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Weight-loss drug found to shrink muscle in mice, human cells

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Re: Weight-loss drug found to shrink muscle in mice, human cells

#401

Post by thefz »

beejiu wrote: post #302
lee wrote: post #300

Earlier quoted context omitted.

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 be…

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.

Re: Weight-loss drug found to shrink muscle in mice, human cells

#402

Post by thefz »

lenerdenator wrote: post #316

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.

> 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?

Re: Weight-loss drug found to shrink muscle in mice, human cells

#403

Post by beejiu »

thefz wrote: post #401
beejiu wrote: post #302

Earlier quoted context omitted.

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 doe…

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.

Re: Weight-loss drug found to shrink muscle in mice, human cells

#404

Post by Kirby64 »

unshavedyak wrote: post #400
Kirby64 wrote: post #395

Earlier quoted context omitted.

> 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 yo…

> 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 bor…

> 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.

Re: Weight-loss drug found to shrink muscle in mice, human cells

#405

Post by notesinthefield »

pogue wrote: post #399
notesinthefield wrote: post #373

Earlier quoted context omitted.

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.

Re: Weight-loss drug found to shrink muscle in mice, human cells

#406

Post by paulpauper »

lenerdenator wrote: post #316

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.

given the low success rates of dieting, around 0 percent, gimmie the Band-Aid

Re: Weight-loss drug found to shrink muscle in mice, human cells

#407

Post by wan23 »

siliconc0w wrote: post #126

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 li…

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.

Re: Weight-loss drug found to shrink muscle in mice, human cells

#408

Post by robwwilliams »

jr000 wrote: post #268
robwwilliams wrote: post #179

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.

Re: Weight-loss drug found to shrink muscle in mice, human cells

#409

Post by robwwilliams »

insane_dreamer wrote: post #187
robwwilliams wrote: post #179

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.

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...

Re: Weight-loss drug found to shrink muscle in mice, human cells

#410

Post by hombre_fatal »

Wytwwww wrote: post #352
hombre_fatal wrote: post #314

Earlier quoted context omitted.

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).

> 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).
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