The Problem of Brain Aging, Peter Fedichev

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#21

I think there are two key errors made by researchers when studying melatonin.

A) A lot of (may be all of) pineal melatonin is injected into the CSF which acts as a reserve of melatonin. It will not come out at the same rate as it goes in. It will come out at a rate determined by the localised concentration. The concentration is higher than serum.

B) melatonin levels inpact on whether rhe ultradian cycle is in parasympathetic mode or sympathetic mode. Although melatonin is gabaergic it is this switch between states that has the biggest effect - not so much the dose. This is my own hypothesis based on my own biohacking, but it appears to be confirmed by the experience of others.

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#22

I agree with @Joseph_Lavelle: challenge the brain. I learned to fly a single engine Cessna in my 50ā€™s. That was way more fun than the Times crossword puzzle. Plus diet, sleep, exercise. I ride a fat e-bike on rocky farm roads and itā€™s when youā€™re not mentally engaged that you crash.

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#23

I did not read the paper so apologies if I am way off base. But generally speaking, there is a healthy-user bias when it comes to vaccination. If you look at Table 1 presented by RapAdmin above and ask, which of these factors are associated with a higher propensity to be vaccinated, I think you will find most of them travel together. Numerous factors are inter-related; higher Townsend deprivation scores are also more likely to have diabetes and depression, for instance. There is a lot of bi-directional confounding.

So with vaccines, it would be wonderful (perhaps not realistic though) to have solid long-term RCTs and see which outcomes are improved.

#24

Iā€™m adding lots of goji berries to my smoothies these days. Any evidence that rapa helps with overall eye health? Not necessarily improvement in vision, which is too much to hope for.

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#25

Brad Stanfield: Donā€™t Take Melatonin Until Youā€™ve Watched This

https://x.com/bradstanfieldmd/status/1695857581347226017?s=46&t=ujBXvjsf5sfNM8J1qi8RfQ

#26

I agree completely that the healthy user bias could be in play as part of the results But what I have seen lately in the science literature are hypotheses that seem to be gaining more traction The paper gives the following possibilities in the introduction to the paper:

" There are multiple theories as to the etiology of Alzheimerā€™s disease (AD). One hypothesis is that infection may play a causative role in the development of AD and Alzheimerā€™s disease related dementias (ADRDs) [1ā€“4]. Viral, bacterial, and fungal infections may increase neuroinflammation, thereby causing or exacerbating neurodegeneration, and subsequently dementia [1, 3]. Vaccines may reduce the risk for developing infections, or limit their severity, reducing an individualā€™s neuroinflammatory burden, decreasing the immune mechanisms that may contribute to the development of AD/ADRD [5]. Alternately, vaccines may activate alternative pathways of the immune system that may alter the risk for AD/ADRD [5, 6]."

An interesting conclusion in the paper was the type of vaccines may matter. A conjugated vaccine for Pneumococcal had a more robust immune response which resulted in less AD than a polysaccharide version.

If you go to Can Alzheimer's Be Prevented? | Alzheimer's Association you will see no listing of a viral or bacterial cause. It reminds me of when the idea that peptic ulcers was caused by the bacterial infection Heliocobacter pylori was considered heretical.

Anyways - I see these commonly accepted things like cold sores and flu as much more dangerous than I previously thought

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#27

It is truly interesting. Thank you for sharing those comments.

I wonder if there are any populations we can look at where infection is more or less common - say, hunter gatherers or etc. - and see if Alzheimerā€™s lines up with that? The obvious problem w/ hunter gatherer groups is they have shorter life expectancies and donā€™t typically develop A. D., so we need a different group to compare against.

So much to learn!

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#28

First, as I have said before, I donā€™t advocate or recommend anyone to take any of the supplements or medications I am taking, nor my diet, fitness routines, etc.

Yes, there are caveats to taking melatonin. As the video plainly states, it is not for children, young people, etc.

N=1
I started melatonin in 1984 on my first trip to Europe. It was suggested to me that should take it to reset my biological clock and reduce the time it takes to overcome jet lag. After, taking melatonin doses of 1 to 3 mg for a few years I started reading articles about its benefits other than as a sleep supplement; anti-oxidant, etc., and I upped my dose to 5 - 10 mg, for the last ten years I have been taking mainly 20 mg doses. Lately, I have been taking 100mg doses.
So in all, I have been taking melatonin supplements for ~39 years. I have never had any adverse side effects.

And yes, I am bragging: I am doing a hell of a lot better than most 82-year-olds.

N=3 My wife and two oldest daughters used melatonin in the 5 to 20 mg ranges during menopause and felt it really reduced the symptoms of menopause.

With all due respect to Dr. Huberman, as a busy man producing YouTube videos, etc., he is mainly parroting what his staff is feeding him. I have no doubt that I have read many many more papers and done more research on melatonin than Dr. Huberman.

Totally ridiculous for both of them to say there were no human studies indicating the benefits of melatonin only mouse studies.

They are both hypocrites IMO. They cite mouse studies when it suits them and then pooh-pooh mouse studies when itā€™s convenient.

(I will add this to my other ā€œrantā€ posts. :grin:)

ā€œMelatonin and the health of menopausal women: A systematic reviewā€
https://onlinelibrary.wiley.com/doi/full/10.1111/jpi.12743

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#29

Huberman is less respectable than even Sinclair.

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#30

I have no idea if that is trueā€¦ but most scientists lose their credibility in my eyes when they start espousing strong opinions in areas far outside their area of expertiseā€¦

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#31

There seems to be a new category lately. The smart person (out of their personal depth) with a staff of ā€œresearchersā€. Attia, Rhonda Patrick, Huberman. From being burned I donā€™t have pure faith in any of them or anyone else. If an influencer deserves it in my opinion, I trust but verify as best I can. And, always, doing nothing is a good option. Iā€™m thinking about a lot of things that I wish I knew what to do.

At the top of the pyramid right now is Kaeberlein. He seems to be a rare combination of fair mindedness, a very good judge of data, and is unbiased, as far as I can tell.

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#32

I have listened to brad stanfieldā€™s video. He advocates for very low dose melatonin taken 1-2 hours before sleep. He considers 10mg to be a high dose. He is unaware of doses of 60,200,400 that are available OTC.

Andrew huberman is quoted warning that melatonin has puberty delaying effects. Also in children melatonin is releaaed all day.

I have glanced at the referenced papers. None consider the fact that melatonin is injected into the CSF. They also dont look at the use of melatonin for sleep extension.

He does however take melatonin himself.

As people know i suggest taking melatonin during the night or time released.

https://twitter.com/sinanmellaart/status/1695891833904140288

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#33

My 3 mg dose is huge in comparison with his. Will reduce mine or even try to sleep without it. Glycine works pretty well too. Itā€™s a pity thereā€™s so much contradictory information almost about everything, not only melatonin. It makes it difficult to make an educated decision, no matter how much you read.

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#34

Pure, unadulterated, YouTube clickbait aimed at gathering more subscribers, hence more fame and fortune.

723Ɨ70 6.8 KB

1093Ɨ663 335 KB
If it wasnā€™t to change our minds, what was the point?
(And if you donā€™t like what I say, donā€™t listen!)

Apparently, Dr. Stanfield didnā€™t bother to read this.

Dr. Brad Stanfield apparently had nothing better to do than to resurrect an eight-month-old YouTube video in order to garner some viewers in hopes that they will buy some of his promoted supplements.

I havenā€™t looked at all of his videos, but at least his latest videos donā€™t carry a similar warning. They should.

Melatonin is IMO one of the safer supplements out there and one of the ones likely to do the most good.

Approximately 71 million adults in America are taking melatonin.

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#35

Apologies, I just found the post on eye health.

#36

Re infection and AD, I posted this under another topic: Can you share your Longevity / HealthSpan Regime? - #562 by cara2023

#37

One of the arguments against Melatonin is that Golden Hamsters who take a quantity of it (I am not sure how much) have smaller testes.

This could be part of its anti-puberty effects,

However, it is available off the shelf in France. It is not even kept behind the counter like medicines like Ibuprofen.

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#38

If it has anti-puberty effect, does it mean that it delays/puts on hold aging? What are your thoughts? Yesterday skipped melatonin before going to bed and slept exactly the same 7 hours as with melatonin (same deep, rem and core).

#39

Its merits from an antiaging perspective lie in the mitochondria. Is there a risk of reversing puberty? Possibly with enough, it may be that more ros are needed to go through puberty. In the end, however, too much ros is a problem. I dont take melatonin to get to sleep. I take it for sleep maintenance or after waking for the side effects.

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#40

Has there been any clinical trials showing proof of safety of ultra high dose melatonin?

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