February 2014
WE DID IT!!!!
WE FOUND IT!!!
I CAN'T BELIEVE IT!!!
How the sweat test is used for diagnosis of CF:
less than 40 = no CF
between 40 and 60 = inconclusive
more than 60 = CF
Our sweat test history:
at diagnosis in Nov 2008: 118mmol/L
May 2013: 90mmol/L
Feb 2014: 59mmol/L
Since May 2013 we have changed nothing except gone up on the dose of Curcumin and Genistein.
IT WORKS!!!
IT REALLY REALLY WORKS!!!
We are currently using 3600mg of Curcumin with piperine and 150mg Genistein (both AOV brand) per day for a weight of 44kg. We spread this out into 4 doses throughout the day, taken with fatty foods and enzymes. A few days before this latest sweat test I found out that dissolving both Curcumin and Genistein in very hot milk, just off boiling point (cow or soy, both are good), greatly improves absorption and I highly recommend it to everyone!
Some might think this could be a coincidence or something that can happen spontaneously. It doesn't. I did not pay attention in Statistics class on how to calculate the chance that this is a coincidence, but if I'd have to guess it would be p=0.0andalotmorezeros1. This doesn't just 'happen' in CF. Below are some graphs from scientific research articles on the new medication (Kalydeco/VX770) for CF that corrects the underlying defect. You'll see that the drop in sweat chloride we have found (minus 59mmol/L) is even greater than what is seen on 150mg of Kalydeco. (please note that the drop from 118 to 59, is coincidentally the same as the absolute result of the sweat test, which is also 59)
 |
It might be interesting to know that the price for Kalydeco (=VX770) is over $300,000 per patient per year. What we use now costs $170 for 30 days, so $2.040 per year. That is 0.7% or the price of Kalydeco!
I will write a page on what we do exactly, what else we give and how we give it, but for now, I really wanted to let you know these results!
It is uncertain which mutations can benefit from the combination of Curcumin and Genistein. At first I thought it would only work for gating mutations (Class 3, see the story below), but there have been some people with double delF508 that have started trying at low doses and have noticed the exact same results as we did in the beginning. So it's definitely worth a try!
If anyone has tried, or is going to try these supplements, I would love to hear from you! Please send me an e-mail at curcumingenistein@yahoo.com
This is how I started this blog in October 2013:
(Before you begin to read the rest, please note I am a CF mom, not a doctor. There is no proof, other than ‘in vitro’ and ‘ex vivo’ tests (and now the sweat chloride test!), that the combination of supplements mentioned below works for CF patients. We think it does, but we are not sure (latest update from users, see 'Early Results'). There is no safety information. We don’t know if this combination is safe for CF patients. There is a lot of information on the use of each supplement separately. They both have a very good safety profile. Even high doses have been used short term without apparent problems. But that is not the same thing as combining the two in a CF patient. I am not recommending the use of these supplements in doses higher than the daily recommended dose by the manufacturer, it might work better in higher doses, but I don’t want to harm anyone with my recommendations……. It’s completely up to you if you want to try. But please be careful! Safety first!)
Our story:
Our son J was born in 2006 and was diagnosed in 2008 with Cystic Fibrosis (S1251N, a so called ‘gating’ mutation and delF508). I soon started researching everything to do with CF, every chance I got, hoping to find something to keep my son as healthy as possible. Slowly we added more and more supplements to his daily routine, based on what I learned.
J is now (2013) seven years old and has stayed super healthy over the last 5 years. His health has actually improved. His lung CT scans are now 100% okay, he has been able to eradicate Pseudomonas after culturing it for a year and half, his liver enzyme levels have returned to normal, so he no longer needs Urso. We were even able to lower his enzyme use to about half of what it was before (he now uses one Creon10 for 20 grams of fat). He shows no symptoms of CF, expect for (partial?) pancreatic insufficiency and a sweat chloride level of still 90 mmol/L (he had 118 mmol/L at diagnosis, so his sweat chloride has dropped 28 mmol/L, but is still very much in the ‘CF range’). He is also ‘off the charts’ overweight (oops…, but hey…they said give him lots of fat, didn’t they?) and his length is well above average for his age. Besides vitamins and supplements he uses no medication other than Creon, some allergy medication and some Macrogol to help keep his stools soft.
The truth is, we didn’t know exactly which of the supplements was doing the trick or if it was a combination of different things. So this year an opportunity presented itself to test some of the supplements on his own (intestinal) cells (‘ex vivo’) and we found what is probably the biggest reason he is doing so well….
It’s the combination of Curcumin and Genistein. They have a synergistic effect. Used together in relatively low concentrations they potentiate his CFTR function substantially (‘ex vivo’ that is).
Would one use only Curcumin or only Genistein in low concentrations, it would probably not make a noticeable difference on CFTR function. However, combine them in the human body and BOOM! It works! Like a magic factory!
There are two research articles that I know of, referring to the additive and/or synergistic effect of Curcumin and Genistein on CFTR.
=======================================================================
First:
J Cyst Fibros. 2011 Jul;10(4):243-52. doi: 10.1016/j.jcf.2011.03.001. Epub 2011 Mar 26.
Curcumin and genistein additively potentiate G551D-CFTR.
Yu YC, Miki H, Nakamura Y, Hanyuda A, Matsuzaki Y, Abe Y, Yasui M, Tanaka K, Hwang TC, Bompadre SG, Sohma Y.
Source
Department of Pharmacology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan.
Abstract
BACKGROUND:
The G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) is a common cause of cystic fibrosis (CF). G551D-CFTR is characterized by an extremely low open probability despite its normal trafficking to the plasma membrane. Numerous small molecules have been shown to increase the activity of G551D-CFTR presumably by binding to the CFTR protein.
METHODS:
We investigated the effect of curcumin, genistein and their combined application on G551D-CFTR activity using the patch clamp technique.
RESULTS:
Curcumin increased G551D-CFTR whole-cell and single-channel currents less than genistein did at their maximally effective concentrations. However, curcumin further increased the channel activity of G551D-CFTR that had been already maximally potentiated by genistein, up to ~50% of the WT-CFTR level. In addition, the combined application of genistein and curcumin over a lower concentration range synergistically rescued the gating defect of G551D-CFTR.
CONCLUSIONS:
The additive effects between curcumin and genistein not only support the hypothesis that multiple mechanisms are involved in the action of CFTR potentiators, but also pose pharmaceutical implications in the development of drugs for CF pharmacotherapy.
Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
=======================================================================
Second:
Curr Pharm Des. 2013;19(19):3521-8.
Curcumin and genistein: the combined effects on disease-associated CFTR mutants and their clinical implications.
Department of Pharmacology, Keio University School of Medicine 35 Shinanomachi, Shinjuku, Tokyo, Japan. yoshiros@sc.itc.keio.ac.jp
Abstract
Genistein and curcumin are major components of Asian foods, soybean and curry turmeric respectively. These compounds have been intensively investigated for their chemical and biological features conferring their anti-cancer activity. Genistein and curcumin have also been investigated for their potentiation effects on disease-associated CFTR mutants such as ΔF508 and G551D. Recently, we investigated the combined effect of genistein and curcumin on G551D-CFTR, which exhibits gating defects without abnormalities in protein synthesis or trafficking using the patch-clamp technique. We found that genistein and curcumin showed additive effects on their potentiation of G551D-CFTR in high concentration range and also, more importantly, showed a significant synergistic effect in their minimum concentration ranges. These results are consistent with the idea that multiple mechanisms are involved in the action of these CFTR potentiators. In this review, we revisit the pharmacology of genistein and curcumin on CFTR and also propose new pharmaceutical implications of combined use of these compounds in the development of drugs for CF pharmacotherapy.
PMID: 23331029 [PubMed - in process]
=======================================================================
(unfortunately these articles are copyrighted and I am by law not permitted to place the full text on this blog)
The research from the second article shows that combining Curcumin and Genistein on G551D ('in vitro') in low concentrations shows a synergistic effect of restoring the gating defect of G551D-CFTR up to around 50% (!!!!) of normal. The authors conclude: "This combination might succeed in activating the mutant CFTR channel up to a therapeutic level."
The research was done on G551D. My son J has S1251N (a Dutch Class 3 gating mutation). So now we know it works on G551D and S1251N.
I have no information on any other mutations it might work for. Logically one could think the combination might also work on other gating mutations (G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, G1349D). One could think residual function mutations like R117H might also benefit or conductance mutations like E56K, P67L, D110E, D110H, R117C, R347H, R352Q, A455E, D579G, S945L, L206W, R1070W, F1074L, D1152H, S1235R, D1270N, 2789+5G->A, 3849+10kbC->T, 3272-26A->G, 711+5G->A, 3120G->A, 1811+1.6kbA->G, 711+3A->G, 1898+3A->G, 1898+1G->A, 1717-1G->A, 1717-8G->A, 1342-2A->C, 405+3A->C, 1716G/A 1811+1G->C, 1898+5G->T, 3850-3T->G, IVS14b+5G->A, 1898+1G->T, 4005+2T->C, 621+3A->G and 621+1G->T.
But as I said, I don’t know. It MIGHT work on more mutations….(and then it used to say here: "Probably not, but I am not sure"…. now (Feb 2104) I'm changing that into:) It is worth a try! Who knows…
The mutations mentioned above will probably also benefit from Kalydeco. But for those who don’t have access to Kalydeco (yet), this combination of supplements might be useful in the meantime.
Just using the daily recommended dose of both Curcumin and Genistein, has made a huge difference. Using higher doses could have more effect, but, especially in the long run, also increases the risk of side effects.
BUT….the weird thing is, the graph from the research article above shows that at LOW concentrations, the combination works BETTER than at higher concentrations. The lower the concentration, the better it works. Completely opposite to what is usually seen. However (!), we’re talking laboratory ‘in vitro’ concentrations, which are extremely high compared to what one would be able to accomplish ‘in vivo’. You’d have to take a bathtub full of Curcumin every hour to get to those concentrations in the blood…… The good thing is, the lowest concentration they use in the test, is probably one that CAN be reached ‘in vivo’. BUT…..we don’t know the effect of the combination on CFTR at even lower concentrations, since the researchers didn’t test that, or to be precise no results of a test with lower concentrations are mentioned in the article. Since the dose-response curve is the mirror image of what one usually sees, until further information on the subject is available, we’ll just have to try and figure out the best dose for ourselves.
What it comes down to is this….. ‘in vivo’ we don’t know what doses or concentrations would work best and at which ratio. You can’t even compare ‘in vitro’ concentrations to ‘in vivo’ concentrations since in an ‘in vitro’ setting there is no blood flow to the cell. The cell literally needs to be bathed in the solution to get it into the cell. In the human body there is blood flow to and through the cell. The blood will take the compounds into the cell. So ‘in vivo’ one would need lower concentrations to reach the same effect as ‘in vitro’.
Here at home with J we are trying different doses and closely observing the effects. If we go up or down on the dose of either one of the supplements, we only change 1 of the supplements at the time and only 1 capsule at a time. We take at least two weeks to observe if there is any noticeable improvement or worsening.
J takes the supplements together with fatty foods and enzymes. Curcumin and Genistein are fat soluable. If you don’t take it with fat (and enzymes) it probably won’t be absorbed by the intestines at all. He takes it divided over at least 4 doses throughout the day.
Absorption is a problem with Curcumin according to most research (even when you take it with fatty foods). However, even in low doses, we have the healthy living proof of our young hero to show that it works. I don’t know where it goes after ingestion, but for him it works. It gets to the lungs!
On the other hand, maybe we don’t want all of the Curcumin absorbed. We might want to leave some Curcumin in the intestine, so it can do it’s work on the intestinal mucosa from the inside and not through the blood, since there is CFTR in the intestine too. We have seen effects on J that might point in that direction.
We have noticed that dissolving Curcumin in hot (soy)milk improves absorption. We microwave about 30ml to boiling point, take it out of the microwave, open one Curcumin capsule, poor it into the milk. Stir, strain a few times, and stir some more until all is dissolved, than mix it into 200ml of chocolate milk (hot or cold). If a seven year old drinks it without complaints, it must be palatable for most everyone. Another idea might be dissolving Curcumin in a cup of hot soup. But this pre-dissolving is not necessary. Just taking a little more Curcumin would give you the same added effect.
So by dissolving Curcumin it is absorbed better, which we notice in the lungs (wet cough), not dissolving it seems better for his digestion (firmer stools) though, to be honest, we are not always sure if the changes in stools we see are an improvement or worsening of symptoms…….). I have to try more combinations to see if this is indeed the case.
All in all, it’s completely experimental. Yes, there is scientific evidence it works in a laboratory setting (‘in vitro’) and on living human cells (‘ex vivo’), but we absolutely don’t know what happens in the CF body (‘in vivo’) after taking this combination of supplements. There is nothing I can say about safety, except for my son taking no more than the daily recommended dose of both supplements (adjusted for his weight) for the last 5 years and noticing no ill effects.
It may have been something completely different that has kept my son healthy, that all this is just a huge coincidence…. Probably not, but I just really don’t know.
Writing this, I have no idea how many people are going to read this and how many questions will come my way. I hope I will be able to answer them….
The brand we use is AOV for both Curcumin and Genistein. It is a Dutch brand (from The Netherlands, that is). It’s Curcumin with added Bioperine (piperine) with a daily recommended dose of 1.200mg Curcumin and Genistein Soy Isoflavone Complex with the daily recommended dose of 440mg complex, containing 97mg pure Genistein. The daily recommended dose is for a person weighing around 70kg. We have been using about half that dose for both supplements for years. At this moment (September 2013) we are experimenting with higher doses (2,400mg of Curcumin and 150mg of Genistein for a weight of 42kg), but as I said earlier, I don’t want to recommend it to anyone, since I don’t know if it is safe.
As it looks now, a good ratio for Curcumin (with piperine/Bioperine) to Genistein would be around 20:1. So, for example, if you take 2000mg of Curcumin with piperine, aim for 100mg of genistein.
As it looks now, a good ratio for Curcumin (with piperine/Bioperine) to Genistein would be around 20:1. So, for example, if you take 2000mg of Curcumin with piperine, aim for 100mg of genistein.
We have not established a most effective dose for J yet. We are just trying and observing. We know it’s doing something, but we don’t know if we can get more effect out of it. He still a young child and he can’t tell us much about what he feels in his body. An older CF patient might have a better ‘feel’ for any changes happening in the body. If anyone wants to try other doses, it’s completely up to you. All I can do is share our experience and knowledge in the hope it can help other people with CF stay as healthy as possible.
Please see the top right hand side for links to other pages or click here:
Our story
Why I started Curcumin and Genistein in the first place
How to start?
What to expect?
Early results
What else do we do/use?
CFTR and Genistein
Curcumin general info
Please see the top right hand side for links to other pages or click here:
Our story
Why I started Curcumin and Genistein in the first place
How to start?
What to expect?
Early results
What else do we do/use?
CFTR and Genistein
Curcumin general info
All feedback is highly appreciated! Please send an e-mail to curcumingenistein@yahoo.com
No comments:
Post a Comment