[QUOTE=Conductor71;829786]Soccertese,

I was wondering this as well. According to research, the responsible component of grapefruit is the phytochemical bergamottin. This is perhaps why Ron had such an extra long duration. It boosts the amount of levodopa in our bloodstreams and then it enhances the COMT inhibition leaving more dopamine up there working for us?

Maybe if we are not on entacapone we do not get the extended on time? Just a guess.

Oh, and our genes play a role. I don't know how many have done this but 23 andMe tests for our genetic dispositions with the COMT gene. The Val/Met SNP also informs how well we respond to COMT inhibitors. 23andme will tell you what alleles you have by looking up SNP rs43680 in browse raw data then see abstract for your response to COMT inhibitors at the pubmed link:


The COMT Val158Met polymorphism affects the response to entacapone in Parkinson's disease: a randomized crossover clinical trial.

Laura[/QUOTE

what i find interesting is that if your detoxifying enzyme activity is inhibited by grapefruit juice and basically l-dopa is absorbed in just a small area of your small intestine via active transport, then i assume you have to have a higher concentration of l-dopa in your tissues and blood, and maybe that translates to a higher concentration in the brain but doesn't seem so, just a longer affect. so as an aside, it seems that the concentration of l-dopa in your brain must reach an equilibrium fairly quickly? i.e., the active transport into the brain gets saturated quickly and somehow shuts down until the concentration in the brain decreases? of course normally it's tyrosine that your brain uses to mfg dopamine but life's too short to research that pathway. amazingly complicated system, wonder how the kidneys look a l-dopa, how much l-dopa ends up in the urine?
and how much better are comt inhibitors vs selegiline and rasagiline, which gives the bigger bang for the buck?

have too much time on my hands.

Ron, I take 3 Stalevo 200's per day..And yesterday, I took a teaspoon of Zandopa, so I could go out fishing

Fishing is very challenging, and as of yesterday, I had gone out three days in a row..Getting any ontime past 7:00 pm, even after taking a teaspoon of Zandopa with my regular meds is unheard of for me.......

I went out fishing today, and took my 3 Stalevos, and a teaspoon of Zandopa..I hauled 25 traps on Thursday, 30 traps on Friday, 20 traps yesterday, and 38 traps today..I havent fished 4 days in a row, in atleast 3-4 years, so you can imagine how tired, and fatigued I am right now

I took my pd meds..(Stalevo 200 mg, and Amantadine 100 mg)..at 7:00 am, this morning, and it usually takes 45 minutes to one hour get on..and I usually go off at about 6:00 pm..Days that I work, I have to take a teaspoon of Zandoa, to insure that I wont go off, while I am working, and I usually, but not always, go off at about 6:30 - 7:00 pm when I take some Zandopa

I dont eat breakfast, because it interferes with my pd meds, but I do have a cup of caffinated coffee

I wish I could get 14 hours out of one dose, but I am thrilled with another 3 or 4 hours of on time

I drank about 6 oz's of pure grapefruit juice and 6:30 am this morning, took pd meds at 7:00, and was on about 7:40 am

I had only had about 5 minutes of dyskinesia, when my meds kicked in this morning, and have had none during the day so far .It is 5:00 pm here now, so we'll see how long I can stay on today

I took my usual drug regimen yesterday, and today

This is probably pre-mature, but..today was day 4 of drinking about 6 ozs of grapefruit juice 1/2 hour before morning meds

I stuck to my regular med regimen..no Zandopa today

I had one day that I was on for an extra 4 extra hours, the other 3 days I went off at about 6:30 - 7:00 pm..Usual off time begins at 5:30 - 6:00 pm

What is different the past few days, especially today/tonight is I started to get dyskinetic at around 6:00 pm, and meds began to wear off..By 6:30 I was off..At 7:30 I got dyskinetic again, which is very rare for me..When the dyskinesia stopped, I was in a semi on/off state..No shuffling, a minmum of freezing episodes, and I could walk fairly well..It is 11:45 now, and I have more movement than usual..Im not on, but Im not off like I usually am at this time of the night

Last night I had a similar experience, only it didnt last as long

Through the past 2 years, since Ive been on Stalevo, my on/off time was pretty predictable..Meds at 7:00 am, and on 45 minutes to one hour later

2nd dose at 10 am..3rd dose at 1:00 pm..Off between 5:00 - 6:00 pm..and when I went off, I stayed off..I cant take 4 doses of Stalevo, because all I get is 2-3 hours of non stop dyskinesia

Now, Im not very well versed in science, chemistry or biology, but I do know that the amount of medication that is absorbed, in the small intestine, and avoids geting metabolized, basically has alot to do with the amount of l-dopa that reaches the brain

I also know from experience, that what I ingest into my gastro system, prior to taking my morning meds, has alot to do with the amount of time it will take for my pd meds to kick in, and how much dyskinesia I will endure to get there

I have gerd..( acid reflux )..and I was taking 20 mgs of Omeprazole every morning with my pd meds, and I would shake and bake for 45 mins to an hour before my meds kicked in

Then, I happened to find and read a clinical study online one night, and it said that the patients were told not to take any anti-acid meds with their pd meds, because the two drugs will compete for absorbtion, and the anti-acid drug usually wins..When I stopped taking Omeprazole in the morning, and took it at night after my pd meds had worn off, the morning dyskinesia was minimal, and occasionally, I had none at all

Anyway, I am going to continue the grapefruit juice every morning, and see what happens

This grapefruit "assist" is very interesting. I'm experimenting with different timing - today I drank a small glass an hour after my first dose at 7:00 a.m. I went five hours between doses in the afternoon instead of my usual three, so that's promising. I wonder if a significant amount once a day is better, or several smaller amounts - so many variables.

I am taking 1 1/2 generic sinemet 25/100 tabs every 2 hours. The meds don't even make it dose to dose and then in the afternoon I have to decrease that or I will get dyskinesia around 2 or 3 in the afternoon that is severe.

On Tuesday morning 12/6, approx 7 in the morning, I drank about 10 ounces of Minute Maid grapefruit juice, not from concentrate and plain grapefruit, not red or pink. I then took my morning dose 1 1/2 tabs. I ate my normal breakfast of cold cereal and milk trying not to otherwise alter my routine. Normally I would expect to have to take a second dose at around 8:30. I have rarely if ever made it to the next dose without feeling some degree of off, perhaps not totally but I can feel it coming on.
I was able to maintain an "on" state until around 1 pm in the afternoon! In fact having to monitor how I was feeling so that I would not go to an "off" state did not even come to mind I was moving about so well.
It worked for me and beyond the having to drink grapefruit juice it was an enlightening experiment. Best of luck to all.

Well it seems to work for most people most of the time. We must be careful and try to get more evidence that it is safe with PD meds. It does seem to be fairly mild so far. Several of us have taken grapejuice with our meds for days without any ill effects.
Wendy is right, there are a lot of variables, iit does not work every time. I have had just one failure, when it did not take effect. We need to build up experience to know do we take the juice before or after the meds. does one glass of juice last all day, or must it be taken throughout the day in small doses. What is the optimum dose level. Yesterday, I tried taking a glass of juice in the middle of the regime at 11-00am when I take a 50mg Stavelo, which normally lasts until 2-00pm, This time I switched off at 4-00pm, so an extra 2 hours. I took the juice at 11-30am, ie half an hour after taking the Stavelo.
It works more often than it fails, but it will be very interesting to find out why it fails on some occasions.
Ron

Most days it has worked for me too Ron..The only problems is morning meds take about 15 - 20 mins longer to kick in, and the evening off period is a bit brutal for about an hour with dyskiesia, and musle cramps in my right leg, but the good news is that I bounce back into a semi on/off state..Im not on, but not off either..Freezing periods have been minimal all night, and my last dose of Stalevo is at 1:00 pm in the afternoon, as it has been for quite some time..I feel like the pd clock has been set back a couple of years

Doing a literature search, there is a massive amount of research on this booster effect. See Rick's list!!! I could not find any adverse effect on PD patients, but that does not mean there isn't any. I just may not have found it. The mechanism, at least with Sinemet is that grapefruit attacks an enzyme that breaks up levodopa in the bloodstream. The overall effect is as if you had takern a larger dose of Sinemet.
Coincidentally, a full page article was published yesterday on the effect, in the UK Daily Mail. It works with other fruit such as cranberries, some citrus fruits.
With an agonist like cabergoline, see the abstract below.

Effect of grapefruit juice on cabergoline pharmacokinetics in patients with Parkinson's disease
M. Nagai MD, PhD1, A. Nakatsuka1, H. Yabe MD1, T. Moritoyo MD, PhD1 and M. Nomoto MD, PhD1
1Clinical Pharmacology and Therapeutics, Ehime University School of Medicine, Touon, Ehime, Japan
Top of page
Abstract
Background: Cabergoline is one of the synthetic ergoline dopamine agonists, which is widely used for the treatment of Parkinson's disease (PD). Cytochrome P-450 (CYP) 3A4 contributes to metabolize Cabergoline. It has been well known that grapefruit juice inhibits CYP3A4 enzyme located in the gut wall. To investigate whether grapefruit juice influences the pharmacokinetics of cabergoline, plasma level of cabergoline in patients of PD was evaluated.
Methods: Five patients with PD treated with cabergoline were enrolled. Plasma concentrations of cabergoline before and after coadministration of grapefruit juice were evaluated. The plasma concentration of cabergoline was determined using a LC/MS/MS.
Results: The plasma concentration of cabergoline increased approximately 1.7 times, when grapefruit juice was taken together with cabergoline. Adverse events were not observed during this trial.
Conclusions: Coadministration of grapefruit juice with cabergoline increases bioavailability of cabergoline. A relatively large therapeutic window of cabergoline may allow the concomitant treatment with grapefruit juice, and this combination treatment may augment the antiparkisonian effect of cabergoline.

I have not tried any more tests at present until I do more searches, but it appears to have real promise of giving a huge boost to our normal drugs. It could enable you to half your regime .
We need to find out what is best for us, drinking a fruit juice with half our normal drugs intake, or taking double that level of drugs.
Ron

Just did a search for cyp3a4 plus turmeric. Turned up a lot of hits:

"It appears that Curcumin from Turmeric and Piperine from Black Pepper (commonly taken together) both inhibit a number of Cytochrome P450 enzymes. P450's such as CYP3A4 and CYP2D6 are responsible for a large amount of drug metabolism and the use of Curcumin and Piperine might explain some of the reactions people are experiencing upon co-administration with drugs such as Benzodiazepines and Amphetamine type drugs... Interesting stuff and something people, especially those using this forum, should be aware of.

http://www.bluelight.ru/vb/threads/5...yme-Inhibition

Wow!, stevem53. Congrats on being able to stay so active. Very impressive, & truly inspirational. Whatever you're doing, keep it up. Dean.