My Parkinson's no arousal diet
 

My Parkinson's no arousal diet

Like many other people with parkinson's disease I noticed that my medication didn't work so well if I took it after I had a meal. In early Parkinson's disease (PD) orally administered levodopa usually works quite well. After a few years the number of uncontrolled off-moments increases. In literature on PD the gastrointestinal system is often seen as the main cause of motor fluctuations in advanced PD. Maral Mouradian wrote the following about what he calls pulsatile therapy:

“The concept of continuous dopaminergic stimulation continues being an important element in the treatment of Parkinson's disease (PD) as well as in pharmaceutical efforts to develop improved symptomatic therapies. The peripheral pharmacokinetic properties of levodopa, including its short plasma half-life and erratic gastric emptying, render the standard oral delivery of this dopamine precursor to the brain pulsatile, manifesting clinically as motor fluctuations. In addition to intermittent pharmacological stimulation, denervation of the striatum as a result of progressive degeneration of nigral dopaminergic neurons is needed for the development of motor response complications.”

I am a firm believer in what in anthropological literature is often called the “emic approach”, the way from within (As apposed to the etic approach). Every patient has a huge potential to monitor the pharmakinetic status of his own body. Just like a carpenter who doesn't need an instrument to see if something is the right size. This does not come natural however; it has to be learned and tuned. I decided to put it to the test. I am a person with Parkinson's disease and suffering from motor fluctuations, on-off phenomena. I'm using levodopa medication for five years now and I fully realize that the honeymoon period is over. Let us have a look at what happens before administered levodopa becomes dopamine in the brain.

The long and winding road
Not much is known about the road that leads to the brain. Levodopa is unstable and it tends to be metabolised into dopamine right after it is taken by the patient. To slow this process down, a Decarboxylase inhibitor like carbidopa or benserazide is added. They kind of protect the levodopa on its way to the brain. As carbidopa and benserazide both cannot pass the blood brain barrier, levodopa will be transformed to dopamine rapidly as soon as it passes the blood brain barrier.

That is what eventually should happen, but it is still a long way to the brain, and the first barrier is the stomach. The longer levodopa stays in the stomach the more of it is lost. If the stomach is empty and the medication is dispersed well it may flush through at once. But most of the time it is not empty and the pylorus will close off the stomach. Periodically the pylorus will open and let some of the content of the stomach in the duodenum.

gastric emptying is delayed and Continuous Dopaminergic Stimulation
Probably due to premature levodopa metabolisation, gastric emptying is delayed. In the stomach levodopa is destroyed rapidly and unfortunately it's only in the duodenum that it's transported into the blood by an active transport system. If the levodopa doesn't reach the duodenum, the medication doesn't work. What an immense difference it makes if the levodopa wouldn't have to pass the stomach is evident if you compare the results of levodopa administered orally and by a duodopa pump. This is called “Continuous Dopaminergic Stimulation“. In the Duodopa®-system, for example, the levodopa is delivered directly into the duodenum (You can find that in the name “Duodopa”) via a flexible tube that is connected to a portable pump. This pomp pump will secure a continuous supply of levodopa/carbidopa during the day (or sometimes during the night too). This has two mayor advantages. First of all, the unreliable stomach is evaded. Secondly the supply is continuous, avoiding peeks. Especially for people with advanced Parkinson's disease, who have a weakened buffer capacity in the dopaminergic neurons, this is an important point.
Mouradian says on this subject: ”Positron Emission Tomographic studies have shown that patients with advanced PD have a greater increase in synaptic dopamine levels after an oral dose of levodopa than those with early, mild disease. Thus, severe loss of dopamine neurons results in the inability of the brain to buffer oscillations in plasma levodopa levels and even aggravates the pulsatile nature of conventional intermittent oral therapy.”(Mouradian).
The stomach is a barrier for levodopa, and slow gastric emptying (GE) causes levodopa to be metabolised before it can be used. But even more as Ruth Hardoff states, levodopa itself causes slow GE:
“Patients with smooth response to levodopa showed slower GE (n = 10; 73.6 ± 25.3 minutes), while treated patients with motor response fluctuations when tested at the on state (n = 13), had much faster GE (49.3 ± 16.2 minutes). This shortened GE in the on state was similar to the GE of normal volunteers. We conclude that gastric emptying time in patients with PD was delayed compared with control volunteers. It was even slower in patients treated with levodopa. This effect of levodopa treatment was reversed to pseudonormalization (normal GE) at the advanced stages of the disease, when patients developed motor response fluctuation.”
(Ruth Hardoff et all)
“Disturbed motility involves the entire gastrointestinal tract (GIT), i.e. esophagus, stomach and bowels, and the symptoms may be as manifold. The causes of these disorders had been controversially discussed in the past. By now, there is a general understanding that they are sequelae of the neurodegenerative process, which - among others - involves the intramural plexus of the GIT and the dorsal vagal nucleus.”
(Jost)

I think the quality of live of many people with parkinson´s disease will very much improved if we find out the best way to administer levodopa without having surgery. To accomplish this the stomach must be emptied right after the drug was administered. In a healthy situation the stomach will be emptied when new food is being consumed, as not to mix half digested food with freshly consumed food.
Probably because too much levodopa previously was converted into dopamine peripherally, this mechanism doesn't work any more.


The Motilium experiment
In this experiment I'm taking motilium twice a day. The first time 15 minutes before I take the rest of my medication (6:00), the second time also before taking the rest (14:00).
Motilium, also known as domperidon, is a peripheral dopamine antagonist. It blocks the dopamine receptors so it prevents peripheral damage by access dopamine. As motillium cannot pass the BBB the dopamine supply in the brain itself is not hindered.
Simple in theory, but for some reason this didn't work out so well. What improved, was the response to levodopa. The levodopa got through, but it seemed to work a terrible short while. Could it be the combination dopamine agonist/antagonist wasn't so sensible after all? It made me think of a previous experiment with Mucuna Pruriens. This also worked worked quite well but very short. Anyway it didn't feel save to continue this experiment. The idea to let the medication pass the stomach swifter still appealed to me however.

Biomarkers
The basics of this diet are what I call Biomarkers. These are symptoms, that appear in almost the same way every time the medication is below a certain level. In the period from 2003-2008 I made an inventory of the symptoms people with Parkinson's claim to have. Over a hundred symptoms were mentioned and there was a lot of difference in the degree those symptoms were experienced. It is a bit like the delta of a river. You cannot predict where the creeks will be but once established you can tell something about the tide by the speed a creek is filled with water. Much in the same way I believe patients can pick some symptoms that are an indication of how levodopa is doing on its way to the brain. The moment medication is starting to work, may be indicated by a starter marker.
End markers may be the moment your tongue starts quivering or your right/left hand starts trembling.
Starter markers could be the moment you feel your prostate or the moment the trembling of some body part stops.
An “over the top” marker indicates that the amount of levodopa is to high. It might be an overdosis indicator. This could be the feeling that you want to move, the urge to stretch some muscles. This is the predecessor of dyskinesias, the involuntary movements that emerge at the top of the therapeutic window.
As we cannot dispose of any instrument to monitor the state our body is in we have to find an alternative. Such an alternative can be found in the the biomarkers I described above. I use them to make my internal observations more objective.
My thesis is that the human body is a an intelligent system in the sense that it has developed a defense against disturbances of the body's equilibrium from the outside world. So if I bring dopamine into this system, where dopamine is in some equilibrium, or interconnection with other systems of neurotransmitters, something will be done to remove this excess dopamine. All sorts of damage would be inflicted if this were not the case. Especially a massive attack on this equlibrium as is, for example the case with a venomous bite, will be bravely responded to. This response may even be so vigorous that it may threaten the life of the victim instead of saving it. This kind of auto immune reaction often occurs. The same mechanism will come into action to remove the dopamine that was suddenly there in our body. Knowing this it is not surprising that we should try to avoid this kind of reaction. The way this is done in this diet, is to aim at sneaking in the medication. This means that dopamine levels may not be raised too brusquely. I use the following principles or tools to shape this Parkinson's No arousal diet:
Take your medication with sufficient water, as to flush it through the stomach. This will work on an empty stomach.
Take the medication on an empty stomach when possible.
If this is not possible eat as little as possible to stimulate gastric emptying, after having taken the medication.
Take medication as soon as the end-marker appears.
Lower the medication of the corresponding dose the next day in case of the over-the-top marker.
Gastroparesis is usually associated with diabetes. Some say it is a natural defense against high blood sugar levels. Knowing this it is may be better not to eat large quantities of sugar.
If not absolutely necessary, avoid taking medication after 22:00. The amount of food taken after every meal increases. The last dose of medication in this diet is followed by a hot meal. This usually takes a lot of time to be digested. It might not be digested the first dose the next morning. If this is the case on a regular basis, I would suggest to take a motilium/domperidon just before going to sleep.
Following this procedure I came to the scheme below. Of course this scheme is suitable for me, for my stage of parkinson's disease

7:00 1 sinemet 62,5 2 requip 1mg (1,5 h)
This is the smallest dose of the day. Don't take any food before or after this. A coffee is OK. When you take this, you should feel relatively comfortable because the night's sleep you just had. In about half an hour this feeling will be replaced by a feeling of relatively well being, caused by the dopamine or the dopamine agonist. You should experience your starter marker now. The reason I don't take more is that I tend to get dyskinesia easily this time of the day. The consequence is that this dose doesn't last very long.
8:30 1 sinemet 62,5 2 requip 1mg (2,5 h)
The second dose is usually the dose that used to work very poor because in the conventional way this dose comes after the first meal of the day. In the study of Monge and others this is said:
“In many parkinsonian patients with fluctuating disease the early morning levodopa dose is more effective than the following dose on the same day. “(Monge et all).
In this diet the second dose works perfectly ) for me.
After this meal I take a full oat cracker or something like that and some coffee. Don't take any butter, proteins or too much fat. No milk.
11:00 1½ sinemet 62,5 2 requip 1mg (2,5 h)
After this dose I take two slices of bread and butter with some marmalade and again a coffee.
13:30 1½ sinemet 62,5 2 requip 1mg (2,5 h)
After this dose I take a light snack like poached salmon and a glass of white wine. I usually take an afternoon nap after that
16:00 2 sinemet 62,5 2 requip 1mg (3 h)
After this dose I take some bread with something like ham or cheese
19:00 2 sinemet 62,5 2 requip 1mg (11 h)

This diet is not complete yet but to me it has brought a lot more quality of life using less medication. Some patients will probably not be prepared to spent this much time on finding the best implementation of this diet for themselves. In this case it is true, you don't get something for nothing.

The striking features of this diet are:
The doses get bigger gradually throughout the day
The timespan between the doses gets larger
The amount of food consumed is larger every dose
These three characteristics are a mere consequence of the thrive to have an empty stomach before taking the pills. So after the first dose you don't eat anything. Of course you can't go on that way. So at a certain moment you have to eat something. Because of that the stomach is no longer empty. This makes it hard for the next dose to reach the duodenum. A way to force gastric emptying is to have another meal after having taken your medication. The stomach is getting increasingly filled until the last meal of the day at 19:00. After that, the long night's sleep will fix that problem for the next day. What if you're not having a long night's sleep?

Half Life
The main reason that you have to take medication so often, is that the effects only last a very short time. An indication of the duration of the working of the medication is what is called “half life”. As medication is taken orally, it takes a while before it is found in the blood. Then the levels of the medication start to rise until they reach the maximum value (Cmax). The timespan between the administering of the dose, and the moment Cmax is reached, is called Tmax.. As soon as the medication enters the bloodstream the body will try to remove the foreign element. So after a certain period the levels in blood plasma will be half that of Cmax. The time between Tmax and this moment, is called half-life.
Half-life is a good indication of the duration of the effects of medication. The sad part is that levodopa only has a very short half-life. So the effects only last a very short time. As a consequence we need to take many doses to last throughout the day.

Literature

Early Non-motor Symtoms Associated with idopathic Parkinson 's Disease
Gastrointestinal Disturbances(presentation)
PD Dr. Woitalla
International Graduate School of Neuroscience
Gastrointestinal disorders in Parkinson 's disease
W. Jost
Deutsche Klinik für Diagnostik, Dept. of Neurology, Wiesbaden, Germany

The Rationale for continuous dopaminergic Stimulation in the Management of Parkinson 's (presentation)
M. Maral Mouradian
UMDNJ-Robert W. Johnson School, Dept. of Neurology, Piscataway, USA

The influence of levodopa on gastric emptying in man.(presentation)
D R Robertson, A G Renwick, N D Wood, N Cross, B S Macklin, J S Fleming, D G Waller, and C F George
Clinical Pharmacology Group, University of Southampton.

Variation in the Dopaminergic Response During the Day in Parkinson Disease.
Monge, Alessandra MD *+; Viselli, Fabio MD +; Stocchi, Fabrizio PhD *; Barbato, Luca MD *; Bolner, Andrea *; Modugno, Nicola PhD ++; Paradiso, Michele MD +; Ruggieri, Stefano MD ++; Nordera, Gianpietro MD *
Clinical Neuropharmacology. 27(3):116-118, May-june 2004.

Role of integrative pharmacokinetic and pharmacodynamic optimization strategy in the management of Parkinson's disease patients experiencing motor fluctuations with levodopa.
Chukwuemeka S. Okereke
Department of Clinical Pharmacology, Clinical Research and Development, Eisai Inc., Glenpointe Centre West, Teaneck, New Jersey, USA

Gastric emptying time and gastric motility in patients with Parkinson's disease
Ruth Hardoff, MD, DSc 1 *, Michael Sula, MD 2, Ada Tamir, DSc 3, Adrian Soil, MSc 4, Avi Front, MSc 1, Samich Badarna, MD 2, Silvia Honigman, MD 2, Nir Giladi, MD 2
1Department of Nuclear Medicine, Technion Institute of Technology, Haifa, Israel
2Department of Neurology, Technion Institute of Technology, Haifa, Israel
3Community Medicine Carmel Medical Center, Technion Institute of Technology, Haifa, Israel
4Elgems (Elscint) Ltd., Haifa, Israel
© 2001 Movement Disorder Society.
email: Ruth Hardoff (harduf@post.tau.ac.il)

In the eleven years Ive had PD, I always wondered why they did not develop a better delivery system. Or at least an alternative one,especially to those havng problems with their meds having to go through the valley of the shadow of their demise..the good old stomach!

Just a few changes and you can feel a lot better
 

I think together we can find a better delivery system. A lot of people would benefit if they just:

- never ate before medication
- didn't eat after the first medication
- take less medication the first dose
- didn't take any medication after dinner
- if needed, add some medication the last dose

Don't experiment too much with medication (except small adaptations)
experiment with food instead.

As you Americans say: "Yes we can!"

no arousal
 

The concept of a "no arousal" diet is very interesting, especially in the context of a larger view of PD as a struggle to maintain an equilibrium or balance in a stressed system. Homeostasis is another term for it. Extremes are to be avoided. Sort of the "Goldilocks Syndrome." Not too hot nor too cold. It is found at various levels in me (us?). Cortisol levels, for example, normally rise to a peak around sunup and then drop rapidly through the morning and begin a slow ascent in the evening to eventually repeat the cycle. But not with PWP. We tend to hover around an elevated flat line. No extremes.

Emergency? PWP seem to keep their heads more than most. Need it done and done right? You could do worse than a PWP. The Parkie Personality is real. No extremes.

But that stability comes with a cost and gets harder and harder to maintain. Stressed out system collapse.

Joop may be onto something here.

this is interesting
 

I believe you are right, that you have found a nutrition plan /meds that works for you and many could beneift. We'd have to make some changes, but many of us are on schedules that must be followed for us to stay "on". Without fail now, the amount it takes for me to stay on, is high enough to cause behavioral changes, slurred speech, and then - even more strange- looking [i'm trying to describe it from one who is looking at me] - my right leg turns into a drum majorette all by itself....kicking out ahead- only not as graceful looking by a long shot...lol.....I"m laughing truly. The whole right side goes....left still trying and keeping balance. i always look tipsy, sound tipsy, what a sight. I just go with the tipsy without even drinking.

It is on a schedule tho, pretty similar and i try very hard to keep track. i suppose you are going to say i have to give up my bowl of ice cream before i go to bed... conflict..lol. Is there no comfort food to be had?

i do see what you are trying to do. thanks for making us aware of this.

With a regimented life, we can move longer , adding vigorous exercise.....that would be vigorous exercise... vigorously...and we are then supposedly going to able to change the illness? Can it replace dopamine and reduce sinemet? I have to lie very still on my back after making a trip to the bathroom at night. No arousal I definitely understand then - have to beat the toe curling to get back to sleep. But who exercises vigorously and does dyskinesia count? pwp need physical assistance to get themselves there. oh sorry off topic but thanks.

i would highly recommend a diet that is PDSpecific and i get closer everyday to purchasing Kathyrn Holden's book - better late than never. i talked to Jaye about it - she visited last week.

Nutrition is such a major factor with pD. We need to analyze it.

;)
paula

Rick,

That's the idea. If you disturb a living system, it will react to restore the equilibrium. If this disturbance is violent, the reaction will be like wise. That is why I think it is better to let the medication sneak in.

When you need medication, the body is in stress, trying to rise the dopamine level. When you add a small amount of levodopa, you will make life easier. When you add too much the system will try to get rid of the excess levodopa or even the excess dopamine.

It's a theory no absolute truth, but I think it is very reasonable.

Joop

Paula,

When I started not eating before or after my first dose of medication, my first and second dose were suddenly over the top, so I had to reduce these doses. It's easier to stay on with this diet. And if you have struggled to loose weight this is the same struggle. Only immediately after dinner you may indulge. This is the time to take your comforting ice cream. For the rest of the day I try to avoid sweets, fats and proteins. But the reward is instantly in my case. There were days that I realized that I had almost been “on” for the whole day. On the other hand the equilibrium is volatile. If I feel some glands in my neck I know that I have to be very cautious.

I don't know what medication you take or what the status of your Parkinson's is. I don't know what the effect for you will be. I don't know, but I sure would like to know. I think together we can make the picture complete.

Joop

Thanks for asking. My status is getting critical and altho i joked about it, it's not funny. I take sinemet every two hours and azilect, plus amantadine for PD. I take Nexium , [acid reflux] synthroid, [hypothyroid] and xanax to sleep - so much sinemet - would never settle down otherwise

I stopped sinemet cr due to unevenness and dyskinesia. I stopped requip because it got to the point where even 2 mg made me sick to my stomach. But the sinemet has me crazy by evening. Obviously overdosed. I don't eat much and need to gain weight. The sinemet takes my appetite away.

I 'm going to have to make medication changes, but whereas you are suggesting a small breakfast, I'm starving at breakfast because I have to force myself to eat for the last half of the day - no appetite.

I am trying to eat fresh vetables and have to have bran flakes and meat most days to avoid serious constipation. Bran flakes are the solution for me - daily.

It gets to the point where it's a choice between food or being on. I do ok with two meals a day, do better if i eat mid afternoon because by evening appetite is gone....and then I sinfully eat a bowl of ice cream at night.

It works for the most part unless i overdue it with food at any point. Absorption is a major factor. I weigh less than I did in junior high - about 12 lb underweight, but wasn't overweight to start with.

I've had PD for at least 20 yrs.


paula

reread and what a whine it ended with. i enjoy conversations that can benefit everyone involved. and can only tell it like it is. That shouldn't be confused with depression or self-pity. :)

A matter of balance
 

I think that most of us have noticed how darned hard it is to get back to ON if we forget to take the next dose. The idea of lost equilibrium makes that a little more understandable to me.

Joop and I briefly talked about the endocrine system's role in all this, and it is all about balance. In the early 20th century a Hungarian scientist named Hans Selye delved into this and coined the term "homeostasis" to describe the balancing act required to maintain inner stability in a fluctuating environment. The leading researcher today on this is Dr. Bruce McEwen. A good article by him for laymen is at http://www.naturalhealthweb.com/articles/McEwen.html

A healthy inner system is like a spinning top and can right itself again and again. But as stresses accumulate, the top wobbles more and more. A big load of meds might be increasing the wobble.

diet and PD
 

Good Morning!

As always an interesting discussion and I find another piece to understanding the puzzle of PD. I do experiment with my food and I find that low fat, low calorie vegetarian diet suits me better and my symptoms are under control.
One thing I noticed is with this diet, my medicines work fast (Absorption is better and efficient) and the effects last longer (half life is better?). Since n=1 and experimental subject and observer is me, its hard to publish it! Nice to hear that others notice something similar!
Vegetarian Diet combined with accupuncture, ayurvedic medicine, I was able to cut down on Mirapex (3mg per day to 2mg per day) and completely stop Carbidopa 25-100 which I used to take in the night. This is my 7th year of PD, I take 1mg Azalect once a day, 1mg mirapex twice a day, 100mg amantadine twice day and Parcopa 25-100 once day. I do not know how my meds compare with others, but I am happy to let go off Carbidopa and trying to bring down mirapex to 1mg per day.

Paula, try eating papaya first thing in the morning about 15-30 min before your medication to regain your appetite. That was one of the components of my ayurvedic therapy and worked for me.

thanks
girija

That's a lot of medication. Too much for me to comprehend I'm afraid. If you change many parameters it's hard to manage. I guess it is necessary and inevitable with so many years of PD.
It's remarkable that the number of women increases when the duration of the disease is longer.

Bran flakes help for constipation, but they may also slow down gastric emptying and thus take away your appetite.

If you change anything, change only one thing at a time so that you know what made the difference.

Joop (I won't have a connection to the internet for a few days)

That is something I also experience. I'm “on”almost all the time. But if there are any stress factors or a lurking virus, I'm in the danger zone. Using those biomarkers I described, I can sense if there is anything unusual, and take some extra medication.
To find out what marked the working of the medication. I made a scheme for the day. In this scheme I logged what medication I took, at what time, and how I felt. I found out that in my particular case, my tongue started quivering as a first off-sign. Next my right hand started trembling. And this was always the same! Now I know when I'll be getting off soon, and take measures.

Joop (I will not have internet access the next few days)