I know there are recent studies out there that say that L/C doesn't - that PD's progression does. So someone just diagnosed might as well start on L/C straight away, right? But does anyone really know? Are the studies funded by the drug companies somehow?
Asking for a recently diagnosed friend. I'm also interested in the consequences of overmedication. Are we damaging our brains by taking too much L-dopa? I'm looking for both opinions, experience, but mostly links to studies. Thanks!
Okay, I'll get the ball rolling. Here is a fairly recent post that should be relevant:
healthunlocked.com/parkinso...
Perfect! Thank you.
Some background on why I'm asking:
My friend Bob is newly diagnosed. He asked me what I knew about Rytary's side effects, since I've taken it for about 4 years. I had to admit that I hadn't really studied the issue, so I started looking around, and what I found shocked me a bit.
It seems that there is (or might be) a big downside to being overmedicated on any dopamine-enhancing drug, such as Rytary or Sinemet (possibly even "natural" L-dopa). I had just increased my Rytary intake and I was feeling really good! I realized I was feeling quite a bit too good, so I've cut back - down to where I was before. I've never seen the issue of overmedication pop up here, so I thought I'd bring it up.
Indications of being over-medicated: glassy-eyed, too confident (takes too many risks); generally acting "high". You get the picture. The theory is that if you're over-medicated, the dyskinesia may come on more quickly (eg at 3 years rather than 5 years).
One tip I'm passing onto Bob: many (most?) MDs (including neuros) will give a too-large initial dose, wait 2-4 weeks and if you seem relatively ok, they leave the dose at that. However, it's quite clear that it can take up to 10 weeks for the entire effect to manifest. The result is that many PWP get an initial dose that's too large and their MDs never adjust it accept upwards as time goes on (or so I've read).
"I've never seen the issue of overmedication pop up here, so I thought I'd bring it up."
Edit: Incorrect statement has been removed.
In the comments section of the following post, there was quite a bit said on this topic (i.e. overmedication):
" ... it can take up to 10 weeks for the entire effect to manifest."
Do you have a reference (link) for that? I've read about a levodopa long-duration response, which is said to occur after a delay of at least 2 weeks (and only in "early therapy").
In the linked article, the second paragraph talks about such a response, and the role of a protein called ΔFosB.
lybrate.com/medicine/syndop...
No, I can't say I do. I'm just remembering a guide put out by the manufacturer of Sinemet that said something about full effects at 10 weeks. Or maybe 2-3 months. I brought it to show my neurologist about 10 years ago just after being diagnosed. But now I can't find the reference. Does anyone else know what I'm talking about?
In my copy of the Madopar PI document (i.e. Prescribing Information), Roche describe a process for arriving at the correct dosage of levodopa. If I've understood it correctly, they say to keep increasing the dose in small steps until either the motor symptoms disappear, or dyskinesia appears. If it's the latter then back off a little.
Note that this process, as written, takes no account of any levodopa long-duration response. Thus the risk of over-medication, it seems to me, is very high.
That's what I was saying/wondering before. Does it suggest a time interval between adjustments?
Age-old question, indeed.
There are many discussions about this here.
I thank C/L causes dyskinesia in some people, but not others -- like all things Parkinson's.
There are comments on this forum from people who have gotten dyskinesia after a few months and even a few weeks on a minimal dose and there are people who have taken the same dose for years and not gotten dyskinesia.
A lot of people refer to the sub-Saharan African study which concludes that it is not the duration of CL therapy, but the dose. It's a big, authoritative study, but this is 1 of those issues where we can find studies that support either position.
PS. In a way, it doesn't matter what the studies conclude (unless there is a study whose results apply to every single person which doesn't ever happen.) What matters is if an individual gets dyskinesia, they may want to cut back on their dose.
MBA wrote: " ... the sub-Saharan African study which concludes that it is not the duration of CL therapy, but the dose."
In my view that should be "the dose relative to the condition of the PwP's dopamine neurons".
Many don't accept the results of the Ghana study, and believe that a strategy of undermedication will pay off in the long run.
Which brings us neatly to the issue of overmedication (which JAS9 wrote about in his first comment). The main concern in this situation is that levodopa could be disease modifying, but in a bad way!
Simon Stott has outlined his view on this in a 2017 blog post about Mucuna Pruriens (spoiler: he is concerned).
"The most potent drug available for Parkinson's disease, levodopa, treats symptoms of the disease but does nothing to either ease or increase its still-mysterious underlying causes, a new clinical trial has concluded."
'Good News, Bad News on Levodopa' - Jan. 23, 2019: usnews.com/news/health-news...
I suggest reading:
The Michael J. Fox Foundation for Parkinson's Research has more about myths surrounding levodopa.
There are studies that support both sides of this issue, too. I believe the executive directors and heads neurology departments at universities, hospitals, and Parkinson's organizations cannot take positions that can be easily refuted and their position, for the moment, is that levodopa doesn't speed up or slow down progression.
I agree with your well stated view.
What JAS9 (and Simon) are concerned about is that overmedication of levodopa could indeed speed up progression.
Yes, either progression of PD or causing / increasing dyskinesia, which may not be exactly the same thing. Or is it? Another question.
IIRC, Simon's concern is based on the observation that the lab mice given more levodopa experienced dyskinesia sooner.
But then they would, wouldn't they, even if they had the same number of dead neurons as the other group?
Jeffreyn,
The word," overmedicated" confuses the issue for me, because if, for example, a person on the minimum dose of Sinemet gets dyskinesia after 2 months, is that being overmedicated? Aren't we then saying that getting dyskinesia is by definition being overmedicated?
This issue of whether not levodopa accelerates progression is surely the most important issue/decision for us, isn't it?
So, what do we do with the major organizations positions that levodopa does not accelerate progression?
Marc
I believe that the position of the major organizations is premised on the (unstated?) assumption that the levodopa dosage has been determined according to a formal process/procedure. For example, the Roche process, as documented in their Madopar PI document, which seem so say to keep increasing the dose in small steps until either the motor symptoms disappear, or dyskinesia appears. If it's the latter then back off a little.
Actually, if it is the latter, you might be given a choice. In my case the Parkinson's nurse told me I could choose the precise dose, based on my preference for a little less tremor relief versus a little dyskinesia. I chose neither, but that's another story!
Overmedication is something else. I've never experienced it, but JAS9 describes it as "glassy-eyed, too confident (takes too many risks); generally acting "high". " Simon seems to be on the same wavelength, as he has used the term "feel good factor" in relation to overmedication.
It might be that overmedication can only be experienced by those who have enough dopamine neurons left. People like me would get dyskinesia first, and then quickly back off.
"... I choose neither." Does that mean you don't take levodopa therapy?
No, it doesn't mean that. What I did was halve the dose and took it twice as often.
Your post is timely, I have been looking into these questions myself. Below is a link to an independent study (not funded by big pharma) on the toxic effects of carbidopa. Parkinsonsclinics.com is a web site for the Hinz Protocol, which makes a strong case for carbidopa toxicity by Vit. B6 deactivation (and others dependent upon B6), and links this effect to an astronomical increase in the PD death rate over the past 30 some years. Dr. Hinz believes the cause of dyskinesia is a drug-induced nutritional deficiency. This is a serious potential side-effect, so why hasn't carbidopa/levodopa been taken off the market? Why can't patients get L-Dopa only pills?
I believe the driver is money. It's expensive to be sick - healthy people don't generate the kind of wealth sick people do. Before I got sick, I rarely went to the doctor. It's ridiculous how frequent of a customer I have become. I want off the mouse wheel! I'm going to give Dr. Hinz's protocol a try if he will take me on as his patient. I make a compelling case study if his protocol shows a measurable positive effect.
In another study relevant to research for my situation, it is stated: More than two million Americans are believed to suffer from some form of neurodegenerative movement disorder, the total cost of which is estimated to exceed $10 billion annually. Because no society on earth is spared the effects of these crippling diseases, the figures for other countries are similar, adjusted for population differences.
JAS9, I applaud you for being proactive and asking important questions.
SE
ncbi.nlm.nih.gov/pmc/articl...
parkinsonsclinics.com/index...
ncbi.nlm.nih.gov/pmc/articl...
Where to begin ...
Maybe just type "hinz" in the search box and press "enter".
Here is a good example of what you'll find:
healthunlocked.com/parkinso...
Thanks!
Thank you but no thanks. Tried that years ago and it didn't work for me. Good luck though.
Dyskinesia is caused specifically by too much levodopa in the brain. Normally patients take more and more levodopa medication as they progress, hence the thought that it causes dyskynesia. There is no cure for Pd and no Pd medication does anything to slow down the progression of Pd. The only way to do that is to do proper exercise. If you want to know more about that, at no cost to yourself then look at my website - reverseparkinsons.net and contact me.
Alternatively, I can tell you more about that, without you needing to leave this webpage.
The target you need to aim for is to exercise at a heart rate of 80% of HRmax (where HRmax is calculated as 220 minus your age) for 40 minutes, 3 times per week.
It's up to you what type of exercise you choose (e.g. cycling, treadmill, rowing, swimming, (fast) walking, etc. etc.).
Unfortunately I am unable to get my heart rate much above 100. I cannot physically move my legs any faster, but I walk at 7 ks an hour which is bloody good for an 84 year old. My resting rate is 52 to 56.
You amaze me John!!👍😊
Thanks Connie. I am not interested in amazing anybody but do appreciate your comment. I am ony interested in trying to get as many others as possible to start doing what is best for their Pd. I know it is not popular but popularity is not my best suit.
You continue to help many John! God bless you!
Thanks Connie
80% of HRmax is 109 for an 84 year old. The study I took my 80% figure from divided the PwPs into 2 groups. The 80 to 85 percent group had no disease progression, whereas the 60 to 65 percent group did have disease progression. So the target is actually somewhere between 65% and 80%. I say 80% just to be sure.
So do I make the 89 to 85 percent? What is the point? I never check my pulse rate because my goal is to walk as fast as I CAN. When I ma doing that I am producing the most GDNF possible, whic keeps my Pd at bay. That is my goal and it works 100%
You would be in the 80 to 85 percent range if your heart rate was 109 (or more). But what I was saying is that the target may not be as high as 80%, and this is because the researchers didn't use enough groups to get a precise result.
Your case actually supports the argument that the target is less than 80% (maybe 75%, maybe 70%, maybe even 66%).
PS. And the point? Well, if we have a heart-rate target to aim for, be it 70%, 75%, or 80% of our own HRmax, then we just need a heart-rate monitor to confirm that we are achieving that neuroprotection target. And we can all choose our own preferred form of aerobic exercise (fast walking for you, stationary cycling for me, maybe treadmill for someone else, ...).
Thanks!
I dont take any pd meds and i dont have dyskinesia. ive had pd for about 7 years. i do have tremors though.
Is this a side effect of c/l or what?
This helped me with the C/L absorbtion 
C/L to determine Parkinson's 
Does dissolving C/L under the tongue give faster ON?
What steps to titrate down c/l safely?
