The latest Kurzgesagd video on exercise seemed to imply that (excepting sudden changes in activity level) caloric burn rate is constant regardless of lifestyle, but if you are sedentary, the "excess" calories are burned "unproductively" (e.g. increased inflammation).

So this seems to imply excess calories are a cause of chronic inflammation.

Also, the ketogenic diet has been shown to significantly reduce inflammation, though I'm not sure if that's from reducing carbs, or reducing something else associated with high carb intake.

> caloric burn rate is constant regardless of lifestyle

This is obviously false as stated, extreme athletes consume vastly more calories than sedentary people of their same weight. Phelps was rather famous for a 10,000+ calorie per day diet but even just manual labors need significantly more calories.

I’m assuming there’s some unspecified criteria such as while sleeping?

It's just plain not true. Claims like this coming out in the past few years are based on Herman Pontzer's research in which he measured activity levels and energy expenditure among the Hadza, a forager group in Africa, testing the hypothesis that they'd be using a lot more energy because of how active they are. He found their energy expenditure on average wasn't actually much different than the average for sedentary Americans and developed something called the constrained energy expenditure model. This just postulates that the human body has various ways of compensating in the long term for high activity levels. If less energy is available for basic life processes that are not critical to immediate survival, those process will be modulated downward. Importantly, one of these is inflammation, which is likely why exercise reduces inflammation. At the very extreme end of this, you see things like Marshall Ulrich when he was attempting to break the record for time running across the continental United States seeing things like his hair and nails stopped growing. Female endurance athletes commonly stop having periods. Male endurance athletes often have reduced testosterone production.

But this compensation is nowhere near 100% and it also isn't clear to what extent this is mediated by food availability and possibly the intensity of the activity. The Hadza don't have a lot of food and they're spending all day walking around. Similar studies have been conducted on the Amish, who are doing far harder manual farm labor and have enormous amounts of food, and these studies found much high energy expenditure among the Amish compared to post-industrial sedentary Americans, as well as an average 9% bodyfat for males for whatever that is worth. Similarly, the experiences of endurance athletes with bad health symptoms like amenorrhea and low bone mineral density are limited to people who feel pressure to be as small as possible and don't eat anywhere near enough food. Those who simply eat more don't have the same experiences.

As you stated, we also have quite a bit of clear cut existence proofs that energy expenditure is not simply constant among all people regardless of activity. Pontzer himself has studied some of these extremes to figure out how much energy a human actually can expend. From what I recall, it seemed to be around 3.5 times whatever your base metabolic rate is, at least in the long run. Over short bursts, energy expenditure can be up to 10 times base. The greatest longer duration energy demands he has seen in the field is the Tour de France for men and pregnancy for women, both of which are about equal and seem to represent the limits of what humans can do. Obviously, the people doing these things are eating far more than they would be if they weren't doing those things. Nutrition advice for athletes is nearly the opposite of what it is for the obese and sedentary. Eat sugar like there's no tomorrow. Get as many liquid calories as possible. Avoid high fiber because it'll sit in your gut forever slowing down all other digestion and making you uncomfortable. There's a reason for this.

Two of my favorite podcasts, Stronger by Science and Iron Culture, was in the former case and is in the latter hosted by one of the researchers who works in Herman Pontzer's lab, and he is constantly expressing frustration over how the findings and model get misrepresented by the time they telephone down to pop science communicators and diet influencers. The model simply says that expending X calories per day in exercise will not result in a net difference of X calories expended in total. It'll be some percentage less than 100. But it won't be 0%. Exercise and activity don't make no difference at all.

I'd never heard of this Kurzgesagt thing, but it appears to be a group of animators that make cartoon explainer videos of basically everything? That might be entertaining but is probably not the best way to learn about the frontiers of contemporary nutrition and exercise science.

Thanks for the info. Sibling comment posted the video I was referring to. The video was apparently made in cooperation with Pontzer: https://sites.google.com/view/sources-workoutparadox

Kurzgesagt mentions that their explanation is an over simplification; generally they are well researched and cite sources.

The video discussed is this one: https://www.youtube.com/watch?v=lPrjP4A_X4s

I enjoy your perspective on this topic!

Glucose and fructose will react non-specifically with proteins in the body, particularly when present in excess. These non-specific reactions are recognized as foreign and/or defective, which triggers inflammation. The apply named RAGE protein is one mediator of this response (https://en.wikipedia.org/wiki/RAGE_(receptor)).

HbA1C results from the non-enzymatic reaction between glucose and hemoglobin. It serves as a measure of your long-term glucose level and is elevated in diabetics.

Low carb diets dramatically reduce this source of inflammation.

This also lines up with something said in the book Lifespan about fasting reducing inflammation.

There is a huge difference between inflammation in response to injury and chronic inflammation caused by lifestyle choices like poor diet.

> caused by lifestyle choices like poor diet

If you can prove this .. which things specifically is this linked to? There is a lot of completely terrible nutrition "science" out there.

That's missing the point. If this technique can result in longer lives for people with both good diets and not, it is a genuinely novel innovation in human life span that can't be replaced with better diet alone.

The question was what are you giving up in exchange? Is this protein's function really just to reduce your quality of life and kill you faster?

It could well be that this protein is good for you when you’re young but not that good for you when you are older.

For example, young people might encounter more new infection sources, and thus need a faster/stronger responding immune system. This protein might be evolved for giving you that, with a side effect of having too strong an immune system at older age.

Evolution may not yet have found a solution that turns down its production at later age, or it might have evolved it at some time, but found its benefits do not outweigh the cost of maintaining the necessary control mechanism.

It’s far from a given that having more humans live to old age has evolutionary benefits.

What happens when you eliminate the "good inflammation" in those with bad diets? Then what? There's likely going to be unintended consequences, naturally. My point, eliminating one symptom usually means eventually creating another.

It's not missing the point. The point is that a lot of people live with chronic inflammation caused by poor lifestyle choices and that results in many diseases later in life, including Alzheimer's.

The point is that chronic inflammation is bad. The comment I'm replying to isn't recognizing that it's just saying "oh inflammation is fine because it's a response to injury" which is very much missing the point.

How much of the consequences of a poor life style can be mitigated by simply reducing the chronic inflammation response by the body?

I'd love it if cheap shitty food wasn't bad for me. At the end of the day a calorie is a calorie and many animals handle the stuff that shortens our life with no problem.

Look at it another way, if dogs can't eat chocolate but humans can, is the problem with chocolate or with dogs?

A calorie is certainly not just a calorie. Different foods are metabolized differently and affect the body in different ways, regardless of otherwise equal caloric values. Take fructose, glucose, and ethanol as an example.

The problem there is with dogs, and has nothing to do with calories. Dogs (and many other animals) are simply not able to tolerate chocolate like humans can. Conversely, humans can't tolerate eating rancid meat and cat poop, but dogs can eat those things easily and not get sick. Lots of substances are poisonous to certain species, and non-poisonous to other species.

Also, the reason chocolate is unhealthy isn't because of the cacao plant, it's because of all the added sugar used to make it taste good, since raw cacao (or cocoa, which you get after cooking it) is horribly bitter.

Chronic inflammation is bad. Is chronic inflammation always caused by auto-immune? Or is it also caused by things like pollutants, poor diet, or other "first world" problems?

I ask because I used to be very concerned with particulate matter (I still am, but I used to too), and it seemed a big problem with that was it triggering inflammation.

It's been a while since I looked into this, but diet is a major factor with inflammation. Sugars, seed oils and grain-fed dairy. (Also if you eat the grains yourself!) Keto lowers it, caloric restriction lowers it (conversely excess calories coupled with sedentary lifestyle increase it), intermittent fasting lowers it.

I forget about exercise, I think it's a case of temporarily increasing it (hours) and then lowering it long-term.

Speaking from personal experience diet plays as much a role as medication in decreasing inflammation. Sugars, gluten, and some* nuts and seeds are indeed pro-inflammatory (many seeds and nuts are anti-inflammatory)

How did you measure inflammation level ?

CRP, Calprotectin are easily measurable, not so sure TNF-Alpha and Interleukins?

I don't think there's a pattern suggesting that. Many autoimmune diseases are more prevalent in less polluted parts of the world. The strongest links appear to be genetic, in that some diseases (e.g., Sjogren's syndrome) are clearly more common in people of certain geographic descents.

I'm not asking if autoimmune is caused by pollution or development. I'm asking if they both have similar effects.

There is no distinction regardless of cause, imo. Stress can epigenetically cause an autoimmune disease, and so can pollution (including smoking), excessive alcohol, processed food diet, sedentariness, etc. Often it is a number of factors that can lead to a chronically overactive immune response.

I forgot to add, some have higher genetic predisposition for an autoimmune disorder, and diet/environment/lifestyle can switch those gene sections on.

Asthma is another example of a terrible problem caused by chronic inflammation.