How food powers the body's metabolism | Hacker News Reader

How food powers the body's metabolism

newyorker.com

221 pointsgautamsomani199 comments

The author profiled in the piece, Nick Lane, wrote a really thought-provoking earlier book called The Vital Question. Addresses some similar points, esp the aspect where biologists have (understandably!) focused a lot on information theory since 1953 DNA discovery. But that they have neglected integrating understanding of energy. By integrating both perspectives, Lane and his collaborators have generated fascinating (and testable) hypotheses about how/where life began in the ocean as well as the sequence of steps that led to eukaryotes and eventually multicellular organisms. Plus has implications for why sex, aging, and death might have evolved! Highly recommend it.

Although a pretty good HS or early college foundation in redox chemistry is pretty needed to get the most out of the book.

Did you read/enjoy TVQ? I have it on my book shelf but so far I haven’t picked it up (:

The Vital Question is the only book I've read cover to cover. I got through about 15% my first attempt and decided I had forgotten too much chemistry to truly appreciate it.

A few years later I undertook an intensive chemistry self-study for reasons unrelated to Lane. After that, I was ready to tackle TVQ again; this attempt went a lot better. Truly loved it and got me thinking and reading related peer-reviewed papers.

I've been thinking about which of his other books to try next but I've gotten to a point where I actually prefer to do problem sets in early/intermediate college-level organic chemistry! Will check back in with Lane in a year or two.

I did. I loved it, and I am only superficially familiar with the chemistry being discussed in the book. It's quite eye opening!

It's phenomenal. There were dozens of thought provoking discoveries and conclusions drawn from what I had previously thought was an esoteric subject.

Nick Lane has also been on some good podcast interviews:

  - Long and in depth on Lex Fridman, plus it was funny because he is about the only guest that didn't play along with Lex's goofy off the dome ideas - https://lexfridman.com/nick-lane/

  - Sean Carroll - a more serious discussion - https://www.preposterousuniverse.com/podcast/2022/05/23/198-nick-lane-on-powering-biology/

one of the more interesting books I've ever read. And I've even gone back to reread parts of it, which almost never happens.

I have read all of Lanes books and I think Sex, Power, Suicide is the best - and probably the easiest / most approachable read.

Sex, Power and Suicide is an extraordinary read. I'm a little frightened to buy his newest Transformer since it looks a little heavy on chemistry. Can anyone comment?

I'm partway through it on Audible. He doesn't pull any punches with the science, but he's such a good writer. A lot of it has been a history of biochemistry in the 20th century - I didn't realize that Krebs and others were so recent.

If you were comfortable with the difficulty of The Vital Question, you can handle Transformer.

FTA: “Although “Transformer” is aimed at laypeople, it’s not a particularly easy read: there are diagrams of chemical reactions alongside talk of succinate, oxaloacetate, and the reduction of this and that. Reading it, I had to consult Wikipedia and Khan Academy.”

This article has a huge flaw: it only talks about glucose metabolism but completely ignores the fat metabolism.

For reference: fat metabolism is equally important, or maybe even more important than the glucose part of it. It should not be ignored, it should be taught.

Otherwise a reader may get a wrong impression that glucose is _the_ energy and then will go to a shop to grab the usual candy, thinking that sugar + oxygen is what makes cellular ATP. But this is only one half of the story. The full formula is:

    sugar + fat + oxygen = energy

But there is a trick. Sugar suppresses fat metabolism and vice versa. This suggests that eating sugar + fat is a bad idea, and it is. But what the average Joe does not know is that:

    fat + oxygen = even more energy

For example, 1 molecule of glucose leads to production of 32 ATP molecules, while one fatty acid molecule produces 48 ATP molecules. ATP is the energy currency in our bodies, so the more we have it the more healthy and energetic we can be.

The catch with fats is that they are slow to get going. Glucose action is instant while the fats need tens of minutes to be engaged in energy production.

Another catch is that fats can be relatively easily damaged rendering them unhealthy. For example, the production of refined vegetable oils uses high temperatures to "squeeze" the oil out of the seeds. This process inevitably damages long chain fatty acids breaking them into shorter pieces and oxidizing them along the way. Such trans fats cannot be consumed by our bodies: their chains are too short to be correctly processed and are too big to pass the mitochondrial membranes. This will gradually lead to a metabolic dysfunction while filling the cells with unprocessable "junk".

But if you consume high-quality fats as a part of a daily low-carbohydrate diet it makes miracles: no belly, better cognition and you don't need so much food anymore. For example, the following products are considered as the sources of high-quality fats: avocado, fatty fish, extra virgin oils, nuts, European round cheese.

The thing is that people don't know this until they hit a health condition that makes them vulnerable and sensitive. We live our lives eating tons of sugar and thinking that this is the right diet because "sugar = energy", but it is not. Articles like this fuel this wrong impression. As the result, we gradually loose our metabolic flexibility and may become seriously sick at some point of our life.

“European round cheese”

This is… vague. What are the qualities of a cheese that make it shift into the ‘high quality fats’ category?

Probably the best bet: naturally produced products without using hydrogenation and too much heat.

From the formal standpoint a high-quality fat product should not contain trans fats or contain just a small amount of them.

Sure: but neither “European” nor “round” provide a heuristic for identifying those qualities.

Edit: to expand, a quick look in my fridge shows the following cheese have no trans fats at all.

- Tillamook’s widely available industrial cheddar - Generic brand feta - Generic low-moisture cheddar - Dutch Gouda

We should probably eat good cheese because it tastes better, but I would imagine that trans fat free cheese would encapsulate most common cheese varieties.

As an FYI, added trans fats have been illegal in the US since a few years ago:

https://www.fda.gov/food/food-additives-petitions/trans-fat

Kraft singles have no trans fat.

Neither does plastic

I find that bringing up American cheese is the single fastest way to establish whether someone knows anything about food or not. It's an excellent filter.

American "cheese"

Congrats; you got caught in the filter.

Congrats; american cheese is still trash

American Cheese is fantastic! Kraft Singles American however is trash and I hate that I have to explain the difference or that some people think that's what all American Cheese is like.

> We live our lives eating tons of sugar and thinking that this is the right diet

I don't think most people think it's the right diet. I think most people know that sugar is potentially harmful. Nobody is espousing the idea that sugar is part of a balanced diet, or that we should be increasing the amount of added sugar in processed foods. Or that we should increase our consumption of candy.

Rather, when we think of sugar, we think of obesity, heart disease, diabetes. Maybe even fructose toxicity?

But highly processed refined carbohydrates are sugar as well. Or at least converted to glucose. We are told, however, that carbs are part of the balanced diet. While that is true the right kind of carbs are important. So people think they are being healthy while loading themselves up with poor quality carbs that are in fact quite unhealthy.

> We are told, however, that carbs are part of the balanced diet. While that is true the right kind of carbs are important. So people think they are being healthy while loading themselves up with poor quality carbs that are in fact quite unhealthy.

I have never heard anyone, even informally, claiming that sugars are a useful form of carbs in the diet. Any source that claims that carbs should be part of a balanced diet is talking about long-chain carbs like starch, not sugar.

I highly doubt many people are seeing carbs listed as an important part of a diet and then deliberately eating more sugar thinking that they are being healthy.

I think th e poster you are responding to is making the point that long-chain refined carbs, which is what you get in e.g. pasta, breakfast cereal, oatmeal, rice, etc. (even if “whole grain”, most of which just adds back fiber but has already irreversible separated that fiber from the carbs) are perceived by many people as part of a balanced diet, etc — but they are basically sugar, because they are metabolized into glucose very quickly.

Hmm, perhaps you're right. I suspect that "highly refined" is an ambiguous term. A quick Google suggests it mostly refers to sugars but also refers to things like rice cakes and white bread that are mostly starchy; maybe it depends, in part, what things it is packaged alongside rather than just the chemical composition of the carbs themselves e.g. whether it is included alongside a fair amount of fibre.

> basically sugar

I think we should be careful here about calling glucose "sugar" and talking about harmful metabolic process because most people think sucrose when talking about sugar. And the potential harm from sucrose, glucose+fructose is quite different than glucose alone. Eating 100g of pasta, what you call "basically sugar", is not at all the same as eating 100g of table sugar. There's just so much room for misinterpretation and miscommunication around food. And in addition, so much is unknown.

You are correct, I was imprecise. 100g of pasta is close to 100g of glucose, while 100g of table sugar (sucrose) is ~50/50 glucose and fructose, the latter of which has a completely separate metabolism.

But both cause a huge glucose spike (ignoring fructose metabolism for now) and in that respect they are quite similar, and very different from basically any other kind of food in terms of metabolic response.

carb != sugar

sugar is glucose + fructose.

The human digestive system metabolizes fructose differently than glucose.

Bears eat lots of fructose prior to hibernation, birds eat lots of fructose prior to migrating south for the winter.

Consuming lots of fructose, say in a large container of carbonated drink dosed with high-fructose corn syrup/sugar, sends signals to your body to stop burning fat and start storing fat.

Ever hear someone say, "I just have to look at food and I gain weight". Well, those people have probably consumed enough fructose such that their body started storing food calories as fat.

see "Peter Attia - #87—Rick Johnson, MD: Fructose—the common link in hypertension, insulin resistance, T2D, & obesity?"

at https://www.youtube.com/watch?v=LbSic4Oo8ME

> sugar is glucose + fructose.

That's not the definition of sugar. Not even if you meant sucrose there (which is different from just a mix of glucose and fructose). Wikipedia puts it:

> Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. ... White sugar is a refined form of sucrose.

I know Wikipedia is not perfect but that matches what I've seen in the past. For example, fructose (by itself) is absolutely a sugar and it would be outrageous to claim it's not because it's not sucrose.

You are correct that that is not the scientific definition of sugar, which is generally any 5 or 6 carbon ring molecule.

However when most people talk about sugar they are referring to table sugar, which is a molecule of glucose (a six carbon ring sugar) chemically bonded to a molecule of fructose (a 5-carbon ring sugar) - otherwise known as sucrose. The first thing your body does when it sees sucrose is split them into a molecule of glucose and a molecule of fructose (this happens in your small intestine). Glucose can be metabolized right away, in any cell, however fructose needs a bit more processing in the liver before cells can use it to generate ATP.

> ... when most people talk about sugar they are referring to table sugar ...

What can I say? (shrug) I disagree, that's not my experience from talking to people in person (about diet; obviously it's a different matter if you're talking about cake ingredients). Anecdotal evidence from replies here on HN seems to agree with you though. Who knows what's more common in reality.

I think jjuel means bread and crackers and pasta and whatnot when they refer to low quality carbs, not sugar itself.

Many forms of carbohydrates are trivially converted to sugars such as glucose when they hit our digestive system, and so are roughly equivalent to eating sugars directly, metabolically speaking.

I’ve been told that adding a healthy dose of fat to a processed carbohydrate is a good way to prevent this instant sugarification process, and so I eat my bread with lots of olive oil or cheese or butter.

Sugars are quite useful, to aid in recovery after strenuous activity.

See: cyclists drinking coke or housing gummy bears after a race.

Many actually do, just not in a direct way. Change the word "sugar" to "carbs" or even "starch", and plenty of people will tell you that you need "good carbs" or the like. That's exactly what I and many others were taught in both high school and college level courses on human health. It's bogus because, for all intents and purposes, you can treat carbs and sugar the same. Lactose and fructose being partial exceptions, of course, and not in a good way.

Speaking of fructose, absolutely there are people promoting sugar as part of a "balanced" diet. You know what's in fruit, right?

Sugar actually was for a time touted as energy you either use or excrete, and that's an idea that's been discredited to the extent that most people know that sugar is considered harmful. They believe this because sugar is indefensible, hence the agriculture industrial complex have thrown it under the bus. Yet they insist that fruits, starchy vegetables, and whole grains are part of a "balanced" diet. What is a balanced diet? A diet with all the essential nutrients despite the presence of exogenous carbohydrates and other things that reduce bio-availability?

A "balanced" diet successfully rebrands sugar as an essential nutrient. As long as it's in the form of lactose and galactose in your "healthy" yogurt, fructose in your "healthy" fruit, and glucose hydrolized from the carbs of "healthy" whole grains, few are the wiser. Even better if you can dump refined sugar into these things anyway and call it "dextrose" to confuse people.

Yes, I know I wrap a lot of things in quotes. I do so because I must emphasize how incorrect these ideas are.

Fructose in unprocessed foods like fruit isn't a problem. Show me a morbidly obese person who got that way from eating too much fruit.

While you don't require carbs to survive that doesn't mean they're harmful or should be completely cut out from your diet.

I have a few clarifying questions:

What else are fatty acids used for? What are the metabolic pathways involved and how do different fatty acids impact our cells?

Can you cite sources for your claims? Research is a passion of mine and I would love to read some literature on the topic if you have any to share.

> What else are fatty acids used for?

Energy storage, hormone synthesis.

> What are the metabolic pathways involved and how do different fatty acids impact our cells?

Triglycerides are used as a substrate for energy production by mitochondria. Short-chain fatty acids with chain lengths < 22 can readily enter mitochondria and be turned into energy. Long-chain fatty acids cannot enter mitochondria; but they can be shortened by peroxisomes, another cellular organelles, to more feasible lengths which then can enter mitochondria. This whole "fatty" metabolic pathway is called beta-oxidation.

Both glucose and lipids are transformed into substance called Acetyl-CoA which is then used by mitochondria to produce ATP. Acetyl-CoA is a common denominator of our energy production pathways.

We can also imagine a software pattern when there is a main implementation (mitochondria working internally from Acetyl-CoA) and two adapters for glucose -> Acetyl-CoA (glycolysis) and lipids -> Acetyl-CoA (beta-oxidation) to simplify the whole thing.

Trans fats cannot be processed neither by mitochondria nor peroxisomes because they belong to a different class of fatty acids. This causes their accumulation inside the cell and a gradual development of a metabolic dysfunction because mitochondria cannot produce enough ATP (energy) from trans fats. If the accumulation is large enough it starts to block other metabolic pathways including glucose pathway. The mitochondrial "hunger" increases even more. Because glucose cannot enter mitochondria anymore, its level is rising leading to a condition known as insulin resistance. What happens next? A person may develop quite a few secondary conditions such as T2DM, hyperlipidemia, neurological and cognitive impairment, various cardiovascular and autoimmune diseases.

> Can you cite sources for your claims? Research is a passion of mine and I would love to read some literature on the topic if you have any to share.

I would gladly do that, but the list would be enormous. Materials on Krebs cycle are probably the best starting points. The next important milestone is to read information about Beriberi and Pellagra diseases because those conditions are caused by mitochondrial dysfunction which in turn is caused by nutritional deficiencies. The next thing to study is that metabolic dysfunction can be acquired not only from nutritional deficiencies but from a condition known as oxidative stress, which in turn can be caused by viruses, bacteria, poisons and so on. It can be acquired from the pathological excess of sugar during 10-20 years. Metabolic dysfunction can also be caused by genetics because some enzymes in metabolic pathways do not work as they should. To get a grasp of that, you can watch "Lorenzo's Oil" movie to see how it happens and what kind of sufferings a person may have.

As you can see, the amount of materials is quite enormous and hardly fits into a web-page-with-links format.

I'm surprised you don't mention lipid modifications of proteins or membrane fluidity, are those not significant functions?

Very interesting and thanks for the post. Any recommendations on good places for further reading on the subject?

I would suggest to take a look at Dr. Berg's videos on YouTube. He has very down-to-Earth and highly educational presentations on this and related topics.

The article was about metabolism, not diet and food. It didn’t deal so much with what people eat, but instead how cells process energy. The dynamics presented in the article are relevant whether you’re eating a high-fat or high-sugar diet.

The article says that "glucose" is the fuel for mitochondria, which is true. But the article does not say that "lipids" are the fuel for mitochondria as well while it should have.

Such asymmetry of presentation may create a dangerous illusion about the glucose as the ultimate nutritional fuel. That illusion may affect nutritional choices of a reader because the article painted glucose as the supposedly purest source of energy.

I may be misremembering, but doesn't fat have to be processed into glycogen in the liver before being available for metabolic consumption?

All this information should be included too! Obviously there is a limit to the article scope but it wouldn’t harm to answer these obvious questions it leaves dangling.

No, fats that come from the food (triglycerides) are directly consumable by the cells.

That can't be right. Triglycerides are the bulk of body fat. Now, presumably if you eat fatty tissue the triglycerides in the food will be broken down by enzymes into simpler molecules that can be absorbed by the intestinal walls, and perhaps those molecules may be directly usable. Is that what you mean? If so, then do you know what triglycerides break down into?

Forgive me for the incomplete reply, but I looked this up last week and one molecule of fatty acid (in this case DHA soecifically) generates 136 molecules of ATP. This makes fat roughly 2x as energetic (from the standpoint of our bodies' metabolism) as the heat measured from burning it (calories) would suggest. Despite this fact, and the fact that I've been eating roughly 3500 calories per day without exercising, switching to a high-fat, low-carbohydrate diet has lead me to lose 10 lbs over the past three weeks. Clearly there's a lot more to metabolism than is even documented in this lengthy article.

Fatty acids are used for far more than just energy

Yes, brain growth and learning/remembering stuff for instance.

I'm talking about specific biochemical mechanisms such as modifying membrane fluidity and getting attached to proteins in post translational modification

The average person doesn't think "sugar = energy". They think "sugar = tastes good". When average Joe with his 20 kilo spare tire is hungry (or probably just bored if he's a Western office worker) and trying to satiate himself with either a small bag of almonds or a Milky Way, his subconscious is going to reach for that candy bar every time. Even having learned the good knowledge you describe, the little 5 year old voice that says "I want it!" is going to overrule the adult brain that should know better.

I spent a summer working* a Dairy Queen in high school. EVERY SINGLE DAY someone, usually obese, would come in, order an extra large blizzard and say "I really shouldn't do this..." while receiving their paper cup of crack.

It is good that you have knowledge and numbers to help you make better choices about your diet. It is unfortunate that knowledge and numbers don't drive better food choices for everyone.

*I wasn't really employed there, my buddy managed the place and I'd hang out and occasionally work the register while he smoked a joint out back.

> Such trans fats cannot be consumed by our bodies: their chains are too short to be correctly processed and are too big to pass the mitochondrial membranes.

Oxidizing lipids doesn't introduce chain rotation about their double bonds (which is the difference between cis and trans fats). This change in structure is why trans fats are solid at higher temperature (for the same types of lipids - think the difference between margarine and vegetable oil). The reason trans fats are bad is we can't process them as easily and they seems to accumulate faster than even saturated fats in our blood vessels, mostly because they are synthetic in nature and we don't have specific enzymes optimized to process them.

> they are synthetic in nature

There are natural sources of trans fats, like vaccenic acid in breast milk.

Very interesting. Two questions: 1. If you could only have three things in your fridge, which would it be? 2. If you and I could never talk again, what single book, article or video would you recommend for me to turn to in order to find my own way through this topic? Thanks.

> If you could only have three things in your fridge, which would it be?

It's a matter of personal taste, but for me it would be: avocado, high-quality cheese, high-quality meat.

> If you and I could never talk again, what single book, article or video would you recommend for me to turn to in order to find my own way through this topic?

Book: "Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition" by D. Longsdale and C. Marrs.

Video: [1]

The materials present information with the focus on specific vitamins, but the knowledge about metabolism is universal and can be applied to all similar situations.

[1] https://www.youtube.com/watch?v=nuIhjlFYYZY

Is there anything to the idea that saturated fats are less prone to blocking glucose metabolism? For example, this guy [1] argues that saturated fats can temporarily suppress insulin signaling to avoid overloading the cell with glucose while the fat is being metabolized.

Anecdotally I have a much easier time handling carb-rich meals since mostly eliminating polyunsaturated fats from my diet. My previous experience was some combination of “food coma” and “noticeably hangry” a few hours later, but now I mostly just feel energetic for a few hours.

Some of the most metabolically-healthy populations in the world eat mostly starches [2] (and maybe 1–2% of calories from PUFAs), so my hunch is that eating low-carb is more of a workaround for widespread metabolic dysfunction than a requirement to be metabolically healthy.

[1] https://fireinabottle.net/the-ros-theory-of-obesity/ [2] https://fireinabottle.net/pontzers-burn-and-metabolic-rate-m...

(It’s worth pointing out that both of these links are from a site that also sells supplements, but they do link back to the primary sources)

Exactly. The idea is to remain metabolically flexible. At the same time, a large part of modern population consume too much carbohydrates ignoring the fat thing altogether. Within 10 or 20 years of such diet, the glycolysis metabolic pathway often gets broken causing insulin resistance.

But it's not only sugar excess that makes that damage, primarily it's the lack of nutrients in processed foods that causes a gradual mitochondrial decline.

For instance, most people consume white sugar because it's cheaper. On the other hand, sugarcane consists of the same glucose + fructose combo as the white sugar but it also contains vitamins, giving us much better chances to remain healthy.

Fats still have some uber-abilities compared to the glucose though. The main one is the ability to "shortcut" the faulty metabolic pathways.

I will give an example. When glucose pathway is broken in a cell, it leads to inability to produce enough Acetyl-CoA in the given cell. Acetyl-CoA is an intermediate substance that is used by mitochondria to produce the ATP. When there is not enough Acetyl-CoA, the ATP output levels drop, causing detrimental effects on health and general well-being. Such cells start starving, degrade and eventually die.

When beta-oxidation pathway is broken, it leads to nearly the same defect, but this time for fats. However, if a person still has at least some number of cells that can do beta-oxidation correctly, those cells can "share" their Acetyl-CoA with other cells through the blood stream. This happens mainly in the liver thanks to the fact that the fats are so powerful that they cause a huge abundance of Acetyl-CoA. And that excess finds its way from the liver cells' mitochondria into the bloodstream, feeding other cells by "shortcutting" their broken glycolysis/beta-oxidation pathways.

The excess Acetyl-CoA from liver gets delivered to every single cell in the body, including the brain cells. Even if a specific cell has subpar beta-oxidation or glycolysis abilities, it still can consume the external Acetyl-CoA without any problem and produce the adequate amounts of energy from it to keep the cell healthy.

That's why a low-carb high-fat ketogenic diet has so tremendous effect on some health conditions - it allows to "shortcut" the subpar metabolic pathways in affected cells allowing them to survive and even heal over time. This is a natural cycle of the body and suppressing it with a sugar too often will cause serious problems over time.

Regarding high-carb low-fat diets: probably they can work given enough nutrients (minerals and vitamins) quite well, probably stretching those 10-20 years of adequate glucose metabolism well into 60-80 years. But still, you better be doing some fasting (or keto) to heal the accumulated damage, at least several times a year.

The obesity is a factor but it is not the cause. For example, Asian people may appear thinner than Westerners, but they are ridden by beriberi more often. (Beriberi is a metabolic condition that is caused by mitochondrial damage due to the lack of vitamins)

Regarding what blocks what it's a complex question. Glucose metabolism blocks lipid metabolism and vice versa for sure, but I have no specific data. From my own observations, glucose is much more potent in blocking the fatty metabolism than the other way around.

I loved reading the article! How the body breaks down food into energy. Looking at life as energetic electrons finding a place to rest. I got goosebumps reading about mitochondrial membranes producing electric fields akin to lightning waiting to strike. The clockwork machinations of the human body as it breaks down complex organic matter into protons and electrons restless for a reunion, and then into a common currency of energy.

I have a disinterested high-schooler's understanding of biology. My field is electricity and physics and computers. So seeing this complex process explained thus was very, very engaging. Very well done!

Also, using metabolism to explain cancer was very enlightening.

"mitochondrial membranes producing electric fields akin to lightning waiting to strike."

Just leaving this here for anyone who is interested; EMFs and their effects on the Mitochondria. This includes ELF-EMF from household wiring.

Manmade Electromagnetic Fields and Oxidative Stress—Biological Effects and Consequences for Health https://www.mdpi.com/1422-0067/22/7/3772

DNMT1 and miRNAs: possible epigenetics footprints in electromagnetic fields utilization in oncology https://link.springer.com/article/10.1007/s12032-021-01574-y

Cellular stress response to extremely low-frequency electromagnetic fields (ELF-EMF): An explanation for controversial effects of ELF-EMF on apoptosis https://onlinelibrary.wiley.com/doi/full/10.1111/cpr.13154

Involvement of mitochondrial activity in mediating ELF-EMF stimulatory effect on human sperm motility https://onlinelibrary.wiley.com/doi/abs/10.1002/bem.20602

Role of Mitochondria in the Oxidative Stress Induced by Electromagnetic Fields: Focus on Reproductive Systems https://www.hindawi.com/journals/omcl/2018/5076271/

Extremely low frequency electromagnetic fields affect proliferation and mitochondrial activity of human cancer cell lines https://www.tandfonline.com/doi/abs/10.3109/09553002.2015.11...

"What causes the Black Shakes? THIS causes it, THIS causes it, THIS causes it. Information overload! Technological fucking civilization."

Prophetic.

I would recommend you read: PEMF - The Fifth Element of Health - https://www.amazon.com/PEMF-The-Fifth-Element-of-Health-audi...

It talks about how our cells are little capacitors and the earth's pulsed EMFs actually help energize your cells. I recommend skipping the first chapter though.

The physicality of the proton pumps (I can never remember which ATPase it is) was new for me. My intro chemistry and biology classes in college really didn't get too far past "proton goes through tube and an ATP appears!"

It is called ATP Synthase.

My go to source is libretext. Glucose is transformed to pyruvate then Acetyl CoA. The Krebs or Citric Acid cycle creates electron carrier molecules. These donate electrons and power four proteins which slowly pump protons into the mitochondria space between its inner and outer membrane. This creates a proton gradient or imbalance as the protons want to diffuse back into the mitochondria. This flow or river of protons power the ATPsynthase which is like a wind turbine and creates ATP for the cell to use.

What is interesting is that plants create glucose in their leaves. But plant cells also consume glucose at night. Or in parts of the plant that cannot create its own energy.

Here is a video animation explaining the electron transport chain. https://youtu.be/LQmTKxI4Wn4

Thanks. Keeping this in a pinned tab till I have a chance to watch it all (I scrubbed through it just now). I love getting to see how things work visually like this.

Oh I went through the wringer with memorizing the Krebs cycle. It's just every time you got to ATP Synthase it was literally just a tube, a few arrows, some comicbook-esque POW shapes, and "ADP" and "ATP" on both ends of the POW. Lmao.

So "oh it's a water wheel that the proton pushes that then pushes the phosphate onto the ADP" is like, "Oh. There's...a whole physical machine and not just magic 'energy transfer'". I just thought it was really cool, though obvious in retrospect.

(I am not a clever man.)

I have slowly gained 30kgs over 20 years. That's 1.5kg a year, or about 4g per day.

4g per day is almost insignificant amount and yet it is enough to make you fat over long periods of time.

I challenge anybody to accurately measure their daily calories intage to within 4g of a target (forgetting for a moment that the target can't be measured accurately either).

This suggests that while I was technically overeating -- by just couple of grams per day -- the problem lies entirely somewhere else -- in our ability to self regulate.

I found trendweight.com super helpful. It would be able to show you the trend overtime. It does something like a moving average overtime of your weight and calls it 'actual weight' whereas day to day fluctuations it treats a bit like noise it's extracting a signal from.

> the problem lies entirely somewhere else -- in our ability to self regulate.

Of course we have a problem with self-regulation. A billion-dollar industry exists whose main goal is to make certain foods more addictive, and yet as a society, the onus always falls on individuals to figure out how to overcome millions upon millions of dollars in research into chemically perfected food that we can't say "no" to.

Yes we can say "no", no matter the billions of dollars some companies may invest in their product.

I can relate to this kind of excuse in case of fat children who don't fully control their eating habits and rely on whatever food their parents make available to them. For self—sufficient adults, it's a pathetic opinion to have about your own level of control.

This is the exact same kind of moralistic thinking that created the opioid crisis. 40% of adults in the US are obese. Not overweight, obese.[0] Not to mention, that study was conducted before the pandemic, it would be interesting to see where the figures are now. At what percentage of aggregate obesity would you consider the issue to no longer be about self-control? And what makes you think we aren't going to hit that figure in the future?

Products are being developed to intentionally surpass our ability to self-regulate, whether they be food, medication, etc. People get paid really good money to sit in labs and figure out how to make their product more addictive, and we're just expected to just be able to say "no" because free will?

0: https://www.usnews.com/news/healthiest-communities/articles/...

I think that’s just a political question with no “right” answer. Some people will believe the government should intervene and control some of these foods, and some people will believe it shouldn’t, that people should be free to make their own choices.

There’s very good arguments to be made on either side, and neither side is the “right” side, it just depends on what your values are.

Personally, I like being strict with my own diet and fitness, but being free to take a break and pig out on whatever junk food I feel like. A world without Coke and McDonald’s would be sad to me, even if it is ultimately healthier for the population in general.

Well, the other conversation to have that doesn’t just cash out into personal consumer choice is who a society lets line their coffers with the vices of others.

I find it harder to argue for why you should be able to enrich yourself at the expense of others while singing “But personal choice!” to wash your hands of it all.

I think the problem is the conflict between the two isn't symmetrical. Those who are trying to convince you to eat Coke and McDonalds aren't playing fair or accurately portraying what they're selling. and will promote research that indicates that lack of exercise[1] or fat[2], and will specifically advertise to children.

Comparing it to tobacco or alcohol for example, I don't think it's wrong to let people chose to consume them, but I don't think it's a bad idea to restrict them being sold to young people or restrict their ability to advertise. Imagine for example a cigarette ad for children. The tactics used are fairly similar.[3]

[1]https://www.ucsusa.org/resources/how-coca-cola-disguised-its...

[2]https://www.npr.org/sections/thetwo-way/2016/09/13/493739074...

[3]https://sugarscience.ucsf.edu/soft-drink-companies-copy-toba...

Right, it was moralistic thinking that created the opioid crisis.

I would like to point out that the deep marketing/priming is what drives you to the product to begin with. The ability to self-regulate our minds and inherently our decision processes is closer to the root of the issue. That requires a fundamental shift in our education which doesn't see any incentives on the horizon to reform itself as long as low attention mindless caffeine/sugar driven zombies are needed to buy all the stuff we are presented with. We already have a deep seated bias towards comfort in our mental architecture. It's quite easy to piggy back on that for marketers to condition our minds. For someone to constantly be aware of this before making a decision is a bit of a stretch especially in our GO culture. The incentives are simply not there yet, the churn of getting fat and losing weight is too profitable to go away. Just like oil derivatives and other friction profiting cycle products.

> it's a pathetic opinion to have about your own level of control.

The first step to improve is to know your weakness. Our strength is intelligence.

T2 Diabetic that keeps a fairly strict keto diet here.

Food is terrible these days. It's hard to get stuff that isn't loaded down with sweeteners, never mind salts and fats. All to make food taste better and to get you to eat it more.

The insidious part about this food though, you can't directly taste the part that makes it addicting. If you stay away from it for long enough you can feel it. You'll eat something seemingly mundane, and suddenly you'll notice, not only does this food taste really good, it tastes absolutely wonderful in every way. If you pay close attention you can feel some deep parts of your monkey brain light up informing you that you best eat as much of this splendid food as possible. Weirdly the food itself doesn't actually taste that good, but some of those deep sections of your poor old monkey brain believes it does.

I hear you, well just eat fresh food, plenty of veggies and fruit. That is the where food science has gotten down right diabolical. Over the past bunch of generations we have modified our own produce, apples are sweeter and tastier, so are pears and watermelon, and things like corn, carrots, tomatoes, onions even potatoes and lettuce.

There is no escape from the things that tells your stupid monkey brain, hey eat this you fool!

---

Before you dog pile on me, I'm diabetic thanks to the genetic lottery, not for a lifetime of bad eating habits. But thank you for your concern.

You've staked out some pretty high moral ground, and a position that can be argued against any personal challenge, so I really hope you're perfect in every way or else karma is coming back hard!

yes, hard to self regulate when so much food is so calorie dense and addicting

The way you say it makes it sound like you only just noticed that you've become fat over 20 years.

I usually force myself to start counting calories again once I go off a weight I'm happy with (readjust my intuition.)

And that means counting calories going in (food) and out (normal resting use per day + potential exercise)

That was a long time ago. I lost most of it about decade ago and turned most of the rest into muscle. Running daily.

Don't count calories. Read this book: https://www.amazon.com/Mini-Habits-Weight-Loss-Suffering/dp/...

Calorie counting does not work (that's exact point of my post). What you need to do is to teach yourself to eat and behave as if you were healthy and this gets down to building right habits and displacing bad food with good food. Notice I am not saying dieting -- removing food you like and leaving void in your diet is a recipe for frustration and breaking your promise. Instead, learn to embrace healthy food and slowly include more of it in your diet and you will naturally start eating less of the bad ones.

> Calorie counting does not work

Works for me. And yes, you shouldn't eat garbage. In other news, water is wet.

As someone who has maintained his weight for roughly 15 years... calorie counting works fine. You're looking for an external source to blame for your internal shortcomings.

How is trying to build right habits trying to blame external source?

It literally starts with observation that current habits are wrong and need to change.

His suggestion is actually healthy lifestyle.

I lost 35 kgs since February this year, up until now in October. I want to lose 10 kgs more, then I'll have 10% body fat and will look fit.

Yes, it's all about ability to self-regulate.

Maybe the root cause is different for different people?

How do you self-regulate? My wife is able to, I'm not very able to. She can just decide to lose weight and does it. I've only successfully lost weight during times when I was so stressed I couldn't eat.

This isn't meant to sound to flippant, but try to increase physicality to the point where you don't have to think as hard about calorie intake. A brisk one hour walk on hills can easily burn 600cal. At the same time, your BMR will go up due to increased fitness

>> A brisk one hour walk on hills can easily burn 600cal

This is optimistic to the point of being close to a lie. Most people walking for an hour are going to burn closer to 250-300 cal. At the pace and terrain to double this you're not really "walking" anymore, and it's certainly not "easy". The idea of "exercising your way out of overconsumption" is entirely flawed and disproven.

A 250-300cal/hr walk is a casual stroll. Don't move goalposts here. Perceived effort will change from person to person. Besides, I meant the number goal is easy, not the effort. But you knew that and wanted to twist my statement to fit your view.

A quick google search results in a range from 400-600cal/hr for brisk, hilly walks. You could also use the word "hike" but that requires nature which some people don't have access to.

>The idea of "exercising your way out of overconsumption" is entirely flawed and disproven.

Obvious one would still be attempting to reduce calorie intake throughout this scenario. But for the people who say "exercise just doesn't make a difference in my weight loss" - that is indeed flawed. You can absolutely exercise your way into a deficit. Perhaps you haven't had that experience. To that, I would say your workload is probably not high enough to experience it.

I cam tell you, that idea works pretty well. With added bonus that you gain stamina and strength.

Exercise is proven to improve your health results.

Just get used to being hungry and your stomach being empty. You don't need to do anything when you're hungry, you won't starve.

I completely agree with this, yet people have a hard time accepting it because hunger evokes so much emotion.

Eating food with a focus on satiation helps with this. It's normal to feel hungry, but you can offset it to a degree with proper food choice. Hell, I'm hungry right now

> How do you self-regulate?

You are not hungry. You are bored. Purge snacks from your house. Purge sodas from your house. Purge sugary anything from your house. Never buy treats in sized over one serving. Only buy one treat at a time.

Are you able to fast for an entire day?

I don't think 10% body fat is going to be achieved through self-regulation/calorie cutting alone.

10% body fat is an EXTREMELY low %. I don't think that is realistic for most people outside very athletic folks. Reducing to 10% body fat requires a significant change in diet, not just reducing consumption, but actively changing your macro mix AND keeping a fairly strict regimen of strength training and cardio to keep the fat off.

I think losing weight as most folks (including yourself I think) agree with is reduction of calories. Then optimization of calories / lifestyle / workout regimen seem to be the next areas.

You trying to lose weight isn't self-regulating, that is you manually regulating your weight.

The fact that you have 30kg excess weight to lose shows that there is an issue with self-regulation.

Except it isn’t really 4g per day in a vacuum. As you gain weight every kg needs an additional ~20 calories per day to sustain its basic processes. So by year 20 you are eating an extra 600 calories per day to sustain that weight plus an extra 4g (~36 calories) to continue to gain weight which is a quite noticeable amount of food.

At this point cutting the equivalent of 50+ oz of coke or a little more than a Big Mac per day would leave you feeling hungry, but that food slowly crept in over time.

An extra 600/day is incredibly easy to get with American food and habits

I was about to pick up some frozen bar for 550 calorie yesterday. I used to eat two on a whim. Never realized that it’s basically lunch.

I think this is a key point. Not just for weight control but for so many things.

It is agonizingly simple to destroy near constant mindfulness with a few moments of mindlessness.

This is why I love trading. You cannot falter. It has changed my personality as well.

Do you mean training or trading as in stock trading?

Stock

Presumably trading meat stock for vegetable stock? ;)

Poker has the same vibe. You need to consistently made good decisions, even in the face of adversity, with the hope that the long run is long enough for those decisions to pay off.

Yep

As fun as it is to make fun of Americans, many European countries aren't that far behind. It is a universal problem.

I think as you age you want to eat more food not less, certainly with the standard American diet. I really haven’t yet found a solution apart from doing up a house myself, 8 solid hours of DIY per day and you’ll lose weight no problem. I lost about 10kg during that time without even thinking about it.

One part of that is higher caloric demand, but the other part is your capacity to burn calories. As you become more fit, your body can draw on more calories in a given moment. Fit people can burn more calories per hour, usually by a large margin

> 50+ oz

Sorry just need to convert that to real units for the rest of the world - 1478.68ml

Nah bugger off, literally no one is drinking 1.5 litres of Coke a day, absolute madness.

600 kcal in other terms is: a sandwich and 2 small pieces of chocolate

2 sausages and two eggs

Coke isnt really more energy dense than orange juice but getts a worse rep, my point being is that if you dont pay attention to the actual energy contained in your food 600 kcal can be inhaled in a whim.

>> 600 kcal in other terms is: a sandwich and 2 small pieces of chocolate

That's a pretty small sandwich, with none of the fun toppings.

I'm an American, and I usually consume about 48oz of Coke Zero a day.. So definitely believable.

Like.... Why?

That sounds horrendous

If you drink it with meals I don’t see why not. Or even as a snack. Coca Cola is delicious.

Its sugary cancer water, why not have... water?

How much is insulin in your geo?

Coke Zero is zero calorie, it has no sugar.

> Nah bugger off, literally no one is drinking 1.5 litres of Coke a day, absolute madness.

I know people who have done that in the past - it's one bottle or 5 cans or 3 medium bottles or 2.6 pints (easily done if you're spending 8 hours a day in the pub as we did at uni.)

(I'm pretty sure I've had periods where I've drunk the daily equivalent in coke, coffee, redbull, etc.)

If only that were true. A day? Try: in one sitting. Convienence stores in the USA have sold 64 oz cups of soda for decades. https://www.delish.com/food/news/a39120/super-sized-beverage...

Anecdotally, I have a family member that drinks nearly 4L a day. He gets two 64oz big gulps from 7/11 every day. Not even diet - it's regular Coke.

yes, plenty of people are drinking that much

How much exercise were you doing during that period? I ask because the same thing happened to me and I wasn't doing any exercise most months.

Overeating becomes much less of an issue if you're doing exercise (as an extreme example look at how much strongmen need to eat to maintain their weight).

A key insight is that muscle requires more calories to maintain than fat reserves, even if they weigh the same.

If you're fat you're probably building decent muscle on your legs just by carrying more weight around all day, but the upper body is a different story and requires training no matter what.

I don't find exercise very helpful. They burn too little calories compared to the effort. I find it way easier to eat less: not doing something is easier to spend effort, and the effect multiplier is bigger.

I should still exercise for other reasons, but not for losing weight.

The calories burned during the exercise matter less than the higher metabolism resulting from having more muscle mass. Especially if we're talking about strength and hypertrophy exercise and not just cardio.

How does this work? I have way more muscle than my wife, but she can eat way more than me without gaining weight. It can't be just muscle mass?

How many calories does extra muscle mass burn daily?

It's definitely not just about muscle mass. But you should compare yourself to yourself only when it comes to self-improvement, since you can't borrow someone else's metabolism. Having more muscle mass is better than not having it for both health and appearance.

When we're talking about slowly gaining weight over time as the OP did, even if muscle only burns a little more energy than fat that could be enough to tip the balance.

There could be a lot of factors: your body size, muscle to fat ratio and body comp, total exercise in a day, the actual caloric amount of the food you are eating (you can eat a lot of low calorie food compared to a single high calorie item for instance), mitochondrial function in your muscles and your ability to clear lactate from your bloodstream. Controlling for all of the variables is actually very difficult.

Most people that eat a lot and don't seem to gain weight are simply not eating that much calorically or exercising a lot. When a more sedentary lifestyle kicks in they generally begin to align more with the general population.

Perhaps the difference comes down to body type (Ectomorph, Endomorph, or a Mesomorph)?

https://www.gq.com/story/body-types-explained-ectomorph-endo...

> I don't find exercise very helpful. They burn too little calories compared to the effort.

Exercise help in much broader ways than just the amount of calories burned on the spot. Take weight lifting for examples, it increases your lean mass, which means it increases your metabolic rate, which means you can eat more and not gain fat. You also spend more calories on your resting days to rebuild your muscles, &c. exercising also tend to curb appetite

I suggest not focusing on what calories it appears the exercise is burning. My experience is that something else is occurring which helps to lose weight and keep it off - I suspect something to do with the microbiome and increasing basal metabolic rate to feed an exercise-trained microbiome (more active? Different makeup for sure).

I struggled for years to get my weight down. Then just walking every day to ensure I was at 10,000 steps managed to move the needle in a meaningful way. Over a few years that turned into running a few times a week, which turned into running daily. In the beginning I had already been counting calories and the calories I was burning walking whatever it took to get from my normal amount to 10k (varied each day) was not enough to justify the weight being lost when compared to calories consumed. It should have been much slower.

> I struggled for years to get my weight down. Then just walking every day to ensure I was at 10,000 steps managed to move the needle in a meaningful way.

Part of this might also be about how exercise generally leaves you feeling pretty good, usually better than after a day that is spent entirely sedentary in my experience. A lot of people crave the instant satiating feeling of eating. Eating often feels good. The exercise might then help by replacing the "make me feel better" feeling that food might give you, leading to you swapping out "unnecessary" feeding and lowering your caloric intake in the process.

I would agree with this thought generally as it certainly happened when I started running, but in the days of just getting my steps in, my use of MyFitnessPal showed that I was eating the same diet with essentially no change to the average daily caloric intake. I did increase my water intake.

I've observed that moderate aerobic exercise often tends to temporarily suppress appetite for some people, myself included. Doesn't work for everyone, though.

My partner swears their caloric cravings increase disproportionately after workouts and feels strongly that reducing food intake has helped them maintain weight far more than exercise. There are probably some genetic components to this (according to our 23andme data, we have very different genomes).

Exercise is key. The problem is people expect exercise to directly burn your fat which is completely false and broken way to look at it.

Then what happens when they don't see results is they proclaim it does not work and drop exercising altogether. What they did not do is stick long enough to actually see the results.

Exercise is to keep your healthy and to improve your internal regulation. It is to keep you feel well so that you don't feel compulsion to eat more just to feel well.

I agree that moderate amounts of exercise are not helpful in losing weight at all. I fluctuate all year between 73kg and 80kg (with a brief stint at 84kg the other year while I wasn't doing any cardio for 6mo and eating way too much takeaway).

In school I used to go to the gym every day for 45mins at lunch, and box 5/6hrs a week, from 14y/o. The last 3/4yrs I climbed 3/4x a week and the last 2 of those I also ran 3/4x a week up to ~40km/wk, albeit inconsistently around my 9-5 and part time uni course.

Every time I cut out one of the sports I enjoy, I am drastically less hungry. Yes, a 5km run might burn ~300cals, but if I'm so hungry I eat a whole extra meal, I'm generally more likely to gain weight. Same for lifting weights, but even moreso - if I go and hit a 200kg deadlift PR I'm going to be hungry the next day, but that 1-2hr gym session maybe burned 100 calories at most. Exercise for weight loss is only useful if "calories in" stays the exact same, and even then it would be way less effort to reduce "calories in" and not exercise (if weight loss is the only goal).

The point at which this stops applying is excessive cardio, ie running 40km+ in a week. That will pretty much always result in a caloric deficit for me, because at that point I'm forcing myself to eat enough food to recover (rather than having to force myself not to overeat). Most people exercising to lose weight (rather than for enjoyment, to push themselves/prove something, or to win a race) don't want to exercise. If you have to commit 6hrs a week to cardio to see any effect, 99% of people aren't interested, so I'd imagine they fit into the "not excessive" category where exercise might make them want to eat disproportionately more than they burned.

Controlling "calories in" (which will guarantee weight loss, as far as the laws of physics are concerned) is always going to be the easiest path to weight loss.

Here is what's very helpful in loosing weight: ketogenic diet. Just try it for fun and see for yourself.

There are two only tangentially related issues here. One is, given you're already overweight or obese, can exercise help you change that? The answer seems to be yes, it definitely can, but it seems empirically that it very rarely works over any appreciable long-term, other than in people who find they enjoy it sufficiently to become at least recreationally serious endurance athletes or at least very active people for the rest of their lives. If your only motivation for exercising at all is to lose weight, it very likely isn't going to work over any meaningfully long span of time.

But the other issue is, given you're a normal-sized, metabolically healthy 10 year-old, will developing a lifelong habit of regular exercise and a generally active lifestyle keep you from ever getting fat in the first place? I don't know that we have any kind of long-horizon, longitudinal research to demonstrate one way or another empirically, but mechanistically, it sure seems like that should be the case, and you can look at manual laborers in developing countries, the Amish, any serious lifelong athletes in sports where being maximally large is not advantageous on its own, as existence proofs that this should help.

I think the comment you're responding to was really asking about the latter scenario. It's not, okay, you spent the last 20 years gaining 30kg, well how active are you now? The question is how active were you over the entire course of the last 20 years? Because it's likely that if you were sufficiently active, you wouldn't need to lose weight at all, and the question of exercising for losing weight would be irrelevant.

Yes exercise helps, and has benefits besides burning more calories. But unless your calorie surplus is small, it's not going to be possible to "burn off" overeating by exercising.

If you need to burn 3,500 excess calories to lose a pound of fat, that means you need a 500 calories per day deficit for a week. A single fast-food burger such as a Big Mac is more than that.

Generalized, you can't make up for bad diet with more exercise.

And, you need a calorie surplus to build muscle. So if you are trying to get strong, you need to eat.

You can't accurately measure "calorie" intake. Calories are units of heat, and don't represent how the human body utilizes energy from food. The number of calories you'll find attributed to a given food are determined by how much heat is emitted by the available macronutrients if they were set on fire in a bomb calorimeter. Humans don't work like bomb calorimeters. This is why calories as a measure of nutrition are nearly useless.

I'm not exactly speaking as an armchair scientist, though I don't have a Phd. I spent over 9 months this last year developing my own tech to measure human metabolic activity and did extensive research into the broader subject, and quit my job in part to focus on it.

Whether you were overeating or not hardly has anything to do exclusively with eating a couple of extra grams. What you were eating and your individual physiology is primarily what dictates how your body will ultimately respond to your food. The vast majority of people in our industrial societies are eating diets that our species barely or never adapted to, and the prevalent macronutrients of said eating creates this illusion that the problem is calories. Our bodies are actually extremely good at self regulating. Problems enter when we get the fuel mix wrong, which is what we're doing when we're eating carbohydrates 3+ times every day.

A good (though imperfect) analogy is the fuel you put in your car. Modern fuel injected cars can actually start on different fuels. You can, for instance, put E85 ethanol fuel in a non flex-fuel car and it will probably start, and there's a chance it will be able to continuously run on it, albeit poorly. The reason for this is a standard car isn't configured to run on ethanol. While it probably can run on it, it's specialized for one particular fuel, which is gasoline. Maybe you can run your gasoline car on E85, but you'll have to step hard on the gas pedal and you will eventually suffer the consequences of poor engine performance. (Ironically, many modern cars can run fine on E85 with a mere software update, but that's a different story)

I would challenge you to gain any meaningful amount of fat mass on a diet of pure animal protein, let alone hold on to existing fat. It's a lot more difficult than most people believe. The satiety signal that follows eating meat, which is a hormonal response, is more powerful and sustaining than a diet based on carbohydrates. Glucose, what most carbs ultimately become, is poisonous to cells, while protein isn't. A diet based on protein means the body doesn't need to use or store the supply of glucose because the necessary glucose can be generated from protein on demand. The way your body responds to these different macronutrients is very different. People counterintuitively lose a lot of weight eating lots of fat because, unlike carbohydrates, fat has little to no insulin response on its own.

Things also get messier when fat and carbs are eaten simultaneously, but I feel like I've mentioned this on HN a bajillion times already.

All this to say that the calorie model for human nutrition should no longer be taken seriously.

Calories might only mean anything as a measure of energy expenditure, but even that measure has little utility to anyone who isn't in the process of dying. Some people succeed in losing weight by restricting the amount of "calories" they are consuming and offsetting the "calories" they eat by performing exercise. Where this falls apart is taking the same exact energy intake and activity level, replicate it in another person, and fail to see the same fat loss results. Below a certain point, yes, you'll see every participant lose weight, but you may also find them to be wasting muscle. Eventually, the effects of "calorie" restriction and carbohydrate intake will catch up with a person and they will suffer for it because neither "calorie" restriction or frequent carbohydrate intake are things that humans are adapted for.

Can you provide any papers or sources relating to this? Would be an interesting read

   All this to say that the calorie model for human nutrition should no longer be taken seriously.

There was no reason to take it seriously in the first place... The people who did that won't be convinced by scientific arguments

> Glucose, what most carbs ultimately become, is poisonous to cells,

Do you mean excessive glucose? I doubt glucose is poisonous, seeing how simple and basic the krebs cycle is.

Glucose is toxic. Granted, even water is toxic at some level, but that threshold for toxicity is much higher than that of glucose. Glucose is a fundamental part of the Krebs cycle, yes, and is not a problem if that glucose is managed and regulated. By default, the human body manages glucose very well. When that system is disrupted either by consuming exogenous carbohydrates as well as consuming carbs and fats together simultaneously, said system begins to fail and that's what can lead to all sorts of problems involving blood sugar.

See Table 1 of "Glucose Toxicity":

https://www.ncbi.nlm.nih.gov/books/NBK278934/

Unmanaged glucose is toxic to every tissue in the body.

Oh, one thing I forgot to mention is that even if intake of "calories" meant something from a physiological standpoint, the calorie counts on food packaging can be wrong by a significant margin. They're allowed to be as wrong as 20%, which can mean hundreds of calories.

https://www.insider.com/calorie-labels-arent-accurate-how-to...

But that's an average. You may have gained much more in one year vs the others. Plus you don't need to notice 4g a day even if that is the level, once you have gained about 1Kg then you know that on average you need to decrease.

Get a fitness tracker.

Seriously.

People always use these online calories calculators. And they can be off my more than 500kcal a day.

That's more than the recommended calorie deficit.

Fitness trackers, while sometimes useful, are considerably overhyped IMO. They're mostly about gamification and the UX inspiring (often inflated) confidence in the results they report, not about yielding fundamentally higher-quality information than online calculators or your bathroom scale or how well your pants fit.

Also, people put too much stock in the 500 kcal/day thing. It's more an example that makes the math work out neatly than it is necessarily something any given person should adopt as a target.

Gaining 4g of fat requires an intake of quite a bit more than 4g of food.

Well, not necessarily true. Your body is not composed of 100% fat. Actually it is composed mostly of water and when you gain 4g of mass most of this gain is from water, too.

I unfortunately can't tell you how efficient body is at digesting various types of foods including digesting pure fat.

Very short-term fluctuations in weight are usually caused by retention and flushing of water. Gaining 30kg over the course of 20 years is not water weight. If you were retaining that much water, you'd be so arthritic feeling I'm not sure you'd able to stand up. Unless you've been very serious and consistent about weight training that entire time, that 30kg is virtually all fat.

>> This suggests that while I was technically overeating -- by just couple of grams per day

I doubt you've hit this average, as it's unlikely you live in a completely controlled vacuum. It's more likely you've had far more noticable and extreme periods of change in both directions, while trending upward as you age and change your lifestyle.

To put it another way: I've gained 6g per day over my entire life. That's not much more than your 20 year example but there's a pretty obvious difference between me as a newborn and present day me.

The problem is people eat by habbit, or by social rules, not by hunger. Naturally we tend more to 2 or 1 meal a day

Additional 30kg increases your resting metabolic rate, and likely activity calorie surplus, sometimes solution is also as simple as fasting a day / skipping a meal once a week to maintain.

After watching https://www.youtube.com/watch?v=LbSic4Oo8ME , I think fructose metabolism is more important these days wrt weight gain.

Consuming a high concentrated dose of fructose, say a large amount of non-diet carbonated soda, results in your body switching from burning fat to storing fat like bears preparing for hibernation or birds before they migrate south for the winter.

Even if you avoid foods with high amounts of fructose, you have to be careful because under the right conditions, eating a sufficient amount of sodium, your body will convert glucose into fructose and your body could then switch from burning fat to storing fat.

I've recently had the most frustrating and confusing time of my life diet-exercise-wise, so this article is very welcomed/interesting.

I work out maybe 5 out of 7 days.. and I'm talking a minimum of 30 minutes of intense cardio, bpm's above 150.. 3 days i'm going to hour-long 'core-sculpt-yoga' which at 93 degrees inside is some of the most intense exercise i've ever done.. and end up leaving near palpitations every time..

On top of all of that work, I *hardly eat anything at all* .. I might take in 2000 calories in a day, but it's typically far less.. a lot of it is also in liquid form, which I know isn't great.

The point is, I've actually gained weight in the past couple of years. Sure, my muscle mass has increased slightly with all of the exercise.. but fat around my midsection has stayed and/or slightly increased. AND IT HAS CONFOUNDED ME TO NO END .. How does someone hardly eat anything at all (but potentially eats poorly, not fatly, but poorly when he does) and who works out more than regularly .. manage to gain weight and maintain or gain fat ??

So I am trying now to eat regularly throughout the day, and we'll see what happens.. Drinking protein shakes every few hours, etc.. to really test this theory on myself.

My usual response to a claim like this would be -- log it. Accurately, with a good scale. Defying physics is hard, and everyone I've ever met who claims to eat a low calorie diet without losing weight is usually undercounting, and usually by a lot.

Measuring body mass doesn’t tell you how much water, muscle, bone too. Could be they are now better hydrated because they are doing a fitness regime.

You should consider reducing the intensity and increasing the length of your cardio. You burn more fat at lower intensities. At high intensity, you burn exclusively carbs. Check out https://uesca.com/carbohydrate-vs-fat-burning-a-comprehensiv...

It's not quite that simple, obviously, but if your goal isn't to increase your running pace but rather just to stay in shape, I'd definitely consider running slower. If you run regularly, 150bpm indicates a moderate-high level of intensity (assuming you're not super young), rather than an easier pace which would consume more fat.

> but fat around my midsection has stayed and/or slightly increased

Are you sure? That could be muscle too. It's hard to tell unless you get a DEXA scan.

Don't worry about gaining weight unless you also have to buy bigger clothes.

Khan Academy MCAT overview of Metabolism. Don't be discouraged by the fact that it's for MCAT prep - it's pretty clear.

https://www.khanacademy.org/test-prep/mcat/biomolecules#over...

I think calorie quality and lifestyle routines calibrate the metabolism just as much as having an active lifestyle.

Enjoying zero calorie beverages (coffee, tea, celery water, etc) goes a long way in optimizing metabolism.

In 2022, there are at least 3 basics that trash any metabolic gains.

1) Steroid/antibiotic infused proteins. There were articles about childhood rectal/colon cancers gaining with the same childhood obesity studies. The links seem obvious. Their body never develops healthy metabolic processes.

2) GMO/herbicide/pesticide infused organics. Again, once introduced into a [growing] body, even the immune system takes a dive, as well as the metabolism. There are certain carbs that make my metabolism crash exactly 24 hours after eating. I just don't buy the product(s) again. They obviously lab rat the masses with several of the food stuff product gimmicks.

3) Microbeads/nanoplastics in the water system. Kind of like CFC's, as the microbeads breakdown in the water systems, the human body is not going to mature like generations past with all the contaminants in the digestive system. Even the sunscreen/beauty products with nanoparticles that embed in the epidermis that melt under UV/sunlight or toxify the body are their own problem. They are already plentiful in the water systems. These are retail consumer products, just as CFC's were. Can you say junk science?

Especially with calorie quality, if you did not adapt to 21st century lifestyles, there should be no expectations of a healthy metabolism.

If diet, exercise and nutrition are healthy, the conversation on metabolism is much different. I'm personally 5% to 7% BMI with decades of zero calorie bevs and an active lifestyle. Never an ounce of extra fat and notice if any meals make changes to my body.

Everybody has to grow old with their own body. I think the junkie paraphernalia with insulin and popping HBP pills was already suss decades ago.

I really enjoyed “A Journey to the Center of Our Cells” by the same author.

https://www.newyorker.com/magazine/2022/03/07/a-journey-to-t...

Thanks for the reference. Also at https://archive.ph/zZYNR.

> In hibernating bears and newborn humans, the turbines generate heat, which is stored in fat. More commonly, though, each turn of the wheel assembles a molecule of adenosine triphosphate, or ATP—the energy currency of our cells.

Interestingly, there is a (very effective!) weight-loss drug called DNP whose mechanism of action is to interfere with ATP generation in this manner. Essentially it makes it so that some non-trivial percentage of these "proton turbines" do not actually generate ATP. This means you burn a lot more calories at rest to generate the same amount of ATP, and also generate a lot of excess heat.

The risk is that if you take too much your core temperature increases too much and you can cook yourself to death. There's no treatment and overdoses are invariable fatal.

DNP doesn't make you healthy and it doesn't reduce hunger. The hard part of reducing body fat and keeping it off is managing hunger.

I don't think you'll find anyone suggesting that DNP is a good idea for weight maintenance or improved health. However, it will definitely help with short term weight loss if it doesn't kill you.

Drug? Or poison?

I don't know what part he plays but Drew Berry is credited in some of the most compelling videos on molecular biology that I've ever seen. They really bring the machinery of biology to life. Most of them are at the WEHIMovies channel on youtube. Here's one on ATP synthesis:

https://www.youtube.com/watch?v=OT5AXGS1aL8

Channel: https://www.youtube.com/user/WEHImovies

If I would have had access to these in high school back in the 90's I probably would have lived an entirely different adult life. It's an incredible aspect of nature that we've somehow just become accustomed to.

Continues Glucose Monitor (CGM) are nowadays the best option to take care of your weight, just like Blood Pressure Monitor are to keep your brain out of strokes !!! Understand the importance of glucose in our body !

The cost on CGMs is what is keeping them out of the mainstream (at least in the US.) If you are non-diabetic and want to use a CGM you're looking at about $10/day out of pocket cost. If Dexcom or Abbott can get a CGM down to $1/day out of pocket they should be insta-buys for everyone over age 25.

This whole discussion missed the central role of oxygen molecule as the ultimate energy source.

Why we need oxygen:

http://dx.doi.org/10.1021/acsomega.9b03352

https://dx.doi.org/10.1021/acs.jchemed.5b00333

Here’s a link without the paywall https://web.archive.org/web/20221028111149/https://www.newyo...

also https://archive.ph/M2VZR

It's such a stark contrast to compare the boring memorization of high school biology, to

the amazing efficiency of our metabolic and respiratory systems and how they sustain us on so little energy.

Why don't they teach this stuff in context?

Because modern education is trash.

This article truly is briliant, the opposite of how 99% of modern teachers teach.

> An atom is like a little solar system, with a nucleus at its center.

What if each atom was a little solar system?

An incredible story!

Somewhere in https://www.youtube.com/watch?v=LQmTKxI4Wn4 or https://www.youtube.com/watch?v=vkYEYjintqU the narrator casually says "... and this is why we breathe oxygen ..."

That's an incredibly well written article. What an educator.

How do I avoid getting fat on my torso/face!

You can't target fat loss. You should just lose fat.

The only answer to this is lowering overall bodyfat percentage. Each individual is predisposed to store fat in different areas across their body.

And if that's not enough, increasing muscle mass to balance it out.

Eat less, do more exercise. Then you'll start to eat more. Just keep up with the exercise part.

You can't control where your body stores fat. Some people just have more rounder faces. My friend is extremely skinny, but if you saw a photo of just her face you'd think she was a little chubby.

There's no such thing as spot reduction: https://en.wikipedia.org/wiki/Spot_reduction

That being said, there are a bunch of liposuction and fat freezing/vibrating/electocuting etc. methods for body/face sculpting.

That's a myth

Coolsculpting is spot reduction.

This is a great writeup and Lane's book looks pretty interesting. One thing I'd add is that knowledge of the Krebs cycle (aka, 'tricarboxylic acid cycle') helps people understand why some dieting approaches seem a bit unwise to biochemists. A simple explanation of the Krebs cycle is that it is a kind of engine that sits at the center of metabolism, but metabolism is not just the breakdown of molecules for energy, it's also the construction of molecules for various cellular needs. Take this quote as a beginning point:

> "...we were told the monstrous names of its component parts—succinate, pyruvate, Acetyl-CoA, cytochrome c—while, on the blackboard, we counted NAD+s and FADH2s, and followed “redox” reactions as they “oxidized” or “reduced” elements."

From a biochemist's point of view, there are about three classes of foodstuffs - carbohydrates (which break down to simple sugars), proteins (which break down to amino acids), and fats and oils (which break down to fatty acds). All those breakdown products are fed in one way or the other into the Krebs cycle (for amino acids, the nitrogen is stripped off and excreted as urea). These energy-producing (i.e. NADH / ATP generating) reactions are grouped under the heading of catabolism. If you entirely exclude any of these three classes of foods, such as by ingesting only protein, the Krebs cycle and affiliated metabolism starts doing some funny stuff. This is the basis of 'eat a balanced diet' advice.

Note that the Krebs cycle also sits at the center of your body's biosynthetic system, which is continually manufacturing the non-essential amino acids, as well as sugar and lipid synthesis, which then form the basis of hormone and neurotransmitter synthesis. The molecules in the above quote are, in various cells, exported out of the Krebs cycle and into these biosynthetic pathways. Unbalancing the Krebs cycle by depriving it of essential feedstocks can thus throw a lot of your body's fundamental systems out of whack. Since the Krebs cycle is highly regulated and somewhat malleable, it can respond in various ways to account for this, but problems can arise over time.

Hence, the best dieting approach for losing (adipose, i.e. fatty tissue) weight is most likely intermittent fasting with a carefully balanced (carbs/proteins/fats) diet, just less food overall. Under such fasting conditions, the fatty tissues get converted to things like ketone bodies and hence to glucose (the brain's primary fuel). Here's a collection of abstracts on how this works in intermittent fasting (it's also related to diabetic issues):

https://www.sciencedirect.com/topics/agricultural-and-biolog...

Note that regular exercise is also good for your health, but that's not necessarily 'burning fat' so much as it is improving your circulatory system, and flushing your lungs with plenty of air, as well as improving muscle tone.

Why do you think we don't have ATP running in the bloodstream instead of requiring each cell to produce it's own ATP?

As in, why don't we have an "energy organ" which runs the Krebs cycle and outputs ATP for the whole body?

Removing the Krebs cycle from each cell would be a ultra-fundamental change, so hard to evolve, but adding the ability to supplement ATP from the bloodstream seems doable.

Lifetime is the issue. ATP and its cousins, and similar energy-transmitters like creatine phosphate, are hot potatoes. The phosphate group rapidly transfers its energy to other molecules in the cell, and exporting it to the bloodstream just wouldn't work, it'd break down in transit.

> "In human beings, for example, the amount of ATP recycled daily is about the same as body weight, even though the average human being only has about 250 grams of ATP. Another way to look at it is that a single molecule of ATP gets recycled 500-700 times every day. At any moment in time, the amount of ATP plus ADP is fairly constant. This is important since ATP is not a molecule that can be stored for later use. "

https://www.thoughtco.com/atp-important-molecule-in-metaboli...

Most of energy biochemistry can be viewed as a system for trapping energetic short-lived species (such as high-energy electrons produced by cytochrome oxidases or the photosynthetic reaction centers) into slightly longer-lived systems (such as protein gradients across a cell membrane) which in turn are converted to somewhat more persistent species (ATP and NAD(P)H) which circulate within cells), and then into the most stable energy stores, like glucose, lactate, etc. which circulate through the bloodstream and transfer energy between cells (with glucose eventually being stored as glycogen in the liver, and eventually, as fatty tissues, or in plants, starchy roots). The times go as nanoseconds -> milliseconds -> seconds -> minutes/hours/days.

"Just less food overall" never works. There are 2 diets that work for weight loss: 1) High-fat, low carb. 2) High-carb, low fat.

Stick to one of those and keep the fat-to-carb ration in a 1:6 or 6:1 ratio based on what you pick (this ration comes from the eg Japanese eating 6x carbs for each 1g fat).

This is why opposing diets like carnivore or the potato diet both work, despite them being on the opposite extremes of the high fat vs high carb spectrum.

But god help you if you mix fats and carbs in the same amount...

The randle cycle is the likely explanation.

Each and every hypocaloric intervention study disagrees with you.

Very wrong.

You should be careful with phrases like "never works" because it makes it trivial to refute your argument.

For example, the only way I've ever lost weight was to simply eat less with no set diet at all. I lost 30lbs this way.

Reply on news.ycombinator.com