Tuesday, March 12, 2013

Atherosclerosis in Ancient Mummies Revisited

Many of you are already aware of the recent study that examined atherosclerosis in 137 ancient mummies from four different cultures (1).  Investigators used computed tomography (CT; a form of X-ray) to examine artery calcification in mummies from ancient Egypt, Peru, Puebloans, and arctic Unangan hunter-gatherers.  Artery calcification is the accumulation of calcium in the vessel wall, and it is a marker of severe atherosclerosis.  Where there is calcification, the artery wall is thickened and extensively damaged.  Not surprisingly, this is a risk factor for heart attack.  Pockets of calcification are typical as people age.

I'm not going to re-hash the paper in detail because that has been done elsewhere.  However, I do want to make a few key points about the study and its interpretation.  First, all groups had atherosclerosis to a similar degree, and it increased with advancing age.  This suggests that atherosclerosis may be part of the human condition, and not a modern disease.  Although it's interesting to have this confirmed in ancient mummies, we already knew this from cardiac autopsy data in a variety of non-industrial cultures (2, 3, 4, 5).
The more important point is that atherosclerosis does not equal heart attack.  Atherosclerosis is an important risk factor, but extensive cardiac autopsy studies have suggested that traditional cultures with near-zero heart attack incidence have coronary atherosclerosis (6, 7, 8, 9).  Although they tend to have less atherosclerosis than industrial populations when adjusted for age, differences in atherosclerosis alone cannot explain their remarkable resistance to heart attacks: other factors must be involved.  These could include the tendency of the blood to clot, the tendency of atherosclerotic plaque to rupture, and perhaps the diameter of the coronary vessels.  

Some have used the mummy paper to argue the view that it's silly to try to eat like our ancestors because they got sick just like we do.  The paper does not support this view, for two reasons.  First, as I said previously, atherosclerosis is not the only risk factor for heart attacks, and we have extensive cardiac autopsy data from multiple non-industrial cultures indicating that the actual rate of heart attacks was very low, even when adjusted for age (10, 11).  And second, although arterial calcification was common in all cultures represented by the mummies, it was less common in the coronary arteries, where it matters most for heart attack risk.  

The paper reported that only 4 percent of ancient mummies showed coronary calcification, with a mean age at death of 36 years (77 male, 44 female).  However, this figure is misleading because it includes mummies in which the heart was absent and no measurement could be made.  If we use the number of mummies that included hearts as the denominator*, the percentage jumps to 15 percent of mummies with coronary calcification.  Two of the 6 mummies with coronary calcification were Unangan arctic hunter-gatherers (2 of the 6 Unangans examined).  These people had an extreme diet and lifestyle by necessity, and it's possible that something about their lifestyle was bad for the coronaries (low plant food intake, constant smoke inhalation?), though the sample size was too small to draw statistical inferences about the Unangan population as a whole.  If we remove Unangans from the analysis, only 10 percent of the mummies exhibited coronary atherosclerosis.

If we want to compare these data with modern populations, we have to compare specifically with studies that examined calcification.  We can't compare with studies that looked at less severe forms of atherosclerosis by autopsy or other imaging techniques (e.g. fatty streaks), because these are much more prevalent than calcification.  Most studies that specifically examined calcification indicate that calcification of the coronary arteries is roughly twice as prevalent in modern populations as it was in the ancient mummies  when comparing people of a similar age (12, 13, 14), though some have found a similar prevalence (15).

This is consistent with autopsy data from contemporary and historical non-industrial populations, which indicates that they do have coronary atherosclerosis, but usually to a significantly lesser extent than modern industrial populations (16, 17, 18).  The mummy data do not overturn our thinking about atherosclerosis; they simply confirm what we already knew from other sources: developing atherosclerosis with age is part of being human, but the modern diet and lifestyle increase its severity, particularly in the coronary arteries, contributing to a higher risk of heart attack.

* For this calculation, I used intact hearts = 1 and heart "remnants" = 0.5 to get an estimated denominator.


Tucker Goodrich said...

Excellent analysis.

Paul N said...

Well, at least here's a case when they can Xray people as much as they want with no adverse effects!

so something(s) in modern life make atherosclerosis more likely to result in heart attacks?

if we suspect dietary causes, I'd place my money on Weston Prices's "displacing foods of modern commerce" (refined flour, sugar, processed foods)

Could also be deficiencies in magnesium, K2, or excess n-6 PUFA, all of which can be caused by said modern foods.

Other lifestyle factors are likely involved too, though its harder to compare those...

Anonymous said...

Theory: those who were mummified were atypical of their cultures -- e.g., royalty -- and ate atypical foods.

Puddleg said...

Isn't it also possible to determine smoke exposure from the mummies? Soot particles ought to be persistent.
It would be nice to rule this out, or compare it between groups.

Anonymous said...

Thanks for this, Stephan. I would like to add that there is a distinct difference between arteriosclerosis, which more or less is a fact of life, and atherosclerosis with inflamed, unstable atheroma. It's impossible to see the difference in mummies.

Gretchen said...

I found the most interesting thing about this article the comment that autopsies of soldiers killed in recent wars had much less atherosclerosis than those killed in Korean war.

What has changed since then?

More kids are probably raised on skim milk. But also, more kids eat fast food and snack more, both types of foods high in unhealthy fats and fast carbs.

There's less phys ed in schools today, and fewer kids walk to school. Does exercise cause atherosclerosis? I don't think so.

Finally, in Korean war, soldiers were drafted. Today they're all volunteer. Is there a difference in the type of young person who volunteers from the type who doesn't?

Gretchen said...

I can't access full text of that article. Maybe the comment about atherosclerosis in soldiers was from a commentary on the article.

Marwan Daar said...

Stephan, have you considered that perhaps their diet wasn't necessarily the healthiest? According to http://www.touregypt.net/featurestories/diet.htm cereals and breads were a staple in their diet.

Also, when you look at the data from this study: http://blogs.discovermagazine.com/80beats/?p=43011#.UUCGxzfSmF3 you see signs of dramatic changes in oral health after the introduction of a carbohydrate rich diet in the neolithic period. Granted, this was a study of European skulls, but still.

Unknown said...

Gee, I didn't even notice that they were counting mummies without hearts in the coronary Atherosclerosis stat. Seems a bit sneaky.

Unknown said...

Also even though it is inappropriate to use this data to compare to modern cultures, if you do, as I pointed out in my post, the rates of atherosclerosis in mummies are much much much lower than in modern populations. For example, in one of the studies referenced in the paper, all modern teenagers had atherosclerosis, whereas the atherosclerosis detected in mummies skews older and is not as ubiquitous.

Jenny said...

The most likely factor that differentiates us and these pre-agricultural peoples is their heavy burden of parasites. There evidence that many of our autoimmune diseases are caused by the absence of parasites our immune system has evolved with would point that way. Since inflammation is a key part of heart disease, an immune system busy fighting worms and other parasites doesn't have the energy or motivation to attack the vascular system.

The other important issue always forgotten in these studies is that those who survived to the age of 35 were the very tough ones. Infant mortality was high and childhood diseases and infections after accidents would have weeded out those with anything but excellent constitions. Letting our weaker babies die would probably cut down on the incidence of heart disease, but I don't recommend it.

BigNanoDoc said...

Very interesting.......now, add to the equation that our studies/science (NanoBiotech Pharma - http://www.nanobiotech.us ) shows that coronary artery calcification is secondary to infection by CNPs (aka Nanobacteria). This “OLD” study shows less prevalence of Coronary artery calcification for several reasons: 1) Over the eons, the infectivity of Nanobacteria has become worse/greater. 2) The average age of death was age 36........not long enough for the CNPs to cause significant
Coronary aretery calcification/vulnerable plaques and plaque rupture--->heart attack. If they would have lived longer, they would have had more coronary artery calcification.

You can review our published science (full articles-not just abstracts) at http://www.nanobiotech.us
Gary Mezo, Chairman/CEO NanoBiotech Pharma

Anonymous said...

excellent critique thank you and i will share it. additionally, they are calling our ancestors from 5,000 years ago "hunter gatherers". seems to me that they should to go back another 5,000 years at least to make that claim. were not these mummies from a post-agricultural, grain eating culture rife with dental decay, arthritis and other modern day diseases of civilization?

Gretchen said...

I think surviving lots of childhood infectious diseases means you have a strong immune system, but I don't think it protects you from heart disease. Sometimes the reverse. Rheumatic fever *causes* heart disease.

Travis Culp said...

Thanks for the post, Stephan.

Personally, my money's on magnesium intake. For those consuming (especially whole) grains, the heavy phytate levels would bind with magnesium to form insoluble complexes that would be excreted. For the Unangans, the low intake of plant matter and maybe soft water (do they drink melted snow?) would greatly decrease magnesium intake.


J Good said...

Maybe this has been said, but is there not a huge difference between pre-agricultural society (AKA Paleolithic) and the time when the mummies were living? These Mummies were very likely relatively mono substance eaters of agricultural based foods like GRAINS. I don't think any useful correlation can be drawn from mummies arterial condition and a Hunter gatherer's condition. They had vastly different diets.

Unknown said...

It's clear that the mummys like medieval age kings ate the Western diet.

BigNanoDoc said...

For those of you with more interest, there was a scientific publication in Nature Genetics Feb 2013
(02/18/13) "Sequencing ancient calcified dental plaque shows changes in oral microbiota with dietary shifts of the Neolithic and Industrial revolutions" Essentially describing Nanobacteria/pathological calcification in neolithic-man's dental calculus....showing an increase in dental calculus as the neolithic man went from hunter-gatherer to farmer. BTW, the pathological calcification found in dental calculus (plaque) is the same calcification as is found in calcified coronary artery plaque.......both infectious and both DIRECTLY secondary to Nanobacterial infection. Again, read the science on our website: http://www.nanobiotech.us
Gary S. Mezo, Chairman/CEO
NanoBiotech Pharma

aluchko said...

Excessive Vitamin D can cause artery calcification, could a factor here be the fact that these people spent a lot more time outside and got a lot more Vitamin D than us?

Sara said...

I wonder about the social status of these mummies. Could it be that the mummies that are easily found (assuming then, in more well documented or larger sites) would be the rich of their time, with more access to rich food and less need for physical activity?

Tom A said...

For what it’s worth:



Tom A said...

Vitamin D supplements can divert calcium from bones to arteries, kidneys etc, but not sunshine.

Gretchen said...

I think this study is interesting, but one shouldn't use it to prove anything about our modern diet.

The only hunter-gatherers in the study were the Inuit, and there were too few to conclude anything. Also, because of their climate, they had a very different lifestyle and different nutritional needs. But popular press suggested all the mummies were paleo types.

Intentionally mummified Egyptians were mostly upper class, which did less physical labor and had a different diet (abundant meat and sweets as well as grains) from lower classes, which ate mostly bread and onions.

Using a study like this to support your pet theory about one nutrient or type of food is one reason our understanding of nutrition is so muddled.

Unknown said...

I've been wondering why this wasn't pointed out. Isn't it obvious? Anyone who knows anything about world history knows the agricultural revolution was ten thousand years ago, while these mummies are from four thousand years ago. They do not represent pre agricultural humans at all. Once we find a pre agricultural human with atherosclerosis then these researchers have some evidence to support the inherent nature of heart disease, but until then they just don't.

Travis Culp said...

Nathalia: I think you'll find that agriculture wasn't unanimously adopted by all human populations globally at the same moment 10,000 years ago.

Jane said...

Travis said 'Personally, my money's on magnesium intake. For those consuming (especially whole) grains, the heavy phytate levels would bind with magnesium to form insoluble complexes that would be excreted.'

This idea is based on experiments in which purified phytate is added to white bread.
'Phytic acid added to white-wheat bread inhibits fractional apparent magnesium absorption in humans'

However the whole grain contains fermentable fibre which promotes Mg absorption.
'Effects of dietary fibers on magnesium absorption in animals and humans'

You could be right about magnesium though, if it's true that rich Egyptians ate white bread. Rich people throughout the ages are suppposed to have done so.

But that doesn't explain atherosclerosis in the other three groups. Perhaps theirs had its origin in episodes of starvation.

Dale said...

Upper class, Nile, four thousand years ago? Definitely eating grains and drinking beer. They'd been cultivating emmer wheat and barley since circa 6,000 B.C.

Anonymous said...

Dr. Guyenet,

Please disregard the comment I sent yesterday, which you have not yet posted. My post was based on the prevailing opinion that the development of civilization along the coast of Peru was based only on maritime resources inasmuch as no evidence of significant agriculture had been found. That is, until recently, as indicated in the attached article which describes discovery of pollen residue from corn and sweet potatoes at the Norte Chico site in Peru. where a complex of small cities arose about the same time as Sumer, circa 3500 bc.


Robert said...

Dear Dr. Guyenet,

We have a paper in press that shows a potential effect of chronic infection (from Chlamydia pneumoniae) on progression of atherosclerosis (as measured by coronary artery calcification).


Chronic infections do seem to exacerbate atherosclerosis and may explain the ubiquity of the condition even in pre-modern man.

Stephan Guyenet said...

Hi Dr. Wright,

Very interesting, thanks for passing that along. Perhaps infection will end up being an important factor in all this-- with the direction of the effect depending on the organism.

BigNanoDoc said...

Robert....FYI: Nanobacteria cause calcification, inflammation and also cause a false positive on chlamydia tests......

Jane said...

About infection: there seems to be a link between infection and low birth weight, and also between low birth weight and cardiovascular disease.

'Prolonged impairment of cellular immunity in children with intrauterine growth retardation'

'Impact of Low Birth Weight and Cardiovascular Risk Factors on Endothelial Function in Early Adult Life'
'..Low birth weight is related to increased risk of coronary heart disease in adults and recently has been associated with vascular endothelial dysfunction in children. ..'

Unknown said...

Hi Dr.guyenet.
I have a question that is off-topic regarding your food reward hypothesis. I have been reading your back and forth debates with Gary Taubes, and was a left a bit confused.
I'd like to know if Food Reward works solely by increasing appetite (and subsequent food intake) or if it also works by stimulating neurochemical pathways INDEPENDENT OF CALORIES.
For example, studies have shown that non-caloric artificial sweeteners are just as fattening as sugar. Is this solely because artificial sweeteners lead to increased food intake?
If we were to do a controlled study, giving the control group a 2000 calorie diet and the intervention group an identical 2000 calorie diet, but supplementing the intervention group's diet with liberal amounts of artificial non-caloric sweeteners; would the intervention group gain more weight even though the diets were Isocaloric?

Stephan Guyenet said...

Hi Marcus,

There is not any serious debate over whether food reward/palatability influences food intake-- it does. Whether this occurs despite homeostasis circuits or because of them is less clear. There is some evidence that reward/hedonic circuits influence energy homeostasis circuits to actually influence the 'defended' level of fat mass rather than just overriding homeostasis circuits.

My personal opinion is that both are true. Reward/hedonic circuits can make you eat even if satiety circuits are telling you 'no'. But they also seem to be able to trigger hunger and reduce satiety itself. There is some evidence that reward circuits can influence energy expenditure, at least in animals, so it may be acting on both sides of the energy balance equation. But that is not 100% certain yet.

I don't know the answer to your final question, but I'd like to.

Stephan Guyenet said...

I want to clarify that it is not "my" food reward hypothesis. I'm simply relaying the scientific consensus that has emerged from other peoples' work in the field. I didn't come up with any of the ideas myself-- I just presented them in a way that's more accessible to the public.

Sanjeev said...

> if Food Reward works solely by increasing appetite (and subsequent food intake)
not necessarily ... sometimes people are driven to eat by "rewarding" food that they actually don't want more of.

rewarding foods drive eating behaviour. I think this can operate independent of appetite.

satisfying appetite is pleasurable and the reward system doesn't necessarily provide pleasure, but rather promises pleasure if the organism does the driven behaviour.

Look up Olds & Milner's rat experiments with stimulating the "pleasure centre"

Sanjeev said...

that's part of the answer to your question, not the whole answer.

Unknown said...

I have been following the Paleo diet for a few months now, and listen to Robb Wolf's podcast regularly.

I have a B.A in archaeology.I've been wondering how Wolf and others concluded that ancient hominids didn't have atherosclerosis and other diseases that we suffer from today. The archaeological record has always stated that yes, these diseases have been around for a long time, so why is this article's topic considered news?

George Adventures In Health said...

What does the data show for modern HG societies, with respect to atherosclerosis?

Surely this data would add to our knowledge of the changes in diet brought about by agriculture and industrialisation?

George Adventures In Health

Unknown said...

I think it is a very old news that cardio and vascular blockages found in a mummy. Even veins are found blocked in some mummies.

Robert said...

Hi Dr. Guyenet,

Here is an interesting review in NEJM from this month examining the mechanisms of acute coronary events, and why plaques rupture, out of Harvard.