So things have been interesting on my end.
I'll start with what I'm taking right now: Multivitamin 2x day (no iron), two 30g whey protein shakes morning and night, 2x sodium butyrate morning and night, 200 mg R-ALA, lialda, mesalamine enemas, and recently added a tiny bit of hydrocortisone to the enemas. The hydrocortisone was a recent addition.
My stools had slowly started becoming more firm, toilet bowl is often much clearer than it used to be, which indicates to me that at least the stools are getting firmer.
However, I was a total dumbass throughout the entire month of June. While I had all of the above in my regimen, every weekend, I was smoking massive amounts of hookah, exposed to second hand smoke, for hours at a time. I did this every weekend of June. According to Pravda, sudden cessation of smoking (which I was doing every single weekend) can exacerbate the problem and people have gone into flares or made flares worse by discontinuing smoking. I was dumb because I was under the impression that hookah was much safer than cigarette smoking until I researched it and learned that they are basically the same. So I had been smoking a ton every weekend. Progressively as June went on, I noticed an increase in symptoms which confused me at first. But then I connected the dots. Smoking hookah and exposure to the second hand smoke every weekend ended up making me flare up slightly after 4th of July weekend. So, lesson learned.
Another thing was that I had frequently thought my lack of urination was due to my colon not absorbing water until I learned the small intestine absorbs 95% of water you consume. So for about
a year and a half, I have been mildly dehydrated, which I'm sure slows down the healing process if you have an injury (our colons in our cases). So drinking more water fixed that problem and I think it might have helped a little with symptom improvement. Also, I may have mentioned that I thought ALA was making me lose hair, and I don't think that is the case anymore. There may be other factors involved there.
Basically, I've noticed improvement in bowel movements and symptoms by trying to approach my UC in terms of reducing peroxide production, inhibiting WBCs, and trying to let my colon rebuild its lining.
Currently I am sick and my rectum/sigmoid area is more inflamed than usual. I presume it the smoking and also holding in bowel movements for much longer that have contributed to this.
What I mean is that as the proximal parts of my colon start to heal, I've noticed that frequency has been reduced. This is great, except that the distal areas of the colon are slower to heal and have a much higher exposure to bacteria and fecal matter which exacerbates the problem. So while it was great that I could go 6-8+ hours without a movement, my rectum was not very happy about
this and started bleeding and swelling up because I held it in so long.
Under Pravda's theory, UC is really a vicious cycle. So as you get better, your colon lining might gain more exposure to fecal matter and bacteria before it is ready to handle it, thus causing more WBC inflitration and exacerbation of the original problem. Pravda emailed me back also saying that peroxides from WBCs also prompt colonocytes to make MORE peroxide. It's a positive feedback loop. There is so much intertia to overcome with regards to this disease. My experience with smoking and rectal flaring from holding in my BMs line up with Pravda's predictions and at least support the idea that UC is an attack against commensal bacteria.
All this leads me to believe that you need the steroids/mesalamine to overcome the cycle, as well as the sodium cromolyn to help the barrier get repaired faster. Anything that can be done to help the barrier get repaired faster and keep WBCs at bay will probably get you out of the vicious cycle.
So basically, I had begun getting better but the regular smoking eventually caught up (before it did, I did see regular improvement) and now holding in my BMs too long have put me out of commission. Once I get out of this, I am going to ask my GI if I could get sodium cromolyn (turns out it can be used for UC, so shouldn't be too hard) and then I'll ramp up my ALA dosage. I'd imagine this will all help, as I was experiencing improvement before.
Also, I asked Pravda about
glutathione levels in all the studies in this thread, and he was kind enough to get back to me a while back on this. He answers his emails, but usually several weeks later.
I can understand your confusion. My paper details the pathogenesis of ulcerative colitis. The studies you cite describe the pathophysiology. In other words Radical Induction is a theory of how the disease begins not what happens after the disease is present.
Ulcerative colitis starts because at one moment in time the oxidative stress (H2O2) present in the colon was greater than the reductive (antioxidant-glutathione) capacity required to neutralize the H2O2 and restore redox balance. This excess H2O2 leaks out of the colonic epithelial cells, which leads to an infiltration of neutrophils and mucosal inflammation.
Once present, the inflammation is self-propagating and indicates insufficient mucosal reductive capacity relative to the amount of H2O2 being produced. The H2O2 produced by the neutrophils can re-enter the mucosal epithelial cells and stimulate them to produce even more H2O2. This initiates a positive bio-feedback loop or vicious cycle that increases H2O2 production over time. The phenomenon is called "ROS induced ROS release". You can read more about it here:
When a cell is subjected to oxidative stress it will upregulate (increase) it's antioxidant capacity. However, when the oxidative insult is too great and too fast it can overwhelm the reductive capacity of the cell leading to accumulation of excess H2O2. Even though the epithelial cell may eventually increase it's glutathione content it's usually too-little too-late to deal with the onslaught of neutrophils streaming in to the mucosa.
There are different factors that influence the glutathione levels in the body. One is the large amount of polymorphic variation among the enzymes responsible for its synthesis. This article has more information on the subject:
Ninety percent of cell H2O2 is produced within mitochondria but mitochondria only contain 10-15% of the cell's total glutathione. Additionally, mitochondria don't synthesize glutathione and must import all it's glutathione from the cytoplasm where glutathione is synthesized. Once depleted it takes several hours to replenish mitochondrial glutathione. So, after a severe oxidative stress that depletes mitochondrial glutathione there is a period in which mitochondria are flooding the cell with H2O2. Once this stage is reached it takes about 3 weeks to overcome the cellular reductive reserve after which H2O2 diffuses to the extracellular space leading to mucosal inflammation.
Starting out with low glutathione levels increases the risk of a radical induction event that can lead to inflammation.
So that's what's going on with me. Hopefully in a few weeks, I can report some actual good news. I've seen some actual promise with Pravda's method, and hopefully adding cromolyn and upping my ALA in addition to everything else i'm doing (as well as avoiding smoking and holding in BMs too long before I'm all healed) will yield full remission. Hopefully.
I am definitely better overall since being diagnosed, that's for sure.
Post Edited (Tunnelvisionary) : 7/15/2015 11:56:59 AM (GMT-6)