#805

I have recently stopped taking TUDCA myself. I have not spotted anything that I would particularly link to it. That does not necessarily mean anything as I keep track of a lot of things and there are continual changes going on. I have dropped it to see if that changes anything - which it would do slowly if at all.

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#806

On air pollution:

  • Prominent role of PM10 in the link between air pollution and incident Parkinson’s Disease 2025: “The association was confirmed testing average PM10 levels during follow-up (18[13–24]% increase of PD risk per 1 μg/m3 increase of PM10).”
  • Causal relationship between nitrogen dioxide and the risk of Parkinson’s disease: Evidence from a Mendelian randomization study 2025: “The main results of the IVW method (odds ratio: 4.701; 95% CI: 1.127–19.615, P = .034) showed evidence for a causal relationship between NO2 exposure and the risk of PD. Heterogeneity analyses was conducted using the MR-Egger method (Cochran’s Q = 1.155; P = .764) and IVW (Cochran’s Q = 1.356; P = .852) demonstrated no statistically significant heterogeneity among the selected SNPs. We employed MR-Egger regression (β intercept = −0.026; SE = 0.058; P = .684) and the MR-PRESSO global test (P = .840), which revealed no significant impact of pleiotropy on the results of the MR evaluation. Based on MR analysis, higher levels of NO2 exposure are causally associated with an increased risk of PD. Consequently, mitigating air pollution could be an important strategy for reducing the risk of PD.”
#807

Urate predicts rate of clinical decline in Parkinson disease

#808

Unfortunately: Effect of Urate-Elevating Inosine on Early Parkinson Disease Progression: The SURE-PD3 Randomized Clinical Trial 2021

Among patients recently diagnosed as having PD, treatment with inosine, compared with placebo, did not result in a significant difference in the rate of clinical disease progression.

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#809

Looks like tryptophan processing is harmed by PM10 ( —> melatonin).

#810

We just finished fundraising a worm lifespan study of a promising longevity molecule indolepropionamide (IPAM). I’ve been doing an extensive deep dive into all literature available on IPAM and related indole molecules for longevity and health and it might be something to keep an eye on for Parkinson’s. This class of molecules has shown some potential for it, and Alzheimer’s.

I’ll be presenting all of the information I find once the study is complete. It should be good.

Here is my original post: 268% Median Lifespan Increase with Indolepropionamide aka Indole-3-propionamide or IPAM – What this is, and why more studies NEED to be funded! - #121 by Neo

This study outlines an indole derivative showing promise for Parkinson’s:
Neuroprotection of Indole-Derivative Compound NC001-8 by the Regulation of the NRF2 Pathway in Parkinson’s Disease Cell Models https://onlinelibrary.wiley.com/doi/10.1155/2019/5074367

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#811

Hmmmm.

Just read this…

Parkinson’s Disease Might Not Start in The Brain, Study Finds : ScienceAlert

Removal of α-Syn from the blood may hinder the progression of Parkinson’s disease, providing new strategies for therapeutic management of Lewy body diseases,"

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#812

All the more reason to protect your kidneys. The best way to do that is with an SGLT2I like Empagliflozin.

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#813

I have spent quite a bit of time looking at PD ALS/MND and other neurodegenerative diseases. Both PD and ALS/MND have very clear links to mitochondrial deterioration. This can, of course, be started off in various parts of the body, but in the end you need to identify what kicks off the balance.

The fact is that dopaminergic and motor neurons need a very large amount of energy generated via OxPhos to function. There is a dynamic equlibrium in all cells that aims to maintain mitochondrial function and normally gets a slow deterioration. If, however, this is kicked off kilter it can deteriorate quickly.

Hence in ALS particularly there are a number of genetic flaws that can cause the balance to be lost more easily.

Removing α-Syn might help as there are feed back systems, but α-Syn is more a symptom of mitochondrial malfunction than a cause of PD.

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#814

Has this been posted before? I can’t find it, but if so, I apologize.

In any case, I think this is a very interesting paper. Obviously it seems that osteoporosis is a downstream effect of PD pathology. However, I wonder if in addressing this downstream pathology through bisphosphonates, these drugs migt not have an upstream effect on PD itself (apart from just the impact on osteoporosis), as sometimes can happen with drugs unexpected pleiotropic effects. I can’t find much data on that - has anyone looked into this specifically?

Parkinson’s disease and osteoporosis: basic and clinical implications

Here’s the trial mentioned:

Trial of Parkinson’s And Zoledronic Acid (TOPAZ)

https://clinicaltrials.gov/study/NCT03924414

I mention all of this because I think that calcium pathways are key to PD pathology, and bisphosphonates address this along certain axis.

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#815

This may be starting out life with worse mitochondria.

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#816

Interesting.

N of 1:
My mom stood up from a chair and fell in her early 60s and broke her hip.

Less than 10 years later, she was diagnosed with PD. We always assumed that fall was an early sign of instability.

In our family it’s hard to know if there is a correlation or not.

I had osteopenia at 40 (osteoperosis now…. And waiting for the results from my dexa, fingers crossed!). My sister had osteoperosis at 62 (she’s improved through using the drugs). All that is to say we are all potentially going to get PD (would be believable with our genes), or osteoporosis just runs in our tiny boned family, and perhaps my mom’s case was not related. Stay tuned….

My mom lost a ton of weight when she had PD. She simply assumed it was because she was moving all the time, and that made sense to me.

I’d love to hear more about the calcium pathways you mentioned.

@John_Hemming Can you list some of best things we can do to improve our mitochondria, please? I know I’m doing some of them, but want to make sure I’m not missing anything.

#817

@Beth, I explored this earlier in the thread, starting with:

And subsequent posts from that through February 4, tons of posts, with some contributions from Antoine. Later, I also posted statin and PD in the brain mechanisms centered around calcium pathways. It’s a big subject,

Separately, I’ve been doing a deep dive on bisphosphonates, and so was interested in whether calcium pathways might also somehow be involved upstream from that in PD apart from osteoporosis. There’s the TOPAZ trial, but I don’t know how broadly they are looking at findings - we’ll see.

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#818

Isradipine failed. Nilvedipine’s results will soon be published. There are different theories at the moment:

  1. CCBs need to cross the BBB to be effective => Intra-nasal CCB delivery?
  2. Not all PD patients might have an issue with Ca2+ homeostasis and some stratification is needed => RCT TBD?
  3. CCBs’ effects might depend on the PD stage: beneficial before diagnosis, detrimental after? This Yale preprint hints at that: Drug Repurposing for Parkinson’s Disease: A Large-Scale Multi-Cohort Study 2025

Conclusion: we don’t know but interesting.

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#819

From that paper:

“Additionally, potassium use, particularly in surgical settings (e.g., gastrointestinal dysfunction), was significantly associated with a lower PD risk”.

How was potassium used in “gastrointestinal dysfunction”?

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#820

Ambroxol back in the news.

**Ambroxol as a Treatment for Parkinson Disease Dementia

A Randomized Clinical Trial**

https://jamanetwork.com/journals/jamaneurology/article-abstract/2835760

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#821

So ambroxol was useless in PDD? At least it’s safe? PDD is even harder to treat than PD, though. Also, I heard that this trial was not well conducted. Several others ongoing ambroxol trials, wait and see…

#822

If Parkinsons is a mitochondrial disease (as I think it is) then you need to treat it as a mitochondrial disease. Any downstream intervention will only have marginal effects as the failures in gene expression will just appear in another symptom (much like aging - which is also mainly a mitochondrial disease IMO)>

#823

If you want to reduce your risk or Parkinson’s disease, it turns out that you may want to stay away from golf courses… or at least living near one. As the study states “living within 1 mile of a golf course was associated with 126% increased odds of developing PD compared with individuals living more than 6 miles away from a golf course.” Part of this appears to be due to pesticides and vulnerabilities with ground water and airborne exposure. So if you live near a golf course, getting a high quality water filter might be in order (this is probably good advice for anyone actually).

Some highlights included:

  1. In the US, pesticide application to golf courses can be up to 15 times higher compared with countries in Europe.
  2. The odds for PD decreased by 9% for every 1-mile increase in distance from a golf course up to 18 miles.

Although this study is limited to Minnesota and Wisconsin, it might make one reconsider living in close proximity to a golf course, given this interesting relationships with Parkinson’s disease.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2833716

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#824

I wonder if golf course tenders keep records, and if they’re public. I’d like to see this. What are they spraying that is so toxic? Herbicide doesn’t do this.

We have to keep records. They can come and look at them whenever they want.

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