Monday, January 26, 2015

Week 1: Off Tauroursodeoxycholic Acid

As noted last time, I was going to end my use of TUDCA when the bottle ran out, which would happen shortly after my Azilect 8-week-maximum-improvement window had ended. The window closed two Thursdays ago (1/15/15). My bottle of TUDCA ran out on the following Saturday, 1/17/15.

Consequently I've now been off TUDCA for a week. I figured it would be good to give a weekly update on any changes I've noticed.

By way of reminder, the plan is to see if being off TUDCA results in a loss of symptomatic improvements I experienced after using TUDCA to distinguish whether it was TUDCA or a second burst of benefits from taking Azilect that caused them. Now that the Azilect window is past, there is slim to no chance of any further improvements from it. I'll go for a maximum of 8 weeks--the time I can be sure all the TUDCA is out of my system--with no significant loss of symptom improvements before deciding the improvements came from Azilect. At any time before that, if I experience significant symptom improvement losses, I'll know that TUDCA was the likely source of improvements.

If the latter happens, I'll then resume using TUDCA and note if the improvements return. I'll also do some dosage increases to see at what point it no longer improves symptoms. If improvements return upon restarting it, that further solidifies that TUDCA was the cause of the improvements.

What I'll do is take each of the symptom improvements I listed on day 5, and using the scale of 1 to 10 (1 = symptom is horrible, 10 = symptom is near or at normal), relative to my experience, I'll give a weekly rating which will show a history of movement for each noted symptom improvement. Following that will be any comments if needed.

So, here we go!

Week 1 After I Stopped Using TUDCA


Low bass notes became functional again

Pre-Azilect: 3
Post-Azilect: 3
With TUDCA: 10
Week 1 off TUDCA: 6

This was the first symptomatic improvement to happen after starting TUDCA, and as you can see, it was dramatic. On day two of taking it, suddenly I could solidly hit the low notes I used to be able to hit before PD came on the scene. It was a complete surprise to me as no medication had changed that. No amount of dopamine had improved it. So I wasn't even thinking about it as something to watch for. Because of this, I felt this symptom improvement could fairly certainly be ascribed to TUDCA because there's nothing Azilect could have done to regain that ability. All it does is allow the dopamine in your body to not breakdown as fast, and so it lasts longer and allows for more buildup as you pump more in via Sinemet.

Early this past week, I noticed I had difficulty getting back down to those low notes. But if I worked at it, I could do it, but the notes were not as solid. This was confirmed while singing in church this Sunday morning, I couldn't hit the lower notes as solidly and with as much volume. Not quite as bad yet as pre-TUDCA, but obviously moving in that direction.

Cogwheel motion

Pre-Azilect: 4
Post-Azilect: 5
With TUDCA: 8
Week 1 off TUDCA: 6

I've noticed a little more difficulty in using my left hand for general movement tasks than while on TUDCA. Key indicator was while washing my hair, my left hand wasn't as able to keep up with my right hand in smoothness and completeness of scrubbing my scalp. A touch of jerkiness appeared.

Typing speed and ease

Pre-Azilect: 4
Post-Azilect: 6
With TUDCA: 8
Week 1 off TUDCA: 7

It's become more frequent as the week moved on, but more periods where typing was difficult. There were times it felt as hard as it did pre-Azilect. The periods when I felt I could type with minimal impedance grew fewer.

Dystonia

Pre-Azilect: 4
Post-Azilect:5
With TUDCA: 8
Week 1 off TUDCA: 6

By the end of the week, I was feeling it more than I had been, in general, while on TUDCA.

Tremors in left hand

Pre-Azilect: 3
Post-Azilect: 5
With TUDCA: 9
Week 1 off TUDCA: 7

Sometimes it is fine, but there are times it has some shaking going on. More so toward the end of the week.

Toe-curling

Pre-Azilect: 4
Post-Azilect: 5
With TUDCA: 7
Week 1 off TUDCA: 6

There was a period while taking TUDCA I could have given it a 9. But in general, I only noticed a slight improvement. Probably due to the increased dyskenisa in my left calf muscle making it hard to indentify changes. That and the sore on my left toe next to the little toe from the toenail fungus giving me pain when any pressure is put on it.

I've noticed only a little change this past week, but that could be my imagination, thus the small amount of change. It is possible I could have kept it near a 7. Future weeks might reveal more, but it is also possible this one will jump around. Some days are better than others. The last few days I'd even say were a 7 or maybe a bit better. I had some problems standing this Sunday morning, but as the service went on, it seemed to settle down some, the dyskenisia that is. It seems when the dyskenisia isn't as bad in that leg, the toe curling does better. So how much is the lack of TUDCA or the dyskenisia from Azilect and Sinemet is hard to nail down.

That's my status for week 1 after no longer taking TUDCA. It does appear that I've lost some symptom improvements, at least in part. Future weeks should give a clearer picture whether these will continue downward or bounce back up due to a circumstance in this past week causing their negative movement. I figure I'll need 3-4 weeks of data before making a determination that the downward trend indicates the improvements were from TUDCA.

But if the loss of low bass notes is any indication, it isn't looking good for Azilect right now. The next two weeks should show if there is any definitive trend. Until next Sunday night/Monday morning, have a great week!

Thursday, January 8, 2015

Day 6: Tauroursodeoxycholic Acid

Day 6, Wednesday, 1/7/15


Final day I'm going to do this daily log. From here on out I'll just comment about it if and when I have anything new to add in addition to my normal notes about how my PD journey is going.

I'll comment on how today went and then provide some concluding remarks about what it all means.

Side-effects: none noticed.

Symptom changes: I won't list them all out like I did yesterday. Overall, today was a little better than yesterday, but not quite as good as Monday, which for me was a peak day on symptom relief, especially tremors. Today I had some slight tremors when holding my hand out, like little movements in my fingers. Nothing major. Typing effort is about the same as yesterday. So all in all, I appear for the time being to have plateaued on my symptom improvement. Whether any long-term benefits will show up as this proceeds, we'll see.

Conclusions


Or to put it another way, what does this prove?

It proves to me that this drug may have produced symptomatic improvements in my Parkinson's Disease.

Read the above carefully. What I'm not saying is that this drug did produce my symptomatic improvements. I do think it is highly likely it did based on reasons I've given these past six days.

  1. My Azilect symptom improvements had plateaued before taking this, leading me to believe I had most probably already hit my maximum benefit I would get from that drug.
  2. The symptom improvements suddenly hit on days 3 & 4 in taking this, and have been sustained thus far. Any other explanation would be due to pure coincidence and thus less probable. The timing of their appearance leans to being from TUDCA.
  3. One of the symptomatic improvements, regaining my low bass note range, had never been affected by increases in dopamine like the kind Azilect would have supplied, and Azilect has no evidence of reviving dying cells, only maybe slowing their rate of decline. It is highly unlikely Azilect played a role in that symptom improvement. Consequently, it is likely the other symptom improvements didn't come from Azilect either.

However, I can't rule out that Azilect kicked in with some additional benefits. as its latest point of possibly hitting maximum benefits is 8 weeks and these increases happened during week 6. Thus my need to do a further test to validate whether or not these improvements happened because of taking TUDCA, which I detailed yesterday.

One note to that plan. I received a call today moving my scheduled neurologist appointment to a later date. So I think I'll keep taking TUDCA until I'm past the Azilect 8 week point, which should be . . .

Doh! I've made a miscalculation on how long I've been on Azilect. Sorry, thought I had that nailed down. Not a big one, just one week difference. I started taking Azilect on November 20th, a Thursday. That would put this Thursday (today for many initially reading this) the end of 7 weeks, not six. I've been taking TUDCA during the seventh week of taking my Azilect. Sorry about that miscalculation on my part.

That means I have one more week to go before the potential Azilect maximum benefits could hit, if they haven't already. So that ends on 1/15. Around then or shortly after that I should finish this bottle of TUDCA I'm working on. So when I run out at the end of next week, I'll not take more until such a time when I can identify that the symptom relief I've gained this past week disappears, proving it wasn't provided by Azilect. Then if they reappear upon restarting TUDCA, I'll know it was that med that did the trick. So the results from that test may be sooner rather than later, as it happens.

Anyway, the only other potential and feasible explanation for these symptom improvements would be the placebo effect: I had enough expectation that this would help that my mind generated enough physiological effects to bring it about without help from the medication.

There is a lot of debate about that. There is evidence it happens, but tends to be upon symptoms your body could feasibly control on its own. Stuff like depression, pain, stimulation or depression of one's bodily systems, stuff like that. One study identified about 34% of the population is susceptible to the placebo effect.

I won't bore you with a lot of details, but I consider the placebo effect highly unlikely in my case. Mainly because I've taken a lot of things that I expected or believed would help my symptoms, some that appeared to have logical sounding scientific backing, yet none of them produced the least amount of symptom benefit. If I were susceptible to the placebo effect, it would have happened to me before now. I'd be here touting the PD curative benefits of magnesium. I'd have no need of TUDCA, Sinemet, or Azilect. It makes no sense why I'd have no placebo effect until this pill.

Despite my leaning toward ascribing these benefits to TUDCA, I'm not ready yet to say they are because of taking this drug. Therefore my statement "may have produced." After the results of the next test, I may then be able to say I'm 99% sure TUDCA is responsible. Until then, the jury is still out.

Also, note that I said, "in my Parkinson's Disease." That's because this is not a full clinical trial study, complete with a double-blind placebo group to rule that out. Because I experienced symptom improvements doesn't mean others will for sure. PD and an individual's reaction to a medication is highly individualized. The only way to determine if a decent subset of PD patients would experience improvements would be clinical trials with a good sampling of participates, and a placebo control group.

So I'm not saying everyone reading this should run out and get some and try it. I'm not promoting this as a cure for PD or its symptoms. I'm not saying it will slow down or stop PD progression, though there are pre-clinical and human clinical trials that have shown it is highly likely to do so.

All I'm saying is at this point is it seems to be working for me. I'm providing one more anecdotal data point in why this drug should be given higher priority on getting through clinical trials and approval by the FDA, if the studies warrant it, than it currently is.

That said, in case someone reading this has a strong desire to try this to see if it works for them or not, I'm compelled to suggest the following recommendations.

  • Check with your doctor before taking this. There are potential issues he may want to check on, potential conflicts with any of your current medications, regular monitoring he may want to do to ensure it isn't messing up your liver or gall-bladder, etc. He may also have recommendations to offer.
  • Do your own research. Doctors make mistakes. Check yourself, for instance, whether it will conflict with anything else you're taking. Those are easy to check on the Internet. Learn what the studies say.
  • Be aware of potential side-effects and follow dosing instructions, like taking with food for the best absorption into your system and to reduce the chance of nausea or diarrhea.
  • Don't rush into it. Or as Treebeard would say, "Don't be hasty." Check out the information well and the recommendations of your doctor, so you're being smart about it. There are low-percentage but potentially deadly side-effects you'll want to make sure you avoid, despite the fact it is well tolerated by most people.

Anything like this carries some risk (nearly every medication actually), but you'll want to not take any unnecessary risks as well. If this is going to stir up some dormant gall-stones, for instance, you'll want to know they are there to avoid that painful outcome.

But it is your own body. Use at your own risk. But you owe it to yourself to know what those risk are before jumping in with both feet. It is up to you.

That's about it for now. Have a great weekend. Until the next time I have something to say, peace.

Wednesday, January 7, 2015

Day 5: Tauroursodeoxycholic Acid

Day 5, Tuesday, 1/6/15


Today I didn't work with my wife; stayed home to get things done. So wasn't on my feet as much. And to see how I handled it, I had some coffee today, most of a cup. That tends to produce a little more jitters a few hours after taking it.

A note about coffee. I've long been a coffee drinker. Even bought green coffee beans and roasted them myself for several years. Best coffee I've ever drank. As a matter of fact, I should try some more of it now, as it may be better handled by my system than what we get at the grocery store.

Anyway, I've talked with a number of PD folk about their coffee intake, and it seems most don't have a problem with it. It doesn't cause them any additional tremors or other nasty symptoms. Yet, for whatever reason, it does with me. If I have coffee around noon, my symptoms will get noticeably worse around 5 to 7 pm. I've noticed when I take it and when I don't. Unless this has become some weird Pavlov's Dog effect mentally, coffee does make my symptoms worse. Just to clarify since I know most PD sufferers don't seem to have this reaction to coffee.

I also had another complication. Too much to go into, but because of taking my Sinemet at an odd time today, and because the second dose would have fallen right in the middle of a high-protein meal, and in part because I forgot to take it any earlier, I ended up skipping it and picking up on my normal schedule when I take the final dose of the day. In effect, I only took two of my Sinemet pills when I normally take three. That's going to affect the results as well.

Here's how it went today.

Side-effects: none to report.

Symptom changes:

No new improvements to mention. I'll give you the current state of previously known improvement.

Low bass notes - still able to hit them solidly. I don't expect this to get any better because I'm pretty much able to sing now what I could before PD. I'm fully back to normal on this symptom.

This is a symptom improvement that I most fully attribute to TUDCA since no medication has affected that. I've been on Sinemet for a whole year and it never got better, even when my doctor doubled my dose. And it isn't likely to be Azilect either because all it does is allow the dopamine in my body to live longer. More dopamine never fixed this. Yet, three days after taking TUDCA, it suddenly improves. While it isn't impossible that the reported neuroprotective effect of Azilect had something to do with this, it is highly unlikely given the timing.

Cogwheel motion - So far I'd say this is being maintained at the new level of improvement. To put it on a scale of 1 to 10, with 10 being "normal before PD", I'd give it about a 7, maybe an 8. Previous to taking TUDCA, I'd say it was a 5, even with improved effects from Azilect by that point. Before Azilect, I'd say 3-4. And now I have times when it is doing closer to an 8 or 9. Not totally normal, but it is substantially better.

Typing speed and ease - Probably due to a combination of the coffee and missed Sinemet pill, today was a little worse than yesterday. Not horrible, but it wasn't as effortless to type, indicating a little less fine motor coordination in the fingers probably due to increased stiffness in the arm.

Dystonia - Stiffness wasn't as good as yesterday for reasons already mentioned. On a scale of 1 to 10, 10 being no stiffness, yesterday was a 7 or 8. Previous to that it was a 5. Prior to Azilect, around a 4. Today I'd call it a 6.

Tremors - Due to the above mentioned factors, I had more tremors than yesterday in my left hand. It wasn't drastic. While yesterday I'd put it at a 9 on the 1 to 10 scale, today it was more like an 8. Minor tremors present, but nothing horrible. Previous to TUDCA I'd put my tremors around a 6, maybe 7. Prior to Azlect, a 4. Maybe 5. Considering I had a cup of coffee and missed a Sinemet pill, that's not too bad, actually.

Toe curling - On this one I'd say I didn't notice any change up or down. Still maintaining the improvement I noticed earlier. But I should note I wasn't on my feet much today since I stayed home. Mostly worked sitting down at my computer. Tomorrow I'll be helping to clean a house and an office building, around 5 hours of work. So I should have a more definitive test of any changes up or down.

I think that covered them all. Did I miss one?

Where I'm going from here


As you may know from previous posts., many of these symptom improvements, while they appeared directly after taking TUDCA so the probability suggests it is the cause of the improvements, I can't rule out that Azilect has provided a new boost of benefits coincidentally at the same time, giving the appearance that TUDCA is responsible. If I'd been smart, I would have waited another four weeks to run this test, after Azilect's longest point of the maximum benefits range--4 to 8 weeks--had pasted. I started this test at the end of my 5th week, conducting my experiment during my 6th week taking Azilect.

Since I can't totally rule out Azilect's influence in these increased symptom benefits, I'll need to do an additional experiment. My plan is to continue to use TUDCA until February 10th. At that time I have an appointment with my neurologist. I'll go over these results with him to get his feedback.

Then during the remainder of February, I'll stop taking TUDCA. I'll watch to see if any of the symptom improvements I gained this week disappear. If they do, then it would certainly be the TUDCA causing them. Then when I get back on it in March, I should see those symptom improvements return, further verifying it is a result of TUDCA, not Azilect.

If I don't lose the increased benefits, then it will indicate that those improvements were a result of Azilect getting a second benefit wind. Then I'll go through March off TUDCA. Mainly because I don't know how long it may take for TUDCA benefits to wear off. Since its main mechanism is to slow cell death and revitalize dying cells, it means once the medicine wears off, there may be a period of time before those cells start dying again enough for symptoms to return. So it may take more than February to confirm that Azilect is the real cause of improvements.

Likewise, if symptoms return to a worse state within a week or two being off of it, I'll have my answer and get back on it. In essence, I'll return to using TUDCA if and when the symptoms it appeared to improve return, whether that is 2 weeks after I stop using it or 3 months.

Naturally I'll keep my readers here informed when those shifts happen. For now, though, I'll make one more daily log post for day 6, and that will be it until I have new info to communicate. I'm ending it just one day short of a week because I'll be out of pocket from Thursday evening until sometime Sunday. I know it would be near impossible for me to pull off a day 7 log post on Thursday night.

Plus, much to my surprise and delight, I think I've shown that TUDCA has potential as a PD symptom treatment. Additionally, if the ASL clinical trial results are applicable to PD cell death, this could be the first medicine to substantially slow the progression of PD. I hope to confirm or dismiss the former in the months to come with my next experiment. The latter will need a clinical trial to confirm it works the same in PD brains as it does in ALS brains and in test tubes on dying PD cells. When we'll see that, who knows.

In the meantime, if my next experiment proves to me my symptom improvements are due to TUDCA, you can bet I'll be using it from here on out unless my doctor tells me I shouldn't for some reason.

Tomorrow, my last daily post on this topic.

Tuesday, January 6, 2015

Day 4: Tauroursodeoxycholic Acid

In case anyone is wondering, I'm only doing this daily report for a week. After that, it will be when I have something new to report in relation to anything, including taking this medicine.

I'll keep it short since I need to get to bed.

Day 4, Monday, 1/5/15

Side-effects: No negative side-effects noticed.

Symptom changes:

The improvement in cogwheel movement continues. I noticed it in particular when I cleaned a couple of toilets in a house and used my left hand to polish some wood. While it wasn't as effortless as my right hand, my movements weren't jerky and I had no problem controlling what I wanted my hand to do.

Likewise, today I had probably one of the longest smooth writing times for a day that I've had in a while. It only bogged down around 3:30 am this morning, about the time I sat down to write out my monthly Tuesday column at the SpecFaith blog (which I wrote, edited, formatted, and posted before 7 am). Now I'm writing this. While it isn't as smooth as most of yesterday, it is still decent. Just my left hand isn't as efficient.

Likewise, I can still sing a low bass note on demand. So that is still persisting as an improvement.

Probably the biggest change today is an improvement to a noticeable degree in dystonia (muscle stiffness/pain) and tremors. I believe I had the least amount of tremors in one day than I've had all last year and a few months before that.

I noticed it distinctly when we ate dinner. I had a sub. When I eat a sandwich, I'm usually holding it with my left hand and it is usually bobbing around. Today, all through eating a fairly long sub (everyone was waiting for me to finish), I held the sub in my left hand with not a tremor to be noticed.

Likewise, as I was vacuuming, I often hang my left thumb on the left pants pocket to let my arm hang loose. That seems to help the dystonia some than if it is just hanging at my side. Today, I felt little need to do that. I believe I even noticed my left arm swinging a little when I walked instead of being stiff as a board. Stiffness and tremors have been noticeably reduced. The only time I noticed any was when I had some stress added like in straining to do something. We'll see if that holds up in the days ahead or whether this was just an exceptional day.

The lower amount of toe curling seemed to also be holding in place as it was yesterday.

So overall, some improvement. Onto day 5.

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.

Sunday, January 4, 2015

Day 2: Tauroursodeoxycholic Acid

Today I doubled the amount I took. Took 2 250 mg pills at 3 pm and another 2 around 9:30-10 pm for a total of 1200 mg today.

In one of the studies I pointed to, they gave 3 dose levels. 15 mg/kg, 30 mg/kg, and 50 mg/kg of a person's weight. It indicated it was well tolerated at all three levels. For me, I weigh around 77 kg, that would translate into 1155 mg, 2310 mg, and 3850 mg respectively. So you can see I'm barely over the minimum dose given to people in that study.

That said, I'm not planning on raising it in the near future. This should be enough that I should see some difference if it is going to make one on symptoms.

Saturday's experience:

Side-effects: none noticed

Symptom changes: nothing noticeable yet that I can attribute to TUDCA. I did have times of no tremors, but I've experienced that before since taking Azilect. I also experienced some tremors. I should add that I would have expected more tremors than I did get when drinking coffee. I didn't get a lot, maybe half a cup, but that always seems to increase my tremors more when I do. I didn't notice any substantial increase in my tremors from drinking coffee. So that is perhaps something. But nothing I can lay at the feet of taking TUDCA yet.

There were some minor changes, but not enough for me to say it is a change as opposed to the normal ups and downs of my symptoms. Except for perhaps one small item that I noticed that could indicate something.

I mentioned my cogwheel symptom. I tend to notice that upon rubbing my wife's back before sending her off to la-la land. Due to the angle, I use my left hand for that. Normally, any rubbing isn't smooth or even. Tonight it did seem smoother and more normal. We'll see if that keeps up.

Sunday morning will be a good test of any progress. That's when I'm standing and singing/chanting for around 2.5 - 3 hours. Azilect has helped with that a lot, we'll see if it is even better or about the same. If it can help the toe curling and leg issues that make standing for that long uncomfortable, that would be a blessing.

We'll see what day 3 will bring.

Saturday, January 3, 2015

Day 1: Tauroursodeoxycholic Acid

I mentioned last time the experiment I'm going to do with TUDCA. The full name the abbreviation represents is in the title. Quite a mouthful. That's why I just use the abbreviation.

I received my bottle of it in the mail Friday, and as of writing this, have taken two doses, one 250mg pill around 2 pm, and one 250mg pill around 8 pm.

Before I get to any results thus far, I'll disclose what I'm currently taking and what my remaining symptoms are by which I'm gaging whether this will help me symptomatically or not. That, however would be only one reason to take it.

Currently, I'm taking 25/100mg of carbidopa/levadopa (generic Sinemet) 3 times a day. I've been taking that dose since January 2014. That helped symptoms significantly, but not completely. I still had considerable stiffness and pain in my left arm, and stiffness in my left leg. Tremors were still visible and when stress is applied, all those symptoms were magnified. But still, as I discovered in my one-week Sinemet holiday the first week of November, I would have been much more stiff and painful without it, to the point typing would be practically out of the question. By the end of that week I'd gone to a two-fingered typing approach, which was much slower but possible. Before I started taking my Sinemet again, even that was becoming too much of a chore.

About mid-November I started taking 0.5mg of Azilect. While sometimes it doesn't do a lot for symptoms, in my case it did significantly. Noticeably, my tremors are minimal (except apparently when I drink coffee) as is the stiffness in my arm and fingers. I'm not noticing any tremors in my right hand even though before I had developed a slight tremor in it as the disease progressed to my right side. I have periods of the day when it is better and worse, probably depending on my Sinemet schedule, which thanks to all the holidays has been messed up a good bit. Will get messed up again as we prepare for a trip next weekend. As mentioned last time, I'm now partway into 6 weeks of taking Azilect. Maximum benefit is supposed to be achieved within 4 to 8 weeks. So I'm in the later part of that range. In the last two weeks, I've not noticed any new improvement in symptoms, leading me to believe I've pretty much reached the maximum symptomatic benefit. If it is still improving, it is in very subtle ways I'm not able to detect.

I'm also taking a slew of supplements, mostly antioxidants, anti-inflammatory, and cognitive support. I won't bore you listing them all out. Mainly to say that I've not changed that in the last few weeks aside from adding in a probotic to the list to improve gut functioning. Interestingly enough, ran across a study indicating that PD patients tended to be missing a whole family of gut bacteria, so adding that was a good move. All that to say, however, that I've not recently added or changed any of my supplements that might account for any new changes upon taking TUCDA. Indeed, I also received a bottle of magnesium taurate, which will add tauramine to my body, something typically missing in PD brains compared to normal ones. But I'm holding off on it for at least three days to make sure any immediate changes can be linked more closely with adding in the TUDCA.

The only question mark is that it is possible the Azilect isn't finished, and could inject a new bursts of benefits coincidentally at the same time as the TUCDA is taken.  Not very likely, but is possible.

My current symptoms not sucuming to my current medication and supplement routine are a mixture of remaining PD symptoms and minor dyskinesia symptoms. Dyskinesia is, by way of reminder, lack of motor control as a side-effect of using Levadopa in the body, which is mostly what Sinemet is. The more of it you take and the longer you take it, the worse those symptoms get.

PD Symptoms left:
  • Minor tremors in left fingers, gets worse under stress and can tremor the whole hand/arm.
  • Stiffness in left arm and leg. Currently not much pain with it. On a scale of 1 to 10, 10 being bad pain, I'd say it is around a 2 in my left arm.
  • Due to stiffness in my left arm and leg, my gait is affected. I walk differently. In this, it seems the Sinemet nor Azilect have had much of an affect on. 
  • Sometimes when I swallow, only noticed when swallowing pills, my throat won't work right and I'll get water down my wind pipe. Usually happens at least once when taking my array of supplements in the morning and night.
  • Less energy than I used to have. Not always as bad, but there are times I seem to run out and my movements get slow and draggy.
  • My left toes want to curl under. Most noticeable when I'm standing or working on my feet. If I'm on them for 3 hours or more, it can hurt as the tips of some of my toes are constantly pushing down on the floor. This is also a symptom which Sinemet only helped a bit and Azilect hasn't seemed to do anything for me.
  • Minor constipation. Mostly kept in check with my magnesium supplement. Before that, it tended to be the battle of the bulge, if you get my drift.
  • Some "cogwheel" difficulties with my left hand. Associated with Bradykinesia (slowness of movement), it refers to lack of smoothness in hand motion, as if when going in a circle your hand acts like a cogwheel, creating jerky movements slowly. The Sinement and Azilect has helped that enough that I was able to use my left hand to cut my hair with the Flowbie last time, when prior to Azilect it was too difficult. But it is still present, just better than its been in many a month.

Dyskinesia symptoms:
  • Slight head movement, like something is pulling my head down at times.
  • Some antsiness in my left leg, such that if I stand for more than a couple hours, it wants to stop holding me up. So it wants to wiggle around.
  • My dyskinesia like I had before, doesn't include rocking back and forth while standing this time. Hasn't become that bad yet.

One symptom I've noticed of late, so I suspect it is a dyskinesia symptom, is embouchure tightening. Seems to happen mostly while I'm working to clean houses, I notice my lips drawing into a tight pull enough that it becomes uncomfortable. I have to keep forcing my mouth to relax.

Another symptom that's been unchanging through meds so far is balance. I've not fallen, but I feel decidedly more unsteady than I used to be. I'd say I've been that way through most of 2014, but it hasn't seemed to have gotten worse yet either. Just there, hanging on the edge. I can still balance on one foot, though. Just not as confidently.

What I'm not having any problem with to speak of, that I was before, is drooling and fuzzy thinking. Which is good.

That's where I stand, and what symptoms I'll be watching to see if they improve.

For day 1 on TUCDA, I had the following results.

Side-effects: Nothing I can detect.

Symptom changes: Nothing I can detect. Tremors and stiffness and all other symptoms appear unchanged.

Based on the lack of any nausea (the most common side-effect of this substance) and what I've read is a minimum effective dose, I'm going to double them for Saturday so I get a whole gram of the med in one day.

Some studies I've read upon which I'm basing the use of this drug as far as safety and effectiveness:

Efficacy and Tolerability of Tauroursodeoxycholic Acid in Amyotrophic Lateral Sclerosis

Safety, Tolerability, and Cerebrospinal Fluid Penetration of Ursodeoxycholic Acid in Patients With Amyotrophic Lateral Sclerosis

Oral Solubilized Ursodeoxycholic Acid Therapy in Amyotrophic Lateral Sclerosis: A Randomized Cross-Over Trial

You'll notice that most all the human clinical trials have been done in relation to ALS, not PD. While the parts of the brain that are dying in each disease is different, what this does show is the results in pre-clinical trials on cells and animals, does indeed translate over to human subjects using the same functional approach, halting/slowing cell death. It also shows the drug is safe to use. There are cases it can be a problem, usually involving diseased livers or gall bladders, but otherwise tolerated by most people.

What we don't know is whether it will prevent PD brain cell death as well as it prevents brain and nerve neuron death in ALS. If it does, and there doesn't seem to be any reason it won't, it would be the first substance to actually slow or stop the progression of PD. So even minus any symptomatic improvement, it may be wise to continue to take this for the possibility of helping me not to get any worse in the foreseeable future.

This was a long one, due to needing to spell out the backstory for disclosure. Future updates should just be what I'm experiencing with the drug. Until then.

Thursday, January 1, 2015

New Year, New Experiment

Happy New Year!

First, update on my Azilect. Have been taking it now for about 5 weeks. Full effect is suppose to be accomplished between 4 to 8 weeks. So I'm pretty much in the middle of that range. The last couple of weeks I've not noticed any signficant change in symptoms, so I think at least for symptoms, I'm at my maxium benefit.

The good news is that its effect upon symptoms has been very good. I'm currently feeling the most "normal" I've felt siince my PD began. Not that symptoms have gone totally away, but they've been siginficantly improved, including my typing speed is much better, though there are still times it doesn't work as well. But the stiffness in my left arm, the pain, is pretty much at a minimum, and my left hand tremor is slight. Additionally, during times of stress, like singing for 3 hours at church on Sunday mornings, is noticably easier, less stiffness and pain and tremors.

The only downside has been the dyskenesia side-effect never went away, if anything has increased slightly. Still not as bad as it was when my Sinemet was doubled, and still manageable, but has stayed there. Slight involunbtary movement in my head and left leg gets antsy and doesn't want to hold me up while standing for a prolonged period of time. The one good bit of news on that front is the involuntary multi-click on the mouse with my right hand that I attributed to my dyskenesia. I got a new mouse for Christmas from my son, Jeremy. So far, it has solved my multi-click issue. I guess my previous mouse was too sensitive.

So the improvement from using Azilect has been a good Christmas present. At the beginning of this new year, I'm going to try something new.

On a  Parkinson's forum I'm on, there has been a couple of people promoting the benefits of UDCA, a type of bile acid naturally produced in our bodies (around 5% of total) that is used primarily by doctors to dissolve a certain type of gall stones. Some studies on cells that have a cell death similar to what happens in Parkinson's brains has shown to have slowed, stopped cell death, even revived dying cells that were dying. So it has been postulated that the drug could potentially slow or halt the progression of PD and help in relieving symptoms. The two guys who have tried it noticed immediate improvement in symptoms the first day taking it, which seems hard to believe, but they swear by it.

While UCDA is a prescribed substance, another form of it that has taurine added to it can be bought over the counter, known as TUCDA. After determining that the risk it is unsafe for me to take was very small, I decided to give it a try and see what it does. So I ordered some from Amazon. It should have already arrived by this point, but should come in tomorrow. So in the next day or two, I'll be able to tell you whether it had a similar effect on me. Stay tuned!

And enjoy your New Year's day, and the 8th day of Christmas. Now, what did I do with those eight maids that are supposed to be milking these cows?