Gang. Just self referred to an idea in response to another post on something I'm doing. This goes back to a post by WackA Mole whereby he showed some study of protective qualities of uridine in relation to ingestion of Levadopa. It combats dyskinesia in theory but I can't remember the practical aspects of the research i.e was it on rats? In Vivo? Etc.
I take 250mg daily butt have read that it's power is amplified by taking under the tongue. I haven't tried this form of ingestion yet as I have capsules but am aware that one needs the accompaniment of fish oil. I take this at the same time. I suppose I just wondered who is trying this too, how you take it, where getting the uridine from. The only down side I can see to this protocol is the cost of uridine which is pricey and when added to the cost of NAC, Q10 etc gets a bit ridiculous in terms of expenditure on an unproven protocol. But, $$ aside, I'd say it's worth a shot. Silvestrov, if you read this, I could do with your thoughts on this one.
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Jeeves, I'm glad you posted this. I have a bottle of uridine in my supplement collection and I couldn't remember why I bought it, so of course I never took it. I need to start writing on the bottles what I bought them for. I look forward to any feedback on whether or not this helps. I started amantadine while back and that does seem to help.
Thanks for your reminder about uridine. Because supplements can get costly, I try to get the vitamins/minerals from my diet as much as I can. Although, I suspect that studies done with uridine showing benefits to Parkies' health would come from high amounts in a tablet/capsule form. Nevertheless, here is a list of foods that contain uridine:
Here is original post by whack-a-mole in Sept 2015 . . ..
URIDINE: Why LD/CD Users Should Consider It
*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...
Parkinson's disease (PD) is a common neurodegenerative disorder that affects millions of people all over the world. Motor symptoms of PD are most commonly controlled by L-3,4-dihydroxyphenylalanine (Levodopa, L-DOPA), a precursor of dopamine, plus a peripherally-acting aromatic-L-amino-acid decarboxylase (dopa decarboxylase) inhibitor, such as carbidopa. However, chronic treatment with a combination of Levodopa plus carbidopa has been demonstrated to cause a major complication, namely abnormal involuntary movements. On the other hand, the effect of this treatment on bone marrow cells is unknown. Therefore, in this study, we aimed to investigate possible genotoxic effects of Levodopa and Carbidopa using male Balb/C mice. Our 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). Furthermore, we showed that simultaneous administration of uridine, a pyrimidine nucleoside, reversed the genotoxic effect of Levodopa and Carbidopa in both assays. Our data show for the first time that Levodopa plus carbidopa combination causes genotoxicity which is reversed by uridine treatment. These findings might enhance our understanding for the complications of a common Parkinson's treatment and confer benefit in terms of reducing a possible genotoxic effect of this treatment.
Sorry for the slow response but this month consists of nothing but work and I finally have more than 1 day off in a row and am glad I can relax.
The article I read about the combination of DHA and uridine prevented and mitigated rotenone-induced striatal and enteric (in the gut) degeneration and formation of alpha synuclein in male mice. Here is the article:
Also, the study showed that rotenone, regardless if it was injected in the mice brain or injested in food, effected the non-rotenone targeted areas. If it was injected into the brain, then the enteric nervous system was negatively effected; if food was consumed contaminated with rotenone, then the brain was effected. The vagus nerve connects the brain & gut is the conduit for the spread of inflammatuon and alpha synuclein.
I have not taken uridune but I think the combination is a good investment. When I started to get sick after being exposed to pesticides....etc....I did something rather extreme - one night I ate fish oil like candy and it was the only time (during the prodromal stage) I felt any relief. I estimate I took approx 6,000 mg of fish oil (12 capsules) and it helped me to sleep, to feel less muscular stiffness, anxiety and depression. I have read that the max daily dose of fish oil is 7,100 mg/day and at that point a blood test is required because fish oil thins the blood (and fish oil shoild not be taken with blood thinners; this combo can, lead to intetnal bleeding.)
I have written that CoQ10 was my most helpful supplement but I have revised my opinion. When I started taking 1,200 mg/day of CoQ10 I was already taking at least 500+ mg/day of DHA/fish oil which was consumed at the same meal. Fish oil is a powerful neuroprotective fat and most CoQ10 is lipophilic (fat soluble) so the fish oil increased the absorption and effectiveness of the CoQ10.
What changed my mind about the importance of fish oil over CoQ10, or made them coequals, was I ran out of high potentcy fish oil and said I will purchase some whenever - I was really busy and thought nothing of it.. What happened? Slowly but surely I started to feel ill again and, if I continued not taking fish oil, my chest fasciculations would have recurred. I originally had chest tremors and they diminished when I tried taking tyrosine, and when the chest tremors subsided chest fasciculations/muscle twitches were exposed. My chest looked like a neurological pinball machine. When I first started taking CoQ10 the muscle twitching disappeared and the remaining (ad libitim) twitching is on my left shoulder...it just twitches... The only time twitching occurs anywhere else in my body is when I am severely sleep deprived.
Thus I make sure I take 2,700 mg/day (900 each meal) with 400mg on CoQ10 every meal.
As for taking uridine under the tongue, under normal circumstances I think it is a good idea but with PD it, along with DHA/fish oil, they both should target the intestines. Since there is evidence that the gut effects the brain and visa versa, by reducing inflammation in the enteric system/gut, you will be reducing inflammation in the brain.
That is my 2 cents and I hope everyone has a good holiday break.
Thanks very much Rich. I had NO idea that you took such large amounts of fish oil nor Q10. I remember your intersting experiences with Mucuna and the oil though! I think my take home thought from your post is just how much of these supplements need to be taken for effect. It must cost you such a lot of money. I’m relatively well paid but I know Mrs Jeeves would raise an eyebrow if my outlay went much above what I already spend! I thought that the role of Q10 had been discredited by science a year or so back? (As regards PD anyway). You obviously feel what you feel but I cut down in my Q10 after reading that conclusion (remember they had lots of PWP on 1200 for ages ?). Anyway, thanks for your advice 😊. One last question: what type of fish oil do you take ? Salmon? Generic? Krill? ........and how do you know that these large quantities aren’t bringing mercury etc into your system?
First, I too do not have a large bank account and I have tried cheap and expensive forms of Coq10 and found I react the same regardless of price so I purchase Coq10 when it is on sale from the local supermarket. The 'buy 1 get one free' special costs me 41 dollars a month for Coq10 and the above story is true for fish oil. My monthly supply of dish oil costs me 17 dollars....neither is going to bankrupt me.
As for trace elements of mercury in fish oil this is a risk I am willing to take because I take NAC - which chelates mercury:
The 400 mg capsule of Coq10 is actually quite good because it contains 400 mcg of piperine to help with its bioavailabity. It must be remembered that Coq10 is mostly manufactured in Japan because it was first discovered and produced in Japan.
As for its demise in PD studies (by the MJF Foundation) it must be mentioned that MJF ONLY tested the oxidized form of Coq10 called ubiquinine. They completely ignored ubiquinol and PQQ (which may help confer neurogenesis)..
....rather short sighted I must say. As we age, say at 40, the body has a more difficult time inter-converting ubiquinone into the reduced form of Coq10/ubiquinol (when needed) so this is a logical supplement to test. Actually, someone already has:
"CONCLUSIONS: This is the first report showing that ubiquinol-10 may significantly improve PD with wearing off, as judged by total UPDRS scores, and that ubiquinol-10 is safe and well tolerated."
100 mg/meal x 3 is considered high dose ubiquinol vs 400 mg/meal of ubiquinone
Also, another discounted supplement fot PD therapy is creatine:
"Results The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years."
But when you combine creatine and Coq10 it may be an effective way to slow cognitive impairment:
The effect of creatine and coenzyme q10 combination therapy on mild cognitive impairment in Parkinson's disease.
"CONCLUSIONS: Combination therapy with creatine and CoQ10 could delay the decline of cognitive function in PD-MCI patients and could lower their plasma PL levels; therefore, this combination therapy may have a neuroprotective function."
This is interesting because caffeine is a purine (chemical category) like uric acid and both C & UA have a serious relationship with improving PD in men but is more ambiguous with women.
UA - men:
"There was no association between urate levels and Parkinson's disease risk in women, the study found."
St. Paul, Minn. – "Women who consume little or no caffeine, but who take hormone replacement therapy, may reduce their risk of developing Parkinson’s disease, according to a study published in the March 11 issue of Neurology, the scientific journal of the American Academy of Neurology. However, HRT may increase disease risk in women who drink the equivalent of more than five cups of coffee per day."
"Studies in women, which to date have not factored in use of hormone replacement therapy, have been contradictory and inconclusive. "
So ladies if you are on HRT dump the caffeine and you are now safe to use the creatine/Coq10 combo. Also you can save your money and skip taking inosine, a uric acid precirsor tested by the MJFF.
This information practically sets up a frame work for his/hers individualized therapy.
Rich. Thanks so much for a really generous post. Excellent and I really appreciate the time taken. You say you’re not fussy re. The quality of the Q10 but do you have a particular supplier as you mentioned Japan? Best wishes, Jeeves.
Hi Jeeves, did you continue with the uridine and did it have any effect? I just found the bottle I bought in the cupboard a while back and are deciding whether to try my husband on it.
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