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Comment by lee | Hacker News Reader

From the article: "...explains this rate of muscle decline is significantly higher than what is typically observed with calorie-reduced diets or normal aging and could lead to a host of long-term health issues..."

The warning isn't that you're losing muscle during weight-loss with these drugs. It's that the ratio of muscle vs fat loss is much greater with the drugs compared to traditional weight loss methods.

It's been well studied that if you exercise and eat enough protein while losing weight, you can retain more muscle.

Losing a lot of lean mass is incredibly detrimental to your longevity and quality of life.

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Even amongst traditional calorie deficits, rapid weight loss results in greater loss of muscle mass when compared to gradual weight loss, even if you lose the same amount of mass overall. I.e. you keep more muscle losing 0.5 lbs a week over 40 weeks than 2 lbs a week over 10 weeks.

> Even amongst traditional calorie deficits, rapid weight loss results in greater loss of muscle mass when compared to gradual weight loss,

This does not make any sense. Why would the body prefer anything over the most dense and available calorie store? Protein in muscle gives shit calories per gram, it is hard to build back and generally less available than fat: the number one energy store, doing exactly what it does.

I don't think anyone knows for sure, but I think the prevailing theory is it being a survival mechanism.

When our ancestors faced famine, it makes sense for the body to shed as much muscle as possible, since this reduces the metabolic rate in the medium-long term.

Muscle is more metabolically active than fat. Although fat can be used up for energy more readily, but muscle takes more energy to maintain. Burning fat just to maintain (unnecessary) muscle doesn't make sense in terms of survival.

Could just be its for winter where you don't need to move much for a few months, otherwise normally you need that muscle to gather food even when starving, someone has to gather it and it wont be someone who shed most of their muscle.

Because the body can only extract so much energy per minute from all of the fat in your body. If that's not enough, muscle is used, etc.

> Because the body can only extract so much energy per minute from all of the fat in your body.

Was curious about this, went hunting for some rough data, this [0] suggests every kilogram of fat held can be drawn down at ~70 food-calories per day.

So someone with 25% body fat weighting 100kg (~220lb) could draw 1750 food calories per day, which strikes me as pretty ample unless they're also adding a bunch of physical activity.

[0] https://pubmed.ncbi.nlm.nih.gov/15615615/

> which strikes me as pretty ample unless they're also adding a bunch of physical activity.

It seems likely we've evolved to reduce energy expenditure in other ways when we regularly induce physical activity, too. Walk 20,000 steps or spend a couple of hours on the treadmill? Your body finds ways to reduce your energy expenditure elsewhere.

https://pmc.ncbi.nlm.nih.gov/articles/PMC4803033/

It's not going to be linear though. 1750 cal per day ~= 73 cal per hour. If, for example, you're already in a calorie deficit for the day, and then do a nice hour long workout (or demanding mental work), you're going to burn some muscle.

Whether or not it makes any sense to you, it's not a matter of any scientific debate - being in a deficit puts you in a catabolic state where the body will break down muscle mass for energy. It does it less if you have lots of protein and are providing frequent muscle stimulus.

Source?

For protein intake helping decrease this: https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fj.13-...

https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.13...

https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.14...

https://www.sciencedirect.com/science/article/pii/S216183132...

https://www.mdpi.com/2072-6643/12/8/2457

For weight lifting helping decrease this: https://www.mdpi.com/2072-6643/11/11/2824

https://journals.physiology.org/doi/full/10.1152/japplphysio...

https://link.springer.com/article/10.1007/s00726-013-1506-0

https://journals.physiology.org/doi/full/10.1152/ajpendo.005...

https://onlinelibrary.wiley.com/doi/abs/10.1002/mus.21780

https://journals.physiology.org/doi/full/10.1152/ajpregu.004...

https://www.mdpi.com/2072-6643/10/4/423

These are just a tiny subset of the studies done - google scholar can find you many dozens more, if you desire. And, of course, the fact that these studies exist it all necessarily implies that you lose muscle mass when in energy deficit, as you will see in the control groups for them.

(Not a doctor) My understanding is that it is more rapid to extract energy from muscle than from fat.

The body breaks down some muscle tissue beacause it can make glucose from by gluconeogenesis. You need about at least 80 g glucose or so per day (brain), even if you do not eat any carbohydrates. The body cannot make glucose from fat.

Can you provide a single high quality (randomized) study demonstrating GLP1 therapeutics are 'incredibly detrimental to [your] longevity and quality of life'?

Consider the type of confounding that occurs in studies of people losing a lot of lean mass: cachexia, restriction to bed, famine.

Traditional weight loss methods have not shown the magnitude of survival benefits wrt cardiovascular disease, joint pain, diabetic complications. Exercise is wonderful, but as a public health intervention it is not sufficient.

If anyone looks at the totality of the high quality GLP1 clinical evidence and concludes these drugs are going to cause a net reduction in longevity and quality of life, then they should step back and assess their process for evaluating information.

Exercise is a public health intervention that actually works in improving health. It may not work to create actual weight loss, but it does improve things like blood pressure regardless.

>>>Losing a lot of lean mass is incredibly detrimental to your longevity and quality of life.

While true, its also true that if you manage to lose substantial fat in the process, it leads to longer and better quality life

> it leads to longer and better quality life

This needs a slight change in wording or clarification, depending on what you meant.

Losing substantial fat when overweight increases your chance of a longer and better quality life than if you had maintained high levels of fat. Losing substantial muscle in that process reduces your chances of the same. It's statistics and never guaranteed.

If I'm reading the study [1] correctly, that conclusion is not warranted.

It appears that they fed the control group and treatment group of mice lots of food to get them fat, then gave them identical normal diets, and gave the treatment group semaglutide.

The semaglutide group lost significantly more weight (fig A.ii) than the control group, and also lost heart muscle.

So it does not seem that they compared to an equivalent amount of weight loss in mice, which is what I'd think you'd need to do to come to the conclusion from the article (actually, not just an equivalent amount of weight loss, but also at the same rate).

[1] https://www.sciencedirect.com/science/article/pii/S2452302X2...

I guess perhaps the better conclusion would be that maybe dosages should be adjusted so that people don’t lose weight too quickly?

In its trials, Ozempic was combined with intervention/guidance from nutritionists and fitness advisors, and doctors are supposed to reproduce this by referring patients. You can't do that with mice.

I think if I were taking Ozempic I would ask my doctor to halve the rate of progression to higher doses to make the whole process easier to manage, not just managing muscle loss but also the whole of life impact. The official protocol is very "crash diet" in style.

Anyone thinking of taking Ozempic should be aware that many people abandon the drug within the first two years, due to too much nausea, diarrhoea and cost.

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