Evolutionary gene loss may explain why only humans are prone to heart attack | Hacker News Reader

Evolutionary gene loss may explain why only humans are prone to heart attack

sciencedaily.com

143 pointsrjzotti121 comments

Since the driver of the selection against the related gene seems to be malaria, I wonder if this is linked to prevalence of body hair on human ancestors.

Bug bites on hairless skin probably had something to do with dying of disease, and the early homonids that had the gene seem to be the ones hit the hardest.

We also see evolutionary markers related to bed bugs, head lice and body lice. Maybe mosquitos and genes linked to a possible malaria pandemic offer more clues.

Malaria is a fascinating one, with the prevalence of sickle cell anemia and G6PD blood deficiency in some populations with high exposure. Both of those cause health issues but they both confer some level of resistance to malaria.

Isn’t the recessive gene for cystic fibrosis also linked to malaria resistance?

Edit: apparently it might be linked to a resistance to cholera.

I was taught (undergraduate genetics) that it was TB, but I see the relevant Wikipedia page also lists cholera, typhoid and diarrhea shrug

As far as I remember, malaria comes in via glycosaminoglycans, and not our sialylated glycans. It could very well be related to our symbiosis with bacteria however.

Edit: I forgot the earlier work demonstrating Plasmodium specificity to NeuGc, so yeah maybe malaria!

On the other hand, cats -- for example -- are highly prone to kidney failure in a way that humans are not.

Cats, being obligate carnivores and lacking a proper mechanism for extracting energy out of fatty acids (e.g. ketogenesis in humans), have actually very efficient kidneys to dispose of all the nitrogen coming from their protein-exclusive metabolism.

Domestic cats are at risk, but that is more a result of domestication and improper feeding (carbohydrate) than evolution or genetics. Unless I am missing something, of course! Care to elaborate?

Whenever I see comments blaming carbohydrate intake for large swaths of problems I find it challenging because I agree and then feel that I am seen as a heretic or extremely gullible.

Do you ever feel that way?

I doubt anyone would think you a heretic for believing that about pure carnivores like cats.

I guess he was extrapolating and referring to the idea that carbohydrate consumption is the root cause of most, if not all, modern diseases. An idea held by many, including me.

To say even most modern disease has to do with carb intake ignores all the diseases that clearly aren't even diet related. You could probably get away with saying most diet related diseases are related to carb intake. I'd say that's a stretch, too, though I do suspect, as you do, that the type and quantity of carbs people eat is underappreciated as a factor in many illnesses.

Yes, absolutely. Some diseases are due to pathogens and such. But those should not be "modern", in the sense that said pathogens might not be exactly new. Maybe you could say anthropogenic diseases such as lung cancer from smoking or esophagus cancer from drinking are modern, though.

What I meant by "modern diseases" in my comment is a group of non-communicable diseases or so-called "diseases of civilization".

"Diet-related" is rather ambiguous, so different lines might be drawn there. As an example, would you say Alzheimer's is a diet-related disease? What about melanoma and/or sunburn?

Ah I either missed or misunderstood the use of "modern" there. I can't speak to the relationship between diet and melanoma or Alzheimer's, but I understand your point.

In Mongolia in rural areas people eat just meat. Dearth from heart decease and liver cancers are leading causes of dearth there. On the other hand, life expectancy in Mongolia is 70 years, while in mostly vegetarian India it is 69.5. Just from that one can easily see that blaming one particular food group is not productive.

Yes, they eat just meat, but smoking prevalence is over 50% [0], and alcoholism is rampant [1].

Bad example, to be honest. In fact, liver cancer can be directly attributed to drinking.

A life expectancy of 70 years under such conditions is actually astonishing.

[0]: https://www.who.int/tobacco/media/en/Mongolia.pdf

[1]: https://www.npr.org/templates/story/story.php?storyId=112485...

Yes.

I don't usually express my opinions on nutrition, metabolism and/or health in general in the open, because I know they go against what is currently mainstream and they would be met (as elsewhere in this submission) with extreme resistance. I can't blame the others, though, as I once was in their same position and know how it feels when deeply ingrained ideas are challenged from the outside.

I have learned to live without the need to be "right", or to educate others when they don't want to be. It is enough for me to apply what knowledge and intuition I have gained over the last years for my own health and well-being. If, at some point, someone wants me to share that knowledge, then I will gladly do it.

Thank you for this. This is very helpful both practically and emotionally.

I also try not to say a word about my beliefs. That was much easier before having children who are offered carbohydrates constantly.

You're very welcome.

Even though I have no children, I can try to imagine what it feels like.

My paternal grandfather died of complications from uncontrolled, insulin-dependent type 2 diabetes. He spent his last years half-blind, unable to move, filled with ulcers and missing several toes.

My father has been hovering around the prediabetic range for many years now, and I live a 5-hour drive away from him. Effectively, he is like a child, with no knowledge of nutrition or metabolism, trying to find his way in a world dominated by a food industry that doesn't have public health anywhere in its objectives.

But it's not just the food industry, although they might have the monopoly of malice in this context. Guess what the diet prescribed by his primary care provider looked like once he was deemed prediabetic. Motherfucking biscuits for breakfast, pasta or rice with lean meat, sugar-laden fruit juice... but counting calories! Exactly the opposite of what I have finally convinced him to eat by chipping away on every holiday visit. He's not exactly following a ketogenic diet, but at least he is starting to figure out what sugar, starch and seed oils do to people, and how the blame was shifted onto the wrong substances (saturated fat and salt, basically). He is even giving intermittent fasting a go!

It's hard when you know that the potential suffering of a loved one is perfectly avoidable with just the right pieces of information.

As you might have guessed, having type 2 diabetes in my immediate ancestry (also in my maternal family) was one of the reasons that led me down the rabbit hole. I now treat nutrition and its effect on health and metabolism sort of like a hobby. I guess there is a component of biohacking in there as well.

“carbohydrate“ is extremely bad term in nutrition. There is fundamental difference between eating whole food plants like potatoes or drinking sugary drinks. Yet both are formally carbohydrates.

What do you think potato starch is metabolized into in your body? Starting in your mouth (salivary amylase).

Potato is not just starch. In fact per calory potato is very dense nutritional wise with all that fiber, minerals and vitamins. In addition there is speed of absorption which for starches is much lower than for simple sugar. Plus starch metabolizes as glucose while table sugar and friends contains 50% fructose.

Which points to an elephant in the room that people miss when use the term carbs. It is the similarity between whole-food plant-based and various forms of keto. They both avoids simple sugars and processed flour mixed with refined seed oils or saturated fats.

Bananas and dates (to name a few fruits) are plants, are whole foods, and are filled with fructose.

A single potato with skin has 6 grams of fiber and around 60 grams of starch.

As for the vitamins and minerals, the only thing found in a relevant amount in potatoes is potassium. Contrast this with eggs, organ meat or even muscle meat.

What would you say is the problem with saturated fat?

Also, out of curiosity, are you vegan?

Yes, I am vegan.

As for saturated fat I have no idea what if any can be wrong with it from human health point of view. Literature and observational studies are contradictory and it all depends on the whole diet. But I do know from personal experience and from some hints from literature that mixing it or vegetable oil for that matter with highly processed starches or sugars is bad.

I expected that. Is it for health or for ethics?

Also, can you please address the other points in my previous comment?

Feel free to reply to any of my other comments in the thread if we have reached maximum depth.

I am vegan for ethical reasons. If one does it carefully, it is not worse than any diet with meat health-wise. So essentially killing animals for food is not necessary and one does it out for pleasure or out of laziness.

As for other points, most fruits are not particularly dense in calories and one needs to eat kilograms of them to consume 100 grams of fructose, which one can get from one bottle of sugary drink. Dates and dry fruits are exceptions, so to minimize fructose exposure one should not eat them in substantial quantities.

As for deficiency, consuming reasonable variety of starchy vegetables and grains with some greens without added oil provides all minerals and vitamins one can get from meat except for B12 as long as one gets enough calories. There are some individuals where a particular component is not absorbed efficiently if it comes from plants, but that is trivial to compensate with supplements. For example, I personally get low on iron (a family run condition) and has to supplement that either directly or indirectly by taking vitamin C with iron-rich vegetables or grains.

I always thought it made sense that the improved efficiency comes at a cost. Our (human) kidneys are not as efficient, and we require a lot more water intake. Then again, we don't have as many kidney problems. This kind of argument certainly _feels_ right ("no free lunch"), but that does not necessarily make it so.

I feel that repeated inbreeding can (but does not have to) cause issues like sensitive kidneys in cats, but it probably also has to do with domestic cats growing relatively old. Things like faulty kidneys (or thyroid issues, or diabetes) bound to show up eventually if cancer does not get them before age 10.

I have the feeling this has much more to do with our self inflicted lifestyle than genetic factors.

Maybe no other animal is just that stupid.

> Maybe no other animal is just that stupid.

Have you ever owned a cat or dog? My experience is that a percentage of them will overeat unless constantly monitored, eat things that are outright dangerous, etc. What is it that makes humans the stupid ones, here?

I wonder whether or not we should distinguish between domesticated animals and wild ones

It would be an interesting (if difficult) experiment but from what I know wild animals will absolutely gorge themselves if they can.

The difference is that in the wild, this is tends to be quickly followed by a resource crash from a normal cycle (e.g. winter crash after summer glut) and / or population explosion.

I don't know that any organism has had evolutionary-scale periods over which to psychologically integrate an access to essentially unlimited (in time and quantity both) resources.

I have seen wild geese eat too much seed from bird feeders and practically lose the ability to fly.

I suspect the correcting mechanism for that is generally predation.

Labradors usually have a genetic disorder that causes them to gorge themselves, so they are highly prone to obesity. They are also very popular breeds in the US.

https://en.wikipedia.org/wiki/Labrador_Retriever#Inherited_d...

This is interesting. Growing up, we had chickens, sheep, goats, cows, horses, dogs, cats and rabbits. And an unfortunate sampling of salamanders, frogs, horny toads, chipmunks, gophers, wild-rabbits, foxes, coyotes, hawks (various types), eagles (a few types), skunks, deer, antelope, raccoons and badgers. (I'm probably missing a few - and I've certainly left out small birds, which require their own reading as do snakes)

Left to their own devices (they weren't each individually heavily supervised - especially when on the range), of the domesticated ones, the only ones that would gorge themselves to death were the horses (when they thought they were getting away with something), with the minor exception of the dogs (who might eat the other animal's grain-based food out of jealousy, and explode their gut because they ate the wrong food because of stupidity)

I did not find that, unmonitored, most animals would eat too much of the wrong type of food for too long (loco-weed for cows might be an exception - but that didn't kill them).

Or no other animal is smart enough to be able to produce an abundance of food for the scale of population that we can. And also no other animal has capitalism which motivates actors to make the food supply as addictive as possible.

> Or no other animal is smart enough to be able to produce an abundance of food

It's not just the abundance of food, it's the sustained abundance. Many species follow a feast / famine cycle which puts pressure on stocking up as fast as possible during feast in order to survive the inevitable famine. This is the evolved instinctual mechanism which gets shot to piece by the "endless feast" available to many individuals in advanced economies (or wealthy enough individuals in pre-industrial economies), even more so combined with the physical "leisure" (limited requirements of extensive physical activity in day to day life).

Most of the other animals get eaten when they stop being athletic.

But some seem fine with layers of blubber. It's a feature, not a bug sometimes.

Other animals usually have a lifespan shorter than the time needed for atherosclerosis to be an issue

And the title is a bit incorrect, other animals do suffer with heart issues/"heart attacks" (usually congenital, but due to old age as well)

> Maybe no other animal is just that stupid.

They very much are, many pets will way overfeed themselves if given the opportunity.

Though it might also be human-inflicted, I don't know if wild animals will do so if provided with effortless unlimited amounts of food.

I would expect so though, most evolutionary environments simply don't set up organisms for an unlimited glut of free energy-dense food, when there's a glut of resources it's usually followed by some sort of crash, so organisms stock up as fast as they can in order to out-compete their peers once resources crash. If the glut doesn't end (which is essentially what modern advanced economies arrived at), neither does the tendency to stock up, because there's probably never been an evolutionary context (sustained for a long enough period) where that was an issue and thus allowed some organisms to outlive others.

There are quite a few instances where wild animals have almost unlimited food and reduced predators, in every instance I’ve heard of, they just breed like crazy.

Yes, even if the crash is not an environmental cycle, a crash will generally occur because the glut of resources allows a population explosion which eventually consumes the available resource.

This is one of the hardest systems effects to explain to people every time there is a deer cull; the population doesn't stabilize, it grows until the food runs out and then crashes with vast numbers of deer starving to death.

That a fair number of people still believe that it's more "natural", and thus better, for the bulk of the herd to starve to death rather than a percentage of the herd being hunted is one of the more curious animal rights positions.

> one of the more curious animal rights positions.

It makes sense from the point of view of "stop messing with it for fuck's sake".

Probably doesn't make the situation better one way or the other of course, deer population explosions are largely caused by humans having removed most of the top predators, and being significant stressors for the rest (https://www.theatlantic.com/science/archive/2019/07/humans-p...). The systems could probably recover if left alone, but that would require isolation (and mayhaps reintroductions) so predators can recover and retake their role, which is unlikely to happen outside of essentially exclusion zones like Pripyat / Chernobyl. Unless they're really unpopular / hard to access, most natural parks might have too much human presence for apex land predators to really be comfortable.

Yeah, I also have that argument all the time ... "the wolves are not coming back to farm country, we need to deal with deer overpopulation since we're the only apex predator left"

Some people are deeply offended by the idea that we are an apex predator.

https://www.youtube.com/watch?v=P9yruQM1ggc

People struggle with certain Trolley Problem formulations as well, probably for the same reason(s).

The unnatural aspect is that we have replaced their natural predators. Perhaps our careful management is sufficient, but there might be unforeseen functions of those predators which we are not fulfilling.

From the introduction: "There are many known risk factors, including blood cholesterol, physical inactivity, age, hypertension, obesity and smoking, but in roughly 15 percent of first-time cardiovascular disease events (CVD) due to atherosclerosis, none of these factors apply."

I wonder if a gone lost hundreds of years ago is somehow _responsible_, then why heart attack related death mostly occured in last 50 years?

It could be that they were not diagnosed as heart attacks before that.

edit: And also maybe general life style differences regarding availability and richness of food, exercise, shorter life spans etc.

In the 19th century, a heart attack may have been recorded as "old age", "sudden death", "apoplexy", "stomach cramps", "spasms", or a lot of other things. As long there weren't any suspicious circumstances I don't think they usually looked into it that closely.

I mean, this was when amputation and leeches was the pinnacle of medicinal triage. Life expectancy hit 49 in 1900 - for most of the 1800s it was below 40, a fact that still blows my mind today.

Life expectancy values were skewed a lot by infant mortality. This doesn't mean your average person died at 50.

Life expectancy @ 5y.o. (not sure about the exact age, but > 1y.o. is fine) is a better value to compare

So people had less time to "wear the heart out", they moved significantly more and their diet probably was better then our average as long as they could eat regularly.

For most their diet probably wasn't better than a modern diet, just different. If you max out at 40 years, it's difficult to tell if your diet is bad in old age.

Farmers and middle-to-lower class people only 90 years ago (as per my grandmother) in my region where mainly eating potatoes, grain, and meat, veggies and fruit were usually only eaten for sundays, since it was more expensive on the market.

That doesn't sound like the pinnacle of healthy diets.

Even farther back, people ate whatever they found or farmed with very little variety. If you don't get old, you can have some very unhealthy diets without much ill effect. Diets around the world in the pre-industrial era have ranged from 100% meat to 0% meat, with grain fruit and starches also ranging all over the 100%-0% scale.

...are you aware that most of that low life expectancy was caused by infant and child mortality? Once you lived past 15, you were expected to stick around at least to your 60s, if not more.

So yes, modern medicine is a Herculean effort in many ways. One of them is that it saves so many of our otherwise very frail and helpless children.

Thanks for this - I was using life expectancy at birth. Looks like it was around 55->60 from 1850->1900 if you lived to 5 looking at this chart: https://ourworldindata.org/uploads/2013/05/Life-expectancy-b...

The greatest risks to your health throughout history were (contagious) diseases and infections. With the advent of sanitation, food safety, modern medicine, etc., their percentage has dropped significantly.

But "you gotta die of something", so when one cause drops in rate, another rises. So if you're stubborn (lucky) enough not to die of anything else, it'll probably be either cancer or heart-related that gets you: up from 12% of all deaths in 1900 to 47% in 2010.[1]

In short, we're more likely to die of affluence diseases[2] if we're not dying of poverty diseases.[3]

[1] https://demography.cpc.unc.edu/2014/06/16/mortality-and-caus...

[2] https://en.wikipedia.org/wiki/Diseases_of_affluence

[3] https://en.wikipedia.org/wiki/Diseases_of_poverty

Interesting, I was always under the impression that chipmunks were susceptible to heart attacks. I can't remember where I read it and I can't find a current source but you are apparently not supposed to harass chipmunks because they can experience stress induced heart attacks when threatened/chased. I've also seen potential evidence for this when my cat chased one around a parking lot only for it to collapse after sprinting around for a solid minute. It was immobile, looked short of breath and eventually died at some point between when I brought my cat in and the next morning.

Rabbits, too.

The whole premise behind this headline seems bogus.

The headline seems bogus but the article says that "naturally occurring coronary heart attacks due to atherosclerosis are virtually non-existent in other mammals." Atherosclerosis is the cause of only "one-third of deaths worldwide due to cardiovascular disease" so other causes could still apply to other mammals. For example, "chimp heart attacks were due to an as-yet unexplained scarring of the heart muscle."

Of course we can give rabbits atherosclerosis by giving them high cholesterol from a diet they don't eat in the wild. But in humans, "in roughly 15 percent of first-time cardiovascular disease events (CVD) due to atherosclerosis, none of these [risk] factors apply," where risk factors include "blood cholesterol, physical inactivity, age, hypertension, obesity and smoking."

So the study explores a possible reason for that.

Elephants that live in savannas in Africa are prone to atherosclerosis, while those living in forest areas are not. [1] discusses that it can be due to food. In savanna elephants are forced to feed on grains and dry grass, while in forest they feed on leaves, which is probably more natural.

[1] Staffan Lindeberg. Food and Western Disease: Health and Nutrition from an Evolutionary Perspective

Ya, rabbits can die of heart attack if you startle them

The important animals are other apes and primates, when considering the evolution of disease. If none of them have it but humans do, then it likely came about recently. This means that it has independently evolved in humans and other animals (like rodents) that may have it. Makes for a misleading headline, though.

Apparently, after their hibernation, bears can have heart attacks too https://youtu.be/wT6GeJ9TsUw?t=52

But that would be from malnutrition, not atherosclerosis.

If this turns out to be true, I wonder if this is something CRISPR could fix...

Pets such as rabbits, hamsters, dogs are also prone to heart attacks. I think it has more to do with sedentary lifestyle. Unfortunately for most pets, it's not by choice.

And foods. Pets don't get the choice to eat loads of sugar and processed carbohydrates. It's usually some form of meats or vegetables depending if carnivore or herbivore.

We could probably edit in a working copy, but I wouldn't be so quick to do that: Sialic acids are all over our cells, and we don't understand what the difference is between the two sialic acid types in terms of impact on molecular environment. One plus side to losing this gene is our ability to do long distance running.

So the benefit of this gene is... we die of heart attacks unless we go jogging regularly? Where do I sign up to get it back?

The other benefit (of not having this gene) is post-birth brain development.

What is a development for animals might be a regression for us.

That's one of our many genetic differences but the article and paper don't include the word "brain." Do you have a source showing that it's related to this particular gene?

Oh, sorry for not including the source, earlier. Here it is: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC129338/

This could also be "fixed" by dietary supplement, but you run the risk of aggravating your immune system. One way to introduce this back into the system is by consuming red meat. The conclusion from this is EMPHATICALLY NOT that to reduce the risk of CVD due to meat consumption you should eat more red meat. The immune effects likely are more damaging.

I'm not sure that I wish CMAH gene back:

> Interestingly, the evolutionary loss of the CMAH gene appears to have produced other significant changes in human physiology, including reduced human fertility and enhanced ability to run long distances.

Reduced fertility doesn't seem for me important, we have a contraception for that. But enhanced ability to run long distances seems very convenient. I can ride a bicycle or walk for hours just for fun of physical exercise, and I'm not going to lose that.

I read somewhere that running very long distances is basically the only physical thing humans can do better than any other animal.

Pretty close. I heard that humans are second after dogs.

Depends on the weather. If it is hot, the sweaty human will win.

Per https://www.quora.com/What-animals-are-better-long-distance-... humans are best in hot arid places, horses are best in cooler temperate zones as the only other sweating animal, and dogs are best in cold climates, where their breathing isn't as badly affected by panting as it would be in hotter climates.

There's a few others. We have phenomenal dexterity and throwing ability, for example. We're also very competitive in other areas that are arguable whether they're "physical" abilities, such as visual acuity and ability to make sounds.

Humans have pretty good visual acuity, but unfortunately birds of prey have us beat.

Same, i heard it was so we could just run down prey we had injured.

Lots of animals can walk long distances just fine. If you don't run long distances, I'm guessing you wouldn't notice any difference.

I believe you would. Anyone would. Body didn't just stop working when you run faster or longer, body gradually develops pain. When you start to feel it, it feels not as a pain, but as a discomfort, which gradually becomes stronger, then it becomes pain, then it grows to an unbearable level. If your running/walking abilities were lower than they are, you would walk slower, to keep the same level of discomfort.

> Lots of animals can walk long distances just fine.

Not like humans. Humans walk faster than most of animals. As I understand it, it is due to aerobic ability mostly, human could absorb more of oxygen per minute and use it to oxidize glucose or fats to get ATP to power muscles. Other animals could absorb less oxygen per minute, so their body could output less power for a long time. Horse have 1 hp, but for relatively short amount of time. Then it needs to rest. Human could catch up with a horse before it managed to process all the lactic acid accumulated while horse moved (it needs oxygen to process lactic acid into ATP). This way human could outrun (or even outwalk) horse. (Maybe not the modern human with a car spending most of his day in a chair, but modern human have a car, so he could move faster than horse and for longer distances. So it does not counts.)

Though maybe it is not just aerobic ability, I think. Horse eats plants with a limited density of energy, it increases mass of horse, making it less energy efficient than human who eats foods with higher Kcal/gramm.

It seems that this guys never tried to catch a shrew.

I've seen a mouse die in a "humane" trap after being carried a couple blocks – I always understood that was from a heart attack. It seems to happen with birds too – stress them out a bit, then dead.

So in what way are "only humans" prone? Are these not heart attacks?

Probably time to agree on what "heart attack" means.

My Dad's heart stopped and he was kept alive by 45 minutes of CPR by burly firefighters - did he have a heart attack? Nope. His heart's pacemaker cells went on the fritz, but it wasn't a myocardial infarction.

A "heart attack" is a myocardial infarction, but many other bad things can happen to your heart.

Perhaps we evolved a heart overclocking ability. Sometimes we just push the heart too hard.

> Atherosclerosis -- the clogging of arteries with fatty deposits

What a way to start an article in a website with "science" in its name.

Atheroma is an accumulation of white blood cells. White. Blood. Cells. Not fat.

"Meat bad, saturated fat bad, eat your necessarily fortified grains and heart-healthy industrially extracted seed oils."

-oma is a suffix that means tumour. E.g. lymphoma.

-sclerosis is a hardening. E.g arthrosclerosis for a hardening of joints.

I fail to see what this has to do with my comment.

The hardening in atherosclerosis is caused directly and exclusively by atheroma.

Atherosclerosis refers to the buildup of fats, cholesterol and other substances in and on your artery walls (plaque), which can restrict blood flow.

https://www.mayoclinic.org/diseases-conditions/arteriosclero...

An atheroma, or atheromatous plaque ("plaque"), is an abnormal accumulation of material in the inner layer of the wall of an artery; it is present in the arteries of most adults.[1] The material consists of mostly macrophage cells,[2][3] or debris, containing lipids, calcium and a variable amount of fibrous connective tissue.

https://en.wikipedia.org/wiki/Atheroma

Pardon my confusion: is this comment for or against the parent?

"Plaque" and "atheroma" are synonyms in the context of cardiovascular health.

Also, both quotes together go to show the ongoing misconception. Nowhere in the first quote are macrophages and other WBCs mentioned (but they are in the second, luckily). I guess this is what happens when you use quotes from different sources, too.

Everything I've ever read says fatty deposits. The NHS website calls fatty deposits "atheroma". You can find multiple definitions of atherosclerosis/atheroma in other places describing them the same way. Wikipedia says:

"While the early stages, based on gross appearance, have traditionally been termed fatty streaks by pathologists, they are not composed of fat cells but of accumulations of white blood cells, especially macrophages, that have taken up oxidized low-density lipoprotein (LDL)."

So whilst it may be more accurate to say they are white blood cells that fed on LDL (and presumably contain fatty substances as a result) there is a long tradition of calling them fatty substances, and there is at minimum a connection to fat.

It seems misleading to try to discount the role of the fat to me. They don't sound like they are just normal white blood cells. Is there any doubt that the fat plays a causative role? I know a couple of cardiologists who say it is clear. Do you have some references for the idea that fat is not relevant?

I see. Yeah calling stuff wrapped in macrophages 'white blood cells' is a bit confusing, given that macrophages will wrap around just about any substance that your immune system tries to remove.

What do those cardiologists say? That fat in the blood (triglycerides) causes atherosclerosis? Or dietary fat? Very different things.

Regarding the mechanism of atheroma formation, I don't have a list of references handy, but maybe this is a good start: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152836/

Also of interest would be the role of high insulin and/or glucose and the damage they can cause to the arterial walls (inflammation is a necessary condition in the formation of atheroma).

The conventional wisdom: fat in the blood is the main thing to worry about (along with genetics) and that lifestyle factors have a big influence on that. So both, really.

Which part of that paper disputes the importance of fat?

I want to call attention to the "oxidized" part of "oxidized LDL" as that's what makes LDL so dangerous. While pathologies of LDL and fat hog the limelight, it's important to keep a close eye on the third villain in the fight against AS and that is immune system pathologies mainly chronic inflammation.

Immune cells kill using peroxides, superoxides and other free radicals. Anyone with an over-active immune system that's triggered easily — allergies, chronic stress, sub-optimal sleep, genetics, exposure to pollutants, metal ions etc¹ — you're better off reducing immune system activity.

So yes, eat less fat but also focus on the immune system. A study found 29% of Japanese babies less than 1 year old had fatty streaks and they were not spending the first 11 months chugging slurpies and McDs.⁴

TL;DR: Dietary fat and adipose tissue/adipocytes involved in AS are two different things⁵, and try not to get oxidized to death by a glitchy immune system while busy chasing fats or the latest fad diet. Fats are just one piece of the puzzle.

---

¹Mechanisms of LDL oxidation: http://sci-hub.tw/10.1016/j.cca.2010.08.038

²This means sleeping better, reducing stress, taking anti-oxidants, reduce insulin triggers i.e., reduce food with IF/ADF/CR³ and reduce carbs

³Intermittent Fasting/Alternate-Day Fasting/Calorie Restriction. This study finds ADF to be superior to CR; if you can stick to it, that is: Differential Effects of Alternate-Day Fasting Versus Daily Calorie Restriction on Insulin Resistance — http://sci-hub.tw/10.1002/oby.22564

⁴https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812791/ - conjecture is the mothers were smokers, see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2644569/ for more info. Pollution should be focused more strongly when it comes to heart health, the evidence is clear.

⁵Any excess energy gets stored as fat, so reduce fat intake but increase protein or carb intake to compensate? No dice, the body will generate fat for you in the form of adipose tissue which will lead to AS in the presence of an unregulated immune system.

Helpful comment. I have an overactive immune system and I'm always on the lookout for ways to get it to relax.

I've done elimination diets and had blood tests to determine foods I react to. I've also met with nutritionists to create meal plans. But over the long term I tend to gravitate back to foods that my family and friends tend to eat which includes stuff that jacks up my immune system (kid didn't finish her mac and cheese? I'm on it!...visit my Italian mom? pasta time!)

So how do you keep to what you know you should do when other people in your life are doing things to the contrary?

I assume you're talking about celiac disease? If you have already sought professional help I don't think there's anything new I can tell you besides the usual suspects like "grit your teeth and stick to the diet" or "find someone who can keep you on track like wife, siblings or friends".

That said, if I was in your position and if I couldn't tackle the problem in any of the standard ways, I'd take an NSAID like aspirin¹ on "cheat" days to temporarily suppress the immune system as an experiment and see how that works. I found a 1982 issue² of The Lancet where someone had the same idea and reports success with this strategy but I'm not even close to a medical professional and this is just one data point so YMMV, caveat emptor etc, etc.

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¹But not ibuprofen or other NSAIDs, those seem to worsen the problem — https://www.thedailybeast.com/research-shows-link-between-ns.... Aspirin however has its own set of side-effects (bleeding risk, may interact with medication you are already taking etc) so strict diet is still the safest, long-term solution for now.

²http://sci-hub.tw/10.1016/s0140-6736(82)90024-1: 650mg Aspirin, 5-15 mins before meals, not after. Again, this is NOT medical advice, it is just one data point.

Atherosclerosis:

https://lmgtfy.com/?q=Atherosclerosis

"When plaque (fatty deposits) clogs your arteries, that’s called atherosclerosis."

~ American Heart Association (https://www.heart.org/en/health-topics/cholesterol/about-cho...)

"Atherosclerosis is a disease in which plaque builds up inside your arteries....Plaque is made up of fat, cholesterol, calcium, and other substances found in the blood."

~ https://www.nhlbi.nih.gov/health-topics/atherosclerosis

"Atherosclerosis refers to the buildup of fats, cholesterol and other substances in and on your artery walls (plaque), which can restrict blood flow."

~ https://www.mayoclinic.org/diseases-conditions/arteriosclero...

For the rest of readers confused about this thread - Peter Attia (longevity & performance focused doctor) did a long blog series on atherosclerosis

https://peterattiamd.com/the-straight-dope-on-cholesterol-pa...

my TL;DR (as a non-doctor): LDL "cholesterol" (actually proteins carrying cholesterol and "fat" (triglycerides) in blood) has a tendency to get "stuck" in artery walls. That causes inflamation, which attracts macrophages which also get stuck, and so on until you get plaques ("clogged arteries") and one plaque breaks off and causes a heart attack. Consuming saturated fat / cholesterol is problematic because it causes a decrease of LDL-sensitive receptors and consequentially more LDL in blood. If I understand correctly, the later part of the previous statement is considered settled science ("we know how it actually works" - 1985 Nobel Prize was awarded for this), while the first part (diet) seems to be somewhat debated and has mostly statistical justification ("evidence suggests") and also depends on an individual's genetics.

Would you please supply references, and perhaps some more context?

judging by the tone and wording, OP just seems like another defensive Keto advocate you find on every post that mentions anything about meat or fat being bad...

So now we're including "survival of the unfittest" as part of evolutionary theory? Sorry, this makes zero sense. If humans really did evolve, then we hit the lottery - several times.

Where did you guys suddenly appear out of nowhere on HN? On a programmer forum, skeptical of evolution?

This is the second time I see skepticism about evolution is brought up on HN comments. Science literacy of the community definitely went down.

Fitness doesn’t mean what you think it means. As others have noted on this post, this mutation confers some resistance to malaria.

When the options are “malaria with high probability from birth onwards” or “heart attack after multiple decades with high probability if nothing else kills you first”, this is fitness.

Besides which, if humans didn’t evolve, you need to explain why the creator didn’t use a better mechanism to prevent us from getting malaria. For example: not creating malaria when they created us.

I like how the headlines explicitly states humans.

For yet another study in ... mice.

There are other options like dogs and pigs which are much better models for human biology, so if you really want to make a claim about subtle effects of human genetics you need to be as close to a human model as possible.

This is entirely ignoring the someone generous leap they make that one single gene mutation is responsible for an increased rate of heart disease. It also doesn’t touch on what the benefits for that gene were (to spread through the gene pool completely it must have some benefit that outweighs the cost)

Further down in the study it says that removing the gene likely occurred because it made humans more resistant to malaria, and somehow it also enhanced the ability to run long distances.

If this withstands scrutiny a chimpanzee study can't be far off, though.

Nah. Primate studies are too expensive, impractical and ethically difficult to justify. Think about the number of subjects you would need for statistical significance ...

At this point this is only a hypothesis. This is clear when they say "may help explain", "may have resulted", and "believe".

#JustSayInMice! https://twitter.com/justsaysinmice

* Hyped-up science is a problem. One clever Twitter account is pushing back.

https://www.vox.com/future-perfect/2019/6/15/18679138/nutrit...

Just for some background for those who weren't aware what is the OP all about. But to be fair, I think this article is actually well-written and doesn't contain sensationalized framing.

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