Long term use of large doses of ldopa. Any risks?

Kinda following on from my previous post about high concentration ldopa supplements.

Several forum members - off the top of my head Strevenmast, ErnieDiaz, Cons10 (sorry if I got any of those wrong) - have reported good short (good symptom relief) and medium (for at least a year or more, and no nasty SE like sudden death or anything) term results from using high concentration ldopa supplements (Like the 99% product from nutravita).

My question, and it is a sincere question rather than an attempt to be provocative, is:

Is there any known or suspected additional risk associated with these doses (2 or 3 grams a day) over and above the ldopa that would be required if they were obtaining equivalent relief from CL?

(Let's assume for a moment that CL works for them as well as ldopa supplement).

As a consequence of there being no Carbidopa or benzaseride involved, the ldopa doses are a lot higher in the supplement case than the prescription med case.

I imagine that, for a given relief level, the same amount of ldopa is hitting the relevant area of the brain. Is that correct?

If that is correct, is the excess ldopa in the 3 gram scenario just being filtered off by the digestive system?

Or is there a risk (that we can conceive of) that the excess ldopa may cause some long term damage?

This is well in excess of my knowledge level and may veer into contentious LID territory (depending on which ldopa induced motor complication tjeory you subscribe to).

Any opinions welcome.

(I know there are some theories around the long term risks of Carbidopa use. I'm not really asking about that as it will cloud the issue here to the point where there are too many unknowns for me to think about this effectively)

[Gioc]

I was wondering what is your current protocol for Pd symptoms?

[WinnieThePoo]

My understanding is that the issue with levadopa as a long term problem, is to do with the levels of dopamine supplementation reached by that time, rather than the duration of prior supplementation

Diskinesia is the main one, and it manifests as a problem with cell grafts, both fetal and stem cell, as well as in high dose dopamine supplementation . That can be a combination effect as my Dad experiences. If he is overdosed and gets dyskinesia, reducing EITHER his Sinemet or his Rotogadine patch strength, fixes the problem.

Clearly there's no levadopa in the Rotogadine patch, so the levadopa per se is not the issue -its the dopamine level / dopamine activation that causes the side effect

The main issue with high dosage levadopa is going to be nausea - it's what was so exciting about Sinemet - and where it got its name (Sin="without" Emet="throwing up"). Someone like my Dad on 200/50 QDS would need 4 gm a day. Many people would feel really sick on that. Sinemet allowed the same level of dopamine to the brain with 1/5th the amount of levadopa

Of course, green tea might also do the trick

[Hidden in reply to WinnieThePoo]

Thanks for that. I hadn't previously thought about non Ldopa dopamine drivers causing dyskenisia.

Re the nausea, you would think so but the locals here that go down that path don't seem to have an issue. Probably varies considerably by patient.

[WinnieThePoo in reply to Hidden]

I might experiment but 1gm Ldopa 4 times a day would be 4x17 of my Dopa Mucuna capsules. That's a lot of swallowing

To be fair, I shouldn't need that much but even 3x8 (equivalent to 100/25 TDS) is a pot every 4 days

[KERRINGTON in reply to Hidden]

I'm taking about 16 Dopa Mucuna capsules ( approx 1 gm Ldopa)daily over 12 hrs. Never have had nausea, infact, nothing makes me nauseous...and I've used lots of different mucuna brands...very strange. I'm still not feeling that great, thinking of tweaking it up.

[SilentEchoes in reply to KERRINGTON]

Would it make sense to buy in bulk and use a scale to measure the dose? I can't swallow pills anymore and opening capsules is a PITA so I try to find bulk supplements. Would like to know a source if anyone has one.

SE

[KERRINGTON in reply to SilentEchoes]

I can't swallow pills either, and have taken to throwing them on my food and chewing with whatever I'm eating, unless it's mucuna, or B1.

As far as mucuna, what % extract are you looking for ?

[Isthistheone in reply to WinnieThePoo]

Hi Winnie. When i first started taking Sinemet I would get extremely sick to my stomach within 15 minutes. Two Neuros and two years later a young neurologist prescribed Sinemet ODT (Oral Dissolving Tablet) . I never had an upset stomach again.

[WinnieThePoo]

"If that is correct, is the excess ldopa in the 3 gram scenario just being filtered off by the digestive system? "

Sort of. Close enough for Jazz. Levodopa is converted to dopamine via the action of a naturally occurring enzyme called DOPA decarboxylase. This occurs both in the peripheral circulation and in the central nervous system after levodopa has crossed the blood brain barrier.

So the levadopa not reaching the brain is converted into dopamine by the DOPA decarboxylase in the peripheral circulation. It's that dopamine in the bloodstream causes the nausea

[Hidden in reply to WinnieThePoo]

Very good. Thanks. Does the 30% 'bioavailability' figure (per wikipedia) represent the brain bit?

[WinnieThePoo in reply to Hidden]

No. Bioavailability represents the blood bit. Of that maybe 20% makes it to the brain ordinarily

[Erniediaz1018]

Are you asking for clinical study results? It seems we will have to wait and see.

[Hidden in reply to Erniediaz1018]

WTP has probably helped refine the question a bit.

If we assume that 30% of the ldopa you ingest makes its way into rhe bloodstream, and then 20% of that gets to the brain, then:

- presumably the 70% that doesn't even get to the blood is nothing to worry about from a long term perspective?

- does the 80% of the 30% have the potential to cause long term issues?

My gut feeling is that it's probably totally fine and that the peripheral circulation dopamine ,(as WTP described) is of no significance other than potential short term discomfort, but I dunno.

[Erniediaz1018 in reply to Hidden]

Same answer, we will have to wait and see just like the doctors and pharma producers do. It’s not like the body is going to have to get rid of more foreign waste than it does with pharmaceuticals so I think I’m making a profitable decision considering the outcome awaiting me on the alternative treatment. I hope you understand my thinking 🧐

[Erniediaz1018]

It’s a very good thought provoking question 🙋‍♂️. By the way I didn’t use any mucuna for the past three days and experienced no withdrawals (as far as it being addictive I don’t believe it). The Parkinson’s I am experiencing is tremor dominant on the right arm and I must confess your inquiry couldn’t have come at a better time, because while off the mucuna the tremor episodes were less severe. I’m thinking taking time off from levodopa wether natural or not will be beneficial.

[Rosenmu in reply to Erniediaz1018]

I took 5 days off, only using essential oils, and no tremor. I did have slight drool issue and none of that on mucuna, so I'm using both now, I'm on a fairly low dose of mucuna.

[NRyan in reply to Rosenmu]

which essential oils and how do you utilize them?

[Rosenmu in reply to NRyan]

I started with Franincense and black spruce, then went to Frank, Cedarwood, black spruce, black pepper, vetiver, and ginger together in a small bottle, then a few drops on the back of the neck and temples. Only use high quality oils. They can also be inhaled and diffused. I chose oils high in sesquiterpenes that can cross the blood brain barrier and oxygenate the brain. I used them straight but lots of people cut them with a carrier oil.

[NRyan in reply to Rosenmu]

Thank you! I'm going to start this. Do you apply every day...how often?

[Rosenmu in reply to NRyan]

I started with 3 times a day then whenever I thot about it, maybe even 5 times a day.

[17Hillview in reply to Erniediaz1018]

That has also been my experience. But it only lasts a few days.

[rescuema]

Observe the result on the TABLE 2 of the below study.

Mucuna high dose resulted in minimal adverse events compared to Levodopa without DDCI and even Levodopa+DDCI with exponentially higher adverse events.

Interesting for sure.

ncbi.nlm.nih.gov/pmc/articl...

ncbi.nlm.nih.gov/pmc/articl...

[Cons10s]

Can you tell me what 1 gram of Mucuna measures in teaspoons? I don’t have a scale.

Mucuna albeit probably not the concentrated version has been used for thousands of years in India. I had read it’s Neuroprotective unlike Sinemet which is a Neurotoxin.

[Erniediaz1018 in reply to Cons10s]

Hi, buy this, it is essential. I own one which I use to weigh every capsule I take. I’m cutting back on the amount of levodopa from mucuna because Chris has a valid point he just seems to come across a bit biased.

Digital Milligram Pocket Scale 50 x 0.001g, Mini Jewelry Gold Lab Carat Powder Weigh Scales with Calibration Weights Tweezers, Weighing Pans, LCD Display amazon.com/dp/B07X1R442K/re...

[Cons10s in reply to Erniediaz1018]

Thanks Ernie, I’ll buy it.

[Juliegrace in reply to Cons10s]

I weighed a 1/4 tsp of the 100% nutrivita MP on my jeweler’s scale this morning. It weighed 586 mg.

[Cons10s in reply to Juliegrace]

Julie this is very helpful.

[Erniediaz1018 in reply to Cons10s]

The 1/8 teaspoon is what I started with because it gave me the best relief when I started experimenting with the nutrivita mucuna until I got the scale.