[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| whose authorization has since been revoked.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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