Negative levodopa

[johntPM]

I first posted this on the Neurotalk forum in 2018. I make a few additions here.

Recently I heard the story of a women who controlled her dyskinesia by eating protein.

Levodopa induced dyskinesia normally occurs when levodopa levels are at their highest (typically between 30 minutes and 90 minutes after taking a dose). It stops naturally once levels have dropped below the dyskinesia threshold. But it would be useful is you could speed up the decline, thus reducing the amount of time dyskinetic.

It is thought that dietary proteins compete with levodopa to get into the blood and through the BBB.

Guebilla and Thiele write [1]:

"[Levodopa's] bioavailability is hindered by dietary amino acids, leading to fluctuations in the motor response particularly in late-stage (stage 3 and 4 on Hoehn and Yahr scale) patients. The routine dietary intervention consists of low-protein (<0.8 g/kg) diets or the redistribution of daily protein allowance to the last meal."

Following on from this you could eat protein containing food with the intention of slowing and reducing the absorption of levodopa. It is in this sense that dietary protein can be thought of as "negative levodopa".

Where might negative levodopa be useful:

- as we have seen, reducing levodopa induced dyskinesia;

- response to mistakenly taking a double dose - as soon as you find the mistake eat protein;

- smooth out the peaks in levodopa levels.

- possibly, by offering an escape route if levodopa levels get too high, it could allow a more aggressive dosing regimen.

I suspect that there is a wide variation in the amounts of proteins that is required for PwP to exhibit this effect.

Looking at possible other forms of negative levodopa, stress is very strong and fast acting. I find that when I'm faced with a stressful situation I can go from being "on" to being badly "off" in a few seconds. (I don't have dyskinesia, so I can't complete the test on myself.) As a treatment, if it works, it would mean creating a small amount of stress to reduce dopamine levels. Perhaps it could be something as simple as putting your fingers in a bowl of iced water.

I would appreciate some guidance as to the ethics of this approach.

I would not recommend experimenting with negative levodopa without your doctor's consent.

Reference:

[1] "Model-based dietary optimization for late-stage, levodopa-treated, Parkinson’s disease patients"

M. Guebila, I Thiele

npj Systems Biology and Applications, 2016

Model-based dietary optimization for late-stage, levodopa-treated, Parkinson?s disease patients | npj Systems Biology and Applications

John

[Smittybear7]

Thanks for the information. I'm very confused about protein. When are you supposed to get the protein you need? Thanks for your help.

[johntPM in reply to Smittybear7]

First make sure that you are affected by protein in the diet. Many PwP aren't. If you are, APDA advise PwP:

"separate levodopa from food intake and take their medication doses either 30 minutes before or 1-2 hours after a meal. But this advice is not easily followed for a whole host of reasons ... "

The article then goes on to look at some more complex cases.

apdaparkinson.org/article/l...

[LAJ12345]

if you are taking the protein to alleviate the symptoms of too much levodopa wouldn’t it be better to just take less? Except in accidental overdose cases.

[chartist]

Assuming that you are taking the appropriate dose of levodopa in the first place, wouldn't it be easier to reduce available levodopa with incremental use of small amounts of iron or B6 as the amounts and timing are easier to control than protein intake? B6 is absorbed quickly and does not readily build up. Another consideration would be a delayed or timed release levodopa product.

Art

[bradykin]

Thanks john for the excellent post.

I have successfully used "negative levodopa" to stop dyskinesias.

I take 4 doses of c/l per day and was experiencing peak dose dyskinesias after the fourth dose.

By eating some protein with my third dose, I was able to stop the dyskinesias after the fourth dose.

LAJ12345 asked: "if you are taking the protein to alleviate the symptoms of too much levodopa wouldn’t it be better to just take less? Except in accidental overdose cases."

I am not sure there is any benefit in taking less levodopa (instead of adding protein).

I think there is a practical benefit to the adding protein approach. It gives you a finer level of control. Nutrition labels allow for a quantum of 1 g of protein. As opposed to adding levodopa, which has a much larger quantum of 1/2 tablet (50 mg of levodopa).

[LeharLover62]

I use it because too much levodopa causes hallucinations for my husband. So if his meds are off during the day and he starts to hallucinate, I give him protein (and avoid sugar and caffeine).

[BPW1]

I recently have been going to the gym right after taking last dose of C/L. I always tired to eat my protein at least 2 hours after my last dose but lately I have been so hungry after my workouts that I eat right after gym and have noticed my dyskinesia at night fades a lot quicker.