Metabolic (energy) deficiency may be the cause of Parkinson Disease (PD)

[Birdie]

Thank you for this information. Both my husband and I have been taking some Sambrosa nighttime cold & flu med due to catching the Omicron Covid a couple of weeks ago. There's an antihistamine in it; Doxylamine Succinate. I'll warn him about it as it seems to be slightly addictive; I've had some trouble sleeping without it now.

Isn't your husband taking thiamine? If yes, thiamine is known to lower high brain serotonin.

Effect of thiamine deficiency on brain serotonin turnover - PubMed

Serotonin turnover has been investigated in regional brain areas of rats made thiamine deficient by pyrithiamine (PT). Following intracisternal injection of [14C]5-hydroxytryptamine ([14C]5-HT), a marked increase in the accumulation of [14C]5-hydroxyindoleacetic acid ([14C]5-HIAA) was found in...

pubmed.ncbi.nlm.nih.gov

and

Effect of thiamine on serotonin levels in magnesium-deficient animals

To clarify the relationship between thiamine metabolism and peripheral vasodilation symptoms seen in the early stages of dietary magnesium deficiency,…

www.sciencedirect.com

This second one explains that you need magnesium too. also this: "Serotonin in stomach and intestine increased in the excess-thiamine, magnesium-deficient group."

It would be nice if the patient would be willing to give a larger dose (1/4teas) of the progest-E a try for a few days (in the evening, before bed). Just a few days, to see if there's improvement.

Thank you so much mostly lurking. Yes, husband is taking thiamine. It should help with all this. Um, he was at 2500mg but found that his nighttime drool slowly increased. We tried a lower dose and no change. So, a few days ago, he started 3000. And, glory be, he reports improvement in drool.

I like the way you put that last paragraph. Could be a helpful way to put it. I did tell him people here thought he should take around 1/4 tsp, so he increased a little. I think the trial you suggest will appeal to him.

Well, I just tried it and he asked what we were trying to improve. I guess it was the drool, which improved with the thiamine dose increase. So. He did respond by saying no improvement is necessary because he is very good, as good as he can be. haha. Funny guy.

 

[Birdie]

The dogma that PD is just a simple dopamine deficiency manifesting in genetically vulnerable individuals is quickly becoming untenable. It is well-known among clinicians that administering dopamine precursors such as L-Dopa, or selective dopamine agonists such as pramipexole has limited therapeutic effects for PD patients and invariably become ineffective after a few years of use. A few months ago, several studies identified serotonin excess as the primary driver of several key symptoms of PD such as tremors and psychosis. The role of serotonin in PD is corroborated by the fact that dopamine agonists that also possess serotonin antagonism properties such as bromocriptine, lisuride, methysergide, etc do not generally use effectiveness with prolonged use. Serotonin has a known, potent, anti-metabolic effect and anti-serotonin agents are now studied as possible treatments for obesity, diabetes, CVD, dementias, and even aging. The study below demonstrates that at its core, PD is likely an energetic deficiency disorder, which would explain both the serotonin excess seen in PD patients, as well as the positive effects of anti-serotonin/pro-dopamine drugs. It also opens the avenue to a number of metabolic therapies for PD, including reduction of endotoxin/LPS, and usage of OTC substances such as aspirin, naicinamide, progesterone, DHEA, testosterone/DHT, salt / baking soda, quinones (methylene blue, vitamin K, tetracyclines, etc), and anti-estrogenic substances (both OTC and pharma drugs), among others. Coincidentally, there is at least one study for any of the substances I mentioned above demonstrating robust therapeutic (and preventative) effect of said substance in a PD animal model. Some of them have already been tested in humans, but FDA demands that clinical trials with thousands of people be conducted before any of those substance can be used on PD patients, despite their proven safety and low cost.

Influence of energy deficiency on the subcellular processes of Substantia Nigra Pars Compacta cell for understanding Parkinsonian neurodegeneration - PubMed
IIT Madras Researchers find Energy Deficiency in some Brain Cells to be a major cause for Parkinson's Disease | Indian Institute of Technology Madras
"...Although it is known that PD is caused by the loss of dopaminergic cells in substantia nigra pars compacta (SNc), the decisive cause of this inexorable cell loss has not clearly been elucidated before. The IIT Madras researchers developed a computational model that showed that energy deficiency might be a major cause of SNc cell loss in Parkinson's Disease. This computational modelling was developed by Dr. Vignayanandam Ravindernath Muddapu, who completed his Ph.D. recently at IIT Madras, under the guidance of Prof. V. Srinivasa Chakravarthy, Department of Biotechnology, IIT Madras. Dr. Vignayanandam Ravindernath Muddapu has now joined the Blue Brain Project, an EPFL-linked research center for postdoctoral research. The findings of this research have been published recently in the prestigious peer-reviewed International Journal Nature Scientific Reports. Elaborating on the important findings of this research, Prof. V. Srinivasa Chakravarthy, Department of Biotechnology, IIT Madras, said, "While existing treatments manage PD symptoms - sometimes with great effect - a cure demands an understanding of the root cause of SNc cell loss. This is the main question addressed in our work: What is the major underlying cause of SNc cell loss in PD?" Further, Prof. V. Srinivasa Chakravarthy said, "It is quite remarkable that loss of neurons in a small nucleus like SNc can have wide-ranging, devastating effects in all the four major domains of brain function - sensory-motor, cognitive, affective, and autonomous. The sequence of the three computational studies suggests that metabolic deficiency within the basal ganglia circuit is the common underlying factor at the subcellular, cellular, and network level in PD. Thus, we have a reasonably comprehensive theory of the pathogenesis of Parkinson's disease." This research was undertaken at IIT Madras Computational Neuroscience Laboratory, which aims to build a simplified model of the whole brain and use it to develop applications in medicine and engineering. Prof. V. Srinivasa Chakravarthy is the head of Computational Neuroscience Laboratory. The computational model showed that: At the subcellular level, metabolic deficiency leads to changes like including alpha-synuclein aggregation, reactive oxygen species production, calcium elevation, and dopamine dysfunction, which are characteristic subcellular changes in Parkinson's disease."

Thank you so much for taking the time to start this thread. You give so much to this forum. We are fortunate.

 

[mostlylurking]

Thank you so much mostly lurking. Yes, husband is taking thiamine. It should help with all this. Um, he was at 2500mg but found that his nighttime drool slowly increased. We tried a lower dose and no change. So, a few days ago, he started 3000. And, glory be, he reports improvement in drool.

I like the way you put that last paragraph. Could be a helpful way to put it. I did tell him people here thought he should take around 1/4 tsp, so he increased a little. I think the trial you suggest will appeal to him.

Well, I just tried it and he asked what we were trying to improve. I guess it was the drool, which improved with the thiamine dose increase. So. He did respond by saying no improvement is necessary because he is very good, as good as he can be. haha. Funny guy.

So good that you have seen additional improvement! I do want to let you know about my experience when I increased my dose of thiamine hcl an additional 500mg, up to 2500mg. Tried it one day. That night I got shooting zapping electrical zaps in my thighs. That's how I learned that 2000mg/day was really my ideal dose. If he complains of strange zaps in his legs at night it might be that his optimum dose has been exceeded.

 

[Birdie]

So good that you have seen additional improvement! I do want to let you know about my experience when I increased my dose of thiamine hcl an additional 500mg, up to 2500mg. Tried it one day. That night I got shooting zapping electrical zaps in my thighs. That's how I learned that 2000mg/day was really my ideal dose. If he complains of strange zaps in his legs at night it might be that his optimum dose has been exceeded.

Just recently he said the nighttime drool was only slightly improved. He's staying at the 3000mg dose for now. We've been adjusting his dose for almost two years now. 3000 is a lot for his size but his ancestors came from an area close to Dr C's patients (Italy) where they need a higher dose than is typical for Americans according to Dr C.

He has high prolactin, gynecomastia.

 

[Birdie]

He should get back on methylene blue. We stopped it when he began cypro which he used only for a week when I'd forgotten it was not good for his prostate enlargement. Today he reports drooling is decreased.

Also, since using IVM for two days and then using Artemisinin 200mg 4 times a week (thanks to @Braveheart ) he no longer has the tiny clots that appeared in his urine.

Potential Alzheimer's, Parkinson's Cure Found In Century-old Drug

A century-old drug, methylene blue, may be able to slow or even cure Alzheimer's and Parkinson's disease. Used at a very low concentration -- about the equivalent of a few raindrops in four Olympic-sized swimming pools of water -- the drug slows cellular aging and enhances mitochondrial...

www.sciencedaily.com

A century-old drug, methylene blue, may be able to slow or even cure Alzheimer's and Parkinson's disease. Used at a very low concentration -- about the equivalent of a few raindrops in four Olympic-sized swimming pools of water -- the drug slows cellular aging and enhances mitochondrial function, potentially allowing those with the diseases to live longer, healthier lives.

 

[mostlylurking]

Just recently he said the nighttime drool was only slightly improved. He's staying at the 3000mg dose for now. We've been adjusting his dose for almost two years now. 3000 is a lot for his size but his ancestors came from an area close to Dr C's patients (Italy) where they need a higher dose than is typical for Americans according to Dr C.

He has high prolactin, gynecomastia.

As we age, it seems to get more complicated. If he is tolerating the higher dose of thiamine it's probably fine. I hope the methylene blue is helpful for him.