Emily raised a great question in response to last Tuesday’s post:
[W]hat of the reports of hunter gatherers having low cholesterol. Is it the product of fringe environments, or low infectious burden, or what?
Let’s look into this. Do hunter-gatherers in fact have low cholesterol? If so, why?
The Claim
As far as I know, this idea originated with and was promoted by the fathers of Paleo dieting, S. Boyd Eaton and Loren Cordain, and their collaborators.
Its first appearance, to my knowledge, was in a 1988 paper by S. Boyd Eaton, Melvin Konner, and Marjorie Shostak called “Stone agers in the fast lane: chronic degenerative diseases in evolutionary perspective” [1]. Here’s their data:
The footnote to Table IV reads as follows:
The published paper has 101 references and takes 11 pages in the journal, yet no supporting references for the cholesterol data were included.
Here is a graph from a 2004 paper by Loren Cordain, William Harris, and some pro-statin medical doctors [2] (thanks Stabby!):
The caption states that total cholesterol (TC) ranges between 70 and 140 mg/dl in hunter-gatherers, and LDL cholesterol (LDL-C) between 35 and 70 mg/dl. However, this claim is unsourced. The paper provides references for assertions that LDL tends to be around half TC, and that modern Americans have TC around 208 and LDL-C around 130, but there are no references for hunter-gatherer cholesterol levels.
The data in this graph seem to be drawn from the Eaton, Konner, and Shostak paper [1]. The Hadza number is the same as the 109.5 mg/dl (2.83 mmol/l) average of the male and female Hadza in [1]; Inuit at 141 mg/dl (3.65 mmol/l) is the same as “Canadian Eskimos” in [1]; !Kung and San (probably the same people) are both listed very close to the 119.5 mg/dl (3.09 mmol/l) average of “Kalahari San (Bushmen)” in [1]; Pygmy looks identical to the 106 mg/dl average of male and female “Congo Pygmies” in [1]. It looks like they just copied from Eaton et al but deleted the Australian Aborigines who in [1] had a male-female average TC of 139 mg/dl (3.59 mmol/l).
Eaton and Konner were sticking to the low hunter-gatherer cholesterol claim in 2010 [3]; they cited only their original 1988 paper [1] when they wrote:
Our review of various health measures in HG and other nonindustrial populations showed that average HG serum total cholesterol was always below 135 mg/dL … [3]
So over 23 years, to judge by these papers, Eaton et al and Cordain et al have yet to cite a peer-reviewed article in support of the proposition that hunter-gatherers had low cholesterol. Where did this idea come from? And is it true?
The Evidence Is Worth Looking Into
The claim that healthy hunter-gatherers had serum cholesterol below 140 mg/dl is quite surprising, given that contemporary populations are healthiest when their serum cholesterol is over 200 mg/dl, and mortality rises and life expectancy falls sharply as serum cholesterol falls below 180 mg/dl. (See Blood Lipids and Infectious Disease, Part I, Jun 21, 2011.)
Are hunter-gatherers – either their diets or their genetics – so different from modern populations? Or is the claim that healthy hunter-gatherers have low serum cholesterol a mistake?
I think this is an interesting question, with implications both for the design of Paleo diets and for our interpretation of serum lipid results. When we discussed HDL, I argued that some dietary methods to raise HDL might benefit us by enhancing immunity (see HDL and Immunity, April 12, 2011; HDL: Higher is Good, But is Highest Best?, April 14, 2011; How to Raise HDL, April 20, 2011). Might a similar strategy for dietary manipulation of LDL be desirable too?
Next Steps
I’ll examine the issue in 3 parts:
- On Thursday I’ll survey the literature on hunter-gatherer cholesterol. What are their numbers really?
- Next week I’ll continue the Blood Lipids and Infectious Disease series by looking at the immune functions of LDL cholesterol. What happens to LDL when people get infections? Is there an optimal LDL level?
- In conclusion of the series I’ll return to the issue of human populations – whether hunter-gatherer, horticultural, pastoral, or modern – and what their cholesterol levels tell us about their health. Why do some populations have low serum cholesterol and other populations have much higher cholesterol?
This might lead us into issues such as: Has there been recent human evolution toward higher cholesterol levels? Are there biological differences in optimal cholesterol levels among different human populations – for instance, Africans and Eurasians, or aboriginal populations and descendants of Neolithic farmers?
Should be fun!
Related Posts
The posts in this series are:
- Did Hunter-Gatherers Have Low Serum Cholesterol?, Jun 28, 2011
- Serum Cholesterol Among the Eskimos and Inuit, Jul 1, 2011
- Serum Cholesterol Among African Hunter-Gatherers, Jul 5, 2011
- Serum Cholesterol Among Hunter-Gatherers: Conclusion, Jul 7, 2011
- Low Serum Cholesterol in Newborn Babies, Jul 7, 2011
References
[1] Eaton SB, Konner M, Shostak M. Stone agers in the fast lane: chronic degenerative diseases in evolutionary perspective. Am J Med. 1988 Apr;84(4):739-49. http://pmid.us/3135745. Full text: http://www.direct-ms.org/pdf/EvolutionPaleolithic/EatonStone%20Agers%20Fast%20Lane.pdf
[2] O’Keefe JH Jr, Cordain L, Harris WH, Moe RM, Vogel R. Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal. J Am Coll Cardiol. 2004 Jun 2;43(11):2142-6. http://pmid.us/15172426.
[3] Konner M, Eaton SB. Paleolithic nutrition: twenty-five years later. Nutr Clin Pract. 2010 Dec;25(6):594-602. http://pmid.us/21139123. Full text: http://ncp.sagepub.com/content/25/6/594.full.
via this link:
Excellent stuff, Paul! I’m looking forward to Thursday’s installment on the real numbers.
I’m looking forward to this too. This blog is more fun than a barrel full o’ raccoons.
I’m not adverse to the idea that some hunter-gatherers had low cholesterol and were healthy, although I still don’t know if any did. Indeed, the optimal range for LDL in Western populations certainly isn’t low, but that is Western populations. LDL will tend to be lower when there is less inflammation, insulin resistance and deficiency. The general population is going to have a good deal more of that bad stuff going on than we do and the ones with the more highly useful LDL (step up from artery-clogging-LDL, eh?) do better, but their optimal range might be lower with less of the bad stuff going on. Still 30 mg/dl scares me. If I had that I would be trying to figure out how to eat a brick of butter without puking. I certainly don’t think higher is worse if it is pattern A and simply the combination of genetics + various lipids.
Stabby,
Dr. Ayers over at the Cooling Inflammation blog argues that higher levels of inflammation in Western countries might be protective against some infectious diseases. Sounds plausible, in the light of the fact that aborigines would go down like flies when contracting some diseases that had been considered mild by the western standards. (well I don’t have any numbers for this, but I presume that this is true based on what I can browse in the archives of my phenomenal memory 🙂
Yup, TC under 160 is when the risks of suicide and accidents and violent death seem to go up – correlatively – also correlates with lower amounts of serotonin in the CSF (which also separately correlates with suicide and violence) – and since lots of fresh cholesterol seems to be needed for the serotonin receptors to work well, there is a plausible biologic link there – of course it is all speculation, and the risk studies were done in modern industrial humans – but it still doesn’t seem to add up to me that a so-called “normal” ancestral cholesterol would be around 130. Wild primates are interesting to compare – but then their brains aren’t nearly as big or as hungry as ours comparitively – what about a dolphin? Hmmm.
Who knows? Maybe the higher cholesterol number shown in the graph for adult Americans is an indication that — all things considered — we have a better health status than any of those primitive peoples. Somewhere I’ve read that many of those primitive folks didn’t have a particularly long life span. And as Emily mentioned, we definitely have an apples-to-oranges situation when we start comparing humans to other creatures.
We all have to die of something. If heart disease is currently “the number one killer,” that means that other, possibly scarier, things are in 2nd- or 3rd- or 217th-place. Attempts to beat down heart disease by beating down cholesterol numbers with drugs might eventually shift heart disease out of first place by causing death from other system failures. But I’m not sure it will be any kind of victory.
How about the HDL, tot cholesterol and LDL of long lived Asian populations? My understanding is that Total Cholesterol is low as is LDL; i do not know about HDL. There sat fat intake is less than ours, and they consume more polyunsaturates, i believe. Any thoughts on that?
Hi Stabby,
Not persuaded that lower inflammation means less LDL … It’s a bit complex … Let’s discuss later in the series.
Hi Tomas,
Diet-induced inflammation does indeed protect against some infections but it usually increases risk of other infections. There are many kinds of “inflammation” and different kinds work against different pathogens. The immune system has limited resources so when it gets inflamed a certain way, there are fewer resources to fight other types of infections.
Aboriginal populations are indeed more vulnerable to infectious disease than Neolithic ones, but it’s usually thought this is due to genetic changes in sensitivity, eg MHC gene changes, not to LDL changes. It’s a question we might get to later.
Hi Emily,
You know my view … TC under 160 indicates high infectious burden … infection in the brain causes low serotonin and all sorts of mental problems … so I think the pathway may be via immune-infection rather than simple cholesterol transport.
Hi Marilyn,
Sage points … you’re anticipating my series.
Hi Steve,
Most East Asian populations have higher LDL, HDL, and TC than European populations. I haven’t seen measures linking LDL to longevity in Asian populations, but I’ll keep an eye out.
maybe its a seasonal thing…like vitamin D levels…
Hi Paul,
Cordain, Eaton, et al., give some references in a 2002 paper. They write:
“Over the past 64 y, anthropological research has consistently demonstrated relatively low serum cholesterol and triaglycerol levels among indigenous populations that derive the majority of their diet from animal products (Bang & Dyerberg, 1980; Bliss et al, 1971; Corcoran & Rabinowitch, 1937; Day et al, 1976; Eaton et al, 1988a; Leonard et al, 1994; Scott et al, 1958; Shaper et al, 1961; Wilber & Levine, 1950).”
Cordain L, Eaton SB, Miller JB, Mann N, Hill K. The paradoxical nature of hunter-gatherer-diets: meat-based, yet non-atherogenic. Eur J Clin Nutr. 2002 Mar;56 Suppl 1:S42-52
http://pmid.us/11965522
Thanks, Rob. I’ve already been through some of those references and I can tell you they come from only 3 peoples — Eskimo, Masai, and Evenki herders — and the Eskimo papers all show mean cholesterol of 214 to 218 mg/dl. The other two peoples are not hunter-gatherers.
It seems like every time someone says “here’s a study that show’s high cholesterol isn’t dangerous” or “lower mortality with higher cholesterol” they’re referencing a total of 210 with and HDL of 100. Since I started eating Paleo my LDL went from 160 to 245 mg/dl with very low inflammation (CRP 0.2)
315… that’s what I consider “high” cholesterol. Curious to see what the HG’s really had. Looking forward to the next installment
This blog continues to be awesome and interesting… I can’t wait to see your later posts!
As I mentioned on Chris Masterjohns blog, I am a bit concerned over high LDL particle counts (independently of particle size or total cholesterol) as that is likely to be an accurate proxy for both LDL receptor function and the average lifetime of an LDL particle in the blood (based on mathematical models of LDL endocytosis). I wish we had some data on the particle counts in hunter gatherers, rather than just total cholesterol or total LDL levels. Perhaps it can be estimated indirectly from the data we do have.
Thank you! This is a great example of how unsupported assertions turn into “facts”.
Someone made an unsupported assertion (deflecting inquiries as to their sources with a variation of “I have discovered a truly wonderful proof of this statement which this margin is too small to contain”); someone else made a nice-looking table in a peer-reviewed paper; others cite the peer-reviewed paper; and voila! An entire table of “facts” has been created out of thin air.
I’m very much looking forward to the rest of this series.
JS
Re those Cordain references that don’t really pan out maybe bring to his attention?
Paul- ah, tha pathogens – but I had yet another patient present with acute suicidally and a bit of paranoia on top of a brewing depression once he started statins a few weeks ago – I can’t help but think the straight-up cholesterol building blocks are vulnerable too. Cholesterol turnover for myelin is slow, but in the synapses more robust…
Most East Asian populations have higher LDL, HDL, and TC than European populations.
Paul: do you have some data to support the above?
For ex, to the best of my knowledge, populations of Okinawins, Japanese and others have lower rather than higher Tot Choles, etc.
Thanks,
Hi Steve,
In last Tuesday’s post I had a table from the JLIT study. Most people were in the 200-239 mg/dl range.
That’s slightly higher than the most frequent TC for Europeans.
during my doctor of pharmacy training, one of my professors made the argument that newborns have a ldl around 60, so we can assume that a ldl goal of <70 is reasonable and safe for most us. this never held much water with me since newborns are physiologically distinct vs adults. Also, the bigger question regarding the safety of lowering a ldl to <70 with something like a statin vs a level that low independent of drug therapy. Any thoughts?
Other animal species can give a hint about the levels of plasma lipoproteins can be handled by evolvable mechanisms.
“Apolipoprotein B mRNA editing in 12 different mammalian species” has a table titled ”Plasma lipoprotein concentrations of 12 mammalian species“ (HDL, LDL, et al.). Some concentrations are moderately high; humans (which humans?) are toward the upper end of the range. (I once found a more suitable paper, but can’t find it this evening.)
Further afield (but still relevant to feasible biological transport mechanisms), “Plasma lipoproteins in fish”, reports plasma cholesterol levels that are >600 mg/dl in many species, >900 in a few, and >1400 in one.
Physical chemistry apparently doesn’t force plama lipoproteins to ”clog arteries“ or wreak other havoc.
Hi Emily,
Statins block everything in the HMG-CoA pathway including CoQ10 which is essential for carrying electrons to Complex III in the electron transport chain. Also it is essential to prevent lipid peroxidation in mitochondria. I would suggest that the statins were disabling his mitochondria which are essential to maintenance of dendrites.
Cholesterol could contribute also, but again I would think brain synthesis of cholesterol is probably more important than LDL import; and statins reduce cholesterol synthesis by a much larger fraction than they reduce LDL levels.
So there’s several pathways by which statins might be responsible without LDL transport being central.
It’s an interesting research question, but we have to keep all the possibilities in mind.
Hi steve,
Yes, newborns have immature immune function so I wouldn’t be surprised to see low LDL levels. But I haven’t researched the issue. It would be interesting to see at what age LDL levels normalize.
I certainly don’t think it’s desirable to lower LDL by statins. I trust the body to give us the optimal amount of LDL. Evolution knows more than medical doctors what the best amounts are of our natural proteins.
Hi Paperdigger,
Fascinating, thanks. I wasn’t planning to take the time to check out the animal cholesterol levels, but it would certainly be interesting.
unsourced!?
you solve it only a physicist & a thinker can.
kudo!
this solves something that bugs me for a while (about HGs low cholesterol)
looking forward to the next article.
Pam (also a physicist)
looking
Statins also directly interfere with G protein coupling on certain serotonin receptors – there are three other types of serotonin receptors that are affected but the mechanisms are not so clear – and statins that are lipophilic (like simvastatin) readily cross the blood brain barrier.
…and one review of cholesterol-lowering diets did show increased psychopathology, but it is fairly old so I haven’t seen the actual study or the quality of it.
Thanks, Emily. Those are good to know.