#161

I’ll start downing bell peppers, that I can do!

I’m here to follow too! My mom had it and my grandmother had ALS and my aunt has something that they can’t figure out… scary genes in my family.

#162

I don’t think it’s that dangerous to use a miniscule part of a nicotine patch, but I might be wrong.

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#163

I feel like that is also what I heard once on Huberman

… but my dad died from lung cancer so I err on side of caution… not to mention the second hand smoke I inhaled with 2 smoking parents in cars when I was little with the windows up!!! Probably the case for many in my generation!

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#164

Sorry for your loss! Nicotine patches doesn’t cause lung cancer, unless you decide to start smoking after using a relatively nonaddictive way of consuming it. Nicotine from patches reach the brain much slower so it is apparently much less addictive.

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#165

Thank you!!! :heart:

He had a heart attack at 40 and quit smoking and became super healthy (strict on no fat because that is what they said back then). But 20 years later, he got cancer.

Good to know about patch vs smoke. Ty

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#166

Nicotine: total BS, don’t do it. Trials failed. It’s something else in cigarettes that protects from PD, but we don’t know what yet (we’ve discussed it above already).

I won’t cite sources because I think I’ve already posted them all, but for PD prevention, what we know:

  • Drink coffee
  • Healthy diet (“MIND diet”)
  • No/low processed food
  • SGLT2 and/or GLP-1 RA
  • Avoid high-dose metformin
  • Telmisartan (and potentially also a dihydropyridine CCB?) and avoid beta-blockers
  • Avoid statins and prefer other lipid-lowering drugs (ezetimibe?)
  • Stress management
  • Sleep hygiene
  • Maintain social connections and an active life (a “purpose”)
  • B12 supplementation (as methylcobalamin?)
  • As much exercise as possible
  • Avoid laxative drugs
  • Prefer non-drug treatments for anxiety and depression (e.g., low-dose lithium?)
  • Avoid pollution (air, water, pesticides, etc.) (eat organic?)

Then, in terms of things that are for now only exploratory, as 1/4 of PD patients have mitochondrial impairment outside the dopaminergic substantia nigra (not the others), agents improving mitochondrial function might help: but which ones? Similarly, the immune system is affected in PD, so there are trials of immunosuppressants (rapamycin hasn’t been proven to work so far). Also, probably avoid viral infections and get vaccinated and in case of bacterial infections, use antibiotics.

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#167

Adssx,
Thanks, this is helpful

Can you talk to me about metformin (and/or sglt2)

I’m on metformin 2x per day because, after wearing a cgm, I discovered I get much bigger spikes than the average person. My bloodwork is good, but the worry for me is contributing to existing heart disease.

I asked my doc about some other medicines you all discuss but he said easy trigger… i just started rapa and ezetimibe and he wants me to be cautious about polypharmacy

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#168

See this: Parkinson's disease - #28 by adssx

Then use the search to find posts about metformin and SGLT2.

#169

Smokeless tobacco (Snus) is also associated with lower risk of Parkinson’s, as well as chewing tobacco.

Results: During a mean follow-up time of 16.1 years, 1199 incident Parkinson’s disease cases were identified. Among men who never smoked, ever-snus users had about 60% lower Parkinson’s disease risk compared with never-snus users [pooled hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28-0.61]. The inverse association between snus use and Parkinson’s disease risk was more pronounced in current (pooled HR 0.38, 95% CI 0.23-0.63), moderate-heavy amount (pooled HR 0.41, 95% CI 0.19-0.90) and long-term snus users (pooled HR 0.44, 95% CI 0.24-0.83).
Moist smokeless tobacco (Snus) use and risk of Parkinson’s disease | International Journal of Epidemiology | Oxford Academic

I don’t think nicotine can be totally ruled out since (1) food consumption of nicotine is associated with lower PD risk (2) the trials testing nicotine was in people already with Parkinson’s. It’s different to treat vs. prevent. Can someone prevent Parkinson’s by taking levodopa, for example? But that recent study did look at decline in functioning and it was worse.

Even if nicotine can be ruled out, then it seems to me it is associated with tobacco and not smoking per se.

The full paper in this could be interesting:

In recent decades, numerous studies have found that smoking or the intake of any form of nicotine, such as smokeless tobacco, exposure to environmental tobacco smoke, or even dietary sources such as peppers, reduces the risk of developing Parkinson’s disease.1 Such observations suggest a potential disease-modifying effect of nicotine in Parkinson’s disease. Many experimental studies, some of them supported by grants from the tobacco industry, have lent support for such a hypothesis.

https://evidence.nejm.org/doi/full/10.1056/EVIDe2300167

#170

Nicotine has been totally ruled out by researchers. The comparison with levodopa is irrelevant: levodopa does not slow down the progression of Parkinson’s; it’s just a symptomatic help.

We’ve already discussed this, so I don’t understand why you bring back this nonsense, see this recent review in the official journal of the International Parkinson and Movement Disorder Society: Parkinson's disease - #77 by adssx

See also this preprint for a potential explanation of the mechanism: Neuroprotection of low dose carbon monoxide in Parkinson’s disease models commensurate with the reduced risk of Parkinson’s among smokers 2024

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#171

This is the editorial commenting on “Transdermal Nicotine Treatment and Progression of Early Parkinson’s Disease”, one of the trials that ruled out nicotine.

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#172

I don’t know how generalizable a change in Total UPDRS score is for preventing the disease in the first place?

#173

Parkinson’s patient moves freely again after world-first implant of lab-grown cells into his brain 2024

Parkinson’s patient Thomas Matsson was the first in the world to receive 7 million lab-grown brain cells in 2023. Today, he can smell and play sports.
“The vision is that it could be given as a one-time treatment and the hope is that the patients can reduce their medication, avoid side effects of the drug treatment and get a long-term good motor effect from the cells for life,” Gesine Paul-Visse, a senior physician in neurology at Skåne University Hospital and adjunct professor at Lund University, told Swedish broadcast SVT in 2023 when the first trials started.
So far, five subjects have undergone surgery using the researchers’ lab-grown cells.
Soon three additional patients will receive a double dose, with 14 million brain cells each.
If all goes well with the first eight patients, the research team will continue with larger studies in collaboration with a pharmaceutical company.
“There is absolutely hope. Absolutely there is!” said Paul-Visse as a message to people living with Parkinson’s disease.

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#174

Open label study, but selegiline improved total UPDRS score:

When is there enough evidence that it might suggest that it prevents PD? :man_shrugging:

#175

They didn’t do a washout period. Without a washout period, you can’t tell if the effects are disease-modifying (slows down the progression) or just symptomatic.

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#176

Thanks, now I understand why the GLP-1 agonist data is so exciting.

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#177

HMCGR inhibition showed decrease PD risk in that pre-print.

Genetic variations in HMGCR were significantly associated with a reduced risk of PD (odds ratio [OR] = 0.54, 95% CI 0.34-0.86).

If that’s true I don’t understand why the simvastatin trial had a negative result.

#178

The preprint found a decreased risk of one specific PD subtype, not of PD itself. And it’s a preprint (from a random Chinese team if I recall correctly?) and it’s an MR. Other MR studies found a potential causal link between HMCGR inhibition and worse cognition: https://www.sciencedirect.com/science/article/pii/S0735109722053086?via%3Dihub

See also this recent (about low LDL, not HMCGR inhibition): Lipids, Apolipoproteins, and the Risk of Parkinson Disease 2019

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#179

No, it sounds to me like it was overall risk.

The SNP’s seems to have reduced hyperlipidemia and CAD risk as expected:

image
image766×166 18.9 KB

HMGCR inhibition did change to a more favorable PD subtype in that MR pre-print as well, compared to an unfavorable one:

Another discovery from this study implied that incorporating HMGCR inhibitors may facilitate the shift
of PD patients from the less favorable PIGD subtype to the more favorable TD subtype.

image
image765×414 93.1 KB

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#180

You’re right “Genetic variations in HMGCR were significantly associated with a reduced risk of PD (odds ratio [OR] = 0.54, 95% CI 0.34-0.86). However, variation in HMGCR was associated with an increased risk of the tremor-dominant (TD) subtype compared to the postural instability/gait difficulty (PIGD) subtype (OR = 8.43, 95% CI 2.12-33.52).” If this MR preprint is correct, it contradicts some other published MR studies. Let’s imagine that others are wrong and this one is correct, then the problem might be with statin’s side effects (and not with HMGCR inhibition itself), for instance their negative impact on the gut and GLP-1 levels that seem so important in PD. But that’s pure speculation at this stage. Still, I think people with PD or at high risk might be better off achieving their LDL/ApoB targets with non-statin therapies if they can (ezetimibe, bempedoic acid, PCSK9i, and hopefully soon obicetrapib). If not, it is still better to take statins and avoid a heart attack, even at a low risk of getting PD in the future.

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