At least 6 Cytochrome P450 enzymes (CYP 450) degrade or metabolize L-Dopa, Azilect and Ropinirole, reducing their bioavalability and lifetime in the brain. They are highly present in the gut, the liver and some even in the brain. Conventional medications largely ignore their presence and action. Herbal remedies such as grapefruit, green tea extract and others contain very effective CYP 450 inhibitors which could increase the efficacy and lifetime of Parkinson drugs, but their use is often discouraged because they can also modify the efficacy of 75% of drugs used to treat other conditions, sometimes leading to overdosing. I have made a survey of some PD drugs degraded by CYP 450 enzymes and the corresponding herbal remedies that may influence their bioavailability.
You should be careful with most statins, blood pressure meds, heart meds, etc, the list is long, since the CYP enzymes reduce their bioavailability (not the efficacy). This is all known and the same applies to most PD meds. That's why they dont stay long in the blood (Not usually more than one passage via the liver, about 90 minutes) Grapefruit juice and green tea extend that by inhibiting many CYP enzymes. But rather than banning GJ, I make the case of using that knowledge with all the proper precautions to extend the lifetime of these very short lived PD meds. My short experience is that it works.
But you must take all the precautions with other meds. Your doctor will probably tell you to avoid it.
Thanks Wriga, this is something I've been looking for for some time to combine with thiamine and niacin. Something that stabilized the levodopa by preventing the highest peak in the blood and then go to zero after more or less an hour and a half. I'll try.
Before you start read the article well and if possible all the références (there are more than 150 pages, esp the first ref by Ramon Cacabelos on CYP coding of PD meds and print out table 1 of this ref for guidance. If you have questions pls ask.
If you're using grapefruit juice to extend the life of a drug, isn't that comparable to increasing the dose of that drug, and if so, how do you know how much of a dose you are ending up with?
In other words, grapefruit juice will cause some drugs to accumulate beyond their intended blood sermon level, won't it? Are you concerned about some drugs accumulating to a toxic level?
That's exactly right. Inhibiting CYP enzymes means that serum levels of drugs dont decline as fast, so with the same intake the peak dose will be higher and later, and could become toxic. To avoid this risk, initial doses should be lower. How much lower ? That will depend on your genetic CYP polymorphism : slow, intermediate or fast CYP metabolisers. We all start off at different levels of CYP activity. CYP inhibition levels the field. PD drugs have an added difficulty in that serum drug levels dont equate to drug levels in the brain. There is bound to be a delay to cross the BBB. During this delay, CYP activity in the liver will be actively metabolising the drug. Hense the short therapeutic life of the drugs. There needs to be a lot of research done to understand this, but just avoiding CYP enzyme inhibitors is not the answer.
The question is, if you’re drinking grapefruit juice to extend the half-life of your PD pharmaceuticals, Mucuna P or anything for that matter, how do you know by how much you’ve extended it? Probably, most PWP are taking a half-dozen pharmaceuticals each of which would be affected differently, i.e., 2 drugs are extended by 10%, 2 by 20%, and 2 by 30%, but What if I don’t want those last 2 drugs extended at all and I can’t stop taking them.
To avoid the risk of their pharmaceuticals accumulating to a toxic level, you advise them to lower the initial dose, but, as you point out, they can't know by how much unless they also know if they are of slow, intermediate, or fast metabolisers, which IMHO not a single person on this forum knows.
The likelihood of us reducing The dose by exactly the right amount so that the efficacy is not diminished, but is extended is pretty close to 0. Also, Isn't there A fair chance Of ending up with more levodopa than was intended?
I appreciate your link and the information you provided, but I feel trying to tinker with the bioavailability, efficacy, and half-life of pharmaceuticals by drinking grapefruit juice is shooting in the dark.
Thanks for your well considered input. I fully endorse your question and sadly I don't have an answer to it. I don't think anyone has. I would however suggest that knowing of the existence of CYP enzymes and their impact on meds but ignoring these impacts is just as worrying or even irresponsable. Shooting in the dark seems to be the standard for PD meds. I still have a valid prescription for a PD med that lets me choose the dosage over a factor of 4 depending on how I feel it's working ! This from an experienced Dr that I respect. Now knowing that one med can impact on another I stopped all meds for 3 days before starting GJ or Green Tea Extract and then tested each one individually and then in pairs to try to find the best dosages and combinations. This is my experience in exact science kicking in even tho biomedecine is much less predictable than physics. It has taken a long time to find what works for me and the job is not finished. I know that for others the results would not be the same. Just for guidance, the impact on bioavailability of CYP enzyme inhibition for PD meds (and others) is not at all marginal ie. not 20 or 30% but very much higher. It can double or triple ! That's why overdosing can be a real problem, but also why the subject is important for meds with low bioavailability,
This information you provided is really important. Thank you for that.
People will have learned from your post that they can end up with considerably more levodopa or any of their other pharmaceuticals than they intended. Unfortunately, it adds another layer of complexity to what is already mind-boggling.
Getting a sustained flow of l-dopa to the brain is key. I doubt that we need very much, maybe only a few mg per day, but without peaks and lows. The first problem is the DDC enzyme. Carbidopa deals with that. If you're talking Mucuna P, this is only partially resolved with Green Tea, but it does help. After that comes the CYP enzymes. They severely limit the half-life of L-dopa. Their inhibition makes a big difference and I believe (no real proof yet) that the combination of Green Tea Extract and GJ works best. Dont overdo either. GJ is persistent and takes days to be eliminated. One avantage I found was GJ stopped nausea when talking Mucuna P. There must be an explanation for this.
I read that even the cbd oil interacts with Cytochrome P450, my mom is taking oil cbd for a few months with a noticeable improvement. also takes 1/2 tablet of modapar, it could be that for now the half tablet was enough thanks to the interaction of the cbd?
Hi dangilio. Yes, but I think grapefruit juice is a more powerful CYP inhibitor. Cbd may have other properties that are useful tho. Madapar contains benserazide that is a peripherally-acting DOPA decarboxylase inhibitor, like carbidopa. In this case green tea extract may be unnecessary for the DDC inhibition and grapefruit juice the best option. Always carefully check on other meds first.
I'm not compétent to give advice or an opinion on particular cases. I limit my interventions as far as possible to compiling facts and observations to try to build up a coherent story or model that peolpe can use to make their own opinions. I haven't put cd oil into this story yet, so I can't answer your question. Sorry.
Cbd oil strongly inhibits CYP 3A4 and 3A5 as does grapefruit juice. But Cbd is also metabolised by other CYP enzymes. GJ is therefore likely to increase the potency of Cbd. Also dont use GJ with codein for the same reason.
My husband is on MP standardized extract 20% L-dopa X 2/day. He drinks green tea with his morning dose and takes Vitamin C. Would the efficacy of MP be even more extended with the addition of GJ? He is not on any conventional drugs except a compounded T4/T3 thyroid med.
I do believe that GJ will help MP last longer. The problem remains that Green Tea is less effective in preventing perpheral decarboxylation than carbidopa, and GJ does not help this. Also thyroid drugs have a narrow therapeutic window. GJ could lead To overdose. What are the molecule(s) he's talking ?
He is taking T4 (45MCG) T3 (5MCG). The doctor and the FM pharmacist increased it to 50MCG and 7.5MCG as a result of the recent test he had, but hasn't started the increased dose yet. He's got a very few left of the old dose to finish before he starts the new one. Actually, we would like to try porcine thyroid hormones, but we will see. . .
I'm absolument not competent to give advice on specific cases, so I can't answer your question. Take a look at my reply to MDAnderson's more general question to see my views. Its a very complex subject.
0.75cl GJ per day ? = 7.5ml, I'm surprised at how little you are taking, Are you sure of your units ? I'm on a full glass = 200 ml. Anyway, pleased it's helping. I would not advise to cut down much on the madapar because you still need the DDC inhibitor to stop peripheral decarboxylation. GJ does not help that.
I strongly believe that 0.75L of GJ per day is too much. Above 0.5L per day, there may be inhibition of CYP enzymes in the liver and that could have a serious effect on the lifetimes of other drugs that people may take. There is a long list of common drugs that can go into overdose when taken with GJ. Futhermore the effects can depend on how much GJ you drink and be dangerously long lasting when the liver is affected.
You must always check with your doctor and read the notice of any drugs you take before drinking GJ.
For more reading see : D.G. Bailey et al.
Grapefruit–medication interactions: Forbidden fruit or avoidable consequences?
ok Albert, I only take madopar and CJ daily was just a test of a couple of days to see if there was any substantial change in the cycles of the ldopa and there is!
I think I will follow your advice and I will settle on 0.250 L of CJ day for one or two weeks. It will not hurt me, but if I use other medicines I would be very cautious with CJ. Thank you very much .
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