Got food cravings? What’s living in your gut may be responsible | Hacker News Reader

Got food cravings? What’s living in your gut may be responsible

pitt.edu

223 pointsgmays147 comments

There's a ton of very new research on this. The big exciting candidate right now is Akkermansia muciniphila, which seems to emit a glucagon-like peptide that moderates appetite [1] (similar to drugs like Wegovy, only maybe without the side effects.) The western high-fat/carb diet also seems to cause Akkermansia populations to drop precipitously, which may be either cause or a separate side-effect of the obesity epidemic.

Apparently supplementing Akkermansia in obese mice has extremely beneficial effects on weight and all sorts of health measures. I tried some from the only supplier in the US and (unfortunately) noticed absolutely no difference, N=1. Still, I am eagerly awaiting the day when someone conclusively nails the obesity epidemic down to something as simple as gut dysbiosis.

[1] https://www.nature.com/articles/s41564-021-00880-5

While I'm fairly convinced that a lot of dysfunction gets a helping hand from microbiota imbalance, including such faraway targets as pulmonary, cardiac, and even neurodegenerative disorders [1], I think there's a simpler culprit: sugar. Metabolism of simple sugars changes biochemical gears, and we as a culture and society are heavy on its use.

[1] https://news.ycombinator.com/item?id=29882347

Sugar definitely seems bad, but doesn't explain why simple fecal transplants are able to replicate many of the health effects of a low-carb diet without the actual diet, at least in some obese mice [1]. (PS I am definitely not an expert in this area, just someone who is tired of eating low-carb to maintain weight, and wondering why other people can just eat normal food.)

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199268/

The whole thing about fecal transplants is that the resulting changes in your microbiome make it so your pull to sugar is weakened. Your diet changes because your cravings change. Imagine how easy it would be if you craved food that was "good for you", or that your cravings for bad food were severely weakened. That's kinda what having a healthy microbiome is like

Grain Brain is an interesting read that covers in a pop-sci way some of the various research being done.

The western high-fat/carb diet also seems to cause Akkermansia populations to drop

The West, typically, eats a tiny, tiny fraction of the fat it used to. And also far less animal fat.

Do you know what went in soups, stews? Bones, with fat, for flavour, and energy, and nutrition.

What were pies made of? Pies, made to allow older apples and such, to be used past their best date?

Loads of animal fat in the crust.

And, especially in Canada, our pork is now leaner than beef was 50 years ago! And our beef is silly lean.

We eat far, far less fat than our ancestors, who would never throw away such valuable, nutritious calories.

If the simple metric is, why were we thin before, and overweight now? And if the answer is "our diet changed", then this logic means we should all be eating about 10x the calories we currently do, in animal fat, and tapering off the rest.

What if all those craving are just simply "the body needs more nutritious fat". Just like our ancestors ate.

What if we crave salty snacks, coated in vegetable oil (potato chips), because our body desperately wants salty fat?

Being overweight is far, far more unhealthy than eating more animal fat daily.

What if the cost of low fat diets, is an irresistable urge which causes weight gain?

If so, low fat diets are, therefore, very unhealthy... because being overweight is far worse.

I’d focus on getting fruit, vegetables, legumes, fiber, and everything that comes with it back into the western diet before I’d look at animal fat as the silver bullet we’re missing.

Too few animal products doesn’t seem like the thing the SAD is missing, either.

Indeed. All this talk about a proper diet without ever mentioning anything but animal flesh and fat.

Can't be the excess food intake. Like too much sweets and meat. No. Fat people are not eating enough fat. It's so simple.

I mean I lost 80 pounds literally eating cheap hot dogs and kimchi for 6 months. It might be that simple.

That's almost zero carbs (if we're talking about "sausage" hodogs, and not "sausage-in-bread-bun" hotdogs)... fat makes you feel full faster and longer, and kimchi add vitamins and almost zero calories, so no wonder you're losing weight :)

Replace those with potato chips and chocolate, and you'll be fat very soon :)

I think the upshot of much of this research is that sugar and fat aren’t directly the issue. That gut bacteria actually have a much bigger impact on both energy expenditure and appetite than we thought. Insofar as diet has a major effect on obesity (in the epidemic sense we’re seeing in the US) it might be due to diet having a harmful effect on gut bacteria. Or it might not. It’s an intriguing hypothesis, and it’s disappointing to see it devolving into an argument about “not eating too many sweets.”

Then there’s the classic lean chicken and tequila diet[1] (plus green vegetables). It’s physically impossible to gain bodyfat on that diet because the storage form of protein is muscle and other lean tissue and the storage form of alcohol is there isn’t one. The body preferentially metabolizes ethanol for immediate energy needs over all other macronutrients. So if you have fat or carbohydrates in your diet they will get stored as adipose tissue, but if you stick to protein and ethanol you’re good.

The above is a joke. However it’s useful to know if you’re cutting and planning to attend an event where you’ll be consuming alcohol. Just skip all carbs and fat that day and eat protein and dietary fiber and you won’t set yourself back at all.

[1] Any lean protein source will do, including bison, grass fed beef, some fish, some pork cuts, and so on. Same for the ethanol, has to be pure spirits, no sugar mixers.

"and the storage form of alcohol is there isn’t one."

Do you have a source for this? I would think at least secondarily it could cause fatty liver or beer belly, even if it's technically using the calories from other sources.

It’s been a while since I Google scholared this and I’m not interested in being an unpaid research assistant. I have no reason to lie, but if you want to check my claims you’ve got the tools at your fingertips.

The essence is that there is no metabolic pathway to convert dietary ethanol into lipids or glycogen. Any unused ethanol is excreted through the lungs or kidneys. Granted ingesting enough ethanol such that it’s too much for your immediate energy needs is a life limiting decision.

I'm 99% sure you're correct on the alcohol reference. From what I've read, alcohol cannot be stored but gets prioritized as caloric fuel for the body. Regarding lean protein, I'm also sure that protein gets broken down into glucose for fuel, and can be stored as such in fat. It's why the keto community is really big on such a relatively low percent of protein and high percent fat in their diet.

That diet probably works wonders because if you have ever tried to eat a bunch of lean meat, it's difficult to get through an entire chicken breast, let alone excess calories it would require you to put on weight.

> Regarding lean protein, I'm also sure that protein gets broken down into glucose for fuel, and can be stored as such in fat.

Glycogenesis is certainly a thing. However every metabolic ward study I read found that there was never a glycogenesis -> lipogenesis pathway observed. Instead excess protein was discarded renaly.

Alcohol is metabolised to ATP and unused ATP will of course be stored as glycogen later. When glycogen storage are full, fat is deposited. Glucose is needed + ATP. High Protein intake will lead to gluconeogensis and create the glucose.

Please link to a metabolic ward study showing ethanol observably being converted into bodyfat through a glycogenesis to lipogenesis pathway. I only found ones saying it never happened, so I’m very interested in any counter example.

You just went from answering someone that asked you for a source with "I’m not interested in being an unpaid research assistant" to asking someone else "please link to a metabolic ward study showing..." in the same thread. Maybe people would feel a bit more generous with their time if you were willing to do the same?

Note that it's called "beer belly" and not "alcohol belly". Beer has a not insignificant number of calories even if you don't factor in potential overeating from intoxication. If by "secondarily" you mean overeating while intoxicated I guess you could also factor in organ damage from drunk driving accidents or fights.

Not just overeating. If the body performs to use the alcohol as energy as claimed, then the normal amount of calories that you already ate would be stored instead of used. Alcohol and it's metabolites can directly cause organ damage.

that's a recipe for gastric cancer

"sweets" are the alternative to fat. That's the point.

There was a concerted effort to reduce fat intake in the United States throughout the latter half of the 20th century, and the timing of this effort lines up pretty well with the beginning of the obesity epidemic.

I enjoyed the documentary Fed Up which claimed that when the low fat craze was beginning, the industry had a lot of excess fat, so you also see a rise in cheese advertising around the same time.

Yeah but it replaced fat with refined sugar. That doesn't mean adding animal fat back is an unconditional improvement

Sure but, to my understanding, the human perception of satiety (“being full”) is far more sensitive to animal fats than refined sugar.

> Can't be the excess food intake. Like too much sweets and meat. No. Fat people are not eating enough fat. It's so simple.

There can be second order effects. For example, it's not that eating a bunch of animal fat will magically get or keep you thin. Instead, it's likely that eating fat you'll not eat as much of it, and even better: eat little to no sweets or other "junk".

I'm not convinced that eating too much meat gets people fat. By that, I mean the meat itself. What I've noticed when eating out, is that meat is often drenched in some kind of syrupy sauce. And I notice that whenever I eat such a meal, I'm left hungrier, or get hungry quicker afterwards, compared to if I eat the same quantity of meat but with just a few spices. Most of the times, I'll find there's too much meat, and not even finish it. But with the sauce? I'll only stop when I'm physically bursting.

Another poster touches on this, talking about satiety. It's very clear to me that some foods just give me the impression of being hungry and wanting to keep on eating them. And it requires a great deal of will power to not indulge. Bonus points for these foods being "bite-sized", when you figure "just one won't make a difference". Only issue is, "you can't eat only one", as the ad says.

Maybe exercise is a component too. We traded manual labor for sedentary desk jobs.

Protein too. Americans used to consume considerably more animal protein, especially red meat. For example the typical Union Civil War field ration included 20 ounces of meat. I don’t have any non military data, but I’d bet that the rations were modeled on the civilian diet.

Yeah but that was for guys marching 10-20 miles per day.

Field rations are hardly representative of normal diets. Meat consumption has gone up since we invented industrialized meat farming, because meat got so much cheaper.

> Americans used to consume considerably more animal protein, especially red meat.

This is not true.

Per capita meat consumption has increased over the last century, with red meat consumption peaking in the 1970s. It looks like total meat consumption has increased about 40% since the early 1900s.

[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045642/

[1] https://www.thedailymeal.com/how-american-diet-has-evolved-o...

If you're going to falsify my claim that 19th century Americans ate more protein and red meat, you may want to find some sources that aren't talking about the 20th century.

Years ago I read about the massive amount of grease (food waste from kitchens) in the London sewer system and thought ~what went wrong in our (my/Western/Euro-centric) culture where we don't use the fat?

Also, if animal fat is important for our health, that's another reason we don't scale well as a species. Seven billion humans and life on the planet continues to groan.

Ties in with the thread about how comicbook stores aren't kid-friendly; we (the relatively wealthy, globally) have been growing accustomed to having whatever sideshow we want as the main course in life. It's an easier life for a few of us in the short run, and an interesting experiment. [0]

[0] https://www.worldcat.org/title/ultimate-hitchhikers-guide-to...

From my perspective:

Pork raised on a small farm has ridiculously pure white fat. Heritage bacon fat turns clear as it is cooked. It's delicious, even unseasoned, and the texture is firm and pleasing. The flavor is nutty.

Industrially raised pork fat is disgusting. It is pinkish gray, milky, and stringy. It does not properly render during cooking (seems like too much connective tissue). It is mostly flavorless, or even acrid, and the texture is more chewy than firm.

The problem with the US farm system is that our food should be more expensive. Eggs, poultry, pork, beef, but also many vegetables. breads, etc, just don't have the dietary benefit that we had in the past. Garden grown celery is almost inedible raw - the flavor is so intense a single stalk can flavor an entire stew. Garden grown carrots are hearty and flavorful.

The quality of the food we are producing tends to be abysmal.

We can can unsaturated fat from olive oil and omega3 from walnuts/flax- or chiaseeds.

<add> ~70% of mankind lives close to water, ie have acces to fish (O3). There are tribes that that don't. When they shoot an ape, they eat the brain (O3) and intestines (unsaturated fats). The meat gets thrown away.

"What if all those craving are just simply "the body needs more nutritious fat". Just like our ancestors ate."

Not necessarily fat, but most produce has lower nutritional value than it did 100 years ago, at least for some nutrients. It sounds like there are a variety of potential causes - soil depletion, synthetic macro fertilizer ignoring micronutrients, selection or genetic modification for larger/faster varieties with plants unable to move enough of certain nutrients to the larger fruit load, longer storage times due to modern supply chains, etc.

People seem shocked when they find out that high-fat diets can be hugely beneficial for weight loss. I couldn't lose weight if it wasn't for keto. And the plus side is once you're used to eating high fat foods, you're just not as hungry. I've been finding myself kind of forcing to eat just to get enough calories now. Although I will say, some of these low carb ice creams are delicious and pack a ton of calories and fat.

> The West, typically, eats a tiny, tiny fraction of the fat it used to. And also far less animal fat.

We dont do the exercise of previous generations.

One study conducted around the early 1900's got ordinary people off the street to carry out a set of physical tasks. What stood out for me was the tasks and time it took to complete, todays special forces people would struggle to keep up with the physical exercise of those from the 1900's.

Yes our diets have changed, we can grow food more quickly, the nutrition of the food is different to that seen in the early 1900's and arguably less nutritious but satisfies the short term needs of an over populated planet.

One example, muscle density is in decline, for example US special forces know that black people have higher muscle density that Caucasians, this means Black people cant tolerate the cold or swim because they dont have the layers of fat seen in Caucasians. To the point Black US special forces have successfully sued the US military over Arctic deployments because they fail in this environment and the US military knew this before deployment.

What the science doesnt tell, is Caucasians used to have the same muscle density and limited amount of fat in/on their body as seen with Black Americans generally.

Carnitine is one of those chemicals which increases muscle density and its similar to Choline, main food source Beef Steak! Even ground beef has substantially lower levels, the mechanical processing removes some of it. Now this shows how science can obfuscate, look at the studies which show Choline aiding exercise and weight loss, Carnitine is structurally similar but studies on Carnitine generally dissuades people from using it for exercise enhancement. So if you didnt know about the structural similarity of the two, you wouldnt link their biological properties together.

There are a lot of chemicals like this and some chemicals which are generally seen as the best FORM to take are not always available in a unadulterated form of bulk consumer amounts, but only as a consumer end product adulterated with other chemicals you dont really wont and in some cases working against the chemical in question.

Diet is a very expensive absolute mind field, fortunately even the medical experts dont know it all because of their instance on injecting some chemicals still!

> The West, typically, eats a tiny, tiny fraction of the fat it used to. And also far less animal fat.

This is false, or at least not supported by any data I've seen.

Fat consumption increased 39% from 1909 to 2000 [0].

Meat consumption increased about 40% from 1909 to 2007 [1].

You are right that many of the fats have changed from animal fats to seed oil fats mostly from the 1970s onward.

[0] https://www.beatalewismd.com/blog/fat-fads-changes-in-fat-co...

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045642/

Still, I am eagerly awaiting the day when someone conclusively nails the obesity epidemic down to something as simple as gut dysbiosis.

That's unlikely to happen. Nutritional content of produce has gone down, people eat fewer home-cooked meals and we drive more and walk less, among other things. So it's not likely to boil down to "This one simple trick!" that can be solved with a simple product one can buy for cheap.

If you look at the timing of the obesity epidemic you notice that it has a very sharp “knee” in the US around the 1970s. It does not coincide with the introduction of fast food or the automobile or sedentary living, and contemporary people exercise more in many cases than they did in the 60s and 70s, with vastly higher BMI as a result. The same pattern occurs in other countries just at later times. And the effect size is huge. Much larger than anything we can achieve with diet and exercise (durably) or even the best weight loss drugs. I don’t know what’s causing it, but “gosh people eat poorly” doesn’t seem like a good explanation. I thought this was a good (amateur, but accessible) summary of some of the stats: https://slimemoldtimemold.com/2021/07/07/a-chemical-hunger-p...

I don’t know what’s causing it, but “gosh people eat poorly” doesn’t seem like a good explanation.

I'm not sure what your point is because what I said boils down to "There seem to be multiple factors, not any one thing."

I've lost multiple dress sizes by improving my health when losing weight wasn't a goal at all. Among other things, that experience informs my views and I don't really know how to engage whatever point you are trying to make that seems to not really engage with anything I actually said.

But thank you for the link. It's got a take I hadn't previously seen.

Me too. But fundamentally I’ve never consistently long-term kept my weight below where my body seems to want it. Enjoy that link. I think they’re right in the early parts but maybe they don’t quite land it at the end.

Available calories went way up (and so did disposable income):

https://academic.oup.com/ajcn/article/91/5/1530S/4597478

Of course availability is not a perfect proxy for consumption, but they are probably somewhat related.

And people got more sedentary over the same period.

That’s exactly when health experts and the government started to heavily promote the low fat diet.

> “gosh people eat poorly” doesn’t seem like a good explanation.

Maybe they drink poorly? One guy shown in Super Size Me drank 8 litres of soda a day IIRC. The body has no use for fructose, it can only be converted in the liver to fat. You can even get a fatty liver from it, like with too much alcohol. Soda is usually sweetend with HFCS (high fructose corn syrup) no?

Fructose is converted into glycogen in the liver, which is then converted into glucose or fat, the body uses fructose just fine.

Regularly consuming 5000 calories of anything sugary or starchy is going to be a problem for most people.

This is a startling and very interesting article. Thank you!

> Nutritional content of produce has gone down

I doubt doubt the findings, but I haven't heard of an epidemic of micronutrient deficiencies. With a lot of micronutrients, you only need so much, and then your body dumps the rest. What you're saying might be true, but I'm not convinced it's a problem.

But there does seem to be an epidemic of "mystery ailments" with no real explanation.

What if that's not some bizarre coincidence and is actually related in a cause and effect manner?

what does a non western diet include that is so much more healthy? In my limited experience it doesn't seem that way or atleast you can pick and choose what you want. Rice is a big thing and white rice has a high glycemic index. or cooking with ghee, or coconut milk or fatty cuts of meat

> Still, I am eagerly awaiting the day when someone conclusively nails the obesity epidemic down to something as simple as gut dysbiosis.

On average, what is the daily caloric surplus (calories in - calories out) for Americans vs. the rest of the world? I suspect going for exotic/complex explanations for obesity may not be necessary, therefore think change is gut bacteria is an effect, not a cause of obesity.

Lot's of other places have a high-carb diet (staples are rice- or corn-based), and yet do not have obesity crises because those areas also have low mechanization, high levels of menial labor and walking

I eliminated food cravings in perhaps an unorthodox method. It wasn't my intention, but I am better off for it I believe. I started with a 72 hour fast (water only). After that, I had a bite of a steamed carrot and the experience immediately after tasting the carrot was the biggest natural high of my life. It was like my brain dumped every pleasure producing chemical into my bloodstream. I started to focus on healthy veggies and fish/chicken with small servings of nuts and avocados. I lost 20 pounds (so far) and don't craze processed sugars like I have in the past. When you stop eating a lot of sugar, the gut biome bacteria chlamydia starves I think, and you are much healthy for it.

> the gut biome bacteria chlamydia starves I think, and you are much healthy for it.

I believe you are thinking of candida which is a kind of yeast which is fungi not bacteria.

I think that you are correct. I have been on Dr. Fuhrman's Eat to Live diet a few times: start by eating no processed food and drastically reduce sugar intake unless it is berries or a little fruit. After about a week, the level of candida in your system is reduced to levels closer to what humans had > 50 years ago. At this point, all sorts of food cravings (especially deserts) go away, and homemade meals from natural ingredients taste very good. The first time I went on this diet, I felt 10 or 15 years younger with lots of energy.

This has been my experience. I have lots more energy and zero cravings and hungry pains are truly a thing of the past.

fungi are smarter and more meticulous than bacteria, so I’m willing to believe they could dictate our preferences

Yes, you are right. candida. Thanks for the correction.

I had a similar experience when we introduced our child to solids - we all ate the same meal so obviously added sugar and salt were out of the question.

Within two weeks I started experiencing flavours that I previously had no idea were there - especially rice has a different taste initially than after it's chewed.

I used to eat those instant ramen noodles every other day. Now I can't stand the salt content.

Dunno if you care or not since they're still not healthy (just starch basically, but, instant ramen without the 'flavor' packet has all sorts of great ways of preparing it. Budget Bytes has some excellent suggestions - https://www.budgetbytes.com/?s=ramen

I was telling people that the carrot tasted like candy to me and they looked at me like I had lost my mind.

You should try some baked vegetables, carrots, potatoes, cauliflower in the oven with a little avocado or grape seed oil and a little balsamic to finish.

The carrots will taste like candy.

The balsamic usually has a lot of sugar in it. If I was trying to reset my sugar cravings I would avoid the balsamic.

I just checked the last balsamic I used, it is 45 calories (10g of sugar, 5g of which is added) per 15mL. While there is more sugar than I expected, I used 1 table spoon or 15mL for a full baking sheet of vegetables. You are right about resetting sugar cravings and to watch out for sugar sneaking into your diet. I find lots of foods at Trader Joe's have more salt and sugar than I would expect.

Starches like rice will taste different if you allow saliva to work on them - your saliva contains enzymes which break down starches into sugars. This is commonly demonstrated in middle school science classes by having kids chew a saltine cracker, and taste how it starts out bland and ends up tasting sweet as you hold it in your mouth.

Honestly that never worked for me. Maybe I was too impatient.

I don't think salt is bad for you.

Eliminating sugars or salt will make you realize just how overly sweet and salty most food that isn't prepared at home is.

It’s wild to me how heavy cream tastes sweet after you acclimate to a low sugar diet. It has something like 1g of sugar for every 12g of fat (if I remember from the label)

And attempting to eliminate sugars shows you just how ridiculously difficult it is to avoid it in the US.

Like, why is there extra sugar in my bread?

Gotta eat your foot long subway cake.

Especially on a budget. It's very hard to find cheap food that isn't full of added sugar

I think I did this too, but in reverse! Unfortunately I couldn’t get to the store fast enough after my 72 hour fast, and my stomach hurt so bad that I ended up eating a Chalupa. Then I gained 60 pounds. Oops.

At least you inspired the weird Pavlovian Taco Bell ad campaign. So that's nice.

Actually anjoying food is, somewhat paradoxically, a great way to control weight.

Watch fat people eat. It's like they are trying to maximise calorie intake. Food is shovelled in. Bites are taken before the previous one is even swallowed. They don't really enjoy the taste of the food, they just want the feeling of hunger to go away as quickly as possible.

Watch how French people eat. It's not about survival, it's about enjoyment. Each bite is savoured. Time is taken to appreciate the food. It's one of the most important times of the day.

French people eat like they're making love. Fat people eat like they're jacking off to porn to deal with the daily urges.

Needs citation.

It's just my observation. Look and see for yourself.

But, quite honestly, there's no way anyone is getting fat unless they are shovelling food into their mouth.

Similarly, I have found that every time I severely limit carbs for a solid 3-4 days my appetite flatlines instead of rapidly rising and falling throughout the day. And everything starts to taste better. And I have way less gas.

> And I have way less gas.

Sounds like you have a gluten intolerance.

Not sure if it's comparable but at some point I couldn't eat anything but raw veggies and after a while my brain started to sense finer taste and flavour in stupid lettuces or tomatoes. Made me realize the modern diet is so filled with supplements (fat, sugar and salt apparently) that it hides everything subtle and blinds you into seeking addictive unhealthy meals.

I didn't realize this until recently, but we don't actually know every chemical compound that's in our blood. As in, I don't believe there has been a study that takes 1 liter of blood and just documents every chemical structure found (at any concentration).

Realizing that + learning about the seemingly vast gut microbiome has definitely led me to feel more humbled about what we know and can predict about human biology.

I now think it's possible (but certainly not proven) that some hard to anticipate cascade of compounds (produced by gut, or foods, or environmental, or whatever) could be responsible for significantly increasing subjective feelings of hunger across the population at large, and this could lead to more calories being eaten than needed.

I'm actually optimistic that this has happened, because then there might be an effective way to reverse the health problems we see... much like removing leaded gasoline seems to have helped reduce crime rates.

The complexity of life is nuts. Once you start learning about how things work, you can see that we only know a tiny fraction of what's going on

I mean sure, I’d love a scalpel but right now we don’t even have a hammer.

It would be fantastic to do something even as simple as shut off the hunger signal for set intervals.

Imagine if you literally couldn’t feel hunger from say… 10am to 6pm. There’s all sorts of cool hacks we do to improve humanity if we could get a grip on cravings.

Organic growth is like “Throw bits into the computer and see whether they make NPM.”

…And the complexity of an NPM project is nuts, actually.

Highly doubt there is a silver bullet. There are likely a myriad of reasons because diets and genetics are so diverse. Sugar is the obvious villain though.

Have you come across the environmental theory of obesity?

https://slimemoldtimemold.com/2021/11/23/a-chemical-hunger-p...

there is this sort of modern attitude toward science that tacitly assumes that we understand some sufficient majority of the nature of reality, when in fact reality is apparently infinitely fractal.

I think most of the gaps in our understanding of biology stem from the scale at which we exist. Most biology takes place at the cellular or even the molecular level, we only see the very far removed macro-scale effects of a myriad of intertwined processes.

hah. not even close. we had moderate success in understanding and modeling some phenomena, but in the grand scheme of things we don’t know much. which is both scary and great if you have a curios mind

Why is it scientists would have us believe that they know everything definitively regarding covid, covid vaccines, climate change, etc?

Literally no scientist has ever said that they know everything definitively about any topic, let alone those.

But we ascribe policy as if they do know 100%.

The fact that politicians are idiots, in addition to surprising approximately zero people, shouldn't be used to impugn science.

I think there's a difference between "we make and adjust policy based on the strongest theory we have with an extra dose of caution" and "we think science is infallible."

Go over to the Atlantic (https://www.theatlantic.com) and read through their coronavirus coverage starting all the way back at the beginning of 2020. You have been sold a lie in your TikTok bubble.

not only that, but our gut is literally the 2nd brain of our bodies. Read somewhere that there are more than 200 million in our gut. To put it in perspective, that’s more neurons that all the neurons in a dog’s brain.

> a study that takes 1 liter of blood and just documents every chemical structure found (at any concentration)

That’s because we don’t actually have the technology to do that. You can test for specific compounds that you know how to test for, and if their concentration is high enough. But there’s currently no way to e.g. go through a given sample molecule by molecule.

Both these comments are a great way of putting it. I never thought about this before. Very interesting.

I thought you would be able to do this with a mass spectrometer. Although you would probably need a lot of blood :)

Exactly, IBM can make movies using individual atoms, surely we aren't too far from being able to look at molecular structures and deduce what compounds are in a sample of blood.

You'd typically need reference samples if you're trying to get a typical lab to analyze compounds via mass spectrometry, which would make identification of unknown substances in blood hard for non-researchers.

A mass spectrometer by itself, will tell you the mass to charge ratio of ions in a sample. In most samples the molecules themselves are not ions naturally and need to be ionized. This can be done using a number of techniques, but a common one is electron impact ionization, where electrons are slammed into molecules causing them to fragment into charged ions. This smashes the molecules up into small charged chunks which can then be analyzed by the mass spec. These mass spectra are good fingerprints for the original molecule and can be mapped back to what molecule must have been smashed to produced them. However, if you try to analyze the mass spectrum of a mixture of molecules that are similar you will not be able to deconvolute the result into any unique answer, i.e. there will be many possible mixtures of molecules that could have resulted in the mass spectrum.

This limitation of mass spectrometry can be overcome by first separating out the mixture of molecules you want to analyze into different fractions before they are ionized and enter the mass spectrometer. One common way to do this is to use a gas chromatography column. This works by first heating the sample so that it turns into a gas, and then passing it through a long column that is packed with a material that will interact with the gas and slow some molecules more than others. Often it is packed with silica. In this way you get the technique called GC-MS (gas chromatography/mass spectrometry).

GC-MS is a fantastic technique for analyzing complex mixtures but it will have its limits if there are too many different types of molecules in the mixture. In blood there will be tiny molecules like O2 and CO2 and giant macro-molecules like DNA. There is no technique I know of that can analyze such a wide range of molecular masses in one go. Plus mass spectrometry doesn't directly give you the structure just the masses of the fragments after you blow up the molecules (or the total mass if a more gentle ionization technique is used as is sometimes done for macromolecules).

I write all this just to explain how there aren't any analytical instruments that you just inject a sample into and out pops all the chemicals and their concentrations. Blood is a amazing soup of different elements and molecules and a full analysis requires a large number of steps and different analytical techniques to get even close to fully characterizing.

What a gloriously through yet understandable explanation of the problem and its context, thank you.

Thank you, I've always wondered about these but was too lazy to check.

Mass spec (at least as of a few years ago) require reference spectra to identify compounds. Without them, you can guess at structure but it's not accurate.

Does anybody know of good research which shows how long it takes the microbiome to adjust if you significantly change diet? New diets can be hard to stick with initially, and it seems like the gut's "needs" may be a real cause of this.

I'm a long-time serial dieter who has radically changed my diet on several occasions now, from SAD to vegitarian to SAD to vegan to SAD to raw vegan to SAD to FODMAP to SAD to McDougall high carb to paleo low carb to meat-centered to (currently) carnivore. (Among others.)

Each time (moving to non-SAD) it takes around six months before I stop naturally losing weight and either stabilize (on carnivore) or start heading back up (on everything else). I attribute this mostly to the microbiome, so by my own N=1 experiments, I'd say about six months.

As a fellow failed dieter, just trying to find something that will work for me ...

So you switch diets because you stabilize and want more weight loss, OR because they stop working? Curious to hear about the switch.

My personal preference is sugar-free. Successful for 2 years from 2016-2018, and now trying low-sugar (not no sugar) since January 2022, and reasonably successful although not much (just 6 lbs about 3%) to show for it.

I was a failed dieter from age 7 to 57. It took me that long to figure out that this body works best on animal products. I was never a particular meat eater and had to be forced to try it by an inability to move my bowels on anything else. But it has reduced and stabilized my weight like nothing else has, while all but eliminating my cravings for SAD food. I really like eating this way now, and get as much or more pleasure from food than ever.

When I switched it was in despair over failure. They all (but the last) stopped working, though I continued to follow them religiously. For years I was an obsessive food diarist, and have books full of logs on what I ate, with charts showing how my weight gradually stabilized well before goal, and started going up again. This followed the trend of my appetite. When I switch diets my appetite goes down, and it recovers gradually over that half-year.

I think going sugar-free is a great move, but from sources like https://high-fat-nutrition.blogspot.com/ have come to think that avoiding seed-oils is even more important, over a span of decades.

imagine all the microbiome meetings and all the unhappy little fellas having to go through a reorg every 6 months. :)

LOL - I snorted ...

Maybe they can 'pivot' in a new direction :-)

need to receive a VC cash infusion immediately to prevent hitting the end of their cash runway!

Infusion of B-round, specially targeting the larger flora in the gut..

I heard that vitamin B-round can help the flora!

yes, but only if they can grow fast enough to make an IPO operation feasible...

This was a good enough question I started researching. TL;DR: Your microbiome adapts quickly, but you don't get to see the full effects for weeks to months.

Turns out, your microbiome will shift significantly within a few days of changing your diet [0]. A more recent study showed that increasing raw vegetables in your diet significantly changed microbiome at about the same speed [1].

However, because the _effects_ of a healthy microbiome are things like better vitamin reception and disease prevention [2] [3], it can take months to see the effects of something like better B12 can take weeks to see [4]. Disease prevention of metabolic diseases takes years to see fully.

[0] https://www.scientificamerican.com/article/the-guts-microbio... [1] https://news.harvard.edu/gazette/story/2019/10/study-finds-g... [2] https://en.wikipedia.org/wiki/Human_microbiome#Disease_and_d... [3] https://depts.washington.edu/ceeh/downloads/FF_Microbiome.pd... [4] https://www.nhs.uk/medicines/cyanocobalamin/

Another link for you https://pubmed.ncbi.nlm.nih.gov/25198208/

It’s very quick: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957428/

There is general research that shows that after about two weeks of limited inputs, bacteria colonies will go dormant, retreating into the structural matrix ("slime") that bacteria produce for themselves. If fed, they will come roaring back relatively quickly. To mostly kill off a species of bacteria, it can take months (6-ish?) of starving them during their dormant state. Sorry, no links, just reporting recollections from general reading that I have been doing.

Stop reading now unless you are interested in cardio-vascular disease.

I started researching this a little over a year ago when I got a cardiac stent to prop open a 99% blockage in the left anterior descending artery. Yeah, I was probably within weeks of having the classic widow-maker heart attack. (I didn't, and I'm now fit and healthy, so I consider myself lucky.) I eventually found a line of research out of the Cleveland Clinic, work done by Dr. Caldwell Esselstyn. His work is based on this: 1. CVD is the result of an injury to the endothelium that first attracts white blood cells to the damage, then cholesterol joins the party and they form "foam" cells that can get under the endothelium and eventually calcify. 2. The endothelium produces Nitric Oxide gas that is both a vaso-dialator and also helps the endothelium repair itself and cleanse itself of non-calcified foam cells. 3. The primary driver of CVD that is associated with the standard American diet is that the diet destroys the Nitric Oxide blood gas.

How does that destruction of Nitric Oxide happen? 1. Carnitine, lecithin, and other proteins found in meat, fish, diary, and oils are metabolized by a colony of gut bacteria to produce tri-methyl amine (TMA). 2. TMA travels to the liver and is metabolized into tri-methyl amine oxdide (TMAO). 3. TMAO enters the blood stream and annihilates nitric oxide, robbing the endothelium of its self-defense mechanism. Eating a meal that feeds that bacteria colony will suppress nitric oxide blood gas for 6 to 8 hours. So, if you eat the SAD at every meal, the level of nitric oxide will never recover.

I am on a mission to starve those little bacteria bastards out. Kill'em all with gleeful murder in my heart. So for about a year I have been on a diet that is most easily described as vegan, with the additional restriction of no oils and high-oil foods. I wish I had some good way of measuring my blood TMAO levels. I don't, so I'm just going by the general rule of being as strict as possible for several months to try to knock the bacteria out as best as I can.

If i remember correctly nitric oxide is/was a pretty popular weight lifting supplement. Did you ever try supplementing it?

> To mostly kill off a species of bacteria, it can take months

Why not just take a course of antibiotics before you start you new diet?

Trying to be selective. I don’t want to screw up my entire gut microbiome.

Something that's always confused me is how I get powerful cravings for sugar, but am relatively untempted by salty foods or carbohydrates, wheras my sister(very close in age to myself) isn't tempted at all by sugar but is a sucker for salty foods. We grew up in a presumably quite similar culinary environment. I've often wondered If the differences can be explained by gut bacteria.

Also, surely the claim that this is the first study to show a link between gut bacteria and food choice is wrong? I'm pretty I've known about the link for years?

I’m pretty sure sugar cravings in my family are simply garden variety hunger. For us “sweet tooth” mostly correlates with missed meals. The brain runs on glucose, so when the body is low on food and blood sugar dips, sugar is the “quick fix” for the brain.

This 100% lines up with my experience, every time I’ve changed my diet I started to prefer the foods I was eating. Instead of palate fatigue, eating something a lot causes me to crave it more.

I used to eat a diet of mostly frozen foods. Then I made an effort to eat more vegetables and suddenly started craving vegetables. I use to prefer high-carb low-fat, then I started eating more meat and gradually shifted to preferring low-carb high-fat, except when I took a break and alternated between the two.

My pet theory is that we have to constantly change our diet, behaviors, etc to move faster than the bacteria and the fungus, otherwise they adapt and start controlling the host.

The fasts proscribed by some cultures might be a way to reset our guests.

People used to have to change their diet seasonally and buy what was available at the local market. Now people can buy the same product year round and get stuck in a narrow diet.

I'm on day 10 of a 14 day water fast. The hunger was very bad for about the first 7 days and now its been nothing. The idea of eating is interesting to me, but the visceral hunger constantly reminding me to eat isn't there anymore. Long term fasting is great like that.

Are you really not eating for 2 weeks?

Yes, really. Some people do it for 30 days or more if they have a very large amount of weight to lose. You have to take electrolytes (potassium, sodium, magnesium), and it should never be done if underweight. I started getting seriously into fasting when I asked all the people I met at longevity conferences who looked extremely good for their age what practices they used. The ones who looked the best for their age were longer-term fasters.

Fun fact, the longest fast was 382 days[1]. The guy started at 456 lbs and ended up at 180 lbs.

[1]https://en.m.wikipedia.org/wiki/Angus_Barbieri%27s_fast

I am very curious about a couple of things regarding that experience, so I hope you dont mind if I ask a question. I want to preface it by saying that I am not trying to dismiss this pracice as inherently dangerous or bad (because I frankly have no idea).

While with 14 days of it probably not being a concern in that aspect, but do people who do it for much longer periods (100+ days, or maybe even less would qualify) not have any atrophy-related issues in relevant systems? Anything related to their intestines and all the way to the exit, wouldn't they lose a significant amount of their ability to do their jobs properly? I am not saying they should be able to start processing 5000kcal of carb heavy food immediately in a single meal after the fasting stops with no issues (as that 5000kcal meal can would give quite a lot of healthy people who dont fast issues as well), but would their intestines actually be able to function fine again? I mean, for something even as banal as sphincter muscles, I am simply lost. Is human body actually that adaptable to handle it like a no big deal?

You could always do the “lite” version like me.

I eat one day and fast the next. I rode this very simple procedure to melt away 40 lbs (was easy). I have been doing this for about 3 months, lately my weights been stable as I’ve skipped fast days.

I also only eat for about one hour on days when I do eat; normally it seems like the sugar rush becomes noticeable at the one hour mark, so even if you eat for the whole hour, that will pause you.

My experience:

1st day of fasting is the hardest. But if you are fasting every other day obviously you’ll get used to it.

You become aware that your imagination (imagining savoring the food etc.) was a big part of your eating. Knowing that it’s easier to not eat.

I don’t know what it’s like to skip food for multiple days (well, more than 2), but for 48 hours between meals, it’s very doable, and stops feeling “heroic” (or needing massive willpower) pretty quickly. It just feels like your stomachs vacation day - which feels good.

> I eat one day and fast the next. I rode this very simple procedure to melt away 40 lbs (was easy).

Do you know how much of this is muscle, fat and water?

Between muscle and fat - a lot, an even mix; I didn't care if it was muscle or fat and didn't do anything to retain muscle. I have a condition such that, for me in particular, protein is hard on my body; so I want to have basically the minimum amount of protein in my diet and, by extension, a low amount of muscle (so as not to have to consume any more protein than is necessary).

As for how much of that was water: my weight still fluctuates with water but in the normal range - 2 lbs up or down, let's say. My weight has stayed in its current range for... weeks now, so I don't think I could call the lost weight 'water weight'.

In long-term fast of more than a week there's the possibility of refeeding syndrome. If the person fasting hasn't kept up with their electrolytes, they can have possibly fatal issues if they absolutely gorge themselves when stopping the fast. When I end the fast, I am going to proceed gently for the first couple of days before resuming a normal diet even though I have used an electrolyte formulation to keep my electrolyte levels at an optimal level.

I'd love to learn more about the longevity conferences you've attended, if you don't mind.

The ones who looked shitty because of long-term fasting probably didn’t attend.

If it works for you, sounds great. But this is survivorship bias 101.

This made my brain go straight to pregnancy. The women I’ve spoken to all describe it as feeling like they’re experiencing someone else’s cravings.

I spent most of my life hating pickles. Suddenly a couple a couple months ago I started craving them like crazy out of nowhere. I bought a jar to the dismay of my wife who hates them, and found that I now loved them. I've in the last couple months gone through 4 jars of pickles.

I have zero explanation. I mentioned it to my doctor even, and he seemed wildly disinterested.

I wonder if something in my gut changed?

I never liked chocolates. Then about 4-5 years back (then late 40s for me), I started eating, and then for the next 2-3 years, I could never resist having a chocolate. Then after some effort from my side, I stopped and now I do not feel as tempted, but I remember the days.

I've been getting some bad acid reflux lately leading to gnawing in my stomach due to a lifestyle with lots of going out recently as the weather gets better and more events start happening and everyone comes out from covid and the winter. Looking forward to a hopefully relaxing May to take it easy for a bit!

It's amazing how much yogurt helps though. It's very noticeable, and very quick.

In case anyone get the idea from reading the article that tryptophan and serotonin are good for you, check out Ray Peat and he has extensive writings on them.

My observation is that there are two type of brains when it comes to processing serotonin. One type processes it quickly and increased serotonin increases good feelings. The other type processes it very slowly and increased serotonin creates all kinds of problems for this type. This type also tends to struggle with slow processing of catecholamines.

According to Ray Peat, serotonin has many other functions in the body and increased serotonin can cause problems. Here is a good read: https://raypeat.com/articles/articles/serotonin-depression-a...

tldr.. whats the best way to stop hunger cravings.. green tea?

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