GLP-1 receptor agonists such as semaglutide act partly through the brain to reduce hunger, increase satiety, and lower spontaneous energy intake. Sustained caloric reduction produces weight loss, including loss of visceral fat around the abdominal organs and ectopic fat stored in tissues such as the liver. These fat depots are metabolically active and contribute to insulin resistance through excess fatty-acid delivery, inflammatory signalling, and disruption of normal insulin action.
As they shrink, muscle and liver tissues become more responsive to insulin, so the pancreas no longer needs to secrete as much insulin to maintain normal glucose levels.
This reduces the compensatory hyperinsulinaemic state that can exist for years before diabetes develops and decreases the probability that impaired glucose regulation will progress toward overt type 2 diabetes.
Those changes propagate into the cardiovascular system.
Better insulin sensitivity and lower visceral and liver fat are commonly accompanied by lower triglycerides, improved blood pressure, reduced systemic inflammation, and better endothelial and vascular function, thereby reducing several mechanisms that contribute to atherosclerosis and cerebrovascular injury.
GLP-1 receptor agonists also have a direct metabolic action independent of weight loss: when glucose is elevated, they enhance pancreatic insulin secretion and suppress inappropriate glucagon secretion, improving glucose control without forcing insulin secretion when glucose is low.
The overall effect is therefore a combination of an immediate GLP-1-mediated improvement in appetite and glucose regulation followed by progressively larger downstream effects from weight and fat loss, which together reduce the metabolic and vascular abnormalities associated with cardiovascular disease and, over much longer periods, potentially with dementia risk.
I'm not great evidence because N=1 and all the confounders, but I found that it absolutely made me much healthier without weight loss. I then went on to increase the dose slowly and have lost a bunch of weight and my labs improved even more, which I attribute mostly to the body mass reduction.
With my labs at my current weight you can not tell that I am a type 2 diabetic. Previously, when I was at this very same weight in the past - all my labs indicated I was prediabetic.
Plenty of anecdata of people who stopped eating certain categories of food and certain conditions they had for a long time went away. In my son's case, a severe case of eczema that persisted for years went away in a matter of weeks after we significantly reduced the amount of hydrogenated oil products available to him to eat.
Sure enough, when we would visit my mom's place which had it, and he'd indulge, the symptoms came back. Same thing when we would buy it at home and he's splurge, he'd have the same problems recur. Cutting it out of the diet is the only thing that correlated highly with the absence of the condition. This happened even after a move from one state to another.
One case, not proof, but definitely repeatable in our circumstances. I have heard a LOT of similar stories. Is it proof? No, but it's an amazingly easy thing to try. It's takes an adjustment, but it intuitively makes sense. Processed food of today is something our ancestors wouldn't even recognize as food. It's just not what our bodies were designed to handle. Some can handle it better than others, but such a processed food and artificial sugar-heavy diet can't be called natural or even healthy.
And the meat they did eat was lean game meat. It was high in unsaturated fats - like our modern day oils. Not like a steak. A steak is a product of farming. It’s a new invention, <10,000 years. Prior, humans ate almost exclusively nuts, fruits and foliage.
Yes oils are “refined”, but humans have been eating unsaturated oils predominantly for almost all of our existence. The proliferation of animal fats is very, very new. Really, it’s past 100 years. Before that meat was rare, it was a delicacy, very expensive for people.
Now, high sugar is a different story. But the oil thing is complex, it’s not as a simple as oil bad animal fat good and natural. No, it’s very unnatural.
Meat only became more of a luxury in the agricultural age where we started squeezing more and more people into smaller and smaller regions which meant there was no longer enough to go around. So plebs got the carbs, and royalty got the protein. FWIW you can also see this in the groups that have ancient traditions dating back far into the past, like the various tribal groups in Russia, Mongolian nomads, etc. Meat, and many highly creative ways of preserving it [1], remain the majority of their diet. They probably don't date back to the paleo, but at least far back enough to falsify the claim that animal fats are even remotely novel.
[1] - https://www.rbth.com/russian-kitchen/334150-dish-kill-kopalk...
Also, simply cutting out junk food will absolutely not reverse fatty liver. You need to eat less and lose weight.
Semaglutide and glp1s resensitize it which is why they have these effects.
My opinion
I've been wary of using online pharmacies due to concerns with knowing what's legitimate and what's not, so maybe a recommendation would help.
If you don't want to share publicly, can you put you contact info in your profile and I'll reach out to you?
In general? Yes. For this specific thing? We haven't even really shown the effects matter for humans.
> If this is caused by the weight loss, it is a little disappointing that public health didn't act quicker - lots of people have been overweight for a century now, so literally 10's of millions of people could have been saved from dementia had action been taken 100 years ago.
Public health has been banging the drum on obesity for decades now. But humans on the whole aren't built to be able to resist hyper palatable calorie dense cheap foods.
Body acceptance movements («it’s sexy to be obese»), a social safety net built around supporting the people taking the least responsibility for their lives (like drug addicts), and a culture celebrating incompetence and throwing merit out the window in the name of DEI.
Is it really a surprise a large percentage of the population is obese, stupid and unwilling to change? It’s simply a fundamentally bad incentive structure on a western societal level.
Blaming individuals for a public health crisis affecting 40% of the population is absolutely silly. There are a lot of individuals like me, who overeat behaviorally, but that doesn't explain the scale of the issue. maybe 8-10% of the population has some sort of eating disorder, the other 30% are just regular people eating an american diet.
If it's hard or not is more of a philosopical question about how much free will we have as people. Statistically they're all hard and not over-eating is the hardest.
Culturally and individually we do a lot of things that probably make the food one even harder
If you drink too much, the common answer is that you need to stop drinking. If you eat too much, we are very reluctant to talk about how you need to eat less. We prefer to talk about how it's someone else's fault and how powerless we are to do anything about it, including comforting lies about how eating less wouldn't work anyway, or how being overweight isn't bad really.
You can prepare healthy meals from basic and cheap foodstuffs like vegetables, whole grains and legumes, eggs, low cost meat cuts etc. You can prepare delicious meals for under $1 each.
Buying prepared unhealthy foods is what is expensive.
People fucking die from obesity every fucking day.
And all you can do is be callous and say "it's not that hard i'm a body builder hurhur." Well so am I. So are a lot of people. The only reason you think that is impressive is because you're a fucking loser edgelord.
It's a disease that kills people. It contributes to like 15% of all deaths in the USA. It ruins people's lives, it makes them suffer.
Would you say this about cancer? It's at about 20% of deaths.
You're not just ignorant. You're pathetic.
we evolved to eat caloric foods, in case of a famine that will never happen in the modern world.
I think we are too soft on people and we let dirtbags get away with way too much in the US but saying "its not that hard" is a cop out.
we get it you're a macho conservative. nobody cares.
At my weight, I'm not a candidate for going on a GLP-1. I'm sure I could find an unethical doctor to prescribe it if I looked hard enough, but I don't want to have the downsides hidden from me.
My weight has been steadily ratcheting up over the years, since I don't have as much room in my life as I used to for living with the discomfort of caloric deficit. If that continues, I will probably become a candidate for GLP-1s, like my immediate family members, just after a decade or so of possibly unneeded striving.
Lots of people are in situations far worse than mine, so I don't feel unlucky — but it would be nice if there were a clearer path forward. While lowering risk for Alzheimer's is not a priority for me, other effects of GLP-1s sound extremely enticing — especially reports of reduced food craving.
I got a concierge doctor who absolutely evaluates what I ask for skeptically, and pay for my GLP medications out of pocket, so I feel ethically totally comfortable with this position. The downsides are real and significant, it's not a "fun" medication, but just the change in how I feel is worth every penny, let alone the massive reduction in heart attack risk, liver enzyme numbers, and so on.
Quit the Wegovy and added a low dose of bupropion, and all of that reversed in a month.
I am overweight, not obese, have an A1C of 4.7, and run regularly. I've never had food noise. YMMV.
That said, I'm extremely prone to side effects, most people I know who have tried them started at maybe half the standard dose and had zero side effects at all. I'm the best possible guinea pig for these things, because if I can tolerate it, almost anyone who isn't frankly allergic or something can.
The other downside, obviously, is injections - you will need to learn how to use sterile technique to inject yourself or pay the incredibly high costs for the pens. The pills are also an option but I have no personal experience and their bioavailability is so low I don't know that I fully trust them.
They will completely change your relationship with food and alcohol, too. Your tastes will probably shift, nearly everybody I know who is on them has essentially given up booze (maybe a couple drinks a year, more or less)
If you feel unable to fix your diet without it, and you think it's safer to get on it, why not make it happen?
I'd say the only unethical doctors here would be the ones not prescribing it for you based on your description of your life and needs.
Guidelines are guidelines, not strict rules for a reason. BMI is not the end-all measurement to decide if you are a candidate for these drugs.
Find a competent doctor who understands GLP-1s and you might be surprised.
Giving GLP-1s to normal weight people doesn’t work well because they can have to work harder to maintain their weight. That can be a real problem as people get older where maintaining muscle mass is important for quality of life and longevity. I remember how hard it was to keep some of my grandparents at a healthy weight, so adding a GLP-1 to a non-obese elderly group is a no-go for study purposes. Going to be hard to separate these effects out.
They seem to also act on some reward mechanism - making some stuff (not just food. Alcohol, gambling, porn, smoking, other drugs have anecdotally been reported to feel less attractive / addictive) have a reduced pull on one's will. They also measurably delay gastric emptying - to the point that some medicines, meant to be taken on an empty stomach, are not safe to take within up to 3 hours from the last meal, compared to one hour or so for other people.
I rather think the opposite is true, that by increasing signals that the body is satiated in many cases it is avoiding a metabolism slowdown caused by hunger.
Which are vastly overblown. I diet every year as part of bodybuilding, at a range of intensities and durations, and have never had issues with sudden metabolic changes that make it harder to lose weight.
For example, I eat too much and started eating less. I now eat normal portions instead of portions fit for 2 people. I have more than enough food and energy, and yet, I am hungry. The hunger is fake, I certainly don’t need more calories. But my body thinks it does based off of its knowledge.
Personally on the whole I’ve had no issues with controlling my weight. I’ve had a couple of isolated instances where I felt hungry all the time and started gaining weight rapidly despite my best efforts. Circumstances changed and it stopped. It sucked and I learned a new level of empathy for the people who get this all the time and not just as a one off.
Edit: although, there are well-known links between overweight and a lot of negative outcomes, and yet people are still too fat.
Obviously, 75% of Americans do not develop dementia. Do more who are overweight develop dementia than those who are not? Well...it's hard to say when 3/4ths of the population is overweight.
It behaved similarly but had a half-life of only a few hours. It required daily injections, and you could feel its effects wax and wane throughout the day.
I was looking for that in particular. The study does say:
"To assess whether the observed effect was mediated by weight reduction, we performed a sensitivity analysis adjusting for change in BMI from baseline to week 104. In this adjusted model, the treatment effect coefficient was attenuated from β −0.092 to β −0.066 (P < 0.001), corresponding to a reduction of 28% in the estimated effect size. This attenuation indicates that 72% of the treatment-associated difference in 20-year dementia risk persisted after accounting for BMI change, suggesting that mechanisms beyond weight loss contribute to the observed proteomic signature modification."
What does treat them like cigarettes mean? Tax them? Ban them within 15 feet of a building entrance? Put warning labels? Is giving or selling French fries to children a crime? Does this apply to food made at home?
A typical burger meal is definitely processed food because the meat is processed mechanically and mixed from different sources (usually with added fat); the bun is made from refined flour and refined oils; and the fries are thinly-cut potatoes blanched and fried in more refined oils. (Not to mention a whole bunch of chemical additives which are the norm rather than the exception; and "hyperpalatability" tweaks which means the food is formulated to taste unnaturally good.)
You could perhaps argue that a home-made burger meal made using whole cuts of meat, a lean wholemeal bread dough, and potatoes roasted in animal fat could count as a healthy/whole food meal, but it would taste different to the typical hamburger meal we all associate with fast food.
Fast food also has an enormous marketing industry behind it which pushes it in unhealthy volume, with maximum convenience, and at (until recently, at least) affordable prices.
The point is that “junk food” is a pretty amorphous and vague category. If you want to enforce portion or calorie restrictions you can do that, but it would have to be way more encompassing of a regulation than targeting “junk food”
Heh, grind your meat
Yes, this is all junk food. It's not that difficult.
Eaten in moderation these things are fine. But they are highly palatable calorie dense meals that are not great for you over time and in huge quantity. A burger is generally speaking a burger, regardless of how fancy. Deep fried stuff is deep fried, regardless of the cut of the vegetable or how organically it was grown.
Your latter question is far more interesting to me. I don't have a solution for that really. Society gets what society demands. I don't know how you'd fix those incentives without seriously horrible second and third order effects.
The reason point 2 is hard is because it’s really difficult to actually draw the line between normal food and junk/ultraprocessed foods in a way that can regulated. You can give guidelines on what a balanced diet should look like and warn away from excess consumption of certain foods, but bans or restrictions are hard.
Well, except for maybe sodas
I think the former makes much more sense than the latter, since it is literally being funded by the govt. That's a reasonable first step, or possibly only step, especially considering that most people on food stamps are also on govt-funded/subsidized healthcare (meaning taxpayers will end up footing the bill when they require expensive treatments resulting in part from an unhealthy diet).
I am sincerely curious to know your opinion.
Amazing that you again allege insincerity, with zero evidence. You then go on to make false claims about what I said and avoid the obvious point that my problem is not with the historical figure that you quoted, but the fact that you injected race into a conversation that was about food.
As for whether you violate the HN guidelines, the number of your recent comments that are greyed out tends to indicate that I'm not the only one who thinks you're out of step here.
I also don't love your injection of flame-bait racial comments, which probably violate HN guidelines.
Even today, a Soda with 'real sugar', at least for me, is far more satiating for thirst or a 'quick sweet treat' than the same brand/'flavor' using corn syrup, that includes both the big chains as well as the local names.
If I drink a soda with sugar in it, I usually wind up wanting water after. If I drink something with corn syrup, I usually just want more of whatever I just had.
Not saying Sugar itself is much better, however, yes, there is research indicating that the two are metabolized differently, so that difference in composition should be considered.
They carry the same health risks if eaten in the same amounts. The only thing that corn syrup could be blamed for here is being too cheap so it shows up in greater quantity and in more products than cane sugar might otherwise.
HFCS is just one of those fashionable things to be "concerned" about so we can all miss the forest through the trees.
Seriously though, it's a dogshit thing to consume whether it is sweetened with HFCS or sucrose.
"Even today, a Soda with 'real sugar', at least for me, is far more satiating"
Did you know that in the acidic environment of a cola, sucrose quickly degrades into fructose and glucose (and if it didn't, your enzymes literally immediately crack sucrose into them). You know, exactly the same fructose and glucose that would be added by HFCS. The proportions differ a tiny amount, but this notion that one is satiating and the other isn't should really send you down a path of self-discovery, where you determine how you fell for nonsense.
Proper sleep, eating less (including liquid calories), and exercising have been the mainstream medical advice for many decades.
Obviously, most people can’t accomplish that for whatever reason, so another solution was needed.
did western society engineer a junkfood-industrial-complex so addicting and so en-sickening that it ultimately required a sort of junk food methadone to wean itself off?
I've never really read much about people using it in this way though and I'm somewhat risk averse, so it's easy for me to keep procrastinating on getting the prescription.
Public health has been trying to get obese people to lose weight forever, what are you talking about. We've known it's bad in enough other ways. It was just really, really hard (at a population level).
Lobbies and general government ineptitude have been a problem longer than obesity and that one needs to be solved first.
I imagine people hundred years in the future will think of our current society rightfully as dumbfucks. But should we be surprised? 50 years ago women didn't have voting rights; homosexuals were incarcerated in western societes; all because of moral and power implications of some powerful men. Not much different with Semaglutide.
Where are you? In the US, women have had full voting rights for over 100 years.
Many many times in US history we've said something is true, but put some big asterisks after them. Slavery is over (except it's definitely still permitted in the US), it's illegal to discriminate based on race (except we allowed redlining for generations and arguably are still fighting it), rape is illegal (unless it's your spouse, then it was legal until '93. And a lesser crime still in much of the country).
Voting is no different. Heck, one might argue we still don't have universal suffrage. People who want to vote but because we've put barriers like underfunding stations, long lines, not giving time off to vote, etc. we're clearly preventing some types of people.
When did all the voter suppression become illegal? 1965.
Good news: the readers of your post don't have to wait 100 years to have that thought.
Given that the drug did not exist until only recently and it took decades to develop with the latest of technology, I don't see how this could have been possible. Stomach surgery has been around for 50 years though, but it's a bigger undertaking than an injectable drug.
When I grew up relatively poor we never ate out or ate junk food because it is ridiculously expensive in comparison. We made our food from cheap ingredients. To save money.
Yes it takes more time and is far more work and is less convenient. US society has valued convenience over everything else for a few generations now. Cheaper it is not.
And it holds true today with my own grocery shopping. Cooking meals and being smart about grocery shopping is far cheaper per meal than buying premade junk. The few times I do have a cart full of products from the middle aisles I am astounded at how expensive it is.
If people are working crazy hours, sometimes it's a struggle to even get time to properly shop for groceries, let alone cook. There's varying degrees of that too;
i.e. I remember the 3-4$ frozen pizzas that could be used as a dinner and leftovers; And yes, at least back then, We could instead buy some chicken, rice, and a can or two of soup or stock to do something way healthier, at the same overall cost per meal...
But it would take an hour or so to properly prepare instead of just tossing that 3-4$ frozen pizza into the oven and letting it do it's thing.
Then throw into the mix where both partners due to work and/or school aren't even home till 8PM, and one of them has to wake up by 7AM to get to work the next morning [0]
I've lived that situation, although thankfully that wasn't every night and we could balance between the healthy self cooked option and the junkish-food-pizza.
But I've also lived the situation where both parties are working late, or the commute is so bad, you're glad you advanced enough you could afford the more expensive, but at least then managable 'taco bell' option.
But then there's the sort of 'generational passing on' where we now have multiple generations raised on carry out, fast food, or microwaved meals. Sometimes where they were never given the teaching or responsibility of cooking because (for reasons similar to above, including more affluent cases) the general concept of 'a home cooked meal' becomes the exception case rather than the norm [1]
[0] - You don't want to eat too late for other health reasons of course...
[1] - And yes, that group really does tend to be less healthy overall from my personal experiences, even if their dining tastes are 'expensive'.
The average American spends 4-5 hours a day on personal screen time, and this skews higher the poorer you get based on a few studies. I've found from talking with folks on the subject many of them are the ones glued to social media and/or the TV.
I agree it's much more convenient to toss a couple pizzas in the oven. I do not agree it's less expensive. I don't know where you're buying your rice or chicken, but even at $4/pizza I can't pencil that out. Chicken comes with free chicken stock if you're buying $5 rotisserie chickens (or whole chickens) and keeping the bones and vegetable ends/etc. around for stock making. This is the level of poor I was talking about. Even at $2.69/lb (the price I paid ~3 weeks ago) for chicken breast, it's going to be cheaper to feed two people than split a whole pizza. Rice is less than 30 cents a serving bought in bulk 50lb bags from a local ethnic store. $1 of rice and a $5 chicken is going to feed around 3-5 people, or give 1 person a lot of leftovers.
I agree one cannot live on just chicken and rice, but one cannot live on just the cheapest frozen pizzas either. I've kinda done both during my life. I lived probably a decade on junk food because I was either too busy or too lazy to do my own cooking like I did growing up. But this was after I started making IT money and could afford it.
> But then there's the sort of 'generational passing on' where we now have multiple generations raised on carry out, fast food, or microwaved meals. Sometimes where they were never given the teaching or responsibility of cooking because (for reasons similar to above, including more affluent cases) the general concept of 'a home cooked meal' becomes the exception case rather than the norm
I definitely agree with this one. Habits and skills are passed down generationally. Someone may not even know where to start looking at youtube for how-to videos to make their own chicken stock for close to free with a $5 crock-pot from the local thrift store these days. And that's probably intermediate level cooking skills, much less beginner level. My wife and I joke about our "depression era cooking" hobby.
I agree there are exceptions, nuance, etc. to this topic. But I get so tired of folks pretending eating home cooked meals is somehow more expensive than an equivalent quality prepared meal. Yes, you can spend as much as you want cooking at home. But the same is true eating out or buying pre-made stuff.
The time factor is certainly very true though. You get much better at it as you practice over the years, but it's always going to be easier and faster to just toss some chicken nuggets into the microwave and be done with it.
This is not moralizing or anything like that. I have lived well over half of my adult life eating junk, and only since getting married to a partner who loves cooking have I turned this back around to my childhood experiences. And we certainly do not optimize very hard for cost - just smart choices by buying stuff on sale, in-season, and in bulk when it makes sense to. I just really cannot square the claim to reality that it's cheaper to eat junk food than it is to eat moderately healthy at home. It's one of those Internet social media memes that just becomes truth by repeating it so much.
Price out a bag of rice, a bag of beans, etc.
> food companies' only interest is in maximizing profit
Pleasing your customers is how profit is maximized.
Besides, I bet if you were faced with two stores, one that charges $x for A, and another that charges $(x-1) for A, you'd patronize the latter store.
If you ignore everything like, including but not limited to, market capture, addictive products, lock-in, information asymmetry, planned obsolescence, dark patterns, captive markets, artificial scarcity, seldom-lucrative-yet-important services and any externality, very true!
A Hershey's chocolate bar is $3.99-$4.99. A banana is maybe 50 cents.
At least 10 to 15-ish years ago, I would actually be closer to agreeing;
You could get Cube or Chuck steak for 3-5$ a pound and potatoes were cheap as hell too. Toss some diced onion in and You'll have a good dinner.
How do I know? Well I grew up in a family where for... reasons[0] we were not that well off for quite a while.
Cube Steak was one of the big things we did for a family meal that Dad cooked. (Chili was his other favorite to make, which was also cheap to do for how much food came out of it...)
However the current prices of beef, I feel like you'd need to have a long standing personal relationship with a local butcher or rancher to make this true.
[0] - My mother's over-propensity for being truly Christ-like in her charity to family and others, also sending myself and my three siblings to Catholic school to avoid the then-absolutely-failed Detroit Public school system were major factors.
While we're at it, a $5 Hershey's bar - Walmart has a 7.56 oz one for $4.52 [1] which claims to be eight servings so again obviously just like a single banana.
[0] https://www.walmart.com/ip/Doritos-Nacho-Cheese-Tortilla-Sna...
[1] https://www.walmart.com/ip/Hershey-s-Special-Dark-Mildly-Swe...
Only question is do you want to spend 1 hour making it and cleaning up.