Nutrition science

I've seen people make the uncharitable presumption that meat-eaters just can't bear to give up the taste. So let me clarify that back in 2013 when I decided to lose weight, I liked meat but wasn't a big consumer. I was ready to go plant-based or even eat nothing but broccoli for a year if that's what it took (young people are extreme like this). So I read up on necessary nutrients, all the vitamins, minerals and their different forms, to find out the bare essential foods to eat.

In my current impression, I had no bias for meat, but I was (and still am) biased in favour of bread and beer, because I like them so much. I also like many vegetarian foods, like tofu, seitan and legumes. I think quorn nuggets beat chicken nuggets.

Since it's common in Sweden to believe plant-based is healthiest, I was surprised to read about retinoids (animal-sourced vitamin A) versus carotenoids (vegetable-sourced vitamin A). How to find vitamins B12 and K2 in an animal-free diet. What role omega 3 plays, how much we need, and what factors might affect how much we need. I followed nerds discussing ideal supplement regimens on forums about human longevity and nootropics.

Time and time again, I found that the nutrient under analysis can be found in some animal tissue or other, together with all the cofactors known to aid its absorption. Often it could be found especially in the "worst" part from a cholesterol perspective, e.g. the egg yolk, the saturated animal fat, the red meat. Animals started looking like a preformulated nutritional supplement from Nature. So that's what I ate. I spent much of my free time that year just geeking out about nutrition, and was at the peak of my health. I virtually couldn't sunburn, my immune system was king, my eyesight improved, my reflexes improved.

Back then, I also enjoyed breaking norms, holding secrets unknown to wider society. Now I use the experience of the keto in-group as a reference for what it may be like to be in a cult, and I'm grateful. I'm not calling them a cult, but all internet echo chambers have tendencies in that direction.

I remained skeptical enough that keto birthed my interest in statistics, so I could read the papers everyone was citing and make sense of them for myself. Thus I got a statistics degree. Overkill? I would soon find bad science everywhere, not just nutrition, so I'm grateful to the field for acting as a sort of trampoline into the deep, deep world of statistics.

These days I don't want to be an iconoclast. I'd prefer if my diet could mesh easily with other people.

My outlook on optimal nutrition is a bit different from 2013-me and more flexible, and I think that biochemistry is so complicated that a reductionist approach focusing on specific nutrients doesn't make sense at this stage of the science.

In Kuhnian terms, the field of nutrition may not yet have gotten out of the stage of pre-science, but I'm not sure if it's that or it's just in the throes of a paradigm shift, or if it's something about its intermix with government politics and the food industry that twists it into a slow-changing mess where famous researchers prefer to admit no mistakes.

Mind that it being a pre-science is not a ding. It's exciting! Uncharted territory!

With that in mind, when ever you optimize a diet for a specific nutrient, I think you're just Goodharting it: targeting a measure and not its underlying cause. Human biochemistry is such a high-dimensional thing that it doesn't seem like a good idea to let a few reductionist findings tell you what to do, without a holistic/full-picture perspective in which all the findings make sense.

Provided, of course, you maintain the falsifiability of that perspective. That is, you'll swap out the holistic framework you're using for a different one when surprising evidence turns up, rather than explain-away the evidence so you can keep the framework unmodified. Any evidence should result in some modification to your framework.

Be like astronomy, not like astrology; be specific in your predictions, don't move the goalposts, be quick to abandon hypotheses, and don't maintain any unfalsifiable claims unless you can causally tie them to a different claim that is falsifiable.

The ancient Romans used the expression via negativa (the "negative road"), for viewing a problem through the opposite sort of lens from how you might first view it.

You may have heard Einstein's popular quote "perfection is achieved not when there's nothing more to add, but when there's nothing left to take away", and for whom that's a new idea, it's an example of applying via negativa.

For nutrition, consider the apparent badness of pesticides, badness of insulin, badness of carbohydrate metabolism, and on and on… even such things as the badness of tetrafluoroethylene (Teflon) cookware, the badness of barbecuing, and the badness of mixing sugar with protein in one meal. Almost everything's bad in some way, so could health be more determined by what you avoid rather than what you include?

Concrete examples:

• to raise vitamin D without incurring risk, maybe we should supplement anything but vitamin D: see Vitamin D.
• to stay Vitamin C sufficient, you may not need to eat fruit, just to avoid grain.

This kind of question crops up everywhere, and it seems to me, absolutely necessary to try to answer.

Everyone should taboo the word "fat", because it has dual meanings: a noun meaning triglycerides (lipid molecules), and an adjective applied to persons to describe their being overweight. It short-circuits our logic sometimes.

• Note the difference if you say "eating triglycerides makes you overweight" rather than "eating fat makes you fat". The first form invites critique, asking for supporting evidence, while we may accept the second with nary a thought if we're not careful.
  • Compare "Eating vegetables makes you green" or "Eating cholesterol increases blood cholesterol", all the same type of error.
• There's a different possible world in which we all collectively decided to tie the word "fat" to carbohydrate molecules, or protein molecules, or even dirt (the Earth's very fat, ey?), instead of triglyceride molecules. Sometimes as a reversal test you can just pretend you were born in one of those worlds, and see if that would make you hear a research abstract differently.

The energy balance hypothesis is the idea that controlling what you put on your plate is a reliable way to control your body weight.

An objection is the 20-calories-a-day thought experiment first written in 1941(?) and repopularized by Gary Taubes around 2012.

Assume these things:

• The energy balance hypothesis is true
• You're lean today
• You want to still be lean 20 years from now

OK, now how precisely do you have to watch the calories on your plate? How much extra will make you clinically obese 20 years from now? The answer is 20 kcal a day.

Please see the video Why We Get Fat (a couple of minutes starting at 28:18).

So what's the problem?

1. First, 20 calories is a difference you cannot account for outside the lab. It's near-impossible even to estimate your calorie intake and expenditure to within 200 calories of the correct answer, even if you measured the quantities of food you ate down to the gram, as the calorie density within any given food also varies, and your body varies in its expenditure, and this variation is unpredictable.
2. Second, it seems an uncontroversial fact that the body's calorie expenditure is influenced by the calorie intake, so that a lower intake means a lower expenditure. Given this moving target, you cannot ever know how much of an excess you are running, with sufficient accuracy for this to be useful.

Either of these injunctions suffice to kill this primitive form of the energy balance hypothesis. You could object that it's not about watching on a daily basis, but a longer timescale: starting to restrict food once your belt is tight, eating more liberally once it doesn't, rinse and repeat. I agree that makes more sense. I wrote this section for three reasons:

• Introduce the thought experiment, in case it's as mind-blowing for you as it was for me at the time
• Point out it's not a sufficient argument (as some may think) against the energy balance hypothesis, and we need more to discredit it
• Point out that calorie counting is cursed to be incredibly inexact, and therefore if anything you must adopt a reactive approach and it's a waste of time to micromanage daily calories

In other news, I doubt even a refined version of the energy balance hypothesis will make sense – the rest of the linked video (Why We Get Fat) is why. If not, then the outcome of the Minnesota Starvation Experiment. Either suffices by itself for me to pay this hypothesis no further attention.

Reductionism and Holism Go Hand in Hand

Anecdata is rightly shunned for most purposes. Even outside the ivory tower of science, followers of a given world-view are happy to disqualify "the enemy camp's" reasoning whenever it relies on anecdata.

Is it always meaningless, best ignored? In fact no, and parts of reality will always elude us if we reject it. It sometimes makes good evidence, so it pays to understand when it does and when it doesn't.

There's a class of hypotheses we can reject after seeing a single piece of evidence. A schoolbook example is the belief "all swans are white"; when you see a single black swan, that should be enough to reject this belief. You don't need to repeat this observation 100 times and obtain a statistically significant result… at a sample size of one, it's already significant. An anecdote, and yet also proof.

If you strongly believed in "all swans are white", you might suspect somebody's covered this one swan in tar. But after observing two or three black swans on separate occasions, you'd still reject it. Right?

The story changes if you hear somebody else say they observed a black swan, but you didn't observe it yourself. Like when someone says they saw a ghost or an UFO, there are a million different plausible explanations for why they thought they saw that or why they are saying that they saw that, all more plausible than the ghost.

In this situation, something that matters is who and why.

• Who's telling you this data?
  • Keywords: sampling frame (or sample size), observer selection, …
  • "What is the sample size from which this information came?"
• Did you directly prompt for the data, or did they choose the topic and serve you the data without your imagining it existed?
  • Keywords: counterfactuals, Texas sharpshooter, observer selection (again) …

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Let me put on my statistician hat for a moment. There are times when it's rational for you to regard anecdata as medium-strength evidence, and times when it's no evidence at all, because of something called selection effects.

If you hear something unbelievable on the Internet or in the news, it usually constitutes next to no support for any general conclusion, because we live on a planet of billions of humans, and freakish events happen to someone every day. No matter how rare, these freakish events get promoted to our attention.

Here is a question of sampling frame… if the frame is seven billion, and you look for data that supports a hypothesis, you will find it, you'll even find a group of hundreds of people for a 'statistically significant' result (cherry picking) – which is why it's so important that the researcher select subjects in a random and transparent way, maybe even outsource the job of selecting subjects to an impartial outside agency.

By contrast, if your (pre-chosen) sampling frame is your immediate family, and you go quiz them about something specific (not "did you ever see anything unbelievable?", but "did you ever see someone hit by lightning?"), it's not likely you turn up any interesting results … but if you did, that would be real information.

If your family has 4 members apart from yourself, and one has seen someone hit by lightning, that's 1 out of 4. Naively then, you could guess that you have a 1/4 chance in your own lifetime to see lightning hit someone, at least with no other information to go on. In practice, you do have more information – you suspect people would talk about getting hit by lightning a lot more if it was that common, so you'd downgrade that 1/4 figure to something smaller, like 1/40.

But notice that the quiz did give you some information. It's a lot more than if you just happened to hear about it on an internet forum, which is approximately no information at all, even though both sources come from one individual making one claim.

What makes the whole difference for you is the sampling frame – how many could have given you the data if it happened to them – and the fact you did or didn't directly prompt for the data under a hypothesis you already held.

That is one of the core lessons of Science, that we incrementally learned through the centuries: you can make information much, much more trustworthy, just by asking for it in a principled way. Information you merely stumble across can only generate a hypothesis, not confirm anything, and least of all generate and confirm in one go. Most hypotheses will turn out to be a wild goose chase, because that's the nature of reality: an ocean of wrong ideas and a handful of less wrong ideas that are useful (and one unknowable full truth).

If you had asked your family about seeing anything amazing happen, and one of them mentions lightning, you'd get 1/4 chance of seeing something amazing happen, but you couldn't conclude 1/4 chance of seeing lightning happen, because the question that prompted this data was not about lightning: that's a specific that you received unasked-for. And you couldn't afterwards, knowing that they've seen lightning, ask them again but this time specifically about lightning: that's Hypothesising After Results Known (HARK), aka post-hoc theorizing. You know what you'll get!

You need new data to confirm a pattern you first saw in an exploratory study. In practical terms, you could extend your sampling frame to "everyone inside this apartment building minus my family" (because of HARK: start clean) and go to your neighbours and ask them about lightning; you'd soon find that the rate isn't anywhere near 1/4, of course.

That's why when you hear about an observational study with concerning results from some foodstuff, you don't worry. You got that data unasked-for, as did the researchers. When a meta-analysis tests for something and the pattern still holds, then you worry.

Key concepts: Non-representative sample of typical cases, cherry picking, … en.wikipedia.org/wiki/Anecdotal_evidence

But… suppose you use someone else's exploratory study as your confirmatory study? (Say what?)

Approach someone else's dataset with your own hypothesis, like "red meat leads to cancer", could you confirm it since you don't know how the dataset looks?

The answer is yes, conditional on your process of how you chose which study to look at. You can only regard it as confirmation if the process didn't introduce bias. If you were to just rifle through lots of studies until you find one that confirms your theory, this is just the same as cherry-picking data on another level: cherry-picking studies. Sure, the subjects in study number 34 showed the pattern, but what about all the people in studies number 1 through 33?

(Google effectively cherry-picks a study for you when you search "red meat cancer".)

What's more rational is to take into account all studies from 1 through 34 and see if the pattern still holds. Even that is problematic since you stopped right when you found a study with the pattern – what's even better is to have chosen ahead of time "I'll look at 50 studies", the exact number isn't important so long as you stick to it no matter whether you find a pattern or not.

Only by that ritual will your findings become real information to you. That's what it means to be willing to accept that you were wrong. Science doesn't work without that willingness; one who lacks it is not doing Science, even though they may be reading papers and doing all the externally visible parts of what looks like science. For a process to become science, it requires a pledge inside the researcher's mind, to tie herself to the mast of accepting whatever the data may say.

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Anyway, this ritual is basically how a meta-analysis or systematic review works (or should work). They don't use a simplistic cutoff like "50 studies", but a cutoff like "all studies above a certain quality". There will not be that many high-quality studies with directly comparable data suitable for answering a research question, which makes it easy. The deeper you dig in the barrel, the lower-quality the studies, so they may as well only look at the cream of the crop.

Even meta-analyses have pitfalls. They must try to counteract publication bias, which is hard because even today, researchers aren't interested in publishing negative findings, so you get a situation such that for every study containing a positive finding, there may have been 49 with the same research question that turned up negative and never got published(!).

Some ways around publication bias is to simply do a new study, better-designed than what came before, or analyze only the studies that were pre-registered (which mean that the researcher agreed, before doing the study, to publish the results no matter how they will turn out).

Happily, pre-registration is becoming more and more common!

A bias that can subtly influence our theories, maybe even bleed into research design, so put a word-handle on it: Bariatric Calvinism and the Threat of Ketogenic Diets

Also: www.lesswrong.com/posts/NRrbJJWnaSorrqvtZ/on-not-getting-contaminated-by-the-wrong-obesity-ideas#On_Some_Conceptions_Of_CICO

en.wikipedia.org/wiki/Nutritionism

George Orwell described newspeak as when you introduce a new word or concept to intentionally affect how people think. I think the term "empty calories" fits this bill.

I read among keto groups that "empty calories" is used heavily by the Coca Cola Company (and the nutritionists they pay off) to whitewash sugar, with the implication that you'll be fine eating sugar ("it's just empty calories!") so long as you also get other nutrients. It's meant to distract from the fact that sugar metabolism itself has negative effects.

If the term makes sense to you, they've won. Try replacing "sugar" with something else, like "paint", and note that it doesn't actually parse if you put "empty" out in front. Empty paint? What is that? Well, what's an empty calorie?

All calorie sources are hormonally active, so just avoid this term.

I find it unnerving how many people bikeshed about nutrition without having even a model of how the body fuels itself throughout the day, what fuel it uses, or what the energy is mainly used for. I mean, how can you start to make a claim about energy utilization when your mental flowchart has unexplored regions on the way between point A and point B?

My understanding is imperfect since I'm not a biochemist, but it's been relevant in some conversations so I will quickly reproduce it here. If anyone wants to mail me corrections, it's welcome.

Researchers so far have classified 18(?) amino acids as essential to humans, because we don't make any or don't make enough of them within the body.

But achieving sufficiency is not as simple as exceeding a fixed minimum of each. The minimum of a given amino acid will move up or down, depending on the other amino acids you have consumed.

When RDIs were born in 1941(?), the intent was to reduce malnutrition symptoms among the populace. But that doesn't say whether an amount is ideal, only that it's good enough.

Also it's interesting… some of it's based on animal studies where the goal is finding out what makes the animal grow fastest – if I remember, the RDI for methionine is based on this. In that case, we could be totally overestimating our "need" for methionine, as lIt's a completely different question from what keeps a human healthy the longest.

I feel someone should figure out an approach to the issue of partial deficiency. It's not detected but may still weaken health, much like an ache can be caused by problems with fascia far from the site of pain – as fascial slings go around the body, wrapping it like a package – a partial deficiency of some nutrient can cause hard-to-diagnose problems because nutrients are always interacting with each other and we only know the telltale signs of an absolute deficiency.

As someone said, "need" is a funny concept. You don't need to eat seafood. You don't need an appendix or legs, either. Maybe we can call it a shorthand for that it'll lengthen our healthspan (which is not just lifespan, but taking into account "healthy life years").

There is a body of established science showing four clinically measurable components of hunger: satiety, satiation, hedonic impact and incentive salience.

This line of thought took a long time to wrap my head around, but it blew my mind well.

So much of reasoning around nutrition, particularly for weight gain and weight loss, relies on background assumptions rarely spoken of:

• Assumption 1: that when the stomach is physically full, that's the main signal for the body to feel satisfied with its intake and not get hungry again for some time
• Assumption 2: that if you eat something more calorie-dense than another, like lipids instead of carbs or fiber or sawdust, you'll be able to consume more calories before the stomach is full, and therefore, your total calorie intake will be higher per meal, and you will end up gaining more weight

Written out like that, it seems to me extremely debatable. Yet, the consequences if it's wrong:

• Calorie density does not matter
• Fiber does not make you meaningfully fuller
• There's no such thing as a "low-calorie food" or a "high-calorie food"!

What's left to watch for then? How do you lose weight if the body is just watching to meet a calorie quota, not a volume quota? How do you choose foods on a diet if there's no such thing as a low-calorie food?

Timeline

• Process of hydrogenation discovered in France
• Procter & Gamble sales halved due to the Sinclair's journalist book documenting conditions in their lard factory. Also due to the rise of electricity, gradually less sales of lard (as we don't need to make candles anymore)
• Procter & Gamble starts hydrogenating oil from cottonseeds, previously a waste product dumped in rivers (not even fed to animals): first margarine born
• Vitamin C discovered, scurvy solved: fruit necessary!
• Vitamin B1 discovered
• 1941(?) RDAs published (by which org?)
• 1948 Framingham Heart Study begins – and continues to this day
• Diet-heart hypothesis born as Ancel Keys starts in on the idea of saturated fat causing heart disease b/c …
• 1970? Sweden publishes world first food pyramid, designed to help consumers shave costs. Very similar to USDA's later food pyramid, which will purport to be for health (not a claim in Sweden's original version).
• Senator George McGovern watches that starvation movie, vows to make a difference, ultimately resulting in the food stamps program (and grain subsidies?)
• 1973 Soviet Great Grain Robbery ensures McGovern loses the presidency
• 1977 McGovern's Select Committee on Nutrition and Human Needs, about to be axed, announces US public health dietary advice beyond just getting everyone fed
• USDA receives mandate to take care of health recommendations(?), giving it a conflicting set of drives
• Luise Light and team of top nutritionists employed by USDA to figure out dietary guidelines
• Luise Light submits research-based food pyramid to USDA
• 1992 USDA pre-publishes(?) distorted version of Luise Light's Food Pyramid, with many times more grain than Light suggested
  • Meat and dairy industries protest to their tiny part of food pyramid, delaying its publishing for a year. Research found that customers won't in fact eat less meat or dairy, so they let it pass.
• 1993 Food Guide Pyramid becomes official

Three radically different diets that have shown good results on humans in clinical practice:

• Whole-foods plant-based diet, as described by Ornish, Esselstyn etc.
• Paleo diets
• The so-called Mediterranean diet

What foods they all ban:

• Industrial seed oils (rapeseed, sunflower, safflower etc)
• Sugar
• "Refined starch" (white flour & rice)

What foods they all allow:

• Vegetables
• Fruit
• Tubers / root vegetables

Source: Death by Food Pyramid

Sailors used to get a mysterious disease, scurvy (caused by vitamin C deficiency), because they brought no fruit on the long voyages. They brought only dried bread and dried meat.

After vitamin C was discovered in the beginning of the 1900s, we finally cured scurvy and everyone accepted the importance of fruit (or sauerkraut-like foods, which last longer aboard). Around the same time, though it didn't make the rounds, the Arctic explorer Vilhjálmur Stefansson wrote about the Inuit people, who could survive off an all-animal diet for nine months at a time without any sign of scurvy, and were in excellent health. Stefansson wasn't perfect (One Thousand Nails in the Coffin of Arctic Explorer Vilhjálmur Stefansson, and His Spawn), but he and another person underwent an experiment at Bellevue Hospital of eating only meat for a year, and they showed the best health of their lives during that time, as measured by the doctors. After returning to the Western diet, their health was always worse.

I assume it was too hard to reconcile these observations with the background of the new vitamin C wisdom, so European scientists shrugged and forgot about Stefansson and the Inuit people.

(This is not how you do science. When something looks contradictory, that's the first place you look – you don't shrug and try to forget it!)

(Even if Stefansson was sneaking fruit in the off hours, this is a case where if he was truthful, you should expect to find many corroborating anecdotes and few contradictory ones – even with self-selection bias, some contraindications should show up on some sites. To date, I've not read a single zero-carber on the internet reporting scurvy, and some claim not touching a plant for decades. Scurvy from zero-carb just isn't heard-of, even outside zero-carb forums, and that's surprising.)

The Inuit ate meat, but not bread. Per via negativa, is it possible that Western sailors got scurvy not because they left out fruit, but because they brought bread?

Two hopefully uncontroversial facts of biochemistry support this (though I may have been misled):

• The body can recycle vitamin C endlessly. To deplete it, something else you're doing has to deplete it.
• Carbohydrate metabolism causes oxidative stress (free radicals, Reactive Oxygen Species), which the body counterbalances by expending antioxidants… such as vitamin C! Not to mention ketones, an antioxidant that cannot be present when bread is part of the diet, leading to greater waste of vitamin C.

If the reasoning is valid, then we can conclude that dietary vitamin C isn't necessary during fasting or on a zero-carbohydrate diet, but when you start eating bread (grain is the only carbohydrate-rich food without vitamin C), then you also have to eat fruit or vegetables to stave off scurvy. Bread causes scurvy! Scurvy is an uniquely grain-caused disease!

Another conclusion is that vitamin C may not be reasonably called an essential nutrient, but what's called conditionally essential – i.e. it depends on what else you eat – and only mistaken for essential because of the universality of grain in the modern diet.

For even more, see www.empiri.ca/2017/02/c-is-for-carnivore.html.

Vitamin D levels can stay fixed regardless of time in the sun (happens to some patients) until you fix a deficiency of one of the bone-health nutrients (calcium, boron, proline …), whereupon blood vitamin D is free to increase. (Reasoning inspired by Why Low 25(OH)D Could Indicate a Deficiency of Calcium Instead of Vitamin D.)

This is a talking point in the "don't supplement" camp: possibly the body refuses to generate vitamin D to protect bone because it would trigger processes that it doesn't have the minerals to support. I'm sure you've seen the news linking vitamin D supplementation to osteoporosis in some cases, and this would neatly explain that.

This makes for a testable theory, because if true, it should be possible in these cases to consume something calcium-rich (or ideally the one food that's rich in all bone nutrients: bone broth), and watch the vitamin D levels magically increase even without going out in the sun any more than otherwise.

In addition, may be a good idea to increase vitamins A and K2 before doing so for D. Quote from Are Some People Pushing Their Vitamin D Levels Too High?, emphasis mine:

Lifeguards in the tropics can reach blood levels [of vitamin D] in the 50’s and 60’s naturally from sun exposure, suggesting these levels are “natural,” although lifeguards in Israel have 20 times the rate of kidney stones as the general population. Kidney stones may be the most sensitive indicator of vitamin D toxicity and are a symptom of vitamin A and K2 deficiency. Thus, I suspect these levels are healthful in the context of a diet rich in vitamins A and K2, […]

A rare vitamin, found mainly in lipids from grass-fed or wild animals, or in aged cheese. Not to be confused with Vitamin K1, which can be found in dark green vegetables (like spinach) among other things, and isn't interchangeable with K2.

The only plant source of K2 is nattō, a soybean product fermented with a particular species of bacteria (not to be confused with tempeh).

About 40% of people have low-normal "serum B12" (vitamin B12 in the blood). Understand that serum B12 is one of the last markers to fall out of normal range, so if it is beginning to drop from normal, you're almost definitely deficient.

This vitamin is a common supplement for vegans because it is only found in animals, with a honorable exception for tempeh, a soybean product fermented with a particular species of bacteria (not to be confused with natto).

Interesting because you can even observe many omnivores being deficient, giving us a theoretic guideline to how much meat we're "supposed" to eat.

Collagen is a type of protein that dominates in bone joints, skin and other "chewy" parts of an animal. Dogs and wolves spend a long time chewing bones in order to get this. If we heat collagen, it turns into a different protein we call gelatin.

The collagen is what makes the chewy parts chewy, and contains the amino acids glycine and proline, which are uncommon in other foods – the chewy parts are our primary dietary source of these amino acids.

Is it important to eat these bits?

Well, I'll just observe that it's common to prescribe something called glucosamine to people with arthritis, because it helps with joint health. And it turns out glucosamine is a member of a category of nutrients, glucosaminoglycans (GAGs), and it works better to supplement all of these. And it turns out that Nature's only source of the full spectrum of GAGs, is also the same place we find glycine. The chewy bits. The gelatinous bone broth.

Apparently it's well-known that glycine, proline and GAGs are building blocks for our joints. How come no one told me this in nutrition class? I don't want arthritis, so a nutrition class that didn't tell me to eat bone broth has failed me.

The body can produce some amounts of glycine of its own, expending folate to do so, so vegans would be wise to eat a lot of beans for the folate.

Your food doesn't just determine your health, it determines the very thoughts you think! Chris Masterjohn's essay Meat, Organs, Bones and Skin highlights a process called methylation which is regulated by the proportions of methionine and glycine in your diet – which for an omnivore, maps to how much muscle meat you eat, compared to skin, cartilage and bone broth. Let me quote a piece:

Two analogies should prove useful to help us understand the need to balance mental stability with mental flexibility. In the first, we could imagine a potter who makes clay flexible by moistening it before attempting to make something out of it. Too little moisture will lead to brittle clay: it is too dry to shape into anything, and applying enough force to change its shape will simply make it break, exposing rough and sharp edges. Too much moisture will make it easy to manipulate, but no shape given to it will hold. The right amount of moisture will make the clay malleable enough to manipulate into something useful or beautiful, and yet stable enough to retain the shape given it.

Similarly, not enough methylation could lead to “brittle” mental states. Such states are difficult to change, but when they do change, the transitions are sudden and without warning. This brittleness could lead to dangerous situations. For example, ordinarily when we get angry, the process is gradual enough that we may realize what is happening to us and stop ourselves from acting out in our anger, or someone else may notice that we are becoming angry and intervene to diffuse the situation. If our mental states are too brittle, however, we may act violently without warning, giving neither ourselves nor those around us any opportunity to recognize what is happening and intervene. Alternatively, too much methylation could make our minds like a bowl of liquid clay: easy to make a mess with, but difficult to shape into something beautiful or useful.

In the second analogy, we could consider our consciousness like a net through which thousands of thoughts fly every day. These thoughts could be about basic biological drives and needs like food, sex, and sleep; they could be about the multitude of things we need to get done; or they could be thoughts that motivate us, whether to do good things or to do things that would get us into trouble. To achieve mental health, our net of consciousness needs enough flexibility that we are able to manipulate it as each thought approaches, choosing either to let it pass through or to hold on to it. This net also needs enough stability, however, to hold onto beneficial thoughts for as long as they are needed. Without flexibility, we hold onto everything that comes our way indiscriminately. Without stability, we cannot hold onto anything at all. With a proper balance, we become masters of our thoughts rather than their captives.

In particular, this is fascinating – emphasis mine:

Vegetarians excrete almost twice the level of a unique marker of glycine deficiency in their urine as omnivores.¹⁷ This suggests that excluding animal products from the diet could not only lead to a generally inadequate level of methylation because of lower intakes of methionine and vitamin B12, but the lower intake of glycine could also lead to transient periods of excessive methylation. This could theoretically result in seesawing between excessive mental stability and excessive mental flexibility.

The purpose of this article, however, is not to denigrate vegetarian diets but to emphasize the importance of nutrient-dense animal foods. A standard omnivorous diet is hardly the ideal. Even omnivores excrete substantial amounts of the marker of glycine deficiency discussed above in their urine. This could be because the typical omnivore fails to make use of skin and bones in their diet.

I spent time on forums about human longevity circa 2013, and one of the first things they like to supplement is choline. It's also popular in the nootropics community, who think it helps your intelligence, at least when combined with racetam drugs, which use up choline.

So what's choline? There are many forms, like phosphatidylcholine and… blah blah blah… and it's present in all animal tissue, but what's interesting: your body will expend choline in order to "neutralize" methionine. As you know, the amino acid methionine is found in large quantities in muscle meat and eggs. Which means that, if you eat muscle meat but not other parts of the animal, you may end up having too little choline. Especially true when you avoid yolks and fatty meat, which do have choline, in favour of lean meat and egg whites, which lack it.

You shouldn't be wasting choline this way – eat glycine-rich foods, see Methionine-glycine balance, to deal with the methionine so you can keep all the choline for your benefit.

What's a good source of choline? Liver! It stands uncontested as the most effective dietary choline source.

For plant sources, the betaine found mostly in spinach (and to a small extent in beetroots, after which betaine is named), can be converted in the body to choline but not a lot. This makes spinach essential for vegans, I think.

Genetics can help. 90% of Japanese people have a gene for converting some methionine to choline (source), but not so many Western people have it.

There are different forms of omega-3. The plant-based version is alpha-linolenic acid (ALA), which you can find in e.g. rapeseed oil and linseed oil. Less than 1% of it (depends on genes?) is converted inside the body to the forms it uses: docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). These convert into each other so they're pretty interchangeable.

Omega-3 in the EPA/DHA form is mainly found in seafood, such as oily fish, and in brains (our brain is 15% DHA by weight, and unsurprisingly, brain health is intimately linked to EPA/DHA intake).

To a small extent it is also found in oysters, some seaweeds, and fat from grass-fed animals, but in tiny amounts compared to something like wild herring.

Deficiency leads to dry skin, poor eyesight, and several brain-degenerative diseases.

People talk about a balance of omega 3 to omega 6, that it should be about 1:1, maybe 1:4 at worst.

In the West, people average eating a ratio around 1:20. I don't know where this number is from but I worry that most of the "1" there is also ALA (Alpha-Linolenic Acid) from seed oils, which the body does not really use, so it's even worse than it sounds.

There have been signs that actually the balance doesn't matter so long as you are getting a certain a minimum of omega-3.

The body converts between EPA and DHA interchangeably, but DHA is ultimately the main form that goes into cellular tissue.

The molecule DHA comes in multiple forms, sn-1, sn-2 and sn-3. Apparently the body uses sn-2 best.

There is more sn-2 in seafood than in fish oil capsules. (How? Does the refinement change the molecule??) caloriesproper.com/vegetable-oil-fatty-acids-are-not-essential/

There's indication (where?) that Inuit peoples and some portion of the Nordic and Irish populations have genes such that they need a huge amount of omega-3. How huge? I don't know, but for perspective, we know the amounts some traditional Inuit groups ate: 14-20 g/day. This corresponds to 400-600 g of herring/mackerel daily.

Now that's probably overshooting their minimum need, but if we say it's half of the low end, that's still at least 200 g of herring daily, or 1.4 kg weekly.

If you have extra Genetic need of omega-3, the problem is that you cannot practically consume these amounts via fish oil capsules. To get one gram of omega-3, you would need three 1-g capsules of regular non-concentrated fish oil, so to get 7g of o3, we're looking at swallowing 21 capsules, or 42 half-gram capsules, in one day.

Every day, 365 days a year; 15,330 capsules a year. The byproducts in this many capsules may give you adverse effects (so I heard). To compound the matter, omega-3 is not as well absorbed in this form than when it comes as part of seafood, so this absurd amount may still be too few.

There's also the monetary aspect. Fish oil is more expensive after processing than when it was still on the fish in question. To frame it differently, if you eat fish just for the omega-3, you're not only paying less for the omega-3, but you get the protein and other nutrients of a full meal without paying anything.

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A different pointer at the correct quantity comes from the research on telomeres. If you don't know about telomeres, in summary they're parts of each cell's DNA kernel that shortens over time. Once they're too short, they can no longer divide. Long telomeres mean long life.

The research connects high "omega-3 index" with less telomere shortening.

Your omega-3 index tells you what percentage of the fatty acids in your blood is omega-3. You can get it tested. People in the USA/EU average 4%. It should be sitting at >8%, which is where the healthiest people are, and possibly much higher (has anyone found a dosage that's too much?).

To achieve >8%, you typically need more than two "servings" of seafood per week—whatever "serving" means. Source: web.archive.org/web/20170620091732/http://caloriesproper.com/omega-3-index/

It's likely that people report "serving" differently, and many people eat lean fish and call it a serving of seafood. So if you make sure to choose wild oily fish, I wager that two normal-size servings per week, whatever that means for you, will suffice.

This result looks quite a bit less than the weekly 1.4 kg I proposed, but that depended on genes. Call this level a floor, I guess.

To reiterate: two weekly servings is a floor. The bare minimum. Like passing school with grade E.

Conjugated Linoleic Acid (CLA) is a fat found mainly in grass-fed ruminant fat, and to a fractional extent in champignons (the common button mushroom).

Interesting because it's an example of a natural trans fat, as opposed to an artificial trans fat, and it's good for health. I don't know how good. It just stuck out to me because it's another thing that's only from animal sources, and only grass-fed at that.

Meat Toxins: What they are, why they exist, how to avoid them

In short, meat doesn't have any toxins, unless the researcher does things to it like

• curing it with nitrite
• smoking it in a barbecue (creates polyaromatic hydrocarbons: PAHs)
• overcooking it
• deep-frying it in seed oils
• cooking it with margarines or other hydrogenated oils
• cooking it together with sugar
• eating it together with sugar
• call it "meat" but it's processed meat, like ham, meatballs &c

When reading studies about meat, always check the Methods section for how they prepare it.

Sometimes people mention cooked meat containing Advanced Glycation Endproducts (AGEs), linked to aging. This fear is safely ignored since even if you burn the meat, the amount is small compared to the AGEs produced in the body just from burning carbohydrates as fuel. If that's not reason for worry, neither is this.

One valid concern is heterocyclic amines (HCA or HA), which form at high temperatures. There's more of these the hotter the meat gets, so gentle cooking methods such as stewing and steaming are better. Similar rules apply to cooking plants, meat isn't special in this regard: all foods are damaged by overcooking.

Do you realize how startling this is? How often can a food be the intense subject of scrutiny and yet discover… \*checks notes\* one toxin?

Here's an important topic. Since organs (especially liver) come out on top so many times for bioavailable nutrients, I want to know how much toxins they've also got. It seems reasonable to suppose that for the same reason they're concentrated in nutrients, they may be concentrated in some kinds of environmental toxins, especially the liver and kidneys which act as filters. I'll look into it later.

I must note that most of us have already accepted consuming toxins in multiple foods, either figuring that the nutrients are worth it, or just not thinking about it. Example: the pesticides on most plants, and the antinutrients in grain, whole grain, and seeds. Few people actually sit down and calculate whether the quantities are worth it, so it would be inconsistent to treat organs specially, it smells more like an excuse to postpone eating them.

We emit the enzyme called amylase to break down starches, in the saliva as well as the intestines. People vary in how much amylase they will produce, due to how many copies they've got of the AMY1 gene.

Now for where it gets surprising. Each of the apes, apart from humans, always have a fixed amount of AMY1 genes. Each species may have 3 copies, or 4 copies, or some other number, but it's constant across that whole species.

By contrast, we humans vary between having 1 to 15 copies!

A takeaway:

• There really is no single ancestral diet. The variation implies we descend from groups with cultures quite unlike each other, even way back in the Paleolithic, some of which ate a lot of plants and some of which did not.

(Sorry, no details yet. But the book I read was Death by Food Pyramid.)

Genes like AMY1 and ApoE4 weigh in on what diet is ideal for you personally. Some people will not do well on a low-fat high-starch diet. For them, starch can cause even worse blood sugar spikes than if they were to just eat straight sugar. As we know, all these blood sugar spikes lead to insulin resistance, obesity and heart disease. For them, a high-carb diet may never be a workable alternative.

(Not a nutrition issue per se… I don't know why I put this here.)

A genetic issue that makes you store excessive amounts of iron in your tissues (won't be visible in blood). By the time your symptoms show up and the health care system realizes what's wrong with you, you'll be in your 40s and a lot of irreversible damage has already built up.

So it's good to check for this before your 30s or so.

Why Westerners have this gene? It helped them survive the Black Plague.

A tiny fraction of people (how tiny?) should avoid eating cholesterol because they have this genetic disorder.

Tip: one of the most respectable books on ketosis is The Art and Science of Low Carbohydrate Living, by Stephen Phinney (MD, Ph.D) and Jeff Volek (RD, Ph.D). Not dispensable reading if you want to discuss nutritional ketosis (a term they coined to contrast with diabetic or alcoholic ketosis).

Sometimes mentioned:

• Increased risk of sudden cardiac event
  • This one's a mystery to me since the heart works more efficiently and stably on a ketogenic diet (it's great for endurance sports). Could be a spurious correlation someone once observed; look into this.
• Thyroid

  • This seems a legit concern, going by at least one hunter-gatherer culture that Weston Price observed, where they would go so far as to feed thyroid glands to couples trying to conceive, taken from animals in mating season (if I remember correctly) when the gland would be enlarged. There must be something behind that. Although it could just be this fallacy www.smbc-comics.com/comic/medieval

    Thyroid activity goes up for some reason with carbohydrate intake, but it seems it can be sufficient to have some carbohydrate feasts every 3 weeks or so to normalize it. In addition, it helps to consume more iodine than the typical Western person does.

• Kidney/gallbladder stones

  • Stones come in many kinds, can be composed of different substances. It's feasible that a sudden diet change could contribute to building some kinds of stones, but it can also be the case that the stones were already there and the gallbladder only started trying to pass them because it's delivering more bile to digest all the dietary fat you now consume (stones having formed because you didn't use the bile enough to keep it moving).

    A benefit of cholesterol is it's used to make bile and may prevent some stones, which is a great reason to avoid statins (cholesterol-reducing drugs). That's all I know.

Sometimes a source will spread FUD (fear, uncertainty and doubt) over a risk of ketoacidosis – this is a great litmus test because it indicates that the source does not tend to do their homework.

Ketoacidosis cannot occur in a healthy person, even if they were to eat nothing at all for months (the most ketogenic diet possible). Per Phinney and Volek, a Very Low Carb diet means blood ketone level maxes at around 3.0 mmol/l, and fasting means it maxes around 5.0. Tiny amounts of insulin suffice to put a lid on it. Diabetic ketoacidosis (DKA) is a runaway process exceeding 20.0 mmol/l due to failure to respond to or produce insulin, and mostly happens to Type 1 diabetics.

This one gets so many people, because it makes sense: when there is glucose present, the body will burn it first, and only then switch to ketone & fat metabolism. Therefore, the body must "prefer" glucose, in the sense that it's a more ideal and healthy fuel. Or?

Problem is, you could use identical reasoning to say that actually, the body "prefers" alcohol most of all.

It burns alcohol first of all, because it's toxic and burning it for energy is a quick way to get the amounts down. Couldn't that be the same reason it then burns glucose before going to ketones and fat? Viewed this way, the argument supports ketones and fat as the healthiest fuels – the body's "preferred" – since having them swimming around the bloodstream doesn't at any point cause an emergency reaction to clear them away.

• Insulin (see Insulin)
• Oxidation (see ROS)
• Inflammation (through the effects of insulin, ROS, cholesterol staying too long in the blood and getting oxidated, and probably other effects)
• Sugar likes to react with protein to form carcinogens. Don't know to what extent this occurs in the intestines (as opposed to on the stove), or to what extent it occurs with starch (as opposed to sugar).

I was told that a carb diet means more oxidative stress, meaning it releases more unnecessary ROS (reactive oxygen species). Mechanisms:

• glucose has more oxygen molecules than do triglycerides, so more ROS byproducts when breaking it down
• ketones are a powerful antioxidant you miss out on with a carb diet
• the lower inflammation and other side effects of carbs also means less oxidation (??) (a bit handwavy)

I don't know anything about the uses of ROS so the whole topic could be a red herring; perhaps expecting a higher oxidative stress on a carb metabolism isn't connected to the reasons oxidative stress has been correlated with bad things.

Touching on a similar topic is RER (respiratory exchange ratio), which measures CO2 in exhaled breath. It's 1.0 on a full carb metabolism and 0.7 on a full keto metabolism, reflecting a fundamental difference in the molecules used (and thus we use it as a tool with which to measure the ratio of fat to carb a person is burning).

Insulin seems to be a hormone of many jobs … and it's the only hormone that will lower blood sugar, a role into which it is press-ganged on a high-carbohydrate diet, but we get side effects because it's not just for that.

The way it accomplishes blood sugar drop is like this. The adipose cells (fat cells) have insulin receptors, so when an insulin molecule passes by in the bloodstream, the cell may snap it up, which consequently stimulates it to snap up more glucose from the bloodstream and store it longterm by way of de novo lipogenesis: assembling molecules of saturated fat (I think specifically stearic acid?) that it can release later.

When all adipose cells are taking glucose out of the blood, obviously the blood glucose level drops. So there you go: mission accomplished. Good work, team! Now for a vaction!

But what happens when you're ingesting large amounts of glucose every day, and the adipose cells rarely have a chance to release those saturated fats, forced to keep making more? They get stretched to fullness and stop listening to the insulin signal. This is called insulin resistance. T

his is fine if it's just a few cells here and there; (and they'll divide into two eventually). But what if all cells are like this? Then the body finds that the glucose level stays high… despite the insulin signal it's putting out. (Apparently the workers are sleeping on the job.) So it has to release more insulin, to overcome the insulin resistance (effectively force-feeding the full adipose cells).

The more insulin-resistant you become, the more insulin you will have to release into the blood for a given meal. (Glucose is toxic at high levels, so this is a sensible response, the best of bad options.) A healthy person does not need to release much insulin, since their adipose cells happily listen.

Where it starts to go wrong is, well, insulin actually has other jobs. And releasing so much insulin, it triggers those other jobs too much.

The result is called metabolic syndrome, a kind of broad category of issues of which diabetes is a subtype. Anyone can get it from chronic high insulin levels, and the principal cure is to consume less insulin-inducing foods… meaning, quite simply, less carbohydrates.

Consequences of metabolic syndrome

• Plaque buildup in blood vessels (eventually a blood clot)
• High LDL (bad cholesterol), low HDL (good cholesterol)
• weight gain
• etc. (?)

We find lectins, phytates, and other(?) antinutrients especially in grain, with even more in whole grain, that cause malabsorption of some nutrients. For this reason, some Paleo-aligned folks argue that given the choice, refined 'white' flour is healthier:

• It's a choice between carbs plus a few antinutrients (white flour), and carbs plus a lot of antinutrients (whole grain). I'll take option 1, please!
• While the carbs in whole grain have a lower glycemic index, it matters less under the theory that it's really total insulin load that causes disease, not glycemic index.
  • I have issues with this one: higher glycemic index food does cause more de novo lipogenesis (even on a calorie-restricted diet!), because it means too much available glucose in a short timeframe. Then you get the abnormal blood lipids associated with heart disease anyway. You could modulate this by not eating that much refined grain at one time, I suppose.

As a final nail in whole grain's coffin, it doesn't make sense to see whole grain as a source of some vitamins/minerals when vegetables, tubers and fruit make cleaner carb sources and you could just eat more of those instead. If you absolutely have to eat grain, maybe you can argue for whole grain's nutrients being worth the antinutrients, but it's a complex thing to figure out (we need to quantify the effects of every substance involved), and just quitting both refined grain and whole grain is a simple approach that saves us effort and doesn't risk some miscalculation.

A note on "lectins", they're a broad category and not all bad: www.fitness-vip.com/nutrition-research/lectins-and-food-toxins-concern.html

All B vitamins are water-soluble. Personal supposition: they could leak out of food when cooked. So we could expect things like ham or dried food to have less B vitamins. Electrolytes (natrium, kalium, magnesium and iodine) could also leak out on the same principle. I don't know about minerals.

If true, this makes it pretty stupid to throw away the broth (the cooking water). Drink it.

I wager the same for fat-soluble vitamins (A, D, E, K), when some fatty food leaks fat during cooking. So when frying fish, scoop up that valuable fish oil. (And protect them from oxidation by having saturated fats in the pan, along with antioxidants such as rosemary.)

Iodine comes from the sea, and may be in coastal soil, and thereby animals and plants living on coasts. It's not unusual for animals living far inland to run into iodine deficiency. Among humans today it is the most common preventable cause of intellectual disability, and though much of the world now uses iodized table salt we are running on a bare minimum of iodine intake, a dangerous line to balance on.

Iodine is found in seafood and seaweeds. Kelp is a cost-effective food, with astronomical amounts of iodine – 1 ml of granulated kelp will give you more iodine than most people get in a day. You can just mix kelp into your salt shaker for convenience. I'm thinking 50-50 kelp vs salt.

Unfortunately, kelp may have high amounts of bromide which cancels out the iodine. I need more info.

There are several reasons we deplete the iodine in our bodies – per Nora Gedgaudas, it's chiefly about the other halogens, see the bromide in pesticides, baked goods, soft drinks and vegetable oils, the fluoride and chlorine in municipal water, etc.

Table salts tend to have iodine added. However, there are multiple naturally-occurring forms of iodine, and at least two necessary forms (iodide and elemental iodine), and table salt only has iodide, and it evaporates within three weeks of opening the box. The amount of iodine you'll ever get from table salt also is low.

If you want to maximize the iodine from table salt, buy new packages often, preferably resealable. If you live alone, buy small packages. That said, you're still only getting iodide, not elemental iodine.

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Other than kelp and table salt, sources of iodine include: plants grown on iodine-rich soil, animals grown on aforementioned plants (should be in the blood like other electrolytes, but it's also been known to be in dairy and eggs; how much is collected in the meat, fat, bones or organs, I don't know), seaweeds, fish, shellfish.

Due to the potential difficulty or cost in making sure your diet has enough iodine, it may be smart to start taking a supplement for the time being.

On a very-low carbohydrate diet, some voice concerns about reduced thyroid function – but it appears this can be remedied by elevating iodine intake, something you should be doing anyway, instead of elevating carbohydrate intake. To recap: with less carbs, adding iodine becomes even more important.

One problem with iodine is that a sudden change in intake can have negative effects – you should build up your intake gradually. Perhaps the level of iodine in the soil where our ancestors lived determined the level in the animals and plants we ate, and thereby the level in our bodies. Since soil would also have determined the level of magnesium and many other substances inside us, it is interesting to ask from which soil we should get food.

The soil is where many nutrients come from – plants grow in it, cattle eats those plants, and you eat those cattle. It is known that the soil has a large effect on the nutritional value of a plant. Things to test in the soil at your local farm include iodine, magnesium, radioactive isotopes, and heavy metals.

As a rule, if that plot of land has been overfarmed or heavily farmed in the past, it is relatively "drained" of nutrients. Prefer land that has been sustainably farmed or not farmed at all.

Consult maps of where isotopes have landed from nuclear disasters and atomic weapons testing – large swathes of your country may be unsuitable (something that is not spoken publicly because feeding the world is hard enough already).

• Dental Health And The Paleo Diet
• Help! My Patient Wants to Fix Her Childs Cavity with…Liver?!?!
• Nutritional Cures for Damaged Teeth

Very strange: there have been signs that a varied diet is worse than a one-sided diet at building gut biodiversity! www.sciencedaily.com/releases/2014/05/140528105252.htm

Read that again. More varied diet -> less varied gut flora. What?! They propose it's because variation supports generalist species.

So how should we eat?

Should we be consistent with our diet, for a consistent flora?

Should we follow different one-sided diets in sequence, to give different cultures a chance to shine and outcompete the others? Maybe that'd cause an unending sequence of Herxheimer-like reactions (where you feel ill health because your previous gut flora is dying off).

To pattern lifestyle after the Paleolithic, it's likely that they would have eaten different foods at different times of year. Stretching out your variation over a year would give you fewer problems with sudden dieoff. Above all, it seems, to keep diversity high, avoid supporting generalist species. That would mean different one-sided diets at different times, and no fruit in the winter.

No mixed meals. That eggs-and-bacon breakfast should definitely be just eggs and bacon, no toast.

You'd have periods with lots of oranges, then periods with lots of apples, then periods with lots of kiwis, and also sometimes periods with no plant matter at all. A lot of variation over the year, but not all at the same time.

But is diversity important? Poor gut biodiversity, as you get after a round of antibiotics, has been linked to diseases like SIBO (small intestinal bacterial overflow), GERD (gastroesophageal reflux syndrome), IBS (irritable bowel syndrome) etc. Adding to that, evidence is mounting in support of a "gut-brain axis": good gut health, good mental health.

Admittedly, there can be many reasons why we see the link. Maybe it's not diversity in itself, but the presence of some specific species.

Early forms of the lipid hypothesis mistook total cholesterol (TC) for a risk factor for cardiovascular disease, so studies in the 1950s-80s only measured the total. Now we know it highly depends on the kind:

• HDL (high density lipoprotein)
• LDL (low density lipoprotein)
• VLDL (very low density lipoprotein)

and a related variable

• TG (triglyceride)

Aside; the term "cholesterol" is a misnomer. The above-mentioned lipoproteins can carry cholesterol among other types of lipids. LDL and VLDL are like taxis carrying a few things be delivered to cells, whereas HDL are like buses scooping up a lot of damaged molecules to be carried back to the liver(?) for breakdown.

It's usually a risk factor to have high TG, LDL and especially VLDL, whereas it's good to have high HDL.

On a low-carbohydrate high-fat diet, sometimes total cholesterol will rise, but it turns out it's always higher HDL and lower LDL/VLDL.

Triglycerides (TG) deserve separate analysis, I suspect. I seem to remember some reasoning that high TG is to be expected when you are in fat-burning mode, whereas it's pathological when you are in glucose-burning mode.

See the Roundup pesticide, in wide use today. I'm told that when they tested whether it's safe for human consumption, they tested only the primary chemical and set safe limits based on that, but the final product that's actually goes in the spray contains other chemicals that boost the primary chemical's effect about 125 times. If true, this concerns me, since then the residue on our plants likely far exceeds the safe limits.

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When they test whether a pesticide is harmful, they test it on human cells in a test tube (called in vitro testing) – they neglect to test the other part of the human animal: the microbes in your gut, and the evidence is increasingly mounting that a good gut flora is necessary for good health.

Many species of these microbes demonstrate severe weakness to pesticides – after all, they're roughly what pesticides are designed to kill. So, for good gut flora… avoid commercial plant food?

(A human body has 15 trillion human cells, and inside the gastrointestinal tract, 150 trillion non-human cells. Going by body count, you are a clonal being of mostly not homo-sapiens. It's not some minor detail, which makes it silly to just test the homo sapiens cells in vitro.)

Organic foods also aren't pesticide-free – they use other kinds of pesticides, that are perhaps less effective per deciliter, but then greater quantities are used. It may be Paleo apocrypha, but I read about one farmer kid saying "I love organic, I can spray it twice as much", which paints a nice picture.

While organic isn't pesticide-free, it tends to be safer(?) to eat. I guess. But, uh, I don't know. May depend on the exact formulation.

There seem to me three ways to avoid pesticides – either grow the food yourself, find a farmer who does it sans pesticide (for you Nordic readers, look up REKO-ring), or purchase food that didn't need pesticide… animals.

On the third option, many questions. I don't know:

• whether pesticide is used on the grass we grow for silage
• whether that pesticide lasts over the months
• the effect on animals health' of giving them pesticide-laden feed
• the effect on the healthfulness to us of their flesh, after that
• ..

www.marksdailyapple.com/why-i-dont-trust-the-acceptable-daily-intake-levels-for-pesticides/

In principle, GMO is cool. It represents a victory over nature, like penicillin and all that, but this put a stopper on my excitement:

The majority (70%+) of genetically modified organisms are modified with pesticide components.

No way to wash off those residues – they're inside and throughout the apple! Concerns that apply to pesticides therefore automatically apply to most GMO today.

Other GMO strategies involve making the food resistant to a pesticide, so that it will not be harmed… and the farmers can then spray massive amounts (since the food survives). It may be very important for us to wash that food with soap, or peel and toss its outermost layers entirely.

In liver, the grass-fed variety has eight times as much vitamin A. I'm not kidding, eight! Not 108% or 180%, but 800%.

Maybe it was a fluke because the amount depends on which animal the FDA/USDA/(who?) tested, but it seems unlikely. If it's a common pattern for vitamin A, what does it say about other nutrients?

People commonly see creatine as a bodybuilder thing – why would normal people need creatine? Actually, bodybuilders may need it the least – they're used to challenging their muscles to the maximum as it is, and I'm somewhat confident this will produce the full MPS reaction (muscle protein synthesis).

For people who don't exercise much, the creatine could mean an extra kick whenever they do lift something, and more energy to make the decision to lift it in the first place. That's just a supposition, but it opens my mind to creatine as a nutrient for normal people. Forget its association to the gym and analyze it like any other nutrient.

Creatine is a naturally occurring substance – about half of your creatine is produced inside your body (if you're an omnivore), the other half is provided from meat, eggs and fish.

What it does is sit in your muscle, just like glycogen and ATP, ready to provide energy. It's a straightforward job.

A difference from glycogen in strenuous exercise is that creatine gets used up almost immediately and recharges in time for the next set of exercise – and for a given set, a tiny portion of the energy comes from creatine. That may be because strenuous exercise is strenuous, it uses lots of energy all at once. Perhaps for less strenuous exercise, such as walking, a greater fraction will come from creatine?

From various Internet anecdotes, people who eat animals often feel no effect taking additional creatine, but vegans experience a significant difference: everything from moving to thinking becomes easier, apparently clearing away "brain fog".

A point on safety. There are various forms of creatine, and the form called creatine monohydrate has undergone extensive study, looking very safe in the prescribed quantities (5g/day), unless you have kidney problems.

Can we extrapolate that if you were a heavy meat-eater you would also experience problems if your kidneys are not working right? Is there a wiki of Nutrition Science results where you could check if this has been checked before?

You need ~3g of leucine to stimulate muscle protein synthesis (MPS). See www.ncbi.nlm.nih.gov/pmc/articles/PMC4558471. So any one meal needs to exceed a certain amount of protein, because if we never stimulate MPS, it's sort of like having a protein-free diet(?).

How much leucine is in 100g of food? From nutritiondata.self.com:

cheese, cheddar           2385 mg
cheese, gouda             2564 mg
egg, whole, raw           1088 mg
fish, herring, raw        1460 mg
yogurt, plain, whole milk  350 mg
beef, brisket, raw (1)    1395 mg
beef, brisket, raw (2)    1637 mg
chicken, raw              1245 mg

So 1.2 to 1.7 grams of leucine in 100 g of meat. So 250 g of meat is minimum at one meal, 300 g a better minimum to be on the safe side.

Aside: This utilizes the mTOR pathway, accelerating aging, which we ought to counterbalance by fasting. Fast and feast.

Very old people maybe shouldn't trigger mTOR that often, so one protein meal a day (and instead have more bone broth), while young people can have two or three, but not sure what my reasoning was for this.

I've been thinking of asking a butcher if this is true, and if they don't know maybe they'll be curious and want to test it.

Muscles and liver contain glycogen, a carbohydrate. It dissipates quickly after the animal is killed, which is why these things arrive to the supermarket with zero carbohydrate (and why liver is not as appealing to us as it perhaps should be). Truly fresh liver can have over 20g glycogen per 100g, the sweetness of a banana.

For muscle meat, butchers usually want to drain it of blood, hang it to tenderize over a long time, before packaging it. That dooms the glycogen. But there seems no reason for liver to sit out and wait in the same way. If organs were a high-value food, I guess they would cut them out as quickly as possible and flash-freeze them.

We learned to do the same thing with fish: I read that at the start of the 1900s, the fish at European fish markets used to smell and taste terrible before someone observed the Inuit freezing their fish immediately on catch (easy to do in the Arctic), and started doing the same, keeping it frozen as it was shipped to Europe, and it improved the flavour considerably. It presumably also conserved nutrients, especially the highly unsaturated fats, which are prone to oxidize in air (go rancid).

So my question: can the liver glycogen persist all the way to the supermarket if you freeze it quickly enough? I bet there would be a market among the Paleo crowd for sweet liver.

EFSA (European Food Safety Authority) says that intake of up to 400mg/day do not raise safety concerns, and that a 200ml cup of filter coffee has 90mg of caffeine. So four cups/day. www.efsa.europa.eu/en/topics/topic/caffeine

"Coffee is a diuretic, it makes you thirsty"? Nevermind the fact you can disprove this in 1 day by drinking only coffee that day and observing that, hey, I'm not thirsty, it's a really interesting topic because it's so simple and yet you see a lot of laymen disagreeing on this point. It becomes a litmus test for who tends to do their homework.

As far as I can tell, this stems from a misunderstanding of the term "diuretic". Diuretic literally means "something that makes you pee". Problem is, plain water is itself a diuretic. Drink more water, pee more, right? Medical articles say "coffee is a diuretic" in the same sense they would say "water is a diuretic".

For us to usefully talk about diuretics, there is a second meaning to the term: something that, by chemical means, stimulates your body to pee more despite supplying no water. And this is the hidden assumption people naturally make when they hear "coffee is a diuretic", since it seems pointless for anyone to say it at all with the prior meaning.

Coffee does have some of this chemical effect… so it's not quite 100% as hydrating as water, but IIRC it's over 99%. It's definitely not negative.

Acid-Base: Does Dietary Acid/Base Balance Matter?

A 2011 meta-analysis by a Netherlands journal concluded that saturated fat wasn't anything to worry about except maybe when combining them with a lot of carbohydrate.

I've found my cruxes. If I believed differently on these points, my nutrition outlook would change in radical ways.

1. ([2022-06-27 Mon] 3:1 for) The ketone argument: Ketones appear so positive for health, how do we explain that if we're not meant to spend much time ketogenic? Ergo we're meant to (let's say >25 weeks a year).

2. ([2022-06-27 Mon] 5:1 for) The insulin argument: A high insulin load (meaning total insulin released in a day) has so many negative health consequences we can point at — though I expect some of the science was done assuming our biochemistries are all the same, which could call for a re-run stratifying people by genes.

   Anyway, with that, and the absence of negative consequences we've found for a state of low insulin, it's safer for you and me and any given person to avoid a highly insulinogenic diet (i.e. a carb-laden diet).

3. ([2022-05-08 Sun] 10:1 for) The EEA argument: The things the typical animal of a given species ate over a lifetime in its Environment of Evolutionary Adaptedness (EEA) reflects so accurately what's healthy for that species, that you can treat these claims as synonymous: "we ate like this in the past" and "this is healthy for us".
   • This implicates grain, sugar and seed oils as pretty suspicious kinds of food.
   • The main carb sources in the EEA are fruit and root-vegetables. Is it easy to gather enough fruit and roots in the wild to consistently feed a tribe? Needs analysis, but I feel no, so very high carb diets do not seem EEA-like.
5. ([2022-06-22 Wed] 5:1 for) There's been a serious publication bias since the 1980s in favour of the low-fat low-cholesterol high-carb whole-grain set of ideas.

I used to count the following among the cruxes above. They're not positively false, but I realized it's hard to use them in support of any conclusion.

4. The human design argument: Among primates, the design of homo sapiens indicates they sought out more meat and particularly animal fat. Alternatively expressed, I think that if I'd try to design an animal to eat plant carbs for a large share (say >33%) of its lifetime calories, I'd design it different.
   • If you want to look at this more closely, there is plenty of bikeshedding online about why e.g. the digestive tract, teeth, bipedal posture and other features mean we're herbivores or that we're carnivores. Bad arguments abound on both sides. Search 'human design vegan' and 'human design carnivore'.

   • [2022-06-20 Mon] In retrospect, I find it hard to draw conclusions from this statement, because there was no single ancestral diet. See The AMY1 gene.

     It could really be the case that we're that flexible (and that we're not just saying so as a way to throw up our hands and walk away from the question). Not flexible in the sense of jack-of-all-trades-master-of-none, but in the sense of master-of-all-trades (in biology that's the same thing): we may have evolved for animal fat and yet now it's totally replaceable if we want?

6. Calories, protein and micronutrients from animal sources frequently appear better-adapted for humans than the same from plant sources
   • to clarify, the chemical forms aren't just more bioavailable, but the amino acid profiles and micronutrient profiles when eating nose-to-tail also support health well
   • (this seems the case for all animals, as even herbivores eat meat opportunistically, and it's a priori reasonable that the building blocks of an animal would be good raw material for the body of an animal, and that its energy stores would be in a good form for the body of an animal to burn)

Why I discarded #6: The fact herbivores can benefit from meat, despite being evolved for herbivory, means we could likewise be so, thus the bioavailability arguments don't by themselves say a lot about what we're evolved for.

Recalling Anichkov's 1913 experiments of feeding cholesterol to rabbits, resulting in buildup of plaque in arteries and organs and behind their eyelids, it's likely that if a herbivore eats too much meat it will be a problem. Even though many of the component nutrients are well-adapted to the rabbit's body and the rabbit needs no sophisticated digestive apparatus to absorb it, if a species didn't evolve to eat something frequently, there will still be a limit to safe consumption.

The question is how much meat is safe – where the answer for a carnivore is simply "any quantity" – and we don't know what this quantity is for a human, but I would like to see the hypothesis tested that the quantity for a human is also "any quantity", provided they eat non-starved ruminants in a nose-to-tail way.

7. Sugar is bad
8. ([2022-06-20 Mon] 20:1 for) Seed oils (rapeseed, sunflower &c) are uniformly harmful
   • because not found in the EEA
   • because all clinically successful diets have excluded them (see Clinically successful diets)
   • because polyunsaturated fat is not great fuel even in theory (as a component of cell membranes it's one thing, but a tiny fraction of intake goes to that application), we see lots of side effects when burning them for calories – oxidation &c…
9. "Processed food" frequently not that healthy
   • but it depends on what "processing" means
10. If an EEA culture had focused on forage over hunt, even for periods, calories would have been predominantly from root vegs, fruit, and the fat in insects such as worms, but not appreciably from nuts and not at all from seeds or grain.
    • The insect point is interesting because it wouldn't occur to many Western theorists. Of course when foraging in the Horn of Africa, there's no way you'd skip over the insects you find along the way. Cultures that left such free lunches on the table would get their numbers overtaken by cultures that did eat all the food they found.
11. ([2022-06-27 Mon] 6:1 for) Fiber is unnecessary
    • End the Fiber Fantasy, comments also enlightening
12. ([2023-10-05 Thu] 2:1 for) Amber O'Hearn is basically right in most nutrition analyses
13. (<2022-Jul-02> 5:1 for) Denise Minger is basically right in most nutrition analyses
14. ([2022-06-27 Mon] 7:1 for) Seafood adds around one decade to both lifespan and healthspan, if you start in your 20s
15. ([2022-06-27 Mon] 3:1 for) In the long term, most or all sweeteners act approximately as fattening as sugar, even non-caloric ones like aspartame
    • This is based on the theory that the insulin response and other reactions to the sweetness are the main fattening factors, and the immediate calories are practically irrelevant.
      • Has anyone tested just eating sweeteners to bring blood sugar down to the point of passing out? This would prove insulin is being released.
16. ([2022-06-18 Sat] 2:1 for) Within 12 months, it's hard to get nutrient overload symptoms from eating only meat, provided the meat is fatty
17. ([2022-06-18 Sat] 3:1 for) Within 12 months, it's hard to get nutrient /deficiency symptoms from eating only meat, provided the meat is fatty
18. The immune system works better in a fasted state
19. ([2022-06-18 Sat] 5:1 for) Staying in a ketotic metabolism for 300 days a year will lengthen an average young adult's lifespan by 5-20 years and healthspan more than proportionately
20. ([2022-06-18 Sat] 20:1 for) When giving an Oral Glucose Tolerance Test (OGTT) to a ketotic person (i.e. feeding them 150g of sugar) causes a hyperinsulinemic response (i.e. they react like a diabetic), it does not indicate a chronic problem with this person: letting them acclimate to carbs for a day first will ensure a normal response to OGTT thereafter.
    • Specification: The above is true for patients that do not already have diabetes. Important related belief (<2022-Jan-29> 7:1 for): a ketogenic diet will never cause the onset of diabetes.
21. Fasting and IF (intermittent fasting) lower the "bodyweight set-point"
22. Sugar raises your "bodyweight set-point"
23. ([2022-06-20 Mon] 25:1 for) The level of glucose and ketones in the blood do not indicate the rate at which each is being burned, you need more information to figure this out.
    • In other words, it is possible to have 5.5 mmol/l glucose (approx 27.5 mmol for whole body) but have those be the same 27.5 mmol in the evening as in the morning i.e. the body cells did not suck any of it up.
24. Vitamins taken in isolation have a different effect from vitamins in food.
25. When a specific nutrient is discovered that we (1) need a relative lot of and (2) is found in few sources, this is evidence that we ought to eat a lot of this source, period – for more reasons than this nutrient in particular
    • This is just letting making holistic and reductionist perspectives inform each other
26. Fat-soluble vitamins and minerals, such as vitamin D, are stored longterm in fatty tissue, and the storage can last for months of fasting (as long as the fat stores do), provided the diet was consistently nutritious before.
    • If the diet was not consistently nutritious before beginning fasting, the body fat liberated during fasting will be proportionately deficient in fat-solubles (50% confident).
27. (<2022-Jan-29> 3:1 for) If you got plenty of sun during the summer, vitamin D levels stay adequate through winter, at least in the context of what's colloquially called a "Paleo" or "Keto" diet.
    1. Related belief ([2022-06-27 Mon] 3:1 for): Even a level as "low" as 35 ng/dl can be adequate, reasoning from Chris Masterjohn.
28. (<2022-Jan-29> 3:1 for) For a majority of the population, exhorting "eat less calories to lose weight" either has no effect in practice or causes weight gain, not loss.
29. (<2022-Jan-29> 2:1 for) Lack of sunlight is an epigenetic trigger for myopia.

Terminology

• "Ketotic person" – someone (1) used to a ketogenic diet and (2) is in a state such that >50% of brain glucose use has been replaced by ketone use
  • assuredly met after eating ketogenic (averaging <20g carb/day) for 3+ weeks

Here are the ingredients of a Purina Test Diet, frequently used as the "high-fat diet" in mouse studies:

• cornstarch
• casein
• maltodextrin
• sucrose
• vegetable shortening
• milk fat
• lard
• AIN93G Mineral Mix/Fiber
• powdered cellulose
• inulin
• soybean oil
• AIN93 Vitamin Mix/Fiber
• corn oil
• L-cystine
• choline bitartrate
• cholesterol
• FD&C Red 40 Lake

This is nothing like how a human would compose a low-carb diet. By contrast, the regular chow will contain actual foods you might find in a human diet: wheat, oats, corn, fish &c.

In 2008, two researchers from UC Davis conducted a literature review of studies containing the keywords "mouse high fat" published in high-impact journals during the year before. Of the thirty-five papers surveyed, only five compared diets where the nutrition was identical but for the fat and carbohydrate content. The rest inappropriately compared a 'purified' chow such as this, to the regular, more whole-foods chow.

You'd think researchers would know better, but apparently not 30 of 35 nutrition researchers. Always check the Methods section of the paper.

Source: Death by Food Pyramid

1. In vitro research
2. Animal studies
3. Case studies
4. Observational studies
5. Controlled trials
6. Meta-analyses

Suppose a study says people eating the Mediterranean diet died less from cardiovascular disease. You have to ask: are they counting just people who died, and checking what they died of? In that case, it would be pointless to adopt the Mediterranean diet. Right? (Think about it for a bit.)

No, what you want to know is also how long they lived. (In fact, that's the only thing you want to know.)

These kinds of pointed research questions are for researchers' eyes only, not for common citizens seeking diet advice. The researchers' goal is to discover the ultimate causes behind cardiovascular disease, knowledge we can then use in myriad ways. The common citizen's goal is to know what keeps them healthy as long as possible, and for that a much more basic outcome variable is called for (like actual lifespan, all-cause mortality); it will be more reliable since it won't depend on chains of reasoning full of possible confounders.

A reason we don't always do that is it takes a long time to wait for people to die. But another reason is that lifespan just wasn't part of the researcher's research question (…or they didn't want to report a worsened lifespan together with better cardiovascular outcome). So always keep the goal in mind, and when you must construct chains of reasoning (or worse, be snuck an implied chain of reasoning), pay attention to what the data at hand could say about the goal and what it couldn't possibly say about it. Eyes on the ball.

The hypothesis that cholesterol in the blood leads to heart disease.

Started by Nikolai Anichkov in 1913 when he found that feeding rabbits large amounts of cholesterol (equivalent to a hundred eggs a day for a human) causes plaque buildup in their arteries, organs, behind the eyelids and other places, with outcomes such as heart disease. However, Anichkov also had this to say.

… we conclude that the harmful effect of cholesterin-rich nourishment is not expressed equally in all types of animals…. The fact that cholesterin has different effects on different animals, even closely related ones, raises the question as to what degree the results described above are valid for human pathology.

Extending the lipid hypothesis, this is the idea that dietary cholesterol or dietary saturated fat raises blood cholesterol, and therefore leads to cardiovascular disease.

See section What if the food volume hypothesis is wrong?

See section Insulin

See section 20 calories a day.

Something about the HPV vaccine.

The China Study: Fact or Fallacy? (links to response by Campbell too)

A prospective cohort started in 1948, currently on its third generation.

The Framingham Heart Study was our first source of discoveries such as

• that smoking is harmful
• … (long list of health discoveries)

Sometimes, people cite the FHS to support a connection between cholesterol-rich diets and heart disease. In fact, neither the FHS nor its descendants showed any such connection!

The study by Ancel Keys, results first published in (?), although it's still running? Observed sixteen regions in seven countries.

The meme of the so-called Mediterranean diet comes from this study, when they noted that people in Crete died least from cardiovascular disease (and lived longest?). However, they neglected to consider the Cretans' Orthodox Christian fasting tradition, and it's super hard to tell whether they had good results from the diet, or from fasting.

• How much land area is used for pasture, that could have been used for agriculture?
• How much good farmland is reserved to feed animals? (How much of that goes to CAFO?)
• How many humans can we feed in theory, if we only use sustainable farming practices, assign all good farmland to producing human food, and only keep as many animals as can live off pasturing on subpar farmland?
  • How is this picture affected by the choice of crop?
  • How is this picture affected by pesticides and GMOs?
  • How is this picture affected if we have people going out to milk the pasturing cattle vs. don't?
  • How is this picture affected by the lifespans we allow the cattle?
  • How is this picture affected by the choice of animal (cow, goat, chicken…)?
  • Crazy thought experiment: following the idea of killing the smallest count of animals for the biggest loads of meat, suppose we only get our meat from blue whales?
• Is rewilding good from an animal-suffering perspective? If not, what are our options for minimzing total animal suffering?