Monday, January 5, 2015

Day 3: Tauroursodeoxycholic Acid

Hello to day 3 on this ride. Sunday, 1/4/15

Before I begin, I need to make a correction on the last blog post. My mind jumped to the figure "1200 mg" in describing what I am now taking on double dose. I had too many numbers in my head and misspoke. 4 250 mg pills a day equals 1000 mg, not 1200. So I'm a little under the "minimum" amount I listed, not a little over it.

Sorry about that. I thought of it sometime Sunday morning, figured I'd correct it in tonight's blog post. Then my wife noticed something didn't add up. Finally, one of the forum members private messaged me about it. Sorry if that confused anyone.

I should also clarify something else. I mentioned the study that gave participants 15, 30, and 50 mg per kg of patient weight. The purpose of that study was:

The objective of this research was to study the safety and the tolerability of ursodeoxycholic acid in amyotrophic lateral sclerosis and document effective and dose-dependent cerebrospinal fluid penetration.
http://journals.lww.com/clinicalneuropharm/Abstract/2010/01000/Safety,_Tolerability,_and_Cerebrospinal_Fluid.5.aspx

Ursodeoxycholic acid is the same compound as what I'm taking, except it isn't bound to taurine. The body actually converts a good part of UDCA into TUDCA once it makes its way through the digestive tract and the liver.

So they gave people in the clinical trial various levels of UDCA in order to determine if patients could tolerate that much and how much of the dose made it into the brain where it is needed. That data was one factor they are using to determine the most effective doses to give people for slowing the progression of ALS.

I was pointing to that study not to indicate what is the appropriate amount I should be taking for PD, but to show that the amount I planned on taking was well within tolerability limits so folks wouldn't worry that I might end up overdosing myself.

Indeed, the experience of researchers looking into using this drug for PD in the UK indicate that the minimum dose in their experience thus far, to see results, is 600 mg/day, while doses beyond 1200 mg/day don't seem to convey any additional results/benefits.

IOW, despite not yet having an established recommended effective dose of UDCA for PD, the best data suggests that 1000 mg/day is high enough I should see results if it is going to do anything. The purpose of quoting the numbers from the previous study was to indicate that I'm not blindly taking an amount that would be dangerous.  That study indicates I could take up to 4 grams a day safely. But there is no purpose for me to take that much. 1 gram a day will do the trick.

Now that we've cleared that up, here are my observations from day 3 of taking TUDCA.

Side-effects: haven't noticed any.

Symptom changes:

This will be a little more difficult today. On one hand, I did notice some symptom changes. On the other, all but a couple I've experienced before since getting on Azilect, so I can't cleanly assign their appearance to taking TUDCA.

Namely, my arm and leg stiffness felt better today. Tremors were at a minimum during my 3 hour service chanting and singing. I did experience some dyskinesia but that is to be expected since that is caused not by PD, but by the meds I'm taking for PD. The only way TUDCA will help that is if it eventually allows me to reduce the amount of Sinemet I'm taking, or possibly no longer taking Azilect. But I'm not going to reduce/eliminate those until I know this is working.

On a quick side note, I'd mentioned the dyskinesia in my left leg is the feeling of it being antsy and not wanting to support me. That was the best I could describe it, but I've felt it inadequate to convey what is going on. This morning, I realized what the dyskinesia effect on my left leg is doing. The movement effect is causing me to pull my knee forward and bend, so it is no longer supporting my body. My "antsiness" is my leg's fight not to let it do that, cause I need it to stand up. When I had doubled my Sinemet back in September, it was bad enough that at times I thought I might have to leave and go sit down. Now it is just an annoyance.

Anyway, since about week 3 on Azilect, my arm and, to an extent, my leg stiffness was greatly reduced. The only Sunday that it seemed to fail was last Sunday, when my tremors, stiffness, and dyskinesia were worse than it had been the previous two Sundays. Not sure what was going on last Sunday in my body, but this Sunday the tremors and stiffness were back to what they had been before as Azilect had an effect. So while they were better in relation to the past Sunday, I couldn't attribute it to taking TUDCA, though there is a chance that adding it may have helped. No way to know on that account.

I mentioned last time about seeing some "cogwheel" movement improvement. Today that stayed the same. Indeed, I was able, in a rough way, to drum-roll my fingers on my left hand smoothly. I could lift with more ease each individual finger on command without moving the others, something that before was difficult to do, much less smoothly. Still not as smooth and effortless as my right hand, but noticeably better.

I also noticed this improvement while washing my hair this morning in the shower. Usually in scrubbing my head, my left hand doesn't keep up with my right hand both in speed and coverage. The cogwheel effect gets in the way of effective movement. This morning I had no trouble with my left hand working in sync with my right, matching its actions.

This is definitely an improvement. The question comes in as to whether this is a result of Azilect fine-tuning its benefits, or a result of adding in TUDCA? Azilect has helped in that department. I've noticed more control in my left hand since taking it the past few weeks. But it hadn't improved over the past 2-3 weeks, and now suddenly it does. It would be easy to debate whether the improvement was Azilect or TUDCA especially since the improvement is minor, but it is a bit suspicious that it had plataued until taking TUDCA.

But there is one more bit of evidence TUDCA may be involved in that result. Until taking TUDCA, my left leg stiffness and toe curling had only minimally been helped by Azilect. I couldn't tell much difference in that area before taking Azilect until today. Again, the result was minor, so could be my mind wanting it enough or the placebo effect in operation, but I did feel like my toe curling while standing for 3 hours was less than it has been. It was still there, but it didn't seem like I had to keep stretching the toes and consciously forcing them to relax as much as I have in the past. Even periods when I forgot about it.

If TUDCA is causing that improvement, it will become evident as the days go by and it gets even better. Once it is obvious it is not just my imagination or wishful thinking, it would be evidence that TUDCA is affecting muscle stiffness and tremors, and thus would be responsible for the cogwheel improvements as well, since Azilect has had little effect on my toe curling. The next few days should tell the story on that point. If no further improvement happens, the source of what I believed I experienced today will be in question.

The other symptom improvement is more definitive. It is a PD symptom I failed to mention in my list earlier. In part because it started months ago but never got any worse. So it just didn't come to mind until late Saturday night, and knowing it would get tested good Sunday morning, I waited to see what would happen today.

Since I was a teen, I've sung bass in church choirs. I'm a barritone, but it's always been easier for me to hit the bulk of the bass range than the tenor range. I could do either but my high range is limited, and it seemed tenor lines tended to require hitting those high notes more often than the bass line required hitting low notes out of my range.

However, since sometime in late 2013 or early 2014, my low range has become shaky thanks to PD. I can sometimes still hit the low notes, but it won't stick. It keeps breaking up or cutting out altogether. And the lowest notes of my range I get no real volume to come out at all like I used to. So the past several months, I've gravitated to tenor lines as now I could hit more notes in that range than I could the bass range.

Saturday night, I was playing around and sang something in a low bass range matching a song that was playing. I was surprised at how rich it sounded, no breaking up, and decent volume. I kept doing it for a while, a little amazed I could do it. I knew Sunday morning choir numbers would tell the story.

This morning, songs I'd been singing the tenor line on because they had too many low notes in the bass line that I couldn't hit with any volume and/or quality before, now I sang. Low and behold, the low bass notes I used to be able to hit, I did just as well as ever.

This is a pleasant surprise. None of the medications or supplements I've taken have had even a slight effect on that symptom. I've been surprised it has never progressed beyond that level. I was sure it was only a matter of time before I was in Linda Ronstadt's situation and would have to bow out of singing because I couldn't hold enough steady notes with the volume and quality to not be distracting. Yet it had never grown any worse since initially losing my lower range, so I've been able to compensate by singing higher keys and tenor lines.

But it had never become any better either. I figured at some predetermined point, my voice would drop from this plateau and become worse. Now, to have it get better offers some hope that this might help prevent that day from arriving, or at least set it back a few more years. And I'm sure this news makes my choir director happy, who I believe is subscribed to this blog.

But the bottom line is neither Sinemet nor Azilect have ever shown any indication of alleviating this symptom. There is a slight possibility that Azilect, in the later days of its maximum benefit range, kicked in with one last burst and improved this symptom it had heretofore had no affect on. While not impossible, it is highly improbable.

So to me, I label this symptom improvement a result of taking TUDCA. We'll see if in the days ahead that improvement sticks, which will solidify that conclusion. I believe, if it does, it would be a stretch to conclude it improved from anything other than taking TUDCA. Just too big a coincidence that it suddenly improved upon taking this substance when nothing else had affected it in the least.

So on day 3, I believe I can chalk one definite symptom improvement up to TUDCA. Other minor improvements may be a result of TUDCA as well, but I think we'll need more time and evidence to know they are real improvements and not a result of only Azilect.

That said, an encouraging sign. Hopefully the first of many.

2 comments:

  1. I don't usually comment, Rick, but I do follow this blog and pray for you. Thumbs up on *any* encouraging signs!

    ReplyDelete