Is levadopa also neuroprotective?
I think this is important question to me because I'm wondering what would be the difference in 20 years between a PwP taking only c/l for the 20 years and another PwP not taking anything for the 20 years... everything else between them remaining constant?
Thank you
Probably the opinions here will indicate the issue is unsettled. Defining "neuroprotective" in the common vernacular, I would say no, it is not.
The difference would not likely be in how much progression has occurred, but instead a better quality of life that would be afforded by replacing shrinking dopamine production.
The vast majority of PWP take levodopa, consider it essential, and are well served by it. I believe it has a life expectancy, albeit in each of us it's different, but I take as little as I can to stretch out its useful life.
PS. Taking levodopa over 20 years would in most cases allow for more exercise to be had and healthier lifestyle changes to occur, so the person who takes C/L would most likely be better off after 20 years, but not because levodopa did it directly.
Thank you for your brilliant reply. The one remaining issue though is that many PwP flap their hands in frustration while trying to manage or minimize the side effects while some few PwP have no side effects at all... So for the many who struggle with these side effects, is it bad enough to negate the positives?
Well I have to say that I think it's an unfair question because you'll probably tell me it varies from person to person and I should ask them individually 😆
There is almost nothing that every person can take that will cause no side effects in anybody, except perhaps water. We run the risk of side effects with every thing we put in our mouth including food, so it's a continuous weighing of the benefit versus the drawbacks.
Very true
While I have almost constant dyskinesia while I take c/l (I don’t take it at night), the alternative of severe bradykinesia and dystonia when I am completely off meds is so debilitating that living with the side effects, difficult though it is, is far better than without the meds.
Hi Juliegrace, I too have diphasic dyskinesia. I was wondering what started first for you...the peak dose or the diphasic? So sorry that you're having to deal with both.
TJ,
I’m really not sure which started first; I was so unfamiliar with it. It’s only as it goes on that we learn the ins and outs of what we experience with this disease.
Julie
Your last sentence interests me, MB, because both consultant and nurse have encouraged me to take a slightly higher dose even though I am doing reasonably well as I am, and happy with my dosage. I told the nurse I would rather continue with the current dose for as long as I felt it was effective. She told me that I should not think of 'saving it for a rainy day', but should get as much benefit as possible in the here and now. The implication was the opposite of what you say about stretching out it's useful life by taking as little as possible. I feel as you do- but it made me wonder!
There are 2 schools of thought on this. The one expressed by the nurse and those of us who believe taking as little as we can, stretches out the useful life. I'd rather have it useful later on when I will need it more than I do now .
If, for example, Sinemet has a useful life of 5 years and you did not take any at all until the beginning of year 6, it would be beneficial to you for the years 6 through 10, when you can expect to be worse off than you were during years 1 through 5.
Thank you for the info
Susan
I changed my reply immediately above.
This topic is so important that it deserves a post all on its own.
The Big question everyone wants to know is, are there any long term benefits in minimising medication, and accepting some wearing off/ down time, or should we just maximise the drugs and get as much relief as possible? After all these years, there should be a settled consensus, but I’ve not read it.
It's very frustrating, yes. I tend to think people dx over 65 (or thereabouts) should just get stuck in, since there's a greater chance they'll pass away from something else before they get to enjoy it if they don't. Younger than that? Much harder to assess, right?
Thanks MBA.
It's my understanding that waiting to start levodopa DOESN'T mean that you are saving or prolonging the years that it will be effective. However, I DO think it's a good idea to take as low a dose as is effective.
When I looked into this question closely a couple of years ago, I found some pretty convincing research saying that people who postponed taking levodopa had a shorter honeymoon period of the drug being effective.
Basically, I think the underlying neurodegeneration continues, and that will make levodopa less effective even if you haven't started taking it.
(I say this as someone who is 4 years in and who still hasn't started taking levodopa regularly.)
Elliott,
It's a tricky question.
If on a scale of 1 to 10, a person who is diagnosed one year ago and has a tremor rating of 1 and takes a 25/100, it might well reduce their tremor to near nothing, whereas a person taking the same dose who is diagnosed 6 years ago and has a tremor rating of 5 might not feel the same benefit because while that dose would replace the same amount of dopamine, and would reduce their tremor the same amount, i.e., from a 5 to a 4, it would feel less effective because there remains as pretty significant tremor.
Or, if taking 4 Sinemet/day causes its useful life expectancy to be 5 years, does taking 1 Sinemet/stay extend its useful life? Intuitively, it seems like it would.
What do you think?
marc
Seems reasonable. I don't think I have much to add beyond what I've already said. I am personally prone to be leery of levodopa, and would tend to take a lower dose, both to mitigate possible adverse effects, and also to prolong beneficial effects.
That's the way I feel and that's what I'm doing, too.
I agree with Marc. No evidence of neuroprotection but if you take advantage of the ability to exercise and improve quality of life, that probably is neuroprotective
Hi Grumpy. Good afternoon.
Enjoy these studies which will attempt to answer your question. Start with the “Gold Standard” study called Elldopa. This study was done a long time ago, but it is fascinating how little has changed in terms of administration and disease progression measurement. It’s like driving a 1960’s Cadillac😁
And we are in 2020!
Next, read the LEAP study which is the most recent.
Hint: Don't get your hopes too high up.
Here they are:
jamanetwork.com/journals/ja...
link.springer.com/content/p...
citeseerx.ist.psu.edu/viewd...
pubmed.ncbi.nlm.nih.gov/306...
parkinsons.va.gov/Consortiu...
Hello pdpatient, many thanks for the links 👍🏼, they look promising to be very informative and educative.
The older studies are probably the better ones because they were done in the "age of innocence", before these studies became politicised, thank you
Grumpy, what makes you think that the studies these days are politicized. I thought that it was only after Trump stumbled upon the scene that the credibility of the medical establishment (along with other institutions as well) came into question.
Apart from the politics involving those governing a country, there is also the politics of powerful entities and their manipulative actions to accumulate more wealth and power
(So in this context, I'm referring to politics as defined in the second of these two online dictionary definitions of politics
1. The activities associated with the governance of a country or area, especially the debate between parties having power.
2. Activities aimed at improving someone's status or increasing power within an organization)
Even before the Trump's drama with hydroxychloroquine, it's been well known that drugs clinical trials are conducted with blatant conflict of interest... due to the fact that most of these trials are sponsored directly (or indirectly) by the big pharma themselves OR by companies and individuals that fund research projects... funding only continues if results are favourable... so results have to come up in their favour
And the main motives are well known- big pharma don't make money and hence loose their massive revenue source to cover their huge investments if cheaper alternative healing medications are discovered. So for the sake of progress we have to experiment with various supplements ourselves 😁
Whenever we get tempted to think, 'if it's good for a mouse, it's good for me," from the VA report;
"Mouse substantia is not nigra – not pigmented
• Presumably equal expression of α-synuclein does not
lead to aggregation/ neuronal demise in mice as it does
in humans
• Mouse lifespan much shorter – most studies ignore the
seemingly essential effects of aging
• A53T α-synuclein mutation in humans is the normal
sequence in a mouse."
"Conclusions
• We have no proven neuroprotective therapies in
Parkinson‟s disease
• We may not get them unless:
– We develop a better understanding of the
pathophysiology of PD
– We develop better animal models
– We develop better biomarkers of progression
– We develop better trial designs"
Hello MBA,
This is a bit off topic... I wanna ask about your PD progress after your FUS PTT procedure, along the line if any my assumptions is wrong please correct me
The last time I checked your profile you mentioned a combination of regressions and improvements with a net improvement of 65% overall, is this level of improvement in all areas still the same OR have things changed for better or for worse?
You also mentioned that the procedure was on your left side... was this your bad side before the PTT procedure?
I asked because I also read (probably on your profile) that you tremor uncontrollably on your right hand after the PTT procedure... was your right side like that before the procedure? If not could it be that improvement in your left side after the PTT procedure made your side right much worse than what it was before the procedure?
Overall, has been continued regression or continued improvement after the procedure?
So far, in your opinion do you feel the PTT procedure is good value for money or do you think that the jury is still out on it?
Many thanks
Hi Grumpy,
The only change since my last report is that the tremor in my right hand has worsened. No, my right hand tremor was not this bad before the procedure. It could be that the improvement in my left side made my right side worse because of some "work around" tricks the brain is capable of, but we cannot know that. I'm treating it as though the progression in my right hand tremor is continuing.
My tremor started in my left hand, so they did the right side of my brain believing that it was controlling the progression.
I do not feel there has been any further regression. My jaw tremor is a little worse than pre-op, but only in bed at night when trying to go to sleep.
I was progressing very slowly before the procedure. Except for my right hand tremor, I do not feel I have progressed since the procedure. I still consider myself to be 65% better off then I was pre-op.
Just this week, Dr. J re-confirmed he would reserve time during the week of March 8, 2021 to do the other (left) side, which I am greatly relieved to hear.
To me, I consider it a no-brainer (pun intended) to be a value worth the money. In my opinion, the jury is in. I fully expect that when I have the other side done, I will be 90% restored to pre-diagnosis condition.
marc
I've no trouble believing your success or the other success stories from Dr J's practice. But the whole 'the side where it starts controls the progression' thing sounds like something of a rationalisation to me, or a bit of a punt. Is this documented in research anywhere, or is just his personal view?
Chris,
the only documentation I know of is in the paper he published which reviewed the outcome of 51 patients. I'll go get it post it as a PS under this comment.
I had never read that either, but he/they were pretty unequivocal about it.
PS. Here it is. I don't remember if it addresses that issue. I will reread it, too.
Good to hear the success is maintained, are you thinking of reducing your c/l to nought sometimes in the future after your right side is done?
I will try and if I can eliminate Sinemet, I will.
No PD drugs have been proven to be neuroprotective.
Like MBAnderson says, it's complicated.
Levodopa is in itself is unlikely to be neuroprotective.In fact, dopamine can be oxidized into metabolites which are toxic oxidants. There was one study with mice which has been genetically altered to have a condition like PD. They were fine until they were dosed with levodopa, then they showed nerve cell damage. However, mice are not humans. How does it work in humans?
For years, some people were concerned about levodopa causing nerve damage. However, there have been studies which have results which DON'T show faster nerve damage in people who take levodopa. This is the current medical orthodoxy.
Nevertheless, I know of one study by a team of Russian scientists whom I trust which DID find increased oxidation of proteins and fats in PD patients who took levodopa as compared to those who didn't.
You also have to be wary of potential b6 deficiency along with elevated homocysteine with levadopa, increasing oxidative stress, elevated toxic burden, and faster progression of PD through compromised transulfuration metabolic pathway. Degraded homocysteine recycling and alterations in cystathionine beta synthase enzyme functions are what probably contributes to PD in the first place.
Levodopa is not neuroprotective.
In the wrong quantities (as in the most of common anti-PD meds) is a toxic and highly addictive drug. I would not define cocain a neuroprotective drug.
See this links for more info:
Drugs Aging. 2013 Aug;30(8):587-92. doi: 10.1007/s40266-013-0090-z.
Dopamine agonist withdrawal syndrome: implications for patient care.
ncbi.nlm.nih.gov/pubmed/236...
The severity and prognosis of DAWS is highly variable. While some patients have transient symptoms and make a full recovery, others have a protracted withdrawal syndrome lasting for months to years, and therefore may be unwilling or unable to discontinue DA therapy
Parkinsonism Relat Disord. 2003 Jan;9(3):175-8.
Neuroleptic malignant syndrome-like, or--dopaminergic malignant syndrome--due to levodopa therapy withdrawal. Clinical features in 11 patients.
ncbi.nlm.nih.gov/pubmed/125...
Rev Neurol (Paris). 1990;146(3):215-8.
[Neuroleptic malignant-like syndrome following levodopa withdrawal].
ncbi.nlm.nih.gov/pubmed/218...
Parkinsonism Relat Disord. 2003 Apr;9 Suppl 1:S3-9.
Malignant syndrome in Parkinson's disease: concept and review of the literature.
ncbi.nlm.nih.gov/pubmed/127...
I ‘m not sure of your point somic. To say Levadopa is not neuroprotective has no connection with dopamina agonist withdrawal syndrome. Nor with neuroleptic malignant syndrome.
There is a connection between LD and DAWS or NMS, known since 1988 (at least).
What causes these two huge (potentially letal) issues can not be considered neuro-protective, IMHO.
Rev Neurol (Paris). 1990;146(3):215-8.
[Neuroleptic malignant-like syndrome following levodopa withdrawal].
ncbi.nlm.nih.gov/pubmed/218...
Ital J Neurol Sci. 1992 Mar;13(2):169-70.
Apomorphine in malignant syndrome due to levodopa withdrawal.
ncbi.nlm.nih.gov/pubmed/159...
Clin Neuropharmacol. 1988 Jun;11(3):278-81.
Successful treatment of levodopa-induced myoclonus and levodopa withdrawal-induced neuroleptic malignant syndrome. A case report.
Hirschorn KA1, Greenberg HS.
ncbi.nlm.nih.gov/pubmed/340...
Actually, the two issues can be separated.
As a comparison:
Nicotine is addictive. Cigarettes are toxic and can cause all sorts of serious health problems. Nevertheless, nicotine may be a neuroprotective agent.
ncbi.nlm.nih.gov/pmc/articl...
I'm grateful for all your links, but it is plausible that levodopa could be addictive and associated with a sometimes deadly withdrawal syndrome AND be neuroprotective.
The evidence suggests that it ISN'T neuroprotective, but we only know that because researchers have looked at the two questions separately.
Somic
To add to EG
There is a difference between DAWS which is quite newly described and relates exclusively to withdrawal of a dopamine agonist such as pramipexole , But not to levadopa, and neuroleptic malignant syndome which relates to a variety of neuroleptic drugs including levadopa but not exclusively.
In the link I attached it is written clearly withdrawal and neuroleptic syndrome following levodopa withdrawal.
So whatever is the syndrome it is due to levodopa withdrawal.
In addition 3-OMD (Three-Oxi-methildopa) is the principal metabolite of levodopa after its conversion to dopamine. It is toxic for neuron
>>>>>>
Recent studies[3] suggest that 3-OMD has some effects on the chronic treatment of L-DOPA. There are some evidences about it:
Higher levels of dyskinesia.
L-DOPA related motor dysfunction.
Inhibition of striatal uptake of tyrosine.
Competition with L-DOPA for the blood–brain barrier transporter system.
Inhibition of dopamine release.
In relation to levodopa[edit]
The most common and important treatment for Parkinson's disease is L-DOPA, used in all patients at any time of the disease evolution. It produces a decrease in symptoms of the disease. In fact, almost all patients that are treated with this drug show a considerable improvement. However, there is a controversy of whether L-DOPA and 3-OMD may be toxic.
Some studies[1] have proposed that 3-OMD increases homocysteine levels, and this amino acid induces cardiovascular disease and neuronal damage. Some other toxic effects could be oxidative DNA damage which can cause cell death, a decrease in locomotor activities and diminishment in mitochondrial membrane potential.
Neurochem Res. 2008 Mar;33(3):401-11. Epub 2007 Aug 24.
The role of 3-O-methyldopa in the side effects of L-dopa.
Abstract
Long-term treatment of L-dopa for Parkinson's disease (PD) patients mood induces adverse effects, including dyskinesia, on-off and wearing-off symptoms. However, the cause of these side effects has not been established to date. In the present study, therefore, 3-O-methyldopa (3-OMD), which is a major metabolite of L-dopa, was tested to determine whether it plays a role in the aforementioned adverse effects. The effects of 3-OMD on the dopaminergic nervous system in the brain were investigated, by examining behavioral, biochemical, and cellular changes in male Sprague-Dawley rats and catecholamine-producing PC12 neuronal cells. The results revealed that the intracerebroventricular (icv) injection of 1 micromol of 3-OMD impaired locomotor activities by decreasing movement time (MT), total distance (TD), and the number of movement (NM) by 70, 74 and 61%, respectively. The biochemical analysis results showed that a single administration of 1 micromole of 3-OMD decreased the dopamine turnover rate (DOPAC/DA) by 40.0% in the rat striatum. 3-OMD inhibited dopamine transporter and uptake in rat brain striatal membranes and PC12 cells. The subacute administration of 3-OMD (5 days, icv) also significantly impaired the locomotor activities and catecholamine levels. 3-OMD induced cytotoxic effects via oxidative stress and decreased mitochondrial membrane potential in PC12 cells, indicating that 3-OMD can damage neuronal cells. Furthermore, 3-OMD potentiated L-dopa toxicity and these toxic effects induced by both 3-OMD and L-dopa were blocked by vitamin E (alpha-tocopherol) in PC12 cells, indicating that 3-OMD may increase the toxic effects of L-dopa to some extent by oxidative stress. Therefore, the present study reveals that 3-OMD accumulation from long-term L-dopa treatment may be involved in the adverse effects of L-dopa therapy. Moreover, L-dopa treatment might accelerate the progression of PD, at least in part, by 3-OMD.
ncbi.nlm.nih.gov/pubmed/177...
Biol Pharm Bull. 2012;35(8):1244-8.
Effects of 3-O-methyldopa, L-3,4-dihydroxyphenylalanine metabolite, on locomotor activity and dopamine turnover in rats.
Abstract
It has been well known that 3-O-methyldopa (3-OMD) is a metabolite of L-3,4-dihydroxyphenylalanine (L-DOPA) formed by catechol O-methyltransferase (COMT), and 3-OMD blood level often reaches higher than physiological level in Parkinson's disease (PD) patients receiving long term L-DOPA therapy. However, the physiological role of 3-OMD has not been well understood. Therefore, in order to clarify the effects of 3-OMD on physiological function, we examined the behavioral alteration in rats based on locomotor activity, and measured dopamine (DA) and its metabolites levels in rats at the same time after 3-OMD subchronic administration. The study results showed that repeated administrations of 3-OMD increased its blood and the striatum tissue levels in those rats, and decreased locomotor activity in a dose dependent manner. Although 3-OMD subchronic administration showed no significant change in DA level in the striatum, DA metabolite levels, such as 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), and homovanillic acid (HVA) were significantly decreased. After 3-OMD washout period (7 d), locomotor activity and DA turnover in those rats returned to normal levels. Furthermore, locomotor activity and DA turnover decreased by 3-OMD administration were recovered to normal level by acute L-DOPA administration. These results suggested that 3-OMD affect to locomotor activity via DA neuron system. In conclusion, 3-OMD itself may have a disadvantage in PD patients receiving L-DOPA therapy.
ncbi.nlm.nih.gov/pubmed/228...
Clearly you do not know the difference between DAWS and NMS and insist they are the same. I refer you to your link above
pubmed.ncbi.nlm.nih.gov/236...
Dopamine agonist withdrawal syndrome: implications for patient care
Dopamine agonists are NOT levadopa therapy
I agree with you: L/C is not Dopamine Agonist and DAWS is not NMS and I don't think I wrote it somewhere
What I'm saying is that, according to the docs provided in the links, it seems that an unpleasant DWA (Drug Withdrawal Syndrome - as ansia, insomnia, depression, allucinations, panic attack, etc etc) and also NMS as can occur in PD patients while doing a Levodopa cold turkey suspension.
But why would any PwP want stop levadopa cold turkey if they are getting symptomatic benefits from it (albeit with some minimal side effects)?
Sure, and I STILL don't see what this has to do with whether levodopa is neuroprotective or not. 
because in the long run it becomes less and less effective and side effects stronger and stronger (what is called end of honey moon) and someone suggests to perform a Drug Holiday to re-establish efficacy
your information is up for debate.
Drug holidays went out 20years or more ago.
I know. They were too cheap and effective for the patient.
I'm doing periodically it and i can say it works.
Remove can be counter-inuitive but is worth to give it a try in case of long term terapy
Really sonic, too cheap and effective? I dont know what you mean by effective and I have never heard this before. I believe they were unnecessary and caused undue trauma to the pwp. If you have no side effects from withdrawal i believe you must be early stage PD.
quote "I dont know what you mean by effective and I have never heard this before." never heard what? that they were effective?
I did it (had to) last year but had to stop it after 24 hours due to heavy withdrawal symptoms. i followed a special procedure with overload of Sodium Ascorbate and vit B but don't know how much it was usefull.
Nevertheless these 24 hours were effective because my autonomous system (neuro-vegetative) was reset (this was what the real scope of the wash-out).
The first dose after the wash out was half of my std dose before and lasted 4 times longer (but sleeping therefore lets say 2 times). This improvement was progressively lost in two weeks until approx half of the previous dose.
This is not necessarily happening to PwP able to resist more days.
Pls note that a research states in 2 weeks the time needed to clean up the body from PD meds and their effects on human body
I was diagnosed 12 years ago, but first subtle signs started 25 years ago. Not a veteran but at least a Senior .... 
When you noticed the first subtle symptoms 25 years ago, why didn't that prompt you to see a doctor? Why did you have to wait another 13 years, especially knowing those remained and were getting worse during those 13 years?
Or did you misdiagnosed the symptoms to be something else?
i now thing (know) they were the first symptoms but at that time none would have never thought to PD. I was 25 and looking an healty and atletic young man. The finer movements started to fail or become progressively more and more awkward and slower and less easy to do as I wanted.
Outside it was not visible and internally the perception was very light and not clear; stress, mood, sleep, time and fatigue were impacting very much. It was a very light internal sensation and it was easy to think about other reasons. Progression was very very slow.
I remember very well i had a PC game to play with the mouse (a point and shot with a gunslinger on video that became less easy to win). The right hand was the first to show the first clear signs and get worst 10 years later. Turning spagetti (i'm italian 
) with the fork became slightly and slowing slower and less automatic At the age of 25 I was having a very beautiful writing and progresivey the numbers 5 and 8 became less simmetric and more scribled. It was graduation time and i was working very hard so it was easy to think to stress and fatigue. Spending hours working on the PC initiated to cause soreness of the neck muscles.
some muscles started to be sore after a 30' walk (lower back pain after 30 minutes standing up or walking). I repeat that it was easy to think about fatigue, stress and age.
To be honest also my miopia may be originated by the disease. At the end it is a loss of very fine muscle control... a neurological issue.
The first symptom I had I think was the soreness of the lower back muscles standing up or walking. I can remember that during a class trip i was the only often stretching the back to get some relief (i was 19 and i was swimming 2 hours x day 5 days x week)
The point and shot PC game mouse was the second sign (at the age of 25) but in the normal use i was feeling all right.
Hope this helps.
Interesting. By effective i meant i had never heard of drug holidays being stopped because they were too cheap and effective.
Some questions if you don't mind.
Why was it necessary to do a washout.
Who recommended it?
How did you know your autonomous nervous system was reset?.
What drugs were you withdrawing from and what were the heavy withdrawal symptoms?
What is the research you refer to that shows you need 2 weeks to clean the body of pd meds?
Thankyou.
.
I had read about “drug holidays” awhile ago. Here is one source:
sorry for this late answer.
1. my autonomous system was ... no more autonomous (neurovegetative dysautonomia) because of meds overload due to an interactions with supplements and night use of L/C to sleep.
2. my neuro
3. L/C meds returned to work again (I was living a paradox effect of L/C meds: they were working the oppposite way (blocking and stiffnessing instead then making me move and relax muscles) - it has been a nightmare which I do not wish to anyone
4. L/C mixed with mucuna with 15% LD
my symptoms: ansia, irregular breath (short and frequent), tachicardia, sweatting, dyscinesia while off, rigidity, tremendus insomnia (66 hours without sleeping) and at the end of the wash out i was laying on the bed unable to move a finger
5. try this link: "Mov Disord. 2000 May;15(3):485-9.
Time course of loss of clinical benefit following withdrawal of levodopa/carbidopa and bromocriptine in early Parkinson' s disease.
ncbi.nlm.nih.gov/pubmed/108...
a wash-out of at least 2 weeks is required to eliminate the symptomatic effects of levodopa/carbidopa and bromocriptine in patients with early Parkinson's disease
"
hope this replies to your questions.
rgds,
sorry for this late answer.
1. my autonomous system was ... no more autonomous (neurovegetative dysautonomia) because of meds overload due to an interactions with supplements and night use of L/C to sleep.
2. my neuro
3. L/C meds returned to work again (I was living a paradox effect of L/C meds: they were working the oppposite way (blocking and stiffnessing instead then making me move and relax muscles) - it has been a nightmare which I do not wish to anyone
4. L/C mixed with mucuna with 15% LD and jumex (selegiline)
my symptoms: ansia, irregular breath (short and frequent), tachicardia, sweatting, dyscinesia while off, rigidity, tremendus insomnia (66 hours without sleeping) and at the end of the wash out i was laying on the bed unable to move a finger
5. try this link: "Mov Disord. 2000 May;15(3):485-9.
Time course of loss of clinical benefit following withdrawal of levodopa/carbidopa and bromocriptine in early Parkinson' s disease.
ncbi.nlm.nih.gov/pubmed/108...
a wash-out of at least 2 weeks is required to eliminate the symptomatic effects of levodopa/carbidopa and bromocriptine in patients with early Parkinson's disease"
i hope too have replied to your questions.
rgds,
In days past patients were sometimes hospitalized for two week "drug holidays.” But that was when the medical community was not ruled by profit.
yes, my neuro remembers this at the beginning of his career. they had to stop because not profittable for the hospitals. now they would not have the resources in terms of competence to manage this cases.
drug holiday (or wash out) is done only when strictly necessary at patient home with assistance by relatives
Julie,
Thanks for the link above. It is to a study done over 35 years ago! There is Another study also 35 years old headed
Reappraisal of temporary levodopa withdrawal ("drug holiday") in Parkinson's disease
“transient withdrawal of therapy has been advocated as a method of dealing with the complications of long-term use of levodopa in the treatment of Parkinson's disease. We retrospectively examined the effect of a 10-day period of levodopa withdrawal, or "drug holiday," in 28 patients”...... the conclusion is
“this investigation indicates that a drug holiday carries some risk and does not improve the efficacy of levodopa therapy or prevent the problems that occur with long-term administration.”
I see absolutely no link to the profit motive being the reason drug holidays are no longer advocated. The reason is they dont work.
Hi Grumpy - check out this commentary in the journal Brain, hot off the press
academic.oup.com/brain/arti...
It seems that levodopa has more tricks up its sleeve than we thought.
It's interesting to see that there is a positive Long Duration Response to levodopa, in addition to a Short Duration Response.
Here's the scientific article that that editorial refers to.
academic.oup.com/brain/arti...
ElliotGreen,
An interview with the authors of easier understanding.
parkinson.it/interviste/ris...
When research is funded by foundations based on donations from PwPs people, the music changes a bit.
My neurologist told me that if the synapses don’t get enough dopamine they just pack up, so when you take it it does nothing and you get no relief. He said they should be ‘swimming in dopamine’.
Consequently I have taken the lowest dose I can manage with since diagnosis, and so far still work and play tennis etc with no one knowing I have PD.
Hi Grumpy77
I've another comment on this post.
l-dopa, the natural equivalent of levodopa, is a transition element between TYR and DP.
TYR is transformed in l-dopa by a feed-back process and then immediately in DP by a uncontrolled process.
this fast and uncontrolled transformation make me think that it is not used for any other purpose by the neurons or the brain.
For this reason too, I don't think it may have any neuroprotecting role or property (like glutathione for example)
it is just a thought ...
i would think if it was an NP it would be shown to slow down progression. IMO Cheers.
Hi Grumpy,
Neuroprotective from what, if we do not know the cause of PD?
Below is the only known cause of PD or rather the one that comes closest to the cause.
(Click on US flag in the top right corner for translation)
parkinson.it/nuove-scoperte....
Here is why MJF is investing on this.
IMHO An excess of unused levodopa spinning in the brain cannot be neuroprotective.
I agree with Astra7, use just enough.
. There used to be an attitude of conserving levadopa to a later stage. This view is no longer held by many neurologists. See following article.
Hikoi, my tax money well spent ... and I quote from your article :
”Acknowledgments
Long-term Levodopa / Benserazide 200 + 50 mg supplies were donated by the 'Grigioni Foundation for Parkinson's Disease' to all patients with Parkinsonism attending the three Ghanaian clinics since December 2008. During the 2010–12 period, levodopa supplies were funded by the 'Lombardia Region', Italy. Funding sources had no role in the writing or any decision about the manuscript.”
Selegiline is Neuroprotective 
HYPERHOMOCYSTEINEMIA AND ITS TREATMENT IN PATIENTS WITH PARKINSON’S DISEASE 2016 (Treat it with folic acid?)
Levadopa
15years taking Ibuprofen, Parkinson's has plateaued!
