691 replies to this topic

[MarcB]

"The Ketogenic diet has been in clinical use for over 80 years, primarily for the symptomatic treatment of epilepsy. A recent clinical study has raised the possibility that exposure to the ketogenic diet may confer long-lasting therapeutic benefits for patients with epilepsy. Moreover, there is evidence from uncontrolled clinical trials and studies in animal models that the ketogenic diet can provide symptomatic and disease-modifying activity in a broad range of neuro-degenerative disorders including Alzheimer’s disease and Parkinson’s disease . . ."

 

 

 

https://www.ncbi.nlm...les/PMC2367001/

[MarcB]

More from the link in my previous post re the Ketogenic diet.

 

"One recently published clinical study tested the effects of the ketogenic diet on symptoms of Parkinson’s disease (VanItallie et al., 2005). In this uncontrolled study, Parkinson’s disease patients experienced a mean of 43% reduction in Unified Parkinson’s Disease Rating Scale scores after a 28-day exposure to the ketogenic diet. All participating patients reported moderate to very good improvement in symptoms. Further, as in Alzheimer’s disease, consumption of foods containing increased amounts of essential fatty acids has been associated with a lower risk of developing Parkinson’s disease (de Lau et al., 2005.)

 

 

[mlsirkis]

http://www.medicalne...kinsons_disease

[MarcB]

I understand grapefruit juice increases the bio-availability by 60% (https://www.ncbi.nlm...pubmed/19948946) and therefore, many who post here feel it should not be taken with juice or food, but isn’t that important only if your dose is at the upper end of the safe level 600 – 800 mg/day?  If my dose is 125 mg, doesn’t the grapefruit juice make that the equivalent of approximately 200 mg?

[Library]

The grapefruit idea sounds good in theory, but is safe only if you take it just once.

Since people vary, you really don't know how much Nilotinib you --personally-- are getting, even if you know how much grapefruit juice does what, when averaged over a population.

Given that Nilotinib inhibits it's own substrate all by itself, more inhibition of 3A4 would increase the (very long!) 17 hr. half life by an unknown amount. If the amount of grapefruit juice added increases it by just 8 hours, Nilotinib would accumulate even with just once a day low dosage. To know that you are daily accumulating Nilotinib with a strong inhibitor is to knowingly seek a lethal dose.

That the dosage for Leukemia is much higher is not a safety feature since that dosage has already killed someone.

What is wrong with the grapefruit idea is that you are messing with how the body gets a toxic substance out of your body while completely in the dark about how much and how fast you are getting rid of it or accumulating it.

Although some people are more susceptible than others, Nilotinib does significantly prolong the QT interval and so for every person, there is a lethal level of the drug.

If it is accumulating, you'll get there. The difference between people is only WHEN you accumulate a lethal dose, not IF.

The point of a washout period of all 3A4 inhibitors before beginning Nilotinib is so that you can establish a known steady-state level of the drug that does the job day after day so it adds up to improvement rather than sudden death.

Giving up our daily Starbucks would be a more intelligent economy.

[MarcB]

The grapefruit idea sounds good in theory, but is safe only if you take it just once.

Since people vary, you really don't know how much Nilotinib you --personally-- are getting, even if you know how much grapefruit juice does what, when averaged over a population.

Given that Nilotinib inhibits it's own substrate all by itself, more inhibition of 3A4 would increase the (very long!) 17 hr. half life by an unknown amount. If the amount of grapefruit juice added increases it by just 8 hours, Nilotinib would accumulate even with just once a day low dosage. To know that you are daily accumulating Nilotinib with a strong inhibitor is to knowingly seek a lethal dose.

That the dosage for Leukemia is much higher is not a safety feature since that dosage has already killed someone.

What is wrong with the grapefruit idea is that you are messing with how the body gets a toxic substance out of your body while completely in the dark about how much and how fast you are getting rid of it or accumulating it.

Although some people are more susceptible than others, Nilotinib does significantly prolong the QT interval and so for every person, there is a lethal level of the drug.

If it is accumulating, you'll get there. The difference between people is only WHEN you accumulate a lethal dose, not IF.

The point of a washout period of all 3A4 inhibitors before beginning Nilotinib is so that you can establish a known steady-state level of the drug that does the job day after day so it adds up to improvement rather than sudden death.

Giving up our daily Starbucks would be a more intelligent economy.

 

Thank you, but now I'm freaked out as I've been taking 125 mg/day with grapefruit juice for 6 weeks.  Is it good enough to discontinue with the juice or should I discontinue the N as well?
 

[Library]

Don't freak.

All you gotta do is :

1. Stop BOTH for two weeks to a month. Let your CYP450 enzymes catch up to any build-up. Since we don't know what your blood level is but we DO know Nilotinib is very slow to clear under ideal circumstances (long half life), don't be in a hurry to resume. Safety first.

2. An EKG would be nice. The squiqqly jagged lines show how long the QT interval is and any arrhythmia.

3. Meanwhile, always carry your cell phone around with you --just in case. Go easy and mindfully through your daily life, lie down if there is any question at all that you are not perfect. Any fluttering feeling in the chest, left arm or chest pain, call the emergency number (911 USA).

4. While you are waiting to get back to zero (so when you resume you will know how much you are getting every day), if you take any prescription (or OTC) medications, you might take another look at 3A4 inhibitors and substrates online.

Different lists will have info on different drugs. View herbs with suspicion, since living things are made of hundreds of chemicals that could compete with Nilotinib for 3A4.

[45rpm]

I've been giving my mother "N" for several months.

 

After reading about the concerns over the build up of "toxins," I now give her two capsules of activated charcoal once a week. This clears out her system. Unfortunately, it also clears out any medications and supplements that she is taking.

[Library]

Activated charcoal is an emergency treatment for poisons that are still in the stomach.

The build-up of Nilotinib is in the blood.

It is the higher blood level of Nilotinib that endangers the heart's QT interval.

So far as I know, only way to remove Nilotinib in the blood is through the CYP enzymes, over time.

This is why drugs that compete with CYP 3A4 are so dangerous when combined with Nilotinib.

(For the medical use of activated charcoal--
see the Mayo Clinic website).

[MarcB]

Don't freak.

All you gotta do is :

1. Stop BOTH for two weeks to a month. Let your CYP450 enzymes catch up to any build-up. Since we don't know what your blood level is but we DO know Nilotinib is very slow to clear under ideal circumstances (long half life), don't be in a hurry to resume. Safety first.

2. An EKG would be nice. The squiqqly jagged lines show how long the QT interval is and any arrhythmia.

3. Meanwhile, always carry your cell phone around with you --just in case. Go easy and mindfully through your daily life, lie down if there is any question at all that you are not perfect. Any fluttering feeling in the chest, left arm or chest pain, call the emergency number (911 USA).

4. While you are waiting to get back to zero (so when you resume you will know how much you are getting every day), if you take any prescription (or OTC) medications, you might take another look at 3A4 inhibitors and substrates online.

Different lists will have info on different drugs. View herbs with suspicion, since living things are made of hundreds of chemicals that could compete with Nilotinib for 3A4.

 

You may well have saved my life -- for which my family and our dog (Margaret) thank you. I do want to resume (but I'll wait a month) because, for me, some risk is better than the no hope alternative of doing nothing.  Seriously, thank you, thank you.  I'll spend the month trying to understand what you've told me.
 

[45rpm]

Activated charcoal is occasionally used as a cleansing and detox agent. It is also used by those with advanced kidney disease to remove toxins from the body.

[Library]

Nothing is completely without risk.

But our situation isn't "Nilotinib-or-nothing" -- forever.

Its "Nilotinib-or-something better" -- coming soon.

In a couple of years, we should have a better choice, or even several better choices from promising drugs already being tested now.

Here is my understanding of our situation:

"Gunk" accumulates imperceptibly for 20 years or more before symptoms appear.

We cannot clear 20 years in 6 months and so we do not want to risk our lives trying.

What we DO want to do is slow additional build up or even slightly reverse it to stay on this side of the tipping point and avoid the point at which the process greatly accelerates.

If we can do this for just two years, we will be candidates for the new medications. All we are waiting for is evidence that they are better than Nilotinib.

So, we are not putting all our hopes on Nilotinib to be "the answer". We need not risk desperately or hope irrationally.

All we ask is that a tiny bit of Nilotinib keeps us off the tipping point.

Even if it only works well enough to keep us just where we are for a couple of years until we switch to the better meds--- then we now have a future to protect -- just like anybody else.

At the very least, by then, our lonely, scary DIY trial will be over and our doctors will be willing to supervise, follow, and test our progress with Nilotinib !

[Library]

Activated charcoal is occasionally used as a cleansing and detox agent. It is also used by those with advanced kidney disease to remove toxins from the body.

[Library]

Activated charcoal has many important uses in absoarbing toxic materials from air, water, and even the stomach.

In Advanced Kidney Disease, the kidneys fail to clear nitrogenous waste ( like urea) from the blood. So, the person reduces the amount of waste to be handled with a low protein diet and swallows activated charcoal to absoarb the rest.

Activated charcoal intercepts the nitrogenous waste in the stomach so it doesn't build up in the blood.

In the case of accidental overdose, it can similarly intercept prescription drugs in the stomach and reduce the amount absoarbed into the blood.

However, once a substance has entered the bloodstream, it is beyond the reach of oral activated charcoal.

[Logic]

All the best for the new year everyone.

 

Round 4 progress report:

 

The N arrived at the testing lab on the 1st of this year.
I have sent the lab everyones addresses and await feedback on the test results

[mlsirkis]

Does anyone know what is meant by --

 

oral B-glucocerebrosidase ?

 

Thanks

 

 

[maxwatt]

For those interested in senolytics such as nilotinib, I'd like to call your attention to this post  http://www.longecity...ndpost&p=801755    

which links to a crowdfunding site for Cellage, a company seeking to develop molecules more specifically targeted to specific senescent cells, not just those that this happens to reach, perhaps with an overly broad sweep.

[Library]

Re: Drug- and non-drug-associated
QT interval prolongation


https://www.ncbi.nlm...les/PMC2909803/

------------------------------------------

I've been trying to think of how to illustrate what's the matter with prolonging the QT interval-- even a tiny bit.

The heartbeat needs to be absolutely regular for the blood coming in to be squeezed out in time for the next amount of blood entering the chamber.

If the heart waits too long to squeeze it out, what happens to the next amount of blood coming in? Where can it go if the chamber is still full?

There isn't anywhere.
The heart has no Plan B.
What happens is sudden death.

And it kills more people than
AIDS,
breast cancer,
lung cancer,
and
stroke
---ALL PUT TOGETHER.

So causing this interval to lengthen is a (very good!) reason that many drugs are pulled from the market.

However, an exception is made for cancer drugs (like Nilotinib). The risk of sudden death is worth it because without treatment, the person will surely die, and the drug will only be taken with very close Oncologist (specialist) supervision. But even WITH medical supervision, Nilotinib has already killed someone.

A second reason that drugs get pulled from the market is that they demand too much of 3A4-- not because more drugs compete for it than any other (making deadly interactions more likely) but because they inhibit their own substrate, making them very difficult to clear and making accumulation to adverse events too likely to be safe.

Again, this is Nilotinib -- but again, an exception is made for a cancer drug. Yes, it MIGHT kill you but without treatment, the cancer 100% will.

Soooooo.....a person who takes it should tread verrrry carefully on what is known to be very dangerous ground.

It IS likely to accumulate and the accumulation makes sudden death more likely---A 1-2 punch --from a kind of drug that would ordinarily be pulled from the market.

AT LEAST :

1. Have a baseline EKG before beginning. Otherwise you won't know if your QT interval is getting any longer. Be sure that with every beat of your heart, the blood has somewhere to go.

2. Food works like a bad drug interaction with Nilotinib.
Only take N on an empty stomach --
at least 2hr after food and then wait to eat at least 1hr. after your dose. No beverages except water.
Be religious about this to avoid accumulation/overdose.

3. Don't start with 150 mg. Instead, start with 50 mg. After 2 months, test with EKG for prolongation of the QT interval.

Note:

Prolongation is common and they don't even know what all can cause it. Many genes do, so the same dose has different effects on different people.

30 % of people got prolongation averaging 31 milliseconds, meaning that some people were experiencing MORE.

3. Do not tolerate ANY prolongation. Even if it is still within normal range, it is showing you that YOU are susceptible. Stop dosing and wait until the interval is back to where you started ("baseline").

4. If there is NO change, then consider another 25mg. (75mg.) After a couple of months, test again.

Most anyone would be encouraged at this point to feel that 150 mg would be OK --but THE OPPOSITE IS TRUE.

As the dose is increased, so are the odds of prolonging the QT interval, so 75mg. is more risky than 50mg.

5. Remember that it took more than 20 yr to accumulate the "gunk" and anything that COULD quickly clear it would definitely kill you.

Perspective: 365x20 yr = 7300 days.
The difference between 1/7,300 of the gunk and 2/7,300 isn't worth dying over.

All you want to do is to clear TODAY'S gunk---no more. That's all it takes to stay off the tipping point. That's all it takes to still be here for the more effective meds.

Would you give yourself a heart attack on your bicycle while they are busy assembling a car for you?

[mlsirkis]

Could someone post the links to the literature that addresses the build up of Nilotinib over time?
I can't find the documents that address this issue.

[MarcB]

One life saved; I had an EKG 10/13/16 and began 10/23/16.  By 11/15/16, I was taking 125 mg/day with grapefruit juice -- really, seriously ignorant.  Thanks to Library's 1/2/17 post, I stopped.  I had an EKG four days earlier (12/30/16) got the report 8 days later (the VA is slow) and my QT interval had lengthened.  Surely, Library saved my life -- and it's not convenient for me to die at this time.  I've scheduled an EKG for the end of this week and if the interval has returned to where it was 10/13/16 (before I started,) I'm going to resume as per Library's post above.

Edited by MarcB, 15 January 2017 - 11:34 AM.

[khalidnt]

Thank you Library for sharing this important information. I've already started with N with 100mg/twice - China made - and I consumed 12g.

 

I will stop for one Week.

[Library]

And you will FOR SURE get an EKG before you resume?

There is no warning for sudden death
---except the EKG ---
and
no other way to know
that you are in the 30% for whom Nilotinib prolongs the QT interval (causes drug-induced heart attack).

DIY Chemotherapy is toxic stuff!

----Library

[Library]

Could someone post the links to the literature that addresses the build up of Nilotinib over time?
I can't find the documents that address this issue.

[Library]

http://www.gistespañ...uala-e75-87.pdf

The accumulation problem is because Nilotinib takes so long to get processed out of the body.

It's half-life is ~17 hours, so with twice a day dosing, every 12 hr. you are taking more when there is still 22 hours of processing time left to get rid of the last dose !

So the left-over accumulates in the blood -- and --because it also increases the QT interval-- at some point there will be enough accumulating in the blood to give anybody a heart attack.

Nilotinib is a chemo drug. Very dangerous.

Even when supervised by a specialist MD, and while following all the rules and safety precautions, it has killed.

If you are going to do unsupervised DIY chemo, you need at least an EKG to show that you could possibly take it without dying.

---Library

[splib]

What about a concept of intermittent dosing like every other day or maybe 2 days on and one day off, maybe that would take care of accumulation. Then I guess the question is if you're getting enough for any therapeutic effect at all. For someone with an already slow progression maybe it won't take much to stop it though. Even just slowing it down more and not even stopping progression would be quite significant. The part that worries me the most about PD is the progressive aspect.

 

I feel similar to what you wrote earlier Library, that the goal is to try and stave off further degeneration until the current round of disease altering therapies that directly target alpha-synuclein are available. At the glacial pace that things seem to move at I'm worried that may be more like 5 or even 10 years out though, but I'd love to be wrong about that!

 

splib

 

[bossmanglb]

I've been giving my mother "N" for several months.

 

After reading about the concerns over the build up of "toxins," I now give her two capsules of activated charcoal once a week. This clears out her system. Unfortunately, it also clears out any medications and supplements that she is taking.

 

 

BTW I'd suggest looking into stinging nettle seed extract for the nephropathy. Some very encouraging anecdotal reports. E.g., 

 

http://jonathantreas...idney-function/

[togl]

has anybody in fourth round group buy received  a package yet? tx..

 

-Tom

[richard hnry]

I have 100 grams of N from the 2nd group buy.  I would like to sell it for $10 a gram.  Anyone that wants it just let me know.

[David Watford]

Some time in the last six months, I watched a UK presentation on Parkinson’s which I can’t find now, but I remember thinking “this is a sane review”. It summarised the known (2015) medically understood as influencers of Parkinson’s. The whole list was only 5 things.

• Smoking
• Coffee
• L-DOPA drugs
• Isradapine (Dynacirc.. a calcium channel blocker for blood pressure)
• And something else which I can’t remember.

 

I see that two drugs that I regularly consume are

• (unfiltered) Coffee is on the list of weak CYP3A4 inhibitors
• Dynacirc – on the list of CYP 3A4 Substrates

Additionally, I have occasionally taken courses of Erythromycin for chest infections (and less occasionally, Prednisone). Both are on the list of CYP 3A4 Substrates.

 

My Parkinson’s diagnosis was made in 2005. For the first 9 years, I used solely Aryuvedic remedies. These kept the disease largely in check for those 9 years. A year ago, I approached a neurologist about Nilotinib, and on their recommendation, started taking Western L-DOPA medication. I did this on the assumption (or more accurately, hope) that this would be a stop-gap. I started Nilotinib in Septmber 2015.

(See http://www.longecity...ndpost&p=791675)

I must mention that the Neurologist was dead against my using Nilotinib, but because I was determined, agreement was made to do the UKPDRS measurements.

(See http://www.longecity...ndpost&p=795067)

As I said then, I restarted at 50mg. Nilotinb per day. But I found that even at this level, adverse effects accumulated over time.

I am extremely grateful for your advice, Library. Thank you.

So I think that my next steps will be:

1. To get another ECG. (I’ve had 2 already, early on)
2. To approach my GP about an alternative to Dynacirc (and also an alternative to Erethromycin).
3. To give up on coffee.
4. To stop taking the Aryuvedic meds.
5. Give myself a fortnight for the CYP3A4 situation to stabilise.
6. Continue with the L-DOPA meds (I’m not getting any side effects yet)
7. Getanother UKPDRS assessment made.
8. Then start back on Nilotinib 50mg for 2 days and then nothing for 2 days.

Any comment welcome.

My sincere gratitude to all contributors.

David

 

 

 

 

[splib]

Hi David, but do you think you've had any positive effects on PD symptoms from the Nilotinib ?

 

re:

> And something else which I can’t remember.

 

Probably Inosine ? There's a trial currently for that, you have to be careful not to ramp it up too high though because it can cause kidney stones or gout. The other thing not on your "influencers" list there is exercise or were you talking pharmaceuticals only maybe. Exercise and inosine kind of go well together, as far as I know the reason why inosine is readily available as a supplement is because it's used by people in intensive exercise regimens. But I think the trial is trying to show a potential slow down of progression, not really big changes.

 

re:

> Smoking

 

Well, for the case of using it as a therapy you use the transdermal patches, not actual smoking because you don't want to get lung cancer. This seems pretty promising because there's a big negative correlation between smokers being significantly less likely to get PD than non smokers. There's a French neurologist who has been pursuing this for a while now it seems, the main source of information I've seen on it is this discussion thread here: https://www.neurotal...ines-magic.html .

 

I've been focusing on exercise 1hr a day and I've been doing the nicotine patch protocol for about a year now, I think the nicotine is helping but it's pretty difficult to say for sure because I'm early stage young onset which often has a slow progression anyway. But a few times that I've forgotten to put on a new patch (or patches now, I put on 2 of them now) I've had bad days which I think is an indication it's doing something.

 

Another one that I had some high hopes for is TUDCA: http://forum.parkins...ew-drug-for-pd/ but it didn't seem to do anything for me and did not agree with my digestion.

 

I also tried Low Dose Naltrexone for about a year but I decided it wasn't giving me any noticeable results so I stopped that. Also tried CBD for a while but not any luck there either for me anyway, I've thought some about higher doses.

 

Some other supplements that I take in the hope of just general brain health are Citicoline+Uridine+DHA , low dose Lithium Orotate, and recently started Xanthohumol+hops, Lion's Mane mushroom extract, and Ashitaba tea.

 

Also I just started Rasagiline 0.5mg a few months ago since I found a cost effective Indian manufactured version, there isn't consensus but it seems a lot of Neurologists think they showed evidence of slowing progression in the Azilect trials a while ago.

 

Then Nilotinib is next up to try.

 

splib.