I guess that’s a good point, but yeah, those are the drugs everyone’s using. so they’re not scary.
When my neurologist saw I was using exenatide he said, “but that has side effects!” and I felt like saying: “But Parkinson’s has side effects too!”
It’s like you said–sure there are risks, but, it’s not like taking any of it is getting in the way of something else–there IS nothing else.
Just because…
I take ambroxol, doxycycline, acarbose, cacao (a lot), theracurmin, mgLthreonate, PQQ, taurine, lion’s mane…and I eat a ketogenic diet. I’m interested in an SGLT2 inhibitor or a tyrosine kinase inhibitor. BTW, I was diagnosed nine years ago. I’m doing pretty well. Manage w/o C/L.
Any of those things under consideration for your list?
And, just wondering, if you get hold of tirzepatide powder, and mix yourself, it couldn’t be delayed release, right?
Thanks for this!
-Amy
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That is surprising on your neurologist - and a bit ignorant to the trials ongoing. I use Trulicity for my patients with PD who feel getting across the BBB is important. The GLP1’s, even if they do nothing for your PD are great longevity drugs, independent of weight loss …
I think there are better candidates than many you are taking … and you are already investing in the most expensive. Incidentally, from Canada (still need an Rx) Trulicity is fairly cost effective.
I’ve got at least 11 items on my list - It’s pretty similar for AD as far as things to try to slow neurocognitive decline.
Tirzepatide has a half life of 6 days … so dosing is generally once per week. I’d not necessarily be rushing to change over from the exenatide until we have trials showing the ones that don’t cross the BBB have the same or better effect. We are in a no data zone on this. We also see data that the GIP activity of Tirzepatide seems very good for neuroprotection …
A multipronged approach is the answer right now in my best estimation hitting multiple pathways, multiple ways.
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adssx
#209
Association of elevated cerebrospinal fluid levels of the longevity protein α-Klotho with a delayed onset of cognitive impairment in Parkinson’s disease patients 2024
Our results indicate that higher CSF levels of α-Klotho are associated with a delayed cognitive decline in PD. Notably, this correlation is more prominently observed in PD patients with GBA1 mutations, potentially reflecting the accelerated biological aging profile characteristic of individuals harboring GBA1 variants.
Klotho seems promising, can’t wait to see a trial on PD!
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The question on this is whether this is the causative item, or just an effect of having PD? Would supplementation help? Not convinced at this time. Additionally, looks quite unlikely the alpha klotho given exogenously will get through the BBB - although, I understand some modifications might do a little better.
This is one where I’d be more interesting in things that might increase alpha klotho as whatever the underlying pathways are that generate this probably will be part of the pathogenesis of neurocognitive decline.
It seems like a good diet, lots of physical activity, avoid vitamin D/Magnesium deficiency, try to slow aging, have solid sleep, and minimize stress are all important. It also seems that Rapamycin will increase alpha klotho … peripherally, but in the brain I don’t think we have data - at least not that I’ve seen.
This is one on the watchlist for me … not yet thinking I’ll be recommending taking this directly until there is more data. Doing things to increase, like those above, make sense, not only for alpha klotho but for longevity anyway.
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This seems like it might be good for everyone, in addition to helping prevent Parkinson’s (if further validation studies continue to validate this research).
Researchers have found that antioxidants from Ecklonia cava, a type of seaweed, may help prevent Parkinson’s disease by protecting dopamine-producing neurons. In mouse models, these antioxidants restored motor function and improved gut health after exposure to toxins.
Cellular studies revealed that these compounds activate the AMPK enzyme and reduce harmful reactive oxygen species, potentially offering a new approach to combat neurodegeneration. This discovery highlights the potential of Ecklonia cava as a preventive ingredient against Parkinson’s disease.
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adssx
#212
Preprint
Tetanus vaccination is associated with decreased incidence of Parkinson’s disease and slower progression 2024
We show that anti-tetanus vaccination significantly reduces PD occurrence, and that both the rate and severity of PD are strongly associated with the time elapsed since last vaccination. These results, which suggest that C. Tetani toxin is involved in PD pathology, are reinforced by findings that antimicrobial treatments that affect Clostridium species are associated with significant changes in disease severity.
Several antibiotic agents displayed a substantial and significant effect in reducing disease severity: benzathine penicillin, which is an intramuscular formulation of penicillin, displayed a significant reducing effect on disease severity (−0.69, P=0.003).
On the other hand, Clindamycin was associated with a significant and substantial increase in disease severity (+0.40, P=0.002). Clindamycin is primarily used to treat infections caused by susceptible anaerobic bacteria, but it is notorious for causing Clostridium difficile colitis, a dangerous condition in which Clostridium bacteria, inherently resistant to clindamycin, colonize the human colon. The observed effect of increasing severity of PD is consistent with a competitive advantage granted by this antibiotic to clostridia, over susceptible anaerobes present in the microbiome, enabling proliferation of C. tetani in a manner similar to C. difficile proliferation following Clindamycin treatment.
Interestingly, we also observed strong apposing effects for two laxative agents commonly used to treat constipation in PD patients. Macrogol (polyethylene glycol), was significantly associated with increased disease severity (+0.34, P<0.001), while ispaghula (Psyllium), a dietary fiber, was associated with decreased disease severity (−0.42, P=0.0004). Since these two compounds primary affect the gut environment, these opposite effects are strongly suggestive of a pivotal role played by an organism which resides in the intestinal microbiome.
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Interesting - I’ll add this to my list of things to investigate with Ecklonia cava. Also @adssx the Tetanus vaccination is interesting 2 fold - one that it has this evidence - and I guess a reason to stay up to date - because prevention of Tetanus isn’t so much a reason. In the U.S. in fully immunized (e.g. got all child/adolescent tetanus vaccines), I believe we still have zero cases of tetanus before age 65 years. So the every 10 year update, really has no evidence - but for prevention of PD - do we get one every 2 years? I doubt there is any other adverse outcome - as all cause mortality needs to be tracked with every intervention and rarely is.
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Tetanus is an unpleasant vaccine for me. Same with the COVID mRNA vaccines. I am a big fan of vaccines, so I accept the trade off. I guess the more my suffering comes from heavy lifting and vaccine side effects the better my health.
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AnUser
#215
I haven’t been vaccinated against whooping cough, so will get the tetanus vaccination again either way as it comes with it.
How is this significant? There are barely any PD cases.
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My pharmacy in an effort to bill my insurance for more things, if not for altruistic reasons, keeps me informed of all the vaccines that I am eligible for.
So, over the years for instance, I have been getting the tetanus vaccine every ten years.
I have had at least two variations of pneumonia and shingles vaccine. Since I believe in vaccines I always get them when recommended by my pharmacy.
I had no idea until recently that vaccines might be giving me additional benefits.
And yes, I don’t think that I have even a remote chance of getting punctured by a rusty nail, etc.,
but I will still get another tetanus shot when it’s due.
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Beth
#217
Great find! I looked and it seems to be a pretty inexpensive supplement.
(I saw a random option for $8 at iherb)
I defer to you experts… Is this a why not and can only help supplement, or is there any potential harm?
@adssx WHOA!!! I haven’t had one in probably 18 years… guess this is a no brainer.
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Beth
#218
I’m with you!
The last couple of covid vaccines were pretty typical for me, but the first 3 gave me side effects 100000x more severe than anyone I’ve talked to. But yet, I happily line up for each and every one!!!
@desertshores I was today years old when learning there were any other benefits! And omg, the shingles vax was soooo awful for me and long lasting, but no regrets! My doc isn’t even a fan of that vax for someone like me (so sensitive), but I said shingles is no walk in the park either!
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This is why I compare it to a heavy session in the gym. You know it’s coming. You know the benefits are lasting and real. And you know it’s going to hurt. (Not the injection, but the side effects.) I’d accept that trade off every time. Plus, you can schedule your vaccines, but you can’t schedule an infection.
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adssx
#220
Association between kidney function and Parkinson’s disease risk: a prospective study from the UK Biobank 2024
Furthermore, changes in eGFR were correlated with alterations in subcortical gray matter volume in regions such as the frontal cortex, striatum, and cerebellum. The clinical prediction model showed high diagnostic accuracy with AUC values of 0.776, 0.780, and 0.824 for 4-, 8-, and 16-year predictions, respectively.
Renal insufficiency is significantly associated with an increased risk of PD, highlighting the importance of maintaining good kidney function as a potential preventive measure against PD.
They used an eGFR of 105 ml/min/1.73 m² as the reference.
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I think the issue is that CKD is caused by senescence of Renal tissue and scarring (patterns of senescence) in the Kidneys. Senescence is a key driver of aging (along with mitochondrial function). Parkinsons is a disease of aging.
All of these systems feed back on themselves via mRNA transcription constraints.
There is of course a further issue in that if the kidneys are not working well everything else suffers.
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adssx
#222
It seems that carbon monoxide is indeed what protects from PD: Low-dose carbon monoxide may explain the paradoxical reduced risk of Parkinson’s disease among smokers 2024
“Building on multiple Phase I and Phase II clinical studies in both healthy people and people with a variety of clinical conditions showing safety of carbon monoxide at the low doses studied here, a clinical trial of low-dose, orally administered carbon monoxide in patients with PD is planned.”
(poke @AnUser)
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AnUser
#223
The paper: Neuroprotection of low dose carbon monoxide in Parkinson’s disease models commensurate with the reduced risk of Parkinson’s among smokers | npj Parkinson's Disease
It could be something downstream from that.
Carboxyhemoglobin seem interesting, FDA threshold is set at 14% for clinical trials according to Wikipedia for safety. There is also endogenous ways the body create it, including with heme:
The most extensively studied pathway is the metabolism of heme by heme oxygenase which occurs throughout the body with significant activity in the spleen to facilitate hemoglobin breakdown during erythrocyte recycling.
Vegetarians also have a higher PD risk, which I assume is lower in heme. There are also multiple natural genetic mutations that increase COHb levels, so why hasn’t this been picked up in Mendelian randomization studies?
adssx
#224
I’m not sure vegetarians have higher PD risk. Also: anemia is protective of PD.
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AnUser
#225
Apparently a non-invasive hemoglobin etc tracker:
Hemoglobin
Pulse Rate Variablity
Oxygen Content
Carbon Monoxide
Methemoglobin (Met)
Pulse Rate
Perfusion Index
Oxygen Saturation
Respiration Rate
Pleth Variability Index
1 Like
adssx
#226
Glucagon-Like Peptide-1 Receptor Agonists and Risk of Parkinson’s Disease in Patients with Type 2 Diabetes: A Population-Based Cohort Study 2024
This study included 89,074 Medicare beneficiaries who initiated either GLP-1RA (n = 30,091) or DPP4i (n = 58,983). The crude incidence rate of PD was lower among GLP-1RA users than DPP4i users (2.85 vs. 3.92 patients per 1000 person-years). An sIPTW-adjusted Cox model showed that GLP-1RA users were associated with a 23% lower risk of PD than DPP4i users (HR, 0.77; 95% CI, 0.63–0.95). Our findings were largely consistent across different subgroup analyses such as sex, race, and molecular structure of GLP-1RA.
They looked at individual GLP-1RAs and surprisingly higher the BBB crossing (dulaglutide > exenatide > liraglutide > semaglutide) the lower the PD protection!!! (poke @DrFraser)
They note:
Really convincing chart with increased protection over time:
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