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Comment by keymone | Hacker News Reader

> However, some proteinand fat-rich foods (eggs, beef, fish, lentils, cheese, cake, anddoughnuts) induced as much insulin secretion as did some carbohydrate-rich foods (eg, beef was equal to brown rice andfish was equal to grain bread).

what? that makes zero sense, at least in case with fat. anybody got quick explanation for this?

Edit: found the TLDR explanation in another part of the paper

> postprandial insulin responses are not always proportional to blood glucose concentrations or to a meal's totalcarbohydrate content. Several insulinotropic factors are knownto potentiate the stimulatory effect of glucose and mediatepostprandial insulin secretion. These include fructose, certainamino acids and fatty acids, and gastrointestinal hormones suchas gastric inhibitory peptide, glucagon, and cholecystokiin(25, 26). Thus, protein- and fat-rich foods may induce substantial insulin secretion despite producing relatively small bloodglucose responses.

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This actually makes a ton of sense and is what people on the sidelines of the insulin debate have been screaming since Gary Taubes starting publishing his work about dietary sugar. Unfortunately it's given people a very non-nuanced view of the science.

The problem is not dietary sugar, it is blood sugar levels, which are elevated by many things (including protein and fat), but more than anything by excess calories. The problem is not peak blood sugar levels, it is average blood sugar levels.

Edit: to quickly reply to your TLDR edit:

> Thus, protein- and fat-rich foods may induce substantial insulin secretion despite producing relatively small bloodglucose responses.

This is only true if you completely ignore everything else going on in the body. Gluconeogenesis is a thing, and just because dietary fat or protein doesn't immediately increase blood sugar levels does not mean long term they don't. This stuff can't just be looked at as "input/output" you have to take into consideration the existing state of the person before the input. /edit

You can reason about this fairly easily: take a caloric intake of 2000 calories consumed all at once vs in 10 meals over the day. The all at once crowd gets a huge insulin spike. Oh no! Fat storage, right? Sure, but what happens the rest of the day when there is no dietary input? Fat burn! The 10 meals/day crowd probably never gets as high blood sugar levels, but also has much higher throughout the day, and accesses fat stores less. But guess what? Net the body is really pretty good at smoothing this stuff out, it's sort of the entire point of fat storage.

Where this gets tricky is that high insulin can eventually lead to low blood sugar dips. People without diabetes can simply wait this out, and the body will start burning fat again and raise the blood sugar. But this also makes many people feel hungry, and so they eat more, which raises their average blood sugar levels, and the cycle continues. Some people have a hard time with this, others do not, but it's really important to understand that the insulin is causing people to consume more calories which is causing damage, not the insulin itself.

Intuitively, you would expect that "drinking from the firehose" is not going to let you capture as much of the water as if you sipped from a trickle, and that same dynamic should apply generally: all customers come at the same time vs an hour, all enemies attack at once vs individually, etc.

Unless, of course, the human body historically faced strong selective pressures to efficiently store energy when you have to eat a lot at once.

> Unless, of course, the human body historically faced strong selective pressures to efficiently store energy when you have to eat a lot at once.

Right, and the intermittent fasting crowd uses the same tricks as Gary Taubes but in reverse: look what happens when you fast! All these great reparative things happen. But it's all basic science and ignores a long term (even 24 hour) view of consumption. Ultimately there might be small, statistically significant metabolic differences between consuming the same number of calories in 1 meal as spread out over multiple meals (ie: 1 big insulin spike vs multiple smaller ones), but we've had a hell of a time showing them, and and even harder time showing clinically significant differences.

Definitely! Don't get me wrong: no matter how intuitive an idea might be, you still need to validate it with experiment.

Spot on. But one of the main reasons fasting protocols “work” is that people are likely to reduce caloric intake and count macros/calories when they only eat in a tiny time window. It is difficult to eat 2k+ calories in a few hours and if you adhere to an intermittent fasting diet you will be much more likely to alter the nutritional profile and caloric intake of food you consume. It is no shocker people are noticing anecdotal improvements in bodyfat composition.

So while the actual intermittent fasting may not make much of a statistical metabolic difference if you hold caloric and macro consumption flat, in reality when people follow a fasting protocol they do not hold consumption flat.

Similarly when people follow ketogenic diets, they tend to eat far less calories. These diets tend to “work” mostly due to caloric restriction.

Are you you saying the work of Valter Longo on repairs, increase autophagy, etc... during long fasts (6 to 10 days) is not valid?

As far as I know the human body absorbs pretty much all the nutrition from the food it consumes, so yes you can drink from the firehose and get it all. Our feces is just the waste we were never going to absorb anyway like fiber and lots of dead fungi and bacteria that grew along the way.

>As far as I know the human body absorbs pretty much all the nutrition from the food it consumes

Not even close, especially when it comes to vitamins, nutrients and minerals. For example, take turmeric which is praised for its anti-inflammatory and anti-oxidant benefits...we will usually not readily absorb the active ingredients unless taken together with black pepper.

Black pepper will also improve nutrient availability in general, because it helps digestive enzyme secretion.

Another example is iron, which generally we readily absorb from meat but not plants, however, consuming iron rich plants together with vitamin c improves our iron absorption up to 6x.

nu·tri·ent

noun

a substance that provides nourishment essential for growth and the maintenance of life.

Turmeric isn't a nutrient. I'm talking about fats, sugars, proteins, which your body hoards every bit of no matter how much is eaten in one meal or spaced out. Of course there are exceptions like if you drink a gallon of oil and you get oily diarrhea, but a normal person absorbs all the calories and energy that is available from the food they consume.

Iron has its own regulation system of absorption and excretion, based on the iron status of the individual. If only we had those checks and balances on our caloric intake!

Yes, turmeric isn’t a nutrient, it’s a spice made up of nutrients.

Believe it or not vitamins and minerals are nutrients.

In nutrition science vitamins and minerals are generally referred to as micronutrients whereas fats, sugars, proteins are referred to as macronutrients.

And no macros are not all absorbed the same. As a general rule the longer someone’s intestines the more macro absorption they will have than someone with a shorter intestinal track. As I have already suggested digestive enzymes play a role, so if someone ate black pepper as I suggested before, that will secrete more digestive enzymes allowing for more absorption of calories and macros. There is also gut bacteria (microbiome) take for example the study of African twins where one is healthy and the other malnourished, where it was determined the malnourished twin with the same diet wasn’t absorbing the same amount of nutrients as the healthy twin because of the difference in their microbiome.

I'm sorry but you really don't know what you are talking about. I think you have accumulated a lot of repeated information from blogs and shoddy websites instead of from science.

https://www.ncbi.nlm.nih.gov/pubmed/?term=calories+black+pep...

This is the only reference I see in pubmed for calories and black pepper and it says black pepper raises the resting metabolic rate, nothing about absorption. And it shows black pepper reducing obesity which would be the opposite of what you are describing.

>”piperine is the major active component of black pepper and, when combined in a complex with curcumin, has been shown to increase bioavailability by 2000%.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664031/

Is there any clinical research showing improved health outcomes for combining black pepper with turmeric?

There are published human and animal Studies showing that piperine enhances serum concentration, extent of absorption and bioavailability of curcumin by 2,000%.

Yes but is there any hard evidence that leads to improved health outcomes in humans?

What’s “hard evidence”?

There are no shortage of published studies about the health benefits in humans. You might start with “Curcumin: A review of its effects on Human Health”. “Research suggests that curcumin can help in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis, Anxiety, and hyperlipidemia.” The same study finds it may also help with exercise induced inflammation and muscle soreness, speeding up recovery in active people and a low dose can provide health benefits for people who have no diagnosed Heath conditions. Available at ncbi.nlm.nih.gov

UCLA just published a study that curcumin improves memory and mood.

I think what he's asking for is long term epidemiological studies, which are hard to come by. I'd have to see the studies you are referring to, but most likely they refer to measurements occurring over a relatively short time period, on a relatively small sample size (or in a lab on animals, or just cells, etc. etc.). This stuff is totally valid, but a lot of it is really hard to detect at a large scale level. You can justify many kinds of diets by looking at the short term biological impact of them, but the reality is that if these diets are so much better it shouldn't be so difficult to detect them in epidemiological studies. The classic example is the widely misinterpreted "China Study" which many people use to justify a vegetarian diet, but in fact did the opposite by proving that the effect size of eating red meat, while statistically significant, was literally 2 orders of magnitude below what would be considered clinically relevant at an epidemiological scale.

Well I didn’t make a single claim as to the medical/health benefits of turmeric/curcumin anyway, not sure why he asked period.

My point is about absorption, and curcumin is the perfect example of my point, by itself it isn’t bioavailable but studies provide “hard evidence” that black pepper makes curcumin 2000x more bioavailable.

Sorry for the dumb question, but given the total calories are the same, does this mean that it is generally healthier to eat one big meal per day rather than 10 small ones?

Given my current understanding from all the intermittent fasting hype lately, it is indeed better to eat big meals rarely rather than small meals frequently. For some reason, your post got me slightly confused because I lack the necessary knowledge to have a proper model about nutrition in place.

The answer to your question is yes.

I’m doing 18:6 or 20:4 protocols, I eat 2 meals per day usually and I like measurements. My blood ketones during my fasting are through the roof, over 1.5 mmol/L after 15 hours of fasting, which indicates deep nutritional ketosis and an indication that lypolisis is efficient.

I can tell you this would not happen if I ate 6 small meals per day. And I know because I measured myself. But it’s also how the body works ... ketosis happens after the liver’s glycogen stores are depleted, which takes 10-12 hours and the switch to burning fat isn’t very efficient and getting less so with age. Your body needs a break from food in order to mobilize the energy in your adipose tissue.

With 6 small meals what actually happens is constant hunger because you’re interrupting lipolysis every time you eat. This happens even with the ketogenic diet, because even meat triggers a hormonal response, small but not insignificant.

Also speaking from my own experience, I suffered from hunger at night, which made me binge. Switched to IF, hunger is now gone. Sounds like a paradox but it really isn’t.

> My blood ketones during my fasting are through the roof, over 1.5 mmol/L after 15 hours of fasting, which indicates deep nutritional ketosis and an indication that lypolisis is efficient.

The problem is that there isn't any real data, on an epidemiological level, that says this matters. I don't mean to be offensive, it's just a weird obsession with the Keto community I don't really understand. Same with insulin spikes. They just don't matter. It's averages over a long period of time that matter. If you're eating two large meals, you're still releasing a lot of insulin, you're still doing the same amount of fat storage, you're just timing it differently. If that works for you, great.

> I can tell you this would not happen if I ate 6 small meals per day. And I know because I measured myself. But it’s also how the body works ... ketosis happens after the liver’s glycogen stores are depleted, which takes 10-12 hours and the switch to burning fat isn’t very efficient and getting less so with age. Your body needs a break from food in order to mobilize the energy in your adipose tissue.

This is a semantic construction that is not supported by the science. You are correct that you would not measure nearly as high blood ketone levels, but you are incorrect in the idea that you wouldn't consume essentially the same amount of fat over the same amount of time given the same caloric inputs. Most people also go into ketosis while they are sleeping.

> With 6 small meals what actually happens is constant hunger because you’re interrupting lipolysis every time you eat.

This doesn't matter. Given the same energy requirements and the same energy inputs you're going to burn the same amount of fat over a 24 hour period regardless of when those inputs come. Anything else is an extraordinary claim that requires extraordinary evidence.

> This happens even with the ketogenic diet, because even meat triggers a hormonal response, small but not insignificant.

Yes, keto is actually a low protein diet as much as a high fat diet. Most people ignore the first part.

> Also speaking from my own experience, I suffered from hunger at night, which made me binge. Switched to IF, hunger is now gone. Sounds like a paradox but it really isn’t.

This is great, and a very real reason for people to try IF/Keto/Other diets. But it does not suggest anything other than a compliance hack that is working well for you.

> If you're eating two large meals, you're still releasing a lot of insulin, you're still doing the same amount of fat storage, you're just timing it differently. If that works for you, great.

Yes, but your body won't be able to use it's stored fat in the presence of insulin. If you keep that up long enough, you can only burn calories coming in. If you eat a lot of meals AND a caloric deficit your body needs to decrease your metabolism, mostly heat, thus cold hands and feet.

> This is a semantic construction that is not supported by the science.

It is. See insulin vs glucagon.

> but you are incorrect in the idea that you wouldn't consume essentially the same amount of fat over the same amount of time given the same caloric inputs

It's about your metabolism not CICO.

> Most people also go into ketosis while they are sleeping.

Well it won't be a deep ketosis. The longer your fast, the lower the insulin, the more body fat will be used.

> This doesn't matter. Given the same energy requirements and the same energy inputs you're going to burn the same amount of fat over a 24 hour period regardless of when those inputs come. Anything else is an extraordinary claim that requires extraordinary evidence.

It absolutely does matter, because your body does not burn a static amount of calories but adapts to the situation. Slowing metabolism is real. If you can't burn energy (low caloric input but frequent meals), your body will do what it needs to survive.

> Yes, keto is actually a low protein diet as much as a high fat diet. Most people ignore the first part.

Yes!

> This is great, and a very real reason for people to try IF/Keto/Other diets. But it does not suggest anything other than a compliance hack that is working well for you.

While it's anecdotal, there are good reasons for this effect.

You don't need to go low carb for a healthy diet, but cutting insulin raising foods for periods of time does have its merit. Take no more than 3 meals a day and leave 12+ hours food-free. Will do wonders for most people.

> Yes, but your body won't be able to use it's stored fat in the presence of insulin. If you keep that up long enough, you can only burn calories coming in. If you eat a lot of meals AND a caloric deficit your body needs to decrease your metabolism, mostly heat, thus cold hands and feet.

Right but what happens when you no longer inputting calories and thus no longer have high insulin? Then you start burning the fat again. You can only keep your insulin levels pathologically elevated if you are eating enough to support that over the long term, regardless of when you eat. Again, your body is very good at supplementing energy needs with fat when it needs to. Again there is no study showing meal time having any impact when calories are balanced, and several confirming the opposite.

> It absolutely does matter, because your body does not burn a static amount of calories but adapts to the situation. Slowing metabolism is real. If you can't burn energy (low caloric input but frequent meals), your body will do what it needs to survive.

Your body adapts to a short term situation (a meal and the small post-prandial period) but in the long term (24 hour period) it makes zero difference.

> Slowing metabolism is real.

Yes but it's also reversible by, shockingly, increasing caloric demand.

To be very clear, the proof required for what you are suggesting is a study with a minimum of 2 groups eating the same exact meals but at different times, and being forced to finish the entire meal and experiencing different outcomes. This has never happened, and based on our current understanding of metabolism never will. Maybe it would change, but this would be a massive massive change in our understanding of how the human body deals with energy.

> To be very clear, the proof required for what you are suggesting is a study with a minimum of 2 groups eating the same exact meals but at different times, and being forced to finish the entire meal and experiencing different outcomes. This has never happened, and based on our current understanding of metabolism never will.

Humans, difference in body composition: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645638/

https://ir.lib.uwo.ca/wurjhns/vol8/iss1/4/

Again difc in body composition in humans, but references to previous studies showing difference in mass in mice:

https://nature.berkeley.edu/garbelottoat/wp-content/uploads/...

Not sure why you're being downvoted, and I appreciate you finding studies.

> Humans, difference in body composition: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645638/

So this study is actually not bad. It has three small flaws that I can find, but is still compelling regardless. It is one of the only studies I have ever seen that did a decent job controlling the food. I'd like to see it repeated and at a larger scale, of course. The flaws are:

1. Malabsorption is a real issue when consuming nearly 2400 calories in a small window. This could be a real confounder with regards to metabolic differences. The malabsorption could be resulting in fewer calories being consumed.

2. Massive withdrawal rate in comparison to other dietary studies. The authors address this, I think reasonably, by concluding that IF is actually really difficult for a lot of people to comply to. This isn't necessarily a strike against IF being metabolically better, but if we dig into exactly why the diet is hard to comply to and force the people who didn't want to comply to comply, we might get different metabolic results. There is a large potential for survivorship bias here.

3. Sample size is tiny blah blah. This doesn't disregard the study but it does limit its applicability.

Good find, though, thanks!

As for the other two, I don't think they meet the requirements really.

> Right but what happens when you no longer inputting calories and thus no longer have high insulin? Then you start burning the fat again. You can only keep your insulin levels pathologically elevated if you are eating enough to support that over the long term, regardless of when you eat.

No, diabetics have an elevated insulin levels for hours after a meal. Like, after 4 hours it's still at the level a non-diabetic peaks at after 0.5-1 hour. Eating many meals will keep your insulin levels high all-day.

> Again, your body is very good at supplementing energy needs with fat when it needs to. Again there is no study showing meal time having any impact when calories are balanced, and several confirming the opposite.

Your body is very bad at burning fat in the presence of insulin. Meal time is only important as to not keep your insulin level elevated all the time.

> Your body adapts to a short term situation (a meal and the small post-prandial period) but in the long term (24 hour period) it makes zero difference.

If you are eating all the time, the short term situation becomes the long term situation, not barely on 24 hour periods but for years on end. This is especially true for diabetics and pre-diabetics, as their insulin level will lower way slower.

This is not to say you can't avoid the whole situation by lowering your calories BEFORE you become diabetic. It may actually be the best way, but the science is far from being set because it's such a complex problem.

> Yes but it's also reversible by, shockingly, increasing caloric demand.

It's reversible by either supplementing more food or allowing your body to access its own resources (low insulin!). Increasing caloric demand (exercise!) will help insofar as you're burning of sugar -> less insulin.

While I'm not a fan of isocaloric studys, this should work, yes. You would also have to factor in a lot of other parameters, like established insulin resistance (probably using Kraft-Patterns)

> This has never happened, and based on our current understanding of metabolism never will. Maybe it would change, but this would be a massive massive change in our understanding of how the human body deals with energy.

I'm genuinely interested as to what your understanding of insulins / glucagons effect on your body's ability to access fat is.

> No, diabetics have an elevated insulin levels for hours after a meal. Like, after 4 hours it's still at the level a non-diabetic peaks at after 0.5-1 hour. Eating many meals will keep your insulin levels high all-day.

I have repeatedly said in this thread this doesn't apply to diabetics, who do have an insulin pathology. Diabetics do need to worry about insulin, non-diabetics do not.

> Your body is very bad at burning fat in the presence of insulin. Meal time is only important as to not keep your insulin level elevated all the time.

There is no science that disambiguates between large spikes followed by zero food in take (IF), and small spikes continually at the same calorie levels. Please feel free to send any study you think does.

> It's reversible by either supplementing more food

Again this is only relevant to the post-prandial window. If you are overweight, and have a slow metabolism, and respond by eating a lot of food, you will not successfully "speed up" your metabolism outside of the prandial window. If you are overweight and start dieting, your metabolism with slow down, but the evidence overwhelmingly shows exercise counteracts this, and that the slowdown is reversible when your body fat percentage lowers.

> If you are eating all the time, the short term situation becomes the long term situation, not barely on 24 hour periods but for years on end. This is especially true for diabetics and pre-diabetics, as their insulin level will lower way slower.

No, this is only true if you are eating all the time and also eating too many calories. . Again, please send a link to a study you think says otherwise.

> While I'm not a fan of isocaloric studys, this should work, yes.

Why are you not a fan of the only kind of study that could possibly prove your point? And why hasn't this study ever been successfully completed? Why have studies that attempted to do this been unable to show any difference in outcomes?

> I'm genuinely interested as to what your understanding of insulins / glucagons effect on your body's ability to access fat is.

I don't really know what you're implying here, but I suspect you are still getting hamstrung by the prandial window. Yes, insulin can block your ability to access fat in the short term, no it will not in the long term, and it does not do so entirely either. If you are eating the same number of calories and thus constantly releasing insulin you are blocking some, but not all, lipolysis. Lipolysis is not a binary, nor is insulin release. You can have both of them happening at the same time, even though insulin is blocking some of the lipolysis.

> I have repeatedly said in this thread this doesn't apply to diabetics, who do have an insulin pathology. Diabetics do need to worry about insulin, non-diabetics do not.

Point taken :-)

> There is no science that disambiguates between large spikes followed by zero food in take (IF), and small spikes continually at the same calorie levels. Please feel free to send any study you think does.

and

> No, this is only true if you are eating all the time and also eating too many calories. . Again, please send a link to a study you think says otherwise.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079942/

> Why are you not a fan of the only kind of study that could possibly prove your point?

Because you're on a circadian clock with lots of hormonal regulations that have huge influence on you. Most people won't feel as hungry on a fat-heavy diet as on a low-calorie (mostly low-fat) diet. Long-term adherence to low-calorie diets is just not working out for most people. Yes, calorie-restriction works in basically every living thing to prolong life. No, people will not do it.

> And why hasn't this study ever been successfully completed? Why have studies that attempted to do this been unable to show any difference in outcomes?

There is evidence. Please don't tell me there is conclusive evidence on anything related to nutrition. The second statement is not true, differences have been shown.

> I don't really know what you're implying here, but I suspect you are still getting hamstrung by the prandial window. Yes, insulin can block your ability to access fat in the short term, no it will not in the long term, and it does not do so entirely either. If you are eating the same number of calories and thus constantly releasing insulin you are blocking some, but not all, lipolysis. Lipolysis is not a binary, nor is insulin release. You can have both of them happening at the same time, even though insulin is blocking some of the lipolysis.

Yes, it's not binary, but the easy way to increase lipolysis is to decrease insulin.

> Yes, calorie-restriction works in basically every living thing to prolong life. No, people will not do it.

Right, this is the point: it's about compliance, which is real and important, but very different from metabolic change.

> Please don't tell me there is conclusive evidence on anything related to nutrition. The second statement is not true, differences have been shown.

No, there is no study showing the same number of calories consumed over different feeding schedules have any different outcomes. I am 100% confident about this. To be clear: there are studies showing people on IF eat fewer calories, and that eating few calories has net benefits. That's great, but that's compliance not metabolism.

> Yes, it's not binary, but the easy way to increase lipolysis is to decrease insulin.

Again, time windows. Please consider time windows. In a 24 hour period this stuff is all neutralized. Or maybe it's not, but we don't have any science showing it's not, and quite a bit showing it is.

Healthier is subjective. Diabetics are taught to eat multiple small meals a day to manage blood sugar levels better.

That of course assuming you're diabetic, otherwise you are totally capable of consuming food either way.

Capable, but it doesn't matter since your blood sugar level will spike higher and for longer with a single large meal even in a non-diabetic individual.

And why, when compared to a constant elevated level from many small meals, is that a bad thing?

What diabetics are told to eat has generally been bullshit for good half a century. The whole low-fat craze and cholesterol horror stories I mean.

> Sorry for the dumb question, but given the total calories are the same, does this mean that it is generally healthier to eat one big meal per day rather than 10 small ones?

We can't answer this confidently, the way I would say it is: there isn't strong evidence to support the idea that either is better.

> Given my current understanding from all the intermittent fasting hype lately, it is indeed better to eat big meals rarely rather than small meals frequently. For some reason, your post got me slightly confused because I lack the necessary knowledge to have a proper model about nutrition in place.

The IF people (along with the Keto people) use a variety of tricks to try and prove their point. There is absolutely not a single paper showing calorically balanced food intake has different clinically significant outcomes. Period, full stop etc. There are tons of papers saying things like if you force people to eat in constrained windows they eat fewer calories (or if you force people to eat high fat diets they eat fewer calories etc.). Those are all useful outcomes: they are "compliance hacks." But they idea that any of these are significantly metabolically different is not at all supported by the science.

As for yourself: nutritional science is weak, and if the nutritional science says do something, and you observe a bad outcome in yourself from doing it, I'd take your own personal data over the nutritional science, frankly. For instance: fiber is a great modulator. If you go to a GI specialist and say "I'm having dietary issues," increasing fiber is usually the first thing they recommend. But also, sometimes that doesn't work and then the next thing is decreasing fiber (FODMAP diet). So it's really hard to make sweeping recommendations because the body is so complex and nutrition involves so many different cooperating systems that can all go slightly wrong.

>>But they idea that any of these are significantly metabolically different is not at all supported by the science.

This doesn't seem correct. IF has statistically significant benefits:

https://www.health.harvard.edu/blog/intermittent-fasting-sur...

(Supporting papers linked at the end)

I'm sorry to just repost my paragraph from above, but I believe I already responded to this:

> The IF people (along with the Keto people) use a variety of tricks to try and prove their point. There is absolutely not a single paper showing calorically balanced food intake has clinically significant outcomes. Period, full stop etc. There are tons of papers saying things like if you force people to eat in constrained windows they eat fewer calories (or if you force people to eat high fat diets they eat fewer calories etc.). Those are all useful outcomes: they are "compliance hacks." But they idea that any of these are significantly metabolically different is not at all supported by the science.

1. These papers do not show different outcomes with calorically controlled inputs, as I mentioned. One of the tricks used by the IF scientific community is to serve the same number of calories and so it looks like the same number of calories were consumed in the abstract. They never are, because if this did happen it would have massive implications for our understanding of the human body. It would require us to be wrong about a lot of things.

2. There is a difference between statistical significance (which could be, but has not been, shown in calorically controlled diets), and clinical significance (which definitely has not been shown in calorically controlled diets, and likely will not).

I agree with everything you are saying and have mostly come to the same conclusions you have except:

It’s obviously not true that for any given set of calories consumed the body has only one option of what to do with them. It can build muscle, store fat, repair heart walls, excrete it, and so forth.

This is determined by a bunch of factors including hormones. So if hormonal balance or other metabolic behavior is modulated by macro (or micro) nutrient intake, then the calorie emphasis might be overly simplistic.

> It’s obviously not true that for any given set of calories consumed the body has only one option of what to do with them. It can build muscle, store fat, repair heart walls, excrete it, and so forth.

Yep, I would not suggest anyone take up a diet of pure sugar, only that if you are trying to use science to set your diet we aren't really confident, at the level of macros, about what makes a difference, but we are very confident about excess calories.

Ok, but I know from personal experience that for me, personally, macronutrient ratio and feeding window both, independently and together, have dramatic impact on my physical appearance, energy level, and mental functioning.

The way you are wording your comments, someone could come away feeling like these things aren’t really worth considering.

It’s like, your comments to me seem like you are technically correct but a person reading them might think “ok, this smart person said the Atkins diet doesn’t really work, it’s all sleight of hand.”

That could be counter productive, because the Atkins diet really DOES work for some people. Proving that it’s likely not working for the reason people think it is can be helpful for accuracy’s sake, but depending on delivery can just become discouraging.

The missing point is these interventions really can be effective. Why they are effective is more of an intellectual exercise.

> They never are, because if this did happen it would have massive implications for our understanding of the human body. It would require us to be wrong about a lot of things.

Yeah, welcome to medicine. If you've ever encountered these things in a non-theoretic perspective (i.e., having some condition), you quickly see that doctors don't know shit.

Perhaps not surprising, given that human experimentation is taboo.

Anyways, how does what you're saying mesh with the fact that extra glucose is stored in your body's reserves while ketones are secreted with urine and breath?

> Yeah, welcome to medicine. If you've ever encountered these things in a non-theoretic perspective (i.e., having some condition), you quickly see that doctors don't know shit.

That is, unfortunately, exactly why I am so acquainted with this stuff, and yeah, it is pretty frightening to have doctors tell you they just don't know. But to be fair, I'm talking about being wrong about fundamental biology, not medicine, in which massive shake ups like that are far rarer. It's also not like this stuff hasn't been studied.

> Anyways, how does what you're saying mesh with the fact that extra glucose is stored in your body's reserves while ketones are secreted with urine and breath?

Not sure what you mean but fwiw glucose is also secreted in urine and breath.

>Supporting papers linked at the end

Not really "supporting papers". Just random papers on the subject, most non-supporting.

E.g. one of linked papers covers a research on "alternate day IF" and concludes: "Alternate-day fasting did not produce superior adherence, weight loss, weight maintenance, or cardioprotection vs daily calorie restriction."

Another is a meta-study that concludes: "Although both treatment interventions achieved similar changes in body weight (approximately 7 kg), the pooled estimate for studies that investigated the effect of intermittent energy restriction in comparison to continuous energy restriction revealed no significant difference in weight loss".

A third of the linked studies concludes: "Research has not demonstrated that alternate-day fasting regimens produce superior weight loss in comparison to standard, continuous calorie restriction weight-loss plans."

So it's just a random "blog" style post, on health.harvard.edu nonetheless, that gives several links, that do not support its thesis.

But a casual reader will think "hmm, the post says IF is good, and gives links to several studies, so the science is solid" (assuming that the links support IF).

Somewhat unrelated, but you seem knowledgeable enough and I have this burning need to ask this question to someone: when prescribed to the average non-diabetic person, does the average diet for diabetics promote improved health? In other words, should we all just be eating as if we were diabetics?

> In other words, should we all just be eating as if we were diabetics?

I assume you mean low glycemic load. I don't think so. I think we should all focus primarily on eating the right number of calories, and the behaviors that get us to do that. If that is Keto, or IF, or Low GI, even something random like afternoon naps then great.

Also, for some populations, like athletes, a low-gi diet would end up resulting in decreased performance. I think it's really difficult to make sweeping dietary recommendations because there are just so many confounding factors.

As a Type 1 diabetic, it's certainly easier to control one's blood sugar eating multiple, smaller meals per day. Specifically, the rate at which the food and insulin are absorbed into the system can vary by a large amount. The smaller the meal (and insulin does needed for it), the less extrme a high/lower blood sugar spike is likely to be.

Yes, I want to point out that diabetics react differently and really do have to manage insulin, it's the idea that metabolically healthy people also have to that is a red herring. Obesity is not an insulin disorder just because insulin is involved. Diabetes is absolutely an insulin disorder.

But what causes an insulin disorder? I thought the argument for eating like a diabetic is so you don’t become one.

You have to be more specific. T1 diabetes is almost entirely genetic, T2 diabetes is almost entirely behavioral. T2 diabetes is caused by eating too many calories. T2 diabetes is reversed by constraining calories, regardless of macronutrient composition.

What about the other fad diet boogeyman, inflammation? Is there any relevance between that and insulin responses? Or anything else?

It's the same idea: talking about spikes vs average. Calories is what matters. Yes, insulin and inflammation can be linked, but also you wont have excess of either on a calorically controlled diet.

Interestingly context can totally reverse the implications here too. For instance: as a weightlifter I want a heavy insulin response and I want a heavy inflammatory response because both of those help build muscle. So even saying that inflammation is bad requires a bit more nuance. It's very complicated, which is why Calories In Calories Out is such a powerful simplification. It doesn't tell you everything, but everything fits into that explanation, and if you can figure out how to control calories a ton of other bad things stop happening too.

I’m more curious from the perspective of someone with a normal BMI. CICO isn’t relevant at that point, as that is a solved problem. It seems like every health blogger has an article for why eating X is bad, where X has exhausted virtually all values.

It sounds like your conclusion is roughly that, sufficient nutrients aside, it doesn’t make a damn bit of difference which columns the calories are under, not just in terms of weight management, but general health.

Yet, I struggle to entertain the possibility that the guy eating a lot of pizza and ice cream and candy is going to encounter health problems a lot sooner than someone of the same CICO eating avocados and chicken and broccoli.

Is one just as good as the other? What about skinny people who get heart attacks?

> It sounds like your conclusion is roughly that, sufficient nutrients aside, it doesn’t make a damn bit of difference which columns the calories are under, not just in terms of weight management, but general health.

My conclusion is that but slightly more conservative: more that science is really hard, and we have not been able to show that macro nutrient composition matters nearly as much as we thought. It may still matter quite a bit, though you'd expect it to be easier to measure if it did, but again science is hard.

> Yet, I struggle to entertain the possibility that the guy eating a lot of pizza and ice cream and candy is going to encounter health problems a lot sooner than someone of the same CICO eating avocados and chicken and broccoli.

I can show you small scale examples of people doing this and not having problems (http://www.cnn.com/2010/HEALTH/11/08/twinkie.diet.professor/...) but I can't show you a strong epidemiological study that confirms this, unfortunately.

> What about skinny people who get heart attacks?

This does happen, though of course far more rarely. Lots of stuff impacts this (genetics etc.), and I don't know nearly enough about heart attacks to comment, but I will say broadly that one of the worst things you can do for your heart, and most of the rest of your body, is to be fat, and the only way to be fat is to eat excess calories.

There seem to be no definitive answer to this, sadly.

But...

My own experimentation (beware of experiments with the sample size of one...) results is that restricting myself eating rarely but in bigger doses makes me feel more healthy and makes keeping / loosing weight much easier. Rarely in this case means something like one large meal a day or every two days or something inbetween.

Now, I attribute this to what happens between the meals.

Just as training to run a marathon is mostly focused on teaching your body to reach into fat stores before your glycogen stores run out I think of fasting in between meals as an excercise for the body in running pathways in the opposite direction.

My understanding is that the fat stores are neither good or bad. Your body uses them to store energy for later with the assumption that it will be extracted at some point.

If you keep yourself satied constantly, keep insulin levels all the time except maybe short time before breakfast, your body is not trained in effectively using the stores. The metabolic pathways for ketosis are unused and underdeveloped.

In that state, as soon as you stop eating and blood glucose levels fall you start feeling hungry. There are other reasons for this happening (misinterpreting not being satiated for hunger) but one of the reasons is that the metabolic pathways for getting back at your fat energy stores are not kicking fast enough to react to demand.

This is of course vicious cycle -- you get hungry quickly so you reach for a snack or something else to immediately satisfy your hunger which further makes sure you never excercise yourself to deal with hunger.

I'm having a hard time with some of the things you are saying here, but my knowledge of how this stuff works is pretty simplistic. I'm curious specifically about the mechanisms for this stuff.

How can fat elevate blood sugar levels?

If you don't have elevated blood sugar from eating a bunch of carbs, what effect does insulin have? Does it cause blood sugar to go even lower?

On gluconeogenesis: I thought this was demand driven rather than supply driven. Insulin apparently is an inhibitor for this. So how does this work?

> How can fat elevate blood sugar levels?

Via gluconeogenesis, but it is, for sure, less effective than protein based gluconeogenesis.

> If you don't have elevated blood sugar from eating a bunch of carbs, what effect does insulin have?

You have elevated blood sugar from having an excess of calories. Dietary sugar is most rapidly converted to blood sugar, but all excess calories are eventually converted via gluconeogenesis.

> Does it cause blood sugar to go even lower?

Yes, and in extremes can cause death.

> On gluconeogenesis: I thought this was demand driven rather than supply driven. Insulin apparently is an inhibitor for this. So how does this work?

Gluconeogenesis first causes the breakdown of protein into available glucose. What the body does with it after that has a lot to do with the body's current energy demands. Insulin is an inhibitor for this, but insulin is also only elevated post-prandial, and most gluconeogenesis happens off schedule from eating (or at the very least after the initial insulin response).

The major error people make when trying to understand this stuff is to focus on too short of a time frame, in this case the very small period right after a meal is consumed, rather than something longer, like a 24 hour period. As soon as you zoom out to 24 hours a lot of these ideas stop making sense because your body has a large amount of resources dedicated to effectively regulating energy expenditure.

It's far too simplistic to argue that it's the average insulin intake that matters. The complex kinetics depends both on rate as well as average / basal dosages. This is a complex system that behaves differently across individuals with varying metabolisms and diets. Spikes can trigger different biological responses that respond to thresholds and equilibria. It's a differential problem, and the answer isn't easy.

> It's far too simplistic to argue that it's the average insulin intake that matters.

I agree, I'm trying to more accurately state what we confidently know based on the available science, rather than what might be true based on our hunches. Insulin spikes being bad are 100% in hunch land.

> The complex kinetics depends both on rate as well as average / basal dosages.

I agree but, again, very little science that disambiguates effectively.

> Spikes can trigger different biological responses that respond to thresholds and equilibria.

Right, this is what the basic science has shown, but what we don't know is what difference this makes within a 24 hour window, or epidemiologically over time.

> It's a differential problem, and the answer isn't easy.

Definitely agree.

Regarding calorie control - has it not been shown that in ketosis your basal metabolic rate and hunger are generally lower? So feeding people static amount of calories isn’t really measuring the same thing to what happens in the wild - eating until satiety?

> But guess what? Net the body is really pretty good at smoothing this stuff out, it's sort of the entire point of fat storage.

Any resource to validate this claim. This is just a reformulation of the CICO argument. Saying the body "is good at smoothing this out" is tautological at saying that the distribution of the calories across the time domain (the IF crow) or accros the macro domain ( paleo peps) doesn't matter. And as i know we don't know that yet.

> that the insulin is consume more calories which is causing damage, not the insulin itself.

Again any claim to this ? Most reference i see have this causation relationship reversed....

> Any resource to validate this claim.

Most IF studies do not show any metabolic difference, and the ones that do do not control for calories. I'm sorry to shift the burden of proof, but I feel like CICO is the default position and additional nuance requires proof, not the opposite. Also I am lazy.

> Again any claim to this ? Most reference i see have this causation relationship reversed....

Yeah totally, so the claim is not that insulin does not cause damage, it is that where we have recorded that damage is directly to cells in labs, but we have not translated this to epidemiological studies. This is sort of like the Schroedinger's Cat of nutrition: we see these effects in the lab at micro scale, but we don't actually see them translate to real world effects when we look for them at the macro scale. One explanation is that with the same way we see insulin causing damage, we see caloric deficit causing repairs. Maybe these cancel each other out when calories are controlled for? I don't have an explanation, but the key is that we don't observe this stuff on the macro level.

> but I feel like CICO is the default position and additional nuance requires proof

Is there really a need to default position ? CICO and the fact that distribution (both in time and macro) of the calorie in matter can both be true. The assumption i do not agree with in CICO is CI is an independent and infinitely controllable variable. Now it's possible that the causal link between a certain macro distribution (let say high carb diet) and weight gain is mediated by CI, but from there it doesnt follow that CI control is an effective way of weight control.

> but we have not translated this to epidemiological studies.

Depends on what you call epidemiological study, but using the diabetic population, the causal link between insulin and weigth gain is pretty strong. The book "obesity code" make of good case for that.

> CICO and the fact that distribution (both in time and macro) of the calorie in matter can both be true.

Maybe they do matter somewhat, but here's the deal: if everyone who was obese in this country all of a sudden started eating a diet that was macronutriently ideal and consumed at the perfect times, but maintained the same number of calories, there would be no difference in the prevalence of obesity. I think the science really confidently supports that position, and I'd be happy to look at anything you think denies it.

> Depends on what you call epidemiological study, but using the diabetic population, the causal link between insulin and weigth gain is pretty strong. The book "obesity code" make of good case for that.

I am very familiar with Dr Fung's work and don't think that any of it makes the case you are trying to make. All of his work provides proof for what I've been saying over and over in this thread: IF and Keto can be great ways to create compliance to a diet, but there is no evidence, including the work of Dr Fung, that shows these diets behaving differently from simple calorie control outside of the compliance aspect.

> if everyone who was obese in this country all of a sudden started eating a diet that was macronutriently ideal and consumed at the perfect times, but maintained the same number of calories, there would be no difference in the prevalence of obesity. I think the science really confidently supports that position, and I'd be happy to look at anything you think denies it.

Again, no. You are tautologically restating CICO. We have no evidence of this being true. You are implicitly assuming that CO will be constant and would be independent of CI... We do not know that to be true.

> I am very familiar with Dr Fung's work and don't think that any of it makes the case you are trying to make. All of his work provides proof for what I've been saying over and over in this thread: IF and Keto can be great ways to create compliance to a diet, but there is no evidence, including the work of Dr Fung, that shows these diets behaving differently from simple calorie control outside of the compliance aspect.

I seem to recall a bunch of animal models where compliance was controlled for and still showed a strong correlation between insulin and set weight.

> You are implicitly assuming that CO will be constant and would be independent of CI... We do not know that to be true.

No, we can reason about this fairly easily knowing the extraction costs of calories from macronutrients. You're correct in that macronutrient content can affect CO, but you're vastly overstating the amount. There is no model of digestion we've come up with that accounts for much more than 10% of calories going to digestion, so even if you max that out, you still end up with pretty similar levels of obesity. We cannot fix this problem without radically reducing the amount we eat, regardless of the macronutrient content.

> I seem to recall a bunch of animal models where compliance was controlled for and still showed a strong correlation between insulin and set weight.

Please send links, all I can do is respond to the specifics of an actual study.

Or higher basal metabolism and higher activity levels ... Both of which would increase CO...

But we're getting out track , my point is simply that CICO expresses a relationship between calorie in , calorie out and the variation in people weigth . It's doesn't say that one can control people weigth using CI. The analogy that Judea pearl uses is that there is a relationship between the number displayed on a thermostat and the temperature outside , but that does not imply that one can control the temperature outside by changing the number displayed on the thermostat

> It's doesn't say that one can control people weigth using CI.

It absolutely says that. Absent other factors changing, a reduction in caloric intake will result in a weight loss. It does not disagree with there also being other inputs to CO.

Yeah I had the feeling that that's where we would disagree. Happy to agree to disagree on this one

> CICO is the default position

CICO is demonstrably bullshit. Vodka and Coca-Cola have the same number of calories, but vastly different effects on a person's metabolism. Just compare a vodka binge drinker with a coke binge drinker.

Also you can't drink gasoline, which has a ton of calories, straight up, so CICO is bullshit.

But to steel man your argument: yes, macronutrient composition obviously matters, but you can lose weight with a low calorie diet of any composition and you cannot lose weight with a high calorie, macronutriently balanced diet.

> But guess what? Net the body is really pretty good at smoothing this stuff out, it's sort of the entire point of fat storage.

So why can't I eat a month's worth of calories in one go and then fast for the rest of the month with water and multivitamins?

You can't fill yourself with that much and if you managed to it won't be absorbed before coming out the other end.

Yeah, this is actually a great question imo.

So the main problem would be nutrient absorption, and there would be a number of problems that would impact it, from literal surface area of your digestive system, to current bacterial populations etc. etc. These problems matter less in a 24 hour window when you are far less likely to hit the same thresholds eating a reasonable amount of food. But basically, you could not effectively break down and absorb all the nutrients quickly enough, and you would have pretty nasty shits/vomiting.

But, let's say somehow you could, and somehow your body ended up storing a bunch of fat. In general, the second half of your statement is totally doable because the human body absolutely kicks ass at energy storage and expenditure. https://www.sciencealert.com/the-true-story-of-a-man-who-sur...

I'm experimenting with IF/keto at the moment, mainly to see if it helps put on lean muscle. For context, I've also been eating relatively clean (low carb, high protein/fibre) for years now.

I take all the internet commentary about low insulin levels (etc) with a grain of salt. I just don't know enough about endocrinology or the current state of research.

That being said, higher carbohydrate intake causes a noticeable spike in how hungry I feel. If I have a moderately carb-heavy dinner (50-100g), I'm ravenous when I wake up, and mentally I'm a lot fuzzier.

Then, like clockwork, they both disappear around 3pm, which I assume coincides with the switch over from metabolizing glycogen to fatty acids.

If I keep carbs under 20g, I'm fine from the moment I wake up. I have mild sensations of hunger later in the day, but nothing like the pangs I get on the higher carb diet.

This seems to be well documented, and most people on the keto diet report similar experiences.

Do you think this hormonal response has no impact on weight loss (or, for that matter, muscle gain)?

> Do you think this hormonal response has no impact on weight loss (or, for that matter, muscle gain)?

That's way too broad a statement for me to blanket agree or disagree with. Short answer: no I definitely don't think that. Long answer: basically everything else I said in this thread.

as a data point, keto helped me put on a ton of muscle. I do lift weights 6 days per week, but I attribute it to increased testosterone. I've been fairly principled in my approach to experimenting with keto, including doing regular bloodwork.

Prior to keto my T was around 450. Post keto (~2 months in), it was close to 800. I was/am eating a ton of fat. I don't measure it (I eat intuitively based on hunger) but I would estimate my fat intake to be around 200g fat/day or more.

Just my personal anecdote. We'll see how long I live for ¯\_(ツ)_/¯

I have personally had to work through this concept...

When in deep ketosis I was experimenting with various types of protein supplements and (surprisingly) found whey would spike my insulin. Of course this seemed odd as my supplement was pure and contained no sugar/no carbs.

After researching come to find out this is well known and in fact whey has a bigger impact on insulin levels than pure glucose. Apparently the amino acids in whey trigger insulin secretion directly in pancreatic beta cells.

Edit:

I thought it kind of funny doughnuts made its way into your fat/protein list and not the carb list.

I'm not aware of any way to check insulin levels from home - how did you do that?

In my case I wasn’t measuring for insulin in the blood I was measuring ketones before and after intake of the various proteins. In the case of whey my ketone readings would be around or above 3 mmol/L and after whey it would be <.5 mmol/L which would be indicative of being knocked out of ketosis through an insulin spike.

Walmart blood strip tester?

Which can test blood sugar and ketone levels - I've never heard of strips for insulin levels.

Did the whey contain artificial sweetener?

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