Comment by mobilejdral | Hacker News Reader

Comment by mobilejdral | Hacker News Reader

I had to triple check the date because I was pretty sure that this was known before. Maybe it is simply the confirmation aspect of it?

Edit:

> Our findings reveal for the first time, that Alzheimer’s symptoms can be transferred to a healthy young organism via the gut microbiota, *confirming a causal role* of gut microbiota in Alzheimer’s disease ...

From: https://faculty.sites.uci.edu/kimgreen/bio/glucocorticoids-a...

Citing many papers

> One early event in AD is an increase in circulating glucocorticoids

You could sum up Alzheimer's as: Diet/Lifestyle + a congenital form of Cushing's syndrome and you have increasing glucocorticoids which imply downregulation of the PVN, less progesterone and low levels of Prolactin reducing oligodendrocyte reducing myelin sheaths. Add in APOE e4 without choline in the diet and you have accumulation of lipids to round it all out.

There is a reason why Omega 3 + B+D vitamins are talked about as preventative as they all reduce inflamation.

See this for example: https://www.grassrootshealth.net/two-nutrients-proven-stop-b...

Edit2: For the curious here is a larger brain dump on the topic with many more links when I had to untangle the pathway earlier this year while working on something else. https://www.reddit.com/r/DrWillPowers/comments/16ae4zy/alzhe...

"You could sum up Alzheimer's as: Diet/Lifestyle + a congenital form of Cushing's syndrome and you have increasing glucocorticoids which imply downregulation of the PVN, less progesterone and low levels of Prolactin reducing oligodendrocyte reducing myelin sheaths. Add in APOE e4 without choline in the diet and you have accumulation of lipids to round it all out."

Can someone translate this into plain English?

I refuse to copy/paste ChatGPT but it breaks it down well enough to help you target specific slices of the statement to google yourself and do your own analysis of the accuracy of the claims.

This shouldn’t come across as “lmgtfy” and also nothing ChatGPT says can be taken as fact, but I do think it provided some helpful restructuring of the original.

I think its probably (mildly) overly pessimistic about some less-supported claims, and it may be worth reviewing the latest work on those claims first.

I personally feel that pregnenolone supplementation had a noticeably negative affect on my mental health. High prolactin would also be somewhat miserable but it makes slightly more sense that it could be better for alzheimer incidence rate. Drugs to lower prolactin, like cabergoline, have profound effects on the brain: https://news.ycombinator.com/item?id=33186046

ChatGPT log can be viewed here: https://chat.openai.com/share/e79afa6f-ee58-42a9-99c1-bd3a1a...

Wow. When someone is so well versed in a topic that everyone else has to use the world's most popular and advanced artificial intelligence to understand what they have just said. Bravo.

I mean, I understood most of it from just hobbyist-level interest in anabolic steroids. Many of those (testosterone, nandrolone, masteron, trenbolone, trestolone) also interact with prolactin and there’s occasional discussion about pregnenolone as well.

So I was able to validate at a surface level that ChatGPT at least didn't completely mangle the meaning, intention, and facts.

But the truth is that the GP shouldnt be viewed as being “so well versed in the topic”. Most of these hormones (even pregnenolone) havent been studied well enough to understand the full effects of manipulating them in otherwise “healthy-ish” people. We know their most powerful effects in niche, extreme situations - so if someone has a true medical issue/emergency related to them we know to raise/lower them to get certain desired effects.

But we really don’t know the vast majority of the effects that subtle changes in these hormones might have. Supplementing pregnenolone seems to cause temporary depression in many of the folks I’ve talked with in the bodybuilding community - myself included (until supplementation is ceased). For me that effect greatly outweighs its potential contribution to Alzheimer’s later in life.

Haha I tossed together that sentance before running to a meeting. I simply know the topic to such detail and intimately that I didn't think to make it simpler. If I had known it was going to be tossed at ChatGPT I would have fleshed it out more. The key thing that ChatGPT missed in its summary was that the entire PVN is often downregulated in Alzheimer's. This is where you get all of the other comorbidities that don't make sense and are red herrings such as thyroid issues and leads to a direct pathway to the reduction of myelin sheaths which is a crucial requirement before dementia.

Once you see the pathway you can't unsee it.

What is PVN?

https://en.wikipedia.org/wiki/Paraventricular_nucleus_of_hyp...

Unfortunately, the parent commenter is making huge leaps of logic and exaggerating the results of various studies. The Reddit source they linked to is from a telehealth medical provider who has invented a new condition and named it after himself. Skimming his writings gives strong pseudoscience / alternative medicine vibes.

For example, Cushing's syndrome is a disorder of extreme excess cortisol. The incidence is estimated to be somewhere between 1 in 100,000 and 1 in 26,000. In other words, it's an extremely rare condition. Suggesting that a congenital form of Cushing's syndrome is behind Alzheimer's wouldn't make sense.

There's a trend in alternative medicine to take a large collection of studies, reduce them to overly simplistic this-causes-that links, then to string them all together to generate misleading conclusions.

In this case, the comment is trying to claim that lifestyle factors combined with an extremely rare 1-in-100,000 condition from birth results in a set of hormonal changes that lead to damage to the insulating layer around your nerves. It's extreme speculation, not indicative of the actual science.

In general, be wary of anyone who claims to have solved complex medical conditions like Alzheimers that are still elusive to actual researchers. I hope it goes without saying that a random Hacker News commenter hasn't figured out what countless researchers have been working on for decades.

I agree with Auromis. The reported research is interesting, and yet is not yet ready for application to human health. It's tempting to leap to conclusions. The top poster takes this too far.

I hope that NIH funds a lot more Alzheimer's research looking for microbial causes, and also, that the technology for understanding gut microbiome continues to develop.

Cushing syndrome is and overarching term that encompases Cushing disease, subclinical Cushing syndrome, paraneoplastic Cushing's disease, and other tumors. subclinical Cushing's was more what I was referring to when I wrote 'congenital form of Cushing's syndrome'. You don't honestly think I was talking about something that is a 1-in-100,000 condition when talking about Alzheimer's do you?

As you want to be pedantic 'Subclinical Hypercortisolism' would be the much more accurate terminology.

There are decades, billions of dollars, and millions of man-hours of research on Alzheimer's.

It's safe to say a paragraph on hackernews saying "oh it's just X", no matter how stuffed with scientific words, does not sum it all up.

For those that are curious and not well verse in research level biology, what kind of food, drink and lifestyle will help maintain a gut biome that prevent Alzheimer

Fatty fish, most nuts (that don't have high omega-6, which is inflammatory), fruits high in antioxidants like berries and dark fruit in general, colorful vegetable, cooking with olive/avocado/sunflower oil, *kefir* which is the champion of all good microbiota inducers

As for avoiding: red meat (high in omega-6), gluten (chickpea, rice, lentil pasta instead of wheat), cooking with hydrogenated oils, preservatives, processed food, refined sugar

The lists could be much longer. Look up anti-inflammatory diet aka mediterranean diet. What I will say is adhering to this diet has done as much for my inflammatory condition as all the medication. With some foods I feel their effect right away (pork, too much sugar), with some it sneaks up as I let it slip for a few days. So I stand by it.

I'm a fermentation freak so I have to highlight how uncooked fermented foods like sauerkraut and the aforementioned kefir play into anti-inflammation [0].

[0]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147091/

What about Ayran (that salty turkish thing)?

What about pickles? Do pickles fit into the nutrition profile we're looking at (Please, think of the pickles.)

Good news, pickles are fermented, so they are good for your gut!

Ayran, on the other hand, contains a lot of salt which probably isn't the best.

kimchi too?

yes. I had to heal my gut and kimchi and sauerkraut plus the occasional Kefir are great. I also take from time to time zinc L-carnosine and L-glutamine, great for the gut as well.

It's also a good idea to get tested for H Pilory.

Sour red cherries are pretty good anti-inflamatory.

https://www.mcgill.ca/oss/article/food-health-you-asked/it-t...

Red meat is not necessarily high in omega 6, and on the contrary grass fed meat can be high in omega 3. Also the debate is still out on whether or not omega 6 is inflammatory or not, and even omega 6 rich nuts are probably health promoting in typical quantities. From my understanding gluten is probably fine for those that don’t have a sensitivity. I think you should caveat your claims about diet since we don’t totally know to an absolute manner yet.

Fair enough, I'll rephrase it this way: most large mammal meat causes inflammation for me and my partner, whereas chicken, turkey, fish, rabbit, etc are all fine (and I should say I used to basically eat meat with carbs). As far as omega fatty acids are concerned, I believe one shouldn't let their omega-6 and omega-9 levels be much higher than omega-3. Gluten is associated with all sorts of issues that I think we will be learning more about in the next few years. There are plenty of alternatives so that one is easy for me. I can still make pasta (chickpea, lentil, brown rice), and use tortillas (almond, chickpea, cassava).

How can you possibly measure inflammation much less attribute it to a single variable?

> How can you possibly measure inflammation

There’s a number of inflammation markers in the blood that can be measured directly via lab test (cRP, ESR, blood cell counts, ...).

Exactly this, I get regular blood work. On top of that, I can feel the inflammation. It is pressure, or warmth. It's a very obvious bodily reaction. Now of course for the average immune system the effects would be more subtle, but could still be noticed in energy levels, focus/attention, etc. And even if not noticeable, low-grade inflammation long term is one of the main factors of age-related decline.

As for attributing a body's reaction to a single food, there's something called the elimination diet where one isolates the variables one at a time. https://en.wikipedia.org/wiki/Elimination_diet?wprov=sfla1

My understanding is that you need a balance between omega 6 and omega 3 and omega 6 is not necessarily bad if its the right ratio between 6 and 3

Among inflammatory substances, alcohol is the elephant in the room. Cutting out alcohol is the lowest hanging fruit in this garden. Unfortunately, people convince themselves that it is perfectly healthy when consumed in small quantities every day. Anybody who monitors their health/fitness parameters with a smart watch will notice how damaging alcohol is.

Yes, 100%. At some point I started to feel negative bodily reaction from a single beer. I also quit smoking cigarettes for the same reason.

Most of this is conjecture though and should taken with a huge grain of salt (if we’re focusing on Alzheimers specifically)

If we're focusing on effects of diet on immune systems, especially those not functioning nominally, it is quite readily available information now. Was not so half a decade ago. The immune system is affected strongly by gut microbiota health, therefore it is a solid base to assume the same applies dietary considerations apply for Alzheimer's.

I'm going to plug a health model rapidly gaining mainstream acceptance by healthcare providers: https://en.wikipedia.org/wiki/Biopsychosocial_model?wprov=sf... It posits that all factors of life are important for overall good health. The TL;DR is that one needs to consider diet, exercise, socialization, hobbies, etc in addition to whatever medication regimen is helping.

The usual. The way we evolved: Avoid processed foods and move (i.e., exercise). Obviously, only take antibiotics when absolutely necessary.

I should have discovered earlier in my life that prescribing antibiotics is the doctors equivalent of „you don‘t get fired for buying ibm“.

What does processed even mean?

Unless I run out in the field and bite a cow, that meat is going to be processed.

Likewise with potatoes, I'm going to be eating unpalatable starchy uncooked potatoes.

> Unless I run out in the field and bite a cow

Oh, how I now want to invent a new fad diet...

Given the question, I'm willing to bet that running is likely to result in a heart attack.

Every kind of food processing has trade offs including cooking which destroys vitamin C among other things.

White rice was historically missing thiamine (B1) found in brown/hole which was killing off a surprisingly large number of people in Asia as it became popular. Now days foods are often fortified with various things to cover the most common and severe issues, but that’s probably not enough on its own.

In terms of highly processed foods you run into various additives. There’s a long list of minimally studied additives/dyes/preservatives/etc being used only for them to later be recalled and replaced with some other poorly studied substances. Ignorance may be a legal defense for Nabisco adding X to their products, but it’s not going to protect your health.

So, the advice is basically to have the absolute minimum amount of processing steps which is a surprisingly useful heuristic alongside having a varied diet including lots of different plants.

I take it you interpret "save money" to mean keep yourself barely fed, clothed and housed, and otherwise consuming the bare minimum so that you can maximize the amount you put away?

If not, you might want to loosen your interpretation of words in other domains, too.

Industrial processing. As a simple rule, the longer the list of ingredients on the food label, the more processed. The ingredients aren't something you'd normally think of as food? More processed.

Basically don't eat food that comes in a box.

Eat fresh or frozen meats, vegetables, fruits, some whole grains.

In most supermarkets, shop around the perimeter and avoid everything in the center aisles.

Another way I've heard it stated: "single ingredient foods." And as you prepare them, try to keep them that way.

For example, adding a ton of butter to potatoes makes them 10x less healthy. More or less, calorically they become fries. Fries taste great but they should be an occasional treat, not a staple.

Keep in mind that if you buy a bunch of "let's pretend it's not processed" "healthy" foods and use them to cook a meal, you're a) creating an ultra-processed meal, and b) it now has a long list of ingredients, you're just not writing it down.

I found this list really helpful to understand:

https://www.bbc.co.uk/food/articles/what_is_ultra-processed_...

In 2023 it means...

An apple...not processed.

An ear of corn...not processed.

Oatmeal...not processed.

Frozen peas...not processed.

Breakfast cereal...processed.

Heat & serve meals in the frozen section...processed.

Yogurt with fruit (and tons of sugar) pre-added...processed.

Soft drinks...processed.

Kid's "Happy Meal"...processed.

And so on.

Btw, Slaughtered and butchered meats !== processed meats.

Recommened book:

- Exercised - D Lieberman

https://www.theguardian.com/books/2020/aug/29/exercised-by-d...

- Burn - Pontzer

https://www.npr.org/sections/health-shots/2021/07/16/1016931...

- Comfort Crisis - M Easter

- Scarcity Brain - M Easter

https://eastermichael.com/

Also recommended, the series "The Foods That Built America" on the History Channel.

p.s. Again, key phrase "as we evolved". Last I checked archeologist aren't digging up McDonald's from eons ago.

Generally, if you buy it on the perimeter of the grocery store, and it has a relatively short shelf-life, it's not processed.

If diet had an effect on Alzheimer's, then those patients that have altered medical diets / starve at the end would show improvement, no?

I think this doesn‘t mean diet can prevent it altogether let alone revert it

From the linked article:

"... something as simple as taking fish oils had reduced dementia risk by 9%. This is equivalent to the risk reduction found from quitting smoking. However, the effect is not the same without B vitamins."

So yeah. My summary simply illuminates the pathway/reason why as well as why there are so many confusing comorbidities.

warm days-old left out fermented milk called Kefir.

You can also make kefir with fruity water if you’re not into animal products.

Generalizing but it seems that harmful microbiota prefers glucose but leaves behind bad metabolic byproducts. Whereas beneficial microbiota leaves behind lactic acid? So maybe lactofermented foods will help.

I've been on a journey of hyper-optimisation of my nutrition for various goals (sport performance, health, intellectual performance, etc). Mediterranean diet seem to be the GOAT in most cases

Unless you are Asian, or an Inuit.

Genetics matter. Eat like your great grandmother.

what if your great grandmother had Alzheimer's

This is impossible to say if you do not know your genetics. For example, being a FUT2 non-secretor will change everything about what you eat. Trust me, I am a FUT2 non-secretor. So in my case I need to eat a lot of seaweed and mushrooms which are both high in fucose (not fructose!).

https://journals.plos.org/plosone/article?id=10.1371/journal...

https://www.frontiersin.org/articles/10.3389/fnut.2020.60617...

> You could sum up Alzheimer's as: Diet/Lifestyle + a congenital form of Cushing's syndrome and you have increasing glucocorticoids which imply downregulation of the PVN,

Wit all else patients on GLP-1 agonists I wonder if the incidence of Alzheimer’s will decline? I wonder if Semaglutide reduces CRP? There are some preliminary indications that it may: https://cardiab.biomedcentral.com/articles/10.1186/s12933-02...

Between weight loss, inhibiting addictive behavior, lowering the risk of major cardiovascular events such as stroke, heart attack, and potentially derisking for Alzheimer’s, we should be pumping GLP-1 agonists out like a wartime effort. Likely contributor to fixing 70+ years of socioeconomic configuration that gave us Western Disease and the trimmings that come with it.

https://www.bloomberg.com/news/features/2023-10-18/glp-1-dru...

T will be interesting to see the side effects of chronic use of these compounds. Still too early to know.

Japan researchers have know about this for years. I don't know if Japan makes a big deal about publishing their findings but I watched a documentary several years ago which that went into very specific detail about the relationship between specific gut bacteria and Alzheimers. No disrespect to King's College - perhaps there is no overlap but this is more of an advancement than it is a breakthrough.

No way this was known before. There may be certain correlations but you have to realize this research effort is different. In controlled experiments if you as the experimenter can "cause" something to happen then you've skipped past the correlation != causation mantra that every Tom, Dick and Jane keeps chanting without fully understanding. At this point you've found causation.

Causal evidence of Alzheimer's? I don't think that's ever been known. The worst case scenario after finding this is that they find out that there's multiple causative sources of Alzheimer's.

sounds like prion disease:

https://en.wikipedia.org/wiki/Prion

EDIT: in the sense that it is similar

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