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.
> 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.
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.
Could just be its for winter where you don't need to move much for a few months, otherwise normally you need that muscle to gather food even when starving, someone has to gather it and it wont be someone who shed most of their muscle.
Whether or not it makes any sense to you, it's not a matter of any scientific debate - being in a deficit puts you in a catabolic state where the body will break down muscle mass for energy. It does it less if you have lots of protein and are providing frequent muscle stimulus.
These are just a tiny subset of the studies done - google scholar can find you many dozens more, if you desire. And, of course, the fact that these studies exist it all necessarily implies that you lose muscle mass when in energy deficit, as you will see in the control groups for them.
The body breaks down some muscle tissue beacause it can make glucose from by gluconeogenesis. You need about at least 80 g glucose or so per day (brain), even if you do not eat any carbohydrates. The body cannot make glucose from fat.
> Because the body can only extract so much energy per minute from all of the fat in your body.
Was curious about this, went hunting for some rough data, this [0] suggests every kilogram of fat held can be drawn down at ~70 food-calories per day.
So someone with 25% body fat weighting 100kg (~220lb) could draw 1750 food calories per day, which strikes me as pretty ample unless they're also adding a bunch of physical activity.
> which strikes me as pretty ample unless they're also adding a bunch of physical activity.
It seems likely we've evolved to reduce energy expenditure in other ways when we regularly induce physical activity, too. Walk 20,000 steps or spend a couple of hours on the treadmill? Your body finds ways to reduce your energy expenditure elsewhere.
It's not going to be linear though. 1750 cal per day ~= 73 cal per hour. If, for example, you're already in a calorie deficit for the day, and then do a nice hour long workout (or demanding mental work), you're going to burn some muscle.
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.
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.
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.
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).
In its trials, Ozempic was combined with intervention/guidance from nutritionists and fitness advisors, and doctors are supposed to reproduce this by referring patients. You can't do that with mice.
I think if I were taking Ozempic I would ask my doctor to halve the rate of progression to higher doses to make the whole process easier to manage, not just managing muscle loss but also the whole of life impact. The official protocol is very "crash diet" in style.
Anyone thinking of taking Ozempic should be aware that many people abandon the drug within the first two years, due to too much nausea, diarrhoea and cost.
> 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/
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.
Natural bodybuilders 100% go through bulking and cutting cycles
No, they don't. They simply eat enough to continue muscle growth and attempt to shed fat before a competition. Any non-competitor doing this is just engaging in quasi-religious nonsense or rationalizing a bad diet.
Bulking and cutting have meaning, and we're not going to turn it into any caloric surplus vs deficit.
Well, I think you should go let the whole natural bodybuilding community that they're doing it wrong, as well all of the PhDs specializing in exercise science, including both the naturals and not.
You need to be in a caloric surplus to efficiently build muscle mass regardless of whether or not you're natural. I'm honestly confused how this is even an argument we're having. No one is saying you need to eat in 5000 calorie surplus as a natural, but everyone still refers to the period where you are in a caloric surplus as a bulk and a period where you are in a caloric deficit as a cut. This is not and has never been restricted to people on gear.
Jeff Nippard is a YouTuber, natural body building pro and record holder, and he takes about his bulk/cut cycle a lot. I don't know how you can so confidently say "No they don't" when it's literally impossible for you to make such a blanket statement.
I don't even have a dog in this fight, but if someone cited a YouTuber—particularly as their first qualifying attribute—as an authoritative source, I'd just laugh.
While some YouTubers may be correct about the things they talk about, or may even be doctors or researchers, I think we're in a pretty sus world if disputes about factual or even anecdotal information can come down to whether someone's watching and getting recommended the same content on a video site designed to exploit chronic viewing habits.
If your crowd does differently, just cite that, if they don't, speak from a place of speculation if that's what you'd like like them to do, because that's basically what watching YouTube does for a person.
I wouldn't cite him as a YouTuber first, but Jeff Nippard is a a reputable source. He's competed and won in natural bodybuilding competitions, set powerlifting records for his province, partnered with PhDs in the field for studies on hypertrophy (and is one of the people leading the charge on 'lengthened partials' as being one of the most efficient ways to build muscle, which the research does agree with.)
He seems like a reputable guy, and everything you mentioned is all probably best case scenario for someone who's not in a regulated profession or who's job it is to produce credible research. I'm not disputing that or him or any of his records (though incidentally it seems like his 1st place wins were in provinces with the fewest people), and I tend to enjoy his content. He also seems to have a bachelor's in biochem, also great, I don't.
I also like a bunch of other channels and have derived what feels like good information from them, I'd recommend them on that basis to people I felt would find it useful or entertaining. Just because I wouldn't cite them as an authoritative source doesn't mean it's a strike against them, it just means I don't think it's fair to tell someone they're wrong because my favorite YouTuber, even if they seem credible, well-natured, and are worth recommending, says X.
There are plenty out there doing good by their viewers and I love that, especially Canadian ones, but it's insufficient for being hyperbolic, imo, about what's impossible to make a claim about, and I don't think arguments from apparent authority are to be encouraged anyway.
In some cases, I've checked the advice of other MD content producers against real practitioners, and they've gave me the thumbs up in terms of credibility, and that obviously changes the vibe a bit, but still I'd hesitate to go too far with that, there's a lot people will do for money and attention.
What an utterly ridiculous extrapolation. These comments are exhausting. Bulking and cutting have a specific meaning, and it doesn't just mean eating at a sufficient caloric surplus to sustain muscle growth. That's simply called eating enough.
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.
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.
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.
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.
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)
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.
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).
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.
> 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.
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.
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.
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.
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).
They are 75% carbs. Don't miss the point in your focus on one thing that I said. Replace it with sweet potatoes, carrots, and any other health promoting vegetable that Americans don't eat (and when they do, without slathering in sugar/fat).
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.
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.
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.
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.
> 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.
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.
>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.
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.
> 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.
> 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.
> 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.
> 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.
What does base metabolic variability have to do with using CICO to modify your weight? The intake is easy to measure. The outtake is empirically knowable by change in weight over time. It’s really that simple.
> What does base metabolic variability have to do with using CICO to modify your weight?
Metabolic syndrom is characterised by the basal metabolic rate reducing in response to reduced calorie intake or increased caloric expenditure. In most of us this is good. It gets the immune system to quit mucking around, for instance. In the obese, however, it can sometimes mean their bodies will literally stop doing essential shit before it will concede and begin burning fat. It will then do everything it can to refill those fat cells.
You can model a human thermodynamically. But to my knowledge, this isn't used in medicine because it isn't practical. (I'm saying this, by the way, as someone who can eat anything and laze around and not gain weight because my metabolism is tuned the other way.)
CICO reminds me of something we do in finance: burying the complexity in a magic variable. For CICO, it's the CO. Because if you decompose it into its active and inactive components. Exercise is the former. But the latter absolutely dominates that term.
> In the obese, however, it can sometimes mean their bodies will literally stop doing essential shit before it will concede and begin burning fat. It will then do everything it can to refill those fat cells.
I’m sure there’s some people that this might apply to, but I suspect it’s a much (much) smaller subset than people that are actually obese. For the rest, just decrease your intake until you lose weight. Not much else.
> You can model a human thermodynamically. But to my knowledge, this isn't used in medicine because it isn't practical. (I'm saying this, by the way, as someone who can eat anything and laze around and not gain weight because my metabolism is tuned the other way.)
Exactly what variables are missing then? We can agree that exercise, although certainly burns some calories, is not really the lever you want to pull if you actually want to lose weight by itself. What other variable besides changing how much food you eat would you suggest?
That's the point of the discussion, imo. It seems to be an area of research. There's a lot of questions in my view. Why are people so addicted to food? Why do some models of caloric restriction not work as well as they should? How do we embed behavioral change, or do some of these people just have to be in misery for the rest of their lives?
It's not a profound statement to say if you starve in a desert you'll lose weight. The question is how we can apply this to real, normal people. Or if it's even possible in a food-weaponized world.
My view is that we're in the realm of addiction more so than simply answering "how" they mechanically lose weight. This is a public health crisis, one we need to be open to exploring.
Again, food addiction and satiety is a different question than if CICO works. If you can't stop eating and cram too many calories because you eat too many... burgers and potato chips or whatever, that has nothing to do with if CICO works. I have yet to see evidence that shows that caloric restriction if properly, truly controlled, does not result in weight loss for the vast, vast majority of obese individuals. People are notoriously bad at estimating calories and knowing how much they eat, so any study that is self-reported is inherently going to be problematic.
Should we do more research to find if anything anything specific that may be causing overeating or food non-satiety? Sure. Is the answer likely to be something that is essentially 'tastier food is easier to overeat, and tastier food is much more available than it used to be'? I suspect that is the likely conclusion.
I think GLP1 agonists are a great tool to be used to create that so-called 'willpower' to stop overeating (or, an easy way to reduce food noise, whatever you want to call it). The next step is figuring out how, as a society, we make it easier for folks to make that lifestyle change without a constant stream of 'willpower drugs' for the rest of their life.
> Again, food addiction and satiety is a different question than if CICO works.
Yes, and again - as i said previously. No one is questioning if CICO works. That's like if questioning if physics works. No one is doing that. The laws of the universe are still intact. Talking about humans is the constructive conversion most people are having.
> No one is questioning if CICO works. That's like if questioning if physics works. No one is doing that. The laws of the universe are still intact.
Other people are, in fact, questioning CICO. Look at the other commenter talking about base metabolism changes.
To put an analogy to this:
Gambling addicts often lose lots of money at casinos. The behaviors that lead to them being addicted to gambling are in many ways likely equivalent to overeating problems. Nobody asks 'why are gambling addicts losing money?' because we know the reason (casinos have the house edge... you always lose on aggregate). And yet, with food, people consistently ask the question 'why are people so obese?' as if the answer isn't very obvious: they're eating too much food. It's purely as simple as that. The behaviors that lead to eating too much aren't nearly as focused on, in my opinion. Much time is spent on 'the kinds of foods eaten' and how specific things are bad for you, which is essentially like arguing that people should play more blackjack and less roulette or something.
> Other people are, in fact, questioning CICO. Look at the other commenter talking about base metabolism changes.
I disagree. CICO is fundamental physics. Just because metabolism changes does not mean you can produce more energy than you take in. CICO always applies, and it's so 'duh' that it's nearly pointless to discuss in my mind.
Their points about metabolism changes is that the details matter. Finding a way to break the cycle will yield more gains with the population than telling people to starve in a desert.
Metabolism changes are metabolism changes. What does the food you eat have anything to do with that, in practice? As far as I can tell, the mix of carbs/fat/protein has little to do with how much your body “compensates” from a surplus/deficit. If you don’t meaningfully have control over that, the only other real lever is how many calories you eat. Finding a way to lower calories without satiety problems or food noise issues ultimately is the solution. Some people do it via lots of low caloric foods (veg, mainly) that still have high satiety. Some people do it with Ozempic. Some people just aren’t bothered nearly as much by a caloric deficit no matter what they eat.
> 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.
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.
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 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.
> 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.
> 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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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:
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!
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.
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.
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.
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?
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.
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.
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.
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.
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.
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.
>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.
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.
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.
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.
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.
> 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.
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.
“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.
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.
> 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.
> 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.
> 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"
I used to be you - in most of my 20s, I found it very easy to just eat well, east less, etc. It didn't take any willpower on my part to be fit. It was trivial. I didn't understand why fat people didn't just do the same things I was doing. I thought they had to want to be fat!
Then I got busy with other things, I had less and less free time, fast food, etc. got more and more convenient. Then the pandemic happened and I started just ordering uber eats twice a day. And suddenly I realized "holy shit, I'm fucking fat."
And then I tried to go back to my earlier habits, and it was hard. Things that took zero willpower on my part suddenly meant spending a significant portion of my day fighting different urges.
Was it within my power to do so? Sure, in theory. Everyone, given no other task to do but focus their willpower on just not eating too much, could likely eat healthier and lose weight. But that's not reality, it's difficult, and it ends up slipping down the priority list behind a dozen or two other things.
But on tirzepatide, my relationship with food nearly immediately reverted back to how it was when I was younger.
The fact of the matter is, America has a huge amount of obese people that know they shouldn't be and know in theory that fixing their diet and exercising would resolve their issues. And yet they still are fat. Very very very few of them want to be that way. And the reason is it is hard to just eat healthier when you have that level of food craving
I was referring to the portion around thinking people should just eat healthier and giving context, as well as explaining why that thinking is flawed for many people.
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.
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."
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.
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.
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.
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.
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.
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.
You might consider doing some body fat vs muscle ratio comparison tests. There are 3 methods that give pretty good results. DEXA, Bod Pod & Hydrostatic weighing. I never investigated it much, but I had a buddy who tried all three & felt hydrostatic was the best and most affordable.
I don't know if these are the best resources, I only gave them a cursory glance. The summary does a good job.
Oh Ive done dexa’s before, I mostly dont care about hard body comp numbers anymore. Part of this latest “journey” is separating my identity from the “stats” of my body, because I was defined by them for so long. I want to spend my time feeling and looking good now.
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.
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.
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".
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.
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.
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
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.
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.
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].
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
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.
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.
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.
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.
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.
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 μg/kg/d for 21 days." That could be vaguely reasonable -- human doses range from, idk, ~36 to ~200 μg/kg/d (2.5mg/week to 15mg/week at ~100kg).
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.
> 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.
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.
> 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.
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.
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.
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.
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.
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.
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.
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.
>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.
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).
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.
>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.
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.
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.
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).
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.
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.
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.
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.
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"
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.
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.
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.
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.
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.
For me my cravings shifted from cookies/candy/ice cream to craving food that actually does something for my training, like a real meal.
Also for me if I go to crossfit after workday ends I don't get cravings the rest of that day. If anything I want to go to sleep instead of eating candy in front of the TV.
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.
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.
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.
> 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.
> 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.
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.
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.
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.
> 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.
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.
The point is that there is a big difference between depleting the store of glycogen, which can reliably be refilled in about 2 hours and the body's disassembling half the muscle mass, which takes many months to build back up if you even can build it back up to the original mass (unlikely if you are old).
No one is disputing that you can restore glycogen or water weight quickly.
But the issue is all of the studies I have looked at look at total FFM which does include the loss there. If you are on these GLP-1s there is water weight you are going to lose and keep off while on them due to the anti-inflammation effects, etc., and that water weight is going to be part of their calculations of FFM that has been lost.
> 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.
> 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.
> 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.
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!
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.
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.
> 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.
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.
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.
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.
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.
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.
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)
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.
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.
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.
> 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.
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.
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.
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.
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.
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.
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.
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.
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?
>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.
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.
> 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?
> 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.
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.
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)
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.)
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.
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?
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.
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)
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.
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.
> 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.
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.
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.
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.
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.
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.
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
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.
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)
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.
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)
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.
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.
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?
"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.
> 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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
"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.
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.
> 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".
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.
> 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.
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.
Could just be its for winter where you don't need to move much for a few months, otherwise normally you need that muscle to gather food even when starving, someone has to gather it and it wont be someone who shed most of their muscle.
Whether or not it makes any sense to you, it's not a matter of any scientific debate - being in a deficit puts you in a catabolic state where the body will break down muscle mass for energy. It does it less if you have lots of protein and are providing frequent muscle stimulus.
Source?
For protein intake helping decrease this: https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fj.13-...
https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.13...
https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.14...
https://www.sciencedirect.com/science/article/pii/S216183132...
https://www.mdpi.com/2072-6643/12/8/2457
For weight lifting helping decrease this: https://www.mdpi.com/2072-6643/11/11/2824
https://journals.physiology.org/doi/full/10.1152/japplphysio...
https://link.springer.com/article/10.1007/s00726-013-1506-0
https://journals.physiology.org/doi/full/10.1152/ajpendo.005...
https://onlinelibrary.wiley.com/doi/abs/10.1002/mus.21780
https://journals.physiology.org/doi/full/10.1152/ajpregu.004...
https://www.mdpi.com/2072-6643/10/4/423
These are just a tiny subset of the studies done - google scholar can find you many dozens more, if you desire. And, of course, the fact that these studies exist it all necessarily implies that you lose muscle mass when in energy deficit, as you will see in the control groups for them.
(Not a doctor) My understanding is that it is more rapid to extract energy from muscle than from fat.
The body breaks down some muscle tissue beacause it can make glucose from by gluconeogenesis. You need about at least 80 g glucose or so per day (brain), even if you do not eat any carbohydrates. The body cannot make glucose from fat.
Because the body can only extract so much energy per minute from all of the fat in your body. If that's not enough, muscle is used, etc.
> Because the body can only extract so much energy per minute from all of the fat in your body.
Was curious about this, went hunting for some rough data, this [0] suggests every kilogram of fat held can be drawn down at ~70 food-calories per day.
So someone with 25% body fat weighting 100kg (~220lb) could draw 1750 food calories per day, which strikes me as pretty ample unless they're also adding a bunch of physical activity.
[0] https://pubmed.ncbi.nlm.nih.gov/15615615/
> which strikes me as pretty ample unless they're also adding a bunch of physical activity.
It seems likely we've evolved to reduce energy expenditure in other ways when we regularly induce physical activity, too. Walk 20,000 steps or spend a couple of hours on the treadmill? Your body finds ways to reduce your energy expenditure elsewhere.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4803033/
It's not going to be linear though. 1750 cal per day ~= 73 cal per hour. If, for example, you're already in a calorie deficit for the day, and then do a nice hour long workout (or demanding mental work), you're going to burn some muscle.
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.
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.
>>>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
> 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.
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/S2452302X2...
I guess perhaps the better conclusion would be that maybe dosages should be adjusted so that people don’t lose weight too quickly?
In its trials, Ozempic was combined with intervention/guidance from nutritionists and fitness advisors, and doctors are supposed to reproduce this by referring patients. You can't do that with mice.
I think if I were taking Ozempic I would ask my doctor to halve the rate of progression to higher doses to make the whole process easier to manage, not just managing muscle loss but also the whole of life impact. The official protocol is very "crash diet" in style.
Anyone thinking of taking Ozempic should be aware that many people abandon the drug within the first two years, due to too much nausea, diarrhoea and cost.
> 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...
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.
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.
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.
I believe you are thinking of 'Body Worlds' [1]
[1]: https://bodyworlds.com/
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.
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...
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.
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.
> 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.
And obviously the heart is going to reduce muscle now that it doesn't need to pump blood through heaps of fat.
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.
What they need is to design some sort of mouse gym.
MouseLifts 5x5 + RAtkins diet
"Gym rats" was already a thing.
I'm always so baffled by people commenting without reading the article first.
> "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
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/
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.
Natural bodybuilders 100% go through bulking and cutting cycles
No, they don't. They simply eat enough to continue muscle growth and attempt to shed fat before a competition. Any non-competitor doing this is just engaging in quasi-religious nonsense or rationalizing a bad diet.
Bulking and cutting have meaning, and we're not going to turn it into any caloric surplus vs deficit.
Well, I think you should go let the whole natural bodybuilding community that they're doing it wrong, as well all of the PhDs specializing in exercise science, including both the naturals and not.
https://www.youtube.com/watch?v=eCpeRdUkegE can walk you through a handful of the latest studies.
You need to be in a caloric surplus to efficiently build muscle mass regardless of whether or not you're natural. I'm honestly confused how this is even an argument we're having. No one is saying you need to eat in 5000 calorie surplus as a natural, but everyone still refers to the period where you are in a caloric surplus as a bulk and a period where you are in a caloric deficit as a cut. This is not and has never been restricted to people on gear.
Jeff Nippard is a YouTuber, natural body building pro and record holder, and he takes about his bulk/cut cycle a lot. I don't know how you can so confidently say "No they don't" when it's literally impossible for you to make such a blanket statement.
I don't even have a dog in this fight, but if someone cited a YouTuber—particularly as their first qualifying attribute—as an authoritative source, I'd just laugh.
While some YouTubers may be correct about the things they talk about, or may even be doctors or researchers, I think we're in a pretty sus world if disputes about factual or even anecdotal information can come down to whether someone's watching and getting recommended the same content on a video site designed to exploit chronic viewing habits.
If your crowd does differently, just cite that, if they don't, speak from a place of speculation if that's what you'd like like them to do, because that's basically what watching YouTube does for a person.
I wouldn't cite him as a YouTuber first, but Jeff Nippard is a a reputable source. He's competed and won in natural bodybuilding competitions, set powerlifting records for his province, partnered with PhDs in the field for studies on hypertrophy (and is one of the people leading the charge on 'lengthened partials' as being one of the most efficient ways to build muscle, which the research does agree with.)
But yes, he is also popular on youtube.
He seems like a reputable guy, and everything you mentioned is all probably best case scenario for someone who's not in a regulated profession or who's job it is to produce credible research. I'm not disputing that or him or any of his records (though incidentally it seems like his 1st place wins were in provinces with the fewest people), and I tend to enjoy his content. He also seems to have a bachelor's in biochem, also great, I don't.
I also like a bunch of other channels and have derived what feels like good information from them, I'd recommend them on that basis to people I felt would find it useful or entertaining. Just because I wouldn't cite them as an authoritative source doesn't mean it's a strike against them, it just means I don't think it's fair to tell someone they're wrong because my favorite YouTuber, even if they seem credible, well-natured, and are worth recommending, says X.
There are plenty out there doing good by their viewers and I love that, especially Canadian ones, but it's insufficient for being hyperbolic, imo, about what's impossible to make a claim about, and I don't think arguments from apparent authority are to be encouraged anyway.
In some cases, I've checked the advice of other MD content producers against real practitioners, and they've gave me the thumbs up in terms of credibility, and that obviously changes the vibe a bit, but still I'd hesitate to go too far with that, there's a lot people will do for money and attention.
You're right. You dont have a dog in this fight.
Thank you for your contribution
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.
What an utterly ridiculous extrapolation. These comments are exhausting. Bulking and cutting have a specific meaning, and it doesn't just mean eating at a sufficient caloric surplus to sustain muscle growth. That's simply called eating enough.
I think you misread my comment.
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.
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.
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.
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.
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)
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.
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.
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).
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.
> 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.
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.
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.
Well the answer to that is to eat more fat.
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.
> 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).
They are 75% carbs. Don't miss the point in your focus on one thing that I said. Replace it with sweet potatoes, carrots, and any other health promoting vegetable that Americans don't eat (and when they do, without slathering in sugar/fat).
> They are 75% carbs.
75% of the calories in broccoli is from carbs, sure, but because the overall calorie content of broccoli is so low, it's still considered low carb.
https://www.nutritionix.com/food/broccoli/1-cup
A 1-cup, 156-gram serving is 55 calories, 11g carbs, and 5g fiber, so is only 6g of net carbs for keto purposes.
How are you getting 75%? I see 10g of garbs in 150g of broccoli. That is closer to 7%.
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.
> 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.
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.
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.
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.
> 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.
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.
>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.
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.
> 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.
> 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.
> 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.
> 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.
> CICO is the formula
This is like trying to solve aerodynamics with Newtonian physics only. It’s not useful. CICO ignores the variability of base metabolism.
What does base metabolic variability have to do with using CICO to modify your weight? The intake is easy to measure. The outtake is empirically knowable by change in weight over time. It’s really that simple.
> What does base metabolic variability have to do with using CICO to modify your weight?
Metabolic syndrom is characterised by the basal metabolic rate reducing in response to reduced calorie intake or increased caloric expenditure. In most of us this is good. It gets the immune system to quit mucking around, for instance. In the obese, however, it can sometimes mean their bodies will literally stop doing essential shit before it will concede and begin burning fat. It will then do everything it can to refill those fat cells.
You can model a human thermodynamically. But to my knowledge, this isn't used in medicine because it isn't practical. (I'm saying this, by the way, as someone who can eat anything and laze around and not gain weight because my metabolism is tuned the other way.)
CICO reminds me of something we do in finance: burying the complexity in a magic variable. For CICO, it's the CO. Because if you decompose it into its active and inactive components. Exercise is the former. But the latter absolutely dominates that term.
> In the obese, however, it can sometimes mean their bodies will literally stop doing essential shit before it will concede and begin burning fat. It will then do everything it can to refill those fat cells.
I’m sure there’s some people that this might apply to, but I suspect it’s a much (much) smaller subset than people that are actually obese. For the rest, just decrease your intake until you lose weight. Not much else.
> You can model a human thermodynamically. But to my knowledge, this isn't used in medicine because it isn't practical. (I'm saying this, by the way, as someone who can eat anything and laze around and not gain weight because my metabolism is tuned the other way.)
Exactly what variables are missing then? We can agree that exercise, although certainly burns some calories, is not really the lever you want to pull if you actually want to lose weight by itself. What other variable besides changing how much food you eat would you suggest?
That's the point of the discussion, imo. It seems to be an area of research. There's a lot of questions in my view. Why are people so addicted to food? Why do some models of caloric restriction not work as well as they should? How do we embed behavioral change, or do some of these people just have to be in misery for the rest of their lives?
It's not a profound statement to say if you starve in a desert you'll lose weight. The question is how we can apply this to real, normal people. Or if it's even possible in a food-weaponized world.
My view is that we're in the realm of addiction more so than simply answering "how" they mechanically lose weight. This is a public health crisis, one we need to be open to exploring.
Again, food addiction and satiety is a different question than if CICO works. If you can't stop eating and cram too many calories because you eat too many... burgers and potato chips or whatever, that has nothing to do with if CICO works. I have yet to see evidence that shows that caloric restriction if properly, truly controlled, does not result in weight loss for the vast, vast majority of obese individuals. People are notoriously bad at estimating calories and knowing how much they eat, so any study that is self-reported is inherently going to be problematic.
Should we do more research to find if anything anything specific that may be causing overeating or food non-satiety? Sure. Is the answer likely to be something that is essentially 'tastier food is easier to overeat, and tastier food is much more available than it used to be'? I suspect that is the likely conclusion.
I think GLP1 agonists are a great tool to be used to create that so-called 'willpower' to stop overeating (or, an easy way to reduce food noise, whatever you want to call it). The next step is figuring out how, as a society, we make it easier for folks to make that lifestyle change without a constant stream of 'willpower drugs' for the rest of their life.
> Again, food addiction and satiety is a different question than if CICO works.
Yes, and again - as i said previously. No one is questioning if CICO works. That's like if questioning if physics works. No one is doing that. The laws of the universe are still intact. Talking about humans is the constructive conversion most people are having.
> No one is questioning if CICO works. That's like if questioning if physics works. No one is doing that. The laws of the universe are still intact.
Other people are, in fact, questioning CICO. Look at the other commenter talking about base metabolism changes.
To put an analogy to this: Gambling addicts often lose lots of money at casinos. The behaviors that lead to them being addicted to gambling are in many ways likely equivalent to overeating problems. Nobody asks 'why are gambling addicts losing money?' because we know the reason (casinos have the house edge... you always lose on aggregate). And yet, with food, people consistently ask the question 'why are people so obese?' as if the answer isn't very obvious: they're eating too much food. It's purely as simple as that. The behaviors that lead to eating too much aren't nearly as focused on, in my opinion. Much time is spent on 'the kinds of foods eaten' and how specific things are bad for you, which is essentially like arguing that people should play more blackjack and less roulette or something.
> Other people are, in fact, questioning CICO. Look at the other commenter talking about base metabolism changes.
I disagree. CICO is fundamental physics. Just because metabolism changes does not mean you can produce more energy than you take in. CICO always applies, and it's so 'duh' that it's nearly pointless to discuss in my mind.
Their points about metabolism changes is that the details matter. Finding a way to break the cycle will yield more gains with the population than telling people to starve in a desert.
Metabolism changes are metabolism changes. What does the food you eat have anything to do with that, in practice? As far as I can tell, the mix of carbs/fat/protein has little to do with how much your body “compensates” from a surplus/deficit. If you don’t meaningfully have control over that, the only other real lever is how many calories you eat. Finding a way to lower calories without satiety problems or food noise issues ultimately is the solution. Some people do it via lots of low caloric foods (veg, mainly) that still have high satiety. Some people do it with Ozempic. Some people just aren’t bothered nearly as much by a caloric deficit no matter what they eat.
> 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.
> 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
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.
Consumption of HFCS and added sugar are both down significantly since 2000, with the decline in the former driving the overall decline in the latter.
> (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.
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.
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 )
> 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'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.
Muscle cells don't get replaced or cleaned. Like neurons, they basically stick around throughout the whole life.
Instead, it's the cells themselves that grow bigger or smaller.
Those muscle mass percentages cannot be right. How were they measured?
I’m assuming that’s lean mass (100% - fat %) rather than muscle mass. Unless that person doesn’t have a skeleton.
Just the total mass minus the fat mass. Any further breakdown is not particularly useful.
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.
And yet.
> 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 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.
> 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.
> 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.
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.
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.
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
How has the gastric bypass affected this person? It would not have occurred to me that the brain would be affected.
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.
I'm sorry to hear that happened to someone close to you, thank you for sharing.
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.
Studies show strength training while losing weight can retain almost 100% of muscle.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5946208/
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.
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.
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.
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.
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.
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.
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.
DEXA scans are accurate and readily available in most cities for about $100. Just do it quarterly or whatever.
I am getting regular DEXA scans
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.
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.
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.
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...
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.
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).
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.
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.
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.
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.
> low dose of Semaglutide
I thought its only approved at standard dose.
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.
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.
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.
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.
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.
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.
A bare glp-1 agonist doesn’t, I think, but the weight loss versions are double-acting and do also slow digestion.
Tirzepatide (Zepbound) is double-acting but semaglutide (Ozempic) isn't. Both are prescribed for weight loss.
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.
It says in the paper they used 21-week-old male C57BL/6 mice, as well as AC16 human immortalized cardiomyocytes
Ah, thanks. I looked but not carefully enough!
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:
https://genenetwork.org/show_trait?trait_id=13035&dataset=BX...
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!
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.
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.
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.
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
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?
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.
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.
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.
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.
This is pretty much exactly what I said?
So... could this be a treatment for enlarged hearts?
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.
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?
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.
>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.
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.
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.
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.
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.
> 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.
I find it significantly easier to eat healthy on tirzepatide, fwiw.
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.
If found the opposite to be true.
I'm eating healthier than ever and don't care for junk foods anymore.
“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.
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.
> 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...
Then fund the stores through the Medicaid funds generated.
Gotta start somewhere.
State-run grocery stores[1] are where changes are actually starting.
https://www.chicago.gov/city/en/depts/mayor/press_room/press...
> 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.
given the low success rates of dieting, around 0 percent, gimmie the Band-Aid
> 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?
> So why don't you just eat healthier now?
I used to be you - in most of my 20s, I found it very easy to just eat well, east less, etc. It didn't take any willpower on my part to be fit. It was trivial. I didn't understand why fat people didn't just do the same things I was doing. I thought they had to want to be fat!
Then I got busy with other things, I had less and less free time, fast food, etc. got more and more convenient. Then the pandemic happened and I started just ordering uber eats twice a day. And suddenly I realized "holy shit, I'm fucking fat."
And then I tried to go back to my earlier habits, and it was hard. Things that took zero willpower on my part suddenly meant spending a significant portion of my day fighting different urges.
Was it within my power to do so? Sure, in theory. Everyone, given no other task to do but focus their willpower on just not eating too much, could likely eat healthier and lose weight. But that's not reality, it's difficult, and it ends up slipping down the priority list behind a dozen or two other things.
But on tirzepatide, my relationship with food nearly immediately reverted back to how it was when I was younger.
The fact of the matter is, America has a huge amount of obese people that know they shouldn't be and know in theory that fixing their diet and exercising would resolve their issues. And yet they still are fat. Very very very few of them want to be that way. And the reason is it is hard to just eat healthier when you have that level of food craving
I am not 20 nor on any drug.
I was referring to the portion around thinking people should just eat healthier and giving context, as well as explaining why that thinking is flawed for many people.
"addictive" is an active word in the sentence you quoted.
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.
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."
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
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...
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.
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...
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.
Can you tell if you're retaining muscle with that combination? Is this a doctor prescribed protocol or a DIY stack?
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.
You might consider doing some body fat vs muscle ratio comparison tests. There are 3 methods that give pretty good results. DEXA, Bod Pod & Hydrostatic weighing. I never investigated it much, but I had a buddy who tried all three & felt hydrostatic was the best and most affordable.
I don't know if these are the best resources, I only gave them a cursory glance. The summary does a good job.
AI Summary (Brave Searc) - Hydrostatic, DEXA, Bod Pod Comparison https://search.brave.com/search?q=hydrostatic+weighing+vs+de...
Oh Ive done dexa’s before, I mostly dont care about hard body comp numbers anymore. Part of this latest “journey” is separating my identity from the “stats” of my body, because I was defined by them for so long. I want to spend my time feeling and looking good now.
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.
How are bodybuilders getting a phase 2 trial drug still in development by Lilly?
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.
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".
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.
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.
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
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.
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.
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/
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
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.
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.
Yea, except without error checking, and fully analog technology.
Although, "single cosmic ray upset events," are just as devastating.
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.
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.
> 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.
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.
Weight loss is not "off label" for this drug.
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."
Well, in vitro.
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 μg/kg/d for 21 days." That could be vaguely reasonable -- human doses range from, idk, ~36 to ~200 μg/kg/d (2.5mg/week to 15mg/week at ~100kg).
> 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.
They found the mice did not suffer from any heart problems, so it’s not surprising.
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
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.
If you’re 20% smaller, it would make sense that your heart could pump 20% less.
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.
> 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.
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.
> 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.
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.
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.
Industry led focus group is not a legitimate source.
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.
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.
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.
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.
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.
no wonder you're depressed
>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.
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).
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.
That's an excellent hypothesis. Wouldn't be surprised at all if that was a component!
>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.
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.
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.
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.
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).
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.
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.
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.
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.
> 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
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.
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"
Apologies; I misread your comment. You are right.
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.
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.
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.
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.
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.
Increasing exercise also goes against reducing food amount, because it makes you hungrier.
For me my cravings shifted from cookies/candy/ice cream to craving food that actually does something for my training, like a real meal.
Also for me if I go to crossfit after workday ends I don't get cravings the rest of that day. If anything I want to go to sleep instead of eating candy in front of the TV.
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.
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.
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.
> 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.
> 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.
A lot of what Americans consume is really crappy carbs and sugar, unfortunately. Even fatty meats would be better than that.
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.
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.
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.
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.
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.
I'd be surprised if either mice or human cells eat "the Standard American Diet"
Even pros on high doses of testosterone and multiple AAS lose some muscle mass when preparing for a show.
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.
Uh, GP is talking about losing muscle itself, not the glycogen in muscle.
Well, these studies look at FFM, which does include your water weight and glycogen stores, so they do make up a portion of it.
The point is that there is a big difference between depleting the store of glycogen, which can reliably be refilled in about 2 hours and the body's disassembling half the muscle mass, which takes many months to build back up if you even can build it back up to the original mass (unlikely if you are old).
No one is disputing that you can restore glycogen or water weight quickly.
But the issue is all of the studies I have looked at look at total FFM which does include the loss there. If you are on these GLP-1s there is water weight you are going to lose and keep off while on them due to the anti-inflammation effects, etc., and that water weight is going to be part of their calculations of FFM that has been lost.
I understand now. Sorry for being slow to get it.
>Fat-free Mass (FFM) Encompasses all of the body's non-fat tissues, including the skeleton, water, muscle, connective tissue, and organ tissues.
Nutrient deficient, sure, protein deficient? Probably not.
The claim that "a majority of Americans" eat a protein deficient diet is absurd on its face.
> 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.
> 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.
> 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.
Part of the problem is that doctors recommendunhealthy diets and will dismiss healthy diets.
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...
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.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!
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.
Americans eat a shit ton of protein. No idea where you got idea that from.
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.
> 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.
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.
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.
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.
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.
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
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.
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)
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.
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.
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.
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.
Add walking for 2h per day is the recommended I’ve seen.
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.
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.
I saw someone mention that they craved heroin less on ozympic.
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.
Appetite comes back yes
It does.
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.
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.
bringing it down is not even half the battle, it's what happens next is the more interesting part
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.
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.
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.
You keep taking the GLP1 agonist, otherwise you gain the weight you lost.
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.
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.
So it smells like bullshit because of your personal anecdote? Or because some scientific evidence or experience you have?
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.
Ozempic can use their cash to start an exoskeleton division.
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?
This study is garbage. You can only trust what the companies that profit from the drugs publish.
There is no way magic weight loss pill with no side effects could possibly go wrong!!!
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.
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.
There's a linked article saying that 40% of the weight loss is muscle.
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.
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?
> 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/article/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.
> 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.
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.
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)
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.)
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.
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.
There are no free lunches in nature.
Don’t care. I’m down 30lbs.
Who would have thought cheating to lose weight would have side effects?
The marketing is astounding.
"Weight-loss drug."
Oh, would that be Semaglutide?
<click>
Hey, would you look at that!
which weight loss drug?
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?
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.
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
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.
There is plenty of garbage in hard science too. Start with
https://arxiv.org/archive/hep-th
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.
> 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.
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.
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.
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.
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.
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.
I’m sure complaining about HN is as old as HN.
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
If you think HN users are normies, I think you might be in a bubble. Normies ain’t this literate.
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.
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)
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.
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)
Yeah, normies suck. I totally only want to hear from people obsessed with the latest computer Science minutia!
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.
What exactly do you think this forum is if you think this forum is above such sentiments?
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.
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.
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.
they might have confused muscle and lean mass/FFM
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?
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.
FFM isn’t entirely muscle, but what other weight would be shed when losing FFM other than muscle?
> 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.
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.
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.
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.
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.
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.
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.
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.
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...
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.
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.
So why not just stay on the drugs?
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.
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.
Can’t you just adjust the dosage to stabilize?
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.
$$$
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.
> 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.
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.
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.
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.
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...
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.
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.
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.
> Bad depression was another side effect
What? Ozempic has been noted for its mild _anti_ depression activity.
both can be true. it can reduce depression in 60% of people and increase it in 10%
I like how they aren't saying Semaglutide in the title in an attempt to perhaps keep it from immediate scrutiny.
The first link goes to the study and it does mention the ingredient: https://www.sciencedirect.com/science/article/pii/S2452302X2...
I am talking about UAlberta's title specifically.
"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.
More likely because the average reader won't know what that is versus the current title which succinctly summarizes it.
https://www.fda.gov/drugs/postmarket-drug-safety-information... Same thing??
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.
> 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".