5 ms·

"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

"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?

Aurornis 3y ago
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.
- entwife 3y ago
  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.
- mobilejdral 3y ago
  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.
andrepd 3y ago
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.
reaperman 3y ago
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 https://news.ycombinator.com/item?id=33186046 ChatGPT log can be viewed here: https://chat.openai.com/share/e79afa6f-ee58-42a9-99c1-bd3a1a264a17 https://chat.openai.com/share/e79afa6f-ee58-42a9-99c1-bd3a1a...
- cabaalis 3y ago
  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.
  - reaperman 3y ago
    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.

Aurornis 3y ago

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.

entwife 3y ago
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.
mobilejdral 3y ago
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.

andrepd 3y ago

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.

reaperman 3y ago

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 https://news.ycombinator.com/item?id=33186046 ChatGPT log can be viewed here: https://chat.openai.com/share/e79afa6f-ee58-42a9-99c1-bd3a1a264a17 https://chat.openai.com/share/e79afa6f-ee58-42a9-99c1-bd3a1a...

cabaalis 3y ago
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.
- reaperman 3y ago
  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.