> 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".
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versions (NOT in an auto pen) that were temporarily allowed due to shortages, but whose authorization has since been revoked.
"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.
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.)
>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.
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
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.
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
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].
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.
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.
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.
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.
> 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.
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.
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.
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.
> 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.
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.
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.
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.
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.
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.
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.
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'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.
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.
>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.
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.
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 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.
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 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"
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.
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'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).
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.
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.
> 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.
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.
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.
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.
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.
>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).
> 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.
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.
> 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!
> 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.
> 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.
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.
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.
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.
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)
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.
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.
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.
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.
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).
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.
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.
At the very least, we should expect to see the same kinds of downsides you’d see for anyone who managed to eat way, way less and lose weight at a multiple-pounds-per-week rate for weeks and weeks on end without taking a drug to do it. They’d be truly miraculous if they achieved their results without even the same cost as doing the same thing without the drug.
No one who brings up Fen Phen seems to grasp how long both that and GLP-1s have been on the market. We're up to 4x Fen Phen's run already (5-years Vs. 20-years). GLP-1 Agonists aren't new, they've just been approved for additional usages.
So why, after 20-years, and millions of people haven't fen-phen-like side effects appeared?
It’s perfectly possible for a new hot to have a severe side effect that won’t be noticed for quite a long time.
Semiglutide appears to have undergone final clinical trials in the US around 2017. Given it hasn’t been on the market terribly long and has only an exploded in popularity relatively recently it doesn’t seem like it would be that hard for it to have a serious side effect in a small portion of the population that hadn’t been detected before due to the limited number of people taking it, the amount of time it takes to manifest, or both.
Obviously it’s providing significant benefit that risk could easily be worth it. But as it gets marketed towards more and more people that won’t be true for all of them.
You do have to factor in the (probable) cost of not using Ozempic, aka keeping the pounds on. It may be imprecise, but as an example, if a person was likely to die within 10 years at their current weight, any bad effects beyond the 10 year mark have to be heavily discounted.
I'm sure there are plenty of people taking it as a shortcut to dropping 10 or 20lb or whatever, but I imagine most people taking it are in the "I need to lose 70+ lb of fat" range.
On the other hand, being overweight takes years off your life:
"Specifically, we found that BMIs from 40 to 44 were associated with 6.5 years of life lost, but this increased to 8.9 for BMIs from 45 to 49, 9.8 for BMIs from 50 to 54, and 13.7 for BMIs from 55 to 59."
I think for some people the roi is measurable and reasonable.
I think this is superstition. Vaccines are a medical intervention that have almost zero downside. There isn’t some mythical cosmic cost-benefit scale that needs to be balanced in every new technology that is deployed.
Vaccines and antibiotics and germ theory are all things that seem “too good to be true” but nevertheless are. Should we be worried that clean fusion power, once commercialized and practical, is going to somehow cause some catastrophic unknown future event just because it yields immeasurable benefit to us?
I think this is just another form of magical thinking.
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.
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.
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.
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.
>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.
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.
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[ 3.0 ms ] story [ 332 ms ] threadThere 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?
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.
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.
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)
>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.
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/
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.
For all of medical science's experience and history with debugging the human body, there's still so much more to understand.
Although, "single cosmic ray upset events," are just as devastating.
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.
> 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.
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.
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
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 only reason I want to lose weight is to eat more freely, won't be useful if I lose my appetite too.
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.
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.
My friend cut usage after he lost weight and finds maintenance easy.
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.
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.
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.
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.
> 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.
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.
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.
Bodybuilders will even take AAS that explicitly reduce catabolism of muscle mass like Anavar and still lose some muscle on cuts.
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.
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.
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.
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.
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.
> Do some resistance training, get some protein
jeez, if people actually did that they wouldn't need the drug to begin with
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.
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.
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.
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 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.
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.
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.
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.
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.
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 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.
It pretty much is that simple. The problem is that simple is not easy.
I did an InBody scan the day I started (8/21) and just happened to have done my second one this morning.
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.
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.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!
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.
Would that we could convert the world to diets like that.
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.
>Fat-free Mass (FFM) Encompasses all of the body's non-fat tissues, including the skeleton, water, muscle, connective tissue, and organ tissues.
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.
Emphasis my own. In short: no evidence this is anything other than due to rapid weight-loss.
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.
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
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.
Have only lived a few decades on this planet and the weight loss trends with pharmaceuticals is wild.
It worked! Kind of. The first few days after every dose it had the opposite intended effect so it wasn’t worth it.
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.
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).
In fact, we've even seen the opposite - that it's cardioprotective.
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.
So if you have hypertension, this might actually be a "good" side-effect?
"Weight-loss drug."
Oh, would that be Semaglutide?
<click>
Hey, would you look at that!
> 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?
So why, after 20-years, and millions of people haven't fen-phen-like side effects appeared?
It’s perfectly possible for a new hot to have a severe side effect that won’t be noticed for quite a long time.
Semiglutide appears to have undergone final clinical trials in the US around 2017. Given it hasn’t been on the market terribly long and has only an exploded in popularity relatively recently it doesn’t seem like it would be that hard for it to have a serious side effect in a small portion of the population that hadn’t been detected before due to the limited number of people taking it, the amount of time it takes to manifest, or both.
Obviously it’s providing significant benefit that risk could easily be worth it. But as it gets marketed towards more and more people that won’t be true for all of them.
"Specifically, we found that BMIs from 40 to 44 were associated with 6.5 years of life lost, but this increased to 8.9 for BMIs from 45 to 49, 9.8 for BMIs from 50 to 54, and 13.7 for BMIs from 55 to 59."
I think for some people the roi is measurable and reasonable.
https://irp.nih.gov/blog/post/2020/01/extreme-obesity-shaves...
BMIs from 40 to 44 is massively obese, not overweight.
I'll try to find the study/abstract later if people care.
You mean like antibiotics? Or vaccines?
Vaccines and antibiotics and germ theory are all things that seem “too good to be true” but nevertheless are. Should we be worried that clean fusion power, once commercialized and practical, is going to somehow cause some catastrophic unknown future event just because it yields immeasurable benefit to us?
I think this is just another form of magical thinking.
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.
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!
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.
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.