*ATTENTION should be paid to Carbidopa/Benserazide and their irreversible, potentially lethal bond with pyridoxal 5'-phosphate. Note the following excerpt from a Oct,2014 PubMed abstract regarding (PLP) the active form of vitamin B6:
"Both drugs irreversibly bind to and permanently deactivate pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, and PLP-dependent enzymes. PLP is required for the function of over 300 enzymes and proteins. Virtually every major system in the body is impacted directly or indirectly by PLP. The administration of carbidopa and benserazide potentially induces a nutritional catastrophe." [as we continue to wonder why the body eventually short circuits]
IMPORTANT TO NOTE!
"During the first 15 years of prescribing L-dopa, a decreasing Parkinson's disease death rate was observed. Then, in 1976, 1 year after US Food and Drug Administration approved the original L-dopa/carbidopa combination drug [Sinemet®], the Parkinson's disease death rate started increasing. This trend has continued to the present, for 38 years and counting.” PubMed, Oct2014: ncbi.nlm.nih.gov/pubmed/253...
WHY URIDINE?
“Chronic treatment with a combination of Levodopa plus carbidopa has been demonstrated to cause a major complication, namely abnormal involuntary movements… study results showed that Levodopa alone or in combination with carbidopa caused genotoxicity in in vivo micronucleus test (mouse bone marrow) and Comet assay (blood cells).”
"Our data show for the first time that Levodopa plus carbidopa combination causes genotoxicity which is reversed by simultaneous administration of uridine, a pyrimidine nucleoside.” PubMed, Aug,2015: ncbi.nlm.nih.gov/pubmed/259...
*To boost Uridine's benefits, it may help to take with your DHA supplement (fish oil):
"Administering uridine-5'-monophosphate (UMP) and docosahexaenoic acid (DHA) increases synaptic membranes (as characterized by pre- and post-synaptic proteins) and dendritic spines in rodents... giving uridine and DHA may partially restore dopaminergic neurotransmission in this model of Parkinson's disease. ncbi.nlm.nih.gov/pubmed/187...
Jeeves, as outlined in the "Uridine" link (below), it depends on the 'bioavailability' of the form used:
"By itself, uridine cannot be taken as a supplement. It must be ingested as one of two compounded forms in order to cross over into the bloodstream in high enough amounts.
"The first form is uridine monophosphate (or UMP), which is generally less expensive and can be taken either orally or sublingually. UMP taken sublingually is seven to ten times more potent than taken orally, although some users report a slight burning sensation when taking it in this manner. The standard oral dosage is 250mg.
"The second form of bioavailable uridine is triacetyluridine (or TAU), which is approximately four to seven times more potent than UMP taken orally. TAU is lipid-soluble, meaning it can only be administered orally and not under the tongue. However, the benefit to this is that TAU absorbs without a problem with food in the stomach, as opposed to UMP where this is questionable. The standard dosage is between 25-50mg."
I currently use the Cardiovascular Research Ltd. brand's 'UMP' version (solely based on price/supplier). Same manufacturer offers both versions - either the Ecological Formulas 'UMP' (300mg) or in the 'TAU' (25mg) formulations - which can be bought online from Amazon, iHerb, etc. I'm sure equally effective product is available from other credible manufacturers.
I don't really understand all that but I do know that the Sinemet J takes doesn't hell one but and I think it's causing him more problem.
After ten years I have got the nurse to try reducing it. It's only been reduced by one hand tablet at night I can already see a difference . And not an advers one
For those people newly diagnosed with PD , I will explain why the above is so important. Those of you , who are eager to take more meds. to eliminate the PD symptoms, this is the catch and this is why some people have advised you to put up with the minor symptoms as long as possible. ( I know you think they are already severe)
The medications have detrimental effects that increase over time and increase with quantity consumed and one reaches a point where the effects are as bad as the PD. My Doctor believes that I am allergic to the PD medications but what is described above may be what is actually going on. Efforts to reduce medication become very very difficult. I have spoken with many people who are at a similar stage as me and are desperately, yet very slowly, trying to to reduce the medication that they take, while accepting an increase in PD symptoms.
Strenuous exercise reduces the PD symptoms and allows for a reduction in medication intake however for various reasons some of us can not strenuously exercise enough for it to work.
Uridine is very interesting, perhaps a way out of this downward spiral. The Mole is our lab rat and he has previously reported that so far he has no problems with Uridne.
I am happy to see that you quote the first, pioneering mention of the Carbidopa connection by doctors Hinz, Stein , and Cole, They developed their amino acid therapy for Parkinson's to meet the nutritional needs of the nervous system WITHOUT any toxic drugs such as Carbidopa. Dr. Alvin Stein told me that his patients do not develop dyskinesias. Since their therapy contains ample amounts of L-Dopa, this indicates that it is the Carbidopa included in the standard drug regimen, and neither the L-Dopa nor the "progression" of the disease, that is creating the torturous involuntary motions known as dyskinesias. I dare to say that all PwPs who desire to avoid that added layer of suffering should take note.
It seems to me that taking Uridine to counteract the toxic Carbidopa, even if it works for humans--and so far it has only been tried on rodents--is but a half-way measure. Eliminating the Carbidopa completely would be the better choice . . . if you can afford the Amino Acid therapy. The latter has been costing me about $500-800 per month and is not covered by my insurance.
Dumps, I agree with your 'eliminate Carbidopa' conclusion - personally, I continue to get by with only mucuna pruriens extract for the l-dopa (no Carbidopa), various critical supplements, and a customized amino acid concoction (sourced from JomarLabs in US).
How much macuna do you take, and what brand do you like? I've tried so many macuna products, but not sure how much to take so it would work for me also how long have you had PD, it's been 4 years form. I take l- tyrosine 5htp, but lately I'm taking neuro replete by Dr. Heinz, can't afford testing that they require, so just winging it for now.
No time at all. There was no "acclimatization period" or whatever you want to call it. The relief of symptoms from a single dose is like that afforded me by a 25/100 CD/LD pill: it takes maybe 60-75 minutes to get into my blood-stream/brain, and then for the next, perhaps, 2-2.5 hours, my tremor (the most distrubing symptom) is abated. The first time I took the Mucuna Pruriens, I felt nauseated briefly and turned pale as if I was experiencing shock. But after that, and ever since, there has been no significant nausea. Roughly last December and January, my on-time shrank down a lot. But Dr. Stein, on basis of a urine test, advised me to increase intake of Tyrosine, and that fixed the problem nicely.
Thank you - very interesting. I guess we all react differently since I have felt no effect yet after three weeks of 4 D5 macuna 3x/day (plus the neuro replete and cysreplete). According to what I have read, this is normal until amino acid balance is achieved. Do you find the overall effect to be equivalent (or better?) to using Sinamet? (I have never used Sinamet) tnx!
Yes, just as good as Sinemet--the "25/100 CD/LD" pill I referred to is none other than Sinemet, which is a mix of Carbidopa and Levodopa. (I have read several times on this site that Sinemet does no help with tremors, but that is definitely not true in my case since Sinemet handled my tremors very well.) If L-Dopa–from Mucuna or wherever–does not help your symptoms, I would guess that either you're not taking enough, or you've been misdiagnosed, and don't actually have classic PD. My own provider says that the L-dopa reaches equilibrium after 5 days (of steady dosing), so any "fluctuations" in the bodily response should wash out long before 3 weeks. Zero response is even more suspect! You ought to check with your provider.
Whack a Mole. Thanks for responding, but I'm slightly confused? The article you pasted declared at the start that uridine couldn't be taken as a supplement but then proceeds to outline several ways that it COULD be taken as a supplement! Am I missing something here? Maybe it all hinges on definition of the word 'supplement'. But I'd appreciate clarification here. Thanks in advance.
It refers to the fact that, like many such nucleocides/nucleic acids, Uridine in its pure ribonucleic acid (RNA) form - as it appears in certain food sources - is suspected to be thoroughly destroyed in the liver and gastrointestinal processes (and thus would not serve as a viable supplement).
Only through one of the referred compounded formulations (UMP, TAU) does it become bioavailable to perform its protective role.
In my opinion one of the big problems with C/L therapy is the ratio of carbidopa to levodopa. Most medicines are 25% carbidopa relative to levodopa, e.g. 25/100. If you need a lot of levodopa and you can easily exceed the recommended amount for carbidopa. That's why I switched to the 10/100 tabs.
I want(ed) to try the 10/100 compound too. My neuro said when I asked for a trial, "everyone (peers) says the carbidopa is not effective in that small amount". So, I did not push anymore for a Rx. However, I wonder if the carbidopa in it's function to slow the metabolism (?) of levadopa and in the way it does that causes permanent change that raises risk of dystonia in my limbs, why use it in increased proportion (e.g. 25/100)? It's way over my head I know. If I was as intelligent as my neuro I could have become a doctor but realistically I never have been that capable in school. I just have to trust the neuro cares for me. But being completely honest, I have seen patients with advance PD presenting dystonia due to meds and I fear it. That's why I never try to take so much 25/100 C/L to try and completely calm my tremor. I use small doses and only when the tremor gets up my arm into my shoulder and tightens my vocal cords. I fear dystonia so much that I am very willing to put up with a lot of cogwheeling in my legs and difficulty handling things due to my hand tremor. BTW speaking of protective roles, I posted awhile back about the irregularity in the potency of my Rx of generic C/L. I try to protect/ensure the potency of my C/L as I go through a 3-month supply by keeping it refrigerated but the longer it stays in the frig, the weaker it seems to be. Is it wrong to keep it at fridge temp (e.g. 38 degrees farenheit)? Anybody know?
BUZZ, It may be helpful to reference the PubMed studies (links above) that implicate Carbidopa/Benserazide in the "permanent... irreversible" deactivation of the critical vitamin B6 (PLP) during your next meeting. Cite the accelerated decline of symptoms and health described in the studies, voice your concern, and discuss Uridine's potential to mitigate the unfolding of CD's side-affects (you can also best discuss CD shelf-life at that time).
I found the following from the Lodosyn (carbidopa by itself) prescribing info helpful:
Patients Receiving Carbidopa-Levodopa Who
Require Additional Carbidopa:
Some patients taking carbidopa-levodopa may not have adequate reduction in nausea and vomiting when the dosage of carbidopa is less than 70 mg a day, and the dosage of levodopa is less than 700 mg a day. When these patients are taking carbidopa-levodopa, 25 mg of LODOSYN may be given with the first dose of carbidopa-levodopa each day. Additional doses of 12.5 mg or 25 mg may be given during the day with each dose of carbidopa-levodopa. LODOSYN may be given with any dose carbidopa-levodopa as required for optimum therapeutic response. The maximum daily dosage of carbidopa, given as LODOSYN and as carbidopa-levodopa), should not exceed 200 mg.
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