Natural occurring molecule rivals Ozempic in weight loss, sidesteps side effects | Hacker News Reader

Natural occurring molecule rivals Ozempic in weight loss, sidesteps side effects

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Delighted to discover this kind of breakthrough is based on a gnarly regular expression:

https://github.com/Svensson-Lab/pro-hormone-predictor/blob/m...

Beautiful yet terrifying. I'm glad that regex isn't something I'll ever have to touch.

The good news is it’s read only- if you’re reading for understanding, you’re doing it wrong :-D

It's not that bad. AutoRegex[0] and regex gen [1] make it more accessible than ever.

[0]: https://www.autoregex.xyz/

[1]: https://regex-generator.olafneumann.org

Heh, I just fed autoregex a regex from one of my projects, and it simply times out. It comforts me to know that billion dollar LLMs have to chew on those just as much as I do.

A proper litmus test, what's causing the hang in your case?

Regex to me, is pattern finding and abstraction taken to the extreme. I like the challenge

Good question. The regex I tried is for extracting amounts in EUR and USD:

  /
  (?<=^|[ \t])
  (?<currency_prefix_with_space>
    (?<currency_prefix>
      €|EUR|\$|USD
    )
    [ \t]?
  )?
  (?<number>
    (?<integral>
      -?
      \d{1,3}
      (?:[\.,]\d{3}|\d*)
    )
    [\.,]
    (?<fraction>
      \d{2,3}
    )
  )
  (?<currency_postfix_with_space>
    [ \t]?
    (?<postfix_or_ending>
      (?<currency_postfix>
        €|EUR|\$|USD
      )
    ) | (?<ending>
          [ \t]|$|\n
        )
  )/x

I'd imagine many nested named capturing groups may trip even the best automated system! I do like the solution though.

I would've probably approached it differently, trying to first get the 'inverted' match (i.e. ignore anything that isn't a currency-like pattern) and refine from there. A bit like this one I did a while back, to parse garbled strings that may occur after OCR [0]. I imagine the approach does not translate fully, because it's pattern extraction rather than validation.

[0]: https://observablehq.com/@dleeftink/never-go-nuts

Thanks for sharing! I have to admit I do not have the necessary brain cycles to spare today, but OCR processing is indeed of interest to me, and I will take a more in-depth look in the upcoming days.

The idea of an exclusionary approach sounds interesting as well. I'll have to think about that a bit.

Check out WordNinja in case regex doesn't cut it! [0]

[0]: https://github.com/keredson/wordninja

Will do, thanks again!

I think what's causing the hang is using the site. I gave it [a-f0-9]{8}(?:-[a-f0-9]{4}){3}-[a-f0-9]{12} and it sat thinking about things for a few minutes. So I tried the reverse and asked it "Match a UUID" and it sat and thought about things.

Now I am enlightened.

Aww shucks, and here I was feeling a wee bit proud of myself for managing to break it.

Regex is one of my favorite things to work with. It's surgery. I love having a very specific problem and a very sharp knife. What I hate is chasing down language or library bugs, or undocumented limitations. Of course I would hate it if I had never used it extensively. Its terseness is harder if you only have to pick it up occasionally.

You'll love this one then!

[0]: https://cardoni.net/parsing-proper-nouns-with-regex/

That regex detects things like "eeieiieeeiA __ 1 2 3__" as a proper noun. I'm confused by the decision to accept any number of leading [ei] and any number of trailing (?:\s+[_\d]+).

It's not perfect for sure, but perfectly suitable for a first pass and then a dictionary sweep or another set of regexes. I guess I like the compactness of it!

It only looks for a single leading “e” or “i”, not any number. I’m guessing those tweaks were added to capture specific proper nouns that weren’t captured by simpler “leading capital letter” regexes, like “iPad” or “eBay”.

"*" is "0 or more" and "+" is "1 or more", it looks for any number of "e" or "i" at the beginning and at least one capital letter. The diagram below the regex is wrong.

Instead of

  [ie]*-?[A-Z]+

it looks like they wanted

  [ie]?-?[A-Z]

There was a product called the eeePC or so. It was a "netbook."

The Asus product line, yes (all three Es apparently stand for "easy"). But Asus write it with a capital E on the front. Still, somebody else might not.

I have done something similar before, to help form an index for a large book. This is what I would consider a relatively simple regex.

The harder ones I have dealt with are those looking for malformed syntax where the closing mark that might be missing could be several thousand characters after the opening mark, or the opening mark itself might be missing, across a data set that is several hundred million characters. So you need something very complex to find all the distinctive characteristics of the content that is supposed to be enclosed - while avoiding the many similar structures that give false positives. Sometimes the technically easier solution is too slow to run (look ahead and look behind, etc), so you need to pivot and use other regex features. It can take a day or two to get right.

Remember to get a license for your code

https://regexlicensing.org/

On the list of disasters, they forgot "parsing html":

https://stackoverflow.com/questions/1732348/regex-match-open...

Huh, I tried sharing the Zalgo answer here, but it didn't quite work, never knew HN wouldn't render those kinds of characters

It did, but I kinda went over the top with it once and dang had to tell me off, so it might be they added filtering.

o, there's your problem. Only half is supposed to go over the top. The rest is supposed to go below.

> Licenses: “No regex licenses have been issued at this time.”

Perfect

Just license 007: License to kill.

Yes, once you have a scalpel, everything looks like a very specific problem ;)

That is the temptation! No requirements, no conventions, no best practices, no nagging boss, just me and total root access to all the files :)

I think it comes down to the syntax being used to make regex. It is borderline an assembly language level of making them. Better language tools would make it easier for people to grok. Basically instead of using chars like ?^()$ and the like lets use words people understand.

It’s not just the syntax. Regex isn’t directly composable (unless you just mash together strings). They cannot define nested structures, I.e. no recursion. They can’t maintain context.

We don’t need better language tools. Better parsers can, and already have, been implemented in libraries.

I’d have a look at parser combinators.

(?R) is very much recursion in there.

> They can’t maintain context.

Is true though, or perhaps "state"? I know I had to come up with an algorithm because regexp alone couldn't do what I wanted (not even advanced features like lookahead, lookbehind, etc.)

I played with parser combinators in Elm and found it very useful c.f. regexes - the issues were mainly down to the Elm implementation. Not sure how effective they are in Rust or Go

As @aranchelk said LL and LR grammars are literally that. They allow you to assign names to regexs and compose them.

Libraries like python's lrparsing [0] let you assign regex's (aka tokens) to variables, then build grammars by combining them using python expressions. For example:

    while_statement = Keyword('while') + '(' + expression + ')' + block
    statement = while_statement | ....
    block = Token('{') + Repeat(statement + ';') + Token('}')

These grammars are more complex, with more rules you have to follow, but also more checking is done when they are compiled. They tend to mostly work once they do compile. So they are what you asked for, but there is no free lunch.

On the down side, lrparsing is pure python so it's slower than python's inbuilt regex's.

[0] https://lrparsing.sourceforge.net/

I'm comfortable with it (having previously been paid to write Perl for several years), but what I don't like is how many other people I have worked with aren't, and just blindly paste in (totally incorrect) regexes from Stack Overflow.

Writing one that does exactly what you want is very satisfying. And with Python you can have named groups extracted into a dict and it just feels like magic.

Is this AGI?

oh god, can you even imagine?

After using a regex that creates AGI researcher will see the world like Neo sees the matrix.

Ask Deepseek to generate a regex for detecting python import statements.

Please, if you write regexes like these, comment them...

A great way to do it is to split them up by concatenating them across a bunch of lines, and put a brief explanation at the end of each non-obvious part (to the right, on the same line).

Plus that also lets you indent within nested parentheses, making it that much more understandable.

I'm baffled when I come across a file like this where the code itself is heavily commented, but a gnarly regex is not. Regexes are not strings, they are code -- and with their syntax, they need comments even more.

One thing I always appreciated about CoffeeScript was its [heregex syntax](https://coffeescript-cookbook.github.io/chapters/regular_exp...), which made regexes clear and easy to document.

Many CoffeeScript constructs were adopted into JavaScript and TypeScript, but unfortunately, heregexes weren't among them.

I agree. I'm pretty sure jashkenas got it from Ruby, which got it from Perl, with the `/x` flag (for extended regular expressions).

Later languages have added support for the `x` flag, including C# and Rust. There is also a stage 1 proposal for JavaScript: https://github.com/tc39/proposal-regexp-x-mode

Nice roundup, and thanks for sharing that proposal!

Notepad++ has /x mode as well.

I probably use regexes the most in notepad++

regex101.com is a lifesaver for parsing esoteric regexes after you've forgotten what they're supposed to do.

Great advice that is a bit redundant with LLMs, no? They're pretty great at all forms of translation.

First, I don't want to waste time feeding something into an LLM that should be commented in the first place.

Second, not at all. An LLM can tell you how the regex works (hopefully). It can't tell you what each piece means in terms of the program's logic. Or at least not always and not reliably.

Welcome to the fascinating world of academic code!

Is that an anti-pattern to put the comment inside the function vs above

Function documentation goes inside functions in Python, explicitly making them self-documenting. That can then be automatically picked up by any other code (like tooling for automatically generating API documentation) formalized as PEP 257, https://peps.python.org/pep-0257

Python will literally assign the content of your docstring (a triple-quoted string at the start of a function) to a special double underscored ("dunder") property called `__doc__` that any code can access; not just docs generators, but your own code as well (pretty dang useful for generating on-the-fly help output!).

Which also means that if you run into weird behaviour where a function doesn't do what you think it should do, you can just fire up the REPL, import that function, type `print(function_name.__doc__)` and presto, you have the documentation right there, specifically for the exact version you're using. You don't even need to leave your IDE if it comes with an integrated terminal.

interesting TIL too bad we don't have auto doc gen (fastapi what I'm working with atm)

edit: not saying it can't be done but our org isn't using auto docs

Yeah, it's one of those "Once you're used to writing doc strings, you have no reason to ever use anything else" but if you don't use them, it can be prohibitively laborious to move whatever alternative you're using over to "PEP-compliant".

(lots of fun dunder functions in Python that make metaprogramming a lot easier, but someone needs to tell you about)

Fluent Python covers a bunch of this stuff.

TIL __doc__! Pretty nifty.

> type `print(function_name.__doc__)`

Or even easier: `help(function_name)`!

https://news.ycombinator.com/item?id=43266546 just got posted about that =D

How is this not more well known? I thought I was a god for discovering dir() but you’re showing that I was nothing but a peon!!!

There's a bunch of "all dunder properties" pages online, any one of them is well worth reading through at least once. So much hidden goodness.

The actual docs on python.org are quite readable and probably a lot more accurate than random blogspam / LLM glurge pages

Why would you assume it's LLM slop when Python's been around for decades? Lots of folks are enthusiastic enough about "Python magic" to have done excellent writeups of literally ever dunder function under the sun on a single page, at a level of detail and excellence that the python documentation, bless its heart, cannot ever hope to match.

- The python docs are there to give you the information you need.

- Passion pages are there to do a deep dive into all the crazy shit you can do with that information =D

> Python will literally assign the content of your docstring (a triple-quoted string at the start of a function)

Any string. Triple-quoted is just multiline strings and works anywhere.

True, I forget some people think a single line is function documentation; any function that's worth documenting is worth documenting properly, and needs multiline ;)

Annoyingly it pushes the type definitions away from the function body when you have a particularly long doc. It’s a cute trick but docs above would have been better.

You know what's cool: IDEs. They can do block folding. The really good ones just auto-fold function docs because you don't need to see those until you do.

It's not just a good trick: it's the right way to do it, and tooling can be (trivially) made to show you only what you need to see until you need to see more.

If we’re assuming an IDE that can arbitrarily change text layout and rendering I don’t see why it matters where the comment goes

I got lost at (?R). IIUC, this is a feature of the "regex" module that "tries to match the entire regex recursively". Fun.

That’s only the tip of the iceberg. Here’s “How Perl saved the human genome project” from 1996:

https://bioperl.org/articles/How_Perl_saved_human_genome.htm...

(And of course all the articles about excel renaming genes, and then people trying to clean up the mess…)

> The study would not have been possible without the use of artificial intelligence to weed through dozens of proteins in a class called prohormones.

I see we’re being fast and loose with the term “artificial intelligence”?

Could be that they relied on AI to generate the gnarly regex ¯\_(ツ)_/¯

Any sufficiently advanced regex is indistinguishable from AI.

Even simple regex ones, since we don't know if they were created by a human or an AI.

I'm trying to think of a funny way to cite Clark's Law, but failing...

Regexes occasionally get called "black magic", and there is is an inverse of Clarke's Third Law: Any sufficiently advanced magic is indistinguishable from technology.

I think you meant “any sufficiently commoditized magic is indistinguishable from technology”, or “any sufficiently analyzed magic is indistinguishable from science.”

With enough if statements, you could create a LLM.

I am still waiting for an LLM trained to focus on effin' regexes and their variants like sed, somebody please do a page with ads for this and you will have a nice little side income and warm fuzzy feeling on top of it.

Natural language -> fully working one, I don't mean some email validators but way more complex stuff. Although, I've recently had a case which was too much even for regexes in any form or spec, then sort of grammar-based parser needed to be done from scratch.

I haven’t had the need for super complicated regexes, but ChatGPT and Claude both worked fine to generate a regex to extract markdown code blocks.

AI is the new, “Algorithm”. It is an overly broad term that basically means, “Technology” to people who use it.

For non-technical people, terms like Machine Learning, Algorithm, Automation, AI, Neural Networks and 'Magical Powers' are synonymous.. Journalists, marketing teams, and executives choose whichever term generates the most hype and clicks.

I like to describe my job as a software engineer as "wizardry" to people. With the way LLMs are writing code, it's only getting closer to writing actual spells.

> "Formerly, when religion was strong and science weak, men mistook magic for medicine; now, when science is strong and religion weak, men mistake medicine for magic."

— Thomas Szasz

"Like a magic crystal mirror, My computer lets me know Of the other world within it Where my body cannot go / The computer is a gateway To a world where magic rules Where the only law is logic Webs of words the only tools" https://mindstalk.net/filk/world.html

My understanding is that the original use of AI was to describe algorithms that solved complicated problems, but only sometimes, and usually through heuristics. As opposed to provably correct algorithms like Dijkstra's.

I think that's how we still use it.

It is a somewhat though provoking question for me where you LLM's fall in automata theory? Are they non-deterministic finite automatons which would make regex's a cousin? Or does it require pushdown automata levels of capability?

Regexes were invented by Kleene in 1951, to describe McCulloch-Pitts neural nets. So, artificial intelligence!

https://www.rand.org/content/dam/rand/pubs/research_memorand...

Jokes aside regexes being AI, lots of protein motifs can be elegantly described by simple regexes. And their classification performance is sometimes perfect.

See the Eukaryotic Linear Motif resource: http://elm.eu.org/elms.

unfortunately, if you do anything computational, when you need to explain it to a journalist/public audience/young person you want to hire/investor/trendchasing early user, you are incentivized to call it "AI".

Neat. I always thought Advent of Code 2015's Day 19 (Medicine for Rudolph) was just an exercise in parsing and validation of production rules against a grammar, and any use of regex in that puzzle solution was purely coincidental ;)

Obligatory xkcd:

https://xkcd.com/208/

A very early one at that

Since it is naturally occurring, it isn't patentable. Which means it is less likely that companies will develop a commercial product from it.

Why pay to get FDA approval, if you don't get a government granted monopoly on it afterwards?

This is one problem with using patents as the mechanism to incentivise development of medicine.

The article did refer to patents.

https://patents.google.com/?inventor=Katrin+Svensson

It would seem they are modifying peptides. Which is patentable.

If the molecule itself is not patentable, the process of efficient extraction or synthesis may be. So, if somebody can come up with it, they may have a thriving business.

The substance in question is a peptide. It's not something you simply extract from a plant using a solvent. OTOH, being a peptide, it's likely easy enough to produce in a genetically engineered bacterium or yeast. Efficient extraction may remain a problem though, because you'll need to select a particular protein fragment (the peptide) from reams of other protein fragments of the bacterial / fungal cells you process.

The extraction problem has been solved for a long time to make recombinant insuline. Before that it had to be extracted from an animals pancreas. These days peptides are often improved using non-natural amino acids to make them more stable and thus longer acting. Semaglutide is a good example. These are synthesized using solid-phase synthesis.

I've always been very, very skeptical of this claim.

If there's an actual natural, identified substance with huge benefits to people, it's going to go gangbusters and you're going to make a lot, LOT of money selling it, even if you're doing it via roadside lemonade stand.

It feels like this claim is usually used to promote cures and treatments with extremely low quality RCTs backing their use as a sort of panacea.

I used to believe the "just do shrooms to cure depression" claims on principle until I looked into the quality of those studies, which is very low. At that point, you're just making stuff up.

Caffeine is an example. Coffee and energy drinks are doing well I'd say.

That’s an excellent point

Caffeine is grandfathered in as a Generally Recognized as Safe food additive. If energy drink companies had to go through clinical trials with no patent protection for each drink formula, they wouldn't make them.

Why was caffeine studied? Why does it continue to be studied?

It’s a lot cheaper to study something in academia than to do a full clinical trial.

The global coffee market is worth $138 billion, the soft drink industry is $556 billion (and growing). The vast majority of which being caffeinated. Starbucks the company is #116 on the Fortune 500 and #1 in food services. There's sufficient economic activity to warrant continued research in the area.

I think the current regulatory regime in many US states allows companies to make a killing off of selling naturally occurring bioactive substances as dietary supplements with few regulatory hurdles.

Kratom, CBD, and delta-8 THC are naturally occurring bioactive substances that are newer to the US market. Both have carved out a pretty nice economic niche with a bunch of claimed health benefits.

A couple of years back, I saw a sign outside a fancy legal highs shop in Fishtown, Philadelphia touting the benefits of kratom as a pre-workout supplement. The insanity that a business was advertising an addictive opioid to healthy, opioid-naive people for better gains in the gym almost makes me want more regulation in this area.

Your point is a bit undermined by the fact that two out of your three examples are cannabis extracts, where cannabis proper - literally a leaf - is still very much illegal and has to be "laundered" through chemical processes to make it less fun and therefore "medicine" instead of "recreational drugs".

I think your point and mine can both be true at the same time. Cannabis is the subject of a past regulatory regime that restricted nearly all psychoactive substances popular at the time (natural or synthetic). The actions of that regime do not go away when the zeitgeist changes. The current regulatory regime is much more dovish, and that is visible in the difference between the controlled status of chemicals that became popular recently versus similar ones that were popular 50 years ago.

Isn't it relatively easy to sell anything "naturally occurring" as a supplement? I think there is very little regulation (of course if you want to claim it's a drug and presumably charge much more for it it's another matter).

Even synthetic research chemicals are generally legal as long as you add a "not for human consumption" label (and they aren't explicitly banned or analogous to other illegal/regulated drugs).

I'm skeptical of your claim because if there's any additional margin to be made doing it artificially, at big-pharma scale history shows that they plenty willing to squeeze every penny out that they can even if it's less effective/natural.

That's true, but doesn't really squeeze natural alternatives out of the market if they're effective.

For example, there's a prescription engineered version of melatonin.

Melatonin is still a huge business.

Red Yeast rice exists, and so does lovastatin (Altoprev)

Right, but there is a free rider problem. Why should a company spend $100 million doing clinical trials to get FDA approval if once it is approved, all other companies can sell it, even though they didn't pay anything? Even if every actor in the market thinks there will be a good return on investment if they get FDA approval, there is a strong incentive to instead wait for someone else to do it and free ride on them. The result is no one acts.

Clinical trials are a significant expense in developing a drug. Kind of makes me think we should award patents not for coming up with some molecule, but instead award them for showing a molecule is safe and effective.

CBD, which doesn't appear to have a fraction of the therapeutic efficacy of something like Ozempic, is a multi-hundred billion dollar industry now with a lot of active research.

Do you have a source for that? Everything I can find online puts global CBD industry revenue at less than $10 billion. And that's everything. The only FDA approved use of CBD (treating seizures), I'm sure is only a tiny fraction of that.

In any case, none of that refutes that there is a strong economic incentive for market actors to not fund FDA approval trials since any benefit will be shared by the entire market.

Lithium is a good counter. It is by far the best treatment for bipolar 1, and its cheap and easy to source. Prices for lithium carbonate and other lithium medicament's are not at all cheap, and there are not a lot of medical companies producing it. There has even been shortages. Instead antipsychotics have been pushed as a preferred treatment, even though the outcomes are worse than with lithium.

Lithium in dosages effective in treating a mood disorder is quite toxic (e.g., to the kidneys) so most of the price is probably to offset the risk of lawsuit awards.

But antipsychotics cause movement disorders and metabolic syndrome.

With regular blood checks its not an issue. You can catch it before the kidneys take damage. Antipsychotics are literally neurotoxic (first gen atleast).

> Prices for lithium carbonate and other lithium medicament's are not at all cheap

You can buy a 3 month supply of Lithium Orotate for like $10. I certainly wouldnt recommend self prescribing this kind of thing though.

It’s not enough dosing to treat bipolar.

You have to dose relatively high in order to have an effect. You’re disrupting your neural sodium-potassium pumps with it.

But it’s still pretty cheap. Hard to charge a lot for a fairly abundant element.

Nitrous Oxide (laughing gas) is both significantly cheaper, and less risky than epidurals for reducing pain during childbirth. Yet, in the US, most hospitals don't even offer it as an option, and I think a major part of that is that patented epidurals have much higher margins, so that is what the medical suppliers push.

I doubt it. It's very commonly offered in the UK and while it's cheap and safe, based on what I've seen it's also not effective at all. Forget the same league, it's not even playing the same game as an epidural. An epidural is a drip of opioids right to your spine. Proper hardcore.

Other mentioned extraction and such, but semaglutide had been known for some time, the other half of the problem is delivery. You’ll notice the article says the calorie intake was decreased an hour later. You need to make it stable, long lasting, and via a delivery method that people can tolerate.

Giving yourself an injection an hour before you eat or an hour before you are hungry isn’t going to work.

If only there was a way for the people to pool their collective resources, maybe each contributing a fraction of their annual income (with a greater contribution proportion at higher incomes), and put those resources towards development of thins that benefit the common good but lack a direct profit incentive. Hmm...

CRISPR is naturally occurring, but got patented to hell.

Nestle is making billions of dollars -- off water.

this is 1000% not true, plenty of naturally occurring substances are turned into profitable medicine, aspirin and insulin are examples off the top of my head.

That’s not exactly true. Cannabidiol (CBD) is naturally occurring and there’s a commercial FDA approved drug for epileptic seizures in children called Epidiolex. If I remember correctly, the patent is for “Oral cannabinoid formulations”.

Even without a patent, companies can get FDA exclusivity but for not as long as a patent grants them so unless the addressable market is huge, it’s a financially riskier bet.

Keyword there being ‘formulation’, not ‘molecule’

A “formulation” is a “molecule” at a specific concentration, in a specific solvent, etc. The patent is still on using CBD.

I'm sorry, your hypothesis is that people will be less likely to try and build products around a naturally occurring weight-loss drug?

Like, less likely than they would be to pay Ozempic to use their patent? I mean, I could believe that if there weren't like Billions of dollars being funneled into weight-loss programs and foods that don't have any demonstrative weight-loss capabilities.

If this actually works and is naturally occurring, I'd be surprised if there weren't like enterprising startups and food companies adding this to existing products within a year or 2.

I feel like the natural occurring property makes it more likely a supplement company will bring it to market without FDA requirements. The path to market should be simpler from my understanding of this space, please correct me if that’s incorrect

Pretty sure this would help save health insurance companies and Medicare billions if it’s a relatively safe defense against obesity and related mortality. There could be a push to get it to market from Medicare? Anyone want to comment with more knowledge of how it could be funded by the government? Note: The current administration is gutting the NIH so those programs and grants are shrinking

> Since it is naturally occurring, it isn't patentable

Supplements are a $50bn business [1].

[1] https://www.grandviewresearch.com/industry-analysis/us-dieta...

I'm late to the party and this is not my forte so I'd differ to many people, but if you patent the natural compound for a disease you can do that. In addition to that patenting it for certain formulations. A case in point is https://en.wikipedia.org/wiki/Dimethyl_fumarate Tecfidera (the drug name for the drug used for MS made Biogen Idec billions of dollars.

The history from wikipedia

The first medical use of fumaric acid was described in 1959 by Walter Schweckendiek, a German chemist, and was a topical formulation for psoriasis. The Swiss company Fumapharm eventually brought Fumaderm, an oral formulation of dimethyl fumarate (along with some monoesters) to market for psoriasis in Germany in 1994.

Based on the efficacy and safety of this formulation, and evidence that dimethyl fumarate was the main active component, an oral formulation of dimethyl fumarate was developed by Almirall. This oral formulation, under the brand name Skilarence, was approved by the European Medicines Agency (EMA) in June 2017, for the treatment of moderate-to-severe plaque psoriasis in adults.

Initial clinical research on the use of dimethyl fumarate for the treatment of multiple sclerosis was conducted by Fumapharm in collaboration with Biogen Idec; Fumapharm was subsequently acquired by Biogen Idec in 2006. Aditech Pharma in Sweden had also been researching oral formulations of dimethyl fumarate for MS and in 2010, the Danish company Forward Pharma acquired Aditech's patents.

You mean like the entire wellness industry reselling fiber and turmeric and black pepper for you at 100x multiples?

This is the press release that is being republished with ads in the post link https://med.stanford.edu/news/all-news/2025/03/ozempic-rival...

https://www.nature.com/articles/s41586-025-08683-y

This seems to be the paper, but its behind a paywall.

Anyone with access can tell me if they publish the 12mer amino acid sequence? Is there more to it (post translational modifications)

Or is it just the peptide?

Note, I have access but this is not my field. I just asked ChatGPT your question after have it read the paper. This is what the response was:

Yes, the paper provides the 12-mer amino acid sequence of BRP: THRILRRLFNLC .

Regarding post-translational modifications, the BRP peptide was synthesized with a C-terminal amidation, which was critical for its bioactivity. The non-amidated version of BRP was inactive in vitro . Additionally, the paper mentions that the C-terminal cysteine (C12) was synthesized as a free thiol .

So, BRP is not just a simple peptide—it has a key post-translational modification (C-terminal amidation) that influences its function.

Very nice, thank you. This indeed answers my question.

"The study would not have been possible without the use of artificial intelligence to weed through dozens of proteins in a class called prohormones."

"the researchers designed a computer algorithm they named "Peptide Predictor" to identify typical prohormone convertase cleavage sites in all 20,000 human protein-coding genes."

so look, when I have to go around talking to normies, they're like, "don't you think AI is going to take over everything?" and for these folks, "AI" means *one thing*: chatgpt or similar LLMs. So when they read this, they're like, "see? AI! we need AI everywhere! chatgpt assistants!" and then I pretty much have to lose my shit and they think I'm crazy, because they have no clue. This is also kind of like how it is deep inside all the corporate hype departments so many of us have to endure where our management is chucking shitty LLM garbage at us all day ordering us to "integrate this ! integrate that! we need AI (by which they mean hallucinating chatbots)".

That is NOT what they used here. They wrote their own algorithm which we'd assume uses some straightforward machine learning approach such as bayesian filtering (edit: it's literally just a python + R script with some training data: https://github.com/Svensson-Lab/pro-hormone-predictor/tree/m...) . and in fact, I bet the researchers are calling this short script "AI" because their investors/bosses/managers are demanding they "use AI". Machine learning is a WAY more accurate term than "AI" which IMO is a completely useless hype term at this point, and it's making our lives as engineers worse having to deal with the whole world thinking robots are taking over and making our bosses obsessed with our having to "use AI" for everything (which is of course because they'd eventually like to have fewer employees).

Is the muscle loss a side effect of the drug or of the weight loss?

eating less calories always has that side effect, you can train and eat protein to minimize it tho just like with regular diet

The loss. You eat less so you're probably eating less protein. And if you used to be heavy then it's safe to say you probably had some muscle mass and you're going to lose that with the caloric deficit especially if you're not exercising.

Lean mass is just non-fat mass. That includes much more than just muscle.

I can't find any evidence that GLP-1 are catabolic to muscle mass. There is no evidence I can find that GLP-1s do anything above what calorie restriction does.

There is a linear relationship between calorie restriction and fat loss down to under 10% body fat. There is so much wrong information on calorie restriction from studies done on people who were literally starving with already very low body fat %. Then apply that to people with 25% body fat is just wrong.

Westerners trying to lose weight don't have this problem. I think part of the obesity epidemic is this insane idea that calorie restriction is bad. Everyone kind of understands the thermodynamics of calories in / calories out. Everyone even kind of understands the benefits of fasting. At the same time though there is this nonsense that if you restrict calories too much you start burning all this muscle mass. It is patently absurd.

Add up the calories of what a 250lb bodybuilder is eating for contest prep to lose fat and you will see they are "starving" too.

YOU ARE ABSOLUTELY CORRECT. READ ^THIS^, FRIENDS.

In the end, it really is just metabolic math. As a former wrestler who did some insane weight-losing in my youth, the muscle mass loss is due to extreme calorie restriction. Besides, just sitting around starving is not a good way to become healthier in the long run, and that's where the muscle loss will be worst. To be a true journey towards better health, dieting should be accompied by at least a lot of walking and some light weight training, in the minimum.

And don't forget your supplements, kids (addressing general readership), because our foods are less nutrient dense in 2025, so find out if some supplements help energy levels on the downslope. Me and my teenagers have taken a sip / mini-gulp of a product called 'Orgain' daily for a month or so, and I have found my energy better, while having less cravings. An entire little 11oz single-size drink is way too much for me (too many vitamins, makes me sleepy), having 'just a little bit' is not at all scientific, but we seem to be thriving on that little bit of supplementation.

And, as always, avoid those processed sugars, kids! Whole sugar cane is very, very good for us, but only in moderate doses. Processed sugar is the crack cocaine of sugar cane, as opposed to just chewing a leaf of the coca plant.

I only wrestled for 2 weeks in 8th grade but have ASICS MATCONTROL 3 on right now. My gym shoes :)

High school wrestling though might push things too far.Many of those guys under heavyweight do not have the bodyfat % to be restricting so much so are actually losing muscle mass.

I know Jordan Burroughs diet that I have seen seemed like maximum micro nutrients for the calorie because how else can you eat to be a 4 time world champion at 74kg?

I am probably half an inch taller than Burroughs and 163lbs is impossible. It is too far. Way too far.

Yeah, I just went down a rabbit hole re-looking this up myself.

It seems that there's nothing unique about semaglutide, and %FFM loss is just a function of how rapidly you lose weight.

The most rapid losers on semaglutide have the same %FFM loss (30%) as bariatric patients, for example.

And if you don't want to lose weight that fast, you can just temper the dose (unlike with bariatric surgery).

Or eat protein and exercise.

I think it's extremely probable that the most rapid losers are running the largest calorie deficit and also the largest protein deficit.

There is an age/hormone variable too.

I would have said just eat protein and work out when I was in my teens, 20s and early 30s too.

I am 48 and not on testosterone, yet. I actually can't recover at this point from workouts that burn enough calories vs working out less but more calorie restriction in terms of fat loss. Even 60 minute walks cause me to be more hungry to be able to recover from than what I can restrict without walking.

I am at the final death throws of natural and not being on TRT basically. I have been pushing TRT out since my late 30s but have gone way too far.

I think the TRT threshold probably be when you can't outrun calorie restriction by working out. For me, that has probably been since 43 or 44. By 46 for sure.

Personally, I don't need GLP-1s. So many people though do.

Keep in mind I am not using GLP-1s myself because I am unsure of the long term risks.

What worries me is if what if in 20 years of use, something with insulin gets blown out?

There is a chance it could be a drug for life like testosterone. We know though how devastating obesity is on health so it is really going to be up to the individual to take the risk. Not really my business at that level.

The drug does not directly affect muscle mass (unless you are already very lean), but heavy people are doing resistance training against their own body weight all the time, so they are strong in the absolute, even if not relatively. Weigh less and your muscles have it easier, so weaken, unless you keep them strong with exercise.

I’m not sure that’s exactly what’s happening with GLP-1 drugs. I lost 40 pounds very quickly on them and hurt my hip then my shoulder then my wrist. Felt like I was constantly getting muscle strains and random injuries.

I started drinking a protein shake once a day and the random mysterious injuries stopped.

I'm on them too, and after being seriously grumpy for a while it dawned on me that not being hungry doesn't mean my body doesn't need satisfying food. I think it's easy to fall into 'don't need to eat, won't eat' and then get some form of malnutrition. I force myself to make good food and just eat less of it, so far it worked *fingers crossed*

What you described doesn’t seem to be in conflict with what he described

If the muscles had been reducing in concert with the reduced musculature needs of my body I wouldn’t be injuring myself.

the caloric restriction that these drugs engender can indeed lead to various forms of under-nourishment. as you point out, your protein needs (as a proportion of calorie sources) go UP when you are in caloric restriction; see PSMF.

A single protein shake typically provides around 22g of protein, which is a small portion of the recommended daily intake for maintaining muscle, generally close to 1g of protein per pound of body weight. As an example, I'm currently on a weight loss diet and have a 180g of proteins target per day. Unless you were significantly under-consuming protein, it's unlikely that the shake alone made a major difference.

Such high recommendations are for people that want to maximize muscle retention / growth not people that just want to be healthy. You can get by on much less.

Right but even on the low end of recommended daily protein intake, 22g would probably still be a small fraction.

The RDA is 0.37 g/pound. For a 180 pound guy, that means 67g of protein. That might sound low, but wait... At least according to this one page I found, 25% of American adults eat below RDA. It's not hard to imagine then that there are many people for whom 22g extra could make a decent difference.

0.37g/pound is on the very very low end though, far from optimal on a weight loss diet.

See this article: https://www.healthline.com/nutrition/high-protein-diet-plan#...

> The Recommended Dietary Allowance (RDA) of protein is 0.8 g per kilogram of body weight (g/kg/bw), or 0.36 g per pound of body weight (g/lbs/bw).

> However, the authors of a 2019 review suggest that this number is often misinterpreted as the ideal number. It’s only the minimum amount of protein required to prevent nutrient deficiencies and muscle loss in most healthy individuals.

> A 2017 study found that participants who ate a high protein diet of 1.34 g/kg/bw (0.6 g/lbs/bw) for more than 75% of the 6-month duration experienced significantly more weight loss than the group who followed the RDA requirements.

> A 2016 review found that eating up to 2 g/kg/bw (0.9 g/lbs/bw) may help promote strength and prevent muscle degeneration.

etc.

Kinda missing the point. For you, supplementing 22g is nothing. For something that is deficient it could be quite a difference maker.

But strength training is required anyone who wants to be healthy [0]. The RDA is just for avoiding clinical deficiency.

[0] https://www.barbellmedicine.com/blog/where-should-my-priorit...

This is likely just from losing weight rapidly in general. We see it with people losing weight from a variety of other sources, too. It's possible GLP-1s might enhance the effect in some way, but it's already a significant enough issue in general that adequate protein intake + some resistance training is important regardless.

I don't think that's the mechanism. A caloric deficit causes your system to metabolize whatever it can. It likes fat because that's energy dense, but muscle is also a good source of energy as well, and the more rapid the weight loss, the more body mass it has to burn.

As far as I know, muscle is only used when fat reserves are depleted or you don't eat enough protein for the brain's personal amino acid supply. I'm not particularly knowledgeable about this, though, maybe an expert can weigh in.

Not an expert, but from my own research muscle will always atrophy to its functionally base necessary mass, there are of course genetics involved in muscle mass retention as well that can’t be overlooked. But you can be in a caloric deficit and your body is burning fat(which often times this leads to lower energy and less intense resistance training) while still losing muscle mass. I don’t believe they’re mutually exclusive.

You’re 100% right though, the key to retaining muscle mass while in a caloric deficit is consuming sufficient protein, or even over-consuming protein. In starvation situations muscle is next up after fat when getting consumed for energy but it seems like for the most part the muscle mass deterioration during significant weight loss periods is a natural side effect of the process and lifestyle required to accomplish it.

>1) compared with persons with normal weight, those with obesity have more muscle mass but poor muscle quality; 2) diet-induced weight loss reduces muscle mass without adversely affecting muscle strength; 3) weight loss improves global physical function, most likely because of reduced fat mass; 4) high protein intake helps preserve lean body and muscle mass during weight loss but does not improve muscle strength and could have adverse effects on metabolic function; 5) both endurance- and resistance-type exercise help preserve muscle mass during weight loss, and resistance-type exercise also improves muscle strength. We therefore conclude that weight-loss therapy, including a hypocaloric diet with adequate (but not excessive) protein intake and increased physical activity (particularly resistance-type exercise), should be promoted to maintain muscle mass and improve muscle strength and physical function in persons with obesity.

https://pmc.ncbi.nlm.nih.gov/articles/PMC5421125/

Any calorie deficit of 500 under BMR and the body will not just consume the fat stores but also muscle. That’s what I learned on the bodybuilding forums at least. Some people went too high on the deficit and ended up losing some muscle definition

It's more likely to happen if your deficit below TDEE is greater than 500 Calories. If you're 500 below BMR, you're almost definitionally losing weight at an unsustainably unhealthy rate, like much greater than 1% of your bodyweight lost per week.

The body needs protein to function (the body is partially built out of protein, and also proteins perform many important functions in the body), and it cannot be synthesized from fat or carbs. The body also has no store of protein. This means that outside of dietary protein, breaking down muscles is the only option.

Secondary to that, the body needs some amount of glucose. The best option for that is stored glycogen. When those stores run out the body can enter ketosis which reduces but does not eliminate the need for glucose. Fat consists of three fatty acids joined by a glycerol part. Most of the energy is in the fatty acids, but the glycerol can serve as a limited supply of glucose. However that is not really sufficient, so to get more glucose, and the other option is breaking down protein.

Both. Muscle loss is due to not eating enough proteins to maintain muscle mass.

You can lose muscle mass without drugs just by eating poorly (and not doing adequate movement)

According to this article, it's a side effect of Ozempic itself. The article goes on to say that the newly discovered molecule can side-step the side-effect and metnioned that "obese mice treated with daily injections of BRP for 14 days lost an average of 3 grams—due almost entirely to fat loss..."

We don't know yet whether the muscle loss is caused by the drug itself or due to the weight loss, there are some studies but I haven't seen any conclusion yet one way or the other.

Anecdotally, a friend of mine was on a diet and exercise regime, then at some point he switched to Mounjaro to reduce cravings, while keeping the same diet and exercise regime (he's a data geek so he documented things pretty well), and his muscle gain maybe slowed a tiny bit, but didn't reverse on Mounjaro.

Sample size of one, but at least it's not zero.

Also sample size of one, but with the weight loss from semaglutide, I've gotten back in the gym and I can now lift more weight than I ever have. It feels fantastic (both the weight loss and being strong)

I envy you. I tried three times and got bad side effects each time, so I've given up :(

I feel for you, friend. The safest way, however, is to make hunger your friend, and walk an hour or two a day. That may not work well with your work schedule, but you can override your body with your mind, unless your mind suffers because of our tech work's energy needs.

And, it takes me a day or two to get past a processed sugar addiction. After those couple of days, the body starts getting used to not having that "crack" energy source be a part of its desire-base.

Good luck, stavros, you can do it! And the sooner you start, the quicker you can get over the initial hump of resistence. Perhaps you can carrot yourself along by knowing that you WILL feel much, much better as the pounds start coming off and your body starts being able to walk a bit further or lift a few more weights. Fight the food inertia, my brother.

If you really want extra help, contact the Creator of the universe in the morning and evening, and ask It for help. If you do that with an intention to be able to better help others, you will find that the universe, itself, will become your ally.

Same for me. Though I started weightlifting 3x a week to combat any potential muscle loss.

I cycle frequently and the impact of the weight loss and added strength has made me feel much faster this year (and it's still rainy/cold season).

It’s just absolutely not the case though. These drugs are now rife in the bodybuilding community, combined with a high protein diet and resistance training muscle will be retained. There is no mechanistic action to suggest that muscle loss would be caused by these drugs, quite the opposite actually.

You can't answer the Ozempic case without looking at research that compares people who rapidly lost weight with vs without the drug, and then looking at the %FFM difference between them.

We know that rapid weight loss causes muscle loss at a higher rate than slower weight loss in general.

GLP-1s might enhance this effect somewhat, but there is nothing definitive.

Adequate protein intake + resistance training can fully counteract it, however. I've even added significant lean body mass while losing fat while on GLP-1s.

It's nearly always a side effect of weight loss, and it's a good thing. It's confusing how people act like it's bad.

If you're obese, your legs are enormously strong with crazy amounts of muscle. Have you ever seen someone obese do leg presses at the gym? They can handle tons of weight.

When you lose weight, you don't need all that extra muscle. If you're carrying around 180 lbs instead of 300 lbs on your frame, all that extra muscle goes away because there's no point in keeping it. This is a good thing.

Even if you go from 200 lbs to 180 lbs, there's a level of muscle you don't need anymore.

Losing muscle as you lose weight is natural and good. Now, obviously you don't want to lose so much that you become weak for your size, but that won't happen if you continue to be physically active. Your body is exceptionally good at maintaining the exact right level of muscle to meet the regular stresses it undergoes. (Provided you are eating enough protein, but that's easy.)

I think the downside is that you don't just lose muscle in your legs and core, but rather you lose muscle mass all over. Yes, this is the expected result of calorie restriction but the issue is that when people lose a lot of weight without taking action to build and maintain muscle the amount of muscle loss they experience can cause other problems. Someone relying on a GLP-1 drug is often someone who isn't very active at all.

> but rather you lose muscle mass all over.

Well, you lose weight all over. You lose fat in your arms and your shoulders don't need to be quite as strong. You lose weight on your face and your neck muscles don't need to be quite as strong. You lose more in your legs, but you're supposed to lose muscle mass all over.

> Someone relying on a GLP-1 drug is often someone who isn't very active at all.

Sure, but that's a completely separate issue. It doesn't have anything to do with weight loss. Being in good strong physical shape is great, but nobody should expect weight loss to magically result in strength. That's like thinking you can stop going to the gym but won't lose any of the muscle you'd previously built up. It's got nothing to do with weight loss though. It's got to do with the fact that you're not working out.

The problem is that fat, sick people lose a lot of weight and muscle mass and then become skinny and frail. It just puts you at risk of other medical issues. In older individuals this can cause decreased mobility and raise the risk of falls. Its well documented in medical literature, that's why people worry about it.

But my point is that this is no different from being skinny and frail in the first place. It has nothing to do with losing weight.

Yes, that puts you at risk. That's why you should exercise, even if it just means daily walks.

The point is, you're not winding up with too little muscle because you lost weight. If you're winding up with too little muscle, it's because you're not being physically active enough. If you're physically active, you won't lose the muscle that you still need even as you lose weight.

> The point is, you're not winding up with too little muscle because you lost weight

Imagine someone eating only candy and pastries, but because they eat so huge amounts, they actually get a half-decent amount of protein. Then they decrease portion size with the help of appetite suppresants.

I explicitly made clear in my original comment:

> Provided you are eating enough protein, but that's easy.

If you're trying to lose weight eating only candy and pastries, then we're having an entirely different conversation...

If you were physically active enough and careful about your diet you likely wouldn't be on a GPL-1 drug. That's the point. People end up in bad shape for a lot of reasons, including injury. The search for a mechanism to burn fat without losing muscle is to help support people who are on GLP-1 drug because for whatever reason they were insufficiently active.

Spot reduction of fat is a myth.

OK? Nobody's talking about that?

>You lose fat in your arms and your shoulders don't need to be quite as strong.

This is literally describing spot reduction of fat.

No, it's literally the opposite.

I was describing how you lose fat all over. And as part of overall fat reduction, you lose fat in your arms, because your arms are one part of all over.

This is exactly why hand-to-hand combat instructors will tell you that fighting an obese person will go very differently than you might think it will.

That is absurd. Muscle mass is a huge predictor of mortality and anyone who isn't actively strength training and maintaining higher levels of muscle would see a health benefit by doing so. The idea that an overweight person has "too much muscle" is nonsense.

The side affect of muscle loss from these glp-1 agonist drugs is a serious downside that everyone should be aware of and try to mitigate if they choose to take them.

> The idea that an overweight person has "too much muscle" is nonsense.

I think you've misunderstood GP. He's not saying they have too much muscle when they're overweight. He's saying that take that exact same amount of muscle, subtract a ton of fat from their upper bodies, then they have "too much muscle" as typically needed for their body mass. I don't agree with their phrasing, but the point isn't "nonsense."

I understand the point. Mine is that an ordinary untrained person will see health benefits and a statistically longer life from more muscle. An overweight person would have more muscle than their non-overweight counterparts (mostly localized to the legs, not upper body), and that is the one and only positive of being overweight. Willfully throwing that away will harm your health, full stop. The muscle loss problem with these drugs is talked about a lot because it is in fact a problem. Not because the medical field is mistaken in thinking it's a bad thing.

Your complaint doesn't make sense to me. The negative health impact of being obese isn't equalized by having a little more muscle mass.

Also, if this is your stance, then GLP-1 is a red herring because you have the same issue with weight loss in general. Weight loss, without increasing resistance training, leads to muscle loss.

There’s negative cardiovascular effects from excess muscle just as with excess fat.

Normally that’s offset by the health effects of the exercise required to gain and maintain them as well as the lack of medical conditions that prevent exercise etc. But a fat person losing weight should inherently lose muscle mass long term assuming no changes to lifestyle.

I was looking for this comment! Not a doctor, but as I understand it muscle is roughly equivalent to fat as far as your heart’s workload is concerned. I thought I also read that muscle movement helps with blood return.

Muscle movement is also necessary for the limbic system to function.

Limbic system is unrelated to muscle movement.

Movement is required for the lymphatic system to function, excess muscle volume doesn’t help.

This is one of those statements that is technically true but not particularly relevant. Obese people are almost never at a level of lean body mass that they would overall be at a good amount of muscle even for a healthy total weight, and rapid weight loss has consistently been shown in studies to reduce more lean body mass than slower weight loss.

Getting to the same level of additional weight from muscles as there is from fat is also incredibly difficult. The average 5'8 person not utilizing AAS would take years of dedicated training, dialed in diet and recovery, etc., to get to 200lb at 15% bodyfat. People get there much faster and much easier putting on fat.

What’s relevant is subjective. I’ll agree it’s far from as important as obesity, but the point is some of this adaptation is good.

As to loss of muscle mass from rapid weight loss, that’s very true but slightly overstated as regaining muscle can occur ~10x as fast as it takes to grow it in the first place. Someone without a significant calorie deficit barring nutritional deficiency or other impediment will regain whatever muscle mass is required for their lifestyle quite quickly. However, people don’t train with weighted vests as among other things it targets the wrong muscle groups.

>muscle mass is required for their lifestyle

The problem here is that the overwhelming majority of people that need GLP-1s have lifestyles that are not conducive to health and have less muscle mass than would be healthy to begin with.

Which is what has me so confounded by this claims - these people already have less muscle than they should for optimal health. Losing any is a significant issue. And without lifestyle intervention, they're not going to regain any of that lost muscle.

GLP-1 drugs are phenomenal and a huge win for health outcomes. But that doesn't mean we shouldn't be telling people the truth about their downsides and what they need to do to counteract them.

Let’s ignore GLP-1, and assume an individual slowly dieted to that exact same weight. What’s going to happen over the following year(s) is their lifestyle causes identical muscle loss.

In that context is this a long term downside of GLP-1 or their lifestyle?

Treating lean muscle mass as an inherent good makes sense when it’s adapted to a person’s current lifestyle. It doesn’t make sense when it’s a temporary situation.

False dichotomy - much of the muscle loss happens because of the rapid weight loss. If you diet more slowly and are not at very high levels of relative musculature you’re not going to lose nearly as much even in the long run, at least prior to advanced age. The newly skinny person might lose some muscle mass on their legs if they dieted down slowly, but it is significantly less likely that they will lose all of the other body-wide muscle mass that they do with rapid weight loss.

Your body will hold on to a surprising amount of muscle. Even people that take PEDs can drop back down to natural testosterone levels and keep ~80% of their gains in the long term. (Actual gains, not the temporary glycogen and intra-muscular water retention that you see with some compounds on cycle.) It takes significant effort for them, but they’re trying to hold on to supraphysiological levels, vs. someone who is trying to hold on to what is already on the lower end of the physiological range.

> False dichotomy

No, you’re looking at the short term effects on a largely irrelevant metric (volume) while ignoring the underlying mechanisms at play.

> Your body will hold on to a surprising amount of muscle.

It’s only surprising if you ignore what going on at the cellular level. Gaining fat or muscle eventually involves gaining new cells and structures like capillaries not just increased the volume of existing cells. This is a really slow process in muscle, but those new cells stick around and can rapidly adapt to stimulus as long as you have a sufficient diet.

So yes in rapid weight loss your individual muscles cells become smaller and less capable but that’s very quick to recover. Longer term, you’ll hit the exact same homeostasis point based on stimulus and long term diet.

PS: If this seems like voodoo magic it’s simply a very old evolutionary response to starvation that predates hominid development. Being able to fairly rapidly lower energy expenditure over say winter and then recover is a major advantage.

> Gaining fat or muscle eventually involves gaining new cells and structures like capillaries not just increased the volume of existing cells. This is a really slow process in muscle, but those new cells stick around and can rapidly adapt to stimulus as long as you have a sufficient diet.

It's an open question if hyperplasia even occurs in adult humans, and if so, under what conditions. MSC proliferation and differentiation is a thing, but none of this is actually particularly relevant to the discussion at hand.

> So yes in rapid weight loss your individual muscles cells become smaller and less capable but that’s very quick to recover. Longer term, you’ll hit the exact same homeostasis point based on stimulus and long term diet.

I'm not talking about hypothetical situations where people treat this more like a cut and then turn their lives around when it comes to resistance training and protein intake, because we know that in large part they don't. We know that a good portion of people on GLP-1 medications become sarcopenic and stay that way. And this whole thread basically started because someone was claiming that the muscle loss was good!

I'm not saying GLP-1s are bad or rapid weight loss is bad - I'm just saying you need to take steps to avoid muscle loss. And a huge amount of people on GLP-1s don't know about or understand these risks.

> I'm just saying you need to take steps to avoid muscle loss.

Do you have any evidence that long term lifestyle isn’t going to result in similar levels of strength?

> if hyperplasia even occurs in adult humans

It definitely occurs in other mammal muscle and some human tissue, and there’s studies supporting it occurring in human muscle. Myofibre splitting for example definitely occurs. https://pubmed.ncbi.nlm.nih.gov/16625366/

I’ll admit there’s controversy here, but I think the default position should be human biology is similar to other mammals unless someone demonstrates otherwise. Otherwise our unwillingness to preform experiments on humans and the expense of primate experimentation is going to create a scientific bias.

> then they have "too much muscle" as typically needed for their body mass

It's a leap to suggest that it's "good" to lose this muscle mass. If you're obese then it's good to lose fat. It's even better to do so while maintaining muscle mass.

Yeah, but whether you do resistance training while losing weight so that you have proportionally extra muscle mass than you had when you were overweight has nothing to do with the GLP-1 drug.

Every time GLP-1 drugs come up, the convo splinters off into topics that have nothing to do with anything unique to the drug. Now we're just talking about general weight loss and that it's good to exercise. Which is a trivial claim.

Yeah that's obviously better. They really meant it's "not bad" rather than "good".

When people read "muscle loss" they think "oh it's going to make me weak and feeble".

Well, no, but I like how muscular I look (even with the extra weight). I wouldn't want to look skinny and lose the weight lifting gains.

The problem is it is bad. People aren't just losing a proportional amount of muscle to fat mass to keep a good ratio - rapid weight loss is more catabolic towards lean body mass than it is with slower weight loss.

And most obese people are below optimal levels of total lean body mass overall even before this - their leg muscles being larger than an untrained person of the same height and an average weight does not mean that their leg muscles are of optimal size, much less the rest of their body.

Sarcopenia is a real risk for any obese person who is rapidly losing weight and GLP-1s are no exception.

Yea what you're replying to is just pure fat-logic that isn't really backed by science. You will lose muscle from calorie restriction - that isn't really in doubt by anyone. However, when cutting weight, you can do a routine that maintains/builds muscle as you cut, to reduce the effect. A body with more lean muscle mass will be able to keep weight off for longer - this has been known, settled, and accepted in weight loss and fitness science for decades now. I've never heard anyone, anywhere posit that muscle loss is good - and would love to see a source, so I can laugh at it.

One insidious thing with these GLP1 drugs, is that they also seemingly affect muscles like the heart. I would not be willing to take one unless the risk of me carrying my weight far outweighed (no pun intended) the risk of the side effects. However, a lot of people seem to be treating it as some kind of miracle fad diet drug, which is concerning.

It also has other side effects like reduced elasticity on skin, etc. I suspect we'll see longer term issues in the next decade from these drugs, and I'm glad alternatives are being explored.

Don't you also need a bigger heart when you gain weight and not need as big of one at less weight? Liposuction and amputations can also result in muscle loss in the heart from it having less work to do.

You don't want to have too much hypertrophy in the heart for sure. My understanding though is that it's very hard (almost impossible?) for it to be a problem without exogenous hormones, or some other condition that allows you to accrue an abnormal amount of muscle mass (e.g. myostatin defficiency).

Edit: I mean someone with a healthy fat percentage body composition. Of course having to pump blood to a 300lb-140kg body is problematic for the heart, be it a mostly fat or mostly muscle body composition. My point is it's just much easier to be fat enough for it to be a problem than muscular enough without exogenous hormones or an abnormal condition.

Yeah, LVH is the big deal there in both cases.

Telmisartan, an ARB generally used for BP management, can actually reverse LVH to a significant degree over time, though. Popular for bodybuilders on large quantities of AAS for that reason.

> Yea what you're replying to is just pure fat-logic

I can't even imagine what that's supposed to mean.

> However, when cutting weight, you can do a routine that maintains/builds muscle as you cut, to reduce the effect.

I literally talked about staying physically active.

The point is, you're going to have however much muscle your workouts and physical activity build/maintain. And you're going to lose whatever extra muscle isn't needed in your workouts. And that's fine, because you probably want well-balanced strength rather than legs that can carry around 300 lbs all day long.

None of this has anything to do with weight loss, except that simply walking around and daily movement becomes less of a workout as you lose weight because you're moving less mass. But it's not the weight loss directly that makes you lose muscle (assuming you're eating protein), it's the reduced physical strain because you weigh less so you're not needing those muscles. Do you get the distinction?

You don't need to work out even more to "reduce the effect" as you say. There's no effect. There's just working out to have whatever muscles you want. Weight loss will never lead to losing the level of muscle you need for your workout.

> I can't even imagine what that's supposed to mean.

Where are you getting your information from?

The reason you want to keep all your muscle on a cut is because that means a higher proportion of the weight that you do lose will be fat tissue.

This is the strictly superior outcome.

If you're "cutting" as part of bulking and cutting, then obviously.

But if you're going from obese to healthy, then your goal isn't to retain all your leg muscle, that's absurd. Your goal is to get to a healthy weight with overall balanced healthy muscle -- not disproportionately large legs.

Nothing is "strictly superior". What is best depends on what your goals are. Bodybuilding and not being obese any more involve wildly different measures of success.

No this is absurd.

The goal for anyone obese is to lose as much fat as sustainably possible.

For any given rate of weight loss, losing a higher proportion of body fat is always better.

This notion of "balanced" healthy muscle is one you've made up that no one else thinks of. I've been on fitness forums for well over a decade and have literally never seen a single case of this.

> The goal for anyone obese is to lose as much fat as sustainably possible.

Correct.

> For any given rate of weight loss, losing a higher proportion of body fat is always better.

That is in direct contradiction to your previous sentence. No, losing the higher absolute amount of body fat is better. While being sustainable healthy.

> I've been on fitness forums for well over a decade and have literally never seen a single case of this.

You may be on the wrong forums then. Most forums don't think all your days should be leg days.

> That is in direct contradiction to your previous sentence. No, losing the higher absolute amount of body fat is better. While being sustainable healthy.

This isn't in any way a contradiction if you're mathematically literate. If the highest rate of weight loss is some rate R, and losing weight without preserving muscle has you losing 0.5R muscle and 0.5R fat, losing R fat and 0 muscle is literally going to lose you more fat at the same rate. This is middle school math, and is literally what anyone who knows what they're talking about suggests, and is validated in the research.

> You may be on the wrong forums then. Most forums don't think all your days should be leg days.

Oh good more shit you've made up. No where did I suggest this. If you're going to engage in bad faith, go away.

Any well-rounded strength program will preserve muscle mass in a cut. You only need to work every muscle twice per week. No leg emphasis needed.

> if you're mathematically literate

No insults, please. I'm sure that if you have good arguments, you won't need to resort to that kind of attitude. And the fact that you're resorting to swearing later in your comment doesn't help you.

> If the highest rate of weight loss is some rate R

That's not a valid precondition. Nobody chooses a rate to lose weight at, and then magically chooses some proportion of fat vs muscle. What actually happens is that you lose fat through eating less calories, and you naturally lose muscle from using your leg muscles less by putting less weight on them, because you weigh less.

> No where did I suggest this.

You did. You literally said:

> This notion of "balanced" healthy muscle is one you've made up

You are arguing that one should preserve all of the leg muscle for a 300 lb body, even once you're 180 lbs. Again, that's absurd. That's going to take a far disproportionate amount of time at the gym on your legs to maintain. You say "No leg emphasis needed." That's completely and utterly false.

You are talking about bulking and cutting for strength training. But you already have a balanced body, I'm assuming. This conversation, on the other hand, is about obese people losing weight. Their muscles are disproportionately in their legs. Do you get that now? Do you understand the concept of a balanced distribution of muscle and strength, e.g. between arms and legs? Or since you're so concerned about having a conversation at a "middle school" level, do you need it explained in even simpler terms?

> No insults, please. I'm sure that if you have good arguments, you won't need to resort to that kind of attitude. And the fact that you're resorting to swearing later in your comment doesn't help you.

I have zero patience for intellectual dishonesty and made up claims as you've repeatedly done.

> That's not a valid precondition. Nobody chooses a rate to lose weight at, and then magically chooses some proportion of fat vs muscle. What actually happens is that you lose fat through eating less calories, and you naturally lose muscle from using your leg muscles less by putting less weight on them, because you weigh less.

Do you not know how thought experiments work? If you lose weight without strength training, you lose less fat and more muscle than if you lost weight while strength training. The numbers were chosen to illustrate that point, not to say those were precisely the numbers you'll see.

And of course it's entirely wrong that you lose muscle in your legs specifically because of the reduction in weight. You lose muscle everywhere you don't use it, which means a smaller proportion of your weight is lost as fat, which means it takes you longer to reach your target body composition.

> You are arguing that one should preserve all of the leg muscle for a 300 lb body, even once you're 180 lbs. Again, that's absurd. That's going to take a far disproportionate amount of time at the gym on your legs to maintain. You say "No leg emphasis needed." That's completely and utterly false.

This is yet more evidence of your complete ignorance of this topic and even what I've been suggesting. Your obsessive fear of having muscular legs blinds you to everything I've said.

Maintaining muscle mass takes far less work than building it. You literally only have to hit your muscles twice per week to do it, which could take anywhere as little as 1-3 hours per week of work if you know what you're doing.

You are objectively and empirically wrong about this and are only demonstrating how much you don't know about this topic.

> You are talking about bulking and cutting for strength training. But you already have a balanced body, I'm assuming. This conversation, on the other hand, is about obese people losing weight. Their muscles are disproportionately in their legs. Do you get that now? Do you understand the concept of a balanced distribution of muscle and strength, e.g. between arms and legs? Or since you're so concerned about having a conversation at a "middle school" level, do you need it explained in even simpler terms?

So much for no insults. Rules for thee and not for me seems like your motto.

If an obese person losing weight is worried about an imbalance, then the solution is not to let their legs atrophy to nothing but to increase the volume of the work for the muscles they fear are lagging so they can experience more growth and catch up, just like anyone else who has ever lifted weights.

These are extremely basic concepts in the field.

And lastly, a topic I should have mentioned earlier, anyone who follows your advice, which is clearly the advice of someone who neither knows what they're talking about nor the advice of someone with a healthy relationship with body image, will inevitably be increasing the risk and extent of lose skin if they avoid strength training. If you don't bother preserving muscle, not only will it take longer to reach your target body composition, you will have end up with less total tissue filling your skin and, short of surgery, you would have to build muscle to fill it up again to reduce or resolve the issue.

Your advice is objectively terrible, rooted in ignorance of basic fundamentals of the space, and will lead people to worse outcomes.

You should in no way be offering advice on this topic to anyone. You will only increase the chances that they give up as their journey takes longer and results in worse outcomes in terms of both health and aesthetics.

>you naturally lose muscle from using your leg muscles less by putting less weight on them, because you weigh less.

That is one cause of muscle loss, but there is a more important factor: when running a calorie deficit, the body removes protein from muscle so that it can turn the protein into glucose for energy. The human body preferentially gets fuel (calories to use to fight infections, digest food, and do the other things needed just to stay alive) from muscle (as opposed to getting it from fat) during times of not-enough-food because it takes more energy (fuel) to keep muscle cells alive than it takes to keep fat cells alive.

We evolved in an environment in which the body had no way to know whether the time of not-enough-food would last so long that it would lead to death. In that scenario, the policy that maximizes the probability of survival is to disassemble most of the muscles first and only then to start to disassemble the fat in the fat cells.

Corollary: most people on weight-loss diets should regularly exercise their muscles especially if they are elderly (because the elderly find it hard or impossible to regain the muscle once it is lost) and should consume a decent amount of protein.

Having a large amount of muscle mass doesn't make you live longer (as far as I know): the case for striving to preserve muscle mass during the aging process is that it gives a higher quality of life.

If we didn't see tons of people reaching their "target weight" on GLP-1 drugs while having unhealthily low levels of lean body mass, you might have a point.

But that is what we do see. I'd argue that they're still in a better place than they were before, and we know that muscle that has been lost recently grows back very quickly when exposed to stimulus and adequate protein and rest, so I absolutely am a full believer in GLP-1 medications.

But if everyone on GLP-1 meds were keeping up with their protein and resistance training, even leg day, there would be very very few that had huge legs. That one portion of their body might be, on average, more muscular than a totally untrained individual, but it's not like being fat is the equivalent of a low bf% bodybuilder when it comes to lower body muscle mass. A formerly 300lb person dropping down to 180 with average genetics is almost certainly going to have smaller legs than someone who has been lifting for a year at the same height/weight.

> One insidious thing with these GLP1 drugs, is that they also seemingly affect muscles like the heart.

Okay so I don't know where I picked this up - it was a decade or more ago - but I always thought the problem was losing weight too fast is what causes bad muscle loss such as from the heart, or from leg/other muscles beyond what's no longer needed from the weight loss. Something like, you're starving yourself so your body starts drawing energy not just from your fat but from anywhere it can.

The idea that people on GLP-1s shouldn't be trying to preserve (or indeed build) as much muscle mass as they can is absurd. It is more important than ever to perform resistance training and make sure you are getting adequate protein.

But this isn't anything special about GLP-1s - the same is true for any sort of rapid weight loss approach, be it diet, GLP-1, lap band, whatever.

And we see improved cardiovascular outcomes independent of weight loss for people on GLP-1 drugs in widespread clinical trials, vs. one mechanistic in vitro study showing loss of heart muscle cells.

There is a huge conflation of cause and effect with respect to muscle mass and longevity.

Low muscle mass is associated a broad swath of illnesses, low activity, and generally poor health.

Muscle mass's power as a predictor is not the same as it's utility as an intervention.

As long as you're not using exogenous hormones, muscle mass can only be achieved with exercise that builds or preserves muscle. I'd say that's a pretty good predictor against frailty, which is strongly associated with mortality among the elderly.

Exactly my point! you have a chain of 3 associations right there. One is nearly tautological and another has backwards causality. Correlation =/= causation.

Something being a good a good predicative indicator does not mean it is an effective intervention.

"Muscle" isn't an intervention.

"Building muscle" is an intervention and has extremely well-documented mechanisms that have a causal role in improving health.

Muscle actually is an intervention for one of the biggest risk factors in metabolic syndrome - insulin resistance.

Muscles use glycogen. They use more glycogen when you're doing the sort of thing that builds muscle, so of course it's even better there, but someone who just genetically puts on more muscle at the same level of activity as someone who puts on less will still use more blood sugar for their muscles, and thus be less likely to increase their insulin resistance.

Ok how do you "intervene" with muscle? Do you surgically transplant it?

It's a thing that exists. Genetic differences are not interventions. Those are also simply things that exist.

An intervention is a change in treatment or behavior that induces a change with effects we want.

Differences between individuals are not interventions.

The intervention of interest is building muscle through strength training.

There's a significant number of posts in this larger thread saying that it is basically just the benefits of exercise that is providing the positive health outcome and not just having the muscle, and I interpreted intervention in a broader manner based on that context.

My point is simply that muscle in and of itself has positive benefits, even if you didn't need to do another healthy activity to maintain or gain it.

There is no backwards causality in the implication that building or preserving muscle that would otherwise be lost can prevent or delay frailty, nor is it backwards to imply that frailty can lead to death (from falls, disease, etc.). I really don't understand what you're trying to say.

True, but frailty in the old age has a reason that cannot fully be mitigated with exercise: depletion of stem cells. The same mechanism will make our blood vessels thin and prone to bursting etc.

"The idea that an overweight person has "too much muscle" is nonsense."

Our bodies like to have a balance of everything.

"Muscle mass is a huge predictor of mortality"

In biology, most such predictors work only up to a point. Massively muscular people don't live to be 120. Bodies don't work in a straightforward fashion, and there are other effects to consider. For example, activation of the mTOR pathway, associated with tissue growth, is associated with shorter lifespan, and mTOR inhibitors like rapamycin seem to be modestly prolonging lives of many species.

Complete nonsense.

My read on past studies is that one area of muscle mass loss that is problematic is around the heart.

Obviously it’s not a problem if an obese person’s quads shrinks 2x because they lift 2x weight every day.

I would think any drastic change to body composition would have its risks, and should be mitigated through healthy diet and exercise. I suspect the detractors are quick to overemphasize such risks because users of weight loss drugs aren't 'earning' it. My counterargument would be that it's better to be underexercised and normal weight than to be underexercised and overweight. And I suspect being normal weight makes exercise more pleasant.

> Losing muscle as you lose weight is natural and good.

It's natural but that doesn't make it good. In particular, muscle loss can cause heart problems because the heart is a muscle. The body's catabolic processes don't distinguish between different kinds of muscle.

I don’t think this is true. My understanding is that the heart is a very unique muscle because it doesn’t grow. If your heart does grow, either by genetic defect or anabolic abuse, it works much worse. So you’ll live a shorter life.

Heart muscle can shrink in extreme calorie deficits which can lead to heart issues, therefore it must grow when leaving such calorie deficits, even if that growth has an upper bound.

Hypertrophy of the heart is a well-known and desired part of improving cardiovascular fitness.

https://en.wikipedia.org/wiki/Aerobic_exercise#Health_effect...

> Have you ever seen someone obese do leg presses at the gym? They can handle tons of weight.

They can't handle reps. It's almost as if muscle has several different properties that are important beyond just "mass."

> When you lose weight, you don't need all that extra muscle.

Sure, but what if I want it? Maybe I want to jump extra high, or want to be able to lift things 120lbs heavier than I could before?

This is silly. I'm a big proponent of GLP-1s (and on one!) but we can and do see people on these reaching sarcopenic levels of lean body mass. The overwhelming majority of people on these drugs should absolutely be doing everything they can to preserve their muscle mass.

(The overwhelming majority of people losing weight in general should be doing everything they can to preserve their muscle mass.)

Having slightly larger quads/hamstrings/calves than the average person doesn't mean they have an optimal amount of muscle mass in their legs to begin with, much less on the rest of their body.

Leg presses are also an absolutely terrible exercise to measure strength and by proxy muscle mass. The angle reduces the weight - generally only 71% - and they are one of the most "cheated" exercises in existence, with people doing what could charitably be called half reps (and is often more like quarter reps.)

I wonder how this molecule will compare with gold nanoparticles [1]. Headline: Gold outperforms common weight loss drugs – and leaves muscles alone

[1] https://newatlas.com/disease/obesity/gold-nanoparticles-obes...

> and leaves muscles alone

But might destroy your bone marrow's ability to create blood cells[1].

1. https://www.mayoclinic.org/diseases-conditions/aplastic-anem...

Does anyone actually believe that GLP-1s directly target muscle tissue?

Losing a ton of weight, especially very quickly, is extremely catabolic. Any substance that prevents this would by definition be an anabolic substance.

If this really has the potential to compete with Ozempic, then it should have a noticeable impact on Novo Nordisk's stock value [1], but we're not seeing that yet.

[1] https://finance.yahoo.com/quote/NVO/

The article refers to results in animals which means it is probably years - maybe a decade - from being approved. Novo’s patent protection expires in 2033 [0] so it could be that the market is not yet worried about a potential competitor that likely won’t get to market before the IP protection runs out.

[0]: https://www.reddie.co.uk/2024/08/30/the-year-of-ozempic-an-i...

And Novo (like many others) is already working on next-generation GLPs that’ll have new patent protection before Ozempic’s ends.

Even so, competition from other GLP-1 drugs and generic semaglutide should make prices and profits lower.

If the companies combined can meet demand

They seem to be able to offer it at $300 if you pay without insurance. The implication being that they make 50 extra bucks because the insurance company only pays $250 for your $1,000 prescription.

I really, really don't think that's a reasonable metric, especially on short timelines.

In a few years, when this has been trialed, approved, there are a few manufacturers? Maybe.

I am reminded of the economist that wouldn't pick up a $20 bill at his feet because if there was a $20 bill at his feet the market would have already picked it up.

"The market" contains people like my dad who asked me if I knew about deepseek... 3 weeks ago...

This assumes that NN won't snap it up themselves.

Indeed, if this becomes a threat I fully expect one of either Novo Nordisk or Eli Lilly to buy them out.

The market is intelligent in the aggregate. In particular this means it's slow to adapt to new information and trends.

They mention AI used to weed out molecules but don't mention how it was used. I'd be interested in know did they use pre-trained models or train one from the ground up.

https://www.sciencealert.com/ai-experiment-generated-40-000-...

For another example, and it actually calls out the name of the program.

I would expect some custom training was needed in order to address this highly specialized use case.

There are 2 primary uses cases emerging where LLMs are proving advantageous.

    1) Summarization --- where the results can be nebulous and it don't really much matter. For example, casual web search.

    2) Research based on trial and error where the nebulous results will be subjected to thorough verification --- i.e. this case.

In any case, the statistical results can be nebulous and using them without verification is a recipe for disaster. For example:

https://www.lawnext.com/2025/02/federal-judge-sanctions-morg...

I don't think it's a matter of firing up an LLM and saying "Hey LLM, please find me a molecule that acts on human GLP-1 receptors but does not have the negative side effects of semaglutide." And it's all like "Certainly! Here are some candidate GLP-1 agonists that blah blah blah..."

It's probably more like AlphaFold -- a statistical model of molecular structure and action, not a language model.

It looks like it's this: https://github.com/Svensson-Lab/pro-hormone-predictor

Annoying that journalists call everything "AI" these days.

Isn't the molecule in Ozempic naturally occurring too?

As far as I know GLP-1 is a naturally occurring hormone but it's not something you can just give people directly. Instead you give them artificial things like semaglutide that work on the same receptors.

GLP-1 is a class of drugs (or molecules). The first known GLP-1 was pretty much just a synthesized version of a naturally occurring compound from the Gila Monster’s venom.

Semaglutide is like a 2nd generation GLP-1 and there are 3rd generation ones in development right now

Semaglutide and co are "GLP-1 receptor agonists" that behave in a similar way to the naturally occurring hormone GLP-1.

We can't give people GLP-1 itself because it breaks down really fast and you'd have to provide it continuously, so we use ones that effect the body the same way over a long period of time.

Ah ah, I see what your original comment meant now! I parsed that completely differently :)

Yes you’re right.

Yeah, halflife of GLP-1 is about 5 minutes.

Gila Monster is a pretty cool name for a lizard

You can but if I recall based on a book I read [0], you’d need to take a pill something like three or four times a day as your body naturally clears GLP-1 very quickly. The chemical has been known since the 90s, the Ozempic breakthrough was binding/mixing it with some chemical of Gila monster venom which makes your body take much longer to break down the chemical (days instead of hours).

[0] Magic Pill by Johann Hari

Isn’t everything naturally occurring? It all originates from earth, where else would it come from?

Solar power isn’t naturally occurring, originates from outside of earth.

It is naturally occurring though.

But does it come from earth?

But earth doesn’t come from earth. It comes from interstellar gasses formed from stellar nuclear fusion and afterwards emitted when the stars turn into supernovae.

Then earth isn’t naturally occurring I’m sorry

Some elements don’t occur naturally and need to be formed artificially / by force by smashing together atoms that would never smash together in nature (in some cases because those atoms in turn also don’t exist in nature).

I suspect chasd00 is making a pedantic point that the atoms are smashing together in nature. Because nature is just everything that happens.

Although pedantic, it does challenge what we really mean when we say "natural". Just like what we mean when we say "chemicals". Everything is chemicals.

> Everything is chemicals.

No, not everything. Atoms, subatomic particles, light, electromagnetism, etc. are not chemicals. There are many things we experience in everyday life that are not chemicals.

> Everything is chemicals.

Free electrons and neutrons aren't chemicals. Free protons are Hydrogen ions though.

With the exception of protons, isolated subatomic particle in general aren't chemicals.

Nicely up-pedanted. Ultimately I meant that saying stuff like "I don't want food with chemicals in it" is sloppy, because food itself is made of chemicals.

As a presumptive juror I was once asked how I felt about "chemical evidence". I responded by arguing that pretty much all evidence is chemical evidence. I challenged the room to contradict me (which they could've, but nobody did).

I ended up on the jury, so apparently this performance successfully masked my pro-defense bias.

"Chemical evidence" turned out to mean measurements of pupil dilation as evidence of an inability to drive safely.

“In nature” means “it would not happen if humans weren’t around”. So no, nature isn’t “everything that happens”. Calcium and californium atoms smashing together to form oganesson would never happen “in nature” without humans using a particle accelerator to drive the process.

I strongly suspect some supernova or black hole jet somewhere has formed oganesson without human intervention. "In nature" usually gets restricted to "on Earth" implicitly, partly for this reason.

Is wheat natural? Aren't humans themselves part of nature?

Since we're being pedantic:

Light isn't chemicals. Sound isn't chemicals, it's the vibration of chemicals. The billions of neutrinos passing through you right now aren't chemicals. Etc. All the matter we interact with in everyday life is chemicals, but lots of things aren't chemicals.

They did specify "molecule". Certainly not every pharmaceutical occurs naturally, and other materials such as Teflon don't either.

We're part of nature and so everything we do is occurring there. Is the real distinction things that wouldn't exist without human intervention? So, like Teflon and plumcots wouldn't be natural but water and plutonium are.

Things that aren't naturally occurring would be supernatural, no?

That's the original meaning of "artificial", something that occurs through art or skill. Humans have always distinguished themselves from the rest of nature, it's part of that. It's not a useless distinction, but it breaks down when 'natural' is considered healthy or otherwise good, and 'artificial' unhealthy or otherwise bad, when that's a non-sequitur.

Now we're arguing semantics. "Naturally occuring" in English means not synthetically produced / found naturally in the environment outside of human influences.

This makes since, but I do like the idea presented before you, that humans are natural, and our evolution is natural, therefor the things that we make are natural too. But then where do you draw the line? If an alien drops a new element on earth, would this then be not ‘natural’? Or is it impossible for anything to not be natural?

Except the definition of natural is a human made concept which means "anything non-human made/consequence" ;)

Such a definition of “naturally occurring” is useless, and thus pointless to entertain.

Besides, it doesn’t “all” originate from Earth. If you want to be really uselessly pedantic, nothing on Earth originated on Earth.

What percentage came from the sun and what percentage came from without the sun?

Very little comes from the sun.

The sun and all the planets and other bodies in the solar system all formed from the same cloud of material. Very little of the matter on Earth is from the sun, and very little of the matter in the sun is from the sun, even.

"The unnatural, that too is natural." - Johann Wolfgang von Goethe (1749-1832)

Semaglutide is grown on yeast then removed with a chemical "cleaver".

You tell me we could have semaglutide beer ?

They are not gonna tell us the source of the molecule? I wanna know which berries or legumes to consume... damnit!!!

My guess to the most probable source is the human body...

Soylenpic...

Pretty hard to go wrong with blueberries. I'm not saying that they contain the molecule, but I mean, they're generally good for you.

What does "naturally occurring" mean in this context?

> Svensson has co-founded a company to launch clinical trials of the molecule in humans in the near future.

At least not so natural that just 'anybody' can put it in a bottle.

I think this is not really a charitable take. For one, nearly everything medical needs certain purity and concentration so you need specialized equipment. For two, even if a chemical is easy to produce by industrial standards, you still need to run trials to prove that it's both safe and actually does what you hope it does.

I wonder what the distinction here is between supplement and pharmaceutical.

Could they have chosen to bring it to market as a supplement?

They could have, but they would have been seen as just another “weight loss supplement”. Which I imagine is a real uphill communication battle to convince people that you’re just not another scam.

I expect it has to be injected. Can you sell injectable supplements?

Well Trump just pardoned Ross Ulbricht who sold unapproved injectable drugs, so you can at least get away with shipping them into the United States, as long as you're not Mexican or Canadian.

Supplements are often marketted with results from clinical trials; although typically not very rigorous trials.

Raising money to do clinical trials doesn't indicate the path to market.

Having to run trials has little to do with the whether the compound is naturally occurring and everything to do with the fact they intend to market it as a drug with specific effects

Most people think "natural" means they can just go into backyard, dig up some root, and get this for free.

But its " Gila Monster’s venom".

So natural, but you aren't going to just go out and eat it like resveratrol from wine.

At this point, 'natural', just means made from atoms, yes atoms are naturally occurring.

>At this point, 'natural', just means made from atoms, yes atoms are naturally occurring.

That pretty much covers everything in the universe. I've always thought it was natural vs synthesized.

See food packaging laws. Natural versus artificial flavorings :)

Have you checked out what qualifies for 'organic' according to laws. The laws aren't a good standard.

I may be missing some of your sarcasm, but "Gila Monster's venom" meets the strictest definition of natural.

Maybe, sarcasm was aimed at 'natural' being 'harmless' and/or common, because it is 'natural'.

When really, just being 'natural', doesn't mean anything really. There are poisons that are 'natural'.

Like resveratrol. Yes, it is natural and its in wine. But you need to drink many gallons a day to get enough to do anything. But people see 'Natural' and wine, and think it is a license to drink a lot.

I would say that the prohormone BPM/retinoic which BRP is derived from occurs in the body and is therefore natural. If it would be a derivate of BRP chemically similar patentable then it would not be natural. Even if BRP is made in the lab it’s still natural. AFAIK one can’t patent natural occurring molecules, only the process to make them.

I wonder if it has to do with patentability

I'm assuming it means occuring somewhere in nature, but then the question is where. Is there some edible plant that contains this, perhaps?

According to the article they tested tens of thousands of amino acid chain peptides and used “AI” to find this one and synthesized it.

Unless we expect that every protein combination exists somewhere in nature, this pretty much by definition isn’t naturally occurring.

Remember, weight loss is a side effect of the Ozempic family of drugs. It was intended as a type 2 diabetes drug and it’s quite successful in that area. Once alternate applications are revealed, drug design gets involved to develop alternatives. Medchemists and marketeers are clever…

> weight loss is a side effect of the Ozempic family of drugs. It was intended as a type 2 diabetes drug and it’s quite successful in that area.

You can’t call it a side effect simply because the drug was first studied for a different condition.

Weight loss is a primary effect of the drug and it’s the indication it was approved for after extensive research.

Many drugs are first discovered while looking for some other effect.

Viagra is a famous example.

As I said, marketeers are clever…. And physicians can prescribe for anything they’d like - pharma is restricted to approvals before advertising.

That's not quite right. The clinical indication for Wegovy (and Zepbound for that matter) is, "As an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial BMI of 30 kg/m2 or greater (obesity)". Obesity itself is the disease the drug is approved to treat.

Now, Wegovy has the same active ingredient as Ozempic (Semaglutide), ditto for Zepbound and Mounjaro (Tirzepatide), and the latter have been prescribed off label for weight loss in the past but it's not just a marketing gimmick. These are different drugs in the eyes of the FDA because they are prescribed for different things (obesity vs. type 2 diabetes).

Different indications and approval to market. Different names for, umm, clarity in the marketplace. Same generic if/when they’re released. I would think this would be way easier than biologics as it’s not that big.

As I said above, they ran it through some amount of clinical trials and got approval to mention it directly. Same drug matter, possibly the same formulations.

Since it is a natural occurring molecule, and given this report detailing it, does it mean that production could be cheap and easy?

I know nothing about the topic, but I do know that insulin is a naturally occurring molecule but it wasn't a slam dunk. For years it was extracted from pig and cow pancreases collected from slaughterhouses and fed into a blender, but it required a lot of development to filter out the non-insulin molecules. In fact, some people would eventually develop allergies to their animal-derived insulin due to the trace amounts of other proteins that would slip through.

One of the first targets of genetic engineering in the mid 70s was putting a human insulin gene into e coli (I think yeast was tried too). But it isn't that easy -- the e coli genome needed other changes to prevent the e coli from degrading the molecule, as it was a waste product as far as the e coli was concerned. It took until 82 or so before that was viable.

But that isn't the end of it. The insulin generated is not active -- it needs to be cleaved from the "cluster" that the generated molecule into individual active insulin proteins. That naturally takes a few hours, which isn't great for diabetics because they need to anticipate their need hours ahead and if they overshoot they can go into a coma, and if they undershoot it takes hours to correct it.

It took years to design "fast insulin" which can be absorbed in under half an hour.

I know all this only because the most recent "Daniel and Kelly's Extraordinary Universe" episode:

https://www.iheart.com/podcast/105-daniel-and-kellys-extraor...

Naturally occurring has little to do with cost of production.

Coral snake venom is naturally occurring and has medicinal uses. $4,000 per gram.

I'm sure coral snake venom would be a lot cheaper if coral snake farms were more commonplace.

It’s not hard to start a venemous snake farm. Most states allow venemous snake keeping with various levels of oversight (some states there is no oversight) I think it has more to do with how hard it is to get venom out of a reclusive rear fanged snake.

The main point is just that “naturally occurring” has nothing to do with price.

I'm disappointed that a lot of the GLP-1 drugs are losing the emergency compounding rules that lowered the price to about $200/month, instead of $500 to $1000/month it will be by April.

A molecule that is a GLP-1 mimetic that has only been tested on animals?

I’ll hold my breath.

I read the article, didn't see what foods contain that molecule.

Humans produce it naturally.

sarm goblins will find a way to ruin this

…in mice!

On Google I find that this is already used to treat diabetes: https://www.mayoclinic.org/drugs-supplements/semaglutide-sub...

here are the side effects;

Side Effects Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common Belching Bloated, full feeling Constipation Diarrhea Excess air or gas in the stomach or intestines Gaseous stomach pain Heartburn Indigestion Nausea Passing gas Stomach discomfort, fullness, or pain Vomiting Less common Recurrent fever Yellow eyes or skin Rare Burning feeling in the chest or stomach Stomach upset Tenderness in the stomach area Incidence not known Anxiety Blurred vision Chest tightness Chills Cold sweats Confusion Cool, pale skin Cough Darkened urine Difficulty swallowing Discouragement Dizziness Fast heartbeat Feeling sad or empty Headache Hives, itching Increased heart rate Increased hunger Irritability Lack of appetite Large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs Loss of consciousness Loss of interest or pleasure Nightmares Pains in stomach, side, or abdomen, possibly radiating to the back Puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue Redness of the skin Seizures Shakiness Skin rash Slurred speech Tiredness Trouble breathing Trouble concentrating Trouble sleeping Unusual tiredness or weakness Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common Hair loss Rare Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site Change in taste Loss of taste Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Maybe this one relates more with the Americans because Ozempic became a trend there: Why are most people jumping on this drug? At least for me, besides all the cliches and stereotypes about the USA people, there's huge access to nutrition, gyms, surgical procedures, capital for buying healthy food, and medicine in general.

> At least for me...there's huge access to...capital.

This is not true for more people in the US than the populations of most other countries.

It's also weird to ask why people would do the obvious easy thing that takes no time or effort over the thing that takes more time and more effort. I bet you also make the exact same decision in a bunch of other contexts every day. Just use the pattern matching part of your brain to apply the same motivation to a new context.

Nutritious food is harder to prepare and/or doesn’t taste as good in some cases, surgeries and other drugs have side effects, gym is a pain to go to.

Also even though the US has high wages, everybody feels vaguely poor and stressed about money for some reason. There are a lot of little nickel-and-dime fees because we don’t have a good safety net, consumer protection, and we don’t have public healthcare.

(I’m not on Ozempic and I recently lost weight by just eating less, but I get why people want it, the alternatives are annoying).

Exercise is great for your health, but it generally has a negligible effect on weight loss because exercise doesn't actually consume that many calories. The biggest benefit of exercise on weight loss is the temporary exercise-induced anorexia that occurs in very high intensity workouts.

You are so full of shit.

I get on the treadmill for 1 hour and consume 700 calories in that hour.

Heavy exercise also causes improved appetite and sleep regulation as it fixes your blood sugar levels. This leads to your demand for food and especially the worst kinds to paradoxically go down for most fat people (they were already eating too many calories)

Calories in and calories out shows that I will durably lose weight over a several month period with 1 hr on the treadmill every other day - a totally doable number for motivated people.

I swear to gosh that all the people who say “you can’t outrun your fork” are fatties.

The issue is that the willpower to exercise for most people is trash. Most people who claimed they did high impact exercise and didn’t see weight loss simply didn’t actually do high impact exercise.

Most obese and very overweight people cannot sustain the output of 700 calories an hour, cardiovascularly (spelling) or with the state of their knees and muscles.

Also, it’s very easy to eat an extra 700 calories especially if you are in the “I worked out so I deserve a treat” camp.

Your lack of understanding comes across in your stance as well as the attitude.

Yes exercise is fantastic for your quality of life years and all cause mortality, but it’s not the whole story.

> Calories in and calories out

This is sort of like trying to fly a plane using Newtonian physics. Like, you can do it. But it’s more an exercise in pedantry than practicality.

My body, for example, loves to frivol away weight. I can eat like a pig and lounge around and my basal metabolism will spike and I won’t gain weight (nor lose much strength, though I do lose definition). Similar for people with metabolic syndrome: their bodies will literally start starving themselves by cutting basal metabolism in reaction to less food or more exertion before they’ll give up some fat cells. Not everyone who is obese has metabolic syndrome. But you’re going against the science if you insist all we need is diet and exercise education.

Americans are overweight.

Our entire food chain is full of preservatives, carcinogens, and things that should not be consumed by living beings .

I've spent small amounts of time in Europe, and each time literally just eating whatever junk food I wanted, I came home losing 10 or 20 pounds. The food outside of the US is just fundamentally better.

Let's say you're a teenager and you want to buy yourself some soda, in America the vast majority of the time you're not getting real sugar, you're getting hyper processed corn syrup. Before you know it all types of weird crap isn't everything you eat. And this has disastrous effects .

Ozempic is really a shortcut to an extremely complicated problem. Realistically if you want to eat quality food you have to move to another country, it's that bad.

This is basically a meme at this point -

Sandwich, US >:|

Sandwich, Japan :O

I don't know what to believe anymore. I think sugar isn't good for you, whether it's "real" processed sugar, or HFCS which is a fructose ratio that is the same as honey, or agave syrup which has even more fructose.

And, other countries have obesity problems too - e.g. Mexico and the UK. Are they tainted by... whatever... is the actual problem (or problems) with the US's food supply?

In mexico (and south and Latin americas) case it’s primarily due to taking our obsession with sugar and multiplying it. They drink even more sugary soda than we do, and their deserts like tres leche cake are so delicious because they are diabetes on a plate.

There’s some misinformation here.

The US does use more additives like BHA or potassium bromate (possible carcinogens—can you name others you’re thinking of?), but their link to obesity isn’t clear. As for soda, ‘hyper processed corn syrup’ I suppose just means high-fructose corn syrup (HFCS)—what’s the big difference you see from sugar? Research, like this meta-analysis (https://pmc.ncbi.nlm.nih.gov/articles/PMC9551185/), shows HFCS and sugar are metabolically similar in typical amounts, no disaster there.

Your weight loss in Europe might be more about activity than food quality. Short trips often mean more walking and exploring, which burns calories, even if you’re eating junk.

This is the truth - and it’s infuriating that assholes like RFK purport to want to remove nasty stuff from our food supply, but outside of total meme shit like a few red dyes and fake nonsense about seed oils being uniquely bad, he’s doing nothing to fix our insanely low quality and under regulated food supply.

I have had exactly the same experience as you every time I travel outside of the USA (luckily I’m already in good shape). I always come back skinnier than I left.

It’s infuriating that the only politicians who I can rely on to significantly regulate the ingredients in our food supply to remove slop will be hard left folks like Bernie Sanders - a breed of politicians which are going extinct.

But yes RFK, moving us to butter and tallow instead of fking seed oils will fix everything!!! (eyeroll)

I think there's just too much money in the way things are set up .

And that goes for almost everything in the United States. It doesn't take a rocket scientist to say food created using natural ingredients is probably better for you than something that came out of a lab. In the name of extending shelf life, everything is just saturated with as many preservatives as possible.

While this is great for something like emergency rations you shouldn't eat this stuff every day.

It's all about maximum profit. They sell us food that's optimized to remain sellable later.

Then this food makes you sick and depressed, so they sell you a bunch of drugs to "treat" that. The goal isn't healthy happy people. It's all about return customers.

> junk food I wanted, I came home losing 10 or 20 pounds.

Maybe you caught some bug or something?

> The food outside of the US is just fundamentally better.

Meh... I'm from Europe and it's about the same, if you are at least somewhat selective about what you eat (and it might be much harder and/or expensive to do that in some places).

It’s a very complicated issue, but I think, at its core, it’s because those other solutions just don’t work.

I mean, they work for a lot of people all the time. But they’ve existed forever, and over the past 50 years the obesity epidemic has only gotten worse.

Clearly, just offering things as available to people is not a systematic solution to this.

I lost ~55 pounds on a similar drug over about 10 months during 2023-2024.

The drug avoids the need for any kind of willpower. You don't have to go out of your way or make lifestyle changes to lose weight. You don't even have to eat different food, but you'll almost certainly eat a lot less of it.

That's just a dramatically preferable proposition than changing one's lifestyle, diet, and habits manually, and then keeping all that going for the rest of one's life.

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