> It has long been known that people can form defenses and thus antibodies against viruses. But antibodies can also develop against polyethylene glycol (PEG), a substance used in cosmetics, food and medicine.
People can develop antibodies against things which are not foreign micro-organisms. TIL.
(Obvious once you think about it. What you really develop antibodies to are proteins on the surface of micro-organisms)
Yes but no. Allergies are a very particular reaction- you don't get allergy symptoms when you're sick. They're predominantly IgE (immunoglobulin E) which is a detector antibody rather than a neutralizing antibody (although those terms aren't really favored now). IgE activates a body response like anaphylaxis.
The antibodies in this study are IgG (the "normal" antibody) and IgM. In this case, these antibodies latch onto and neutralize/clean up the antigen. They cause much less of an immune system activation, and can act like a passive defense.
TL;DR: allergies are a subset of antibodies for substances, and in this case the antibodies found were non-allergenic.
I don’t think the news here is that PEG can be targeted by antibodies (research companies have been manufacturing anti-PEG antibodies for decades), but that anti-PEG arises naturally (and frequently!) in the adaptive immune system.
Might be a good biomarker to adjust dosing and estimated pharmacokinetics of PEGylated drugs; it might make sense to take another look at PEG-based therapies that failed Phase II/III with this new finding in mind?
PEG is not a protein. And you can definitely get antibodies against anything. There's an idiot researcher trying to get people to make antibodies against cocaine.
The bonkers thing about this is that adding PEG is supposed to be a strategy to get things to evade the immune system.
> People can develop antibodies against things which are not foreign micro-organisms. TIL.
Well yeah- that's how many (most?) resistance to toxins works. When you are given pit viper antivenom, it's literally a bunch of sheep antibodies that attach to the venom molecules and neutralize them and/or make them easier to get rid of.
You do the same thing for novel toxins as you develop a tolerance to them. Alcohol and peroxide have specific enzymes that are produced to break them down, but the immune system is responsible for a ton of stuff.
I am not an expert but I do know it's heinously complex- there are tons of different pathways that are activated by a combination of foreign substances and/or different types of cellular damage (not to mention location in the body). Anaphylactic allergies are controlled by different types of antibodies in different cells that react to different types of damage, normal allergies are a whole other thing, blood antibodies are yet another (multiple types!) of thing...
Biologists are amazing. It seems like picking diamonds off the beach. The book documenting the (public) operation of a new CPU is 10k+ pages long, but a single mammalian cell (taking up <<.001% of the area) makes that CPU look like a joke.
many grades of peg are liquid at room temperature; the others are highly water-soluble. you've probably never seen an object manufactured from peg in your life. that's why people don't normally call it 'plastic'
Tons of common plastics are made from plants. PLA, the most common FDM 3d printing plastic, is made from corn. Ethylene in particular is also naturally occurring- it's one of the most important plant hormones.
Not a plastic and it is commonly found in food and cosmetics.
>evidence shows the existence of a detectable level of anti-PEG antibodies in approximately 72% of the population, never treated with PEGylated drugs, based on plasma samples from 1990 to 1999. Due to its ubiquity in a multitude of products and the large percentage of the population with antibodies to PEG, hypersensitive reactions to PEG are an increasing concern.[39][40] Allergy to PEG is usually discovered after a person has been diagnosed with an allergy to an increasing number of seemingly unrelated products, including processed foods, cosmetics, drugs, and other substances that contain PEG or were manufactured with PEG
Perhaps this is something you already know but nevertheless as long as you are able to relax and remain calm throughout the procedure nobody should stop you from choosing to just take some benzos and do some breathing exercises throughout the procedure.
(Not a doctor but I worked briefly on endoscope tech in the past) The use of propofol depends greatly on their protocol and the country you are in, but it is not something mandatory to perform a colonoscopy. In some places they give it to everyone in others they give to people that are at a higher risk of freaking out and messing with the procedure. My point is just that it is not indissociable from the procedure itself.
When I lived in Germany, I learned that one interesting, cultural aspect is that they don’t drink nearly as much tapwater as in America.
This means everyone buys water in plastic containers at the grocery store, all this plastic is PET-based, and PEG is always present in small quantities in that water (because water is slightly acidic, and acids disassociate the PET molecule).
As a German I find that to be a pretty wild generalization, especially comparing it to the US where tap water quality varies massively (Oregon vs say Michigan (Flint...)). German tap water tends to be quite good. I live in Berlin, where tap water is excellent (albeit with a lot of minerals/calcium). The vast majority of people I know drink tap water, sometimes filtered, sometimes with CO2 added, but tap water nontheless.
> As a German I find that to be a pretty wild generalization
Most generalizations that come from someone taking a short trip to another country are like this: Someone visits a foreign country, interacts with a couple dozen people in a small area, then projects that experience on to the entire country.
I think almost everyone does it when they’re young and they first start traveling. It’s not until you’ve gained more exposure to the size and diversity of the world that you realize you can’t draw conclusions about entire countries from a couple of experienced.
It's funny how impressions can differ, because my impression as a German visiting the US a couple times was that people there have an aversion towards drinking tap water.
That being said, the takeaway from this study shouldn't be that this is peculiar for the German population, it just happens that the Max Planck Institute for Polymers is located in Germany.
And Germans tapwater tastes much better than US tapwater, there is no chlorine
I drink a lot of tapwater (though usually as tea)
I used to drink bottled water, because it is sparkly. I like sparkling water much more than ordinary water.
But I got tired of carrying so many bottles
I bought a CO2 device that should make tapwater sparkling. But lacked fuzz and my mother donated it away. She donates all my stuff
>This means everyone buys water in plastic containers at the grocery store, all this plastic is PET-based, and PEG is always present in small quantities in that water (because water is slightly acidic, and acids disassociate the PET molecule).
My mother only buys glass bottles because of that.
'glycol' just means an organic molecule with two hydroxyl groups
peg is a polymer of ethylene glycol (which monomer is, incidentally, deadly, while peg is generally considered nontoxic)
certainly some functional groups can be intrinsically toxic (organotin compounds come to mind) but you have hydroxyl groups on damn near every molecule in your body, including all the water molecules
> peg doesn't have two hydroxyl groups, it has thousands, because it's not a glycol, it's a polymer of ethylene glycol
PEG does have exactly two hydroxyl groups: one at each end of the polymer chain.
The rest are ether linkages, not hydroxyl. You're right that PEG is quite different from ethylene glycol monomer, but be careful accusing people of being ignorant when your own chemistry knowledge is not the best.
more seriously, i wonder if something like this is a cause of the obesity pandemic: an unrecognized widespread immune response to a novel food additive provoking continuous low-level inflammation
though probably not peg itself; e1521 is not in that many foods, not like xanthan gum or nanoparticles of titanium dioxide
I think the primary cause of the obesity epidemic is the widespread availability of cheap calorie dense food and a few hundred million years of evolution devoted to making biological machines designed to consume as much calorie dense food as they could find.
the fact that no-one is getting fat by drinking litres of olive oil would seem to conclusively disprove your hypothesis as previously stated
the cost of edible oil has not been a bar to access to calorie-dense foods for at least centuries if not millennia
clearly the proximate cause of obesity is eating more and metabolizing less (both by way of lower exercise and lower basal metabolism). but why are people doing that? did they lose the gene for willpower in a single generation? that seems implausible
it seems to closely follow industrially-mass-produced foods, but the relevant feature of those foods is clearly not that they are more convenient or higher in calorie density than a can of crisco or an amphora of olive oil; they aren't
Olive oil is a natural laxative. If you're gaining weight on olive oil, I'd be impressed, beyond how one would keep it down due to taste and texture.
People aren't gaining weight on olive oil because people aren't consuming it in mass quantities required to gain weight, if one could even do so after having your intestines coated by oil. But many are consuming highly processed foods which is shown to lead to less optimal health outcomes.
> clearly
Clearly a post on HN doesn't make for a scientific study!
it's true about the laxative effect! you'd have to use a different oil. and it's true that steatorrhea ensues if you try to get all your calories from fat
but things like halvah, lemonade, buttercream frosting, and white chocolate are still a lot older than the obesity pandemic
None of those would have been common as we know them today. Refined sugar was expensive until ~industrialization. And HFCS simply didn't exist, which is what people are really discussing when they talk about sugar, refined foods, and the obesity epidemic.
industrialization was still 100 years before the obesity pandemic
the hypothesis that hfcs is significantly different in its nutritional effects from sucrose was interesting and has some anecdotal support but is not well supported by evidence so far
'refined foods' have many other nontraditional ingredients introduced around the same time as hfcs, like polyethylene glycol, and we might actually be talking about those instead
Right, no one is getting fat because of fat! It's the catbohydrates that make you fat! And humans eat butter and olive oil since climbing down the trees. Eating fruit and cane is a world domination scheme by the oppressing caste.
Let's be real though - sugar tends to be a lot more palatable than butter, especially when baked or dissolved in acid. I could eat an entire bag of crunch bars, but set me down with a box of sticks of butter and I'm not going to make much progress.
Fats also tend to be more filling, and aren't as addictive as sugar, especially refined sugar.
So I think the real cause here is we've discovered novel ways for making huge amounts of calories both palatable and addictive in a way things have never been before.
The closest I can think of is fruits, and they come with a lot of fiber, and again if you make it into juice, it tends to still not be palatable to drink gallons of it. Whereas people will literally drink a 2 liter of coke in a single sitting.
i think it's almost certainly something about industrially-mass-produced food that tubs of butter don't share, so i think you're a bit closer to the mark. and sugary drinks are surely an especially bad food even among industrially-mass-produced foods
clearly calorie density alone is not it. and i don't think it's even as simple as 'palatability'. even if you mix cacao, butter, sugar, vanillin, and citric acid into candy, you can't get people to live off the candy
and brown sugar mixed with dried lemon juice and oil has been cheap for... significantly longer than the 50-year-old obesity pandemic
Modern fast food is deliberately engineered to make it as addictive as possible while still being palatable and cheap to produce, in order to maximize sales.
That sounds more nefarious than I intended, so let me rephrase it. Modern fast food is the result of rapidly iterating, debugging, and optimizing recipes in a huge market for the last 70 years, leaving only the best selling, low cost, consistently reproducible recipes and discarding the rest. This process naturally selects recipes that contain lots of junk calories and bring in the most repeat customers.
Although many of the ingredients and similar foods have been around for centuries, it wasn't possible to do this kind of agile cooking on a massive scale until after WW2.
this is clearly a thing that has happened, and it is a crucial link in the chain, but there's still a missing link.
wouldn't it be more profitable if those recipes happened to have low caloric density, like coca-cola? then you could sell each customer six meals a day instead of three, and they'd be more profitable because they'd mostly be made out of water, which is cheaper than deodorized canola oil and palm oil, much less potatoes, texturized soy protein, mechanically separated chicken, and beef. you'd maybe have to include enough cellulose and xanthan gum to make it seem solid, but that wouldn't overcome the cost savings from removing the expensive calorie-bearing ingredients. it's even legal!
yet fast-food consumers have been gravitating to the macronutrient-rich menu items, not texturized carboxymethylcellulose jello, which would undoubtedly be widely available if it sold well. so they are following their homeostatic regulatory system to seek calories
their homeostasis is just broken
what broke the homeostasis?
i don't think it's an intentional thing or even a means to improve sales. if wendy's breaks your homeostatic feedback and mcdonald's doesn't, will that help them competitively? no, because their metabolically damaged customers will still eat at mcdonald's, except for the most loyal ones. if wendy's goes out of business, it'll take a generation for mcdonald's to see the result in terms of declining sales. even then, they're unlikely to be able to recognize that the demise of wendy's is the reason for their troubles
it's plausible that it's nothing more than 'ultra-palatable food makes you overeat, which disrupts your homeostasis'. but i'm skeptical of that because people seem to be able to eat very palatable food occasionally, or even often, without disrupting it
Coca-Cola is indeed highly profitable, but American consumers have indicated time and again that they want some real bread and beef to go with that Coca-Cola. They want to feel reasonably full, and they can't come back 6 times a day no matter what, because they have to work in order to pay for your burger.
You're not going to make a large profit if you diverge too far from this social norm. Don't think like a startup, because we're talking about traditional multinational businesses here.
i don't think it's a question of social norms. if people were adhering to pre-mcdonalds social norms, they wouldn't be going somewhere besides their house (a restaurant, but one without waiters) and sitting on brightly colored plastic benches eating mechanically separated chicken glued together with modified food starch cut with texturized soy protein
people's appetite is evidently for calories, and they commonly regulate their caloric intake or metabolic rate to within 0.5% in order to maintain their level of obesity. social norms are not capable of that kind of precision
consider, if you gain only 5 kg in ten years, which many obese mcdonalds eaters in the usa do, that's a caloric excess of 5 kcal per day. half a gram of fat per day. that's 0.3% of a metabolic rate of 1666 kcal per day or 0.2% of 2500 kcal/day. if they were to eat 0.3% less calories than they were burning instead of 0.3% more, they'd be losing 5 kg every ten years, not gaining it
so the homeostatic feedback mechanism is almost working. it's clearly not completely broken. its error is well under 1%. but it does evidently have a systematic error across the population. and fast-food optimization for profit by itself is an insufficient explanation for that
You can get fruits and fruit juices in your winter months, that is newer. OJ came in small glasses because it too was a luxury.
But HN linked an article a few years back about some research indicating that in the 1980s people ate as many or more callories, and got on average less physical activity, but were significantly less overweight. They reaction was that it was wrong, because thermodynamics, but the thermodynamic argument is a vast oversimplification. We can and do excrete plenty of energy such that other organisms post process our waste. Fat in particular can go unused with little notice. We can burn or conserve energy in ways that are hard to measure by just observing behavior. Given that complexity, it wouldn't surprise me that chronic inflammation could be a culprit. It could be the removal of a burden too, such that we are more efficient at processing calories. The food equivalent of meth amphetamine being available everywhere and cheaply doesn't help either, but enough people are studying it that I don't think it will be one simple thing.
Food is part of the equation (marketing and availabity as well as ingredients)
But then there's the rise of the car, and of screen-based jobs/lifestyles, and other little conveniences that remove any last little bits of physical effort from life, from takeaway delivery to dishwashers to power tools.
For me, soda with hugh fructose corn syrup is way easier to drink a lot of than soda with sugar too.
In my mind, the industry trend of 'reduced fat' products that tend to have increased sugar, and the substitution of HFCS for sugar both contribute towards easier over consumption of calories.
> So I think the real cause here is we've discovered novel ways for making huge amounts of calories both palatable and addictive in a way things have never been before.
I was just thinking about this earlier today.
I had a friend whom I would swear was actually, literally addicted to McDonald's burgers and fries. He wouldn't usually go seek out just any old burgers and fries, so I have a hard time saying he was addicted to them in general. I think that McDonald's (and to be clear, I am not blaming the Golden Arches here) had just some right taste that he could not help himself.
I don't like food particularly much at all, so I have never really felt like "oh that was so good I want more," but I can kind of see what you are saying here.
Fruits are not calorically dense. A huge ripe pear can be incredibly delicious and sweet, and only has like 100 calories. The best peach you've ever eaten is like 60-80. It would be pretty challenging to eat a calorically problematic portion of them.
A better example is probably nuts. Nuts are super calorically dense, and it's easy to loads of them.
Yeah that's what I meant by the fiber - they cut the density substantially and would fill you up super fast. And just juicing them gets you into palatability problems - try drinking a gallon of raw apple juice. (Vs drinking a 64oz large coke).
Both of those until very recently were extremely expensive to the point of luxury for many, as well as much more difficult to effectively use a lot of cheap and easily.
Effectively zero people are chugging bottles of Olive Oil they buy from the corner store.
There just is no comparison whatsoever to modern processed foods set for immediate consumption and tuned for maximum taste and pleasure response.
Edit: to refute some other points downthread.
> the cost of edible oil has not been a bar to access to calorie-dense foods for at least centuries if not millennia
I believe this to be false. Even my grandparents saw things like olive oil and real butter as luxury items. Crisco started to exist because it was cheap. It took hours of work to turn these items into palatable calorie-dense foods, if that was even the outcome.
Today? The average working class person goes out to fast food multiple times per week. This was a luxury even in my time growing up. Culture has simply changed, and (bad) food has gotten to be incredibly cheap and easy to access.
> it seems to closely follow industrially-mass-produced foods, but the relevant feature of those foods is clearly not that they are more convenient or higher in calorie density than a can of crisco or an amphora of olive oil; they aren't
I'm not sure how you could come to such a conclusion? That is pretty much the sole feature of those foods. Readily available highly-addictive and highly calorie dense foods fit for immediate (or near it) consumption. No magic woo-woo explanations needed. We simply teleported society into a place literally surrounded by cheap easy to access food typically hundreds of feet away at any given time and then wondered what happened to "willpower" as if it ever existed in such a manner.
if you're from the usa, your grandparents could buy corn oil and margarine, and didn't see them as luxury items; but their generation didn't make a diet out of it
conventional convenience foods like mcdonalds hamburgers, coca-cola, and twinkies are about 3, 0.5, and 4 kilocalories per gram; olive oil and butter are 9. healthier foods like whole-wheat bread, eggs, eggplant, and fatty steak are 2.5, 1.5, 0.4, and 3.5 calories per gram. calorie density is not what makes eggs healthier than coca-cola
your hypothesis would also imply that people on low-carbohydrate diets consisting of fatty meat and cheese would rapidly gain weight, but instead they lose it
in case it wasn't clear, i think the explanation that the obesity pandemic is due to a sudden decline in willpower is unlikely
people hoard good food in their vaults while giving other people their bad food as quickly as they can, because the government has decreed that bad food is equivalent to good food?
that's total nonsense. gresham's law doesn't apply to food
It's also the simple fact that the average blue collar worker hasn't seen rising wages since the 80s. All the money accrued to the top, and the workers were left trying to make the same value of take home pay stretch farther and farther.
The reason most people think inflation sucks is because modern society would rather collapse than pay workers in line with historical norms.
>It's also the simple fact that the average blue collar worker hasn't seen rising wages since the 80s.
You probably need to define what you mean by average blue collar worker as there are many ways of looking at this data (and it is often difficult to even find the estimated levels of transfer payments being given).
For example, this Fed chart shows CPI adjusted median household income rising from around 57 thousand to around 75 thousand today:
https://fred.stlouisfed.org/series/MEHOINUSA672N
I’ve always assumed the problem is that price increases don’t count as inflation if they come with a “quality” increase, but that doesn’t help someone who now needs to spend more to survive.
So it can both be true that inflation-adjusted wages are rising and it is becoming harder to make ends meet.
A wage that supported a cowboy with two sets of clothes, a house that wouldn’t pass any building codes, a horse instead of a car, and no phone is not going to support a modern worker even if “adjusted” for inflation.
False equivalence. This doesn't help advance the debate. The amount of olive oil in the average diet is minuscule relative to the amounts of sugar or palm oil.
it helps advance the debate by conclusively showing that caloric density is not the only relevant factor, or even a dominating one, and that in fact nuance is important, which is my point
there are lots of simple, well-known explanations, and they are all wrong. that was one of them. 'it's sugar' and 'it's hfcs' are two others that have popped up in this thread
sesame oil, corn oil, sunflower oil, coconut oil, and palm oil have the same caloric density as olive oil, are roughly as digestible, and have been cheap and cultivated by humans for far longer than the obesity pandemic. i'd mention suet and lard, too, but it turns out that those have somewhat lower digestibility, so i don't want to confuse the discussion
by contrast, sugary foods commonly have about the same caloric density as healthy foods
so i think caloric density is clearly an important factor (you won't get fat by pigging out on lettuce and tomatoes unless you add salad dressing) but the comment i was rebutting gave the following simple, clear, and wrong explanation of the obesity pandemic
> I think the primary cause of the obesity epidemic is the widespread availability of cheap calorie dense food and a few hundred million years of evolution devoted to making biological machines designed to consume as much calorie dense food as they could find
and that just isn't an accurate description of the situation
Why mention butter? It is delicious in morning tea or coffee and somewhat pricey having been imported from Ireland. I'm in the recommended weight, while some of the fattest people I know consume loads of low-fat products.
because butter's caloric density is 7-9 kcal/g, higher than the 'cheap calorie dense food' being blamed for the obesity pandemic, yet the widespread availability of butter (in some societies) starting ten thousand years ago did not cause widespread obesity, even when it wasn't pricey
this shows that the explanation is wrong; cheap calorie-dense food is not enough to cause widespread obesity
probably the loads of low-fat products you're talking about are packed with sugar and modified food starch, though, as well as xanthan gum, guar gum, carob bean gum, dibutylhydroxytoluene, carboxymethylcellulose, aspartame, polyethylene glycol, all kinds of novel food colorings including titanium dioxide nanoparticles, antifungal additives like propionate, and so on. some of these don't occur naturally, and others aren't traditional food ingredients. it wouldn't be very surprising if one or more of those novel additives affected hormone balances, inflammation levels, or intestinal microbiota in a way that promoted overeating and inactivity. some of them are well-known to affect intestinal microbiota
this is the first time i've seen one that provoked an antibody response, though
i think i'm going to go buy a delicious, cold coca-cola now
Have you ever known anyone to say “I think I’m going to go buy (and eat) a delicious, cold stick of butter now.”? And even if you have, they’re clearly the outlier. The point everyone else is making that you are missing is that even if calorie-rich foods were widely available in the past, the presence of calories alone doesn’t drive appetite – the food also needs to be palatable. Modern processed food is both calorie-dense and engineered to be highly palatable. This is new, and unlike what historical humans generally experienced and evolved around.
the point you think everyone else is making that i am missing is actually the point that i have been trying to make
you say
> the presence of calories alone doesn’t drive appetite
while, although you think i'm the one in this conversation that disagrees with you, the comment that i've written all this verbiage to rebut says exactly the opposite
> I think the primary cause of the obesity epidemic is the widespread availability of cheap calorie dense food and a few hundred million years of evolution devoted to making biological machines designed to consume as much calorie dense food as they could find
i agree with you that the obesity pandemic is almost certainly due to modern processed food, which is new, and unlike what historical humans generally experienced and evolved around
your hypothesis is that palatability (of calorie-dense food) is the relevant difference; i think that's a plausible hypothesis. but i'm not sure that modern industrial food is more palatable than the calorie-dense elements of traditional diets (elsethread i mentioned halvah, but we could also mention longaniza, pizza, ham, bacon, cheese, funnel cakes, pepperoni, buttered pancakes with syrup, onigiri with katsuobushi and so on), and even if it is a difference, that doesn't prove that it's the relevant difference
there are a lot of other differences, and i think we should investigate them, because your hypothesis is far from the only plausible hypothesis
People are reaching for expense, but I think that's the wrong explanation, it's cost/availability + palatability + caloric density. Olive oil has maybe one or two of those, but it's missing the key ingredient of palatability. Not many people want to guzzle olive oil.
I myself find good olive oil to be quite tasty, far more so than soybean or canola, and I don't think I'm in a tiny minority there. Dipping bread directly in olive oil (sometimes seasoned with a little garlic or whatever) is very common in Mediterranean diets.
This is extremely disingenuous. You cannot drink anything more than a little bit of olive oil without serious gastric consequences, which is why most of history involves using a little bit of vegetable oil here and there for the other desirable properties. Nevermind the fact that nobody could afford large quantities of ANY food, and even after we brought the potato, a way more efficient means of growing calories, to europe, most people still couldn't afford more than sufficient quantities of calories. Even then, there are arguments to be made that such potato growing was an important element of significant population growth after it became popular.
Meanwhile, you average normal person nowadays CAN eat a bag of potato chips in one sitting, without gastric consequences. Then they can compensate for eating half a pound of salt by following it up with half a candy bar for something sweet. Or maybe they got a milkshake with their burger or something.
... Right around the green revolution where we figured out that we can pour fertilizer and water on crops and they grow really well, which lead to high fructose corn syrup in everything and its sugar composition (high fructose) leads to obesity. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3522469/
It's really not that deep. Anybody tracking calories and logging food will quickly realize that the comment you're replying to is correct. You have to make very thoughtful choices when choosing your foods because it's easy to eat 2-3x your TDEE with the current available foods that are sold. Most of it is calorically dense junk.
It doesn't look like obesity is infectious, so calling it a pandemic doesn't seem appropriate. The cure is eating less and exercising more. Many have done it.
the cure you suggest fails on 95% of obese people, though like many pseudoscientific quack cures, it does appear to work at first, and actually does work in a few cases
the implied etiology doesn't hold up to the most casual critical thinking: resting and eating have been part of every human life since long before there were humans, but the obesity pandemic is only 50 years old. this is like attributing deaths from dengue to "bleeding" and recommending that people bleed less
Diet and exercise absolutely does work. It's just that when you frame the intervention as TELLING people to eat less and exercise more, it is very ineffective. So from a physician's standpoint, it's not a great approach.
Education and socioeconomic status correlate with lower obesity rates, healthy diet, and exercise.
The “sudden” change is easy to see in the supermarket. Most people don’t shop at Whole Foods, Sprouts, or Central market. Go to Walmart and admire all of the densely caloric colorful boxed foods.
Did you know young people actually use door dash/uber to get their fast food? It’s wild. So not even expending a few calories to get it but also wasting a bunch of cash.
Stress is a leading cause of inflammation. Financial insecurity causes stress and lack of free time to exercise or prepare meals. Hard to separate the variables.
The drive to eat and what is strongly influenced by gut biome. Fecal transplants have created new food preferences.
Even saying diet and exercise are the proximate cause may be an oversimplication. We know that the same level of activity and food intake can produce different results in different people. That doesn't violate thermodynamics. There are caloric expenditures that are not measured in such studies, like incomplete digestion and thermal regulation.
People shouldn't eat what they are eating, and they should have alternatives that are healthy for them (which also varies by person, but is almost never equal parts transfat and fructose with a petroleum based dye to make it pretty and to cut the sweetness, enough salt to cure a whole pig).
Beyond the fact that just telling people to do so is ineffective, my experience is that most people have a very poor idea of what is and isn't calorie dense (I've been there!), how many calories they consume in snacks, or how to eat in a way that leave you feeling full without gobbling down calories.
I've been around people who made legitimate good-faith efforts to diet and eat "healthy", but have no idea that "just a bowl of rice to go with it" and "I need my afternoon milk tea" and maybe another snack are like 500+ extra calories each day, that hardly even leave you full.
A very small proportion of obesity is secondary to hypothyroidism which isn’t supplemented with synthroid/thyroid hormone, hypothalamic/pituitary axis dysfunction, adrenal corticotroph, or exogenous corticosteroids. If viruses are blamed its going to be pseudoscience to sell pills.
An accepted rule of nutrition/diet/physiology is that an excess of 3,500 calories will lead to a gain of 1lb of fat.
The basal metabolic rate for an adult in the United States is 1,731 calories (numbers based on averages returned in google, 38.1 years old, 5’11, 181 lbs).
So 1,731 calories for a sedentary person is really easy to surpass. If they surpass that by a few hundred calories a day then they’ll gain a pound every 10 days(ish). After ballooning up they can jump on the ozempic train and lose weight. Or just stay obese.
If you don’t know anyone on ozempic then I’ll share - the weight loss appears mostly due to discomfort. Eating what they used to do becomes very uncomfortable due to abdominal pain/nausea and constipation. So they calorie restrict and they start to lose weight because they’re below their BMR.
Ozempic was also shown to modify BMR even after controlling for the change in body mass. It is doing something else in addition to aversion therapy. Probably several somethings else, not all of which we understand or would want.
But again the calorie counting is an oversimplication as mentioned in other posts. Elegantly simple, and so attractive. Caloric restriction will always work in the absence of the endocrine issues you mention. And in the absence of other issues we haven't discovered or don't understand yet. The vast majority of hypothyroidism is due to autoimmune related inflammation (Hashimoto's). The normal cause for that is childbirth related immune response. But plenty of other autoimmune diseases are virally triggered, quite possibly even diabetes. Combining that with the way gut biome impacts appetite and processing efficiency, we can't just pretend telling people to eat less and better and exercise will matter no matter how hard we work on education. Ozempic is a bandaid that rich people will use and will slow down discovery of all the multitudes of ways modern life has conspired to cause obesity.
>the cure you suggest fails on 95% of obese people
This has nothing to do with "Diet and exercise don't work" and everything to do with the fact that every single fat person KNOWS they are fat, already KNOWS diet and exercise are the solution, and has likely already tried diet and exercise in some way and couldn't manage it. People usually get fat because eating calorie dense foods feels good and people are desperate for anything to feel good because the average person has spent the last 6 decades being squeezed for every last drop of wealth by the ownership class, which it turns out is a very stressful experience.
Diet and exercise are extremely difficult to tack onto your existing life if you aren't already predisposed to it, and if you are already predisposed to it, you probably aren't fat because you have a healthy diet and exercise!
My mom's family grew up eating fried lard(!) as a regular food. Not a single one of them got overweight because they had regular exercise when they played with friends or did chores like tending the garden or worked the potato fields, and because they literally could not afford to eat enough lard to get fat
The reason that food insecure households are fat is not some magic bullet substance that we will be able to remove from our life, but because for a lot of Americans, you buy your groceries at dollar general or walmart and the frozen nuggets are cheaper than a pound of chicken thigh.
Easy to say, but your body isn't a static system. It is going to respond to the lack of food(or increased exercise). And that response may be the actual problem for people. Maybe your body will say "Oh, I'm only getting 1500 calories a day now? Okay, we will just be sleepy, miserable, with no energy or motivation, until we get our calories"
Just speaking from personal experience, I’m fat because I eat cake and ice cream every day and walk 6,000 steps on a good day. I don’t really see a mystery here tbh.
The prevalence of sugar in modern diets along with how ludicrously industrialized food has become, particularly in America, is likely still the main cause for obesity rates.
People point out all these other secondary factors but we should really focus on the 80%, the big ticket item.
It's damn near impossible to find nutritiously acceptable breakfast, lunch and dinner choices near the office in big cities in America. From the American perspective, the choices are all fine because that's all people know. But relative to what you can find in Europe or even Latin America, the alternatives are downright appalling.
What city do you live in? There is a huge array of healthy low calorie options near me all the way to pure vegetarian/vegan places.
There is a ridiculously strong correlation between sedentariness and obesity. We our more sedentary than ever before and then remote work/school increased it again.
I believe a person struggling with weight is basically determined in their childhood. Only in childhood will the body build new fat cells and the number of fat cells determines hormonal production of leptin and others which trigger hunger cues for the rest of life. Basically a fat child will permanently be hungrier for the rest of their life due to increased numbers of fat cells. If you’re a skinny and active kid you will permanently have an easier time to keep weight off. And before you blame food again sedentariness has increased among children immensely as well.
yes, that is true, and we know several reasons for it, but it is irrelevant both to the narrow issue of whether fat cells produced in childhood derange your caloric intake regulatory homeostasis thereafter, and to the broader issue of why there's an obesity pandemic
It certainly was rarer but this was a known phenomenon occurring at least back in the 1960s
Off the top of my head I know there’s a speech of JFKs where he advocates for child health saying quote “there’s nothing more unfortunate than fat chubby children”
Various industry sources and think tanks (with various biases, including IfG, IEA, Czarnikow) suggest sugar consumption has fallen very significantly in the UK and Australia since 1970, without any apparent impact on obesity rates.
However, I can't find trustworthy original academic research on it, which makes it difficult to draw any firm conclusions. In any case, it doesn't appear that sugar consumption has risen dramatically in the last 50 years in the UK, yet obesity rates (and associated metabolic diseases) have continued to rise. Most research seems to suggest sugar is a marker of an unhealthy lifestyle rather than the cause, but the cause still seems to be essentially unknown. It is true that countries that eat very little sugar tend to have lower obesity rates, but that seems mainly to be because they are usually extremely poor.
In my opinion, there's more evidence that low fibre and easily digestible food is a bigger culprit than sugar, but the evidence is very poor quality on all sides.
there's also evidence that sugar consumption in the usa a century ago was already high, and the hadza famously eat mostly honey in july and august, so i think that while sugar is probably a contributor, it's probably not sufficient by itself
it would be pretty surprising to find that, say, propionate intake suppressing intestinal yeast growth was a major cause of the obesity pandemic. but it certainly seems to be something about industrial food manufacturing that goes beyond just caloric density and macronutrient balance, and additives seem like a promising place to look
i mean the village baker a century ago didn't put calcium propionate in his bread so it wouldn't get moldy, he just threw the moldy bread out
Obviously there could be many factors. I want to point out, though, that a caloric deficit is a marginal difference. That means small changes in the base calorie intake can lead to a many-fold increase in your caloric deficit.
As an example, let’s say you go from a healthy adult at 18 years old and 160 lbs, to an obese adult at 40 and 300 pounds. That’s 140 pounds over 22 years. If a pound of weight is gained after 3,500 excess calories, then this person only consumed roughly 60 extra calories a day. If they consumed only 20 excess calories a day, they would be 195. Overweight, but still relatively healthy. It doesn’t take a lot of sugar to add 40 or 60 calories to someone’s diet and leave everything else unchanged.
and there are many people like you! yet a century ago you could have eaten cake every day if you wanted, though not ice cream, and in many places, many people already had office jobs to which they could take the subway. why did your counterparts in new york not have an obesity epidemic? somehow they didn't want to eat cake instead of food, and they felt restless if they had so little activity
clearly diet and exercise are the proximate causes of obesity, but what has so deranged our diet and exercise?
Sure, but something has made far more people make choices like yours than ever used to. We don't yet know what that is. We probably should.
Our individual choices are ours to make, but they don't happen in a vacuum. Cultural signals, environmental factors, biological processes, uncritically reinforced habits, etc all shape what choices we're inclined towards and what choices look implausible or untenable.
There's been a shocking shift in weight management and general wellness over the last hundred years, that seems to creep into every country that assimilates with " modern" culture, and it's prudent that we collectively understand why, because we probably should do something about it on that same collective scale.
How have the labor trends shifted in the last 50, 100 years?
Labor intensive jobs(also calorie intensive) are down. Even the jobs that remain have more of the physical demands taken out i.e. using an airgun to frame up a house instead of a hammer.
> Sure, but something has made far more people make choices like yours than ever used to.
Not a big mystery there. Food used to be expensive and cakes only available in special occasions. Now I can get a cake delivered to my home within half an hour without getting up from my chair and it costs me about 15 minutes worth of paid work.
Cake and ice cream did exist 50 years ago, and I doubt it was any healthier back then. Anyway, nobody doubts that excessive calorie intake causes obesity. The question is whether some chemicals in food cause an increased desire for excessive calorie intake, e.g. via confusing our hormone system.
Most thin people aren't just thin because they eat less, they are thin because they don't have a disposition for binge eating. They just aren't as hungry.
> Cake and ice cream did exist 50 years ago, and I doubt it was any healthier back then.
Cake and Ice cream 50 years were ago were likely healthier and would have been healthier still going farther back. They'd have likely used fewer ingredients, less sugar (and less HFCS), and contained fewer microplastics/PFAS. Much of the ice cream sold in stores today can't even legally call themselves ice cream! They're "Frozen dessert products"
I would think that metabolism is a clearer target considering the direct link between genetics and enzymes, not to say that your proposal isn’t still possible this just seems more proximate. That being said I’m not an expert at all and could be totally wrong.
The presence of antibodies isn’t as big of a signal as we once thought.
There have been several companies developing antibody tests for various things, including your body’s own natural receptors. They have been appealing to people with chronic illnesses as an explanation for unexplained symptoms. For example, implying that if their tests show antibodies to certain receptors then that is a diagnostic clue.
Then some researchers started using one of the company’s tests with a control group (healthy volunteers) and discovered that healthy people had the same antibodies at the same rates as the sick people. They couldn’t differentiate between the sick group and the healthy group at all by the presence of antibodies.
So there’s a lot more to this than simply looking for antibodies to a substance. I don’t know enough about the topic to say exactly what that nuance might be, but after reading the research and talking to some experts in this field I don’t put much weight in simple binary analyses of antibodies.
1) this is a simple molecule, not an organism that can react to the threat. As you said, it would be interesting to be evaluate whether the antibodies actually have an effect, but they probably have, else they likely wouldn't have been detected at all.
2) the blood samples were taken from patients. It would be interesting to evaluate blood samples from the population at large.
> As you said, it would be interesting to be evaluate whether the antibodies actually have an effect,
The article has a quote from the researchers about how the antibodies could remove a future PEG nanocarrier from the patients' system:
> "The antibodies formed against PEG attach themselves to the coated nanocarriers, thus counteracting the effect that is actually desired: the nanocarrier becomes visible to the immune system and is removed before it can exert its effect," explains Katharina Landfester, director of the department.
I don't know if there are other consequences outside of this. Having your body become good at removing a foreign substance doesn't sound like a bad thing, except in the case where you might want that foreign substance to help deliver a drug.
To point (1), antibodies against non-alive substances are how you get things like allergies and autoimmune diseases. Your body goes "holy shit pollen!" and makes you break out in hives or "holy shit gluten!" and makes your guts inflamed.
Not all the time, obviously, and it depends on the type of antibody.
I'm not sure how much more "alive" you expect something like pollen to be (or most allergens, which are usually proteins or protein fragments). Nobody is claiming that antibodies are binding to whole-cats or whole-dogs. They normally bind to protein, and sometimes to protein-coupled-with-small-molecules.
It's fairly notable for there to be Abs against synthetic molecules, even if PEG is technically organic, and a relatively large molecule.
? The person I was replying to mentioned "not an organism that can react to the threat," which I took to mean a bacterium or virus. The former of which is definitely alive, and the latter debatably so.
What I was trying to convey is that your immune system regularly responds to things that are not active invading organisms. Peanut butter is organic, sure, but it's not a living creature that your body needs to shut down. Doesn't stop some people's immune systems from firing up regardless.
Hence also: "it would be interesting to be evaluate whether the antibodies actually have an effect"—allergies are one way that antibodies can have an effect against an otherwise inert/harmless substance.
Antibodies do not target bacteria or viruses. They target protein that are present on bacteria or viruses. Protein are not alive, but they are a component of live organisms.
Protein present in peanut butter come from the plant that produces peanuts, which is just as alive (if not more) than microorganisms.
The only difference between the two are the time scales involved, and the natural selection forces in play... But that seems irrelevant here.
Your immune system has no notion of whether an antigen is alive or not. One way or another, it makes no difference. For the allergy example, there is nothing special there either. Your body is reacting to the allergen (a protein) in essentially the same way it would react to a helminth (or rather, to helminth protein). It doesn't know the difference.
> Protein present in peanut butter come from the plant that produces peanuts, which is just as alive (if not more) than microorganisms.
Right, but peanut butter itself is not alive. I never claimed that it's inorganic, only that a morsel of peanut butter is not a living creature, and specifically not a living creature that makes (most people) sick.
> Your immune system has no notion of whether an antigen is alive or not. One way or another, it makes no difference.
This is also what I was trying to convey, albeit in laymen's terms. As I understood it, the person I initially replied to wondered what would happen if your immune system reacted to a(n organic but) non-living substance. And the answer is that your immune system still reacts, but the reaction doesn't accomplish anything useful or necessary, and that's why no one likes having MS or a pet dander allergy. At least when your immune system reacts to a coronavirus, it's for a good reason—to clear out the virus.
To help clear up the disagreement: the difference I had in mind is that things like peanut butter and PEG cannot adapt to escape the immune response. Viruses and bacteria can. Antibodies against them can be detected after an infection, but they might not be effective at all.
> it would be interesting to be evaluate whether the antibodies actually have an effect, but they probably have, else they likely wouldn't have been detected at all.
You're right. The antibodies to PEG are detected after a very severe reaction or after testing following many bad reactions to seemingly unrelated substances so for some people it's having a very harmful effect. PEG can even cause anaphylaxis. Reactions can become increasingly severe with repeated exposure too, so someone mildly sensitive to PEG today could end up in the ER at some point in the future.
Our bodies seem to see PEG as a hazard so I hope alternatives are found for it.
PEG is in vape cartridges as a solvent. I’ve read the rationalization that “food grade” PEG is probably safe there because doctors use PEG to help with organ transplants, but missing from such a simple analysis is that you end up breathing PEG into your lungs with a vape pen, certainly different than anything studied thus far with organ transplants. Can’t be good, man. I mean, like all our other exposure to low-grade toxicity, it won’t kill you by itself, but I’m not interested in being a beta tester for inhaled PEG.
Anyway, maybe this is a more common route for PEG exposure besides Miralax.
A interesting collateral effect is that Polyethylene Glycol is used to concentrate and catch viruses (adding common salt). Maybe it acts the same in the gutters and is seen as "a virus" by the immune system?
PEG here is polyethylene glycol. It is used as a laxative agent and also as a bulking agent for making other medications. I wish it was deciphered right in the headline.
168 comments
[ 2.6 ms ] story [ 213 ms ] threadPeople can develop antibodies against things which are not foreign micro-organisms. TIL.
(Obvious once you think about it. What you really develop antibodies to are proteins on the surface of micro-organisms)
Well, talk about a worldview-changing moment.
The antibodies in this study are IgG (the "normal" antibody) and IgM. In this case, these antibodies latch onto and neutralize/clean up the antigen. They cause much less of an immune system activation, and can act like a passive defense.
TL;DR: allergies are a subset of antibodies for substances, and in this case the antibodies found were non-allergenic.
Might be a good biomarker to adjust dosing and estimated pharmacokinetics of PEGylated drugs; it might make sense to take another look at PEG-based therapies that failed Phase II/III with this new finding in mind?
According to the PEG wiki, that has apparently been known for decades.
The bonkers thing about this is that adding PEG is supposed to be a strategy to get things to evade the immune system.
Well yeah- that's how many (most?) resistance to toxins works. When you are given pit viper antivenom, it's literally a bunch of sheep antibodies that attach to the venom molecules and neutralize them and/or make them easier to get rid of.
You do the same thing for novel toxins as you develop a tolerance to them. Alcohol and peroxide have specific enzymes that are produced to break them down, but the immune system is responsible for a ton of stuff.
I am not an expert but I do know it's heinously complex- there are tons of different pathways that are activated by a combination of foreign substances and/or different types of cellular damage (not to mention location in the body). Anaphylactic allergies are controlled by different types of antibodies in different cells that react to different types of damage, normal allergies are a whole other thing, blood antibodies are yet another (multiple types!) of thing...
Biologists are amazing. It seems like picking diamonds off the beach. The book documenting the (public) operation of a new CPU is 10k+ pages long, but a single mammalian cell (taking up <<.001% of the area) makes that CPU look like a joke.
That's plastics for you folks...
[0]: [Translated from German](https://www-aerzteblatt-de.translate.goog/archiv/217236/COVI...)
Plastic implies it is solid, which is wrong.
>evidence shows the existence of a detectable level of anti-PEG antibodies in approximately 72% of the population, never treated with PEGylated drugs, based on plasma samples from 1990 to 1999. Due to its ubiquity in a multitude of products and the large percentage of the population with antibodies to PEG, hypersensitive reactions to PEG are an increasing concern.[39][40] Allergy to PEG is usually discovered after a person has been diagnosed with an allergy to an increasing number of seemingly unrelated products, including processed foods, cosmetics, drugs, and other substances that contain PEG or were manufactured with PEG
https://en.wikipedia.org/wiki/Polyethylene_glycol
the plural makes me curious; for medical reasons?
It's not that onerous, except that I assume going under propofol + midazolam comes with cognitive risks each time, and this might be cumulative.
With that in mind, no idea how the risk/reward math of regular endoscopy/colonoscopy checkups works out.
(Not a doctor but I worked briefly on endoscope tech in the past) The use of propofol depends greatly on their protocol and the country you are in, but it is not something mandatory to perform a colonoscopy. In some places they give it to everyone in others they give to people that are at a higher risk of freaking out and messing with the procedure. My point is just that it is not indissociable from the procedure itself.
This wasn’t olden times, it was just a decade back.
I promptly gagged, pulled out the scope and vomited.
Do you have any sources for this? I'm also wary of going under, even if it's once every 3 years.
This means everyone buys water in plastic containers at the grocery store, all this plastic is PET-based, and PEG is always present in small quantities in that water (because water is slightly acidic, and acids disassociate the PET molecule).
Most generalizations that come from someone taking a short trip to another country are like this: Someone visits a foreign country, interacts with a couple dozen people in a small area, then projects that experience on to the entire country.
I think almost everyone does it when they’re young and they first start traveling. It’s not until you’ve gained more exposure to the size and diversity of the world that you realize you can’t draw conclusions about entire countries from a couple of experienced.
I think "everyone buys water in plastic containers" is a bit of an overestimate.
That being said, the takeaway from this study shouldn't be that this is peculiar for the German population, it just happens that the Max Planck Institute for Polymers is located in Germany.
Where I'm from we drink tap water with no filter etc.
I drink a lot of tapwater (though usually as tea)
I used to drink bottled water, because it is sparkly. I like sparkling water much more than ordinary water.
But I got tired of carrying so many bottles
I bought a CO2 device that should make tapwater sparkling. But lacked fuzz and my mother donated it away. She donates all my stuff
>This means everyone buys water in plastic containers at the grocery store, all this plastic is PET-based, and PEG is always present in small quantities in that water (because water is slightly acidic, and acids disassociate the PET molecule).
My mother only buys glass bottles because of that.
'glycol' just means an organic molecule with two hydroxyl groups
peg is a polymer of ethylene glycol (which monomer is, incidentally, deadly, while peg is generally considered nontoxic)
certainly some functional groups can be intrinsically toxic (organotin compounds come to mind) but you have hydroxyl groups on damn near every molecule in your body, including all the water molecules
PEG does have exactly two hydroxyl groups: one at each end of the polymer chain.
The rest are ether linkages, not hydroxyl. You're right that PEG is quite different from ethylene glycol monomer, but be careful accusing people of being ignorant when your own chemistry knowledge is not the best.
my own level of ignorance is life-threatening in a life form that is literally made out of molecules
i appreciate your efforts to ameliorate that predicament ;)
more seriously, i wonder if something like this is a cause of the obesity pandemic: an unrecognized widespread immune response to a novel food additive provoking continuous low-level inflammation
though probably not peg itself; e1521 is not in that many foods, not like xanthan gum or nanoparticles of titanium dioxide
https://en.wikipedia.org/wiki/Inflammation#Interleukins_and_... is probably a good place to start reading
And no-one is getting fat by drinking litres of olive oil or eating tubs of butter.
It's a combination of more high-calorie convenience foods and a more sedentary lifestyle than even just 50 years ago.
the cost of edible oil has not been a bar to access to calorie-dense foods for at least centuries if not millennia
clearly the proximate cause of obesity is eating more and metabolizing less (both by way of lower exercise and lower basal metabolism). but why are people doing that? did they lose the gene for willpower in a single generation? that seems implausible
it seems to closely follow industrially-mass-produced foods, but the relevant feature of those foods is clearly not that they are more convenient or higher in calorie density than a can of crisco or an amphora of olive oil; they aren't
People aren't gaining weight on olive oil because people aren't consuming it in mass quantities required to gain weight, if one could even do so after having your intestines coated by oil. But many are consuming highly processed foods which is shown to lead to less optimal health outcomes.
> clearly
Clearly a post on HN doesn't make for a scientific study!
it's true about the laxative effect! you'd have to use a different oil. and it's true that steatorrhea ensues if you try to get all your calories from fat
but things like halvah, lemonade, buttercream frosting, and white chocolate are still a lot older than the obesity pandemic
the hypothesis that hfcs is significantly different in its nutritional effects from sucrose was interesting and has some anecdotal support but is not well supported by evidence so far
'refined foods' have many other nontraditional ingredients introduced around the same time as hfcs, like polyethylene glycol, and we might actually be talking about those instead
Fats also tend to be more filling, and aren't as addictive as sugar, especially refined sugar.
So I think the real cause here is we've discovered novel ways for making huge amounts of calories both palatable and addictive in a way things have never been before.
The closest I can think of is fruits, and they come with a lot of fiber, and again if you make it into juice, it tends to still not be palatable to drink gallons of it. Whereas people will literally drink a 2 liter of coke in a single sitting.
clearly calorie density alone is not it. and i don't think it's even as simple as 'palatability'. even if you mix cacao, butter, sugar, vanillin, and citric acid into candy, you can't get people to live off the candy
and brown sugar mixed with dried lemon juice and oil has been cheap for... significantly longer than the 50-year-old obesity pandemic
so, what changed? why is food now so addictive?
That sounds more nefarious than I intended, so let me rephrase it. Modern fast food is the result of rapidly iterating, debugging, and optimizing recipes in a huge market for the last 70 years, leaving only the best selling, low cost, consistently reproducible recipes and discarding the rest. This process naturally selects recipes that contain lots of junk calories and bring in the most repeat customers.
Although many of the ingredients and similar foods have been around for centuries, it wasn't possible to do this kind of agile cooking on a massive scale until after WW2.
wouldn't it be more profitable if those recipes happened to have low caloric density, like coca-cola? then you could sell each customer six meals a day instead of three, and they'd be more profitable because they'd mostly be made out of water, which is cheaper than deodorized canola oil and palm oil, much less potatoes, texturized soy protein, mechanically separated chicken, and beef. you'd maybe have to include enough cellulose and xanthan gum to make it seem solid, but that wouldn't overcome the cost savings from removing the expensive calorie-bearing ingredients. it's even legal!
yet fast-food consumers have been gravitating to the macronutrient-rich menu items, not texturized carboxymethylcellulose jello, which would undoubtedly be widely available if it sold well. so they are following their homeostatic regulatory system to seek calories
their homeostasis is just broken
what broke the homeostasis?
i don't think it's an intentional thing or even a means to improve sales. if wendy's breaks your homeostatic feedback and mcdonald's doesn't, will that help them competitively? no, because their metabolically damaged customers will still eat at mcdonald's, except for the most loyal ones. if wendy's goes out of business, it'll take a generation for mcdonald's to see the result in terms of declining sales. even then, they're unlikely to be able to recognize that the demise of wendy's is the reason for their troubles
it's plausible that it's nothing more than 'ultra-palatable food makes you overeat, which disrupts your homeostasis'. but i'm skeptical of that because people seem to be able to eat very palatable food occasionally, or even often, without disrupting it
You're not going to make a large profit if you diverge too far from this social norm. Don't think like a startup, because we're talking about traditional multinational businesses here.
people's appetite is evidently for calories, and they commonly regulate their caloric intake or metabolic rate to within 0.5% in order to maintain their level of obesity. social norms are not capable of that kind of precision
consider, if you gain only 5 kg in ten years, which many obese mcdonalds eaters in the usa do, that's a caloric excess of 5 kcal per day. half a gram of fat per day. that's 0.3% of a metabolic rate of 1666 kcal per day or 0.2% of 2500 kcal/day. if they were to eat 0.3% less calories than they were burning instead of 0.3% more, they'd be losing 5 kg every ten years, not gaining it
so the homeostatic feedback mechanism is almost working. it's clearly not completely broken. its error is well under 1%. but it does evidently have a systematic error across the population. and fast-food optimization for profit by itself is an insufficient explanation for that
But HN linked an article a few years back about some research indicating that in the 1980s people ate as many or more callories, and got on average less physical activity, but were significantly less overweight. They reaction was that it was wrong, because thermodynamics, but the thermodynamic argument is a vast oversimplification. We can and do excrete plenty of energy such that other organisms post process our waste. Fat in particular can go unused with little notice. We can burn or conserve energy in ways that are hard to measure by just observing behavior. Given that complexity, it wouldn't surprise me that chronic inflammation could be a culprit. It could be the removal of a burden too, such that we are more efficient at processing calories. The food equivalent of meth amphetamine being available everywhere and cheaply doesn't help either, but enough people are studying it that I don't think it will be one simple thing.
10.1016/j.orcp.2015.08.007
But then there's the rise of the car, and of screen-based jobs/lifestyles, and other little conveniences that remove any last little bits of physical effort from life, from takeaway delivery to dishwashers to power tools.
Exercise used to be an unavoidable part of life.
In my mind, the industry trend of 'reduced fat' products that tend to have increased sugar, and the substitution of HFCS for sugar both contribute towards easier over consumption of calories.
Not with that attitude you're not.
> So I think the real cause here is we've discovered novel ways for making huge amounts of calories both palatable and addictive in a way things have never been before.
I was just thinking about this earlier today.
I had a friend whom I would swear was actually, literally addicted to McDonald's burgers and fries. He wouldn't usually go seek out just any old burgers and fries, so I have a hard time saying he was addicted to them in general. I think that McDonald's (and to be clear, I am not blaming the Golden Arches here) had just some right taste that he could not help himself.
I don't like food particularly much at all, so I have never really felt like "oh that was so good I want more," but I can kind of see what you are saying here.
A better example is probably nuts. Nuts are super calorically dense, and it's easy to loads of them.
Effectively zero people are chugging bottles of Olive Oil they buy from the corner store.
There just is no comparison whatsoever to modern processed foods set for immediate consumption and tuned for maximum taste and pleasure response.
Edit: to refute some other points downthread.
> the cost of edible oil has not been a bar to access to calorie-dense foods for at least centuries if not millennia
I believe this to be false. Even my grandparents saw things like olive oil and real butter as luxury items. Crisco started to exist because it was cheap. It took hours of work to turn these items into palatable calorie-dense foods, if that was even the outcome.
Today? The average working class person goes out to fast food multiple times per week. This was a luxury even in my time growing up. Culture has simply changed, and (bad) food has gotten to be incredibly cheap and easy to access.
> it seems to closely follow industrially-mass-produced foods, but the relevant feature of those foods is clearly not that they are more convenient or higher in calorie density than a can of crisco or an amphora of olive oil; they aren't
I'm not sure how you could come to such a conclusion? That is pretty much the sole feature of those foods. Readily available highly-addictive and highly calorie dense foods fit for immediate (or near it) consumption. No magic woo-woo explanations needed. We simply teleported society into a place literally surrounded by cheap easy to access food typically hundreds of feet away at any given time and then wondered what happened to "willpower" as if it ever existed in such a manner.
conventional convenience foods like mcdonalds hamburgers, coca-cola, and twinkies are about 3, 0.5, and 4 kilocalories per gram; olive oil and butter are 9. healthier foods like whole-wheat bread, eggs, eggplant, and fatty steak are 2.5, 1.5, 0.4, and 3.5 calories per gram. calorie density is not what makes eggs healthier than coca-cola
your hypothesis would also imply that people on low-carbohydrate diets consisting of fatty meat and cheese would rapidly gain weight, but instead they lose it
in case it wasn't clear, i think the explanation that the obesity pandemic is due to a sudden decline in willpower is unlikely
Meanwhile, the amount of fat available has gone up 40%, while protein supplies have risen closer to c. 10%.
It is absolutely anti-data to imply that previous generations had access to the same amount/mix of food/calories as we do today.
https://ourworldindata.org/food-supply
It’s Gresham’s “law”: “bad money drives out good”, but applied to food.
https://en.m.wikipedia.org/wiki/Gresham's_law
that's total nonsense. gresham's law doesn't apply to food
The reason most people think inflation sucks is because modern society would rather collapse than pay workers in line with historical norms.
You probably need to define what you mean by average blue collar worker as there are many ways of looking at this data (and it is often difficult to even find the estimated levels of transfer payments being given). For example, this Fed chart shows CPI adjusted median household income rising from around 57 thousand to around 75 thousand today: https://fred.stlouisfed.org/series/MEHOINUSA672N
https://fred.stlouisfed.org/series/LES1252881600Q
So it can both be true that inflation-adjusted wages are rising and it is becoming harder to make ends meet.
A wage that supported a cowboy with two sets of clothes, a house that wouldn’t pass any building codes, a horse instead of a car, and no phone is not going to support a modern worker even if “adjusted” for inflation.
so fuck historical norms actually
That "real" is doing a lot of heavy lifting.
Nuance is important.
there are lots of simple, well-known explanations, and they are all wrong. that was one of them. 'it's sugar' and 'it's hfcs' are two others that have popped up in this thread
by contrast, sugary foods commonly have about the same caloric density as healthy foods
so i think caloric density is clearly an important factor (you won't get fat by pigging out on lettuce and tomatoes unless you add salad dressing) but the comment i was rebutting gave the following simple, clear, and wrong explanation of the obesity pandemic
> I think the primary cause of the obesity epidemic is the widespread availability of cheap calorie dense food and a few hundred million years of evolution devoted to making biological machines designed to consume as much calorie dense food as they could find
and that just isn't an accurate description of the situation
no it hasn't. for most of that timespan approximately no-one outside of the eastern Mediterranean even knew what an olive was
this shows that the explanation is wrong; cheap calorie-dense food is not enough to cause widespread obesity
probably the loads of low-fat products you're talking about are packed with sugar and modified food starch, though, as well as xanthan gum, guar gum, carob bean gum, dibutylhydroxytoluene, carboxymethylcellulose, aspartame, polyethylene glycol, all kinds of novel food colorings including titanium dioxide nanoparticles, antifungal additives like propionate, and so on. some of these don't occur naturally, and others aren't traditional food ingredients. it wouldn't be very surprising if one or more of those novel additives affected hormone balances, inflammation levels, or intestinal microbiota in a way that promoted overeating and inactivity. some of them are well-known to affect intestinal microbiota
this is the first time i've seen one that provoked an antibody response, though
i think i'm going to go buy a delicious, cold coca-cola now
Then you dump calories on top of those metabolic changes (and appetite stimulation by the carbs) and you pack on the weight.
you say
> the presence of calories alone doesn’t drive appetite
while, although you think i'm the one in this conversation that disagrees with you, the comment that i've written all this verbiage to rebut says exactly the opposite
> I think the primary cause of the obesity epidemic is the widespread availability of cheap calorie dense food and a few hundred million years of evolution devoted to making biological machines designed to consume as much calorie dense food as they could find
i agree with you that the obesity pandemic is almost certainly due to modern processed food, which is new, and unlike what historical humans generally experienced and evolved around
your hypothesis is that palatability (of calorie-dense food) is the relevant difference; i think that's a plausible hypothesis. but i'm not sure that modern industrial food is more palatable than the calorie-dense elements of traditional diets (elsethread i mentioned halvah, but we could also mention longaniza, pizza, ham, bacon, cheese, funnel cakes, pepperoni, buttered pancakes with syrup, onigiri with katsuobushi and so on), and even if it is a difference, that doesn't prove that it's the relevant difference
there are a lot of other differences, and i think we should investigate them, because your hypothesis is far from the only plausible hypothesis
But I agree that the obesity could be boosted by chemical contamination. It should be treated as a disease and not as just a sin.
I myself find good olive oil to be quite tasty, far more so than soybean or canola, and I don't think I'm in a tiny minority there. Dipping bread directly in olive oil (sometimes seasoned with a little garlic or whatever) is very common in Mediterranean diets.
Meanwhile, you average normal person nowadays CAN eat a bag of potato chips in one sitting, without gastric consequences. Then they can compensate for eating half a pound of salt by following it up with half a candy bar for something sweet. Or maybe they got a milkshake with their burger or something.
https://en.wikipedia.org/wiki/Infectobesity
the cure you suggest fails on 95% of obese people, though like many pseudoscientific quack cures, it does appear to work at first, and actually does work in a few cases
the implied etiology doesn't hold up to the most casual critical thinking: resting and eating have been part of every human life since long before there were humans, but the obesity pandemic is only 50 years old. this is like attributing deaths from dengue to "bleeding" and recommending that people bleed less
diet and exercise is clearly the proximate cause of obesity, but the question is what drives diet and exercise, and what changed so suddenly?
The “sudden” change is easy to see in the supermarket. Most people don’t shop at Whole Foods, Sprouts, or Central market. Go to Walmart and admire all of the densely caloric colorful boxed foods.
Did you know young people actually use door dash/uber to get their fast food? It’s wild. So not even expending a few calories to get it but also wasting a bunch of cash.
The drive to eat and what is strongly influenced by gut biome. Fecal transplants have created new food preferences.
Even saying diet and exercise are the proximate cause may be an oversimplication. We know that the same level of activity and food intake can produce different results in different people. That doesn't violate thermodynamics. There are caloric expenditures that are not measured in such studies, like incomplete digestion and thermal regulation.
People shouldn't eat what they are eating, and they should have alternatives that are healthy for them (which also varies by person, but is almost never equal parts transfat and fructose with a petroleum based dye to make it pretty and to cut the sweetness, enough salt to cure a whole pig).
I've been around people who made legitimate good-faith efforts to diet and eat "healthy", but have no idea that "just a bowl of rice to go with it" and "I need my afternoon milk tea" and maybe another snack are like 500+ extra calories each day, that hardly even leave you full.
An accepted rule of nutrition/diet/physiology is that an excess of 3,500 calories will lead to a gain of 1lb of fat.
The basal metabolic rate for an adult in the United States is 1,731 calories (numbers based on averages returned in google, 38.1 years old, 5’11, 181 lbs).
So 1,731 calories for a sedentary person is really easy to surpass. If they surpass that by a few hundred calories a day then they’ll gain a pound every 10 days(ish). After ballooning up they can jump on the ozempic train and lose weight. Or just stay obese.
If you don’t know anyone on ozempic then I’ll share - the weight loss appears mostly due to discomfort. Eating what they used to do becomes very uncomfortable due to abdominal pain/nausea and constipation. So they calorie restrict and they start to lose weight because they’re below their BMR.
But again the calorie counting is an oversimplication as mentioned in other posts. Elegantly simple, and so attractive. Caloric restriction will always work in the absence of the endocrine issues you mention. And in the absence of other issues we haven't discovered or don't understand yet. The vast majority of hypothyroidism is due to autoimmune related inflammation (Hashimoto's). The normal cause for that is childbirth related immune response. But plenty of other autoimmune diseases are virally triggered, quite possibly even diabetes. Combining that with the way gut biome impacts appetite and processing efficiency, we can't just pretend telling people to eat less and better and exercise will matter no matter how hard we work on education. Ozempic is a bandaid that rich people will use and will slow down discovery of all the multitudes of ways modern life has conspired to cause obesity.
This has nothing to do with "Diet and exercise don't work" and everything to do with the fact that every single fat person KNOWS they are fat, already KNOWS diet and exercise are the solution, and has likely already tried diet and exercise in some way and couldn't manage it. People usually get fat because eating calorie dense foods feels good and people are desperate for anything to feel good because the average person has spent the last 6 decades being squeezed for every last drop of wealth by the ownership class, which it turns out is a very stressful experience.
Diet and exercise are extremely difficult to tack onto your existing life if you aren't already predisposed to it, and if you are already predisposed to it, you probably aren't fat because you have a healthy diet and exercise!
My mom's family grew up eating fried lard(!) as a regular food. Not a single one of them got overweight because they had regular exercise when they played with friends or did chores like tending the garden or worked the potato fields, and because they literally could not afford to eat enough lard to get fat
The reason that food insecure households are fat is not some magic bullet substance that we will be able to remove from our life, but because for a lot of Americans, you buy your groceries at dollar general or walmart and the frozen nuggets are cheaper than a pound of chicken thigh.
[1] https://twitter.com/mold_time/status/1412827749828513800?s=2...
People point out all these other secondary factors but we should really focus on the 80%, the big ticket item.
It's damn near impossible to find nutritiously acceptable breakfast, lunch and dinner choices near the office in big cities in America. From the American perspective, the choices are all fine because that's all people know. But relative to what you can find in Europe or even Latin America, the alternatives are downright appalling.
"Food manufacturing" should be a banned term.
There is a ridiculously strong correlation between sedentariness and obesity. We our more sedentary than ever before and then remote work/school increased it again.
I believe a person struggling with weight is basically determined in their childhood. Only in childhood will the body build new fat cells and the number of fat cells determines hormonal production of leptin and others which trigger hunger cues for the rest of life. Basically a fat child will permanently be hungrier for the rest of their life due to increased numbers of fat cells. If you’re a skinny and active kid you will permanently have an easier time to keep weight off. And before you blame food again sedentariness has increased among children immensely as well.
Off the top of my head I know there’s a speech of JFKs where he advocates for child health saying quote “there’s nothing more unfortunate than fat chubby children”
However, I can't find trustworthy original academic research on it, which makes it difficult to draw any firm conclusions. In any case, it doesn't appear that sugar consumption has risen dramatically in the last 50 years in the UK, yet obesity rates (and associated metabolic diseases) have continued to rise. Most research seems to suggest sugar is a marker of an unhealthy lifestyle rather than the cause, but the cause still seems to be essentially unknown. It is true that countries that eat very little sugar tend to have lower obesity rates, but that seems mainly to be because they are usually extremely poor.
In my opinion, there's more evidence that low fibre and easily digestible food is a bigger culprit than sugar, but the evidence is very poor quality on all sides.
it would be pretty surprising to find that, say, propionate intake suppressing intestinal yeast growth was a major cause of the obesity pandemic. but it certainly seems to be something about industrial food manufacturing that goes beyond just caloric density and macronutrient balance, and additives seem like a promising place to look
i mean the village baker a century ago didn't put calcium propionate in his bread so it wouldn't get moldy, he just threw the moldy bread out
As an example, let’s say you go from a healthy adult at 18 years old and 160 lbs, to an obese adult at 40 and 300 pounds. That’s 140 pounds over 22 years. If a pound of weight is gained after 3,500 excess calories, then this person only consumed roughly 60 extra calories a day. If they consumed only 20 excess calories a day, they would be 195. Overweight, but still relatively healthy. It doesn’t take a lot of sugar to add 40 or 60 calories to someone’s diet and leave everything else unchanged.
clearly diet and exercise are the proximate causes of obesity, but what has so deranged our diet and exercise?
Our individual choices are ours to make, but they don't happen in a vacuum. Cultural signals, environmental factors, biological processes, uncritically reinforced habits, etc all shape what choices we're inclined towards and what choices look implausible or untenable.
There's been a shocking shift in weight management and general wellness over the last hundred years, that seems to creep into every country that assimilates with " modern" culture, and it's prudent that we collectively understand why, because we probably should do something about it on that same collective scale.
Labor intensive jobs(also calorie intensive) are down. Even the jobs that remain have more of the physical demands taken out i.e. using an airgun to frame up a house instead of a hammer.
Not a big mystery there. Food used to be expensive and cakes only available in special occasions. Now I can get a cake delivered to my home within half an hour without getting up from my chair and it costs me about 15 minutes worth of paid work.
Most thin people aren't just thin because they eat less, they are thin because they don't have a disposition for binge eating. They just aren't as hungry.
Cake and Ice cream 50 years were ago were likely healthier and would have been healthier still going farther back. They'd have likely used fewer ingredients, less sugar (and less HFCS), and contained fewer microplastics/PFAS. Much of the ice cream sold in stores today can't even legally call themselves ice cream! They're "Frozen dessert products"
I see what you did there. :-) I myself was momentarily confused when I saw "PEG".
There have been several companies developing antibody tests for various things, including your body’s own natural receptors. They have been appealing to people with chronic illnesses as an explanation for unexplained symptoms. For example, implying that if their tests show antibodies to certain receptors then that is a diagnostic clue.
Then some researchers started using one of the company’s tests with a control group (healthy volunteers) and discovered that healthy people had the same antibodies at the same rates as the sick people. They couldn’t differentiate between the sick group and the healthy group at all by the presence of antibodies.
So there’s a lot more to this than simply looking for antibodies to a substance. I don’t know enough about the topic to say exactly what that nuance might be, but after reading the research and talking to some experts in this field I don’t put much weight in simple binary analyses of antibodies.
1) this is a simple molecule, not an organism that can react to the threat. As you said, it would be interesting to be evaluate whether the antibodies actually have an effect, but they probably have, else they likely wouldn't have been detected at all.
2) the blood samples were taken from patients. It would be interesting to evaluate blood samples from the population at large.
The article has a quote from the researchers about how the antibodies could remove a future PEG nanocarrier from the patients' system:
> "The antibodies formed against PEG attach themselves to the coated nanocarriers, thus counteracting the effect that is actually desired: the nanocarrier becomes visible to the immune system and is removed before it can exert its effect," explains Katharina Landfester, director of the department.
I don't know if there are other consequences outside of this. Having your body become good at removing a foreign substance doesn't sound like a bad thing, except in the case where you might want that foreign substance to help deliver a drug.
Not all the time, obviously, and it depends on the type of antibody.
I'm not sure how much more "alive" you expect something like pollen to be (or most allergens, which are usually proteins or protein fragments). Nobody is claiming that antibodies are binding to whole-cats or whole-dogs. They normally bind to protein, and sometimes to protein-coupled-with-small-molecules.
It's fairly notable for there to be Abs against synthetic molecules, even if PEG is technically organic, and a relatively large molecule.
What I was trying to convey is that your immune system regularly responds to things that are not active invading organisms. Peanut butter is organic, sure, but it's not a living creature that your body needs to shut down. Doesn't stop some people's immune systems from firing up regardless.
Hence also: "it would be interesting to be evaluate whether the antibodies actually have an effect"—allergies are one way that antibodies can have an effect against an otherwise inert/harmless substance.
Protein present in peanut butter come from the plant that produces peanuts, which is just as alive (if not more) than microorganisms.
The only difference between the two are the time scales involved, and the natural selection forces in play... But that seems irrelevant here.
Your immune system has no notion of whether an antigen is alive or not. One way or another, it makes no difference. For the allergy example, there is nothing special there either. Your body is reacting to the allergen (a protein) in essentially the same way it would react to a helminth (or rather, to helminth protein). It doesn't know the difference.
Right, but peanut butter itself is not alive. I never claimed that it's inorganic, only that a morsel of peanut butter is not a living creature, and specifically not a living creature that makes (most people) sick.
> Your immune system has no notion of whether an antigen is alive or not. One way or another, it makes no difference.
This is also what I was trying to convey, albeit in laymen's terms. As I understood it, the person I initially replied to wondered what would happen if your immune system reacted to a(n organic but) non-living substance. And the answer is that your immune system still reacts, but the reaction doesn't accomplish anything useful or necessary, and that's why no one likes having MS or a pet dander allergy. At least when your immune system reacts to a coronavirus, it's for a good reason—to clear out the virus.
You're right. The antibodies to PEG are detected after a very severe reaction or after testing following many bad reactions to seemingly unrelated substances so for some people it's having a very harmful effect. PEG can even cause anaphylaxis. Reactions can become increasingly severe with repeated exposure too, so someone mildly sensitive to PEG today could end up in the ER at some point in the future.
Our bodies seem to see PEG as a hazard so I hope alternatives are found for it.
I'm not in any position to dispute the claimed facts but the way you phrased this hits many of the same beats as what we used to call an urban legend.
Anyway, maybe this is a more common route for PEG exposure besides Miralax.
Just a thought