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greyenlightenment  investments: META/FBL, TSLA, TQQQ, TECL, MSFT ...  1yr ago (npr.org)   2623 thread views

Eli Lilly releases data for a new weight-loss drug to tackle obesity : Shots - Health News : NPR

npr.org

This drug is a true gamechanger

In the SURMOUNT-1 study, people who took the highest dose of tirzepatide, most of whom had a BMI of about 30 or higher but did not have diabetes, lost about 21% of their body weight during the 72 week study. As researchers point out, for people who have bariatric surgery, typical weight loss is about 25% to 30% of their weight, one or two years after the surgery. In the tirzepatide study, 36% of people taking the highest dose lost 25% or more of their body weight.

this is comparable to bariatric surgery

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According to your theory, what is the path from tasty calorie-dense food to a decrease in basal energy expenditure (BEE)?

the problem is the "CI" side of "CICO"...a tiny cookie has 70 calories. It would be effortless for a typical person to overeat them.

But why is the typical person storing the calories as fat, instead of raising their temperature by .3 degrees or making them energetic? And if they are overeating, why are they not feeling satiated? When I'm satiated (not just "full" or "no longer hungry") I have no desire to eat anything at all. The idea of eating becomes repulsive.

You seem really confident that people are eating more now than is historically normal. Outside of war or famine, I've seen evidence that people in the past consumed many more calories.

Did the French eat less than Americans in the 30 year period when the obesity epidemic was exploding in America? The answer is absolutely not! The french “disappeared” an additional 214 calories per day per person during this time. This means that a 50 year old living in America in 1990 would be four times as likely to be obese as a French person despite being responsible for disappearing 2.4 MILLION less calories between the ages of 20 and 50.

It also looks like the median American ate around 3500 calories a day in 1939.

Do you have any evidence you've seen that we are actually eating more calories today?

I've presented evidence that the calories out side has changed, not due to activity going down, but due to people's basal calorie expenditure going down. The amount of calories someone in 2020 burns just by sitting on the couch is less than the amount of calories someone in 1920 burnt by sitting on a couch, and according to the researcher, "The surprising conclusion is we spend less energy when resting now than individuals did 30-40 years ago! The magnitude of the effect is sufficient to explain the obesity epidemic."

Even if we are eating more calories today, and this is due to increased convenient "hyperpalatable" foods, do you have any explanation for the decrease in basal calorie expenditure? (Keep in mind, this is not referring to total energy expenditure, it cannot be explained by saying we're less active today because that is not what is being measured.)

because humans store excess energy as fat, unlike other animals, which do this more poorly. This seems more possible than humans somehow having a slower metabolism over timeframes that cannot be explained by evolution

I am sorry if I gave the impression that I believed there was an evolutionary selection pressure to lower BEE. However, now might be a good time to point out that the earliest mammals had ways to store fat and enter a state called Torpor - low body temperature, high fat storage, low energy expenditure, higher hunger levels. Echidnas are one of the older branches from the mammal family tree - they lay eggs and exude milk from their skin instead of concentrating it in a nipple. They enter a state of torpor. Bears famously enter a state of torpor. It seems to be common to mammalian metabolism and remnants of it remain in most mammals. It is almost universally useful, for humans included, to lower metabolism during famine, dry periods, winters, etc.

When mammals are not in torpor, they store body fat in a specific ratio: Saturated, Mono Unsaturated, and Poly Unsaturated fats are 4:5:1. When it is time to enter into torpor, mono-unsaturated foods become more available and body fat becomes more unsaturated, closer to 2:7:1

There are a lot of mechanisms that go on inside a cell that can cause a metabolism bottleneck. Once the bottleneck occurs, they body can no longer expend the calories as energy and instead has to store them as fat. I'm not going to go into it here and now. When I get around to it, I will write an effort post on this and will tag you.

I think it is more likely that this is an effect of the other major cause of obesity: A Decrease in physical activity.

It sounds like you didn't read the twitter thread in my first post, but Active Energy Expenditure (AEE) has actually increased over time. Basal Energy Expenditure is the amount of energy you use just to keep alive. Adjusted for body composition (it's known that muscle expends more basal energy than fat), the amount of Basal Energy Expenditure has decreased over time.

How do we get back, then?

That is the question, isn't it? This playlist looks into a lot of what might have gone wrong. His primary theory is substituting poly-unsaturated fats (PUFA) for saturated fats, but there are a few other things we could be looking at.

Unfortunately that just tells us how to stop digging the hole, it doesn't tell us how to fix it. There are people who report removing PUFA and increasing Saturated fats stopped weight gain, but it didn't make their weight go down significantly. However, it did make their temperature go up, which might be an indicator their BEE went up as well.

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