleansing’ (twenty-eight days) achieved significant improvement in activities of daily living and as assessed by the Universal Parkinson’s Disease Rating Scale (UPDRS), with alleviation of tremor, bradykinesia, rigidity and cramps noted. This improvement was not seen in five patients who received the medication without prior cleansing. Interestingly, sialorrhea was exacerbated in all patients. Analyses of powdered samples in milk, as administered to patients, indicated that each dose contained about 200mg L-DOPA"

[silvestrov in reply to Farooqji]

I am glad you posted this because this book is a must read if you want to understand the evolution of PD therapy to the levodopa era. It is an excellent book:

healthunlocked.com/parkinso...

[reedboat2]

Thanks for the study on MP + Ws. I take no pharmaceuticals, and I do take MP, every 6 hours, total around 1gm / day. After reading the study I took a capsule of Ashwagandha, 400mg, from the company Organic India. We'll see how it goes.

[Greenday]

Rich, The actual levodopa concentration in Zandopa may not be as the one displayed in the post image.

The following study provides a different insight:

Analysis of Levodopa Content in Commercial Mucuna pruriens Products Using High-Performance Liquid Chromatography with Fluorescence Detection

liebertpub.com/doi/pdf/10.1... .

They also tested Zandopa with HPLC-FD and the result didn't correspond to 3.33% or 250mg levodopa. The full study costs approximately 50$ to view. The actual product label does not claim any specific levodopa content.

[parkie13 in reply to Greenday]

Greenday, so what is the actual content in zandopa? Thanks

[Greenday in reply to parkie13]

According to the study: 333-374mg Levodopa per 7.5g of product powder (Batch; March 2011; February 2013; ). That is 4.44% to 4.98% levodopa

"One limitation of this study was the lack of assessment of multiple batches of a single product. The results are therefore batch specific and do not account for the possibility that other batches of that brand may have levodopa amounts closer to label claims" (Note: Zandopa label doesn't claim any specific levodopa content).