What Are the best Neuroprotective Agents and Why?

[Jonas]

My stack list are:
Fish Oil DHA heavy
Coffee and Green Tea
L-theanine and 2 Eggs daily
Vit B complex and Magnesium
Exercises

[Walter_Brown]

Canagliflozin
Metformin
Galantamine
Calais
Choline

[Bicep]

You mean Cialis ? 20 characters

[Walter_Brown]

Yes, PDE5 inhibitors

[Melih]

first place: social bonds

[desertshores]

“What Are the best Neuroprotective Agents and Why?”

I am sure that there are some.

However, I need help finding scientific evidence for any drug or supplement that has any solid evidence that it is neuroprotective.

A few that I use are supposedly helpful such as increasing blood flow to the brain etc. such as, Ginkgo biloba, huperzine A, and bacopa monnieri, but they are mainly cognitive enhancers.

Some nootropics such as the various racetams may be neuroprotective, but we only have Russian studies to back that up.

[nikney]

glynac+selenium, astaxanthin, lithium

[Curious]

The flavonoid fisetin reduces multiple physiological risk factors for dementia...

The neuroprotective effects of fisetin, a natural flavonoid in...

Who knows, maybe there is a role for fisetin in being a neuroprotective agent?

[adssx]

What does neuroprotective mean? Smoking cigarettes is neuroprotective for Parkinson’s disease, but it increases the risk of Alzheimer’s disease and multiple sclerosis.

If we define neuroprotective as “lowers the risk of AD and PD” and “slows down the progression of AD and PD post-diagnosis,” then the only things that are proven are coffee/tea, sleep hygiene, stress management, good hydration, cognitive activity, and physical exercise.

Then, for the unproven but with some degree of evidence, I’d say from the most to the least “sure”:

1. GLP-1RA (especially those that cross the BBB?)
2. Telmisartan (at least for those with elevated BP)
3. SGLT2i (but maybe not canagliflozin?)
4. Low-ish dose lithium?
5. Methylcobalamin (B12, homocysteine factor)?

On other things:

@Jonas

Magnesium

Evidence is very weak, elevated levels might be associated with a higher risk:

• Magnesium and Cognitive Health in Adults: A Systematic Review and Meta-Analysis 2024
• Elevated circulating magnesium levels in patients with Parkinson’s disease: a meta-analysis 2018
• Parkinson Symptom Severity and Use of Nutraceuticals 2023
• CSF Mg and Ca as diagnostic markers for dementia with Lewy bodies 2009
• Patients with dementia with Lewy bodies have increased calcium and magnesium levels in CSF 2008

@Walter_Brown

Yes, PDE5 inhibitors

Very weak and conflicting evidence: Large Study Finds Viagra Is Linked to Almost 70% Lower Risk of Alzheimer's - #129 by adssx

@Walter_Brown

Canagliflozin

Maybe not: Association of Sodium–Glucose Cotransporter 2 Inhibitors With Time to Dementia: A Population-Based Cohort Study 2022: “When stratified by different SGLT2 inhibitors, dapagliflozin exhibited the lowest risk (aHR 0.67 [95% CI 0.53–0.84]), followed by empagliflozin (aHR 0.78 [95% CI 0.69–0.89]), whereas canagliflozin showed no association (aHR 0.96 [95% CI 0.80–1.16]).”

@Walter_Brown

Metformin

Associated with a higher risk of Parkinson’s disease in almost all studies. Although it might be protective at low-dose (below 500 mg/day): Parkinson's disease - #28 by adssx

Even for dementia, the evidence is weak: No association between metformin initiation and incident dementia in older adults newly diagnosed with diabetes 2023. But here again, it could be that low-dose is neuroprotective but higher doses are detrimental.

[Jay]

Walter_Brown, Galantamine sounds interesting. What brand do you use and how do you dose it? What effects do you notice? And, Calais, what is it?

[Walter_Brown]

I take 4mg from an Indian pharmacy: Galamer 4

[CronosTempi]

Hey, what happened to the alleged protection against PD afforded by the TD/TDAP vaccine, not to mention vaccine effects based on the uk biobank data. There are also many hints about some kind of link between vaccines and lower dementia rates, lower dementia=neuroprotective, no?

FWIW, that’s one of the reasons why I get vaccines - the possible pleiotropic effects on neuroprotection. Highly speculative, but hey, there are few downsides, so I don’t mind buying this very cheap lottery ticket… in case it pays off, that’s a big win.

[adssx]

Oops you’re so right I forgot vaccination that seems to be a low-risk/high-reward strategy.

[LongevityDude]

Plasmogens from Prodrome such as Neuro and Glia oil products. Peter Diamandis has started taking this. Research on cognitive health looks promising.

Prodrome | Plasmalogen Supplements for Brain Health

[Bicep]

I thought @CronosTempi might mention it because of the video posted. Clearly lutein is an important neuroprotective agent. Also an IL-11 inhibitor and longevity supp.

[Mdecrasto]

Methylene blue, perhaps? My husband has been taking it for 2 weeks and going to a spectrum light therapy capsule at least 3 to 4 times a week (7 wavelenghts including 660nm). Results so far? Increased energy even after a restless night due to some issues with our senior dogs, improved mood, chronic tinnitus gone, recent surgery scar disappearing quickly, and eczema healing nicely. And the best part: blue mouth, tongue, and urine.

[CronosTempi]

Well, yes, I could’ve mentioned lutein, but he was talking specifically about PD when he counted off all those that affected PD, but didn’t mention TD/TDAP.

But yes, there’s a whole bunch of neuroprotective agents, however as I mentioned in the lithium thread, my issue is with tightening up the definition of what neuroprotection is and how do we measure it. So, if you say, protects against PD, that’s a tight definition. But when you say things like “makes the brain 6 years younger”, as in that notorious thread I have chosen not to participate in, then I find that extremely handwavy, laden with assumptions and suppositions, and of dubious validity - just think of how broad a physiologic category “younger brain” is, and if picking a handful of arbitrary markers really encompasses the totality of that claim.

Same with “neuroprotective” - too handwavy. Something concrete, like “wrt. PD”, ok, but otherwise it’s too much hot air. YMMV.

[Joseph_Lavelle]

Drugs? I don’t know. But here is stuff to ponder…

“Good for the heart? Good for the brain”. Is the old way of thinking about it. The new new thing is gut health: “Leaky gut? Leaky BBB.”

Eat for a healthy gut microbiome (lower inflammation) and exercise to build mitochondria, lower BP, reduce inflammation

I think good sleep to let the glymphatic system do its job has to be mentioned as well.

Watch for iron overload. Iron is associated with neurological diseases.

[curt504]

All background can be found on youtube for these peptides. Lots of evidence for protective as well as restoritive benefits from PTST/TBI cases;

Peptides: cerebrolysine, semax / selank. Plus the anti inflammatory; BPC-157 + TB-500.

Part of brain/neuro protection is low/lowering inflammation. I would put the ketogenic diet where measured ketones (ketomojo meter) are >>1.0 ideally into 2.00+ (difficult). Soo soo many cases of restoration where ketones are held >2.0. For normal folks just getting ketones into 1.0 + ;periodically is protective.

Alzheimer’s is often called type 3 diabetes so low glucose + low insulin is highly protective.

We wear a CGM 80% oof the time as a traffic cop an make sure our glucose (thus insulin) stay low. My wife tests ketones daily…

IMHO diet; ketogenic diet is 10x, maybe much more then 10x more effective then any of the nutricals mentioned. Then the peptides then the nutricals.

Good luck, curt

[DrFraser]

There is a good option on Amazon of a 12 mg capsule to avoid tongue and teeth issues.
I personally feel it makes a significant difference in mentation, and take 1 capsule every AM, and days I work in the ER take 1 mid day.

Amazon.com: Methylene Blue (USP Grade) Pharma Grade Supplements, Capsule Form,...

I don’t know if this is neuroprotective, but it certainly seems to enhance brain function, as does NAC Ethyl Ester.

@约瑟夫_拉维尔 I think gut health is critical, and looking at a test like KBMO has for looking at whether you have altered gut permeability is a sensible approach. But once you’ve cleaned your diet up, it would seem like the items @adssx has mentioned all make sense.

@curt504 Interesting on the keto diet - I guess it depends on diet quality - and it is difficult to craft a keto diet that doesn’t increase every other part of mortality, from vascular disease to cancer. Yes the brain uses either ketones or glucose for energy - my approach is to maximize insulin sensitivity in the brain with things like GLP1’s and SGLT2-i. I’ve not seen any convincing evidence showing a keto diet is helpful for neurocognitive decline, but I’d love to see some, if you find any. Overall, I pursue a diet rich in polyphenols and complex carbohydrates - a typical WFPB, which I believe the evidence supports this approach. Naturally making sure one optimizes Omega 3 index, Vitamin B12 and Homocysteine.