I often feel I am sometimes unresponsive to levodopa. I wonder if these bacteria come and go.
In addition to the most important matter of controlling symptoms, another place this matters is that we could be excluded from clinical trials for being unresponsive to levodopa when it is not because we do not have PD, instead it would be because we have the specific gut bacteria.
science.sciencemag.org/cont...
same study
My Naturopath pointed out that protein in the system stops levodopa’s effectiveness.
Thanks Marc.
Shouldn't they try intravenous L-Dopa to remove the doubt (and potentially help a lot of people) ?
You mean injectable, like B-1? Probably could, but might be too expensive?? Also, perhaps a lot of PWP couldn't or wouldn't do injections.
“The dope on L-dopa metabolism
The efficacy of L-dopa treatment for Parkinson's disease is hugely variable between individuals, depending on the composition of their microbiota. L-Dopa is decarboxylated into active dopamine, but if the gut microbiota metabolize L-dopa before it crosses the blood-brain barrier, medication is ineffective. Maini Rekdal et al. found that different species of bacterium are involved in L-dopa metabolism (see the Perspective by O'Neill). Tyrosine decarboxylase (TDC) from Enterococcus faecalis and dopamine dehydroxylase (Dadh) from Eggerthella lenta A2 sequentially metabolized L-dopa into m-tyramine. The microbial L-dopa decarboxylase can be inactivated by (S)-α-fluoromethyltyrosine (AFMT), which indicates possibilities for developing combinations of Parkinson's drugs to circumvent microbial inactivation.”
Interesting that a probiotic recommended a while back called AOR probiotic3 has Enterococcus faecium in it. I wonder if it is similar to faecalis?
“Tyramine (TIE-ruh-meen) is an amino acid that helps regulate blood pressure. It occurs naturally in the body, and it's found in certain foods. Medications called monoamine oxidase inhibitors (MAOIs) block monoamine oxidase, which is an enzyme that breaks down excess tyramine in the body.”
“Passionflower contains the MAO inhibitors harmaline and harmine. It also contains several flavonoids that are MAO inhibitors, including apigenin, kaempferol and quercetin.
Nutmeg
Nutmeg (Myristica fragrans) is an evergreen tree native to the Spice Islands. The seed of the tree is called nutmeg, and mace is the seed covering. Nutmeg essential oil contains myristicin, which can be toxic in large doses. Myristicin is an unselective MAO inhibitor, meaning it acts on both MAO-A and MAO-B. Nutmeg also contains the MAO inhibitors kaempferol and quercetin.
Turmeric
Turmeric (Curcuma longa) is a yellow root used in Asian cooking and traditional medicine. A study reported in Psychopharmacology found that curcumin inhibited both MAO-A and MAO-B and increased the levels of serotonin and dopamine. When the researchers combined curcumin with piperine, an alkaloid found in black pepper, they found this enhanced the effect of MAO inhibition.
Kava
Kava (Piper methysticum) is a green shrub native to the Pacific Islands, where it's used as a relaxing beverage. The active ingredients in kava are called kava pyrones or kavalactones. A study in Pharmacopsychiatry found that six kavalactones were MAO-B inhibitors and increased dopamine levels in the brain. In order of potency, they are: desmethoxyyangonin, methysticin, yangonin, dihydromethysticin, dihydrokavain and kavain.“
link.springer.com/article/1...
This says E. Faecilis can grow on mannitol where E. Facium cannot. Interesting. So if people have the faecilis bacteria that degrades l-dopa and then take mannitol they are just breeding their bad bacteria?
Good info. Thanks.
Seems like it would be, but I don't have a clue. I've been concerned about xylitol, trehalis, and mannitol for just this reason, i.e., feeds bad bacteria.
Good question. Unfortunately, we are not scientists, and personally, I have problems following all these discoveries and honestly confuse me even more. However, Wriga's research on GJ and its inhibition of CYP enzymes works!
I'm not sold on this. It is, essentially, the same thing is taking Mucuna and Sinemet together, i.e., no way to know how much levodopa you're ingesting. If one drinks grape juice every day, it continues to reduce the amount of 3A4, perhaps, to a negligible point where it might take 10 days to fully recover. 3 A4 does not bounce back in a few hours.
If you take too much Sinemet and get dyskinesia, the dyskinesia goes away soon as you stop, but I can imagine in this GJ scenario, the dyskinesia could last for days.
And, thirdly, 3 A4 is perhaps the primary digestive enzyme so what does diminishing it well below what your body would naturally produce do to everything else, food and pharmaceuticals, you're taking? From Albert's paper we know that continuous use of grapefruit juice might diminish 3 A4 to 1/10 of its normal volume which means everything else that it would normally metabolize is not being normally metabolized.
Too much of many supplements can become toxic.
Looks to me like this is ripe for unintended consequences??
I am fundamentally against taking pharmaceuticals in unknowable doses.
You say grape juice, do u mean grapefruit juice?
I meant grapefruit juice, but other citrus also inhibits 3 A4.
Despe,
Allow me to make another 'argument.'
I don't know that there's anything about levodopa that makes mixing it with grapefruit juice unique. As we know, 3A4 metabolizes fully 50% of all pharmaceuticals. Many antidepressants also target neurotransmitters. If you were depressed and taking antidepressants, would you take grapefruit juice to boost their effect? What about drug for hypertension, high cholesterol, chemo drugs, diabetes drugs, heart arrhythmia drugs, psoriasis drugs, antibiotics? If you knew grapefruit juice would boost the blood serum level of any of these drugs, would you drink it for that purpose? I think not. Exactly the same thing.
Marc
Marc,
None of the medications you have listed are consumed by my husband , but I will bear that in mind just in case he starts any meds. Talked to our pharmacist today, and he agreed with GJ and inhibition of enzymes allowing more levodopa into the brain. He also suggested that consuming 8oz of GJ is not a lot to cause problems.
Albert is continuing his research, and I hope we'll have more information on GJ and its enzymes inhibition.
PS. Yes, 1/2 tablet of Sinemet with a 15% L-dopa (40mg) MP works great! My husband is taking them together every night before bed, and he is very happy with the result.
Good.
Shouldn't they be instructions about the consumption of all the meds with GJ? My husband was on Atenolol and Synthroid a few years ago. He was drinking GJ then, and no instructions on avoiding drinking GJ with those meds. We both have been drinking GJ before we knew about GJ and its inhibition of 3A4 enzyme. We didn't start drinking GJ after PD, we always did, instead of soft drinks. No adverse reaction then, none now. I assume the amount is the problem, not the moderate consumption. But again I am not a scientist/pharmacist, just a lay person.
Maybe you've been lucky -- so far.
I'm not a doctor either, but I've never let that stop me from practicing medicine, although you may have noticed I do not ever make recommendations to take or not take drugs.
My only point is this; grapefruit juice will either increase or decrease the availability of 50% of the pharmaceuticals by an unknowable amount. That it will either increase or decrease levels is 1 point, but my concern is that it does this by an unknowable amount.
1 of the sites (I forgot which one) says the effectiveness Synthroid is reduced by grapefruit juice, which would explain why he is had no adverse reaction. But, clearly, reducing the availability or serum level of the pharmaceutical can put a person at risk for the very purpose they were taking the drug.
If you are taking a drug to prevent a heart attack and grapefruit juice diminishes its effectiveness the adverse reaction may be a heart attack.
Grapefruit juice increases the availability of levodopa, but does it also increase the availability of carbidopa in the same proportion? Does that matter?
If I wanted more levodopa, I'd take more levodopa. Increasing your blood sermon level of levodopa by a grapefruit juice (probably) has no effect on it's propensity to induce dyskinesia like Mucuna does. The only reason I would take the fruit juice and Sinemet, is if I were paying for it or any drug cash out of my pocket, the grapefruit juice would serve the purpose of stretching out the supply.
One last point is that the quote below and Albert in his paper said the grapefruit juice will reduce the presence of 3 A4 by 50% for 24 hours, so when you drink grapefruit juice again the following day your reducing the amount of 3A4 from a reduced amount. 50% of 50% of 50% of 50% eventually becomes a very small amount.
"Taking medications at a different time from when grapefruit juice is consumed will not prevent the interaction."
drugs.com/article/grapefrui...
"The effects last because grapefruit-mediated inhibition of drug metabolizing enzymes, like CYP3A4, is irreversible;[29] that is, once the grapefruit has "broken" the enzyme, the intestinal cells must produce more of the enzyme to restore their capacity to metabolize drugs that the enzyme is used to metabolize.[11] It takes around 24 hours to regain 50% of the cell's baseline enzyme activity and it can take 72 hours for the enzyme activity to completely return to baseline. For this reason, simply separating citrus consumption and medications taken daily does not avoid the drug interaction.[9]"
en.wikipedia.org/wiki/Grape...
I will not argue with you. Perhaps Albert is the right person to address your concerns. I did my own research plus asked our pharmacist. Maybe we have been lucky.
I sincerely hope this did not sound like we were arguing. I expressed this to Albert. No response.
Believe he is working on it.
PS. It is not just its impact on pharmaceuticals that concerns me. It can reduce the nutritional value of food and sups, too. Just as important.
Don't know anymore, Marc. Everything is so confusing. What contradicts what, one supplement/vitamin is good and later on we read that it has its downsides, etc. etc. At times, I want my husband to just drop everything, it's so overwhelming. 
I hear you. Hang in there, though. You are clearly on top of things. Your husband is lucky.
You are a good, caring person, too.
Seems very important!
Do you notice any difference if you take it with a 'carminative' like mint tea (some seem to work by suppressing bacterial metabolism)?
Wow!
Hi. Bit confused. Love to hear more please. Thanks. Anita
I had been overly sensitive to and consequently unable to take very much levodopa. I am now able to take it apparently due to a change in my gut flora.
That's encouraging. I think I'm the same. I get little or nothing from levodopa. What did you do to change your flora?
I am one week on in taking Symprove to see if I can make a positive change to my gut (e.g. energy levels and ER LDopa effectiveness on bradykinesia and tremor at current dosage). Its a 3-month trial for me and I will post. No negatives so far - apart from the taste! It does contain E.faecium
Kevin
Let us know how it works. $$$
The pricing seems out of line with what it is. But if it works then I am hoping that I can keep my biome in shape with good nutrition so I won't need to stay on it.
Kevin,
I don't know a lot about probiotics, but I've read in a few places that you should try for 50,000,000,000, guaranteed live and 15 strains. I don't know for sure that that's true, just what I've been going by lately. I used "Raw Probiotics, ultimate care" from Garden of life. It has 100,000,000,000 CFU and 34 strains. It, too, is expensive, but not quite as bad. Because of the cost, I take one a day for a couple weeks, then one every 2 or 3 days to stretch out my pennies. Keep us posted how yours is working.
MBA - see my reply to Parkie below.
Hello park bear
I think I may have the same problem as you with levodopa. May I ask you what change you made to your got flora?
Many thanks!
Accidentally swallowed minute quantities of chlorhexidine gluconate mouthwash. Hard to believe it could make any difference.
Got any other suggestions? Doesn't sound FDA approved to me.
I gave this a try and I think either this, or long term low dose B1, worked with increasing levodopa carbidopa absorption. I will write a post with more details, but wanted to mention that this may very well be working. Thanks Bear.
Fascinating! I have been on high dose B1 for over a year. Look forward to your post!
PB,
Are you still on chlorhexidine gluconate? If you are, are you just gargling or swallowing a small quantity? I have an unopened bottle which dentist prescribed when I had a tooth extraction (actually husband was prescribed the same when he had a tooth extraction, too).
Thank you!
No, I quit after only using it a few days. Per instruction I had been swishing and spitting but not rinsing, leaving a residue in my mouth. What little that got swallowed came from that residue.
My getting some decent Levodopa Cabidopa absorption was short lived. Maybe some kind of placebo effect...
Levodopa response is back to nearly nothing positive again, while Levodopa induced dystonia has gotten worse and worse. This is so discouraging...
The little while when I felt levodopa finally worked coincided with the chlorhexidine test, as well as with long term b1.
Although still on b1 and tried another round of chlorhexidine these last few days, I keep deteriorating.
How about you Bear, do you still feel chlorhexidine positive effect on your levodopa absorption? (Are you still using chlorhexidine?)
So sorry to hear of your difficulties. I only used chlorhexidine for a few days. It did seem to remedy my levodopa intolerance and since then I have continued to benefit from levodopa. I wish I had some brilliant idea to solve the dystonia issue but I do not. Hot showers, mechanical massagers, menthol lotions, magnesium chloride "oil", and yoga / stretching all help to mitigate the problem. I have also observed I have good days and bad days when I think I am deteriorating, then good days return. So keep at it and hang in there!
I can assume that gut bacteria are less active when we are fasting. So it seems like L-DOPA will be more effective if to take it on an empty stomach.
Levodopa is likely more effective on an empty stomach, but that would be because there's no protein or B6 to impair its absorption. I don't know if gut bacteria (in your intestines) are more or less likely to do their thing if your stomach is empty.
Protein screws mine.
I used to be overly sensitive to levodopa but im now able to take it due to a change in my gut flora.
Research dated 2014 about C/L and rising PD death rate
Problems with Supplements
