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Scott's most recent post had someone linking to an article in the Atlantic about debunking a study, I went and read it and got sucked into the Atlantic rabbit hole.
Link one: Don't avoid romance says more people are single nowadays and unhappier nowadays because more people have avoidant attachment styles in the past, with some (mostly circumstantial) evidence that the amount of avoidant attachment is increasing. Ends with an exhortation to not be avoidant but doesn't examine the question I would have thought would be of interest, which is why more and more people don't have healthy attachment styles. (Aftereffects of higher divorce rate? Internet usage? Weaker community institutions? Microplastics? I'm just spitballing ideas but wouldn't a marked societal-leve change in people's psychology be something you'd want to investigate the causes of?)
Link two: The Ozempic Flip Flop as someone who gets full very quickly and doesn't have a very strong appetite, I've never really had good mental image of what it's like for normal people with normal appetites let alone obese people with obese appetites. This article in particular presents people who lost weight, noticed immediate massive benefits in their life they're desperate to keep, and yet still can't keep the weight from coming back. It is just the satiety setpoint being set so high it's torture for them to not eat to the point of overeating? I'm trying to match it to my own points of reference for "willpower" struggles but failing. I force myself to go to the gym despite not enjoying exercise, but that's forcing myself to do something, not forcing myself not to do something, so generally speaking once I overcome the activation barrier of inertia the hard part is over. I intermittently (deliberately, as opposed to non-deliberately) fast and can be hungry and craving food but to a pretty easily overcome extent. But what makes someone — who for months now has been eating much less — be unable to maintain the amount they've been eating for months but instead be compelled to keep eating more even though it's actively physically hurting them (and costing them in other ways, like socially). How much stronger incentive can you get? It makes me feel like at some level for some people food is an addictive substance like drugs. (And also still trying to understand how this gets spread — is it really hyperpalatable foods? Something else? We can watch countries become more obese... Whatever the underlying thing that makes someone susceptible to this is, it does appear to be something a country can acquire)
Yes.
The mechanism via which the body "hungers" is somewhat complex, but can be usefully simplified down to the action of ghrelin, a hormone produced in the stomach which makes you hungrier, and leptin, which does the opposite.
Surprisingly, obese people have more adipose tissue, which produces leptin. However, it ceases to have the usual satiety inducing effect, as the body becomes resistant to its action. The way this is perceived is the body interpreting the lack of signal for being full as a sign of starvation.
And starvation sucks. Other than disease, it's probably what's killed the most humans in all of history, and you can imagine that it's a very unpleasant state that the individual feels compelled to rectify. The easiest solution being to eat more, till the pain goes away.
They're also being struck with a double-whammy. In lean people, eating causes suppression of the levels of ghrelin, in obese people, it doesn't. So they feel less full, with the same amount of food, as compared to those at a healthy weight. Hence they feel compelled to not just eat, but eat excessive amounts for the sake of relief.
I can only reiterate that starving sucks, and the body will drive you crazy in order to avoid that feeling. It's too dumb to know or care that you are, objectively, perfectly well fed. Waterboarding feels just as bad as actual drowning despite the ~nil risk of death.
While doctors usually feel compelled to tell their patients to watch their weight and diet, this almost never actually works. I consider myself a pragmatic one, and advice that isn't actioned in practise is about as useless as advice that doesn't work at all. I was on the Ozempic hype-train well before it was cool.
My mother is very obese, and has been for over half her life now. She's diabetic, and has developed fatty liver with hepatic fibrosis. Her own commitments to working out and dieting never held. She's a doctor herself, so she knows, on an intellectual level, what the risks are. She's been driven to tears by the scolding she gets from my grandpa or my dad who genuinely care for her and want her to lose weight, and after gentle suggestions failed, were driven to tough love.
None of it worked. She loved to eat, and reducing her caloric intake was pure agony. For a long time, I was resigned to the seeming inevitability that she'd head into cirrhosis, and I'd have to steel myself up for a liver donation. It's a nasty, nasty surgery, nothing like giving away a kidney. It leaves a grossly disfiguring scar, leaving aside the significant risk of death during and after the procedure. I'd do it for my mom, because I do love her.
Eventually, when Ozempic, or oral formulations of semaglutide, became available in the Indian market, I badgered her into seeing her endocrinologist and getting it prescribed. Despite the initial nausea and diarrhea, she eventually adapted, and lost the lost weight she's ever managed, and kept it that way. Right now, my priority is hounding her into going to that gent again and getting that dose upped, it's well overdue.
Exhortations to exercise failed. Asking her to watch her portion size and not snack failed. Driving her to tears failed.
The pill didn't.
When people get on their high horse and claim that using drugs to solve your problems is a crutch, it takes everything I have to not tell them to go fuck themselves with a rusty pole. It saved my mom, fuck you. Nothing you have to offer, including your empty words, comes close.
To hell with willpower. A world where we can power through our problems with pills is a better one as far as I'm concerned.
I'm a doctor for many reasons, but ranking highly among them is that I have an urge to find solutions to problems that actually work. Telling people to use their will to get over depression or diabetes doesn't, and the same is true for obesity. Claiming the moral high ground and virtue signaling? Doesn't beat adding years of healthy lifespan.
Thank you!
(If it wasn't clear in my original post, I'm a willpower skeptic, I think it's profoundly stupid to assume obesity is a willpower problem, even if I don't know how to imagine the experience of what it feels like to fight the urge to eat without using willpower as a proxy for the challenge)
Many things about basic biology aren't common knowledge! I don't see a specific reason for why this isn't better known.
There's a single drug called metraleptin, which was once considered immensely promising for treating leptin resistance. Didn't work, failed miserably in trials.
It does, however, work excellently in a rare genetic condition called congenital leptin deficiency, and is occasionally used for lipodystrophy. The difference is that CLD patients lack leptin in the first place, which is giving them the recombinant version helps, whereas obese people have bodies that ignore leptin levels, regardless of how much more we can throw in.
GLP-1 drugs sidestep the whole problem by using an entirely different pathway (I did say I was simplifying! Keeping my head straight about how exactly Ozempic works gives me a headache)
We don't really know how bariatric surgery works.
I'm not kidding here, we genuinely are rather unsure about the mechanism of action. Most of the commonly advanced suggestions were found to be wrong or inadequate at best.
Yes, these do help a little bit, but nowhere near as much as Ozempic does.
Hunger is surprisingly complicated, and has multiple mechanisms behind it.
The act of chewing and tasting sends signals to the brain that prepare the body for food (this is the "cephalic phase response"). This can satisfy the "oral fixation" component of hunger, the simple desire to be chewing on something.
The stomach wall contains mechanoreceptors that sense stretch. When you eat a large volume of food (like a huge salad or a bowl of broth), these receptors are activated, regardless of the calorie content. Trying to fill yourself with low calorie food is an approach known as "volumetrics", and it works okay.
I don't think just drinking water would work as well, because you'd need an uncomfortable amount to fill your stomach, and the body would quickly realize that it's just water, without calories. The ancestral environment definitely had water, and didn't have diet coke (citation hopefully not needed). If starving people tried to keep themselves content by going to a pond, it was probably weeded out quick.
My apologies for giving you the impression that was targeted at you. It was meant entirely for the people who think the usage of Ozempic is some kind of moral failing, and they're not an imaginary strawman, at least not on Twitter. I don't seem to recall much in the way of pushback against Ozempic here, barring people who still have reservations about its safety profile (it's remarkably safe, we have evidence for that claim, and loads of it).
Is it safe in the two senses of:
Doesn’t cause any appreciable loss of strength, at least not beyond what losing that amount of weight would normally do via not eating (exercise held constant)
One can stop taking it without any negative consequences beyond just the loss of the benefits?
I’m interested in taking it but haven’t done a deep-dive into the subject yet. Any resources you’d recommend?
You will lose muscle along with the weight, if you solely use it for weight loss without additional exercise. But the degree of muscle loss is about the same as going on a diet, fasting, or, if memory serves, bariatric surgery. If you exercise alongside, you can stave most of this off.
Indeed. You will regain roughly half the weight you lost in a year of use after a year of disuse. But no other negative effects, to the best of my knowledge.
(I take oral semaglutide, so I'm putting
moneypills where my mouth is.)Scott, as always, has an excellent write up:
Why does Ozempic cure all disease?
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