https://github.com/Svensson-Lab/pro-hormone-predictor/blob/m...
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…)
I see we’re being fast and loose with the term “artificial intelligence”?
https://www.rand.org/content/dam/rand/pubs/research_memorand...
See the Eukaryotic Linear Motif resource: http://elm.eu.org/elms.
— Thomas Szasz
I think that's how we still use 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.
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.
Instead of
[ie]*-?[A-Z]+
[ie]?-?[A-Z]https://stackoverflow.com/questions/1732348/regex-match-open...
Regex to me, is pattern finding and abstraction taken to the extreme. I like the challenge
Now I am enlightened.
/
(?<=^|[ \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
)
)/xI 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.
The idea of an exclusionary approach sounds interesting as well. I'll have to think about that a bit.
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('}')
On the down side, lrparsing is pure python so it's slower than python's inbuilt regex's.
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.
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.)
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.
Any string. Triple-quoted is just multiline strings and works anywhere.
- 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
edit: not saying it can't be done but our org isn't using auto docs
(lots of fun dunder functions in Python that make metaprogramming a lot easier, but someone needs to tell you about)
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.
Many CoffeeScript constructs were adopted into JavaScript and TypeScript, but unfortunately, heregexes weren't among them.
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
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.
"LLM says X" is the new "I Googled it and here's a copy/paste of the top result". It adds literally nothing of value to the discussion.
Unless of course the discussion is specifically about the quality of LLMs - in which case you should be vetting the answer yourself so you can actually say something meaningful about it.
What value does a link to a source that's not held to any standard to be informative do? Seems a waste of everyone's time to me.
However, I also think it's valid to question what it adds to a conversation if someone is quoting it verbatim. Would we be happier if HN was like Quora and automatically added an AI response to everything?
That or I must be a lot more LLM-accepting than most of HN.
I have been waiting to ask someone this.
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.
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.
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.
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).
You can buy a 3 month supply of Lithium Orotate for like $10. I certainly wouldnt recommend self prescribing this kind of thing though.
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.
For example, there's a prescription engineered version of melatonin.
Melatonin is still a huge business.
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.
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.
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.
Giving yourself an injection an hour before you eat or an hour before you are hungry isn’t going to work.
https://patents.google.com/?inventor=Katrin+Svensson
It would seem they are modifying peptides. Which is patentable.
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.
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.
Supplements are a $50bn business [1].
[1] https://www.grandviewresearch.com/industry-analysis/us-dieta...
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.
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?
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.
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.)
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.
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."
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.
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.
When people read "muscle loss" they think "oh it's going to make me weak and feeble".
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.
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.
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.
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.
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.
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.
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.
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.
This is the strictly superior outcome.
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.
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.
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.
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.
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.
Where are you getting your information from?
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.
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.
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.
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.
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.
Something being a good a good predicative indicator does not mean it is an effective intervention.
"Building muscle" is an intervention and has extremely well-documented mechanisms that have a causal role in improving health.
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.
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.
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.
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.
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.
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.
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.
> 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...
This is literally describing spot reduction of fat.
(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.)
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.
https://en.wikipedia.org/wiki/Aerobic_exercise#Health_effect...
Obviously it’s not a problem if an obese person’s quads shrinks 2x because they lift 2x weight every day.
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?
They can't handle reps. It's almost as if muscle has several different properties that are important beyond just "mass."
I started drinking a protein shake once a day and the random mysterious injuries stopped.
[0] https://www.barbellmedicine.com/blog/where-should-my-priorit...
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.
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.
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.
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.
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).
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.
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.
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.
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).
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.
I think it's extremely probable that the most rapid losers are running the largest calorie deficit and also the largest protein deficit.
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.
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.
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.
You can lose muscle mass without drugs just by eating poorly (and not doing adequate movement)
"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).
[1] https://newatlas.com/disease/obesity/gold-nanoparticles-obes...
But might destroy your bone marrow's ability to create blood cells[1].
1. https://www.mayoclinic.org/diseases-conditions/aplastic-anem...
Losing a ton of weight, especially very quickly, is extremely catabolic. Any substance that prevents this would by definition be an anabolic substance.
[0]: https://www.reddie.co.uk/2024/08/30/the-year-of-ozempic-an-i...
In a few years, when this has been trialed, approved, there are a few manufacturers? Maybe.
Annoying that journalists call everything "AI" these days.
For another example, and it actually calls out the name of the program.
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.
https://www.lawnext.com/2025/02/federal-judge-sanctions-morg...
It's probably more like AlphaFold -- a statistical model of molecular structure and action, not a language model.
[0] Magic Pill by Johann Hari
Semaglutide is like a 2nd generation GLP-1 and there are 3rd generation ones in development right now
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.
Yes you’re right.
Besides, it doesn’t “all” originate from Earth. If you want to be really uselessly pedantic, nothing on Earth originated on Earth.
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.
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.
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.
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.
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.
Things that aren't naturally occurring would be supernatural, no?
Unless we expect that every protein combination exists somewhere in nature, this pretty much by definition isn’t naturally occurring.
At least not so natural that just 'anybody' can put it in a bottle.
Could they have chosen to bring it to market as a supplement?
Raising money to do clinical trials doesn't indicate the path to market.
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.
That pretty much covers everything in the universe. I've always thought it was natural vs synthesized.
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.
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.
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).
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.
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...
Coral snake venom is naturally occurring and has medicinal uses. $4,000 per gram.
I’ll hold my breath.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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?
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.
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).
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)
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.