[HN Gopher] Weight-loss drug found to shrink muscle in mice, hum...
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       Weight-loss drug found to shrink muscle in mice, human cells
        
       Author : Eumenes
       Score  : 338 points
       Date   : 2024-11-20 23:53 UTC (23 hours ago)
        
 (HTM) web link (www.ualberta.ca)
 (TXT) w3m dump (www.ualberta.ca)
        
       | therein wrote:
       | I like how they aren't saying Semaglutide in the title in an
       | attempt to perhaps keep it from immediate scrutiny.
        
         | neom wrote:
         | https://www.fda.gov/drugs/postmarket-drug-safety-information...
         | Same thing??
        
           | therein wrote:
           | > Unapproved GLP-1 Drugs Used for Weight Loss Yeah that would
           | be perfect. But editorializing it to the point of calling it
           | `weight loss drug`, just feels like it is begging for the
           | reaction of "oh yet another weight loss drug".
        
           | TylerE wrote:
           | No. That's talking about the compounded versions (NOT in an
           | auto pen) that were temporarily allowed due to shortages, but
           | whose authorization has since been revoked.
        
         | rzzzt wrote:
         | The first link goes to the study and it does mention the
         | ingredient:
         | https://www.sciencedirect.com/science/article/pii/S2452302X2...
        
           | therein wrote:
           | I am talking about UAlberta's title specifically.
        
             | rzzzt wrote:
             | "Semaglutide Reduces Cardiomyocyte Size and Cardiac Mass in
             | Lean and Obese Mice" was also written by UoA researchers. I
             | don't see anything nefarious in the choice of the title for
             | the news blurb.
        
         | skeaker wrote:
         | More likely because the average reader won't know what that is
         | versus the current title which succinctly summarizes it.
        
       | polishdude20 wrote:
       | It seems the article isn't just saying it's heart muscle that's
       | being lost but regular muscle in general. Even more so than in a
       | low calorie diet.
        
         | sfink wrote:
         | There's a linked article saying that 40% of the weight loss is
         | muscle.
        
           | com2kid wrote:
           | Outside of cardiac muscle, which is a bit worrisome, 40% of
           | weight loss being from muscles is incredibly typical for any
           | diet that sheds pounds.
           | 
           | There are very complex dietary regimes that can be followed
           | to minimize this, but most studies have shown that they don't
           | save any time compared to losing weight and then working to
           | get the muscle back afterwards.
           | 
           | > Dyck's study comes on the heels of a commentary published
           | in the November issue of The Lancet by an international team
           | of researchers from the U of A, McMaster and Louisiana State
           | University who examined emerging research showing that up to
           | 40 per cent of the weight lost by people using weight-loss
           | drugs is actually muscle.
           | 
           | This is, again 100% typical of what happens with caloric
           | restriction.
        
             | throwup238 wrote:
             | Literally the next line after the 40% quote:
             | 
             |  _> Carla Prado, a nutrition researcher in the Faculty of
             | Agricultural, Life  & Environmental Sciences and lead
             | author on the commentary, explains this rate of muscle
             | decline is significantly higher than what is typically
             | observed with calorie-reduced diets or normal aging and
             | could lead to a host of long-term health issues --
             | including decreased immunity, increased risk of infections
             | and poor wound healing._
             | 
             | Do you have a source that 40% muscle loss is typical for a
             | caloric restriction diet without GLP1 agonists?
        
               | com2kid wrote:
               | > Do you have a source that 40% muscle loss is typical
               | for a caloric restriction diet without GLP1 agonists?
               | 
               | OK I actually checked up on this, and it is more like
               | 30%, but that number gets worse as you get older. For
               | young healthy men it can be 20%, but as you get older
               | that number gets worse and worse.
               | 
               | I'd want to see a comparison of a similar cohort of
               | people going on a calorie restricted diet of the same
               | magnitude, with a similar (lack of) activity levels.
               | 
               | The study at https://www.thelancet.com/journals/landia/ar
               | ticle/PIIS2213-8... compares people who had less overall
               | weight loss on a pure calorie restricting diet, which,
               | well, by definition isn't the same thing.
        
             | loeg wrote:
             | > There are very complex dietary regimes that can be
             | followed to minimize this
             | 
             | The dietary regime isn't complex -- just consume a LOT of
             | protein. Something like 1-2 g/kg/d. And non-dietary: do
             | strength training.
        
               | devmor wrote:
               | Yep, I can anecdotally confirm as I'm on such a routine
               | right now.
               | 
               | I started losing weight from severe obesity with a
               | caloric deficit but noticed I was also feeling weaker in
               | general (aside from the tiredness that comes with eating
               | under your TDEE).
               | 
               | I started going to a trainer and he had me change my
               | macros so that I was consuming about 200g of protein per
               | day in addition to 4 days per week of full body workouts
               | on top of my cardio.
               | 
               | Since then I've lost an additional 150% of my initial
               | weight loss, and have gained moderate muscle mass on top
               | of that.
        
               | com2kid wrote:
               | This works until it doesn't.
               | 
               | Professional body builders do bulk/cut/bulk/cut because
               | after awhile you can't lose weight and put on muscle at
               | the same time, especially if you want to get to the point
               | of being shredded.
               | 
               | (well you can do it, but there is no benefit over bulking
               | and cutting)
        
               | loeg wrote:
               | This comment is not responsive to mine. I am talking
               | about minimizing muscle loss during weight loss, not
               | losing weight and putting on muscle at the same time. And
               | bodybuilders do exactly what I said during their cut
               | phases -- to minimize muscle loss. (Most people losing
               | weight on these drugs are not bodybuilders.)
        
         | derektank wrote:
         | From the commentary,
         | 
         | >Studies suggest muscle loss with these medications (as
         | indicated by decreases in fat-free mass [FFM]) ranges from 25%
         | to 39% of the total weight lost over 36-72 weeks. This
         | substantial muscle loss can be largely attributed to the
         | magnitude of weight loss, rather than by an independent effect
         | of GLP-1 receptor agonists, although this hypothesis must be
         | tested. By comparison, non-pharmacological caloric restriction
         | studies with smaller magnitudes of weight loss result in 10-30%
         | FFM losses.
         | 
         | Comparing weight loss of different magnitudes is kind of
         | comparing apples to oranges. Of course, it's not really
         | possible to get persistent, large magnitude weight loss any
         | other way than by using these drugs, so I understand why the
         | comparison was made.
        
       | jongjong wrote:
       | As a coder, I'm realising more and more that the human body isn't
       | so different from a computer. When you try to fix something
       | without having complete understanding of all the relevant parts
       | of the system, you will invariably introduce new issues. With a
       | machine as complex as the human body, it seems inevitable that
       | the field of medicine would be a game of whac-a-mole. Finding
       | solutions which don't create new problems is hard and should not
       | be taken for granted.
        
         | kylehotchkiss wrote:
         | Add on that there is no complete understanding of this system
         | with all the Unknown Unknowns etc and you can see why we should
         | test this stuff better before letting hims.com just disperse it
         | across the american populace
        
           | jongjong wrote:
           | Yes 100%. That's why I never understood the rollout of MRNA
           | vaccines during COVID. It's like pushing a massive code
           | change straight to production during peak traffic and without
           | the normal phased rollout. I totally understand where
           | conspiracy theorists are coming from. That didn't seem right.
        
             | kylehotchkiss wrote:
             | yeah, it's too bad the tech didn't have a better way to
             | gain peoples trust (through some other breakthrough with
             | the normal set of clinical trials). I think the solve was
             | impressive (tell cells to produce a protein that looks
             | exactly the same as the viruses and place it outside the
             | cell to piss off antibodies) but protein-protein
             | interaction data is hard to come by. Maybe these guys can
             | figure it out https://www.aalphabio.com
        
             | UniverseHacker wrote:
             | It made sense to me- they made a risk vs benefit decision
             | under high uncertainty, factoring in the massive harm that
             | the ongoing pandemic was already causing. There had already
             | been 12 years of human clinical trials for other mRNA
             | vaccines, and they still did extensive clinical trials for
             | the new covid vaccine before rolling it out.
             | 
             | In hindsight they were exactly right- and they saved at
             | least tens of million of lives by acting quickly[1].
             | 
             | [1] https://pmc.ncbi.nlm.nih.gov/articles/PMC9537923/
        
           | moduspol wrote:
           | Perhaps--though worth keeping in mind that the overwhelming
           | alternative is just lifelong obesity, along with all the
           | negative impacts from that.
           | 
           | At least at a societal level, some increased rates of
           | pancreatitis and a little suboptimal muscle loss are peanuts
           | compared to what high obesity rates do to people at scale.
        
         | GauntletWizard wrote:
         | A computer is much more likely than your body to have small,
         | self contained parts that just function. Your body is the
         | result of millions of years of accidental evolution - See the
         | canonical example of the laryngeal nerve in a giraffe. Computer
         | programs are often designed to be small and modular. They might
         | have to worry about memory layout shifting because some other
         | program grew - That's nothing like your spleen trying to occupy
         | the same physical space as your stomach and causing digestion
         | issues.
         | 
         | For all of medical science's experience and history with
         | debugging the human body, there's still so much more to
         | understand.
        
         | akira2501 wrote:
         | Yea, except without error checking, and fully analog
         | technology.
         | 
         | Although, "single cosmic ray upset events," are just as
         | devastating.
        
           | UniverseHacker wrote:
           | There's tons and tons of error checking- we have at least 5
           | different error correction and repair systems in DNA, cell
           | cycle checkpoints, and extreme redundancy and feedback
           | homeostasis at nearly every level. Every individual cell has
           | it's own 4 copies of almost every critical gene- two of each
           | chromosome made up of two strands of DNA each. Human bodies
           | can function 70+ years, sometimes with no medical care-
           | something no computer or man made complex machine comes close
           | to.
           | 
           | Beyond specific diseases we understand, it's still mostly a
           | total mystery why we aren't immortal- we have not yet
           | identified what is the basic mechanism of aging, or why it
           | happens at different rates in different species, and mostly
           | our systems are fundamentally capable of repairing and
           | regenerating almost anything, but for some reason get worse
           | and worse at doing so over time. Moreover, this doesn't seem
           | to happen in all organisms- there are many animals that live
           | ~4x human lifespans, and at least one species of jellyfish
           | that is biologically immortal.
        
             | akira2501 wrote:
             | Redundancy is not error checking. The "error correction"
             | mechanisms are actually just "proofreading" mechanisms and
             | are almost entirely local and centered around
             | transcription. Common mode errors are harder to induce due
             | to the plain redundancy of DNA pairs but also not
             | impossible, and once induced, are impossible to locally
             | notice or correct. In some cases the "error correction"
             | machinery is the cause of these induced errors. The result
             | is genetic disease and/or cancer and is a case of missing
             | error _checking_. Perhaps my definition was exceptionally
             | parsimonious.
             | 
             | > with no medical care [...] something no computer or man
             | made complex machine comes close to.
             | 
             | That's because we get far more units of "work" out of our
             | machines than the person living for 70 years with "no
             | medical care." Some people live just 30 years with no
             | medical care too. And the machine does not need to sleep.
             | We eat food they eat lubrication oil. I don't think this
             | was a good analogy.
             | 
             | > it's still mostly a total mystery why we aren't immortal
             | 
             | While we haven't pinpointed the mechanism, we have a pretty
             | good idea of why, and where in the system we should be
             | looking for the answers.
             | 
             | > but for some reason get worse and worse at doing so over
             | time.
             | 
             | You are a living Ship of Theseus and these "error
             | correction" mechanisms are not perfect. Aside from this
             | there are known genetic disorders which alter the rate at
             | which people age. This is not nearly as mysterious as
             | you're making it out to be.
             | 
             | > there are many animals that live ~4x human lifespans
             | 
             | And what are their resting respiration rates?
             | 
             | > and at least one species of jellyfish that is
             | biologically immortal.
             | 
             | In theory. We haven't found an immortal one yet. They all
             | die. They're also nowhere near our level of biological
             | complexity or capability.
        
               | UniverseHacker wrote:
               | > Redundancy is not error checking
               | 
               | Yes, you are right that DNA repair mechanisms are not
               | technically error correction in the sense that the term
               | is used in computer memory and storage, where any
               | isolated error is mathematically guaranteed to be
               | correctable. You clearly have a bio background, but my
               | intent was to point out in a simplified way to non-bio
               | people that biological systems do have mechanisms to deal
               | with errors. I incorrectly assumed that you didn't have a
               | bio background, and I can see that my message would have
               | seemed a bit condescending- my apologies.
               | 
               | > While we haven't pinpointed the mechanism, we have a
               | pretty good idea of why
               | 
               | I study metabolism and have observed things that aren't
               | compatible with any of the leading theories- which I
               | suspect are all dead ends. We are definitely missing
               | something big still. In particular, I feel like the big
               | anti-aging startups are throwing good money after bad, by
               | massively funding researchers with mostly played out dead
               | end ideas. Tech billionaires funding this stuff are re-
               | playing the same scenario as the ancient Chinese emperors
               | and their mercury based elixirs of immortality in modern
               | times IMO.
        
         | ben7799 wrote:
         | I like the analogy that biologists are making code changes
         | (especially with genetic therapies) without actually
         | understanding the machine code specification or even having a
         | copy of the source code.
         | 
         | It's like a hacker flipping bits in a binary trying to figure
         | out what's going to happen.. except the hacker at least can
         | look up the complete machine code.
        
       | wizzard0 wrote:
       | well that's a weight reduction too!
       | 
       | on a more serious note, could it be that the load on the muscle
       | gets lower so they adjust?
       | 
       | 8% reduction for 30% body weight reduction sounds reasonable to
       | me at first glance
        
       | cm2187 wrote:
       | > _emerging research showing that up to 40 per cent of the weight
       | lost by people using weight-loss drugs is actually muscle_
       | 
       | That's the sort of headlines that smells like bullshit to me.
       | 
       | My understand of those drugs is that they don't actually make you
       | lose weight, they just cut your appetite so you can follow a diet
       | to lose weight without hunger hammering at the door. So to start
       | with, if that's the case, all they are observing is the effect of
       | a diet. Not sure the diet drug has much to do with it.
       | 
       | Then I went from 133kg to 88kg with these diet drugs. Even though
       | I exercised every day, I am sure I also lost some muscle mass as
       | well, just because I don't have to carry 45kg every time I make a
       | move anymore. Seems logical and would probably be concerned if it
       | was any other way.
        
         | taeric wrote:
         | Yeah, folks don't like thinking that obese people have a lot of
         | muscle needed to move around. And losing weight is losing all
         | weight.
        
         | hnthrowaway0328 wrote:
         | Just curious, does your appetite come back whence you cut off
         | the meds?
         | 
         | The only reason I want to lose weight is to eat more freely,
         | won't be useful if I lose my appetite too.
        
           | 0xB31B1B wrote:
           | Appetite comes back yes
        
           | andreareina wrote:
           | It does.
        
           | xeromal wrote:
           | I saw someone mention that they craved heroin less on
           | ozympic.
        
           | cm2187 wrote:
           | You don't lose taste, you lose your appetite, which means you
           | can resist the temptation to eat easily, and you feel full
           | very quickly. That doesn't prevent you from eating what you
           | like, but it does help you to not eat too much of it, which I
           | hope is not what you mean by "more freely".
           | 
           | The appetite comes back when you cut the meds, but it's an
           | appetite based on your new weight. But if you then go on a
           | some suggar rampage, you will regain weight and your appetite
           | will grow too.
           | 
           | Those drugs are merely a guard rail to complete a diet
           | successfully, but if people do not change their eating
           | habbits, the same causes will produce the same effects after
           | they cut the meds.
        
             | hnthrowaway0328 wrote:
             | Thanks, that's good enough. I have been going to weight
             | loss for over 6 months but I'm stuck between 79 and 80kg.
             | It's a bit difficult to add more weight lifting because I
             | tended to hurt myself, so eat less is better.
        
               | andy_ppp wrote:
               | Add walking for 2h per day is the recommended I've seen.
        
               | hnthrowaway0328 wrote:
               | Thanks, 2h is a bit too much for me, so what I do is
               | about 3-4 10-12 mins walk-sprint walk reps. Basically
               | half walk (3.5m/h) and half sprint-walk (4.4m/h). I wish
               | I could do more but my joints are not really good.
        
               | theendisney wrote:
               | Just walking is better. You get a steady burn. If you do
               | high intensity you burn calories for a good while
               | afterwards. Mild intensity doesnt do much.
        
               | throwaway2037 wrote:
               | > It's a bit difficult to add more weight lifting because
               | I tended to hurt myself
               | 
               | Did you try slightly lower weight and higher reps? It is
               | worth trying as an experiment. Current scientific
               | literature says that 5-30 reps is the ideal range for
               | gaining muscle mass. And, as you said, the relative
               | heaviness of weights to the person makes a big difference
               | for injury risk.
        
             | andy_ppp wrote:
             | What I've found is foods I could usually binge on like
             | pizza I'm quite full on GLP-1 inhibitors and can quite
             | happily stop at half or 2/3 of a pizza. Usually I'd have
             | eaten the whole thing (12" think napoleon style pizza
             | Americans) and want more, refined carbs I never feel full
             | from.
        
           | vundercind wrote:
           | Experiences vary but I worried I'd, like, not enjoy food on
           | it.
           | 
           | Nope, not a problem. I just get full much faster and am even
           | more prone to simply not eating when I'm busy, than I already
           | was. Not as food-focused when idle, but I still snack a
           | little or whatever.
        
         | denkmoon wrote:
         | god... 133kg down to 88kg, that's like a dream to me. Years of
         | trying to get under 100 by 'traditional' calorie restriction
         | diet & exercise.
        
           | throwaway14356 wrote:
           | some fun study sort of concluded that the ratio carbs vs fat
           | and protine is the entire mechanic. fat people who eat almost
           | nothing eat only carbs thin people who can eat huge amounts
           | every day eat a lot of fat and protein. Both eat other things
           | just not as much.
        
             | throwaway14356 wrote:
             | I really eat a lot. When my gf cooked more and the potato
             | meat ratio changed from 1:3 to 3:1 I immediately started to
             | grow fat. I had her adjust it to 1:1 and started eating
             | lots of sausages and chicken legs between meals. 500g to a
             | kg per day worth of extra food. My body fat declined
             | rapidly.
        
           | renewiltord wrote:
           | One of my friends has tried many fad diets, etc. and he
           | finally just went and paid cash for a GLP-1 and he's lost a
           | lot of weight and is feeling much better. If I were in that
           | situation, I would just do the same.
        
             | twelve40 wrote:
             | bringing it down is not even half the battle, it's what
             | happens next is the more interesting part
        
               | turbojet1321 wrote:
               | You keep taking the GLP1 agonist, otherwise you gain the
               | weight you lost.
        
               | renewiltord wrote:
               | These drugs are like psychedelics. There are lots of non
               | users talking about them like they know them but all they
               | did is read stuff in popular media.
               | 
               | My friend cut usage after he lost weight and finds
               | maintenance easy.
        
               | twelve40 wrote:
               | lol well you, on the other hand, sound like the real
               | deal! direct personal experience unlike all those posers,
               | right? except why do you keep bringing up your friend
               | then?
               | 
               | This is a really stupid argument, your data point of "one
               | friend" or even two or more friends with unspecified
               | timeline is useless. The only thing that has any meaning
               | is a formal study with a large number of participants
               | over many years of observations.
        
               | renewiltord wrote:
               | Dude, it's simple. You have already made a choice and you
               | choose the first pop culture article that matches that
               | and then start talking about studies this and studies
               | that. I know it, you know it, and everyone else knows it.
               | 
               | And I get that it's fun but when you're called out on it
               | you don't have to get upset. Ten years from now, either
               | you will realize how comical you were being or you will
               | still be the same. It's better for you if it's the
               | former. That's all I'm going to tell you, for your own
               | good.
        
         | firecall wrote:
         | Interestingly, when I was part of a weight loss diet study at
         | my local university I actually gained muscle whilst losing
         | weight.
         | 
         | I had multiple full body dexascans during the programme.
         | 
         | I didn't change my exercise routine at all. I wasn't hitting
         | the gym or doing weights, just my usual basic cardio.
         | 
         | And I gained muscle and lost ~10kilos in weight.
         | 
         | It wasn't much muscle, but the amount of muscle was higher than
         | before.
        
           | philipbjorge wrote:
           | The latest research I've pulled suggests that DEXA scans are
           | fairly inaccurate and aren't a reliable way to measure body
           | composition even for the same person across time.
           | 
           | MRI is the gold standard, everything else is pretty loosely
           | goosey.
           | 
           | Sorry, no references but this comes up pretty often in the
           | science based lifting communities on Reddit and YouTube if
           | you want to learn more.
        
             | cthalupa wrote:
             | https://macrofactorapp.com/body-composition/
             | 
             | Estimates in level of inaccuracy on the high end ranges
             | from ~5% to ~10%
             | 
             | If you see your lean mass going up in DEXA, your muscles
             | are getting larger, and you're getting stronger,
             | particularly across a wide variety of exercises where CNS
             | adaptation can't explain the strength gains, they're likely
             | broadly accurate.
             | 
             | Mine have all tracked quite closely with what I'm seeing in
             | the mirror and what is happening when it comes to the
             | amount of weight I'm moving.
        
         | throwup238 wrote:
         | The next line of the article after that 40% quote:
         | 
         |  _> Carla Prado, a nutrition researcher in the Faculty of
         | Agricultural, Life  & Environmental Sciences and lead author on
         | the commentary, explains this rate of muscle decline is
         | significantly higher than what is typically observed with
         | calorie-reduced diets or normal aging and could lead to a host
         | of long-term health issues -- including decreased immunity,
         | increased risk of infections and poor wound healing._
         | 
         | The rather obvious problem is that these GLP1 agonists don't
         | improve your diet. If you continue to eat a protein and
         | nutrient deficient diet (which is probably a majority of
         | Americans) with caloric restriction on top of that, that leads
         | to excessive muscle loss that you wouldn't see in a weight loss
         | diet. This normally doesn't happen without GLP1 agonists,
         | because these diets are too difficult to stick to for most
         | people. Those who stick to them usually turn to nutritious high
         | satiety whole foods that help combat the negative effects of
         | caloric restriction.
         | 
         | Losing weight without losing muscle mass is _very_ hard. It
         | requires extreme diets like a protein sparring modified fast
         | where 80%+ of your calories are from lean protein while running
         | a 50% caloric deficit. If this research is correct, then using
         | GLP1 agonists shortcuts the feedback loops that make the diets
         | hard to stick to, but they shift the tradeoffs from weight to
         | overall nutrition.
         | 
         | "When a measure becomes a target, it ceases to be a good
         | measure" and all that.
        
           | chunky1994 wrote:
           | I'd like to see the diets in the study that are specified as
           | the "calorie-reduced diets". (Can't seem to find the paper).
           | If it's the same as the Standard American Diet, this muscle
           | loss is quite explainable. I think the mitigation is
           | relatively easy though, if you want to shift the p-ratio,
           | recommending a daily high protein shake would do a lot to
           | stave off muscle loss (and even more if resistance training
           | is applied of course). The exercise addition is probably the
           | hardest to adhere to.
        
             | groby_b wrote:
             | I'd be surprised if either mice or human cells eat "the
             | Standard American Diet"
        
           | loeg wrote:
           | I'm pretty skeptical of the "this rate of muscle decline is
           | significantly higher than what is typically observed with
           | calorie-reduced diets" claim. I suspect we're comparing
           | apples to oranges rather than doing like-for-like comparisons
           | at equivalent calories.
        
           | andy_ppp wrote:
           | Yeah, my four donuts per day fill me up just fine or an extra
           | large milkshake and a burger and I'm done for the day with
           | food is definitely happening for some people. Let's wait and
           | see these drugs might prove to be very beneficial and more
           | testing definitely needed.
        
           | zemvpferreira wrote:
           | >Losing weight without losing muscle mass is very hard.
           | 
           | I was with you up to here. In my experience it's easy to
           | maintain a huge proportion of your lean tissue during a
           | weight loss diet: Do some resistance training, get some
           | protein, and don't lose weight too quickly.
           | 
           | There's no need to go to the extreme of a PSMF - which will
           | still have you lose a bunch of muscle on account of being too
           | big a deficit. If you can keep your calories reasonable while
           | on a GLP1 agonist, there doesn't seem to be any reason you'll
           | lose an exaggerated amount of muscle.
        
             | hehehheh wrote:
             | Intuitively, if you can lift a modest bench press (not
             | novice, maybe beginner-intermediate) and you keep training
             | and you consume a few fewer calories (not starve) why would
             | you lose your strength.
        
               | Panzer04 wrote:
               | Because the body does not make it easy to keep the same
               | muscle with less fat.
               | 
               | For most people, it just doesn't really matter, because
               | their strength is so far below their peak capability it
               | won't be hard to cut some weight while maintaining
               | strength. The closer you get to the edge of capabilities,
               | though, the more it will matter.
        
               | cthalupa wrote:
               | If you are outside of your noob gains period and keep up
               | your protein intake and resistance training you will
               | minimize your muscle loss, but you'll still see some.
               | 
               | Bodybuilders will even take AAS that explicitly reduce
               | catabolism of muscle mass like Anavar and still lose some
               | muscle on cuts.
        
             | Kirby64 wrote:
             | For the average overweight person? I disagree. The average
             | obese person does little to no resistance training, eats
             | very little protein, and wants to lose weight fast so
             | they're not paying for expensive GLP1 drugs for a long
             | period of time.
             | 
             | You're asking folks to make three separate changes: start
             | exercising, change their diet to add protein, and use GLP1s
             | to reduce food amount. And reducing food amount already
             | goes against adding protein, so whatever protein they were
             | getting is going to get cut even further.
        
               | astrange wrote:
               | Increasing exercise also goes against reducing food
               | amount, because it makes you hungrier.
        
               | XorNot wrote:
               | I mean when I needed to lose weight (15kg, 85kg -> 70kg)
               | I started with calorie restriction, and as a result of
               | that actually looked at what I was eating and realized I
               | was incredibly low on protein, and then from that added
               | some daily light exercise partly just to avoid getting
               | bored and wanting food.
               | 
               | So this isn't really 3 separate unrelated changes. Also
               | at least in my experience, people tend to regard high
               | protein things as the "energy dense" part of a meal - the
               | problem with a lot of carbohydrates is they're not very
               | filling.
               | 
               | The biggest problem with exercise is it's an awful way to
               | lose weight - you don't burn that many calories, it makes
               | you hungrier, and then your body optimizes to burn even
               | less calories as you do it.
        
               | Kirby64 wrote:
               | > So this isn't really 3 separate unrelated changes. Also
               | at least in my experience, people tend to regard high
               | protein things as the "energy dense" part of a meal - the
               | problem with a lot of carbohydrates is they're not very
               | filling.
               | 
               | Who are these people? I suspect a lot of people who are
               | overweight/obese and taking GLP1 drugs have very little
               | to no concept of proteins role in their body composition.
               | Essentially all a GLP1 drug does is modulate down your
               | hunger (and you get full faster). That does not give you
               | any of the tools or skills to create a diet or exercise
               | plan. Both of those require intentional planning,
               | research, skills, and time. They're definitely 3 separate
               | things.
        
               | cthalupa wrote:
               | I'm someone that used to be fit and lifted regularly. Got
               | busy, got lazy, got fat. Tried multiple times to get not-
               | fat after getting fat, and found it to be too difficult
               | for me, despite it not being something I struggled with
               | for many years earlier on in adulthood.
               | 
               | Getting on tirzepatide made it trivially easy for me to
               | get back to a better diet, start exercising, etc. I do
               | have to force myself to have an extra protein shake to
               | hit my macros, though.
        
               | Kirby64 wrote:
               | I think you're trivalizing the ease at monitoring your
               | diet for someone who has never done this before. 'Macros'
               | as a concept is foreign to probably 90%+ of the
               | population I suspect. Unless you go extremely strict on
               | calorie/macro counting, it will just be hard to know
               | exactly how much you're taking in. It basically becomes
               | another hobby for at least a few months until it becomes
               | somewhat natural to do.
        
             | twelve40 wrote:
             | > In my experience it's easy
             | 
             | > Do some resistance training, get some protein
             | 
             | jeez, if people actually did that they wouldn't need the
             | drug to begin with
        
               | throwaway2037 wrote:
               | I must disagree with your comment. Personally, I have
               | witnessed so many people struggle for years with their
               | weight. Being overweight and struggling to lose weight
               | must be a 50 factor model: Multiple social, economic, and
               | mental/physical health factors. These GLP1 drugs really
               | are a game changer.
        
               | twelve40 wrote:
               | disagree with what? I said dieting, not cutting muscle
               | and sticking to it long-term for most people is absurdly
               | hard, which you seem to echo with "struggle for years"
        
               | throwaway2037 wrote:
               | Apologies; I misread your comment. You are right.
        
             | phil21 wrote:
             | Bodybuilders I know seem to have a a very difficult time
             | keeping their muscle gains while on a cut, I don't know why
             | someone who is not in a gym 5+ days a week and on an
             | extremely optimized heavy protein diet measured down to the
             | gram would expect otherwise.
             | 
             | Is it possible to go very slow and keep most of your lean
             | muscle mass? Sure. Is it practical? I have my doubts.
             | 
             | Part of the effectiveness of these drugs - for me at least
             | - is that results are rapid and that is a self-reinforcing
             | feedback loop. Diets that had me losing 1lb/week were
             | simply too boring and unmotivating for me to keep up beyond
             | a few months. A few days of vacation "cheating" and you
             | wipe out a month or more of incredibly difficult to achieve
             | loss. Restricting yourself mentally in what you eat every
             | day adds up to exhaustion over time.
             | 
             | Some folks can manage to lose very slowly while also
             | adhering to a strict calorie deficit of a few hundred per
             | day, while also being consistent with resistance training.
             | I'd say the evidence shows that these folks are in the
             | small minority.
             | 
             | I will say more evidence is needed for this drug class -
             | especially where the harm reduction principle may be a bit
             | iffy outside of obese folks. However it was life changing
             | to me in the way it let me change my eating habits to very
             | healthy protein and veggies as my primary calorie intake,
             | as well as made going to the gym on a strict schedule
             | motivating enough to actually come out at the end with a
             | better bodyfat to lean muscle ratio than where I started.
             | 
             | These gains have continued since I hit my goal weight - and
             | now I'm starting to become one of those folks who the BMI
             | no longer applies to in a good way. I do wish there was a
             | good way to test heart muscle mass like there is lean body
             | mass with a DEXA scan as I'm curious if my increased
             | regular workout heartrates translates into building back
             | any heart muscle mass like it did other lean muscle.
             | Certainly a concern to keep an eye out for!
             | 
             | I'm curious as you are if folks who are slow responders and
             | live active lifestyles see the same muscle loss the hyper
             | responders do. For reference I lost over 100lbs in just
             | under 9mo. I absolutely lost considerable muscle mass, but
             | have since put it back on and then some.
        
               | ohyes wrote:
               | I feel like a cut is a very specific type of weight loss
               | where the person gets down to an unusually low body fat
               | %. It's to the point where each bit of fat loss is a
               | significant portion of your body's fat reserves. It seems
               | different from when there is an abundance of easily
               | accessible fat to burn.
        
               | cthalupa wrote:
               | Well, bulking and cutting cycles are pretty common for
               | anyone beyond the beginniner stage when wanting to add
               | muscle mass, even if they're more recreational or a
               | powerlifter or whatever. It's just way more efficient to
               | be in a large enough surplus to make hitting your macros
               | easier and then diet after than it is to try and be super
               | careful about it. The powerlifters aren't worried about
               | getting down to that show ready <10%, they're just trying
               | to not be fat, and they still lose some muscle.
        
               | kbos87 wrote:
               | It isn't hard to imagine that the last 10% of mass a
               | bodybuilder has added was hard won and easily lost. That
               | isn't representative of most people.
        
             | turbojet1321 wrote:
             | It's notoriously hard to lose fat without also losing
             | muscle. That's why bodybuilders bulk well past their target
             | muscle mass before they cut for competition. I agree that
             | you can do a lot to mitigate it through protein intake and
             | resistance training, but you'll almost certainly still lose
             | muscle when you're in caloric deficit, regardless.
        
               | throwaway2037 wrote:
               | I'm not sure why this is so heavily downvoted. You raise
               | some good points. I would add: The era of comical bulking
               | is coming to an end. More and more scientific literature
               | points to _modest_ calorie surplus is the key to muscle
               | gain (along with regular weight training).
        
               | anon84873628 wrote:
               | Furthermore, this effect is dependent on genetics. What
               | is no problem for one guy in the comment thread could be
               | very challenging for another.
               | 
               | Also, "just do proper resistance training" is a bit of a
               | stretch when we're talking about what is practical to
               | expect of the masses taking Ozempic.
        
               | zemvpferreira wrote:
               | I don't mean to be rude but there are worlds of
               | difference between your average SAD-fed 300lb person
               | going from 60% to 30% bodyfat and a 259lb bodybuilder
               | going from 20% to 5%. As long as you are minimally
               | reasonable, catabolism is a luxury problem.
        
             | cthalupa wrote:
             | So, yes and no.
             | 
             | If you're doing resistance training for the first time in
             | your life or the first time in years, noob gains will
             | outpace loss if you train hard and get adequate protein.
             | This is the case for a lot of people on these GLP-1s, at
             | least at the start.
             | 
             | But if you have a massive quantity to lose, as in a multi-
             | year process, you won't be able to keep up the noob gains
             | for the entirety, and then yeah, you're going to basically
             | just be training hard and shoving protein down your face
             | just to keep the muscle loss minimal.
        
           | llamaimperative wrote:
           | > The rather obvious problem is that these GLP1 agonists
           | don't improve your diet
           | 
           | My understanding from initial anecdotes is this is actually
           | literally wrong. Which was surprising to me, too. But people
           | on GLPs tend to prefer more nutritious food (high protein and
           | high fiber). I'm not sure if this has been studied directly
           | in clinical trials yet but I know that food manufacturers
           | have been reorienting their products _toward_ healthier meal
           | configurations in response to the GLPs.
           | 
           | I predicted the exact opposite of this, but so far I _appear_
           | to have been wrong.
        
             | throwup238 wrote:
             | I've heard that anecdote from HN users many times but based
             | on my meatspace social group of (mostly) California
             | yuppies, that effect is vastly overstated. Even some of the
             | diabetics I know on Ozempic have started using it as an
             | excuse for a shittier diet. Now my sample size is barely
             | ten people on Ozempic/Wegovy so take it with a grain of
             | salt and what not, but I'm skeptical.
             | 
             | I bet there's a large group of people - possibly over
             | represented on HN and other online communities - that just
             | need a little nudge to suppress their cravings and eat
             | healthier, but that's far from universal. For a lot of
             | people, they wouldn't even know where to start to eat
             | healthier except choosing a salad over a burger at the
             | takeout menu. Even with drugs masking cravings, many people
             | just haven't had good health or culinary education.
        
               | llamaimperative wrote:
               | Odd Lots (Bloomberg finance podcast) had an episode back
               | in June or something interviewing a food design
               | consultant, and their focus groups came back very
               | strongly in favor of healthier meal compositions. Agreed
               | though, it's hard to know things :) Hopefully some real
               | studies on this will be done soon.
        
               | leoqa wrote:
               | Industry led focus group is not a legitimate source.
        
               | llamaimperative wrote:
               | Uhhhh, in general this is true, but in this particular
               | scenario they have a stronger incentive than almost
               | anyone to understand true preference shifts created by
               | these drugs.
               | 
               | It doesn't mean they end up with the correct findings,
               | but they are absolutely incentivized to try to produce
               | correct findings.
               | 
               | Lazy and inapplicable heuristics are not legitimate
               | insights.
        
               | adastra22 wrote:
               | Depends on the focus group. Some are put together too
               | establish that a product is wanted. Those are junk and
               | useless. Others like this are designed to tease out
               | trends and their accuracy is very valuable to the
               | companies that commission them.
        
               | throwup238 wrote:
               | Did the consultant describe the change in focus group
               | results or just the latest ones?
               | 
               | I was under the impression that consumers have been
               | asking for healthier food compositions for decades,
               | probably since the 70s or 80s when all the FUD around fat
               | started. Maybe GLP1 agonists bring their buying choices
               | more inline with the focus group results which would be
               | an interesting phenomenon.
        
               | llamaimperative wrote:
               | I forget the design of the experiment but I remember
               | feeling that my prior assumptions (which were in line
               | with GP) were potentially wrong, so it must've been
               | moderately convincing. I work in clinical trials so I'm
               | not a _complete_ buffoon on experiment design, but
               | accordingly I 'm also aware a good experiment is
               | obscenely difficult to conduct, and obviously this was
               | nothing close to an actual RCT.
        
               | burnt-resistor wrote:
               | I take mirtazepene because it's the only antidepressant
               | that works for me; unfortunately, it's also a massive
               | orexigetic. And also unfortunately I have original
               | Medicare that doesn't cover semaglutide until I develop
               | additional heart problems or diabetes, so I'm forced to
               | buy compounded semaglutide for 10% of the retail cost
               | (but still higher than the rest of the world) out-of-
               | pocket from a local large, retail, independent pharmacy
               | that wouldn't risk bankruptcy selling fake medications.
               | 
               | And I don't eat meat for non-dietary reasons that include
               | existential risks to all of humanity:
               | 
               | - Pandemics - Where did the "Spanish" flu (and influenza
               | A, Asian flu, HK flu, and 2009 pandemics) and COVID come
               | from?
               | 
               | - Antibiotic resistance - Most classes of antibiotics
               | used in humans are also used to make industrially-farmed
               | animals grow faster, leading to greater antibiotic
               | resistance and more potential bacterial pandemics too
               | 
               | - Climate change - 17%, at least
               | 
               | - Air pollution - Not just the smell of pig crap in the
               | air
               | 
               | - Water pollution - Ag runoff has been ruining river
               | delta systems
               | 
               | - Soil pollution - (It's gross)
               | 
               | - Fewer available calories for total consumption
               | 
               | - More expensive foods by less supply and more demand
               | 
               | (Never bother with "meat is murder" dramatic preaching
               | because most people who eat meat suffer from cognitive
               | dissonance preventing them from admitting their lifestyle
               | choice causes animal cruelty.)
               | 
               | When I was on and could afford semaglutide, I improved my
               | diet by consuming a high protein product with a low
               | calorie breakfast nutrition supplement. I'm sure I
               | probably could've accomplished similar with a
               | multivitamin and a protein product. What I need to change
               | is eating more low calorie, high fiber fruits and
               | vegetables that don't taste like cardboard or a mowed
               | lawn. My diet has gone to shit again because the
               | insatiable, all-consuming (no pun intended) hunger has
               | returned. I can't afford semaglutide right now so I must
               | become unhealtier than simply obesity in a similar but
               | lesser way than women who can't get surgeries until
               | they're septic and dying from failed ectopic pregnancies
               | before it will be covered... because somehow obesity is
               | completely my lack of willpower when I wasn't obese
               | before mirtazapine.
        
               | 123yawaworht456 wrote:
               | no wonder you're depressed
        
             | throwaway2037 wrote:
             | This observation is very interesting. I hope that it is
             | studied more closely and we can read some peer reviewed
             | research on the matter. One idea popped into my head: Could
             | _part_ of the cause be that people 's mood and self-esteem
             | improves during (GLP1 agonist-induced low hunger) weight
             | loss? TL;DR: If you feel like shit about yourself (and
             | body), then you are more likely to eat poorly, and vice
             | versa.
        
               | llamaimperative wrote:
               | That's an excellent hypothesis. Wouldn't be surprised at
               | all if that was a component!
        
             | astura wrote:
             | >My understanding from initial anecdotes is this is
             | actually literally wrong. Which was surprising to me, too.
             | But people on GLPs tend to prefer more nutritious food
             | (high protein and high fiber).
             | 
             | Not only that but prescribers and patients have noticed
             | that GLP-1 agonists also appear to significantly reduce
             | people's consumption of drugs like alcohol, nicotine and
             | opioids. At least in some populations.
             | 
             | Much more research is needed but right now it's extremely
             | promising that they will have a place in addiction
             | treatment in the future.
        
               | llamaimperative wrote:
               | Yep! So far it looks like GLPs might just be a generic
               | "craving-reducer." Pretty wild stuff if it holds (and we
               | continue not to see significant adverse effects).
        
           | ohyes wrote:
           | > Losing weight without losing muscle mass is very hard.
           | 
           | Yes it is.
           | 
           | > It requires extreme diets like a protein sparring modified
           | fast where 80%+ of your calories are from lean protein while
           | running a 50% caloric deficit.
           | 
           | I'm not any sort of expert but that sounds frankly,
           | dangerous. I don't see how you do something like that without
           | damaging your liver.
           | 
           | It's very possible to lose weight and gain muscle, but you
           | have to be at just the right body composition (not lean and
           | not obese) and then there's a question of "over what period
           | of time"?
           | 
           | Any duration under a month is probably pointless to measure
           | unless you have some special equipment. Any duration over a
           | month and it's kind of obvious that it is possible. Eat a
           | balanced diet without junk, work out regularly, and keep the
           | calories to only what is necessary.
        
             | throwup238 wrote:
             | _> I'm not any sort of expert but that sounds frankly,
             | dangerous. I don't see how you do something like that
             | without damaging your liver._
             | 
             | I haven't seen any credible research that a healthy person
             | can damage their liver from excessive protein intake.
             | Someone suffering from liver disease needs to be careful,
             | sure, but evidence that it would harm a healthy liver is
             | practically nonexistent.
             | 
             | That said, PSMF is explicitly _not_ a sustainable diet and
             | proponents generally don't claim it to be. It's a short
             | term diet meant to preserve muscle mass under extreme
             | caloric restriction (under 1.2k calories).
             | 
             |  _> Eat a balanced diet without junk, work out regularly,
             | and keep the calories to only what is necessary._
             | 
             | If it were as simple as that, we wouldn't be having this
             | conversation.
        
               | turbojet1321 wrote:
               | > If it were as simple as that, we wouldn't be having
               | this conversation.
               | 
               | It pretty much is that simple. The problem is that simple
               | is not easy.
        
           | pottertheotter wrote:
           | This is true. I just lost 30 pounds over 3 months and 17% was
           | muscle. I thought I was eating a lot of protein, but I've
           | upped it today.
           | 
           | I did an InBody scan the day I started (8/21) and just
           | happened to have done my second one this morning.
        
             | sheepscreek wrote:
             | I don't think we can expect to retain 100% of muscle mass,
             | and losing just 1/5th sounds like a good outcome.
             | 
             | I've understood that generalizing anything in today's time
             | is a losing game. I know many people with IBS/GI issues and
             | I am also sure they have different underlying causes. Our
             | gut biome and how digestion works in general needs to be
             | researched much more.
             | 
             | I don't know why progress has generally been so slowly on
             | that front. For instance, GLP-1 was discovered in the
             | 1970s. It took us another 40 years to commercialize it in
             | the form of Semaglutide and another 10 years to get it
             | ready for human consumption.
        
           | throwaway2037 wrote:
           | > nutrient deficient diet (which is probably a majority of
           | Americans)
           | 
           | This is bullshit. Literally, I Googled for: what percent of
           | americans have nutrient deficient diet?
           | 
           | First hit is some blogspam trying to sell me "Nutrient
           | Therapy". Second hit is CDC: https://www.cdc.gov/nutrition-
           | report/media/2nd-nutrition-rep...                   > The
           | Second Nutrition Report found less than 10% of the U.S.
           | population had nutrition deficiencies for selected
           | indicators.
           | 
           | Another thing that people frequently overlook, since post
           | WW2, the US has been "fortifying" grains with essential
           | minerals and vitamins. That means when people eat cereal and
           | bread from the supermarket (usually highly processed), there
           | are plenty of minerals and vitamins. Say what you like about
           | the highly processed part, few are nutrient deficient.
        
             | anon291 wrote:
             | Part of the problem is that the standards are incorrect. If
             | you go by dietary standards, you are eating way too many
             | carbohydrates and likely eating too many times a day,
             | especially if you do not have an active job.
             | 
             | Most people should mainly be eating fat and protein with a
             | decent amount of grains and fruit and vegetables. However,
             | the standard advice is to eat a lot of grains, some fruit
             | and vegetables, a modest amount of protein, and little fat.
             | This is awful and leads to very high hunger. Especially if
             | you eat multiple meals a day, as is also commonly
             | recommended, this is a recipe for being ever hungrier day
             | by day.
             | 
             | It wasn't until I eschewed all advice, started eating one
             | big meal a day and maybe one snack and matching my carb
             | intake with my fat intake that the hunger that I had known
             | since childhood magically disappeared and I lost 25 lbs
             | (and am losing more). Finally a 'normal' weight seems not
             | only in sight, but extremely easy!
        
           | throwaway2037 wrote:
           | > Losing weight without losing muscle mass is very hard.
           | 
           | Lots of amateur body builders can do it. There are whole
           | training guides about how to lose body fat, but maintain as
           | much muscle mass as possible. Granted, they are probably a
           | minority because they have higher discipline and motivation
           | than the average population.
        
             | cthalupa wrote:
             | Even pros on high doses of testosterone and multiple AAS
             | lose some muscle mass when preparing for a show.
        
           | uxp100 wrote:
           | Nutrient deficient, sure, protein deficient? Probably not.
        
           | voisin wrote:
           | > If you continue to eat a protein and nutrient deficient
           | diet (which is probably a majority of Americans)
           | 
           | Is it true the majority of Americans eat a protein deficient
           | diet? I always thought there was too much protein in the
           | western diet - nearly at every meals versus how we would have
           | evolved with somewhat limited access.
        
             | dgfitz wrote:
             | So, lots of foraging for food that grows on plants and the
             | occasional bison?
             | 
             | Would that we could convert the world to diets like that.
        
             | whythre wrote:
             | A lot of what Americans consume is really crappy carbs and
             | sugar, unfortunately. Even fatty meats would be better than
             | that.
        
           | ipsento606 wrote:
           | The claim that "a majority of Americans" eat a protein
           | deficient diet is absurd on its face.
        
           | bongodongobob wrote:
           | Americans eat a shit ton of protein. No idea where you got
           | idea that from.
        
           | anon291 wrote:
           | Part of the problem is that doctors recommendunhealthy diets
           | and will dismiss healthy diets.
        
           | wisty wrote:
           | Losing glycogen stored in muscle is not a huge issue IMO, as
           | it should come back fast. Stuff that's easy to gain is
           | usually easy to lose and vice versa.
        
             | hollerith wrote:
             | Uh, GP is talking about losing muscle itself, not the
             | glycogen in muscle.
        
               | cthalupa wrote:
               | Well, these studies look at FFM, which does include your
               | water weight and glycogen stores, so they do make up a
               | portion of it.
        
         | adrian_b wrote:
         | See the actual research article:
         | 
         | https://www.sciencedirect.com/science/article/pii/S2452302X2...
         | 
         | This study on mice was suggested by a previous publication:
         | 
         | https://www.thelancet.com/journals/landia/article/PIIS2213-8...
         | 
         | where it had been noticed that in humans "the muscle loss with
         | these medications (as indicated by decreases in fat-free mass
         | [FFM]) ranges from 25% to 39% of the total weight lost over
         | 36-72 weeks", in comparison with muscle loss of only 10% to 30%
         | when the weight is lost just by eating less, without
         | semaglutide.
         | 
         | So with semaglutide, a larger fraction of the weight loss
         | affects muscles than when the same weight is lost by
         | traditional means.
         | 
         | While for other muscles the loss of mass may not be so
         | important, the fact that at least in mice the loss also affects
         | the heart is worrisome and it certainly warrants further
         | studies.
        
           | petesergeant wrote:
           | > Studies suggest muscle loss with these medications (as
           | indicated by decreases in fat-free mass [FFM]) ranges from
           | 25% to 39% of the total weight lost over 36-72 weeks. _This
           | substantial muscle loss can be largely attributed to the
           | magnitude of weight loss, rather than by an independent
           | effect of GLP-1 receptor agonists_ , although this hypothesis
           | must be tested. By comparison, non-pharmacological caloric
           | restriction studies _with smaller magnitudes of weight_ loss
           | result in 10-30% FFM losses
           | 
           | Emphasis my own. In short: no evidence this is anything other
           | than due to rapid weight-loss.
        
             | adrian_b wrote:
             | The part highlighted by you was just an optimistic
             | supposition made at the time when the first article has
             | been published. That supposition only expressed wishful
             | thinking that was not based on any data.
             | 
             | The study on mice published in the second article has been
             | made specifically to test this optimistic supposition and
             | the results have shown that it had been false, i.e. the
             | weight loss caused by semaglutide is different from the
             | weight loss caused only by calorie restriction.
             | 
             | More studies are needed to elucidate whether this effect of
             | semaglutide is really harmful or maybe it can be reversed
             | or avoided by combining the medication with a better diet,
             | e.g. with a higher protein intake.
        
         | makeitdouble wrote:
         | I don't have it at hand [edit: [0]] but there are a number of
         | studies showing exercice had more health impact than weight
         | loss (you can combine both of course, but just losing weight
         | has less benefits)
         | 
         | As you point out, losing muscle is common in a diet, and the
         | researchers are well aware of it. Their point was that this
         | aspect is not pushed enough and is drowned by the losing weight
         | part.
         | 
         | From the paper:
         | 
         | > Dismissing the importance of muscle loss can create a
         | disconnect between patients' increased awareness of muscle and
         | the role it plays in health, and clinicians who downplay these
         | concerns, affecting adherence to and the development of
         | optimised treatment plans.
         | 
         | [0] https://journals.lww.com/acsm-
         | csmr/Fulltext/2019/08000/Effec...
         | 
         | For the "Fitness Versus Fatness" part for instance
        
         | colordrops wrote:
         | So it smells like bullshit because of your personal anecdote?
         | Or because some scientific evidence or experience you have?
        
         | jostmey wrote:
         | Biology is super complicated with lots of surprising
         | dependencies between different biological pathways. So it is
         | possible. That said, I am skeptical as well. For example, if
         | the body sheds 15% of its weight, does the heart naturally
         | shrink by 15% as well? With so many people taking these drugs,
         | there is enough data to begin to profile the rare risks of
         | these drugs in humans (the clinical trials would have found any
         | of the obvious risks)
        
         | NoPicklez wrote:
         | The article does dissect the difference between weight loss
         | drugs and dieting in general. Where they found that muscle mass
         | loss was higher in those that took the drug as opposed to those
         | who followed a calorie restricted diet.
         | 
         | To your point, the drug is absolutely to do with it if by
         | taking the drug people need to be more mindful of the types of
         | food they eat, if they have a smaller window to consume
         | nutrients.
         | 
         | It is most certainly a contributor and for some who may not
         | exercise like you, or consume an appropriate level of protein
         | this research may show that those taking the drug need to focus
         | on a more protein right diet.
        
       | PlunderBunny wrote:
       | I like the way the title ends with "human cells" as if the main
       | reason it was there was to cut off (?) all the people that
       | respond with " _In mice_. "
        
         | loeg wrote:
         | Well, in vitro.
        
       | xyst wrote:
       | folks, this is why I lean on skepticism in regards to "off label"
       | usage (ie, weight loss).
       | 
       | Have only lived a few decades on this planet and the weight loss
       | trends with pharmaceuticals is wild.
        
         | ahahahahah wrote:
         | Weight loss is not "off label" for this drug.
        
       | delichon wrote:
       | It also decreases gut motility, which helps with the intended
       | effect of appetite suppression. Young healthy people tend to
       | shrug at that. As an old person that takes it right off the menu
       | even before I read about accelerated sarcopenea. Maybe it's the
       | same effect on the peristaltic muscles.
        
         | vundercind wrote:
         | A bare glp-1 agonist doesn't, I think, but the weight loss
         | versions are double-acting and do also slow digestion.
        
           | loeg wrote:
           | Tirzepatide (Zepbound) is double-acting but semaglutide
           | (Ozempic) isn't. Both are prescribed for weight loss.
        
         | AuryGlenz wrote:
         | I tried taking it for IBS for that reason.
         | 
         | It worked! Kind of. The first few days after every dose it had
         | the opposite intended effect so it wasn't worth it.
        
       | httpz wrote:
       | Some of the side effects of semaglutide are just a result of
       | eating less calories.
       | 
       | Without a control group who also ate the same amount of calories
       | but without the drug, it's hard to know if the side effect were
       | directly caused by semaglutide or just a result of being in a
       | calorie deficit.
        
         | hackernewds wrote:
         | well it does lead to less eating so it indeed a side effect. if
         | control group ate the same amount there would be no weight loss
         | to begin with.
        
       | renewiltord wrote:
       | This is going to be a non-result. It won't matter. The win from
       | losing weight will easily outclass all of this. This drug should
       | be in wide circulation. When the patents expire, we will enter a
       | new era of American health.
        
       | loeg wrote:
       | So like, it's interesting that this happens in mice, but we did
       | not see increased heart disease in human RCTs of these drugs.
       | 
       | Maybe the mouse dose is just absurdly high? "Mice were then
       | administered semaglutide 120 mg/kg/d for 21 days." That could be
       | vaguely reasonable -- human doses range from, idk, ~36 to ~200
       | mg/kg/d (2.5mg/week to 15mg/week at ~100kg).
        
         | 7e wrote:
         | They found the mice did not suffer from any heart problems, so
         | it's not surprising.
        
         | cthalupa wrote:
         | > but we did not see increased heart disease in human RCTs of
         | these drugs.
         | 
         | In fact, we've even seen the opposite - that it's
         | cardioprotective.
        
       | DidYaWipe wrote:
       | So... could this be a treatment for enlarged hearts?
        
         | FollowingTheDao wrote:
         | Interesting!
         | 
         | People do no realize how wide spread the GLP1 receptors are in
         | the human body. GLPL1R is expressed on all muscles so heart
         | muscle will be effected:
         | 
         | https://pmc.ncbi.nlm.nih.gov/articles/PMC5939638/
         | 
         | https://www.proteinatlas.org/ENSG00000112164-GLP1R/tissue
         | 
         | The way these drugs help loose weight is by increasing cellular
         | activity by stimulating adenylyl cyclase and increased
         | intracellular cAMP levels. It is not that hard and not a
         | msytery to anyone who can think straight about human
         | metabolism.
        
       | LeoPanthera wrote:
       | It's my understanding that if you have hypertension, your heart
       | muscle grows thicker as a consequence of working harder against
       | your blood pressure, which reduces the flow capacity of your
       | heart.
       | 
       | So if you have hypertension, this might actually be a "good"
       | side-effect?
        
         | rootsudo wrote:
         | I was also thinking if in used with testestrone, which is
         | dangerous because the heart is a muscle and unintended
         | consequence of trt is heart muscle growth which decreases blood
         | flow.
        
       | akira2501 wrote:
       | The marketing is astounding.
       | 
       | "Weight-loss drug."
       | 
       | Oh, would that be Semaglutide?
       | 
       | <click>
       | 
       | Hey, would you look at that!
        
       | bastawhiz wrote:
       | The research says
       | 
       | > Together these data indicate that the reduction in cardiac size
       | induced by semaglutide occurs independent of weight loss.
       | 
       | Which does sound concerning. It's the drug, not the weight loss,
       | that causes the muscle loss.
       | 
       | I guess the question is whether it's better than nothing. Is the
       | loss in lean muscle a worse outcome than remaining obese?
        
       | oksurewhynot wrote:
       | I thought this was known about older GLP-1 antagonists like
       | semaglutide, which is why there's some excitement around the
       | newer dual-action types like tirzepatide? My understanding is the
       | newer drugs cause substantially less muscle mass loss.
        
       | CyanLite2 wrote:
       | If you're 20% smaller, it would make sense that your heart could
       | pump 20% less.
        
         | dgfitz wrote:
         | Uh, I think most highly in/shape people have normal sized, very
         | healthy hearts and their bpm is like 45.
         | 
         | Their hearts are not physically smaller, nor did they shrink
         | during their build-up to current physique.
         | 
         | Saying things like this is harmful at best. Please don't.
        
       | wileydragonfly wrote:
       | Don't care. I'm down 30lbs.
        
       | jmward01 wrote:
       | I wish discussions would focus on all source mortality instead of
       | single stat x. If the all source mortality data comes back
       | favorably you could read the interpretation of this data 100%
       | opposite: regular calorie restricting diets fail to reduce heart
       | size... Point being, without all source mortality data to back up
       | that this is a bad thing it is a very hard stat to care about.
        
       | GenerWork wrote:
       | I hope they re-run this study with retatrutide vs semaglutide.
       | Apparently retatrutide does a better job at preserving muscle,
       | and some bodybuilders will take small dosages (.5 - 1mg a week)
       | of it in order to lose stubborn fat but keep muscle.
        
         | loeg wrote:
         | How are bodybuilders getting a phase 2 trial drug still in
         | development by Lilly?
        
           | cthalupa wrote:
           | China. It's trivial to purchase retatrutide, semaglutide,
           | tirzepatide, and a wide variety of other peptides from
           | Chinese labs, and for pennies on the dollar compared even to
           | compounding pharmacy prices.
        
       | acyou wrote:
       | The study found that heart muscle decreased in both lean and
       | obese mice. So any observed muscle loss might not be just from
       | losing body mass and not having to work as hard.
       | 
       | But if you're already lean and then go on a calorie deficit (as a
       | result of decreased appetite from taking the drug), then muscle
       | mass will be lost through metabolism of muscle and other tissue.
       | 
       | Then the study states further that the proportion of muscle loss
       | is higher than expected from calorie restriction alone.
       | 
       | My gut feeling here is that where there's smoke there's fire, and
       | I predict dramatic class action 40 years in the making, either
       | like tobacco, or like baby powder, depending on the actual long
       | term health outcomes.
       | 
       | And, this is great research! We need more like this ASAP!
        
         | derbOac wrote:
         | Yeah, I think caution is needed with a single study, especially
         | with mice, when drawing conclusions about people.
         | 
         |  _However_ , this study is suggesting that semaglutide causes
         | _more muscle loss than would be expected based on calorie
         | change alone_ , not just that weight loss is accompanied by
         | muscle loss.
         | 
         | A lot of comments seem to be missing this critical part of the
         | study.
         | 
         | I wouldn't be surprised if this doesn't replicate, but what
         | they describe isn't quite what you might assume based on some
         | of the comments in this thread.
        
       | ramesh31 wrote:
       | >My understand of those drugs is that they don't actually make
       | you lose weight, they just cut your appetite so you can follow a
       | diet to lose weight without hunger hammering at the door.
       | 
       | While acknowledging that the mechanism is different, this was the
       | same effect of Ephedrine, which went through a similar craze as
       | Ozempic before the full complications were known. My bet is that
       | this will be similar, where the risks end up being outweighed by
       | the benefit for extreme obesity and diabetics, but that the
       | cosmetic weight loss aspect of it will become outlawed or highly
       | regulated.
        
       | dyauspitr wrote:
       | Sounds like a perfect counter to using steroids in bodybuilding
       | which can cause an enlarged heart. I wonder if we will start
       | seeing GLP-1 in bulk cut cycles more moving forward.
        
       | talkingtab wrote:
       | It concerns me how discussions, such as this one go on HN. This
       | is an important topic. With the epidemic of obesity we now find a
       | drug that appeals to a large number of people. This is an
       | important topic as well.
       | 
       | What is the current comment receiving most of the comment?
       | 
       | "That's the sort of headlines that smells like bullshit to me"
       | 
       | That's the sort of comment that smells like bullshit to me. What
       | kind of place is this?
       | 
       | Many times I find the posts on HN interesting, but increasingly
       | these kind of comments make me wonder about Y Combinator. Is this
       | really the best they can do?
       | 
       | And for us readers who are supposed to be so called hackers, is
       | this the best we can do?
        
         | throwaway2037 wrote:
         | I agree 100%. Those kinds of comments have no place, and add
         | little to nothing to the discussion. Many HN discussions
         | outside of pure tech invite all kinds of crazy and uninformed
         | comments -- health/diet, finance/economy, etc.
        
         | elevatedastalt wrote:
         | The HN you are yearning for disappeared about 8-10 years ago
         | when it was largely taken over by normies and people way
         | outside the hard-core-tech fold. It's not very different from
         | Reddit front-page now if the topic is even remotely political.
         | 
         | For purely technical topics you expect good quality discussion,
         | but those threads barely get comments in the two digits.
        
           | patrickhogan1 wrote:
           | Yes sometimes the loudest voice definitely rises to the top
           | and it's annoying, but I also think it's a condition that too
           | many new members don't know how to use the upvote button.
           | 
           | I also think it's a symptom that HN does not allow enough
           | people to use the down vote button. you could be a commenting
           | member for years and not be able to downvote or you could be
           | somebody who posts a few click bate links you copied from
           | another aggregator and all of a sudden you have the ability
           | to downvote. It's pretty dumb.
        
             | elashri wrote:
             | From my observation it is hard to get to 501 karma points
             | by the karma gained from submissions than through comments.
             | So for comments every 1 upvote equals 1 karma. But for
             | submissions, god only know what is the conversion rate /s.
             | I think there are many factor. But I think this mechanism
             | is to limit people creating accounts and mass down voting
             | anything they don't like. So it is trying to solve another
             | problem. However upvote power should be limited for new
             | accounts (I don't know if this already the case)
        
               | patrickhogan1 wrote:
               | I might be biased in my perspective because I tend to
               | focus on links that make it to the front page. It's true
               | that many links end up languishing in obscurity.
               | 
               | I just think the level of effort involved is different.
               | For instance, the person who posted the link to the study
               | we're now discussing earned 199 points with far less
               | effort than you put into replying to my comment. Many of
               | the links posted are copied from Reddit, Twitter,
               | Slashdot, etc.
        
               | elashri wrote:
               | I am sure what he actually got is much less than that
               | number. If you got 200 up votes to a comment then that's
               | 200 karma, but with submissions it is different, maybe
               | dang can shed some light on that. Also what gets traction
               | depends on a lot of things that you will find that most
               | people will have the vast majority of their submissions
               | have little to zero activity. So it is not that easy,
               | some will manage to do it but the purpose is to limit
               | that to something manageable. Then I think dang is
               | managing both up voting ans down voting rings. With up
               | voting being harder (everyone can do that)
        
           | seizethecheese wrote:
           | I'm sure complaining about HN is as old as HN.
        
             | nfw2 wrote:
             | Specifically comparing HN to reddit is old as well. It's
             | mentioned in the guidelines to not say HN is turning into
             | reddit. The examples of this shared in the guidelines go
             | back to 2007
        
           | britzkopf wrote:
           | Yeah, normies suck. I totally only want to hear from people
           | obsessed with the latest computer Science minutia!
        
           | parpfish wrote:
           | If you think HN users are normies, I think you might be in a
           | bubble. Normies ain't this literate.
        
         | anon291 wrote:
         | I have noticed this too. The site guidelines say 'no low effort
         | comments', but low effort comments that fit the general
         | zeitgeist are often allowed, while well-thought-out ones that
         | disagree are downvoted. If anyone has a suggestion for an
         | alternative forum focused on technology and science, I really
         | would love suggestions.
        
         | PittleyDunkin wrote:
         | What exactly do you think this forum is if you think this forum
         | is above such sentiments?
        
         | devmor wrote:
         | After I saw yesterday's thread about politics in science was
         | flooded with new sockpuppet accounts named after slurs
         | spreading filth and downing everything they don't agree with I
         | no longer expect anything meaningful from comments here.
        
           | dluan wrote:
           | HN only works when you have a working assumption that people
           | commenting here are smarter than you. It encourages respect
           | and good faith engagement of content, instead of ad hom,
           | concern trolling, and cargo culting.
           | 
           | It's been years since I've had that mindset when entering any
           | thread above a certain number of comments.
        
         | tamimio wrote:
         | For that reason HN should just remove the down/up votes,
         | because it will turn this place to an echo chamber like reddit,
         | these brownie points are useless.
        
         | NotYourLawyer wrote:
         | To be fair, that comment was about the claim:
         | 
         | > emerging research showing that up to 40 per cent of the
         | weight lost by people using weight-loss drugs is actually
         | muscle
         | 
         | Which is... obviously bullshit.
        
           | sabbaticaldev wrote:
           | they might have confused muscle and lean mass/FFM
        
           | _heimdall wrote:
           | The source article links to a reference for the 40 percent
           | claim, which itself links to a couple articles that aren't
           | available without a JAMA account.
           | 
           | I can't read the original sources there, but what makes you
           | say its obviously bullshit?
        
             | bcoates wrote:
             | From the abstract:
             | 
             | "Studies suggest muscle loss with these medications (as
             | indicated by decreases in fat-free mass [FFM]) ranges from
             | 25% to 39% of the total weight lost over 36-72 weeks. This
             | substantial muscle loss can be largely attributed to the
             | magnitude of weight loss, rather than by an independent
             | effect of GLP-1 receptor agonists, although this hypothesis
             | must be tested. By comparison, non-pharmacological caloric
             | restriction studies with smaller magnitudes of weight loss
             | result in 10-30% FFM losses."
             | 
             | The "surprising" part is kinda bullshit, and implies
             | there's something special about glp-1s. It is the opposite
             | of surprising that weight loss includes a lean mass loss.
             | 
             | That said, being skinnyfat is probably bad for you and the
             | idea that you should work to preserve/build muscle and not
             | _only_ lose weight is a good one.
        
               | mr_toad wrote:
               | FFM isn't entirely muscle, but what other weight would be
               | shed when losing FFM other than muscle?
        
               | nordsieck wrote:
               | > FFM isn't entirely muscle, but what other weight would
               | be shed when losing FFM other than muscle?
               | 
               | I'm not an expert, but I have to imagine that most of it
               | is muscle.
               | 
               | After dramatic weight loss, a person will probably lose
               | some bone - particularly in the lower body - due to
               | decreased loading.
               | 
               | I know body builders sometimes eat extremely high protein
               | diets (more than 1 g/lbs of body weight) and lift quite
               | hard to try to hang on to as much muscle mass as
               | possible. And they still lose some when cutting.
        
               | cthalupa wrote:
               | Water weight is a big one, and is part of your FFM. I
               | lost 10lb of water weight in my first 24 hours on
               | tirzepatide.
               | 
               | Some of it is likely bone density as well. You can
               | prevent the bone density and muscle loss with proper diet
               | and exercise, though.
        
               | hombre_fatal wrote:
               | Googling it, 70% of FFM is water.
               | 
               | Yeah, I've swung 10lbs in 24 hours just going from well
               | fed to fasted without water. And it certainly wasn't fat
               | I lost, just water and I'm surely any mass in my...
               | various tracts.
        
           | kiba wrote:
           | You lose muscle when you lose weight, especially if weight
           | loss is rapid. This is why it's important to be physically
           | active when you're losing weight. It doesn't matter if you're
           | on drug or not.
        
         | abtinf wrote:
         | I agree with your desire for what HN should be, and disagree
         | with your assessment that the top voted comment doesn't support
         | it.
         | 
         | HN is the only forum I know of that has broadly grasped that
         | most so-called "science" outside of the hard sciences and
         | mathematics is complete garbage and driven by funding needs.
         | The world is awash in non-knowledge. This is an extremely
         | serious issue.
         | 
         | Building the skill to rapidly come to a preliminarily judgement
         | of a headline is crucial.
        
           | PaulHoule wrote:
           | There is plenty of garbage in hard science too. Start with
           | 
           | https://arxiv.org/archive/hep-th
        
           | echelon wrote:
           | > disagree with your assessment that the top voted comment
           | doesn't support it.
           | 
           | Did you read the paper or skim its abstract, figures, and
           | conclusion? I'm not so sure that commenter did, or they may
           | have cited this,
           | 
           | > Because we report smaller cardiomyocytes in cultured cells
           | and in mice treated with semaglutide, it is tempting to
           | speculate that semaglutide may induce cardiac atrophy.
           | However, we do not observe any changes in recognized markers
           | of atrophy such as Murf1 and Atrogin-1. Thus, we cannot be
           | certain that semaglutide induces atrophy per se or if it
           | does, it may occur via molecular pathways that have not been
           | identified herein.
           | 
           | > Building the skill to rapidly come to a preliminarily
           | judgement of a headline is crucial.
           | 
           | You can't judge this paper based on the popsci headline.
           | 
           | > most so-called "science" outside of the hard sciences and
           | mathematics is complete garbage and driven by funding needs
           | 
           | Based on my reading of the figures and conclusion, I don't
           | think you should call this paper garbage.
        
           | kiba wrote:
           | The most reliable source of knowledge we have are in the
           | science. This is further reinforced by technological
           | development that validated the sciences, although at time the
           | technology may precede the science.
        
         | burningChrome wrote:
         | The cure for obesity isn't a pill.
         | 
         | Remember in the 80's and 90's when exercising and being healthy
         | was considered a cool thing? Remember there was a gym on every
         | corner and people were all about looking good and being
         | healthy, eating healthy and living longer?
         | 
         | Then somewhere. . .
         | 
         | - We started normalizing obesity.
         | 
         | - We started this whole "body positivity" trend that
         | celebrating morbidly obese people like Lizzo as positive role
         | models was a good thing?
         | 
         | - We started introducing fat mannequin models in retail stores
         | because being obese shouldn't have a stigma?
         | 
         | Obesity is a problem because we, as a culture have completely
         | _normalized_ obesity. Instead of promoting healthy diets and
         | exercises and saying being obese has consequences like
         | shortening your life and will make you susceptible to various
         | diseases like diabetes and heart disease? All we 've done is
         | told people its ok to be obese and eat sugary drinks and over
         | processed foods, because you can just have surgery and that
         | will fix it. Or you can take a pill and that will fix it.
         | 
         | IT WON'T.
         | 
         | IT NEVER WILL.
         | 
         | We've gone down a road that is staggeringly dangerous because
         | we've accepted being morbidly obese as something that's
         | completely normal.
        
           | PaulHoule wrote:
           | No, some chemical or chemicals got added to the environment
           | around 1980.
           | 
           | All I can say is try losing 20 pounds and keeping it off for
           | two years and how easy it is. Fat shaming might make a
           | difference but I suspect it would be like knocking off 5 lbs
           | from the average where you really need to knock off 50 lbs.
           | 
           | You only started seeing Victoria's Secret getting fat models
           | in the last few years, the obesity epidemic on the other hand
           | started in the Regan years. Maybe it's like taking your belt
           | off when you get heartburn (though I know if I go that route
           | pretty soon I'm going to need suspenders) Try
           | 
           | https://arxiv.org/abs/q-bio/0312011
           | 
           | for a theory that may be wrong but fits the chronology.
        
           | kiba wrote:
           | This is nonsense. The majority of the population don't want
           | to be fat, ugly, and unhealthy and want to persists in
           | maintaining good healthy habits in which they don't eat junk
           | food.
           | 
           | People who promotes fat positivity are ridiculed.
           | 
           | Blaming it on culture overly simplify the issue, which is
           | going to be a complex mix of interacting causes.
        
           | watwut wrote:
           | What are you talking about. Obesity was and still is
           | something super common to make fun off for years.
           | 
           | In the 80, there was less stigma to being obese then now.
        
         | PaulHoule wrote:
         | It is my own perception that HN has gotten worse in the six
         | months but these sort of "meta" discussions can be as much part
         | of the problem as part of the solution or possibly a bad smell.
         | 
         | My take it this.
         | 
         | The median scientific paper is wrong. I wrote a wrong paper.
         | The average biomedical paper doesn't fit the standards of the
         | Cochrane Library mostly because N=5 when you need more like
         | N=500 to have a significant result. Since inflationary
         | cosmology fundamental physics has been obsessed with ideas that
         | might not even be wrong.
         | 
         | It's well known that if you lose a lot of weight through diet
         | (and even exercise) you are likely to lose muscle mass. With
         | heavy resistance exercise you might at best reduce your muscle
         | loss if you don't use anabolic steroids and similar drugs. That
         | you could have changes in heart muscle with using these weight
         | loss drugs isn't surprising for me at all and it's the sort of
         | thing that people should be doing research both in the lab and
         | based on the patient experience.
         | 
         | (Funny you can get in trouble if you do too much exercise,
         | spend 20 years training for Marathons and you might get A-Fib
         | because you grew too much heart muscle instead of too little.)
         | 
         | A lot of the cultural problem now is that people are expecting
         | science to play a role similar to religion. When it came to the
         | pandemic I'd say scientists were doing they best they could to
         | understand the situation but they frequently came to
         | conclusions that later got revised because... That's how
         | science works. People would like some emotionally satisfying
         | answer (to them) that makes their enemies shut up. But science
         | doesn't work that way.
         | 
         | The one thing I am sure of is that you'll read something else
         | in 10 years. That is how science works.
        
         | photochemsyn wrote:
         | The developers of these new peptide-based hormone-acting drugs
         | like semaglutide(ozempic) could be called biohackers, but the
         | system they're hacking on - the human endocrine system - is a
         | delicate system. Introducing semi-synthetic mimics of native
         | hormones can go wrong in all kinds of ways, and hormone-
         | analogue drugs have a poor track record (anabolic steroids,
         | DES, etc.) so extra caution makes sense.
         | 
         | Semaglutide is based on a 31-amino acid polypeptide that mimics
         | the human GLP-1 hormone. At position 26, the lysine side chain
         | is conjugated with a fatty diacid chain, to slow degradation
         | and prolongs half-life, and there are some other modifications.
         | However, the target - the GLP receptor - is not just expressed
         | in the intestinal tract but all through the body, in muscle,
         | central nervous system, immune system, kidneys and others. So
         | some unexpected effects beyond the desired ones are likely.
         | 
         | Semaglutide was recently shown to have potent effects on the
         | heart, and possibly beneficial to certain heart disease
         | conditions associated with obesity. Makes me suspect this drug
         | should be restricted to clinically obese cases where strong
         | intervention with close medical supervision is needed. However
         | for healthy people who just want to lose a relatively small
         | amount of weight it really doesn't seem wise.
         | 
         | "Semaglutide ameliorates cardiac remodeling in male mice by
         | optimizing energy substrate utilization..." (June 2024)
         | 
         | https://www.nature.com/articles/s41467-024-48970-2
        
         | seizethecheese wrote:
         | Disagree. The "hacker ethos", to me, is laypeople taking a
         | crack at things without pretension.
         | 
         | Your comment lacks any substantive argument about the comment
         | you complain about.
         | 
         | Apparently the topic is "important". To me an appeal to
         | importance when policing style spells like bullshit.
        
       | et2o wrote:
       | This is most likely a good thing. It isn't killing cardiac
       | myocytes, it's probably assisting with reverse remodeling. Fits
       | with why we know it helps in heart failure.
        
       | quantumwoke wrote:
       | Seems like some of the comments need to learn that a big
       | hypertrophic heart is much worse for you than a normal sized
       | heart. Folks: GLP-1s have demonstrated benefit from heart
       | failure, and this heart muscle change is probably mechanistic in
       | that.
        
       | 7e wrote:
       | "Dyck, who is the Canada Research Chair in Molecular Medicine and
       | heads up the Cardiovascular Research Centre, says his team did
       | not observe any detrimental functional effects in hearts of mice
       | with smaller hearts and thus would not expect any overt health
       | effects in humans."
       | 
       | This makes sense. If fasting hurt your heart many of your
       | ancestors would have died early. There is strong selection
       | pressure to survive extended fasts.
        
       | siliconc0w wrote:
       | It's pretty clear that GLP-1 should be prescribed with protein
       | powder. When your appetite is crushed you don't go for the
       | chicken breast, you go for what is immediately appetizing
       | (usually carbs+fats like pizza or fries). IMO this and a lack of
       | resistance training (which should also be prescribed) probably
       | makes up a large % of the muscle loss on these drugs. The problem
       | is that the FDA only looks at dumb measures like weight lost, not
       | body fat % when approving these drugs.
        
         | meragrin_ wrote:
         | > When your appetite is crushed you don't go for the chicken
         | breast, you go for what is immediately appetizing (usually
         | carbs+fats like pizza or fries).
         | 
         | Um, when your appetite is "crushed", nothing is particularly
         | appetizing. That is the entire point. It allows one to make
         | better decisions or pass on eating.
        
         | cthalupa wrote:
         | I find it significantly easier to eat healthy on tirzepatide,
         | fwiw.
        
         | technofiend wrote:
         | That may be your experience, it wasn't mine. I eat _very_
         | healthy on Ozempic but yeah of the 60 lbs lost so far some of
         | it is noticeably muscle because I don 't exercise enough. The
         | next 60 lbs of fat lost will hopefully be me swapping fat for
         | muscle from weight lifting and swimming.
        
         | phil21 wrote:
         | Tirzepatide let me stay away from the immediately appetizing
         | junk food and almost exclusively eat a clean diet focused on
         | protein.
         | 
         | My experience matches at least a dozen folks in my personal
         | bubble. It's sort of the point of the drug or it wouldn't work
         | very well.
         | 
         | Totally agreed on resistance training. The one thing I would
         | change would have been starting that in a serious manner as
         | soon I started the drug vs. waiting. Prescribing it is silly
         | though - if that worked we wouldn't need the drugs to begin
         | with.
        
         | jf22 wrote:
         | If found the opposite to be true.
         | 
         | I'm eating healthier than ever and don't care for junk foods
         | anymore.
        
         | mostin wrote:
         | That hasn't been my experience. I've been on liraglutide
         | (Saxenda) for a month and a half or so and if I feel like I
         | can't finish a plate of food I'll eat just the protein and
         | leave the carbs, where I would've eaten everything before.
        
         | wan23 wrote:
         | Going to add to the chorus here. One of the reasons these
         | things are so successful is that it kind of kills the crave
         | factor of eating. You don't get that feeling where you feel
         | like you want to keep eating something addictive like pizza or
         | fries just because it's there. It's why the packaged food
         | companies are freaking out - all their work to engineer snacks
         | where they can "bet you can't eat just one" is defeated by
         | these, at least for now.
        
       | kbos87 wrote:
       | There are a lot of people here citing loss of muscle mass as a
       | side effect of GLP-1s, when the reality is that weight loss
       | almost always comes with muscle loss.
       | 
       | For me, that hasn't even been the case. I'm down 40lbs on a
       | relatively low dose of Semaglutide and my muscle mass has
       | moderately increased over the last 6 months. The hysteria over
       | this is totally unfounded.
        
         | mgiampapa wrote:
         | Likewise, I did (and continue to do) keto for the last 6 months
         | and lost 50lbs. 3 Weeks ago I started Semaglutide while
         | continuing to do keto and it's just made everything easier.
         | I've lost another 10lbs in the 3 weeks, am logging all my meals
         | and taking macro goals into account. What's better is that
         | because I was already "fat-adapted" as they say in /r/keto, my
         | body isn't starving in a caloric deficit. It's just burning
         | more fat as ketones.
         | 
         | Yes, I am trying to hit 100-150g+ of protein per day, yes I am
         | in a caloric deficit. No, I don't feel like I have lost any
         | muscle mass, but I do feel a lot more active at 60lbs lighter.
        
         | NavinF wrote:
         | Yeah I've always found that complaint confusing. Of course you
         | lose muscle when you eat less food. It'd be weird if that
         | didn't happen. (Assuming you don't train hard or take hormones)
        
         | cthalupa wrote:
         | Yep. I started resistance training 5x a week about a month in
         | on tirzepatide and even with a severely restricted caloric
         | intake (I just can't eat enough), I've gained LBM.
        
           | xk_id wrote:
           | How did you measure the increase in LBM? This requires very
           | advanced technical equipment. My suspicion is that you have
           | noticed an increase in muscle volume and assumed it to be an
           | increase in muscle mass. Those are largely due to water
           | retention and increased blood flow. They revert quite quickly
           | after you stop exercising for about a week.
        
             | kridsdale1 wrote:
             | DEXA scans are accurate and readily available in most
             | cities for about $100. Just do it quarterly or whatever.
        
             | cthalupa wrote:
             | I am getting regular DEXA scans
        
             | phil21 wrote:
             | Does ability to lift weight also decrease in about a week?
             | I was recently out of town for over two weeks and came back
             | with the ability to lift roughly the same amount I was able
             | to prior to leaving.
             | 
             | My DEXA scans seem roughly correlated with the amount of
             | weight I can do in my regular sets, which has increased
             | about 50-70% depending on which muscle group you are
             | talking about.
             | 
             | This is with heavy resistance training 3 times a week and
             | Pilates once a week.
        
               | cthalupa wrote:
               | A good portion of the strength related to any specific
               | lift is CNS adaptation up until a certain point (and most
               | new lifters won't hit that threshold for quite some
               | time), so strength on a lift you've been doing regularly
               | isn't necessarily a good indicator. Building muscle will
               | of course increase your strength too, but I've doubled my
               | squat since getting back into lifting while certainly not
               | doubling the muscle mass of the respective muscles.
        
               | phil21 wrote:
               | Fair enough. I didn't mean a 1:1 correlation in 50% on a
               | Dexa means 50% more strength, just would expect my
               | lifting ability to go down if I lost muscle mass (or if
               | it were water weight to begin with). Neither have
               | decreased much if at all during breaks, so I'm fairly
               | convinced it's "real" so to speak.
               | 
               | Looking through my weightlifting app my best tracked
               | exercise (leg press) increased about 250% from start with
               | a 60% (roughly, speaking from memory) increase in lean
               | muscle mass as measured by a DEXA scan. If I remember
               | when back from dog walks tonight I'll update that with a
               | real number off the actual data.
               | 
               | I was a total newb at lifting though, so those early
               | gains came quite quickly.
               | 
               | I am curious as this is a concern I have for long term
               | health.
        
         | BartjeD wrote:
         | It predicts long term consequences on health. Not immediate
         | ones. You wouldn't have noticed at all. Unless you measured
         | your heart muscle weight.
         | 
         | It's good to work out. Perhaps it offsets any loss.
         | 
         | I get that it's upsetting and might contradict what you think.
         | 
         | At this stage we don't know for sure. It's something you might
         | want to keep in mind. Especially if you take this drug without
         | working out.
        
           | peteforde wrote:
           | If someone is taking this medication for the right reasons,
           | the risks of taking it are far lower than those associated
           | with obesity and diabetes.
           | 
           | Also, concern of losing muscle mass on GLP-1 agonists (and
           | diets in general) is well known and typically explained by
           | the responsible MD to the patient.
        
         | diath wrote:
         | You did not lose 40 pounds of fat while building lean muscle
         | tissue unless you're BOTH relatively new to weightlifting and
         | use PEDs, in which case, the "hysteria" is justified for an
         | average person.
        
           | cthalupa wrote:
           | Just the former is likely enough over a 6 month span, even
           | without great genetics. That's only a 1.6lb/week loss. Noob
           | gains can be huge.
        
             | diath wrote:
             | A caloric deficit that allows a continuous weight loss of
             | 1.6 lbs a week for 6 months is significant enough to
             | completely wreck your hormonal profile and put you in
             | constant catabolic state, I doubt you would be able to put
             | on any noticeable amount of muscle mass even during your
             | noob gains phase in that context.
        
               | cthalupa wrote:
               | I've seen it happen with people even prior to the GLP-1s
               | - prior to an injury derailing my last attempt to lose
               | weight, I lost 30lb at an even faster rate and had 3 DEXA
               | scans showing consistent increases in LBM.
               | 
               | This conversation does make me wonder about whether or
               | not it would make sense to make the option available for
               | people to go on exogenous testosterone (and yes
               | potentially even women) while on these to help prevent
               | muscle loss.
        
         | arcticbull wrote:
         | Studies show strength training while losing weight can retain
         | almost 100% of muscle.
         | 
         | https://pmc.ncbi.nlm.nih.gov/articles/PMC5946208/
        
           | scruple wrote:
           | Anecdotally, it takes far less strength training than one
           | would expect, too, to maintain muscle mass. From what I've
           | experienced, 30 minutes a week, given sufficient stimulus, is
           | enough.
        
             | cthalupa wrote:
             | There are more and more PhD researchers focusing on
             | resistance training these days, and yeah, it turns out the
             | minimum effective dose is waaaaaay lower than we previously
             | thought.
             | 
             | https://www.minimumdosetraining.com/ - free training
             | program + links to a bunch of studies the author was
             | involved in on this specific subject.
        
               | scruple wrote:
               | I love this so much, thanks for sharing. I have my own
               | minimum effective dose protocols that I use when life is
               | kicking me in the face but I am going to try these on for
               | size during the coming holiday season.
        
         | inamberclad wrote:
         | Anecdotes don't equal data. "Always" and "never" don't exist in
         | medicine. I'm sure that your experience is accurate to
         | yourself, but these studies have to cast a wider net since
         | there is always variability in results.
        
           | epistasis wrote:
           | The post you are replying to didn't say "always" it said
           | "almost always," wich is perfectly cromulent. And it's also
           | consistent with all the literature I have seen too.
        
         | apwell23 wrote:
         | > low dose of Semaglutide
         | 
         | I thought its only approved at standard dose.
        
           | cthalupa wrote:
           | There is a dosing schedule for all the GLP-1s, with what is
           | considered the minimal therapeutic dose being several times
           | your initial dose.
           | 
           | However, a lot of people either see results on these initial
           | doses, and plenty of people find them to be effective as
           | maintenance doses.
        
             | AuryGlenz wrote:
             | I took it for a bit as a non-overweight person and the
             | minimum dose was absolutely enough for me to have a hard
             | time eating enough to maintain my weight.
        
         | Etheryte wrote:
         | Your sample size is one. Imagine how a study saying this would
         | get picked apart if their sample size was one. You have no idea
         | whether you're in the middle of the normal distribution bell
         | curve or at one of the extreme ends.
        
         | FollowingTheDao wrote:
         | I would be more concerned about the thyroid cancer when taking
         | these drugs...
         | 
         | https://scholar.google.com/scholar?as_ylo=2024&q=glp+1+thyro...
        
           | cthalupa wrote:
           | The two meta-analysis are interesting, I think.
           | 
           | https://www.liebertpub.com/doi/abs/10.1089/thy.2023.0530
           | 
           | > Overall there is no conclusive evidence of elevated thyroid
           | cancer risk.
           | 
           | https://dom-
           | pubs.onlinelibrary.wiley.com/doi/full/10.1111/do...
           | 
           | > Our meta-analysis showed that GLP-1RA treatment could be
           | associated with a moderate increase in relative risk for
           | thyroid cancer in clinical trials, with a small increase in
           | absolute risk. Studies of longer duration are required to
           | assess the clinical implications of this finding.
           | 
           | It's potentially a possibility, but the absolute risk seems
           | to still be quite low.
        
       | mistercheph wrote:
       | There is no way magic weight loss pill with no side effects could
       | possibly go wrong!!!
        
       | robwwilliams wrote:
       | Not a solid paper---more like an abstract. I could not find any
       | information on the strain or type of mice they studied. Data from
       | one strain often fails to generalize to others. Trying to leap to
       | human implications is beyond risky.
        
         | insane_dreamer wrote:
         | If you're trying to prove a positive benefit, then leaping from
         | mice to humans is risky. If you're concerned about possible
         | negative effects of something, then mice is a good place to
         | start.
        
         | jr000 wrote:
         | It says in the paper they used 21-week-old male C57BL/6 mice,
         | as well as AC16 human immortalized cardiomyocytes
        
       | tomhoward wrote:
       | I'm not commenting specifically on the heart-muscle aspect of the
       | study, but it shouldn't be a surprise that the weight loss from
       | this drug is significantly attributable to muscle loss; it almost
       | always is when dieting. It's the same with keto/low-carb or any
       | other kind of caloric-restrictive dieting (which Ozempic
       | facilitates).
       | 
       | The modern weight-loss programs I'm seeing now (at least those
       | aimed mostly at middle-aged men) emphasize consuming significant
       | amounts of protein (2g for every 1kg of body weight each day) and
       | engaging in regular resistance training, in order to maintain
       | muscle mass.
       | 
       | The article addresses this:
       | 
       |  _To keep muscle strong while losing weight, Prado says it is
       | essential to focus on two main things: nutrition and exercise.
       | Proper nutrition means getting enough high-quality protein,
       | essential vitamins and minerals, and other "muscle-building"
       | nutrients. Sometimes, this can include protein supplements to
       | make sure the body has what it needs._
       | 
       | Perhaps there needs to be more formal research into this, and a
       | strong recommendation made to everyone using these drugs that
       | this kind of diet and exercise plan is vital.
        
         | jjallen wrote:
         | For the people who lift weights while on this/these drugs, how
         | much lean muscle do they lose?
         | 
         | The point is is that most people lose muscle because they're
         | not lifting. You will lose muscle if you lose weight no matter
         | the cause, if you are not lifting weights.
        
           | phil21 wrote:
           | Not sure how much I lost during, but a substantial amount. I
           | have been working out since about 20lbs from my goal weight
           | and now roughly a year later - and have gained strength
           | (based on the numbers I can lift) from before I lost 100lbs.
           | 
           | I don't think it would have been possible to not lose
           | substantial muscle mass while rapidly losing 100lbs over 9mo,
           | even with extreme resistance training added to the mix. While
           | DEXA scans are not super accurate, I've put on about 17lbs of
           | muscle since my first scan 10mo ago, while maintaining a 12%
           | or less bodyfat ratio.
           | 
           | That said, I've been eating extremely healthy both before and
           | after being on the drug which helps a lot. The drug simply
           | gave me the mental space to avoid the binges which were my
           | particular problem. That and it controls portion sizes to
           | European dinner vs. American restaurant sized meals for me.
        
             | Agingcoder wrote:
             | 100 lbs that's significant. What are the implications of
             | rapidly losing weight ? ( I'd expect even your body image
             | changing to not be very easy )
        
           | cyberax wrote:
           | > For the people who lift weights while on this/these drugs,
           | how much lean muscle do they lose?
           | 
           | I was 92kg when I started on liraglutide (I was doing GLP-1
           | agonists before it was cool!) and 67% of muscle mass (61kg).
           | I'm now at 69kg and 82% of muscle mass (56kg). I'm doing
           | weight and resistance training twice a week, in addition to
           | aerobic training.
           | 
           | One nice thing, while muscles don't become more massive, they
           | for sure become more pronounced and visible with weight loss.
        
             | scotty79 wrote:
             | I'd bet you are stronger now despite slightly lower muscle
             | mass.
             | 
             | Probably the muscle tissue people lose first are crappy
             | cells. Weak, nonfunctional, senescent or even maybe some
             | muscle embedded fat.
        
             | metafunctor wrote:
             | Those muscle mass percentages cannot be right. How were
             | they measured?
        
               | NovemberWhiskey wrote:
               | I'm assuming that's lean mass (100% - fat %) rather than
               | muscle mass. Unless that person doesn't have a skeleton.
        
           | scruple wrote:
           | I know 2 competitive athletes (both MMA) who experimented
           | with it. Both came off of it within ~6 weeks because of
           | complications, mostly related to mood (they got very, very
           | temperamental on it). The athletes in my sphere know about it
           | but aren't interested. The 2 who experimented have a non-
           | trivial social media presence and, ultimately, that is what
           | drove them to experiment.
        
         | Cthulhu_ wrote:
         | It's why the medication should never be given to people on its
         | own (although I'm sure it happens all the time), but should be
         | a part of a comprehensive weight loss, exercise and dietary
         | plan. Same with other invasive weight loss treatments, you
         | can't just get a gastric belt or whatever fitted if you ask for
         | it, you need to do the work yourself first, and you get a diet
         | plan assigned if you do end up with one.
         | 
         | It's the same with e.g. human growth hormones, one theory is
         | that Elon Musk is / has used them, but without the weight
         | training that should go with it, so his body has developed
         | really weirdly.
        
         | jajko wrote:
         | I've heard this feedback on Ozempic et al from my wife who is a
         | GP some 6 months ago, when I mentioned how US is too much in
         | comfort zone and addicted to HFCS to actually lose weight
         | permanently, ever, so in good old weight-losing fads fashion
         | they will just throw money at the problem, experiencing
         | somewhat variable success and who knows what bad side effects.
         | 
         | My wife told me exactly this - potentially all muscle mass loss
         | (and she made sure I understood that 'all' part), yoyo effect
         | once stopping, potentially other nasty long term/permanent side
         | effects, and overall just a bad idea, attacking the problem
         | from a very wrong direction. Just look at musk for example - he
         | pumps himself with it obsessively and the results even for
         | richest of this world are... not much there (or maybe his OCD
         | binging would make him 200kg otherwise so this is actually some
         | success).
         | 
         | Then all the folks come who say how to helped them kickstart a
         | positive change, like its something against those facts above.
         | All the power to you, just don't ignore facts out there and
         | don't let emotions steer your decisions. You only have 1 health
         | and it doesn't recharge that much, and that short time we have
         | on this pale blue dot is significantly more miserable and
         | shorter with badly damaged health.
        
           | JumpCrisscross wrote:
           | > _like its something against those facts above_
           | 
           | I've seen multiple friends go from eating like shit,
           | including chugging sodas, to not compulsively ordering
           | dessert and no sodas in the house. I think all of them have
           | since quit Ozempic, each seeing some rebound but nothing
           | comprehensive and, most notably to your argument, not in the
           | behaviour modifications.
        
             | MrMcCall wrote:
             | The only way to lose weight without damaging oneself is to
             | combine more exercise with less eating, which means
             | becoming comfortable being hungry. Yes, it's difficult --
             | especially after developing bad eating habits over a long
             | time -- but moderation is required in all things. It takes
             | a long time to become overweight, so the ramp down to a
             | leaner existence must necessarily take a significant amount
             | of time, or there's going to be added risk.
             | 
             | Just like in programming, there is no silver bullet;
             | there's only hard work.
        
               | vundercind wrote:
               | That's true for an _individual_ , but if you're looking
               | at a population then you're seeing a situation where we
               | have _zero other solutions_ that are actually effective
               | at curbing obesity. The only  "natural" way to solve it
               | is probably to overhaul our entire culture, redesign our
               | cities and neighborhoods, et c., and that's not
               | happening.
               | 
               | Skinny people move to the US and get fat. They're not
               | skinnier back in their home country because they've got
               | greater willpower or are harder workers, but because
               | _they aren 't in the US_. If harder work isn't why
               | skinnier countries are skinnier, we shouldn't expect it
               | to help us out of our problem, and indeed, we have
               | _nothing_ else we 've studied that is terribly effective
               | over time, and certainly nothing cheap enough to deploy
               | on a large scale.
               | 
               | Again, yes, for an individual your perspective is the
               | only thing one has (well... until these drugs) but
               | looking from a policy level, it's useless.
        
               | MrMcCall wrote:
               | A person's body mass is nothing more than the combination
               | of what a person eats and what a person does in their
               | life.
               | 
               | The only really effective policy is to inform people that
               | that is the simple, honest truth of every single person,
               | and that the quality of food we eat is important in that
               | equation.
               | 
               | Eat better food, be more active. Yes, it is difficult,
               | especially for us peasants.
               | 
               | But that is science. I hope a miracle drug helps folks
               | preyed upon by the food industry, but side effects of
               | that industry's drugs leave me skeptical of their being
               | lastingly beneficial.
        
               | vundercind wrote:
               | > The only really effective policy is to inform people
               | that that is the simple, honest truth of every single
               | person, and that the quality of food we eat is important
               | in that equation.
               | 
               | It's literally not effective. As in, well-studied, isn't
               | effective.
               | 
               | Again, it's the only guidance one has to go on,
               | personally, so it's fine to hold onto that as an
               | individual navigating the world, but it is emphatically
               | not _effective policy_.
        
               | MrMcCall wrote:
               | I wrestled in high school and college, my friend. If you
               | don't eat and work out a lot, you _will_ lose weight,
               | guaranteed. It 's the nature of the human body; it's
               | thermodynamics and biochemistry and hard as hell as we
               | get older, especially when poor.
               | 
               | But sure, it's not effective but only because people have
               | a hard time fending off our cravings. It requires
               | breaking our cycles and learning how to eat better and
               | eat less and do something other than lay around watching
               | tv.
               | 
               | As to policy: if we curbed the corps' ability to profit
               | off our ill-health, then we'd surely be doing something
               | positive for society. It would also be very helpful to
               | have cleaner air and more and larger parks that are safe
               | for one and all. What can I say, I dream big.
               | 
               | Personally, I recommend everyone avoid any and all
               | refined sugar and alcohol, as they mess with our hormones
               | and gut biome. And that's very difficult for 2024
               | America, evidently.
        
               | hollerith wrote:
               | >I wrestled in high school and college, my friend. If you
               | don't eat and work out a lot, you will lose weight,
               | guaranteed. It's the nature of the human body
               | 
               | That is like dismissing a bug report because "it works
               | fine on my machine", though.
        
               | vundercind wrote:
               | Yes, it works if you do it. No, relying on it to get a
               | population to lose weight doesn't work, even if that
               | population has self-selected for wanting to lose weight
               | and you educate the _hell_ out of them.
        
               | unshavedyak wrote:
               | > I wrestled in high school and college, my friend. If
               | you don't eat and work out a lot, you will lose weight,
               | guaranteed. It's the nature of the human body; it's
               | thermodynamics and biochemistry and hard as hell as we
               | get older, especially when poor.
               | 
               | No one is questioning CICO.
               | 
               | The part being questioned is why it's more difficult for
               | others. For example, my wife and I share an almost
               | identical diet and activity level, yet i struggle to keep
               | weight on and she struggles to keep weight off and with
               | similar lifestyles. CICO works of course, but not only do
               | our bodies innately do different things with the calories
               | that they process but we simply experience that world
               | differently.
               | 
               | I could drop down to unhealthily thin levels without even
               | trying. She would be in misery even trying to maintain my
               | weight.
               | 
               | This isn't an excuse necessarily. Rather just saying
               | there's a lot of information beyond simple CICO that
               | we're missing. Complexity in biome, addictive behaviors,
               | and a full on assault from the food industry.
               | 
               | The ease i have in weight loss is not due to my own
               | efforts. Thin people shouldn't break their arm patting
               | themselves on the back, because imo it's usually not due
               | to our own will.
        
               | Kirby64 wrote:
               | > The part being questioned is why it's more difficult
               | for others. For example, my wife and I share an almost
               | identical diet and activity level, yet i struggle to keep
               | weight on and she struggles to keep weight off and with
               | similar lifestyles. CICO works of course, but not only do
               | our bodies innately do different things with the calories
               | that they process but we simply experience that world
               | differently.
               | 
               | If you and your wife eat the same diet in the same
               | quantities, it's no surprise she would have a propensity
               | to gain weight and you wouldn't unless she's substanially
               | larger (i.e., taller and/or heavier) than you. Women in
               | general just burn fewer calories for similar sized vs.
               | men. That said, this is ALL population averages. Everyone
               | knows someone who seems to be able to eat literally
               | anything and never gain weight... it likely is just as
               | simple as their metabolism is such that they burn more
               | calories than the average person. Population variation
               | will always lead to some people with outliers both in
               | high expenditure and low expenditure.
        
               | unshavedyak wrote:
               | > it likely is just as simple as their metabolism is such
               | that they burn more calories than the average person.
               | Population variation will always lead to some people with
               | outliers both in high expenditure and low expenditure.
               | 
               | That's the point though. I'm saying that we burn calories
               | at different rates. We burn fat at different rates. We
               | have different rates of addiction, cravings, etc.
               | 
               | Just saying CICO is the same boring and borderline
               | inaccurate language that has led to nearly zero change in
               | the population at large. may as well just tell them to
               | use physics correctly to lose the weight, because it's
               | the same effective language.
               | 
               | To even determine CICO is fraught with difficulty and
               | inaccuracy in both CI and CO. You can hand make
               | everything, weigh every ingredient, and even then you
               | struggle to determine how much you're CO. At best you'll
               | have an estimated CO but then what do you do when your
               | weight isn't changing? you have to start adjusting the
               | math because clearly you're not burning as much as you
               | think you are.
               | 
               | This is made much, much worse with the fact that we don't
               | actually burn that many calories with exercise. And even
               | with what is burned, the rate of burn changes drastically
               | based on your current weight and how long you've been
               | losing weight.
               | 
               | The fact is, the point is, CICO ignores all the real
               | challenges and thereby all the real problems people need
               | to understand and face.
        
               | Kirby64 wrote:
               | > The fact is, the point is, CICO ignores all the real
               | challenges and thereby all the real problems people need
               | to understand and face.
               | 
               | I think we'll have to disagree here. At the end of the
               | day CICO is the formula. That obviously doesn't account
               | for the human factor in regards to the adherenace rate,
               | but it does, fully encompass the 'if you were a robot and
               | were fully adherent how do you lose/gain weight' method.
               | 
               | > To even determine CICO is fraught with difficulty and
               | inaccuracy in both CI and CO. You can hand make
               | everything, weigh every ingredient, and even then you
               | struggle to determine how much you're CO. At best you'll
               | have an estimated CO but then what do you do when your
               | weight isn't changing? you have to start adjusting the
               | math because clearly you're not burning as much as you
               | think you are.
               | 
               | I won't say it's 'easy', but it's also not particularly
               | hard either with the multitude of widely available food
               | databases for measuring calories in. As for calories out,
               | it's arguably even simpler: measure your weight every
               | day, take the average across the week, and watch your
               | weight trend week over week. Calories out can be
               | calculated simply by comparing calories in vs. weight
               | lost/gained... and extrapolating. It's simple math, and
               | very effective in my experience.
               | 
               | > This is made much, much worse with the fact that we
               | don't actually burn that many calories with exercise. And
               | even with what is burned, the rate of burn changes
               | drastically based on your current weight and how long
               | you've been losing weight.
               | 
               | Essentially irrelevant if you follow my above suggestion
               | for how to measure calories out. It's just part of the
               | bucket of calories burned, so as long as you're
               | reasonably consistent with the amount of exercise you do
               | then your averaged weight will account for any exercise
               | based caloric expenditure.
        
               | consteval wrote:
               | > The only way to lose weight without damaging oneself is
               | to combine more exercise with less eating, which means
               | becoming comfortable being hungry
               | 
               | No, not really. Yes, this is how you lose weight, but
               | this is not how you have to be to be a healthy weight.
               | 
               | I'm thin, I don't exercise, and I'm not hungry. I feel
               | great.
               | 
               | I can sit around and jerk myself off about discipline,
               | but the truth is I have none. I have done absolutely
               | nothing to be in this position, it's all luck and factors
               | far beyond my comprehension.
               | 
               | if a drug is able to induce that same feeling in others,
               | I say go for it. It sucks that a normal caloric intake
               | translates to pain, hunger, and constant brain noise for
               | a large segment of the population.
        
           | 462436347 wrote:
           | > addicted to HFCS
           | 
           | HFCS consumption (along with added sugar consumption in
           | general) peaked in 2000 and declined steadily until 2020:
           | https://news.ycombinator.com/item?id=38094768
        
             | hombre_fatal wrote:
             | It doesn't give me much confidence bringing it up at all in
             | this convo. As if replacing HFCS with cane sugar (55% vs
             | 50% fructose) changes anything about junk food.
        
         | 0xEF wrote:
         | Diet and exercise. It always comes back to that, yet people
         | avoid it like the plague.
         | 
         | The modern weight loss program you described is pushed because
         | that's what people want; an extremely low-effort methodology
         | that yields extremely high results.
         | 
         | The idea that their is some silver bullet to weight loss has
         | dominated the US health market for ages now because selling
         | someone a pill that they don't have to do anything but swallow
         | and be cured is really, really easy.
         | 
         | Having gone through my own weight loss journey, I have seen
         | first hand how attractive that is and fell for it myself twice.
         | So have loved ones, one whom is no longer the same person
         | because they got gastric bypass which resulted in a massive
         | change to gut and brain chemistry, something that we seem to be
         | just figuring out is connected. My own journey is not over, but
         | there are no longer any medications or supplements involved,
         | because I can say with authority that none of them work without
         | good nutrition and physical exercise.
         | 
         | As I realized this and just put more work into eating better
         | and doing more activities (I did not join a gym, but started
         | riding my bicycle more, walking neighbor's dogs, and doing
         | body-weight exercises at home, etc, making it more integrated
         | into my day rather than a separate event I could skip), I lost
         | a healthy amount of weight and got stronger.
         | 
         | It took a lot longer, of course, than what the pills promised,
         | but that's the trick of the whole weight loss industry...and
         | make no mistake, it is an industry. Short-term results in
         | exchange for your money. It was never about helping people be
         | healthier and always about myopic profits, therefore we should
         | not be trusting any claims these companies make that their
         | silver bullet is the correct one, finally.
         | 
         | And yet.
        
           | in_a_hole wrote:
           | How has the gastric bypass affected this person? It would not
           | have occurred to me that the brain would be affected.
        
             | 0xEF wrote:
             | We were surprised, too. Their personality changed to be a
             | lot more aggressive and they started compulsively lying,
             | then stealing things from stores, and some strange draw
             | toward self-harm and getting "corrective" surgeries.
             | Previously, this person was typically pleasant, if not a
             | little outspoken at times.
             | 
             | There is suspicion that they had a pre-existing mental
             | health issue they were hiding, and the very fast changes
             | that happened in their body triggered it to either manifest
             | or get worse. We are left guessing because they refuse to
             | see any doctors that won't just write prescriptions for
             | meds or minor elective surgeries, now.
             | 
             | These days, more and more evidence is piling up about the
             | gut-brain connection, but no conclusions are being drawn
             | quite yet. Though, from my own experience, it is not
             | difficult to convince me that one certainly impacts the
             | other.
        
               | in_a_hole wrote:
               | I'm sorry to hear that happened to someone close to you,
               | thank you for sharing.
        
           | jstummbillig wrote:
           | > The modern weight loss program you described is pushed
           | because that's what people want; an extremely low-effort
           | methodology that yields extremely high results.
           | 
           | I think it's a mistake to think of it as what people want.
           | It's what people can do.
           | 
           | We have to acknowledge a fundamental struggle that we have
           | with dieting and working out. Pretending it's just hard, when
           | statistics show what is true at a societal level, will not
           | bring us solutions.
           | 
           | We need something else. Either that's massive societal change
           | to i.e. approach something like the diet/workout culture you
           | have in Japan. That's hard. Or, as with many other of our
           | health problems that we can't just will away, it's drugs.
           | 
           | Not believing in progress here, when drugs progress
           | everywhere, is unnecessary. Current generations might have
           | issues. Drugs will be better. We won't.
        
             | 0xEF wrote:
             | I still disagree. Simplicity and convenience is what people
             | not only want, but demand. And this extends beyond weight
             | loss solutions to our modern world of ever-converging
             | technologies creating ever-complex systems under the guise
             | of efficiency. Multiple cultures have supported these
             | values since the times of snake-oil salesmen, which did not
             | exactly vanish with history, as we so often forget. Look at
             | products like Optavia, Xenedrine, etc.
             | 
             | It keeps happening because the market wills it to, but not
             | without good reason. It is perfectly rational to want
             | something to be easy, especially now as our modern lives
             | are inundated with a tremendous amount of stressors and
             | tasks we must constantly attend to. So yes, we wish for
             | convenience, but it is not the solution we always need.
        
               | jstummbillig wrote:
               | > Simplicity and convenience is what people not only
               | want, but demand.
               | 
               | Hmm, that is not my experience generally. People will
               | take insanely ineffective routes if that is what the
               | system pushes them toward, without taking much offense.
               | 
               | For example, on the topic of health/weight loss: Weight
               | Watchers or yoga classes are huge industries while also
               | being insanely elaborate and expensive ways of eating
               | better and moving your body.
               | 
               | I agree with you that, for example, drugs are currently
               | not a solution to these problems. But what I propose is:
               | they are going to be. And they had better be because
               | there is no other effective solution poised to work at a
               | societal scale. We just can't help ourselves. "Just eat
               | the salad and walk every day" simply did not do the
               | trick. We tried. While it works on a mechanistic level,
               | of course, it does not work in practice. Blaming people
               | for their inability to fight their nature is just
               | inhumane and not how we usually progress: we fix reality
               | for ourselves.
               | 
               | While it is not impossible to design a society that is
               | healthier (see: Japan), it's at such odds with our
               | current culture, and societal change is slow. We should
               | certainly get to work on this decades-long project, but
               | we should also treat this like any other health issue
               | that costs billions of life-years and find a more
               | effective intervention.
        
               | autoexec wrote:
               | > Blaming people for their inability to fight their
               | nature is just inhumane
               | 
               | It'd be nice if people didn't have to fight their nature.
               | Our society demands we act in ways that are unhealthy and
               | unnatural. We're forced to sit in chairs 8+ hours a day
               | from very young ages. Children have teachers making sure
               | they stay in their seats, and workers have supervisors
               | enforcing inactivity either in person or using webcams
               | and software. Companies like Amazon insist that their
               | employees piss in bottles or wear diapers because leaving
               | their workstation, even to use a bathroom, will get them
               | fired. The demands of our daily lives and the design of
               | our environments keep us from living the way we've
               | evolved to live and it's normal and should be expected
               | that many people will struggle with that reality more
               | than others.
               | 
               | Either our society and environment needs to change, or
               | our biology and chemistry need to change. Turns out, it's
               | easier to change ourselves than it is to change the
               | massive systems designed by greed and exploitation that
               | we're forced to live in. We'll adapt. Today it's with
               | drugs. Tomorrow it may be genetic manipulation.
        
               | s1artibartfast wrote:
               | I think some people feel strongly about this issue
               | because it seems like giving up on societal change, which
               | IS necessary for many reasons besides just weight. Even
               | if GLP-1 drugs are safe and long term effective for body
               | fat, they are still a band-aid for a deeper problem. The
               | deeper problem is that people feel and express less and
               | less agency and control over their personal lives. This
               | manifests in many forms, such as depression, anger,
               | cynicism, addiction, loneliness, and personal stagnation.
               | Weight loss will do little to improve these measures
               | while the average American watches 4 hours of TV and is
               | devoid of community.
               | 
               | Im hopeful that these drugs can give people a toehold to
               | tackle these deeper issues, and try to emphasize that
               | they are not a panacea.
               | 
               | People are a product of society, and society is a product
               | of people. If we want to live better people will have to
               | change too.
        
           | NovemberWhiskey wrote:
           | I don't think anyone is disputing that changes to diet and
           | exercise are required.
           | 
           | Based on people who I know have been taking these drugs, they
           | make it much _easier_ to reduce calorie intake by promoting
           | satiety. That's the benefit.
           | 
           | Doing the rest of your life while you feel hungry is not fun,
           | and willpower is not infinite.
        
           | 1234letshaveatw wrote:
           | I don't know it is always avoidance when it comes to diet and
           | exercise. I think oftentimes it comes down to overscheduling.
           | I like to exercise, I like to eat healthy. Those two are
           | oftentimes the first things on my chopping block when I am
           | hurried
        
         | Sheeny96 wrote:
         | Whilst it is 95% calories in calories out, keto (not low carb,
         | as low carb doesn't include high fat) can be good for muscle
         | retention whilst in a defecit - as more foods that you consume
         | naturally have higher protein (I utilise keto when looking to
         | drop body fat, consuming a lot of slightly higher fat cuts of
         | meat as a replacement for the carb calories, so chicken thighs
         | instead of breast, 10% ground beef,etc). The higher fat content
         | correlates to higher testosterone count, and higher protein
         | means greater muscle retention.
        
           | 5636553454654 wrote:
           | Carbohydrate as an energy substrate is well-known to be more
           | muscle protein-sparing when in a deficit than fat, so
           | assuming protein is equal, expect to lose more muscle on keto
           | than low-fat:
           | https://r.jordan.im/download/nutrition/hall2021.pdf (c.f. p.
           | 347, the bottom central and bottom right graphs)
        
             | greentxt wrote:
             | Carbs are harder to control for many people, and less
             | forgiving. A side effect of keto is decreased appetite. A
             | side effect of carbs is overeating.
        
               | hombre_fatal wrote:
               | Only when "carbs" is a euphemism for junk food. Which
               | probably exists because Americans don't eat carbs like
               | beans and broccoli. And instead of eating them, they get
               | told online that they should avoid all carbs.
               | 
               | It's a devious euphemism that screws the people over the
               | most that should be eating more beans and broccoli (et
               | al).
        
               | s1artibartfast wrote:
               | Carbs is also colloquialism for calorie dense grains and
               | cereals. Broccoli is like 5% carbs by mass. Bread is 50%
               | carbs by mass. It is a hell of a lot easier to
               | overconsume the latter, spike your insulin, and get into
               | a cycle of cravings.
               | 
               | There is no boogie man trying to scare people away from
               | broccoli.
        
               | consteval wrote:
               | > There is no boogie man trying to scare people away from
               | broccoli
               | 
               | I disagree, everyone I know who has been on a keto dietic
               | consumes little to no fruits or fiber. Honestly, I'm not
               | sure how they use the bathroom successfully with such
               | little fiber ingestion.
        
               | bityard wrote:
               | I ate only keto for years and I'm getting back to it now
               | so I have some experience to speak of.
               | 
               | You are correct, fruit is mostly sugar so no fruits. Some
               | keto adherents allow the occasional handful of berries,
               | but I found that just made me unreasonably hungry later
               | on. Not everyone has this reaction, though.
               | 
               | There is plenty of fiber in above-ground vegetables. And
               | even if there wasn't, it's not like eating only meat
               | would kill you, humans evolved on the plains and/or
               | jungles of Africa where meat was almost all that was
               | easily available.
        
               | s1artibartfast wrote:
               | If you are talking very specifically about a ketogenic
               | diet, then fruits actually do have too many carbs to
               | maintain ketosis. In that case, it isn't some irrational
               | fear, but reality.
               | 
               | Re fiber, A significant portion of the population (maybe
               | a majority) doesn't need much fiber to use the bathroom.
               | It seems like this need is a common situation that people
               | assume is a universal truth. Further, fiber can lead to
               | constipation for many people.
        
               | cthalupa wrote:
               | Fruits, yes, because it will kick you out of ketosis.
               | Fiber, every keto adherent I knew would eat fiber in
               | reasonably large quantities because keto often causes
               | constipation, and a lot of the substitutes for things
               | with "regular" carbs were high in fiber.
        
               | Wytwwww wrote:
               | > broccoli
               | 
               | Have almost no carbs or any calories, they are basically
               | just water. Like you'd need to eat 1kg just to get 300
               | calories (less than in e.g. 100g chickpeas).
        
               | Kirby64 wrote:
               | Adherence may be a concern for lots of types of carbs,
               | but that doesn't change the conclusion that keto (i.e.,
               | very little to no carbs) is worse for muscle retention
               | when keeping caloric content equal. Also, as others have
               | pointed out, not all carbs lead to overeating
               | necessarily. Likewise, not all keto diets are going to
               | lead to decreased appetite.
        
         | ANewFormation wrote:
         | The percents are very different. For example in bodybuilding
         | one normally 'bulks' while working out, because it maximizes
         | muscle gain. But then naturally this needs to be paired with
         | cutting, unless you're a Greek Grizzly, but the total muscle
         | loss is relatively negligible, especially when maintaining a
         | proper high protein diet.
         | 
         | At 40% muscle loss you're getting awful close to losing weight
         | while increasing your body fat percent!
         | 
         | But of course you're right that diet+exercise is key but for
         | those maintaining such, they wouldn't end up on these drugs to
         | start with.
        
           | snozolli wrote:
           | _For example in bodybuilding one normally 'bulks' while
           | working out, because it maximizes muscle gain. But then
           | naturally this needs to be paired with cutting_
           | 
           | This comes from professional bodybuilding, where people are
           | using steroids, along with various, uh, interesting chemicals
           | on the cut[1]. It has almost no benefit to (real) natural
           | bodybuilders. It's closely tied to cycles of steroids.
           | 
           | [1] Ephedrine, Albuterol, Clenbuterol (literally only
           | approved for horses in the US), DNP, and probably more that I
           | haven't heard of. Here's an NIH article on the dangers of
           | DNP, to put it in perspective:
           | https://pmc.ncbi.nlm.nih.gov/articles/PMC3550200/
        
             | sickofparadox wrote:
             | In order to gain more muscle mass, at some point you need
             | to be in a caloric surplus. You can't make something out of
             | nothing - your body needs the extra resources to make
             | itself bigger.
        
               | Funes- wrote:
               | You do know that your metabolism can pull energy out of
               | your fat storages, right? And that metabolism is
               | extremely flexible and adaptable, to be sure? Your body
               | certainly isn't pulling out a calculator every night
               | before you go to sleep to determine whether you've eaten
               | in excess or not for the day, and then deciding to build
               | muscle or not based on that alone. That's ridiculously
               | simplistic, and wrong. It's a multitude of processes
               | working constantly, and factors like exercise, protein
               | intake or adaptation to ketosis, just to name a few, are
               | of the utmost importance. Some people tend to think of
               | the human metabolism as a calorimeter, when it couldn't
               | be farther from it.
        
             | automatic6131 wrote:
             | The most important cutting aids are the same ones in
             | bulking - AAS like testosterone and its close (cheaper)
             | variants like trenbolone and methylated testosterone but
             | yeah, the interesting chemicals are featured too.
             | 
             | Most natural bodybuilders recommend the 'clean bulk' where
             | one simply eats the same cutting foods but in larger
             | proportions. And also not to be too strict in general -
             | that way lies disordered eating, binges, purges etc.
        
             | s1artibartfast wrote:
             | Are you claiming that a drug free person can gain as much
             | muscle mass while in a calorie deficit as while in a
             | calorie surplus?
             | 
             | If so, I would be very curious to _that_ reference.
        
             | cthalupa wrote:
             | Natural bodybuilders 100% go through bulking and cutting
             | cycles.
             | 
             | Outside of noob gains it is incredibly difficult for a
             | natural to add muscle mass when in a calorie deficit and
             | recomposition at maintenance calories is also inefficient
             | in the vast majority of cases.
             | 
             | They won't bulk the same way someone on gear does, but it's
             | still the most efficient way to add muscle mass in the vast
             | majority of cases.
        
         | jasonlotito wrote:
         | To be clear, these recommendations are already made very
         | clearly before you take the medication. There is absolutely
         | nothing in your comment that isn't already clearly spelled out.
         | Your last paragraph is literally already being done.
         | 
         | This isn't a surprise unless people ignored reading about the
         | drugs before taking it and ignored the doctors.
        
         | cma wrote:
         | On top of that wouldn't even liposuction already reduce heart
         | muscle over time because of the lower amount of vasculature
         | extent afterwards? Less volume to need to pump through and less
         | metabolic and oxygen demand.
         | 
         | There is significant heart remodeling after even things like
         | major amputations because of the changing demands on the heart.
        
         | gonzo wrote:
         | > (2g for every 1kg of body weight each day)
         | 
         | This equates to a 300lb male consuming 272g of protein per day.
         | There are 139g of protein in 1lb of chicken breast.
         | 
         | The RDA to prevent deficiency for an average sedentary adult is
         | 0.8 grams per kilogram of body weight. A 300lb male needs about
         | 110g/day at this RDA.
        
       | diath wrote:
       | The problem with appetite suppression drugs is that they simply
       | make you not feel hungry, but do nothing to fix your lack of
       | discipline and self-control, I'm sure most people who lose weight
       | on these drugs, and then come off, will just go back to their bad
       | habits.
        
         | echoangle wrote:
         | So why not just stay on the drugs?
        
           | diath wrote:
           | You technically could but the idea here is to cut the excess
           | bodyfat percent and get into the healthy range, rather than
           | to keep losing weight, which itself is also unhealthy, but
           | once you become dependent on the drugs to maintain your
           | weight, without fixing your habits, you will just go between
           | getting off the drug, binge eating, gaining the weight back,
           | and hoping back on the drug and losing weight while barely
           | eating, I can't imagine bouncing between such two extremities
           | being good for your health.
        
             | echoangle wrote:
             | Can't you just adjust the dosage to stabilize?
        
               | phil21 wrote:
               | Yes, you can. Or most people can. It's called a
               | maintenance dose and is usually the minimum dose
               | available for the particular drug you are on.
               | 
               | As these become more common and doctors more aware, the
               | dosing guidelines will become much more nuanced and
               | dialed in.
        
             | cthalupa wrote:
             | Well, lots of people back off those dosages once they reach
             | their goal weight and have minimal difficulty maintaining.
             | As we know more about the long term effects of staying on
             | the drug, it's totally possible it might make sense just to
             | keep on it.
             | 
             | But as someone who spent a good chunk of their early
             | adulthood having no problem with healthy habits and then
             | slowly slipping into tons of bad ones, getting on
             | tirzepatide has made it as easy for me to make those
             | healthy choices that I made when I was in my 20s. Ones that
             | I struggled with mightily after I got fat.
             | 
             | Hopefully more and more people will use them as a tool to
             | help them get things back and order and then stay there,
             | whether or not they keep taking it.
        
           | bluSCALE4 wrote:
           | Most kill you. If I didn't misread articles on ozempic, they
           | can cause digestive problems where food rots in your stomach.
           | Bad depression was another side effect which blows my mind
           | since you'd think looking better would make you feel great.
           | And these were the minor things.
        
             | cthalupa wrote:
             | > digestive problems where food rots in your stomach
             | 
             | I assume you mean gastroparesis - this is an _extremely_
             | rare side effect
             | 
             | > Bad depression
             | 
             | Again, pretty rare side effect.
             | 
             | If you think these are the minor things I'm confused as to
             | what you think the major side effects are.
        
               | Elinvynia wrote:
               | Gastroparesis is literally the method of action of GLP1
               | agonists. It slows gastric motility. Gastroparesis is
               | literally slowed motility of the stomach (where 20% of
               | food stays in your stomach after 4 hours). It doesn't
               | matter why, that is the literal diagnostic criteria, ergo
               | it literally causes gastroparesis.
        
               | cthalupa wrote:
               | Your position does not match that of medical researchers.
               | 
               | https://jamanetwork.com/journals/jama/fullarticle/2810542
               | 
               | https://pmc.ncbi.nlm.nih.gov/articles/PMC10874596/
               | 
               | https://pubmed.ncbi.nlm.nih.gov/38443105/
               | 
               | Or more plainly worded
               | 
               | https://www.healthline.com/health-news/ozempic-wegovy-
               | stomac...
               | 
               | Some people develop permanent gastroparesis.
        
             | tokioyoyo wrote:
             | I don't think you realize the amount of people have taken
             | Ozempic or similar drug. I'm lucky enough that I haven't
             | had issues with body weight, but if I believe the stats
             | (and my observations in real world confirm it), about 15%
             | of adults are on it.
             | 
             | If it was "killing people", we would be seeing it literally
             | everywhere. We're not talking about a small scale 50K+
             | observation... we're talking about literal millions.
        
               | echoangle wrote:
               | This says 6% are currently on a GLP-1 drug and 15% have
               | ever taken one in their life:
               | 
               | https://amp.cnn.com/cnn/2024/05/10/health/ozempic-
               | glp-1-surv...
        
               | tokioyoyo wrote:
               | Fair, I remembered my stats wrong. But it's still 15M
               | people in US that are actively on it. That's a lot of
               | people.
        
               | bluSCALE4 wrote:
               | Really just meant it kills you if you plan on using it as
               | a lifelong solution. I don't have an obesity problem but
               | if I did, this is one of those drugs I'd journal about
               | daily to keep track of how it's affecting me.
        
               | tokioyoyo wrote:
               | Where is any source about it, other than "it just feels
               | wrong, people shouldn't cheat their way out of obesity"?
               | Sorry for being obtuse, but I have very close friends for
               | whom it changed their lives.
        
             | cyberax wrote:
             | > Bad depression was another side effect
             | 
             | What? Ozempic has been noted for its mild _anti_ depression
             | activity.
        
               | adgjlsfhk1 wrote:
               | both can be true. it can reduce depression in 60% of
               | people and increase it in 10%
        
           | andbberger wrote:
           | $$$
        
         | AlexandrB wrote:
         | K. But getting to a healthy weight by means of discipline and
         | self control has a ~1% success rate[1]. That's dismal.
         | 
         | I wouldn't blame anyone for choosing the drugs over dying
         | early.
         | 
         | [1] https://www.healthline.com/health-news/obese-people-have-
         | sli...
        
         | toast0 wrote:
         | If you find it hard to control your eating when you always feel
         | hungry, taking a drug to reduce your feelings of hunger _is_
         | self-control. It 's exactly looking at your body as a system
         | and controlling it.
         | 
         | Maybe you can titrate off the drug and in a perfect world, the
         | hunger signal doesn't come back on all the time; that'd be
         | great. Maybe, while on the drug, you've developed eating habits
         | that you can continue while off the drug, even though you feel
         | hungry all the time, again. Maybe, it's just too hard to ignore
         | the hunger signal, and you need the drug for a lifetime.
         | 
         | That's not to say these drugs are necessarily wonderful.
         | Previous generations of weight loss drugs came with nasty side
         | effects that weren't immediately apparent. Fen-Phen was a
         | wonder drug until it ruined people's heart valves. Stimulant
         | appetite supressants have issues because they're stimulants.
         | Cigarrettes have appetite supressant properties (not
         | surprising, nicotine is a stimulant), but they're cigarettes.
         | 
         | Personally, I don't have an overactive hunger signal; so when I
         | eat poorly and gain weight, it's on me. But other people I know
         | have a totally different experience with hunger. If your body
         | is telling you all the time that you need to eat, it's hard to
         | say no. Just like it's hard not to scratch when your skin is
         | itchy. I can resist itchyness sometimes, but when it's
         | constant, I'm going to scratch.
        
         | globular-toast wrote:
         | Yeah, I am sceptical, but we'll have to see how it pans out.
         | 
         | Vanishingly few people succeed in exercising discipline and
         | self-control long term. But obesity is caused by food addiction
         | and the idea is once you've kicked the addiction and got over
         | the withdrawal etc then it's gone and you no longer have to
         | fight it. I don't "exercise discipline" to stay thin. I just
         | don't eat copious amounts of junk food because I'm not addicted
         | to it.
         | 
         | So if the drugs are used to soften the withdrawal symptoms such
         | that people can learn to like real food and kick the addictive
         | crap then that's good. But if they're used as a magic pill with
         | no other lifestyle changes then I'm sure people will just go
         | back to what they were doing before once those pangs come back.
         | 
         | I'd still rather we went after the industry peddling the
         | addictive shit. We went after the cigarette companies. But food
         | companies seem untouchable.
        
       | dukeofdoom wrote:
       | If it causes cellular damage, it might be a big problem. "Some
       | studies indicate that only about 1% of heart cells are renewed
       | each year in younger people, dropping to about 0.5% by age 75.
       | This means that a significant portion of heart cells remain from
       | childhood into old age."
        
       | raverbashing wrote:
       | Keyword: "in mice"
       | 
       | Second gotcha: how much of the decrease is just attributed to the
       | lower mass of the subject after the weigh-loss treatment
       | 
       | Though it's one good reminder that "catabolism" and "anabolism"
       | are less selective than we wished to
        
       | Anotheroneagain wrote:
       | I've been warning people for a long time that the drug only fakes
       | the signal of fullness from the gut, and only makes you starve
       | yourself. It doesn't actually fix anything.
        
       | heisenbit wrote:
       | It may be worth considering that a heavier person needs a
       | stronger heart than a lighter one. The heavier weight also acts
       | as a constant load/training. Without some degree normalization we
       | won't know whether this is normal or concerning.
        
         | Etheryte wrote:
         | This is a very thoroughly studied phenomenon. The hearts of
         | obese people are generally more muscular as you say, but not in
         | a good way, so I wouldn't compare this to training. In
         | overweight people, the heart walls get thicker and the volume
         | of blood that the heart pushes out with each stroke is
         | decreased as a result. This means their heart needs to beat
         | faster to reach the right throughput and their heart is under
         | constant strain, kind of like having your car overrevved at all
         | times.
         | 
         | With exercise, the heart muscles grow in a different way, and
         | the volume of blood contained inside is not reduced. So without
         | looking at the heart itself, we can't even tell whether a lot
         | of muscle is good or bad, we also need to look at the rest of
         | the context.
        
           | ben7799 wrote:
           | I think doctors can figure out real quick which version of
           | heart enlargement you have.
           | 
           | The athletes heart is going to beat at 1/2-1/3 the rate at
           | rest compared to the obesity-enlarged heart and a stress test
           | is going to show the athletes upper heart rate limits are
           | much much higher.
        
             | Etheryte wrote:
             | This is pretty much exactly what I said?
        
       | lofaszvanitt wrote:
       | Erm, when you lose weight you usually lose muscle too. So
       | compared to people on a diet and people on ozempic, what's the
       | plus percentage of muscle loss?
        
       | crazygringo wrote:
       | I'm always so baffled by warnings about losing muscle when losing
       | weight.
       | 
       |  _Of course_ you do! If your body is tens of pounds lighter, then
       | you don 't _need_ the extra muscle to lug it around. This paper
       | is about reduction in heart muscle, and _of course_ your heart
       | doesn 't need to be as strong because there's less blood to pump
       | and less tissue to fuel.
       | 
       | When you gain weight, you also increase the muscles needed to
       | carry that weight around. If you see someone obese at the gym
       | doing the leg press, you may be astonished at how strong their
       | legs are. When you lose weight, you don't need that muscle
       | anymore.
       | 
       | Our bodies are really good at providing exactly the amount of
       | muscle we need for our daily activities (provided we eat
       | properly, i.e. sufficient protein), so it's entirely natural that
       | our muscles decrease as we lose weight, the same way they
       | increased when we gain weight. Muscles are expensive to keep
       | around when we don't need them.
       | 
       | Obviously, if you exercise, then you'll keep the muscles you need
       | for exercising.
       | 
       | But this notion that weight loss can somehow be a negative
       | because you'll lose muscle too, I don't know where it came from.
       | Yes you can lose muscle, but you never would have had that muscle
       | in the first place if you hadn't been overweight -- so it's not
       | something to worry about.
        
         | bArray wrote:
         | I wondered about exactly this.
         | 
         | The study is actually a published letter [1], and it doesn't
         | appear to account for this. Science Direct even published a
         | study about this in 2017 [2]:
         | 
         | > Weight loss, achieved through a calorie-reduced diet,
         | decreases both fat and fat-free (or lean body) mass. In persons
         | with normal weight, the contribution of fat-free mass loss
         | often exceeds 35% of total weight loss, and weight regain
         | promotes relatively more fat gain.
         | 
         | We already know how to reduce the effect of this, the person
         | simply needs to increase exercise as the weight is lost in
         | order to maintain lean muscle mass.
         | 
         | [1]
         | https://www.sciencedirect.com/science/article/pii/S2452302X2...
         | 
         | [2]
         | https://www.sciencedirect.com/science/article/pii/S216183132...
        
           | toxik wrote:
           | Meta comment here, but Science Direct is an aggregator, and
           | it doesn't make sense to talk about it as publishing.
           | Elsevier published the referenced work in the journal
           | "Advances in Nutrition", vol 8, issue 3, pp. 511-519.
        
         | antihero wrote:
         | What they need is to design some sort of mouse gym.
        
           | zenomadic wrote:
           | MouseLifts 5x5 + RAtkins diet
        
             | gonzo wrote:
             | "Gym rats" was already a thing.
        
         | halgir wrote:
         | I'm not qualified to interpret results, but this paragraph
         | stuck out to me:
         | 
         | > Using mice for the study, the researchers found that heart
         | muscle also decreased in both obese and lean mice. The systemic
         | effect observed in mice was then confirmed in cultured human
         | heart cells.
         | 
         | So it also happened for already lean mice (though no mention of
         | whether they still lost fat), and for cultured human heart
         | cells (so not a by-product of needing less muscle to pump blood
         | through a shrunken body).
        
         | ThinkBeat wrote:
         | Then a study concentrates no comparing muscle weight loss by
         | traditional dieting, that is a change in what someone eats, to
         | weight loss via drugs.
         | 
         | It is not immediately clear if the muscle loss happens faster
         | (probably) what the immediate impact of that is, and whether or
         | not you lose more muscle mass on one or the other.
        
         | codingdave wrote:
         | > Our bodies are really good at providing exactly the amount of
         | muscle we need for our daily activities
         | 
         | That is exactly the risk. Our bodies are really good at it. But
         | we are taking drugs that may change what our bodies do. Even a
         | small bit of extra heart muscle loss may push as below where
         | our bodies would have left us naturally. Is that dangerous? Are
         | there people who need to worry about it? How do we know whether
         | or not that should be a concern? It raises questions, and is
         | worthy of discussion, even if we do land at answers that say it
         | is an acceptable level of risk.
        
         | lee wrote:
         | From the article: "...explains this rate of muscle decline is
         | significantly higher than what is typically observed with
         | calorie-reduced diets or normal aging and could lead to a host
         | of long-term health issues..."
         | 
         | The warning isn't that you're losing muscle during weight-loss
         | with these drugs. It's that the ratio of muscle vs fat loss is
         | much greater with the drugs compared to traditional weight loss
         | methods.
         | 
         | It's been well studied that if you exercise and eat enough
         | protein while losing weight, you can retain more muscle.
         | 
         | Losing a lot of lean mass is incredibly detrimental to your
         | longevity and quality of life.
        
           | beejiu wrote:
           | Even amongst traditional calorie deficits, rapid weight loss
           | results in greater loss of muscle mass when compared to
           | gradual weight loss, even if you lose the same amount of mass
           | overall. I.e. you keep more muscle losing 0.5 lbs a week over
           | 40 weeks than 2 lbs a week over 10 weeks.
        
             | thefz wrote:
             | > Even amongst traditional calorie deficits, rapid weight
             | loss results in greater loss of muscle mass when compared
             | to gradual weight loss,
             | 
             | This does not make any sense. Why would the body prefer
             | anything over the most dense and available calorie store?
             | Protein in muscle gives shit calories per gram, it is hard
             | to build back and generally less available than fat: the
             | number one energy store, doing exactly what it does.
        
               | beejiu wrote:
               | I don't think anyone knows for sure, but I think the
               | prevailing theory is it being a survival mechanism.
               | 
               | When our ancestors faced famine, it makes sense for the
               | body to shed as much muscle as possible, since this
               | reduces the metabolic rate in the medium-long term.
               | 
               | Muscle is more metabolically active than fat. Although
               | fat can be used up for energy more readily, but muscle
               | takes more energy to maintain. Burning fat just to
               | maintain (unnecessary) muscle doesn't make sense in terms
               | of survival.
        
           | IG_Semmelweiss wrote:
           | >>>Losing a lot of lean mass is incredibly detrimental to
           | your longevity and quality of life.
           | 
           | While true, its also true that if you manage to lose
           | substantial fat in the process, it leads to longer and better
           | quality life
        
             | mathgeek wrote:
             | > it leads to longer and better quality life
             | 
             | This needs a slight change in wording or clarification,
             | depending on what you meant.
             | 
             | Losing substantial fat when overweight increases your
             | chance of a longer and better quality life than if you had
             | maintained high levels of fat. Losing substantial muscle in
             | that process reduces your chances of the same. It's
             | statistics and never guaranteed.
        
           | crazygringo wrote:
           | If I'm reading the study [1] correctly, that conclusion is
           | not warranted.
           | 
           | It appears that they fed the control group and treatment
           | group of mice lots of food to get them fat, then gave them
           | identical normal diets, and gave the treatment group
           | semaglutide.
           | 
           | The semaglutide group lost significantly more weight (fig
           | A.ii) than the control group, and _also_ lost heart muscle.
           | 
           | So it does not seem that they compared to an equivalent
           | amount of weight loss in mice, which is what I'd think you'd
           | need to do to come to the conclusion from the article
           | (actually, not just an equivalent amount of weight loss, but
           | also at the same rate).
           | 
           | [1] https://www.sciencedirect.com/science/article/pii/S245230
           | 2X2...
        
             | AuryGlenz wrote:
             | I guess perhaps the better conclusion would be that maybe
             | dosages should be adjusted so that people don't lose weight
             | too quickly?
        
           | cactca wrote:
           | Can you provide a single high quality (randomized) study
           | demonstrating GLP1 therapeutics are 'incredibly detrimental
           | to [your] longevity and quality of life'?
           | 
           | Consider the type of confounding that occurs in studies of
           | people losing a lot of lean mass: cachexia, restriction to
           | bed, famine.
           | 
           | Traditional weight loss methods have not shown the magnitude
           | of survival benefits wrt cardiovascular disease, joint pain,
           | diabetic complications. Exercise is wonderful, but as a
           | public health intervention it is not sufficient.
           | 
           | If anyone looks at the totality of the high quality GLP1
           | clinical evidence and concludes these drugs are going to
           | cause a net reduction in longevity and quality of life, then
           | they should step back and assess their process for evaluating
           | information.
        
             | watwut wrote:
             | Exercise is a public health intervention that actually
             | works in improving health. It may not work to create actual
             | weight loss, but it does improve things like blood pressure
             | regardless.
        
         | jmcgough wrote:
         | I'm always so baffled by people commenting without reading the
         | article first.
        
           | crazygringo wrote:
           | > _" Please don't comment on whether someone read an
           | article."_
           | 
           | https://news.ycombinator.com/newsguidelines.html
           | 
           | If you care to actually have a conversation about the
           | article, feel free to respond to some specifics I provided
           | here:
           | 
           | https://news.ycombinator.com/item?id=42204741
        
         | lm28469 wrote:
         | > Our bodies are really good at providing exactly the amount of
         | muscle we need for our daily activities
         | 
         | The problem is that the average joe's daily activity is
         | incompatible with an healthy muscle mass. After 30 if you don't
         | actively exercise you lose muscle mass, if you're obese, 50 and
         | starve yourself or take drugs that make you lose more muscles
         | than necessary you won't gain them back ever unless you do some
         | form of serious resistance training
         | 
         | https://hips.hearstapps.com/hmg-prod/images/triathlete-aging...
        
           | ben7799 wrote:
           | Some years ago there was a crazy science exhibit going around
           | museums in the US that had human cadavers preserved with some
           | plasticizing process where you could see different tissues.
           | They also had cross sections.
           | 
           | They actually had an exhibit showing the effects of obesity
           | on tissues. This was before fat acceptance became a thing.
           | That was really an eye opening exhibit showing shrunken
           | muscle tissue, shrunken hearts, shrunken/squeezed lungs,
           | etc.. in obese people.
           | 
           | Kind of opened my eyes as to how crazy the changes are.
        
             | verst wrote:
             | I believe you are thinking of 'Body Worlds' [1]
             | 
             | [1]: https://bodyworlds.com/
        
             | ceejayoz wrote:
             | You're describing it backwards.
             | 
             | Obesity tends to cause heart _enlargement_
             | (https://radiopaedia.org/articles/obesity-cardiomyopathy),
             | _larger_ muscles (as you 're doing essentially built-in
             | weight training just walking around), and organs don't tend
             | to shink; cross-sections show a pretty similar body cavity
             | (https://www.cultofweird.com/medical/human-body-slices/) -
             | the fat largely goes on top of it.
        
             | isk517 wrote:
             | It was a really great exhibit, watch a smoker regret his
             | life choices in real-time when given the chance to hold a
             | lung taken from a smoker.
        
         | paulpauper wrote:
         | _When you gain weight, you also increase the muscles needed to
         | carry that weight around. If you see someone obese at the gym
         | doing the leg press, you may be astonished at how strong their
         | legs are. When you lose weight, you don 't need that muscle
         | anymore._
         | 
         | Anyone can put up impressive #s on a leg pres. Try the bench
         | press instead. No one impressed by leg press.
         | 
         | In regard to the oft claim of obese people being stronger or
         | more muscular, not really. Studies show that obese people carry
         | only a tiny extra 'lean body mass' compared to non-obese people
         | when matched for height, age, and gender, and much of this
         | extra mass is organs, not muscle. Otherwise, the extra weight
         | is just water. Sometimes it is even less because obesity
         | impairs movement, leading to muscle loss due to inactivity.
         | 
         | If obese people seem strong it is because the fat reduces the
         | range of movement for certain lifts like the squat and bench
         | press, so it's possible for obese people to put up impressive
         | numbers owing to having to move the weight less distance. Same
         | for pushing movements, e.g. linemen, as being heavier means
         | more kinetic energy, but this is not the same as being stronger
         | in the sense of more muscle output. This is why obese people
         | are not that impressive at arm curls or grip strength relative
         | to weight, but wirey guys can curl a lot relative to weight or
         | have a lot of grip strength. An obvious example of this is
         | overweight women having worse grip strength compared to men;
         | the extra fat does nothing.
        
         | bityard wrote:
         | I don't mean to target your comment specifically because it's
         | obvious you know the difference, but I'm continually annoyed by
         | the conflation of fat and muscle as "weight," even by medical
         | professionals who should know better.
         | 
         | We should not be talking about losing "losing weight" as a
         | substitute for saying "losing fat," which is what most people
         | mean. Likewise, when people say they want to "gain weight",
         | they almost always mean they want to "gain muscle."
         | 
         | Why does this matter? Trying to manage one's health or fitness
         | as "weight" gives (most) people the wrong idea about what their
         | weight number represents, and what to do to improve their level
         | of fitness and dial in on the anatomically appropriate amount
         | of body fat. As an example, it's possible (although admittedly
         | unlikely) for one to work hard to gain muscle and strength
         | while reducing body fat and stay exactly the same weight the
         | whole time. Their overall health, fitness, and longevity will
         | be significantly improved but pop fitness will tell them that
         | they haven't made any progress at all.
        
           | watwut wrote:
           | The other thing is conflation between health and fitness. If
           | you are below overweight range, no matter where you are,
           | loosing additional fat is unlikely to make you healthier.
           | 
           | At some level of fat, which is actually more then "thin", you
           | are perfectly fine. Further weight loss is about aesthetic or
           | athletic performance, but has zero effect on health or even
           | slight negative estimated health effect.
        
           | s1artibartfast wrote:
           | That doesn't strike me as a real problem.
           | 
           | Everybody already understands that "losing weight" means
           | losing fat, not muscle. They don't leave the doctors office
           | after a weight warning thinking they need to stop going to
           | the gym.
           | 
           | Likewise, nobody is scared of gaining muscle because they
           | think it will be bad for their health.
        
         | shaky-carrousel wrote:
         | And obviously the heart is going to reduce muscle now that it
         | doesn't need to pump blood through heaps of fat.
        
         | thisislife2 wrote:
         | > _When you gain weight, you also increase the muscles needed
         | to carry that weight around._
         | 
         | I can't figure out how relevant that is. From what I've seen of
         | obese people they always struggle with limited mobility, which
         | often only improves with physiotherapy (or other forms of
         | exercises). Sumo wrestlers are huge but can move faster than an
         | equivalent obese person because (I assume) they have stronger
         | muscles due to their regular regimented training and diet. Does
         | this mean they have more muscle mass than fat compared to an
         | equivalent obese person? Does more muscle mass indicate
         | stronger muscles?
        
           | cthalupa wrote:
           | Well, based on my DEXA scan from before I started on
           | tirzepatide, if I had dropped to 20% BF with my starting LBM,
           | I would have been in close to the best shape of my life. I
           | certainly have a lot of extra muscle in my legs from carrying
           | my fat ass around.
           | 
           | > Does more muscle mass indicate stronger muscles?
           | 
           | Yes. Strength for specific movements involves CNS adaptation,
           | but if you look at the top tier of powerlifters, ranking them
           | within a weight category by MRI muscle mass would produce
           | basically identical results to their actual rankings.
        
       | bArray wrote:
       | To reply to a now deleted comment about weight loss:
       | 
       | You will still lose "muscle", and some of that will be in the fat
       | embedded into the muscle.
       | 
       | I would recommend checking out some of the learnings from the
       | keto diet. You may or may not subscribe to it, but they had to
       | very carefully tread these lines when the body was essentially in
       | starvation mode. A few things I know of:
       | 
       | 1. You have to maintain a certain amount of protein intake (~10%
       | to ~20%) to prevent your body burning lean muscle mass.
       | 
       | 2. Too much protein gets converted into sugars, these in turn are
       | easily stored as fats.
       | 
       | 3. Maintain exercise, use it or lose it.
       | 
       | 4. Don't over-exercise. "Exercise flu" results in limited
       | performance and muscle loss through gluconeogenesis. You break
       | down muscle and convert it to energy due to lack of
       | carbohydrates.
        
       | kozikow wrote:
       | I used Ozempic for couple months. I lost 25kg over 6 months
       | (120kg -> 95kg).
       | 
       | I gained muscle, as I started weightlifting (modified 5x5 program
       | 3-4 times a week) and was supplementing with protein isolate
       | (about 50g a day).
       | 
       | My subjective feeling is that even if "Ozempic makes you lose
       | muscle faster than the same caloric deficit without it" is true,
       | this effect is very small.
       | 
       | Vast majority of muscle loss comes from no resistance exercise,
       | low protein, much faster weight loss than possible "naturally".
        
       | lenerdenator wrote:
       | I was wondering when the other shoe would drop.
       | 
       | These drugs are turning into a band-aid on the fact that it's
       | more profitable to sell addictive, high-calorie foods in the US
       | than foods that promote long-term health.
       | 
       | We'll decay people's heart muscles before we put a tax on
       | unhealthy food to help fund Medicare and Medicaid.
        
         | autoexec wrote:
         | > These drugs are turning into a band-aid on the fact that it's
         | more profitable to sell addictive, high-calorie foods in the US
         | than foods that promote long-term health.
         | 
         | The food is most of it, but it also doesn't help that our
         | environments and society don't allow for as much mobility and
         | exercise as our bodies evolved to expect. You can't force
         | people to sit in a chair for 8-10+ hours a day staring at
         | screens and then be surprised when a bunch of them are
         | unhealthy. It's more profitable if you ignore people's health
         | and keep them in place and working on task without interruption
         | though so here we are.
        
         | omegaworks wrote:
         | > a tax on unhealthy food to help fund Medicare and Medicaid.
         | 
         | Fully 13% of the population lives in an area with restricted
         | access to grocery stores[1]. Couple that with car-centric anti-
         | pedestrian development[2] and you have a definitively societal
         | problem. Addressing that with taxes on the individual will not
         | address these causes, only shift the burden further onto the
         | poor.
         | 
         | 1. https://www.aecf.org/blog/communities-with-limited-food-
         | acce...
         | 
         | 2. https://www.economist.com/finance-and-
         | economics/2023/11/09/i...
        
           | lenerdenator wrote:
           | Then fund the stores through the Medicaid funds generated.
           | 
           | Gotta start somewhere.
        
         | thefz wrote:
         | > These drugs are turning into a band-aid on the fact that it's
         | more profitable to sell addictive, high-calorie foods in the US
         | than foods that promote long-term health.
         | 
         | What I don't understand about these drugs is:
         | 
         | Ok, you are taking the medicine to lose weight, but are you
         | eating the same shit as before in the process?
         | 
         | The answer is always "pfft no, I am going to eat healthier"
         | 
         | So why don't you just eat healthier now?
        
         | paulpauper wrote:
         | given the low success rates of dieting, around 0 percent,
         | gimmie the Band-Aid
        
       | mensetmanusman wrote:
       | Ozempic can use their cash to start an exoskeleton division.
        
       | msarrel wrote:
       | This study is garbage. You can only trust what the companies that
       | profit from the drugs publish.
        
       | brodouevencode wrote:
       | There are no free lunches in nature.
        
       | mslack616 wrote:
       | I'm a fan of open bodybuilding, so I've been following the
       | Ozempic usage trend for a while now. Given the findings on this
       | study, I can see how it may become an essential drug on
       | bodybuilders stacks.
       | 
       | Hunger reduction + supraphysiological muscle gain from steroids
       | and growth hormone - (heart) muscle reduction = win/win?
       | 
       | Heart problems are one (of many) of the main problems these guys
       | face, so I won't be surprised if Ozempic is used to kind of
       | "balance" the effects of other drugs.
        
         | adbge wrote:
         | Another potential synergy for bodybuilding is that these GLP1
         | drugs ought to help maintain insulin sensitivity in the face of
         | supraphysiological doses of HGH. Specifically I have the
         | impression that tirzepatide and retrarutide are more effective
         | here than semaglutide, as they possess additional mechanisms of
         | aiding glucose disposal.
        
       | csours wrote:
       | These comments make me very sad about scientific literacy. 342
       | comments and 'control' appears 12 times (before this comment).
       | 
       | Without proper control you could also say that weight loss is
       | associated with loss of heart muscle mass.
        
       | pogue wrote:
       | It would seem wise to potentially add a low dosed anabolic
       | androgenic steroid like Anavar (Oxandrolone) [1] during a course
       | of Ozempic. This would help keep skeletal muscle in tact during a
       | calorie deficient period. A low dose wouldn't be expected to
       | cause much, if any, side effects. But it's something that would
       | be best put through rigorous studies.
       | 
       | But bodybuilders have been using tricks like these for decades
       | (obviously at much more ridiculously high amounts) that work
       | quite successfully for this exact purpose.
       | 
       | [1] https://en.wikipedia.org/wiki/Oxandrolone
        
         | heroiccocoa wrote:
         | There are non-steroidal OTC supplements that are specifically
         | anti-catabolic instead of anabolic like HMB[1], a metabolite of
         | the amino acid leucine, and also widely used in the fitness
         | community. Personally I have no idea which is preferable
         | though, or whether anti-catabolism is something actually
         | positive, as we know the importance of autophagy of senescent
         | cells for longevity. Most of the literature I read suggests the
         | less growth signalling, the better longevity, with the only
         | exception being the frail elderly.
         | 
         | [1]
         | https://en.wikipedia.org/wiki/%CE%92-Hydroxy_%CE%B2-methylbu...
        
           | cthalupa wrote:
           | Most data on HMB shows that it is effective in preserving
           | muscle mass in people with cancer cachexia or the eldery,
           | results are generally not great for those without specific
           | diseases or of younger age.
           | 
           | I'm still taking it because it's cheap and I figure I might
           | as well, but anavar is likely significantly more effective.
        
             | pogue wrote:
             | Yes, HMB is another compound that would be potentially very
             | beneficial during catabolic times such as extreme weight
             | loss. The typical dosage would be 3g/day.
             | 
             | Examine has done excellent write ups on all the research
             | related to it, which can be found below. They recently
             | paywalled the bulk of it, but it's still on the wayback.
             | 
             | https://web.archive.org/web/20240310004421/https://examine.
             | c...
        
         | notesinthefield wrote:
         | I have done exactly this. I stack semaglutide with ~ 1 ml
         | testosterone and .35 ml of anavar weekly. I've transitioned out
         | of regularly competing in powerlifting to running and yoga
         | everyday. 47lbs down in 5 months and havent felt this good
         | since college.
        
           | pogue wrote:
           | Can you tell if you're retaining muscle with that
           | combination? Is this a doctor prescribed protocol or a DIY
           | stack?
        
             | notesinthefield wrote:
             | I have had three major bouts of weightloss so I can say
             | with some confidence im retaining muscle in my lower body
             | (because of the return to running) but have lost a lot in
             | my chest and back from the significant reduction in heavy
             | lifting but the muscle definition is better. This is almost
             | exactly what we expected to happen and yes, Im working with
             | an actual sports focused md. Insurance costs for HRT and
             | wegovy were through the roof.
        
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