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.
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.
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.
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.
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).
> 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
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.
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).
> 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.
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.
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.
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.
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.
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.
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.
> 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?
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.
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.
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.
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.
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/
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.
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.
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.
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.
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.
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.
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.
> 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.
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.
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.
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.
> 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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
> 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.
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.
Meanwhile I’ve been on ozempic since 2021 and have lost significant muscle mass despite gaining 50 pounds (the drug helps with my diabetes but does nothing to my appetite).
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)
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.
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.
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.
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.
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.
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.
C57BL/6 – the canonical inbred fully homozygous mouse that unfortunately is used as the “HeLa cell” of almost all experimental murine biomedical research. I understand the reason this happened, but there is no excuse in 2024 to use just one genome (and an inbred one at that) to test translational relevance.
Consider this work a pilot worth testing in NZO, DBA, A, C3H and BALB strains and some F1 hybrids. Whatever the results they should have good generality to mice in general.
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.
Yes, you are right, but ideally a team should test several genetic backgrounds of mice. Almost all cancer treatments have some negative effects. It is crucial to know what genetic and exposure variables to avoid to maximize therapeutic benefits.
Cadmium in some strains of mice is highly toxic to male testes. But if, as in the C57BL/6J strain, you have a “lucky” transporter mutation, then no problems at all. This kind of variability has been known since the turn A. Garrod in the early 1900s. And ignored by many.
Here is the data on the cadmium example I just mentioned:
Readit News
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.
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.
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.
While true, its also true that if you manage to lose substantial fat in the process, it leads to longer and better quality life
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/S2452302X2...
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...
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.
> 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).
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.
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...
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.
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.
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.
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.
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?
> 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.
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.
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
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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.
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.
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/
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This isn’t a surprise unless people ignored reading about the drugs before taking it and ignored the doctors.
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.
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.
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.
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HFCS consumption (along with added sugar consumption in general) peaked in 2000 and declined steadily until 2020: https://news.ycombinator.com/item?id=38094768
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.
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.
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.
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.
There is significant heart remodeling after even things like major amputations because of the changing demands on the heart.
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.
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.
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.
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.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5946208/
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.
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.
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.
https://scholar.google.com/scholar?as_ylo=2024&q=glp+1+thyro...
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.
I thought its only approved at standard 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.
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.
It worked! Kind of. The first few days after every dose it had the opposite intended effect so it wasn’t worth it.
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.
C57BL/6 – the canonical inbred fully homozygous mouse that unfortunately is used as the “HeLa cell” of almost all experimental murine biomedical research. I understand the reason this happened, but there is no excuse in 2024 to use just one genome (and an inbred one at that) to test translational relevance.
Consider this work a pilot worth testing in NZO, DBA, A, C3H and BALB strains and some F1 hybrids. Whatever the results they should have good generality to mice in general.
Cadmium in some strains of mice is highly toxic to male testes. But if, as in the C57BL/6J strain, you have a “lucky” transporter mutation, then no problems at all. This kind of variability has been known since the turn A. Garrod in the early 1900s. And ignored by many.
Here is the data on the cadmium example I just mentioned:
https://genenetwork.org/show_trait?trait_id=13035&dataset=BX...