Who Wants to Make the Case for UDCA/TUDCA? - Cure Parkinson's

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Who Wants to Make the Case for UDCA/TUDCA?

Bolt_Upright profile image

Now that I've dropped Glycine CC suggested I focus on TUDCA. Turns out I had tried and stopped TUDCA but circling back it looks like I should have kept it up!

The questions I'd like to answer in this thread are:

1: Should I be taking TUDCA and why/why not?

2: How much TUDCA should I be taking?

PS: I know TUDCA is in Restore Gold.

47 Replies

Tauroursodeoxycholic acid (TUDCA) is neuroprotective in a chronic mouse model of Parkinson's disease 2020 pubmed.ncbi.nlm.nih.gov/333...

Example of a study of questionable validity. Pretreatment with the test substance prevented toxic damage. In the case of actual Parkinson's the toxic damage is already done:

"Pretreatment with TUDCA protected against dopaminergic neuronal damage, prevented the microglial and astroglial activation, as well as the DA and DOPAC reductions caused by MPTPp. "

in reply to park_bear

So it does not restore but might protect

park_bear profile image
park_bear in reply to

...Against a parkinsonism caused by a bad street drug

in reply to park_bear

Might Might

Might protect

Not making any claims

rescuema profile image
rescuema in reply to

You're correct and we shouldn't be dismissive of the finding.

'Together, these results suggest that autophagy may be involved in the progression of PD and that TUDCA may attenuate these effects. "

park_bear profile image
park_bear in reply to rescuema

It is possible that TUDCA/UDCA could be useful - I am not claiming the contrary. What I am saying is that this sort of study is poor evidence. Any of the following could pass this kind of study yet be useless in Parkinson's. Any substance that:

• Interferes with absorption of MPTP

• Interferes with MPTP crossing the blood-brain barrier

• Interferes with uptake of MPTP by neurons

• Promotes rapid metabolism of MPTP

• Complexes with MPTP and thereby inactivates it

in reply to park_bear

Have you read about the Minnesota study and the Sheffield study? I have while multitasking which is obviously less than optimum but I do what I can.

Edited to add:

I have heard (not verified) that the Sheffield phase 2 UDCA study will be ending in a month or so. I assumed things are not on schedule but perhaps I am wrong.

in reply to rescuema

I read that TUDCA + doxycycline has been or is being studied for amyloid clearance. RC UK I think.

UDCA is reliant upon ones system to create TUDCA so if the system is impaired it seems to me that bypassing this process and going straight to TUDCA may be a valid course if that is a valid course exists.

rescuema profile image
rescuema in reply to

To get a compound approved for humans can cost an enormous amount of time/money and no for-profit entity will willingly invest such a fortune with no recourse for patent protection and recoup via future profit stream. That's the current state of this world no matter what "incurable" disease, but any research that contributes to enlightening our understanding of the complex Parkinson's disease helps toward the collective knowledge although a model will most likely be imperfect and won't apply for all given differing etiology. UDCA is FDA approved while the over-the-counter TUDCA isn't, so a clinical trial of UDCA is a shorter path to clinical approval and Drs' assent and ability to recommend use without liability. In the meanwhile, we can leverage what we understand so far given the existing studies including small trials, historical use/effects, and myriad anecdotal testimonials. The fact that Doxy has been shown to be therapeutic short-term in certain (not all) people with PD also can be interpreted with strong ties to certain pathogens with disease pathology and a case for a more sustainable improved microbiome.

in reply to rescuema

I was following and agreeing until I got toDOXY. Doxycycline?

Sorry

rescuema profile image
rescuema in reply to

CC, while doxy along with other antibiotics has shown to reduce amyloid aggregation, no one to date clearly understands the contribution of tau-associated neurodegeneration nor of abnormal phosphorylation/aggregation pertaining to disease etiology and progression. Until we clearly understand for sure which mechanism instigates the shifting of the normal to the pathological condition leading to tauopathies, I believe in the fundamental importance of restoring beneficial gut microbial homeostasis especially in light of the recent growing scientific evidence for microbiota-gut-brain axis critically affecting health. The below review may help elucidate.

mdpi.com/2072-6643/13/1/37/pdf

LAJ12345 profile image
LAJ12345 in reply to

They should perhaps swap doxy for berberine.

Tauroursodeoxycholic Acid Improves Motor Symptoms in a Mouse Model of Parkinson's Disease 2018 pubmed.ncbi.nlm.nih.gov/296...

Complete study here: repositorium.sdum.uminho.pt...

Would need to look at the details to assess the validity of this one:

" TUDCA administration, either before or after MPTP, significantly reduced..."

Found the full study: repositorium.sdum.uminho.pt...

Lots of good stuff in the discussion section of this 2018 study repositorium.sdum.uminho.pt...

Strikingly, TUDCA administration, prior to or after MPTP,significantly prevented the MPTP-mediated increase in swim-ming latency, improve gait quality and decrease foot dragging. TUDCA treatment also prevented the decrease of spontaneousactivity and ability to initiate movement, as well as the tremorsinduced by MPTP.

Overall, results show that MPTP-injected mice present mo-tor symptoms that resemble human parkinsonism. Moreover,as in humans, motor symptoms were aggravated throughouttime in parkinsonian mice, proving that the experimentalparadigm is adequate. Strikingly, in TUDCA-treated animalsPD motor symptoms were absent or mild, and no aggravationwas observed in any evaluated parameter. In a medical per-spective, in the context of a chronic progressive neurodegen-erative disease like PD, these results are significant. TUDCAmay prevent neurodegeneration of still healthy neurons andglial activation, keeping a larger pool of dopaminergic neu-rons, which may account for the delay of disease and symp-toms progression.

Loss-of-function mutations of parkin are the major causeof recessively inherited early-onset PD and wild-typeparkin may also be inactivated by post-translational modi-fications in sporadic PD [24, 60], which leads to impairedmitochondrial turnover. Herein we observed that MPTP-injected mice showed significantly decreased expressionof parkin, whereas treatment with TUDCA maintainedparkin levels and most notably of phosphorylated parkinin the striatum. PARIS, a parkin target that accumulatesupon parkin inactivation, was concomitantly increased inthe striatum of MPTP-injected mice, but not when animalswere treated with TUDCA. These results are in accordancewith our previous observations, showing that TUDCA trig-gers parkin expression and phosphorylation in the striatumof MPTP-injected mice [35]. We have previously demon-strated that parkin activation is an early event occurringin vivo after MPTP administration [35]. Moreover, we havealso shown using in vitro systems that parkin mediatessome of the neuroprotective effects of TUDCA in neuronalcells upon MPP+exposure [35]. Interestingly, here weshow that modulation of parkin by TUDCA in the presenceof MPTP is maintained throughout longer time periods,confirming that this activation is an important mechanismunderlying TUDCA neuroprotective role in experimentalPD. The fact that parkin is involved in mitochondrial turn-over makes it a perfect candidate to be a TUDCA mediator.The pharmacological upregulation of parkin by TUDCA iscrucial in the context of PD and other neurodegenerative disorders where mitochondria also play a key role, anddeserves further investigation.

Additionally, parkin and DJ-1 form a complex to promotedegradation of misfolded proteins and their PD-pathogenicmutations impair E3 ligase activity of the complex [61]. Interestingly, DJ-1 protein expression was increased in thestriatum of animals treated with TUDCA. This is also in ac-cordance with our previous observations, in the striatum andmidbrain from mice treated with MPTP for 3–6h,showingthat DJ-1 expression was upregulated when animals receivedTUDCA before MPTP [34]. These results suggest that DJ-1 isalso an important target protein mediating TUDCA neuropro-tective effects in vivo.

Taking in consideration our previous and present work,data strongly indicate that TUDCA promotes neuroprotectionthrough the maintenance of a healthy mitochondrial pool in MPTP-intoxicated mice.

Although we found that TUDCA was not protective to-wards MPTP acute toxicity, the results presented here arepromising and indicate that TUDCA improves motor perfor-mance in MPTP-intoxicated mice, although longer/higherTUDCA dosage, as well as different time-points of adminis-tration following MPTP injection, should be optimized to ex-tend the neuroprotection. The demonstration of the preventionand/or the alleviation of symptoms together with the demon-stration of the pathways triggered by TUDCA should contrib-ute to a subsequent clinical trial in humans and future valida-tion of the therapeutic application of this bile acid in PD.

Ursocholanic acid rescues mitochondrial function in common forms of familial Parkinson’s disease researchgate.net/publicatio...

Exactly:

"Previous drug screens aiming to identify disease-modifying compounds for Parkinson's disease have typically been based on toxin-induced in vitro and in vivo models of this neurodegenerative condition. All these compounds have failed to have a reliable disease-modifying effect in subsequent clinical trials. We have now established a novel approach,.."

[Emphases added here and above]

TUDCA in the Treatment of Prion Disease maes.umn.edu/seelig67-018 (some people think PD is a prion disease)

To conclude, we present here evidence that TUDCA and UDCA can interfere with the seeding efficiency of prions and provide neuroprotection in prion-infected brain slice cultures, with pilot studies indicating some efficacy in vivo. The upstream effect that we describe in the present study complements the diverse array of downstream neuroprotective mechanisms of these bile acids and increases the potential for efficacy in human prion disease. Further studies in prion-infected animals will be required to fully elucidate all other mechanisms of action in prion disease, but the fact that these agents may act at different levels of the pathogenic cascade, coupled with the advantages of being orally bioavailable, permeable to the blood-brain barrier, nontoxic and FDA-approved for human use, make these natural compounds promising alternatives for the treatment of prion diseases.

Here is an UDCA trial that was supposed to start in 2016 but has not started: Brain Bioenergetics in Parkinson's Disease and Response to Repeated Oral UDCA Treatment clinicaltrials.gov/ct2/show...

The hypothesis is that repeated oral dosing of UDCA will result in increased brain ATP levels in individuals with Parkinson's disease.

Measure plasma UDCA levels in individuals with PD at baseline and after four weeks of repeated high doses of oral UDCA (50mg/kg/day).

At 77 kg that would be 3850 mg a day for me.

in reply to Bolt_Upright

As I messaged, 2,250 is the low dose in the Sheffield trial

Another study that has not started: Trial of Ursodeoxycholic Acid (UDCA) for Parkinson's Disease: The "UP" Study clinicaltrials.gov/ct2/show...

There is strong evidence from previous research and the work carried out by other groups that UDCA rescues the function of the mitochondria (mitochondria are the "powerhouse" of the cell) in PD patient tissue and other models of PD. This suggests that UDCA may slow down the worsening of PD.

UDCA has been in clinical use for the treatment of liver disease (primary biliary cholangitis) for over 30 years. The investigators therefore know that it is safe and well tolerated in patients with liver disease but the investigators don't know yet whether this is also the case in patients with PD. Furthermore, the dose used for patients with liver disease (15 mg/kg) is not high enough for UDCA to get into the brain. The investigators therefore need to double the dose to 30 mg/kg. This higher dose was also safe in clinical trials for liver disease, but is currently not used routinely in clinical practice.

Bolt Note: I am pretty sure TUDCA is more bioavailible so probably don't need this 30 mg/kg. For my, 77 kg, this would be 2310 mg.

in reply to Bolt_Upright

I believe that TUDCA is more bioavailable. Why is UDCA being trialed and not TUDCA? I suspect bc UDCA is a pharma and TUDCA is OTC

WinnieThePoo profile image
WinnieThePoo in reply to

I wouldn't get hung up on the OTC pharma thing. The Sheffield trial is using the generic which probably costs less than the OTC. But a generic is still a licensed product and will be a reliable consistent formulation which would be important for a trial

in reply to WinnieThePoo

You would need a much higher dose of UDCA. TUDCA has better bioavailability. But UDCA is regulated so risk is reduced. Cheap TUDCA often contains UDCA according to random not verified sources.

This is interesting because it compares UDCA to TUDCA: Efficacy and Safety Study of TUDCA Compare UDCA to Treatment Chronic Cholestatic Liver Disease-PBC clinicaltrials.gov/ct2/show...

Both arms were given 750 mg and then they would compare biomarkers for results. Unfortunately no results posted. Might be able to track them down. Would really help figuring out TUDCA dosing.

ncbi.nlm.nih.gov/pmc/articl...

in reply to WinnieThePoo

Good findingTUDCA may be better (better is open to interpretation of course)

UDCA relies on the body to do what it’s suppose to to create TUDCA but if ones system is not functioning optimally that could be impaired.

Bypassing this process and going straight to TUDCA may be better.

I tried TUDCA early on and it did not do anything for me. It can be synthesized in the lab, but some TUDCA is obtained by abuse of Bears, which is way not okay. See MBAnderson's comments here: healthunlocked.com/cure-par...

in reply to park_bear

Current TUDCA has nothing to do with bears.

You don’t know if it did nothing.

It is not for symptoms. It’s not for disease reversal. It’s for slowing progression.

Science of Pd posted about a Minnesota trial for UDCA and it’s being trialed at CPT. Sheffield UK has info.

To my knowledge

UDCA + taurine in the body results in TUDCA

Bolt, I message you leads to research but please, no credit Just trying to help to direct towards things that might be fruitful

clinicaltrials.gov/Provided...

Human studies relevant to this application: A pilot study conducted by Dr. Samuel Klein, also at Washington University in Saint Louis, treated 10 obese, insulin-resistant adults with 1.75 g/day for 4 weeks with no adverse events17. TUDCA was given to 16 liver transplant recipients at 500 mg/day for 12 months with no drop-outs or toxicities observed. A cohort of subjects with primary biliary cirrhosis were treated with 500-1500 mg/day of TUDCA for 6 months, with diarrhea reported as the only side-effect. Several human studies have shown that use of TUDCA is well tolerated in many populations including amyloidosis16, primary biliary cirrhosis18-20 and liver transplant21.

Chronic toxicity has been studied in dogs for up to 26 weeks with treatment of up to 400-600 mg/kg/day (30 x that of the proposed dose) with no observed toxicity. Rats treated with 2-20 times the proposed dose showed no evidence of carcinogenic effects after 24 months of treatment (see attached, “animal toxicity”).

1.5 Dose Rationale and Risk/BenefitsA weight based regimen for TUDCA will be used, administering it in 3 divided doses which corresponds to an average dose of 20-25 mg/kg/day accordingly using 1750 mg daily for patients <75 kg and 2000 mg daily for patients ≥75 kg.It has been shown that TUDCA at the dose of 25mg/Kg/day can achieve maximum composition in the serum and bile in patients with primary biliary cirrhosis19. Previous clinical studies also have shown that 1 to 6 months of TUDCA treatment with 1750mg/day is efficacious and safe in patients with different diseases, including primary biliary cirrhosis19, 27, 28, liver cirrhosis29, HCV-related chronic hepatitis30 and insulin resistance17. Animal studies also suggest that TUDCA appears to be very well tolerated even at high doses.

They have a placebo group in an 18 month ALS trial :(

Dose is 1 gram twice a day after meal.

Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS (TUDCA-ALS) clinicaltrials.gov/ct2/show...

Here is another ALS Tudca trial. Small study. Did slow down progression, but looks like by only about 24 weeks. Was 2 grams a day. Completed in 2014. Not the miracle I was hoping to see.

Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis

ncbi.nlm.nih.gov/pmc/articl...

ALS TUDCA Chart

Another interesting trial: A Trial of Bile Acid Supplementation in Patients With Multiple Sclerosis clinicaltrials.gov/ct2/show...

Like most others, 2 grams a day.

Check out this secondary outcome measure:

Gut microbiota [ Time Frame: Baseline to 16 weeks ]

Change in composition of the gut microbiota assessed using shot-gun metagenomic sequencing in first morning stool specimen.

Tauroursodeoxycholic Acid May Improve Liver and Muscle but Not Adipose Tissue Insulin Sensitivity in Obese Men and Women diabetes.diabetesjournals.o...

Twenty obese subjects ([means ± SD] aged 48 ± 11 years, BMI 37 ± 4 kg/m2) were randomized to 4 weeks of treatment with TUDCA (1,750 mg/day) or placebo.

CONCLUSIONS These data demonstrate that TUDCA might be an effective pharmacological approach for treating insulin resistance. Additional studies are needed to evaluate the target cells and mechanisms responsible for this effect.

Anti-inflammatory effect of Tauroursodeoxycholic acid in RAW 264.7 macrophages, Bone marrow-derived macrophages, BV2 microglial cells, and spinal cord injury 2018 nature.com/articles/s41598-...

Conclusion

TUDCA inhibits the LPS-stimulated inflammatory response in RAW 264.7 macrophages, BV2 microglia cells, and BMMs. TUDCA suppresses expression of inflammatory cytokines in SCI rat model. The results here suggest that TUDCA can serve as a useful anti-inflammatory drug and that it is potential alternative drug for SCI (Spinal Cord Injury).

Neuroprotective effects of TUDCA in Parkinson’s disease: dissecting the anti-oxidant and anti-inflammatory effects of this bile acid in the mouse cerebral cortex 2017

repositorio.ul.pt/bitstream...

Even thoughthe exact mechanisms that leadto neurodegeneration in PD remain elusive, studies suggestthat togetherwithoxidative stress, defectsin mitochondrialdynamics and inflammation contribute to disease pathogenesis(Bose & Beal, 2016). Causes and consequences of mitochondrial dysfunctionsare represented in FigureI.5 and Figure I.6.

PD Pathology

Okay, I'm at 500 mg twice a day now. I will try to ramp up to 1000 mg twice a day. Seems to be no downside for side effects and a fair amount of upside. Maybe not a silver bullet but worth a dozen pellets in my shotgun shell.

My husband's father developed PD in his 80s and for the past 5 years my 67 year old husband himself has had tremor-dominant PD, the tremor in his right hand and leg being the most bothersome symptom and getting pronounced in recent months. He has been prescribed Azilect but hasn't started taking it yet. He sleeps well so I'm wondering if melatonin would still be a good idea? I'm impressed by all the amazing research I read courtesy of you all including @Bolt_Upright, @Chartist, @cclemonade and others on this site- and would be grateful if any of you could list your current "stack" in its entirety.

Hello goldengrove, so sorry to hear about your husband's situation. Feel welcome to message me any time.

I should add that I have not been diagnosed with PD. I have been diagnosed with REM Sleep Behavior Disorder. My neurologist says it will eventually be PD and I do have a still left shoulder and left leg. I am trying to stop things where they are.

I should add: There is a chance none of anything I do does anything beneficial. Exercise is the only thing scientifically proven to delay progression.

Here is my latest thinking (I need to get TUDCA and Curcumin on this list):

I, high school graduate Bolt, believe these are all helpful, but I can't be sure of any of them. I have posts on all of them. Make sure you look at the cautionary post on Niagen.

Zeolite:

New perspectives in iron chelation therapy for the treatment of Parkinson’s disease 2019 healthunlocked.com/cure-par...

You All Must Think I Own a Zeolite Mine healthunlocked.com/cure-par...

Now this is an interesting study on Zeolite. As far as heavy metal detox, powdered Zeolite Clinoptilolite seems to be the best. healthunlocked.com/cure-par....

Zeolite Clinoptilolite: Therapeutic Virtues of an Ancient Mineral healthunlocked.com/cure-par...

Butyric Acid

Why Am I Taking Butyrate? healthunlocked.com/cure-par...

Niacin

Vitamin B3 trial results healthunlocked.com/cure-par...

Niagen alleviates Parkinson’s disease symptoms but downregulates dopamine metabolism? healthunlocked.com/cure-par...

Resistant Starch

Effects of Resistant Starch on Symptoms, Fecal Markers and Gut Microbiota in Parkinson’s Disease – The RESISTA-PD Trial healthunlocked.com/cure-par...

Royal Jelly and Propylis

More Bee Stuff: Synergistic action of propolis with levodopa in the management of Parkinsonism in Drosophila melanogaster - 2020 healthunlocked.com/cure-par...

Thanks so much, Bolt_Upright! Can I ask why you don't have Melatonin on your list? I had imagined you might have taken it for the REM sleep behaviour disorder as well as for its potential value in your stack? Not a medical opinion I hasten to add - I'm retired and uninsured!

Sorry, I did not include my entire list. Yes, I take 10 mg of melatonin at night.

I take 100 mcg of selenium and 600 or 750 of Inositol too, but that is because I have Hashimoto's Thyroiditis.

And started Sulforaphane. This looks hard but it's not. Reach out if you want the cliff notes: healthunlocked.com/cure-par...

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