I've been meaning to write this post for a long time. For at least a year now, a portion of the CF community has been experimenting with "the Combo", or the combination of curcumin plus genistein supplements to help modulate CFTR function. This intervention is proving to be very helpful for many people who try it, yet it is a complicated issue. The impacts are somewhat mutation-specific, and the rate of digestive absorption of these herbs varies person to person, thus the dose must be deduced via personal experimentation.
I have experimented with the Combo myself, and after several rounds of going on and off of it for months at a time, I have determined that it does in fact provide significant enough symptomatic relief for me to notice and be willing to pay $100/month for it.
In this article I will discuss what the Combo is and how it was discovered. I will let other folks who have done more research on the subject give you the nitty-gritty of what the Combo does on the cellular level (I've provided the links below). Next I will discuss how I've used it and how it's made me feel.
What is the Combo?
The Combo is a combination of two plant-based supplements: curmumin and genistein. Curcumin is a constituent of the Indian herb turmeric, which has been used in Ayurvedic medicine for centuries. Recent research has show turmeric, and curcumin specifically, to have anti-cancer, anti-viral, wound healing, and CFTR-modulating properties  (for refresher on CFTR function, visit this page). Genistein is a constituent of soy beans, and alongside its phytoestrogenic effects, it has been shown to modulate CFTR gating. Specifically, in-vitro research has been done on the G551D mutation of CF to show that the combination therapy of genistein and turmeric potentiates CFTR gating . In other words, it makes the CFTR work better, which if translated to the human body, would alleviate many of the symptoms related to cystic fibrosis. The two constituents work synergistically, meaning that when used together, the result is more than the sum of their parts. For example, if curcumin supplementation alone provides a 1% improvement in CFTR function, and genistein alone provides a 4% improvement, together they might provide a 25% improvement! No clinical research (i.e. human trials) have completed on this subject so far, but a study on the Combo's impact on CF patient symptoms is currently underway in the Netherlands (thanks to Samantha in Holland).
The point of taking the Combo is essentially to improve the functioning of the CFTR enough that chloride can now move out of our epithelial cells (including lung and gut cells) in more sufficient amounts. This will cause water to follow the chloride and leave the cell, thinning out the mucus layer outside of the cells. The result would be a more watery mucus and if you did a sweat test, a lower (and more normal) test score. Several people (including Samantha's son) have been able to significantly reduce their sweat test scores with the Combo.
How was it discovered?
There has been some in-vitro research on the subject in the last couple of years, but what got the CF community started on experimenting with this therapy were the efforts and writings of a couple of smart and determined CFers including Francis Xavier Via, and a CF mother, Samantha. Francis pioneered a lot of the initial work on the Combo, and Samantha helped educate the CF community at large. Samantha's experimentations helping to better her young son's health (who has CF) through diet and herbs, she saw that when she fed him soy milk and turmeric together, the consistency of his mucus and the quality of his cough seemed to change. She did some research and determined that it was the genistein and the curcumin (respectively) that were creating the changes. So she began using isolated supplements of each of the constituents, in different combined doses, to see what worked best for her son. She has posted much of her research and experimentation on her website, http://dutchmagicfactory.blogspot.nl.
As a result of her work, others have done more research and experimentation and have contributed to the community's overall knowledge base. This is true grassroots medical research at its best! One experimenter created this website (http://www.potentiate.info), which has links to more scientific papers on the subject. CFers from all over the world have now started experimenting with the Combo over the last year, and many have found it to give them significant improvements in their health. One of the most interesting things about the Combo is that it can be used synergistically with Kalydeco to make its CFTR potentiation even more effective. I am hopeful that when the ivacaftor+lumacaftor drug for the DDF508 mutation (that's me) comes out next year, the Combo will help it work better for me. We shall see.
I began experimenting with the Combo about a month after I started my experiments with inhaling essential oils. I think a large part of the effectiveness of the oils was the conjunctive therapy with the Combo. However, I didn't come to discover my most effective dose for the Combo until about two months later. It took a lot of trial and error experimentation, and a few periods of going without it for weeks (I kept running out).
Since the beginning I have been using two brands predominantly and these seem to work well (plus they are the cheapest I could find): Life Extensions Super Absorbable Soy Isoflavones (for the genistein) and Vitacost Turmeric Extract Curcumin C3 Complex with Bioperine (1160mg per serving). I get both of these from vitacost.com. I started with a twice-a-day dose of 1 capsule of each, which consisted of 28 mg genistein/genistin, and 550 mg of curminoids. I used the ratio guidelines provided by Samantha and others to determine how much of each plant I should use. I didn't feel much difference on this dose so I increased it to 3xday. A month later I increased the dose to 2 capsules of genistein (56 mg genistein/genistin) and 3 capsules of curcumin (1650 mg curcuminoids) 3xday. At this dose I finally began to notice a significant difference in my mucus and a slight reduction in the level of lung inflammation. At one point I tried higher doses (4 curcumin and 3 genistein 2xday, then 3xday) just to see what would happen, but the 3 curcumin and 2 genistein dose seemed to change my symptoms the most. I take the capsules with a fatty snack or meal (at least 10g of fat, to be safe) and try to space the doses as close to 8 hours apart as I can. Curcumin is fat-soluble constituent, so must be taken with dietary fat.
It took a few days of subtly tumultuous symptoms, but about 3 days after starting the 2 genistein/3 curcumin dose I began to notice my sputum was a bit thinner and easier to cough out. It didn't take so much effort to do my acapella and huffing as it usually did, and it took less time to clear out the crackles I usually hear at the end of my treatments in the morning. My energy levels began to improve slightly. I noticed my fasting blood sugars and post-meal blood sugars were also slightly reduced, so it seemed my insulin-sensitivity was improving. Although I cannot attribute all of these changes directly to the Combo since I was inhaling essential oils at the time as well, I did notice that using the Combo did seem to make the EOs more effective. Several months later, I had to go on 3 months of minocycline and bactrim orally. The first month I did not use the Combo, and the last two months I did use the Combo. I noticed that the Combo seemed to make the antibiotics work better. I had less cough and less lung inflammation, and my mid-day fevers didn't zap as much of my energy. In addition, my fasting blood sugars and insulin sensitivity improved while on the adjunctive therapy.
As I mentioned, dosing is different for everyone depending on their mutation, body weight, and the way they digest and absorb foods and xenobiotics. Samantha gives some guidelines on suggested ways to start dosing here. Much of the digestion and absorption of plants and their constituents depends on the make up of the gut microbiotia. Our gut bugs break down and help us absorb plant nutrients, especially those contained in a complex polysaccharide matrix. It has been shown that using isolated herbal constituents in their active forms (like genistein, for example) may not be as effective as ingesting the precursors to their active forms (like genistin) as they naturally occur in whole plants, because gut bacteria break down the whole form of the precursor molecule into its active form, maximizing its absorption . In other words, in order to maximize digestive absorption of plant-based constituents, especially polyphenols, it is necessary to take them as close to their whole forms as possible, and it is necessary to have healthy gut microbiota that can properly break down these chemicals for uptake. If the active, isolated constituents are taken in their pre-metabolized form, they are absorbed across the intestinal wall at a lower rate, thus you will need a higher dose. Therefore, taking a supplement with both genistin and genistein in it is likely the best solution. In addition, it is once again a good idea to pay attention to the health of your microbiome, and to supplement with probiotics and fermented foods to boost your healthy gut flora if need be.
This is an addition to the original post: Since my last hospitalization 2 months ago, I discovered that afterward, the Combo at my regular dose (3 curcumin + 2 genistein) was not working as well for me. That is, it was not thinning my mucus as much as it usually does. Thus, I upped the dose to 4 curcumin + 3 genistein, and that seemed to do the trick. I can't afford to do that dose 3 times a day (that's like $168 a month right there), so I decided to take this higher dose 2xday instead of 3xday. That seems to work alright, and I try to take it at least an hour before my twice a day breathing treatments, so that I have loose mucus when I want to cough stuff out. But why was the dosage change necessary? Well, I believe that when I got my last course of IV antibiotics in the hospital, it shifted my gut flora enough that the metabolism of these herbs became less efficient, so now I need to take a higher dose to elicit the same effect. I am taking probiotics and eating sauerkraut to try to restore the diversity that I once had, but that will take some time. Hopefully at some point in the near future, I will be able to drop the dose back down to what it was before.
There are a few things to be aware of before starting the Combo. The first is that in a few sensitive people, a irritation or allergy can develop in reaction to curcumin. It doesn't seem to cause any problems at first, but after about a month of using the Combo a few people may experience an increase in lung inflammation, spasmy coughing, and mild allergic symptoms. If this occurs, go off the Combo for a few days to see if the symptoms improve. If they do improve, then you might have a curcumin sensitivity or allergy.
Secondly, I noticed in myself that several times when I was going either on or off of the Combo, I would wake up the next day with a small bit of blood streaked in my sputum. This was not enough blood to make me alarmed, but it was something that happened several times. I have no idea why this could have happened, but I think it's at least worth noting, especially if folks have pre-existing issues with hemoptysis (I have in the past) or blood clotting issues. However, once on the Combo for several days, it seemed to reduce my risk for coughing up blood, so maybe something strange was happening in the transition period. I am not well-educated enough on the specifics of CFTR function to make an educated guess as to why this would happen, but it doesn't worry me enough to stop taking the Combo.
Thirdly, Samantha has noted that in her young pre-pubescent boy the use of very high doses of genistein (way higher than what I was using) may have caused some strange symptoms in him, some of which seemed to indicate that the phytoestrogens in genistein were messing with his endocrine system and causing what appeared to be signs of an early puberty (at age 8). The symptoms were reversed after reducing the dose. However, later she hypothesized that the signs of early puberty may have appeared due to his excess body weight (body fat being hormonally active), and that in order to prevent these symptoms she simply needs to reduce his calorie intake and have him lose some weight. There have been no other reports that any other children using the Combo have had any symptoms similar to what her son experienced, probably because most CF kids are underweight, not overweight. But it is something to keep an eye out for, just in case. Also, if you have any estrogen-sensitive tumors or cancers, you may want to talk to your doctor before taking genistein. Plus, if you are pregnant or breast-feeding, you may not want to introduce phytoestrogens into your body this way.
Why is the Combo important?
The Combo is an important discovery because it can help reduce CF-related symptoms and improve CFTR function for many people with a simple, unpatentable plant-based solution. While we are waiting for the Vertex drugs to become available to us (for those of us who have compatible mutations) this may help us feel better and reduce the number and severity of lung infections we experience. Secondly, for those who are currently on or will be on a Vertex drug, and that drug is not providing them with the symptom relief that they were expecting, the Combo may work synergistically with the drugs to potentiate the CFTR. Thirdly, for those CFers living in countries that have not yet approved the Vertex drugs for use, and therefore cannot get access to them even if they have compatible mutations, the Combo may be a helpful therapy to use in the meantime. It is not a one-to-one replacement for the Vertex drugs, but it is certainly better than nothing in many cases, as long as you can discover the right dose. Lastly, for those with CF mutations that are not targeted by any CFTR-modulating drugs currently in existence or in development, the Combo may be helpful in the absence of a pharmaceutical solution.
If you are embarking on an experiment with the Combo and would like to help the efforts of citizen-based science, contact Samantha via her website. She is collecting data from people who have done this self-experimentation.
 Curcumin and genistein: the combined effects on disease-associated CFTR mutants and their clinical implications. Y Sohma, 2013. http://www.ncbi.nlm.nih.gov/pubmed/23331029
 Isolation of human intestinal bacteria metabolizing the natural isoflavone glycosides daidzin and genistin. HG Hur, 2000. http://www.ncbi.nlm.nih.gov/pubmed/11195098