Monday, May 7, 2012

Beyond Ötzi: European Evolutionary History and its Relevance to Diet. Part II

In previous posts, I described how Otzi was (at least in large part) a genetic descendant of Middle Eastern agriculturalists, rather than being purely descended from local hunter-gatherers who adopted agriculture in situ.  I also reviewed evidence showing that modern Europeans are a genetic mixture of local European hunter-gatherers, incoming agricultural populations from the Middle East, neanderthals, and perhaps other groups.  In this post, I'll describe the evidence for rapid human evolution since the end of the Paleolithic period, and research indicating that some of these changes are adaptations to the Neolithic (agricultural/horticultural/pastoral) diet.

Humans have Evolved Significantly Since the End of the Paleolithic

Evolution by natural selection leaves a distinct signature in the genome, and geneticists can detect this signature tens of thousands of years after the fact by comparing many genomes to one another.  A landmark paper published in 2007 by Dr. John Hawks and colleagues showed that humans have been undergoing "extraordinarily rapid recent genetic evolution" over the last 40,000 years (1).  Furthermore:
...Neolithic and later periods would have experienced a rate of adaptive evolution [more than] 100 times higher than characterized most of human evolution.
"Adaptive evolution" refers to natural selection (e.g., evolving the ability to digest the milk sugar lactose in adulthood), rather than genetic change by random drift.  From a later paper published in Science (2):
In general, we find that recent adaptation is strikingly pervasive in the human genome, with as much as 10% of the genome affected by linkage to a selective sweep.
In other words, the authors estimate that the rate of adaptive evolution since the development of agriculture has been more than 100 times faster than during most of the Paleolithic period, and that as much as 10 percent of the genome shows evidence of recent evolution in European-Americans, African-Americans and Chinese (although some of this predates agriculture).  This suggests that we may have evolved as much over the last 10,000 years as we did over the previous 1 million year interval!  Just to give you an idea of the significance of that genetic distance, one million years ago the closest thing to a human was Homo heidelbergensis, a burly, thick-browed hominid that used spears to take down large prey (3). 

This rapid rate of genetic change was driven by at least two factors (Cochran and Harpending. The 10,000 Year Explosion. 2009):
  1. A major change in environment, and thus a change in selective pressures on the genome.
  2. A large increase in population.  The higher the population base, the higher the likelihood that adaptive mutations will arise by chance.
Some of these Adaptations are to Diet

Looking at the archaeological record of early agriculturalists, it's clear that they experienced severe physical stress, including stunting and skeletal abnormalities that indicate nutritional and infectious stress (Cohen and Crane-Kramer. Ancient Health. 2007; Cohen. Health and the Rise of Civilization. 1991).  Looking at the human genome, it's clear that it has changed substantially since the adoption of agriculture.  If we believe that the Neolithic grain-focused diet contributed to the ill health of early agriculturalists, it must have exerted a significant selective pressure on the genome, and therefore it is an inevitable conclusion that some of the genetic changes that have occurred in the last 10,000 years in populations eating a Neolithic diet are adaptations to this diet. 

To give you an idea of how fast genetic adaptations to diet can arise and spread, let's return to the example of lactase persistence (4).  Normally, humans lose the ability to digest the milk sugar lactose after infancy, rendering them lactose intolerant in adulthood.  Certain genetic mutations break the switch that turns lactose production off after childhood, allowing continued lactose digestion in adulthood.  These mutations arose independently multiple times in human history, in Europe, Africa and the Middle East (5).  They appeared shortly after the acquisition of dairy as food.  In each case, a mutation arose in a single individual and rapidly spread throughout the population.  The most common mutation in Europeans arose in one person ~7,500 years ago, and today is present in 80 percent of Europeans and people of European descent.  This illustrates how rapidly evolution and dietary adaptation can occur, although there's an even faster means of evolution that I'll get to later.

Another example is salivary amylase copy number.  Amylase is an enzyme that digests starch into glucose, and salivary amylase is a version of the enzyme that's contained in saliva.  Different people produce different amounts of salivary amylase, and this corresponds to the number of copies of the salivary amylase gene they carry in their genome (6).  Populations that have historically eaten a high-starch diet tend to have more copies, and their genomes show evidence of recent natural selection favoring high copy number due to gene duplications (7).  European-Americans, Japanese, and Hadza hunter-gatherers tend to have high copy number, suggesting adaptation to regular starch consumption, while several traditionally low-starch hunter-gatherers and pastoralists including Biaka, Mbuti, Datog, and Yakut tend to have low copy number.

It's worth noting that there's a lot of variability in the European-American and Japanese samples, with copy number ranging from 2-15 in the European-American sample.  Most people cluster in the 4-10 copy range.  Salivary amylase copy number correlates with glucose tolerance-- more copies is associated with better glucose handling-- but the mechanism remains unknown (8).

Chimpanzees only carry two copies (one on each chromosome), less than any known human population, consistent with the fact that they eat very little starch (despite getting a substantial amount of carbohydrate from fruit sugars).  The increase in salivary amylase copy number presumably occurred after humans diverged from chimpanzees, and probably reflects increasing reliance on starch as a food source during human evolution.

Mutation and selection is one path to adaptation, but there's actually another much faster path.  Each human contains essentially the same set of genes as every other human, however, different people often carry different versions of the same genes.  These different versions are called "alleles" of a gene.  Eye color, skin color, hair color, hair texture and blood type are all common examples of traits where different alleles of the same genes create different physical outcomes.  In any population, there's a pool of common alleles, each present at a different frequency.  Changing the population frequency of pre-existing common alleles is the most rapid form of natural selection because it doesn't rely on new mutations arising spontaneously.  Allele frequencies can change dramatically in as little as one generation if there's a strong selective pressure.  For example, if there were a global epidemic of a deadly virus that only infected people with blood type A (or, more likely, people with a particular immune system-related allele), the frequency of that allele could greatly decline within only a few years.  Mutations within a gene result in a new allele, which can then be subject to natural selection, as in the case of lactase persistence, but waiting for the right mutation to occur takes a lot longer than selecting from a pool of alleles that are already present in a population.

As one would expect, changes in allele frequency (even in the absence of new mutations) are one of the genetic forces that has permitted the rapid adaptation of humans to unique environments throughout the world (9).  For example, there are specific allele patterns related to digestion and metabolism that associate with populations that have ancestral dietary patterns dependent on grains or tubers:
A SNP (rs162036) that is strongly correlated with a diet containing mainly the folate-poor roots and tubers lies within the methionine synthase reductase (MTRR) gene, which activates the folate metabolism enzyme methionine synthase and is implicated in spina bifida (22). Perhaps the most interesting signal comes from a SNP (rs4751995) in pancreatic lipase-related protein 2 (PLRP2) that results in premature truncation of the protein and is strongly correlated with the use of cereals as the main dietary component (Fig. 2). Several lines of evidence support an important role for this protein in a plant-based diet. First, unlike other pancreatic lipases, PLRP2 hydrolyzes galactolipids, the main triglyceride component in plants (23, 24). Second, a comparative analysis found that the PLRP2 protein is found in nonruminant herbivore and omnivore pancreases but not in the pancreases of carnivores or ruminants (25). Our results show that the truncated protein is more common in populations that rely primarily on cereals, consistent with the hypothesis that this variant results in a more active enzyme (26, 27) and represents an adaptation to a specialized diet.
These patterns reveal the traces of rapid changes in allele frequency that presumably underlie dietary adaptations.


Patterns of Genetic Change

I just described several examples of rapid, recent human evolution to a change in diet.  If we take a broader look at the types of genes that have undergone recent selection, they cluster predominantly into several categories (10, 11, 12):
  • Immunity
  • Skin pigmentation
  • Brain development/function
  • Food digestion/metabolism
  • Sensory perception (including smell)
  • Muscle-related genes
  • Assorted cell signaling pathways
Some of this is expected, knowing that the late Paleolithic and Neolithic environment brought major changes in pathogen exposure, latitude (in some populations), physical demands, social and cognitive demands, and diet.  Each genetically distinct population (e.g., European, African, Asian) has a unique suite of recent adaptations that helped it thrive in its own ancestral environment, although many of the genetic processes that have occurred are broadly similar between populations. 

We have a broad outline of the kinds of processes that have been subject to recent natural selection in humans, and in some cases the location and function of the selected gene variants are known.  However, the truth is that in most cases where we know natural selection has occurred, we don't know exactly where the variant in question resides, what it does, and often we don't even know what gene it's in.  The point is that the large majority of recent genetic adaptations in the human genome remain totally uncharacterized, and judging by the patterns observed among the mutations we do understand, a number of them are probably adaptations to the Neolithic diet that remain to be explored.

I think it's clear at this point that modern Europeans, and many other populations with long-term ancestral Neolithic diets, carry meaningful genetic adaptations to the Neolithic diet.  However, there's a major caveat here.  The presence of adaptation does not imply that we're completely adapted to the Neolithic diet-- we may only be partially there.  This is a concept I'll explore in the next post. 

184 comments:

Matt Lentzner said...

Really enjoying this series! Thanks.

brec said...

Um... according to my 23andme genetic profile, SNP rs4751995 has versions A and G, and my genotype is AA.

Alas, I am ignorant of what this implies as to my potential consumption of Wheaties.

Bog said...

Stephen,

while pushing your "appeal-to-tradition"-fallacy you miss an important concept: "correlation does not equal causation". I am sure you've heard the favourite one liner of every fad diet promoter more than once, yet you still fail to comprehend it fully.

Now, what's the likelihood that grains had an inherent, causal role in the reported decline of health among Europeans at eve of Neolithic period? Very weak (pay attention to the second paragraph).

Stature and robusticity during the agricultural transition: Evidence from the bioarchaeological record.


Mummert A, Esche E, Robinson J, Armelagos GJ.


Abstract
"The population explosion that followed the Neolithic revolution was initially explained by improved health experiences for agriculturalists. However, empirical studies of societies shifting subsistence from foraging to primary food production have found evidence for deteriorating health from an increase in infectious and dental disease and a rise in nutritional deficiencies. In Paleopathology at the Origins of Agriculture (Cohen and Armelagos, 1984), this trend towards declining health was observed for 19 of 21 societies undergoing the agricultural transformation.

The counterintuitive increase in nutritional diseases resulted from seasonal hunger, reliance on single crops deficient in essential nutrients, crop blights, social inequalities, and trade. In this study, we examined the evidence of stature reduction in studies since 1984 to evaluate if the trend towards decreased health after agricultural transitions remains. The trend towards a decrease in adult height and a general reduction of overall health during times of subsistence change remains valid, with the majority of studies finding stature to decline as the reliance on agriculture increased. The impact of agriculture, accompanied by increasing population density and a rise in infectious disease, was observed to decrease stature in populations from across the entire globe and regardless of the temporal period during which agriculture was adopted, including Europe, Africa, the Middle East, Asia, South America, and North America"

Moreover, the authors of the above paper identifying the most likely factors for plummeting health record completely miss the point which you much to your credit highlighted: changing population. Followed by Bergmann's rule the newcomers to Europe were of shorter stature (genetical trait).

Naeem said...

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Stephan Guyenet said...

Hi Bog,

You seem to have a remarkable ability to read what you want to read in a paper. First of all, the senior author on that paper is George Armelagos, who co-edited "Paleopathology at the origins of agriculture" along with Dr. Mark Nathan Cohen, which is one of the books I cite frequently on this blog. I suggest you read it if you have a good medical library handy. Just like the paper you cited, and just like I've been writing, it points to both nutritional and infectious stress as reasons for the poor skeletal health observed in the archaeological record following the adoption of agriculture. This is well-established in the archaeology community, so I'm not sure why you feel the need to be an "archaeology confusionist".

The reference you cited in your last comment about the Tarahumara (which I deleted because it was again extremely disrespectful) also did not support your wild claim that cultures who maintain serum lipids below 150 do not show any sign of atherosclerosis. In fact, the paper had nothing to do with atherosclerosis, it was about serum lipids. If you can find me a single human population, any population at all, that does not show any sign of athero while aging, I'll nominate you for a Nobel prize, because at this time none have been identified.

Regarding the "appeal-to-tradition fallacy" that an animal is best suited to the diet it evolved on, I suggest you eat eucalyptus leaves for a month and get back to us.

You are a mess, man! Pull it together. If you had manners, I'd let your sloppy thinking slide, but you don't.

Asim said...

I'd also like to point out that animals in the wild get atherosclerosis.

http://www.springerlink.com/content/qj3382576021vj58/

Steven Sashen said...

I just want to know how and why greater height became synonymous with improved health and shorter height became proof of the opposite.

Tuck said...

Great post, Stephen.

Stephan Guyenet said...

Hi Steven,

Agreed. There are a number of skeletal markers besides height that indicate nutritional stress that were increased in early agriculturalists. However, short stature does not necessarily equal nutritional stress. In combination with the other markers, the sudden drop in stature of early agriculturalists probably does represent poor health/nutrition. However, non-industrial cultures throughout the world today are short by modern standards, yet they are typically quite healthy metabolically speaking (although to be complete, they do generally suffer from infectious diseases).

Bog said...

Stephen,

"The counterintuitive increase in nutritional diseases resulted from seasonal hunger, reliance on single crops deficient in essential nutrients, crop blights, social inequalities, and trade".

what part I did not understood? Does the above text enunciate that grains had a causal role in poor health record of early agriculturalists? No!

Speaking of Tarahumara tribe, I am not sure whether there has ever been recorded a case of atherosclerosis among them. This could be possible, after all the total serum cholesterol which was around 134mg/dl was just the average. Some people had higher levels. These were the people whose diet Pritikin popularized in the 1970' as he succesfully reversed his own atherosclerosis.

People who keep their cholesterol under 150mg/dl most of their lives cannot develope an atherosclerosis under normal circustances, something that Bill Roberts (the chief editor of American Journal of Cradiology) & Bill Castelli from the Framingham study has kept telling us for ages (Castelli et al. Circulation, May 1977), that's why there's not a single US based cardiologist who would have operated such a person. This fact has been illustrated in numerous epidemiologic studies (Papua new highlanders and many Central-African populations with their traditional diet are good examples as well). The China study included a cohort from Guizhou county, around 250 000 people, not a single coronary heart disease related death during the 3-year follow-up, people had their cholesterol around 120mg/dl. Very powerfull.

Anyways, it's understandable that you were not too keen on the Taramahura paper:

"Since in the experimental dietary cholesterol is sine qua non for the development for the experimental atherosclerosis, especially among the sub-human primates, the finding of linear association of dietary cholesterol intake and plasma cholesterol concentrations in man further undergirds the evidence relating dietary factors to hypercholesterolemia and atherosclerotic coronary heart disease".

The paper also pinpoints the reason why we cannot observe this link (dietary-plasma cholesterol) in Western cohorts, but establish the link immeadiately when we are not dealing with high risk group where elevated cholesterol is the norm.

I recommend that you go thoroughly through the whole text and perhaps (maybe) blog about it. No need to get me a nobel, I am merely just parroting widely known info.

http://www.ajcn.org/content/31/7/1131.long

polyhex said...

I have nothing to add to the discussion but just wanted to say how much I am enjoying this series.

Stephan Guyenet said...

Hi Bog,

I'm getting the distinct impression that you don't understand my position on grains or cardiovascular disease.

What do you think the statement "reliance on single crops deficient in essential nutrients" is referring to, in agricultural populations where the "single crop" is a grain? Over-reliance on grains causes health problems. That's what they're saying, and that's what I've said. I don't think including some grains in the diet is harmful, which is why I eat both grains and legumes myself regularly. You can see to this day that populations who eat a heavily grain-focused diet develop health problems. For example, mineral deficiency rickets is common in African Bantu who have insufficient access to non-grain foods.

The quote you referenced about dietary cholesterol being the sine non quo for atherosclerosis is not accurate (because even wild herbivorous animals develop some atherosclerosis), although it does accelerate atheroscerosis in animals that are not adapted to dietary cholesterol, but not in humans. It's well known that dietary cholesterol has a minimal influence on serum lipids in humans, which is why that hypothesis has lost steam in recent decades. Even Ancel Keys didn't believe it 50 years ago.

The argument that the Tarahumara have a low CHD rate due to their low cholesterol intake is ridiculous. What about the Masai, who live mostly off whole milk and blood, and 50+ autopsies and hundreds of ECGs have never found evidence of an infarction? Their cardiac health is much better characterized than the Tarahumara. The Tarahumara have a diet and lifestyle that's totally different from how we live today, so to point the finger at cholesterol specifically, especially considering the results of controlled cholesterol feeding trials in humans, is really stretching it!

You said, "People who keep their cholesterol under 150mg/dl most of their lives cannot develope an atherosclerosis under normal circustances" You keep confusing atherosclerosis with heart attacks. Show me a single study that demonstrated a complete absence of atherosclerosis in people with TC below 150. One single study. I guarantee you that study does not exist.

I agree that total cholesterol below 150 mg/dL is associated with low (but not zero-- that is a myth that MRFIT handily dispelled) heart attack risk. I have never disagreed with that, which is one of the reasons why I don't think you understand my position. I suggest you re-read my posts on heart disease and get a better understanding of my position so that you can argue against it rationally if you're still feeling belligerent.

Dylan said...

"People who keep their cholesterol under 150mg/dl most of their lives cannot develope an atherosclerosis under normal circustances"

This is false. I used to work in the medical records department of a hospital and can tell you definitively that there were patients that had chronic heart problems including heart attacks that had cholesterol below 150. Not even borderline cases, I'm talking about low 100's.

allison said...

Alcohol tolerance is a good example of the rate at which dietary genetic changes can occur in populations. Beer and wine (including mead) have been consumed in Europe (and eariler in the Fertile Crescent) for 5000-6000 years. Europeans have some of the highest rates of alcohol tolerance, whereas Native Americans have some of the worst, having only been exposed to alcohol in the last 500 years.

agame said...

Hello Dr. Guyenet,

I have been reading your blog for a few years now (although I have never commented), and would first like to thank you for all the time and effort you put into educating us common folk.

My question to you pertains to a comment made by Mat Lalonde at the AHS last year. He pointed out that (while agreeing with your current argument that epigenetics play an extremely important and relevant role in the evolution of our species) because cereals and the like do not substantially inhibit our reproduction and proliferation, it is unlikely that there would be enough selective pressure to elicit substantive evolutionary changes (save the early type 1 diabetics and celiacs of the agricultural revolution who would have been subject to such selective pressure). I recognize your caveat somewhat addresses this question, but it seems that it might still undermine the claim that agriculturalists would have had any significant adaptive traits that might dilute the hunter-gatherer genetic pool? Thank you again, and I look forward to your response.

~Austin

Tyler said...

I have just a quick question about grains:

If we are generally adapted to eat grains, would that still apply to modern dwarf wheat? It's been pretty heavily genetically modified, right? Would that affect our tolerance?

Go Meat! said...

Hey Stephan, I love the blog. You mentioned that early agriculturalists suffered from severe diseases and shortened height. Was this because they were not preparing their grains and legumes properly (soaking, grinding fermenting)? Or were they preparing them correctly and still facing illnesses? Or did they make grains a large part of their diet, which led to many ill effects?
Secondly, on the subject of height, pastoralists have been renowned for their tall figure. Weston A Price found a pastoralist group whose women averaged above 6 feet and whose men came near 7 feet. Is this level of height and unhealthy and unnatural due to the rather sudden appearance of dairy? Or is it simply a sign of outstanding nourishment and superb healthfulness?
Thirdly, on a random note, what do you think of Injera? Would you consider properly fermented teff a "safe starch", or would it still have harmful properties?

Bog said...

Stephen,

this "reliance on single crops deficient in essential nutrients" means that relying on single-crop is not beneficial. People in modern societies do not rely on single crops. I eat oatmeal for breakfest, millet for lunch and barley for dinner. The paper does not establish a ground for your speculation that reliying heavily on grains as such is harmful. English is not my first language but I can still grasph the meaning.

Saying that dietary cholesterol has minimal influence in serum lipids is completely irresponsible. This has been proven by metabolic-ward type feeding experiments by Harvard professor Hegstedt who even commented that Keys dietary cholesterol position was the only position he had it incorrect. By saying the opposite would equal to claiming that the Darwinian foundation for our current biomedical paradigm is flawed. This is not the case. You haven't really done your home work and you certainly did't read the Taramahura paper I wired you with, the authors explain the issue in quite detail manner.

You may want to check this paper as well (2010).

Dietary cholesterol increases the susceptibility of LDL-C to oxidation, vascular inflammation, oxidative stress, and postprandial hyperlipemia and potentiates the harmful effects of saturated fat, impairs endothelial function, and increases cardiovascular events.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989358/

I should have pointed out the lifestyle patterns of Taramahura and Papua Guinea folk. Smoking and drinking is a widespread problem among these populations, yet they still virtually lack coronary heart disease due to low intake of animal producys. And, no, I don't confuse anything with strokes here. The Japanese have high levels of strokes (due to high salt intake, smoking, high blood pressure) but have have traditionally have very low levels of coronary heart disease.

I cannot say that 150mg/dl cholesterol levels maintained thoroughout the life guarantee 100% success in terms of absence of coronary heart disease, but under normal cincumstances the data implies so. Framingham study has lasted almost 40 years, we have about 5-6 individuals who have died under these conditions due to coronary event, and it's strongly believed that's these people had some kind of malfunction.

In respect,

Bog

Bog said...

Ouh...and Masai is on its way to becoming an equal myth to that held of Ancel Keys by the fad diet promoters (I am impliying to the widespread notion that he actually was selective with the data which completely false premise).

Masai have atherosclerosis, despite having genetically extremely efficient cholesterol cleaning mechanism something which 99,9999% people in the world do not have on similar extent. There's nothing in Masai which would challenge the lipid-theory.

For more about Masai, I recommend primitivenutritions videos of them (videos 27-28) on youtube. The guy has done great work about them (cancer, rheumatoid arthirisis, atherosclerosis is all common among these pastorals).

Dylan said...

Well, Bog, sometimes you have to wonder about the validity of "the data" when you have a real world person telling you that in the real world clinical treatment setting, that data does not hold true. This wasn't a few exceptions, I'm talking about absolutely no correlation between cholesterol and patients with chronic cardiac problems.

Stephan Guyenet said...

Hi Go Meat,

I think there were probably multiple nutritional problems facing early agriculturalists, including:

-Over-reliance on a single food source, so less complete nutrient profile
-Generally low mineral availability of whole grains compared to other foods, low mineral content of potassium, no vitamin C
-Possibly it took them a while to invent good prep methods for grains such as soaking and fermenting. Not sure about this
-Lack of complementary foods like legumes and domesticated animals, which probably came later
-Heavy reliance on gluten grains, so a fraction of the population may have developed celiac and/or other forms of gluten sensitivity
-Much higher carbohydrate intake without proper dental hygeine increases tooth decay risk

Also, sendentism and higher population density increase pathogen exposure, which was a big factor.

Stephan Guyenet said...

Hi Bog,

I'm not going to argue with you about the grains thing-- the paper you cited clearly supports my position and Cohen and Armelagos are also quite clear about it in the books of theirs I have read. I recommend "Health and the Rise of Civilization" by Dr. Cohen.

Not sure where you're getting your information but I think you have been misled about dietary cholesterol. From a review paper:

"Clinical feeding studies show that a 100 mg/day change in dietary cholesterol will on average change the plasma total cholesterol level by 2.2–2.5 mg/dl, with a 1.9 mg/dl change in low density lipoprotein (LDL) cholesterol and a 0.4 mg/dl change in high density lipoprotein (HDL) cholesterol. Data indicate that dietary cholesterol has little effect on the plasma LDL:HDL ratio. Analysis of the available epidemiological and clinical data indicates that for the general population, dietary cholesterol makes no significant contribution to atherosclerosis and risk of cardiovascular disease."
www.ncbi.nlm.nih.gov/pubmed/11111098

The Framingham study, the Health Professionals Follow-up Study, the Nurse's Health Study, and many other major prospective studies have shown that egg consumption is not associated with heart attack risk (with the possible exception of diabetics in one large study). Eggs are the richest source of cholesterol in the US diet. That's why Dr. Walter Willett has said:

"Heart-wise, although a single egg yolk contains about 200 milligrams of cholesterol — two-thirds of the daily recommended intake — for most people, cholesterol in food has little effect on cholesterol in the bloodstream... The largest study looking directly at the relationship between egg consumption and heart disease showed no link between eating up to one egg a day and the risk of developing heart disease or having a stroke."
http://harvardpartnersinternational.staywellsolutionsonline.com/HealthNewsLetters/69,H0312k

This is mainstream science, the majority scientific view-- and in 2012, the position that dietary cholesterol contributes to CHD in humans is not very well populated by researchers.

Regarding the health of the Masai, yes every non-industrial culture has health problems, including those that eat dairy, and those that eat grains. However, what we're talking about here is heart attack risk, and the traditionally-living Masai have a risk of approximately zero (even among the elderly), according to extensive autopsy studies and ECG. They are not genetic anomalies in terms of their cholesterol clearance ability-- Dr. George Mann addressed that issue in his papers. They handle dietary cholesterol efficiently like almost all humans (as discussed in the review paper above) and other animals adapted to eating flesh.

I agree 100% that people like traditionally-living horticultural cultures in New Guinea and agricultural Bantu, both of which have a traditionally low-animal food diet, have a vastly lower CHD risk than affluent people today. That is an interesting finding, and it's one that I've covered in blog posts and talks I've given. However, the finding is not unique to cultures that don't eat much animal food, which is what I'm trying to explain. You can't pick and choose only cultures that support the particular dietary philosophy you're adhering to. Same as the Masai, the Bantu, New Guinea highlanders and other agricultural/horticultural populations throughout the world had their own suite of health problems. All of them had short life expectancies by modern standards. However, virtually none of them had the obesity, metabolic disease, and heart attack risk we have today, which is one of the reasons they interest me so much.

I'm curious, are you a follower of Dr. Caldwell Esselstyn? He is a strong advocate of keeping TC below 150 mg/dL via diet (ultra low-fat vegetarian) and drugs and your arguments sound very much like his. No offense but you write like someone with very strong ideological convictions about diet.

Stephan Guyenet said...

Hi agame,

If you look at the skeletal record, it suggest the likelihood of nutritional stress in early agriculturalists. The degree of nutritional stress would have been more than enough to reduce reproductive success. Anyone who could evolve ways to minimize the nutritional problems would have had a reproductive advantage. Besides, natural selection can operate beyond reproductive years in humans, which is why all human cultures have postmenopausal women. Elderly people can aid the survival of their offspring (and thus genes) even if they aren't actively producing offspring. I think all this is corroborated by the genetic findings of selection at diet-related loci.

Hi Tyler,

It may have been exacerbated by breeding efforts because the gluten content has been increased for better bread baking abilities. As for the idea that hybridizing and genetically selecting wheat would inherently make it more toxic, I say nonsense. We've done that for all of our plant food crops, not just wheat. It's hypothetically possible that it could make a food more toxic, but it's equally possible that it could make it less toxic. We're talking about genetic changes that have been selected for gradually over thousands of years, not genetic tinkering in a lab.

Bog said...

"The paper you cited clearly supports my position."

What they meant was that the early agriculturalist did the mistake of cultuvating just one specific crop instead of variation. Yes, you will encounter problems incase you base you diet solely on one food.

"The Framingham study, the Health Professionals Follow-up Study..."

I tried to be pre-emptive and show you the Taramahura paper, since the scholars already in the 1970's knew what was going on. Context. You basically saying to me that we cannot show association with smoking and lung cancer since the data shows that reducing smoking from three packs per day to two packs per day is not associated with reduced lung cancer rates.

In the WHI trial, both groups ate equally as much animal protein and showed equally low fiber intake (around 16g per day, one big pear-fruit has about 8g) and had equally high LDL. The variation of the diet was minimal and context was that of a choice between low-fat dough and regular dough.

Egg consumption hasn't much role in heart disease in the context of high-risk group where virtually everyone show already elevated plasma cholesterol. We need aggressive nutrition intervention to show any benefits of skipping eggs. In other words, we need a reference population who eat eggs either zero or once or twice per week. That is, we need a group with healthy starting point.

The authors of the Taramahura paper refer to the USA: "Virtually no one consumed the Tamahura food pattern"

Guynet wrote: "This is mainstream science, the majority scientific view and in 2012, the position that dietary cholesterol contributes to CHD in humans is not very well populated by researchers".

You are referring to mainstream science that no one working with lipid-research is taking seriously.

Jenkins et al.(2010)

"Recent media reports reflect the remarkable effectiveness of the sustained propaganda campaign of the egg producers’ lobby!...".

"Diet is not just about fasting cholesterol; it is mainly about the postprandial effects of cholesterol, saturated fats, oxidative stress and inflammation. A misplaced focus on fasting lipids obscures three key issues. Dietary cholesterol increases the susceptibility of low-density lipoprotein to oxidation, increases postprandial lipemia and potentiates the adverse effects of dietary saturated fat. Dietary cholesterol, including egg yolks, is harmful to the arteries".

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989358/

The problems with cohort data from homogenously eating Western populations have been indicated numerous times by top lipid-researchers

A diet-heart: problematic visit
http://www.ajcn.org/content/91/3/497.full

I think it's bizarre that you refer to something what Ancel Keys said sixty years ago when his collagues at that time already disagreed with him. As if his words of WHI would be somehow more important than extremely tightly controlled metabolic ward studies done by Hegstedt among others.

In regards to Masai,

There's a world before primitivenutrition -youtube serie and world after the primitivenutrition video serie.

The Masai has genetically exceptionally unique cholesterol feedback mechanism. Something you or your fellow, ethnic-brethren, Euro-Americans do not have.

Two studies:

1) The Masai of East Africa: some unique biological characteristics.

The masai show completely different absorption, synthesis and excretion of cholesterol as opposed to white-Americans.

2) Cardiovascular disease in the tropics. IV. Coronary heart disease.

Stephen, you are also covered in this video. I recommend it, It's about the Masai and the Tokelauns

http://www.youtube.com/watch?v=MfAOHWUD_TI&feature=plcp

In respect,

Bog

Bog said...

"All of them had short life expectancies by modern standards. However, virtually none of them had the obesity, metabolic disease, and heart attack risk we have today, which is one of the reasons they interest me so much.

I'm curious, are you a follower of Dr. Caldwell Esselstyn? He is a strong advocate of keeping TC below 150 mg/dL via diet (ultra low-fat vegetarian) and drugs and your arguments sound very much like his. No offense but you write like someone with very strong ideological convictions about diet".

Esselstyn did nothing unique, basically Pritikin discovered all this by studying extensively and rigirously the epidemiologic data. He was particularly interested about the staggering difference between coronary heart disease rates after and during the war in Europe and concluded that atleast stress cannot have any causal role in the aethiology of the disease. What would be mores stressing than war? Not a single Esselstyns or Ornish patient has received another cardiovacular event after adjusting to diet pattern and cholesterols under 150mg/dl.

Take a look at the China Study, there different cohorts with hundred of thousands of people, which guaranteed steady flow of very old people as well, despite the average life-span is short in some of the Chinese regions due to lack of sanitized loo's and antibiotics. Im more of a follower of Bill Castelli from the Framingham study:

"You know, we know that if I can get your total cholesterol down around let's say 100 to 130 or so, and I have maybe not quite a billion people on the earth like that, and those people cannot get atherosclerosis. You know in the China Study, for example, when Chou En-lai was dying of cancer he started a study in China just like the Framingham Study. The only difference was it was in 880,000,000 people so it was a little larger than the Framingham Study. But you know they found these villages in China where you couldn't get a heart attack or you couldn't get diabetes and the women couldn't get breast cancer and you know their total cholesterol were 127, but the chances we could ever get Americans down that low with diet and exercise are not good".

http://www.prescription2000.com/Interview-Transcripts/2011-02-18-william-castelli-heart-disease-lipids-transcript.html

Bog said...

"I'm not going to argue with you about the grains thing - the paper you cited clearly supports my position."

What they meant was that the early agriculturalist did the mistake of cultuvating just one specific crop instead of variation. Yes, you will encounter problems incase you base you diet solely on one food.

"The Framingham study, the Health Professionals Follow-up Study......egg consumption is not associated with heart attack risk"

I tried to be pre-emptive and show you the Taramahura paper, since the scholars already in the 1970's knew what was going on. Context. You basically saying to me that we cannot show association with smoking and lung cancer since the data shows that reducing smoking from three packs per day to two packs per day is not associated with reduced lung cancer rates.

In the WHI trial, both groups ate equally as much animal protein and showed equally low fiber intake (around 16g per day, one big pear-fruit has about 8g) and had equally high LDL. The variation of the diet was minimal and context was that of a choice between low-fat dough and regular dough.

Egg consumption hasn't much role in heart disease in the context of high-risk group where virtually everyone show already elevated plasma cholesterol. We need aggressive nutrition intervention to show any benefits of skipping eggs. In other words, we need a reference population who eat eggs either zero or once or max twice per week. That is, we need a group with healthy starting point.The authors of the Taramahura paper refer to the USA: "Virtually no one consumed the Tamahura food pattern"

Guynet wrote: "This is mainstream science, the majority scientific view and in 2012, the position that dietary cholesterol contributes to CHD in humans is not very well populated by researchers".

You are referring to mainstream science that no one working with lipid-research is taking seriously.

Jenkins et al.(2010)
"Recent media reports reflect the remarkable effectiveness of the sustained propaganda campaign of the egg producers’ lobby..."

"Diet is not just about fasting cholesterol; it is mainly about the postprandial effects of cholesterol, saturated fats, oxidative stress and inflammation. A misplaced focus on fasting lipids obscures three key issues. Dietary cholesterol increases the susceptibility of low-density lipoprotein to oxidation, increases postprandial lipemia and potentiates the adverse effects of dietary saturated fat. Dietary cholesterol, including egg yolks, is harmful to the arteries".

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989358/

The problems with cohort data from homogenously eating Western populations have been indicated numerous times by lipid-researchers

A diet-heart: problematic visit
http://www.ajcn.org/content/91/3/497.full

I think it's bizarre that you refer to something what Ancel Keys said sixty years ago when his collagues at that time already disagreed with him. As if his words of WHI would be somehow more important than extremely tightly controlled metabolic ward studies done by Hegstedt among others.

In regards to Masai,

There's a world before primitivenutrition -youtube serie and world after the primitivenutrition video serie.

The Masai has genetically exceptionally unique cholesterol feedback mechanism. Something you or your fellow, ethnic-brethren, Euro-Americans do not have.
Two studies,

1) The Masai of East Africa: some unique biological characteristics.

The masai has completely different absorption, synthesis and excretion of cholesterol as opposed to white-Americans.

2) Cardiovascular disease in the tropics. IV. Coronary heart disease.

Stephen, you are also covered in this video. I recommend it, It's about the Masai and the Tokelauns
http://www.youtube.com/watch?v=MfAOHWUD_TI&feature=plcp

In respect,
Bog

Bog said...

I wrote a long blog post which keeps dissappearing. Weird

I won't go to that anymore hopefully it will re-emerge soon.

Anyways, couple more issues with the Masai, as concluded their feedback mechanism for cholesterol is totally of different caliber as opposed to Euro-Americans. Masai makes a genetic outlier, yet they are probably the sickest group of non-industrialized pastorals ever existed, and what's amazing is that they manage to accumulate all these autoimmune diseases, cancers and atherosclerosis with a diet of not more than 1700 kalories per day per man. The amount of calories consumed in rural China f.ex was in many parts over 3000 daily for males.

As a European or Asian you could not find worst dietary example than Masai. Ironically the neighbouring tribes that eat quasi-vegan diets are completely disease free.

Links for the references are in the primitivenutrition serie.

The Masai model, part 1
http://www.youtube.com/watch?v=NnXF4qgrg5Q&list=PLCC2CA9893F2503B5&index=29&feature=plpp_video

Bog said...

Sorry Stephen,

I am not intending to spam your blog. However, I wrote this post which took a lot of time. English is not my first language. I am entitled to have visible and stay as visible:), hence I split it in two.

"I'm not going to argue with you about the grains thing - the paper you cited clearly supports my position."

What they meant was that the early agriculturalist did the mistake of cultuvating just one specific crop instead of variation. Yes, you will encounter problems incase you base you diet solely on one or two foods.

"The Framingham study, the Health Professionals Follow-up Study......egg consumption is not associated with heart attack risk"

I tried to be pre-emptive and show you the Taramahura paper, since the scholars already in the 1970's knew what was going on. Context. You are basically saying to me that we cannot show association with smoking and lung cancer since the data shows that reducing smoking from three packs per day to two packs per day is not associated with reduced lung cancer rates.

In the WHI trial, both groups ate equally as much animal protein and showed equally low fiber intake (around 16g per day, one big pear-fruit has about 8g), in addition they had hequally high LDL. The variation of the diet was minimal in the control group and the context was that of a choice between low-fat dough and regular dough.

Egg consumption hasn't much role in heart disease in the context of high-risk group where virtually everyone show already elevated plasma cholesterol levels. We need aggressive nutrition intervention to show any benefits of skipping eggs. In other words, we need a reference population who eat eggs either zero or once or twice per week. That is, we need a group with healthy starting point.

The authors of the Taramahura paper refer to the USA: "Virtually no one consumed the Tamahura food pattern"

Guynet wrote: "This is mainstream science, the majority scientific view and in 2012, the position that dietary cholesterol contributes to CHD in humans is not very well populated by researchers".

You are referring to mainstream science that no one working with lipid-research is taking seriously.

Jenkins et al.(2010)
"Recent media reports reflect the remarkable effectiveness of the sustained propaganda campaign of the egg producers’ lobby..."

"Diet is not just about fasting cholesterol; it is mainly about the postprandial effects of cholesterol, saturated fats, oxidative stress and inflammation. A misplaced focus on fasting lipids obscures three key issues. Dietary cholesterol increases the susceptibility of low-density lipoprotein to oxidation, increases postprandial lipemia and potentiates the adverse effects of dietary saturated fat. Dietary cholesterol, including egg yolks, is harmful to the arteries".

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989358/

Bog said...

The problems with cohort data from homogenously eating Western populations have been indicated numerous times by top lipid-researchers, not only in regards to eggs.

Jeremiah Stamler referring to bogus meta-analysis on saturated fats.

A diet-heart: problematic visit
http://www.ajcn.org/content/91/3/497.full

I think it's bizarre that you refer to something what Ancel Keys said sixty years ago when his colleagues at that time already disagreed with him. As if his words or WHI would be somehow more important than extremely tightly controlled metabolic ward studies done by Hegstedt among others.

In regards to Masai,

There's a world before primitivenutrition -youtube serie and world after the primitivenutrition video serie.

The Masai has genetically exceptionally unique cholesterol feedback mechanism. Something you or your fellow, ethnic-brethren, Euro-Americans do not have.
Two studies,

1) The Masai of East Africa: some unique biological characteristics.

The genetic uniqueness of Masai has been known already from the 1970's. The masai's absorption, synthesis and excretion of cholesterol is of completely different caliber as opposed to white-Americans.

2) Cardiovascular disease in the tropics. IV. Coronary heart disease.

Stephen, you are also covered in this video. I recommend it. It's about the Masai and the Tokelauns
http://www.youtube.com/watch?v=MfAOHWUD_TI&feature=plcp

In respect,
Bog

Bog said...

Besides, Stephen

you didn't get quite right your "mainstream 2012"-view either, and instead pushed Willet's views, probably the only subject (eggs) where you two share common ground.

From the IOM:

"There is much evidence to indicate a positive linear trend between cholesterol intake and low density lipoprotein cholesterol concentration, and therefore increased risk of coronary heart disease"

http://www.nap.edu/openbook.php?record_id=10490&page=769#p2000dc1a9970769001

The exceptions to the above is ofcourse Western population who have collectively already so staggeringly high plasma cholesterol levels that marginal value of one egg to serum lipids is.... marginal. Something that has, again known already been known for about 40 years as the authors of the Tarahumara paper explained in detail. A paper which I wanted to post you in order to avoid this silly argunment. But my plans didn't go as planned since you didn't even give a rudimentary glance to the paper.

Anyways, Masai are cool, they are prime example of lipid-theory: low serum cholesterol, low incidence of heart disease.

"In contrast to white-americans who have a limited maximal absorption capacity of 300mg of cholesterol, the Masai could absord more than 650mg cholesterol. Compared with the 25% suppression of synthesis found in white Americans, the Masai could suppress 50% of their endogenous cholesterol synthesis".

Cardiovascular disease in the tropics. IV. Coronary heart disease.

Isn't it amazing? This stuff has been known for over 40 years, yet many people have never even heard of it, eventhough the same people show great interest to both lipid theory and the diet patterns Masai and even lecture other people about it. Amazing how people can get it 180-degrees incorrect in the year 2012. If people would just look at the data instead of relying on poor fad science, we would have nothing to argue with.

Unknown said...

Bog,

You are working from several flawed premises.

Item 1: most work from the "China Study" is an exercise in foolishness at best and so is disturbing as a buttress to your anti-animal-foods position. Have you read the original monographs on which the eponymous book is based? Do you understand how multivariate statistical analysis works? Perhaps you could kindly tell me the corrections that Campbell and colleagues used to generate their purported correlations, because nowhere in the public representation is this information given?
Why is the fact that, in their mortality survey, wheat is the single most important dietary factor negatively affecting mortality never mentioned in public by Campbell? (Oh wait, he probably "corrected" that "raw finding" out of existence, but please tell me the specific corrections and their rationale so we can actually have a rational discussion of the original monographs).

Item 2: Where is the scientific proof that holding TC below 150 confers "immunity" to heart disease? No, the anecdotal clinical experience of Esselstyn's hand-selected patients does not count. (Hint: if such definitive evidence existed based on a decades old theory and simple lab measurements, don't you think it would be common supposition in the clinical and scientific literature?)

Item 3: There is limited to no biological rationale for thinking that TC per se, let alone intake of dietary cholesterol, has anything to do with the underlying process that actually causes atherosclerosis: an as yet poorly described process of LDL degeneration and *subsequent* infiltration and consequent inflammation. There is a priori reason to expect that SFA intake should be protective relative to PUFA, for instance, and neutral with respect to carbohydrate. As a starting point, I recommend going back to Anitchkov's cholesterol-fed rabbit model which already established that massive intravenous injections of pure cholesterol couldn't cause atherosclerosis even in an herbivore! Dietary cholesterol intake is frankly irrelevant for CHD risk.

Item 4: You are systematically ignoring the wider picture on the health of hunter-gatherer's and other non-industrialized peoples. There is a vast body of literature demonstrating human's adaptations to at least partial carnivory, including efficient and safe cholesterol handling in the metabolically healthy. Where are you getting your data on the Masai? I'm sorry, youtube videos don't count.

In summary, it is clear that you have an ideological position to defend: veganism, or some other "whole plant foods" type diet. You won't catch me calling plant foods unhealthy (humans are not pure carnivores) but neither are the right animal foods (human's are well-adapted omnivores my friend). I know it sounds unfair to put it this way, but defending the healthfulness of omnivory is the only sane conclusion from the literature, whereas advocating pure carnivory or veganism on the other hand, are clearly ideological extremes.

Chris

Tyler said...

Stephan,

Thanks for the reply! If you have another free minute after thwomping our friend Bog here, I just wanted to clarify something:
I thought a majority of wheat produced was a product of "genetic tinkering in a lab" by Monsanto and the like. I know that humans have introduced new foods and had it work wonderfully for us in our evolutionary history, so my question is whether or not these recent adaptations to grain would apply to modern GMO grains, or whether they should be viewed as a new food altogether.

Thanks again,
Tyler

Bog said...

To argue that dietary cholesterol does not have effect on serum lipids is just insane.

Apparently even Ancel Keys corrected his stance on the issue, in 1984 he reviewed 39 controlled feeding experiments.

44. Keys A. Serum cholesterol response to dietary cholesterol. Am J Clin Nutr. 1984;40:351–9.[PubMed]

Here's Hegstedts review

45. Hegsted DM. Serum-cholesterol response to dietary cholesterol: A re-evaluation. Am J Clin Nutr. 1986;44:299–305.[PubMed]

Here's just a tip of the Iceberg

Connor WE, Hodges RE, Bleiler RE. The serum lipids in men receiving high cholesterol and cholesterol-free diets. J Clin Invest. 1961;40:894–901. [PMC free article][PubMed]

Mattson FH, Erickson BA, Kligman AM. Effect of dietary cholesterol on serum cholesterol in man. Am J Clin Nutr. 1972;25:589–94.[PubMed]

Sacks FM, Salazar J, Miller L, et al. Ingestion of egg raises plasma low density lipoproteins in free-living subjects. Lancet. 1984;1:647–9.[PubMed]

Lehtimaki T, Moilanen T, Solakivi T, Laippala P, Ehnholm C. Cholesterol-rich diet induced changes in plasma lipids in relation to apolipoprotein E phenotype in healthy students. Ann Med. 1992;24:61–6.[PubMed]

Knopp RH, Retzlaff B, Fish B, et al. Effects of insulin resistance and obesity on lipoproteins and sensitivity to egg feeding. Arterioscler Thromb Vasc Biol. 2003;23:1437–43.[PubMed]

Knopp RH, Retzlaff BM, Walden CE, et al. A double-blind, randomized, controlled trial of the effects of two eggs per day in moderately hypercholesterolemic and combined hyperlipidemic subjects taught the NCEP step I diet. J Am Coll Nutr. 1997;16:551–61.[PubMed]

There's not single lipid-researcher on the face of this planet who takes Willet-show seriously. Why? Study design, short follow-up, lack of statistical power, high risk cohort without proper control group, etc exactly as Jenkins & Co informs us (2010).

Stephan Guyenet said...

Hi Bog,

Your comments got caught in my spam filter. I've published them. I can see that you feel very strongly and are not going to budge. I think we'll have to agree to disagree here.

Bog said...

@Stephen,

ok, buddy. Thanks for tolerating opposing views. But now my posts appear as duplicate. I though it got through the filter simple because of the lenght of the post.

@Unkown,

Campbell and Co gave free access the whole raw data from China. This was extremely exceptional, and I have never seen anything equivalent. Usually scholars never do this because of data abuse issues. I think he did mistake. He explained that they wanted to be very transparent because of the controversial nature of their findings. Campbell and the chinese fellows were responsible only of the study design. Richard Peto from Oxford sorted out the data.

I am off...

cheers

Jenny said...

Is it possible that the decrease in stature in neolithic agricultural societies occurs simultaneously with the huge growth of population tha occurs in the same epoch because the agricultural lifestyle allows less robust children to survive into adulthood?

In a hunter/gatherer world it's possible that only the largest strongest children could survive. Once a child was 3 and too old to be carried by the mother, if they couldn't keep up, they weren't going to last long. A settled lifestyle allows far more offspring to survive, though it does bring with it the diseases that happen only in larger populations.

I was shocked when doing some research last month to discover that there were only about 5,000 Inuit in all of Arctic Canada in the 1920s. That number ballooned to over 41,000 by the mid 1990s after most had given up their traditional lifestyle.

The Inuit today are not as healthy as they used to be but obviously far more of them survive to adulthood than used to be the case. The traditional lifestyle kept the number of surviving offspring very low.

Robert Andrew Brown said...

You will find the videos Bog is referring to here

http://www.youtube.com/watch?v=6bSdnQ1MKGo&feature=relmfu

The language suggests a clear underlying vegan agenda.

The site includes this video

http://www.youtube.com/watch?v=egqf7k5Lzhk&list=PLCC2CA9893F2503B5&feature=plcp

We are all interested in the impact of a variety of dietary strategies, and optimal human health, and that includes veganism.

The two videos I have looked at contain some very interesting material, but I have great difficulty with some of the conclusions reached, and denigration of the ethics of researchers who hold opposing views.

I would much rather have seen the author make a convincing case based on nutrition and physiology that veganism was the optimal diet.

Stephen said...

Fantastic series!

In the back of my mind I always though that genetics had to play some kind of role since humans are a global species and eat an extremely varied diet.

I used to be cold, hard paleo type. I've now evolved into a Weston Price type.

Onward through the fog.

Go Meat! said...

Sally Fallon argues that many hunter gatherer indeed consumed grains; she cites the Australian Aborigines and the California Native Americans as examples. Do you find this to be true? Even if they did eat grains, I imagine that they were a very small part of the diet and very well prepared. Native Americans went through great lengths to at least prepare nuts; making walnut oil was a week long process. Also, they did an outstanding job soaking their corn to avoid pellagra.

Don! said...

The Japanese have high levels of strokes (due to high salt intake, smoking, high blood pressure)

Why are you so sure the high incidence of strokes in Japan is due to those things? Japan has a high incidence of hemorrhagic stroke, which is linked with low cholesterol.

Bog said...

Ouh...last words.

"I can see that you feel very strongly and are not going to budge. I think we'll have to agree to disagree here".

I will budge the very first moment the IOM budges on their stance on coronary heart disease and dietary cholesterol. I am afraid two poorly designed epidemiologic studies with mutltiple red flags in them together with the Masai are not enough. It's all about the balance of evidence. I am sure you've heard about it.

Extraordinary ideas requires extraordinary evidence.

What I want from you the next time you give a lecture about Masai is to address these important points:

1) Masai are a prime example of the lipid-theory. Low total serum cholesterol, low incidence of heart disease. If you going to eat loads of high-fat dairy products, make sure not to eat over 1700 kalories a day.

2) The Masai are not a prime example of cholesterol ingestion. They are the contrary. A genetic outlier.

"In contrast to white-americans who have a limited maximal absorption capacity of 300mg of cholesterol, the Masai could absord more than 650mg cholesterol. Compared with the 25% suppression of synthesis found in white Americans, the Masai could suppress 50% of their endogenous cholesterol synthesis".

Cardiovascular disease in the tropics. IV. Coronary heart disease.

3) Masai did not escape many of the diseases that has been associated with animal-based diets: autoimmune diseases, cancers, rheaumatoid arthirisis. You can also point that these diseases are completely alien to most of Central-African tribes living on quasi-vegeterian diets.

You can also entertain your audience by telling them this:

4) One guy who studied them, Mann, was reknown cholesterol confusionist who used extremely pejorative language about the health establishment during his lifetime. Founding about the fact that the arteries of Masai was after all plagued with atheromas must have been very unpleasant finding for him and afterwards the explanations he came up with can be most likely taken with a grain of salt.

Cheers

Sara said...

Stephan, could you please tag all your Otzi posts as Otzi (or Oetzi, which would be the usual way to write it without the umlaut), so that they are easy to link to?

Jane said...

Bog, the authors of this paper you gave on eggs and cholesterol http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989358/

..clearly think it's oxidised cholesterol that's the problem. Eggs might not be toxic to people with good antioxidant defences.

High serum cholesterol has been linked to copper deficiency. Have a look at this from copper researcher Leslie Klevay.

'..the Western diet is frequently low in copper. Copper deficiency is the only nutritional insult that elevates cholesterol (7), blood pressure (8), and uric acid; has adverse effects on electrocardiograms (7, 9); impairs glucose tolerance (10), to which males respond differently than do females; and which promotes thrombosis and oxidative damage. More than 75 anatomic, chemical, and physiologic similarities between animals deficient in copper and people with ischemic heart disease have been identified. Copper deficiency is offered as the simplest and most general explanation for ischemic heart disease.'
http://www.ajcn.org/content/71/5/1213.full

Not long ago I had some correspondence with Richard Peto and Colin Campbell of the China study. They did not know about Klevay's work, and I think this is why they believe saturated fat causes heart disease. Klevay found that a high-fat diet causing heart disease in mice did not do so if they were given extra copper.

The problem with animal foods, if it can be called a problem, is that meat is very high in iron, and dairy is very low in copper. Without copper, iron cannot get out of cells. This means that a diet very high in animal products can cause cellular iron overload, which is implicated as a cause of many diseases.

Bog said...

Damn...it's difficult to leave...I am trying

@Jane

Good point. The authors definitely address to role of eggs to serum lipids. Those with healthy baseline are very susceptible for the increase in serum lipids caused by egg cholesterol, this is a clinical, well established fact that not even well-informed confusionists cannot deny.

However, as you pointed out, Jenkins (the founder of "GI"-concept) is not so worried about the marginal increase of one egg to ones serum lipids, they are worried about, inter alia, the oxidative, pro-inflammatory effects on the endothelium lining of our arteries which is the primary reason we need to try to avoid eating cholesterol.

In regards to your enquiry. No! F.ex. Spence one of the authors of the paper (The director of stroke prevention and atherosclerosis research centre in London) has publicly disclosed that eggs are not suitable food for human consumption, and definitely not for people at risk for cardiovascular disease. He has further addressed that there's not a single Canadian (his audience) who is not in the risk group for cardiovascular disease. According to Spence "the only Canadians who should eat eggs regularly are those with terminal illness". At that point it doesn't matter what you do, you are going to die anyway.

The whole story is here:

http://nutritionfacts.org/video/avoiding-cholesterol-is-a-no-brainer/

Why would you want speculate with your antioxidant status when you can just eat a healthy plant-based diet and avoid eggs all together. I assume no one is forcing you to eat these cholesterol bombs. People like the Tamarahumara indians who eat healthy, unrefined plant-based diet diet 99% of the time can eat one egg here and there but for Western people a total ban for eggs is a good start.

According to Guynet one of the best dietary advices is to skip grains. If I remember correctly in his old blog post. I'll give you a second opinion. One of the best dietary advice is to skip saturated fat and cholesterol. With that advice alone you are going far. I admit it's not the trendiest, "hipster" opinion on the market, not an advice you will sell 20 millions book with but it's a good ever-green in my opinion :)

Cassandra said...

I second what Sara said. I'd love to share the Otzi posts in particular with some friends and it would be far easier to send a link to the tagged posts.

Asim said...
This comment has been removed by the author.
Asim said...

"According to Spence "the only Canadians who should eat eggs regularly are those with terminal illness". At that point it doesn't matter what you do, you are going to die anyway."

Really, your going to live forever on a plant-based diet?

Asim said...

"In the past year, two studies funded by egg marketing agencies led to media reports promoting the benefits of eggs."

So the egg lobby is more powerful than the statin industry and pharmaceutical companies, which supposedly don't influence 'accepted wisdom'?

"However, the consequences of high cholesterol intake in those at increased risk of cardiovascular disease WHO ARE SEDENTARY AND NOT LOSIGN WEIGHT – especially when already consuming relatively high levels of saturated fat – give reason for concern."

Really, this is science? A guy who subjects himself to a diet that clearly lacks any concern for health, when he eats an egg, may cause his cholesterol to become oxidized proves that 'eggs are bad' and shouldn't be eaten?

How many times does it need repeating that correlation does not prove causation?

Asim said...

I especially like this one:

"Possible confounding of cholesterol intake from eggs with other risk factors, such as smoking, have been raised as a concern. However, the careful work of Markus et al (55) showed that cholesterol intake, independent of smoking and other risk factors, increased carotid intima-media thickness."

And when we look at the careful work of Markus:

"Subjects were counseled to follow a low-fat, low-cholesterol diet. At every clinic visit, data were obtained on body weight, dietary intake, alcohol consumption, and tobacco use."

So essentially, the good old scientists had no idea what their subjects ate and were content to rely on what they were told.

Asim said...
This comment has been removed by the author.
Asim said...

Do we really need to actually examine critically how much 'supporting' evidence against egg consumption is based upon the following:

"Incident nonfatal myocardial infarction, fatal CHD, and stroke corresponding to daily egg consumption as determined by a food-frequency questionnaire."

I especially love it when the questionaire about food practices is based upon an 8-year follow-up.

Asim said...

As an side, unless you run as often as the Tarahumara, to the point you even adopt long-distance running competitions as part of culture going way back in time, one really has no point in trying to justify their diet as the reason for the well-being.

BTW, they ate eggs regularly, twice a week.

http://www.ajcn.org/content/31/7/1131.full.pdf

So essentially, the Tarahumara ate natural foods, and got plenty of exercise. They probably slept well too. But blame the meat and eggs...

Stephan Guyenet said...

Hi Bog,

What Mann pointed out about the Masai is that they're a genetically heterogeneous population. This is because they had a habit of raiding neighboring agricultural tribes for wives. They are not genetic outliers. There's a more parsimonious explanation for why they have a higher cholesterol tolerance: they have a habitually high cholesterol intake.

You say that "autoimmune diseases, cancers, rheaumatoid arthirisis" are caused by animal food. That is another outlandish claim with no credible evidence to support it. The only people who make this argument are vegan ideologues who are not thinking clearly about the evidence. If it were so clear-cut, nutrition researchers would be recommending vegan diets for health, but to the contrary, most researchers recommend avoiding vegan diets. As you said, extraordinary claims require extraordinary evidence.

I don't think the Masai diet is ideal by any means, however it does clearly support the hypothesis that a high intake of SFA and cholesterol are not sufficient to cause CHD, which is exactly what I was using them to demonstrate.

Within the context of typical diets, dietary cholesterol from whole foods such as eggs and meat has no discernible effect on CHD risk in humans. That is well established and widely accepted at this point. I interact with cardiovascular researchers who study this stuff on a weekly basis. They know full well that humans react differently to dietary cholesterol than rodents and monkeys. Cherry picking a few references does not change that fact.

When you feed dietary cholesterol to a rabbit or monkey, you can easily increase TC by 5 to 10-fold, and yes that does produce atheroscerosis. But when's the last time you saw a study where they gave humans dietary cholesterol and their TC went from 200 to 1,000 mg/dL? It doesn't happen.

"Clinical feeding studies show that a 100 mg/day change in dietary cholesterol will on average change the plasma total cholesterol level by 2.2-2.5 mg/dl, with a 1.9 mg/dl change in low density lipoprotein (LDL) cholesterol and a 0.4 mg/dl change in high density lipoprotein (HDL) cholesterol. Data indicate that dietary cholesterol has little effect on the plasma LDL:HDL ratio. Analysis of the available epidemiological and clinical data indicates that for the general population, dietary cholesterol makes no significant contribution to atherosclerosis and risk of cardiovascular disease."
http://www.ncbi.nlm.nih.gov/pubmed/11111098

"Based on these studies, the association between dietary cholesterol and CHD risk is, if anything, minor in nature. This is consistent with the finding that an increase in dietary cholesterol intake results in only a minimal increase in the total/high-density lipoprotein cholesterol ratio. Taken together these studies suggest that the association between dietary cholesterol and CHD is small, as most subjects can effectively adapt to higher levels of cholesterol intake."
http://www.ncbi.nlm.nih.gov/pubmed/16596800

This is what modern review articles conclude, and IMO this is the only reasonable conclusion one can come to by a thorough and dispassionate (non-agenda-driven) consideration of the evidence.

Stephan Guyenet said...

Ha, the Tarahumara eat eggs! That is hilarious. Nice find Asim.

Eva said...

Jennie, that's an interesting idea about agriculturalism perhaps allowing more weaker children to survive to adulthood, ie perhaps it thwarted survival of the fittest to some extent. Certainly, there are likely factors we have not yet thought of. HOwever, by that reasoning, physical characteristics should have continued to decline, but instead there was a rebound as we (apparently) adapted to the agricultural life over time. More likely, what constituted 'fittest' probably just changed a lot.

Anyway, it's nice to see someone being realistic about continuing evolution. IMO, the attitude that there has been no evolution since the paleo makes the paleo movement look foolish.

Unfortunately, it may be just a case of many people responding better to simpler ideas. I do think there has been some evolution, but as others have pointed out, there will be some alive now that did not get many of the 'newer' genetics and still do better on or even really have to have more older foods. And there are those whose ancestors were only just recently still huntergatherers, like the native americans, who are much less likely to have many of the 'new' genetics. And there has also been a very very rapid shift in recent years to all new foods beyond just grain eating. So it seems likely that our food changes are moving faster than our likely ability to fully evolve.

I do think it's worth noting that unhealthy populations tend to have low fertility, which is what has been happening globally in recent years and all the more so in so called 1st world countries. Evolutionary pressure now is probably greater than ever.

However, even pressure to be able to eat low nutrition chemical laden foods and still give birth will likely not necesarily result in really good health in old age. And now with older people not as directly contributing to survival of grandchildren, the overall population advantages to having many healthy older people surviving will probably not be so high as it once was. Likely, there is little current societal survival advantage to having long lived healthy older people.

The advantage is probably now on those who can eat crap and still give birth, but who may well die young afterwards leaving room and resources for the new generation.

Asim said...

Not a problem Stephan...

Much appreciate your blog and work.

Unknown said...

To round off Stephan's references, here are three mainstream meta-analyses assessing the influence of saturated fat on heart disease outcomes and risk factors. None of them are pushing a pro-saturated-fat agenda by any reasonable standard, in fact Micha and Mozaffarian come out slightly negative against it (whereas the other two are neutral, except Ramsden et al. suggest that palmitate consumption is possibly problematic and should be reduced in favor of monounsaturates or laurate+ stearate...)


Micha, Renata, and Dariush Mozaffarian. “Saturated Fat and Cardiometabolic Risk Factors, Coronary Heart Disease, Stroke, and Diabetes: a Fresh Look at the Evidence.” Lipids 45, no. 10 (2010): 893–905.

Ramsden, Christopher, Keturah Faurot, Pedro Carrera-Bastos, Loren Cordain, Michel De Lorgeril, and Laurence Sperling. “Dietary Fat Quality and Coronary Heart Disease Prevention: A Unified Theory Based on Evolutionary, Historical, Global, and Modern Perspectives.” Current Treatment Options in Cardiovascular Medicine 11, no. 4 (2009): 289–301.

Siri-Tarino, Patty W, Qi Sun, Frank B Hu, and Ronald M Krauss. “Meta-Analysis of Prospective Cohort Studies Evaluating the Association of Saturated Fat with Cardiovascular Disease.” The American Journal of Clinical Nutrition 91, no. 3 (March 1, 2010): 535–546.

We also have to contend with highly paradoxical findings (for instance the French paradox) or, the research in Australia demonstrating a massive risk reduction for folks eating full-fat as opposed to low-fat dairy:

Bonthuis, M., M C B Hughes, T I Ibiebele, A C Green, and J C van der Pols. “Dairy Consumption and Patterns of Mortality of Australian Adults.” European Journal of Clinical Nutrition 64, no. 6 (April 7, 2010): 569–577.


Implicating saturated fat as a cause of heart disease also does not square with the historical evidence- SAFA consumption of the US did not increase prior to the emergence of widespread CHD after WW I. The only dietary factors that had been in rapid change in the years preceding was a drastic increase in the use of sugar (see Stephan's posts on this or read John Yudkin's original book), and the beginning of substitution of animal fats with industrially-produced oils...

Finally, we may discover that infectious disease afterall underlies at least a critical part of the CHD process:

Azambuja, Maria Inês, Aloyzio Achutti, and Richard Levins. “The Inflammation Paradigm: Towards a Consensus to Explain Coronary Heart Disease Mortality in the 20th Century.” CVD Prevention and Control 3, no. 2 (April 2008): 69–76.

Chris

Asim said...
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Asim said...
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Asim said...

As an aside Stephan, this paper may be of interest to you, especially in light of this discussion on CVD and 'fat'. Let us know your thoughts, if any:

http://www.nature.com/nature/journal/v472/n7341/full/nature09922.html

As an aside, Stephan Hazen just won the inaugural Top 10 Clinical Research Achievement Award for this paper on the gut flora and it's relation to CVD risk, so it's recognized amongst a crew of experts, and further, it was published last year, meaning it's the latest in research.

http://www.cleveland.com/metro/index.ssf/2012/04/developing_a_cardiovascular_ri.html

http://www.cleveland.com/healthfit/index.ssf/2011/04/cleveland_clinic_researchers_f_2.html

Asim said...

Chris,

Just to make a comment regarding 'dietary changes', I'd add antiobiotics into the picture.

It is really a dietary factor, considering it dramatically alters the state of the gut flora, which in turn has impacts on how food affects the body.

nothing91 said...

"BTW, they ate eggs regularly, twice a week."

LOL @ Bog

Bog said...

"Ha, the Tarahumara eat eggs! That is hilarious. Nice find Asim"

1) Ofcourse they ate eggs, what do you think I've tried to explain you the whole time. With healthy baseline there's a linear relationship with dietary cholesterol and plasma cholesterol

"...the finding of linear association of dietary cholesterol intake and plasma cholesterol concentrations in man further undergirds the evidence relating dietary factors to hypercholesterolemia and atherosclerotic coronary heart disease".

The above is what the authors of the Tarahumare paper concluded. Compare to IOM:

"There is much evidence to indicate a positive linear trend between cholesterol intake and low density lipoprotein cholesterol concentration, and therefore increased risk of coronary heart disease"

http://www.nap.edu/openbook.php?record_id=10490&page=769#p2000dc1a9970769001

2) Guynet wrote: "Within the context of typical diets, dietary cholesterol from whole foods such as eggs and meat has no discernible effect on CHD risk in humans"

As I have already pointed out the lipid-researchers have known atleast fifty years that you cannot really show an association of dietary cholesterol intake to serum lipids on a high risk group. The readers of this conversation must be already familiar with this.

"The lack of relationship between dietary cholesterol and plasma cholesterol concentration in Americans with these relatively high intakes....Under conditions of similar high dietary intake the wide range of plasma cholesterol levels in Iowa children indicates the impact of genetic-metabolic factors in setting homeostatic level of the plasma cholesterol level and not the cholesterol in the diet as it is. When populations consuming low-cholesterol, low-fat diet are looked at the same perspective, a completely different pattern emerges".

Stephen, this is the money-line, the million dollar quate of the study (I know your ego forces you not to understand it, but for others):

"Apparently the level dietary cholesterol intake in the Tarahumaras is below the so-called treshold level above which differences in intake do not affect plasma-cholesterol concentrations. We suggest from various metabolic-studies that this treshold may well be in between 100-300mg/day of dietary cholesterol"

http://www.ajcn.org/content/31/7/1131.full.pdf

3) The lack of association of dieteary cholesterol intake and plasma cholesterol concentrations is problem of only in high risk cohorts. We can easily show the association in tightly controlled metabolic-ward type feeding experiments where more aggressive feeding procedures can be utilized.

Ancel Keys reviewing 39 metabolic-ward studies.

Keys A. Serum cholesterol response to dietary cholesterol. Am J Clin Nutr. 1984;40:351–9.[PubMed

Bog said...

"What Mann pointed out about the Masai is that they're a genetically heterogeneous population"

4) What Mann said is completely irrelevant. We know whether the Masai is genetically unique in terms of their cholesterol clearance mechanism, or not. And they are.

The Masai of East Africa: some unique biological characteristics.

"The high ratio of phospolipid to cholesterol and bile-acids to cholesterol in their (Masais) gallbladder bile explain the extreme rarity of cholesterol gallstones"

http://www.ncbi.nlm.nih.gov/pubmed/4103135

Why do you keep insisting that Masai are not a genetic outlier with extremely high caliber cholesterol feedback mechanism?

5) This may come out as a surprise. BUT, the Masai did not eat that much cholesterol. They eat very little anything. The Masai male consumes typically only 1700kals per day, compared to 2500kalories consumed by average American.

The masai have been traditionally on a low-calory diet regimen and walk about 30km daily, yet they end up having atherosclerosis. Doesn't sound too good to me.

Bog said...

6)Guynet wrote "You say that 'autoimmune diseases', cancers, rheaumatoid arthirisis' are caused by animal food. That is another outlandish claim with no credible evidence to support it"

I was thinking papers like these:

Br J Nutr. 2000 Nov;84(5):589-95.
The role of meat in the expression of rheumatoid arthritis.

and these:

Most authoritative ever report on bowel cancer and diet: Links with meat and fibre confirmed

http://preventcancer.aicr.org/site/News2?abbr=pr_&page=NewsArticle&id=20691&news_iv_ctrl=1102

and these:

“Researchers at the University of California, San Diego School of Medicine, led by Ajit Varki, M.D., have shown a new mechanism for how human consumption of red meat and milk products could contribute to the increased risk of cancerous tumors. Their findings, which suggest that inflammation resulting from a molecule introduced through consumption of these foods could promote tumor growth, are published online this week in advance of print publication in the Proceedings of the National Academy of Sciences (PNAS)”.

http://www.eurekalert.org/pub_releases/2008-11/uoc--her111308.php

A tightly controlled metabolic ward study with human participants found NOC arising from heme iron in meat forms DNA adducts in the colon, a risk factor for cancer.

http://cancerres.aacrjournals.org/content/66/3/1859.full.pdf

Numerous tightly controlled metabolic ward studies with human participants have confirmed that heme iron from meat significantly increases the production of cancerous N-nitroso compounds (NOC) in the digestive tract.

http://cancerpreventionresearch.aacrjournals.org/content/4/2/177.full.pdf

Bog said...

7) Guynet wrote: "If it were so clear-cut, nutrition researchers would be recommending vegan diets for health, but to the contrary, most researchers recommend avoiding vegan diets. As you said, extraordinary claims require extraordinary evidence".

I Guess vegans have hijacked prestigeous American institutions:

"This reaffirms AICR's recommendation for people to eat a plant–based diet, including foods containing fiber, such as whole grains, fruits, vegetables and beans".

Well, not really. The American health institutions may not openly embrace vegan diets on population level, yet they do not raise concern about them. Moreover, these institutions recommend "plant-based diets".

Here's a paper W. Willett co-authorated (2010), Relation of food cost to healthfulness of diet among US women.

What did Willett crew recommends?

"The purchase of more nuts, soy and beans and whole-grains and less spending on red and processed meats and high-fat dairy may offer best investment for dietary health".

8)@Unknown

There's not a single lipid-researcher who takes these meta-analyses seriously. I already wired you with a link to article by Jeremiah Stamler. Frank Hu one of authors of biggest meta-analysis showing little association of saturated fats to heart disease warned about the dangers of saturated fats in january 2012. Not even the authors of these papers take their papers seriously. Ronald Krauss, a lipid-researcher paid by Atkins foudation and Dairy Counsel recommends low-carbers to change animal fats to vegetable fats.

http://www.youtube.com/watch?v=Sw5-a-5y6P4&list=PLDBBB98ACA18EF67C&index=14&feature=plpp_video

Walter Willet, the principal scholar of the WHI recommends people to avoid butter and high-fat dairy products and shift to "plant-based diets".

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Unknown said...

Bog,

Your argument has degenerated into the proverbial moving goal post. You are claiming that all diets can be grouped into one of two categories: vegan, versus everything else that contains more than a miniscule amount of SAFA/cholesterol. Against a vegan background, cholesterol and SAFA have a linear relationship to blood lipids and therefore CHD, whereas against the other background, there is no dose-response relationship.

I'm sorry to put it this way, but that is just bogus.
If your theory posits that atherosclerosis is caused by blood lipids glomming onto/into the artery walls, just by virtue of their presence and concentration in the blood, then you need a dose-response relationship to demonstrate your theory. More cholesterol/LDL ---> more atherosclerosis.

On the other hand, if you accept as has been known since at least the 80's, if not longer, that LDL must first be modified (hint: oxidize or degenerate) before it can play it's role in this complex process, then there is no longer any reason to expect the dose-response relationship necessarily. Other factors would over-ride the significance of absolute TC levels. Fortunately, this is indeed consistent with the bulk of epidemiological evidence- crucially with the fact that correcting for TC/HDL ratios abolishes any predictive power of TC, which is why all the mainstream reviews evaluate TC/HDL primarily. Other factors include antioxidant status (esp. CoQ and E, but also copper) and LDL patterning. Thus, it is possible for an LDL measurement to increase, but for risk to decrease (the particle count often stays the same, but the size increases which is protective).

So, which version of the "lipid hypothesis" you subscribe to matters. Since we've demolished the association of SAFA/cholesterol with CHD in a manner consistent with the most up-to-date version of the lipid hypothesis, you have now switched the goal-post to this all or nothing nonsense.

Congratulations, you win. It is an assertion that cannot be disproven given current knowledge- although it doesn't seem very plausible, there may be a kernel of truth in that for some people, some of the time, these kinds of diets can be therapeutic. I don't deny that much.

Before I cease this debate altogether, let me just say that I find your confidence in speaking for the whole community of researchers astonishing. How do you know that no one takes those review articles seriously? Your repeated linkage to youtube belies your "insider" knowledge, and seems to focus on a vegan propagandist series. The editorial you reference is not at all unusual- when the rumblings of a new consensus begin appearing, it is not unusual for the "old guard" to go on the defensive. Editorials accompanying pieces like that are often meant to play "devil's advocate".

Anyhow, I'm done with this conversation because there is really no way to definitively disprove your assertion. Many of your other statements have been non-responsive to criticisms articulated by myself or Stephan.

I wish you well in your pursuits, although we must, indeed, agree to disagree...

Chris







.

Bog said...

@Chris

The whole debate is just silly. Incase you want to be bullet-proofed against atherosclerosis you follow what Bill Castelli has disclosed numerous times: people who maintain their total serum cholesterol under 150mg/dl do not get an atherosclerosis. This is the 2012 mainstream view. This is backed by 40 year old Framingham study.

William Roberts, the chiefeditor of American journal of cardiology explains it all here:

The Cause of Atherosclerosis

"Thus, although not clearly established at this time, to prevent atherosclerotic plaques, the serum LDL cholesterol must be <70 mg/dL, the serum total cholesterol certainly <150 mg/dL, and the high-density lipoprotein (HDL) cholesterol >20 mg/dL. The latter—surely a surprise to most readers—is in patients with a serum total cholesterol level about 130 mg/dL and a LDL cholesterol level of about 60 mg/dL. Exactly what HDL cholesterol level is required to prevent plaques is unclear at this time, but clearly if the LDL cholesterol is very low (eg, 50 mg/dL), then a low HDL cholesterol—as long as it is >20 mg/dL—appears not to be dangerous. Ideal may be equal serum HDL and LDL cholesterol levels or an HDL cholesterol > LDL cholesterol. In summary, the recommended guideline numbers—particularly those for primary prevention—are intended for decreasing the risk of atherosclerosis events, not for preventing formation of atherosclerotic plaques".

http://ncp.sagepub.com/content/23/5/464.full

95% of White-Americans have no chance in maintaining healthy cholesterol levels if consuming eggs or any other cholesterol laden foods regularly. You need to be genetically very gifted to do so.

Stephen likes the mainstream view, so here you go:

Cholesterol myth club on par with flat earth society.
http://www.ncbi.nlm.nih.gov/pubmed/2296560

Bog said...

The very moment dietary cholesterol stops having dose-dependent linear association to your blood lipids, the very moment you are in the high risk category for sudden cardiadic death: the most common cause of death in Western cultures.

Apart from Inuits (Inuit fossils show extensive traits of atherosclerosis and osteoporosis despite the fossils dug were in their 20's at the time of their death, national gepgraphy june/1987), there has never existed a single group of hunter gatherer's who would have their total serum cholesterol over 150mg/dl, everything above is atherogenic. Parasites or their modern version, statins are paleo-dieters best friend. (It's irrelevant what's the pathway that lowers your LDL, diet, parasites or statins; a healthy plant-based diet has no negative side-effect, though)

Eric said...

Bog,

Please stop, if you want to make these arguments get your own blog. You claim Stephen is guilty of "appeal to tradition" while you blatantly trot out an "appeal to authority".

"95% of White-Americans have no chance in maintaining healthy cholesterol levels if consuming eggs or any other cholesterol laden foods regularly. You need to be genetically very gifted to do so. "

I am a white american that goes through, at least, a dozen eggs a week, daily dairy, and meat almost daily. I also enjoy pork regularly and eating out occasionally. My last cholesterol number was TC 123 with HDL of 50 and Tri of 36.

Of course I am a healthy weight, get plenty of exercise, sleep, and lead an otherwise healthy lifestyle; but I guess those numbers are just a genetic fluke ;-)

Before you answer that take into account that before I was healthy ( Obese, weak, no exercise, sleep deprived, and eating the SAD ) my TC was still under 150, but the ratios sucked and I have a strong family history of atherosclerosis. I should have just left it alone since it would be impossible for me to get CAD since my TC was under 150.

Stephen,

Love the work, can't wait for more installments.

Asim said...

"Why would you want speculate with your antioxidant status when you can just eat a healthy plant-based diet AND AVOID EGGS ALL TOGETHER. I assume no one is forcing you to eat these cholesterol bombs. People like the Tamarahumara indians who eat healthy, unrefined plant-based diet diet 99% of the time CAN EAT ONE EGG HERE AND THERE and there but for Western people a total ban for eggs is a good start."

Let us re-iterate that the Taharahumara did not just egg eggs here and there, they ate eggs REGULARLY, twice a week. For a guy trying to establish eggs as evil, to the point they should be avoided all together, and in the same breath try and spin away clear-cut evidence of REGULAR egg consumption by the Tarahumara, when confronted with it, is about as ridiculous as it comes.

Again, the Tarahumara, as part of their culture, run regularly, miles upon miles, not only for purposes of hunting, but for the sake of running being looked highly in their tradition. The amount of running they did and do burns up their calories, meaning they rarely ever are in a situation where they constantly are consuming calories.

They also eat meat, though not regularly. They are not vegetarians and they are surely not vegans.

Any joe-blow, who reduces his calories and eats whole foods, whatever the food type, and starts to exercise regularly will see a drop in his numbers. It's been established over and over and over again.

Again, there is nothing but false correlation under the guise of science.

Asim said...

I find this idea about certain human beings not having atherosclerosis as absurd. As Stephan has stated multiple times, animals in the wild get astheroclerosis. In fact, young people get it as well. It varies in degrees.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1853041/

I can bet you even the Tarahumara get it and one would find it, if one performed autopsies on the dead bodies.

Asim said...

"The high ratio of phospolipid to cholesterol and bile-acids to cholesterol in their (Masais) gallbladder bile explain the extreme rarity of cholesterol gallstones"

http://www.ncbi.nlm.nih.gov/pubmed/4103135

Why do you keep insisting that Masai are not a genetic outlier with extremely high caliber cholesterol feedback mechanism?"

Can you please provide proof that the ratios in the gallbladder are a result of genetics and not simply because of their lifestyle?

You seem to be engaged in a lot of circular reasoning.

Unknown said...

http://www.prescription2000.com/Interview-Transcripts/2011-02-18-william-castelli-heart-disease-lipids-transcript.html

I assume this is where Bog's quotes from Castelli are coming from. If you read the interview, you'll see his views are actually more nuanced. Follow the Framingham risk calculator if you're interested. In particular, he mentions the Rotterdam study- and specifically supports the healthfulness of 100% grassfed animal products. He points out, correctly, that those products are the only way to get significant K2 (which has been shown to reverse coronary calcification). Another highly protective compound only found in ruminant animal foods (and in proportion to their grass-feeding) is CLA.

The problem with the TC <150 argument is that it is being derived from Framingham study which is observational. What they are catching in such a massive sample is an extreme end of a statistical distribution: the people with hyper-active LDL receptors- who are indeed at very low risk for CHD (the inverse of familial hypercholesterolemia). A higher receptor activity means LDL turnover is high- it sits around in the bloodstream less, and therefore has less chance to degenerate and infiltrate endothelium.

Therefore, it is incorrect to say that this is caused by a low TC per se, particularly given the oveall statistical superiority of TC/HDL. It is also incorrect to infer that lowering cholesterol to <150 through diet (or statins) will confer the same protection- that is just ad hoc reasoning.

To establish that requires a separate intervention trial, properly randomized. The Ornish trial he referenced was small, and the overall mortality data are a wash. As with Esselstyn's (and Fuhrmans..yadayada) protocol, there is a good alternative explanation: by driving total fat intake <10%, PUFA intake plummets, and the body converts excess carbohydrates into...*drumroll*...saturated fat! Therefore, LDL particles are both less abundant (probably), but much more importantly, better protected from oxidation (because they will have incorporated fewer PUFA's and more SFA's into their membrames).

The only way to settle this matter is to do a similarly rigorous, randomized intervention study pitting dietary strategies against each other: Ornish-Fuhrman-Vegan versus Paleo-esque (with 100% grassfed animal products/wild-cold-water-fish+ safe starches, but still lots of veggies/fruits). I predict both will be equally therapeutic and protective as far as atherosclerosis goes, but the paleo-esque plan will give better overall mortality and numerous other benefits, and will have dramatically higher satisfaction and adherence.

This has been an interesting conversation, as I believe your views indicative of a certain vegan-ist fringe. Although I've offered several indirect disproofs and numerous contrary pieces of data, I concede that it is impossible to properly refute at this point (as I said before).

Best of luck to you!

Chris

Asim said...

"Parasites or their modern version, statins are paleo-dieters best friend. (It's irrelevant what's the pathway that lowers your LDL, diet, parasites or statins; a healthy plant-based diet has no negative side-effect, though)"

Again, stupid statement and it's based upon circular reasoning. Again, the claim is that the beneficial effects of statins is because it lowers the LDL, which again is unproven. For example, statins have been shown to elevate vitamin D levels across the board.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2075568/

How does one not argue that the reason statins are beneficial is not because of LDL lowering, but because it raises vitamin D levels, which can be done safely in other ways as well?

In fact, this brings me to the LATEST analysis of the Masai and their vitamin D levels:

http://blog.vitamindcouncil.org/2012/01/25/new-study-vitamin-d-levels-of-the-maasai-and-hadzabe-of-africa/

I especially like thise one about vitamin D levels in vegetarians:

http://www.ncbi.nlm.nih.gov/pubmed/1623855

But they like to attribute the levels to osteomalacia, as if the osteomalacia wasn't caused by their 'plant-based' diet.

Further, again, this is an example of "you can't have your cake and eat it to." If statins have negative side-effects and if statins are benenficial because they lower LDL, then why doesn't the same logic tell you that the lowering of LDL is what causes the other negative effects?

Bog said...

@Eric

I come from a coutry where dietary habits are similar than that of the USA. 85% of the adult population here cannot even keep their cholesterol under 195mg/dl. I seriously doubt whether the US makes the exception, although I don't have the data at hand.

If what you say is true, then there's two possibilities: you either possess extremely efficient cholesterol cleaning mechanism and thanks to genetics cannot get atherosclerosis pretty much eventhough you tried. The second alternative is that you have some kind of a malfunction.

"More dispute has arisen regarding the association of low cholesterol and mortality in elderly persons. For example, in the Honolulu Heart Program low cholesterol was associated with greater mortality risk. Obvious explanations for the association are intervening factors that both increase mortality risk and decrease the cholesterol level. In the nine-year follow-up of the Helsinki Aging Study, mortality risk was associated with both lowered cholesterol synthesis and lowered cholesterol absorption, which reflect terminal decline and lead to lower serum cholesterol levels. These associations are not identified, and the relationship between cholesterol and mortality becomes distorted unless the follow-up is long enough"

http://content.onlinejacc.org/cgi/content/short/44/5/1002

What do you mean by appeal-to-authority? Are you suggesting people should do their own critical thinking on Phd level lipid research? LOL. What I suggest is that pay some effort to try to understand where authorities get their ideas. It's too easy to adhere to conspiracy theories these days.

@Asim

don't worry, most people in the West die with very low-cholesterols. We have fat diabetics who after having had their cholesterol sky-high much of their life time gets it reduced to under 150mg/dl with statins in weeks and die and end up skewing that statistics resulting in fodder for the confusionists. Everyone can get their cholesterol down in few weeks with modern drugs, buth the plaques in the arteries won't vanish in weeks. So it's about the context as well, the duration of low-cholesterol keeping matters equally much.

During the 40-year old history of Framingham study, 5-6 people have end up dying from heart disease eventhough they fall into the 150mg/dl treshold and adhere to correct context as well (according to recent interview by Castelli). One has been affirmed to suffer from malfunction and there's a strong suspect that the same applies to the rest as well, although not confirmed. Few things in life are 100% guaranteed, but some things are closer to it than others. Guizhui county in China did report a single death from coronary heart disease during the 3-year follow up. 250 000 people and virtually everyone had their cholesterol under the 150mg/dl treshold.

Bog said...

"Again, stupid statement and it's based upon circular reasoning".

Cholesterol confisionist do not like the fact that statins do pretty damn impressive job in lowering death rates,

Lancet CTT collaboration (2010)

They come up with ridiculous BS ideas of "anti-inflamtory effects of statins". BS that you only hear in drug manufacturers brochures. No one who designed these drugs and know how they work takes this balony seriously. The reason why they work is clear, they lower the LDL.

I am too tired to go even go there...look for primitivenutrition response serie dor the references.

Bog said...

"Why do you keep insisting that Masai are not a genetic outlier with extremely high caliber cholesterol feedback mechanism?"

Because the paper says so, I just don't have the time to write it all down for you. I cannot use the copypaste function with this material.

Masai do not each much more cholesterol than Americans, they eat very little anything, just 1700kals per day.

Bog said...

@Unknown/Chris

No on the field takes paleo-balony, appeal-to-nostalgia crap seriously. Red meat is associated with increased cancer risk in multiple extremely tightly controlled metabolic-ward studies, it alters the DNA in the colon, where the meat stays too long. Transit time of the food in the colon are the keywords here. Plants do better job.

Paleo "meat-eating is encoded in our genome"-crew should be in bed with the intelligent design -whackjobs.

Castelli adheres fully to the "vegan propaganda".

"You know, we know that if I can get your total cholesterol down around let's say 100 to 130 or so, and I have maybe not quite a billion people on the earth like that, and those people cannot get atherosclerosis. You know in the China Study, for example, when Chou En-lai was dying of cancer he started a study in China just like the Framingham Study. The only difference was it was in 880,000,000 people so it was a little larger than the Framingham Study. But you know they found these villages in China where you couldn't get a heart attack or you couldn't get diabetes and the women couldn't get breast cancer and you know their total cholesterol were 127, but the chances we could ever get Americans down that low with diet and exercise are not good".

"KIRK HAMILTON: But what would the diet be if you didn't have drugs and you could get everybody to do exactly what you wanted diet-wise in the United States? How would you reverse the heart disease?"

"DR. WILLIAM CASTELLI: Well you'd have them on a pure vegetarian diet and not getting fat on the vegetarian diet."

Asim said...

"Masai do not each much more cholesterol than Americans, they eat very little anything, just 1700kals per day."

You seem to just make things up as you go along.

1. So if the Masai eat as much cholesterol as Americans, that would mean they would be eating the typical Western diet, right? Which would mean enormous amounts, right?

2. The following paper once again contradicts your assertions:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1799077/?page=1

According to this paper, they ate 3000 Calories a day, 66% derived from fat. That is double your claims.

Let's see what excuse you fabricate out of thin air this time...

Asim said...

"Because the paper says so, I just don't have the time to write it all down for you. I cannot use the copypaste function with this material."

You seem to have a lot of time to write about you not having time.

I know the paper says so, but that's speculation as these same type of papers essentially assert. It's still circular reasoning.

You do realize that phospholipid's include choline and lecithin right. Based upon your erroneuous logic, we can attribute the ability of the Masai to synthesize cholestrol properly because they eat foods high in choline and lecithin. And you know where they come fromm in heavy doses right?

Asim said...

"Red meat is associated with increased cancer risk in multiple extremely tightly controlled metabolic-ward studies, it alters the DNA in the colon, where the meat stays too long. Transit time of the food in the colon are the keywords here."

Wait, your seriously going to argue this point... Really? Meat takes longer to transit than plants?

Stephan Guyenet said...

Hi Bog,

I don't have the time to read your comments, but I'm noting here that you are being a nuisance due to your serial commenting. I've been running this blog for a long time now, and I've encountered many anonymous troublemakers with extreme viewpoints like yours (vegans, anti-plant carnivores, raw fruitarians... they often have a similar approach to interpreting scientific evidence). I offered you a respectful way out, but you insisted on embarrassing yourself further. This is your second warning, and there will not be a third.

Stephan Guyenet said...

Bog, you got your two warnings, you ignored them so now you're gone. I've deleted your last two comments. Bon voyage, buddy.

Asim said...

BTW, since when did China become the standard of health. They have essentially surpassed 'vegetarian' India and become the diabetes capital of the world. They have the highest stomach cancer rates as well.

"They come up with ridiculous BS ideas of "anti-inflamtory effects of statins". BS that you only hear in drug manufacturers brochures. No one who designed these drugs and know how they work takes this balony seriously. The reason why they work is clear, they lower the LDL."

I especially love this comment... So the drug manufacturing brochures aren't about the amazing effects of statins to lower LDL cholesterol, but the anti-inflammatory effects of statins?

LeonRover said...

We Irish have a sayin'

"You can take the man out of the bog

But

You can't take the bog out ofb tyhe man".

d said...

After skimming all of Bog's comments, all that comes to mind is that little all cause of death U curve for total cholesterol.

Robert Andrew Brown said...

Why Bog is so wedded to certain views is unclear.

He does himself a disservice, because he / those he works with ? have clearly invested a good deal of time in research and have found some truly interesting material

eg here

http://www.youtube.com/watch?v=0GD_9UXHg_k&feature=bf_prev&list=PLCC2CA9893F2503B5

The suggestions of early seed consumption are fascinating.

The is no question that meat production is an 'inefficient' use of resources, and global food resource pressures are increasing.

There are also valid ethical questions.

It is important to consider and hone all sides of the argument.

I just wish he would not impugn the motives of proponents of dietary movements to which he is ideologically opposed, and address some of the counter arguments proposed, rather than adopting what is in effect a dogmatic position.

Given it is evident he or somebody has done a great deal of reading and research, an approach on his part that was more nuanced, would at the least have lead to some fascinating discussions. As it is sadly we have, lost the opportunity for a fascinating and informative debate, because of a dogmatic approach, and denigration of others who right or wrong in their positions are only trying to do the same as Bog, improve human health and well being.

Jurmaine Health said...
This comment has been removed by the author.
Jurmaine Health said...

Thanks for sharing information about diet, evolution, native diet, paleolithic diet etc. Good work keep it up !!!

Soft Tissue Injury

greeksquared said...

"When Chinese immigrate to America it is proven that their genome evolves at 1000000x the old rate since their children can digest milk after just one generation"

Signed common sense

Jane said...

Robert, thanks for that video. Very interesting.

David L said...

Caveman diet here:

How the cavemen ate: Cookbook reveals 77 recipes stretching right back to the Stone Age (and they taste surprisingly good!)

Read more: http://www.dailymail.co.uk/sciencetech/article-2139560/How-cavemen-ate-Cookbook-reveals-77-recipes-stretching-right-Stone-Age-taste-surprisingly-good.html#ixzz1ul0JLONA

Frank said...

Hi Robert

What part do you think should be more nuanced? At some point you need to take a stance, and based on his material he's taking the stance that meat increases diseases risk, that SFA & cholesterol are unhealthy, and that our diet should be primilary plant-based, and that a well rounded diet in 2012 does not need meat if you want to avoid it for ethical reason.

People are accusing Plant Positive of vegans propaganda but they are missing the point. He said multiple time in the comments section on youtube that he is vegan for ethical reason, that he could hardly make a case agaisnt minimal animal food consumption, and that his role is not to tell people how to eat. Hardly a propagandist,

Criticizing the Paleo diet, saying that it's root in the evolutionnary concept does not make any sens, saying that the science is still correct in regard to cholesterol and SFAs, that grains and legume and not unhealthy, that low-carb is unhealthy, etc, etc, is far from the same than pushing a vegan agenda. But I can see why people would confuse the two, because it comes from a vegan.

I'm no vegan personnally and I still think the conclusion he reach are valid and well thought.

As for Bog, I just wish he would have been much less agressive and would have listen to Stephan more. Stephan is the most flexible and open-minded blogger in the Paleo world, and he said multiple time that he's not agaisnt grain and legume per se, he don't buy into the CHI hypothesis, etc etc, so I don't think it was fair for Bog to try to call him out the way he did.

I'm still hoping for more individuals to take the time to watch the primitive nutrition series with an open mind and judge for themselves. He makes some pretty damn good points in regard to the paleo diet that needs to be adresses.

Stephan Guyenet said...

Hi Frank,

I hear what you're saying. I would have reacted much differently to Richard (Bog) if he had not acted like a child throwing a temper tantrum. He didn't realize going into it how much we actually agreed on, but it didn't matter because all he wanted was a fight. I don't plan on watching Plant Positive's YouTube videos, because I'm not too keen on watching some anonymous guy with an unknown scientific background try to rake people over the coals. That kind of attitude is a guarantee that no one in the community he's critiquing will learn from it. That being said, I'm sure I'd agree with some of it. In particular, I certainly agree that blood lipids are related to heart attack risk. However, I think the role of dietary cholesterol and SFA are probably minor if anything. Excess body fatness is a better explanation for elevated lipids, and as opposed to dietary cholesterol and SFA, body fatness has been repeatedly associated with serum cholesterol in observational studies.

The "animal foods are unhealthy" camp has been around for a long time. I often see a lot of cherry picking that goes into it-- let's pick on the worst animal foods and give a pass to plant foods. There are certainly certain contexts where animal foods can be harmful. If you eat a lot of processed meats like bologna or high-heat cooked meats like bacon, or you eat your meat as a fast food hamburger, yes you might make yourself sick eventually. If you have an iron storage disorder, you're better off avoiding red meat. But you can also make yourself quite sick eating plant foods such as white bread, donuts, candy, sweetened soda, and potato chips. Does that mean we should avoid all plant foods, or just the junk? The key is to select high-quality fresh ingredients, and prepare them yourself in a healthy manner.

As it stands, the evidence as I understand it strongly suggests that the "ideal" human diet contains high-quality plant and animal foods, consistent with our evolutionary history and physiology.

Stephan Guyenet said...

PS- I forgot to add-- the Masai are not the only culture that have low serum cholesterol in the face of a higher dietary cholesterol intake. Hunter-gatherers eating wild meat also have low TC. In fact, as far as I'm aware ALL non-industrial cultures have low cholesterol by modern standards, regardless of their animal food intake.

The paper Bog cited showing a strong correspondence between dietary cholesterol and serum cholesterol in the Tarahumara is interesting, but if it were applicable to us, it would suggest that even a modest amount of dietary cholesterol (140 mg/d) could raise TC by 100 mg/dL in humans! Well, a number of clinical trials have been done on this (and yes, some of them explored the low end of the range including a cholesterol-free diet), and dietary cholesterol does not have anywhere near that kind of effect in people who are not Tarahumara. Going from no cholesterol to a high cholesterol intake (let's say 500 mg/d-- twice what most Americans eat) on average will increase TC by about 15-20 mg/dL in short-term feeding studies, with some of that coming from LDL and some coming from HDL. The total effect on CHD risk is unclear because of the complex way it affects lipids.

Returning to the Tarahumara, based on what we know from controlled feeding studies, going from the low to the high end of Tarahumara cholesterol intake (20 to 140 mg/d) should increase TC by less than 10 mg/dL in a Western population, and again some of that is HDL.
www.ncbi.nlm.nih.gov/pubmed/1534437

Frank said...

Hi Stephan

Thank you very much for you comment.

Yes indeed I think in the end your diet would be much closer to what Bog recommend than what he seems to think. That's why I hoped he would have come into this debate with a less agressive style, as clearly he had not a good grasp of what you think is a healthy diet.

I hear you on the anonymity of Plant Positive but he's still bringing fresh evidences to the table and has a very great perspective on the Paleo diet. I don't think it really matter who delivers a message, the information in the message only are important. He offers a scientific reference for every claims he makes, so it's up to the reader to dig further if he wishes to.

There are still various biological plausible mechanisms by which meat could be harmful and this trend is repeatably observed in observationnal study (biological plausibility + animal studies + epidemiological studies in human are starting to be good enough evidence to avoid something on the basis that it could be harmful) so I think at this points it warrants to be cautious with meat consumptions- as in the quantity seen in LC/paleo type diet.

I personnally think the evidence as a whole points to a whole-food, plant-based diet with occasionnal (once a day, maybe even once every 2 day) animal product consumption. Obviously, it's impossible to have a clear cut-off number of animal product consumption at which diseases risk really start to increase so we could probably argue on this for some time, but in the end, I don't think we run much risk by reducing animal product close to a minimum needed for carninutrients and B12, and not go beyond this.

re: the masai

One point that Plant Positive repeatably makes in the series is that most traditionnal cultures had parasite infections which lowers cholesterol. That would go a long way explaining how these cultures could eat so much animal products and still have low TC.

PS. I just want to make sure i'm not coming off as a dogmatic, Plant Positive follower. I've got absolutly no business into this else than finding the diet that will give me the longest, diseases free life. I just think this guy presented a lot of very interesting material and has asked great questions.

Thanks again for taking the time to consider my comment.

Frank said...

Forgot to add

I don't have an as good grasp of the science as he does so I can't comment to well on the causal role of dietary cholesterol and SFAs vs. the role of body fatness, but I can only once again recommend that you watch to whole serie as many of this is discussed in greater length.

And obviously we agree and he would on the role of processed vs whole food. But there still is biological plausibility for unprocessed meat, especially red.

Stephan Guyenet said...

Hi Frank,

There are biologically plausible mechanisms by which meat could be harmful, I agree. However, if you look hard enough, there are biologically plausible mechanisms by which almost any food could be harmful. Brassicas contain goitrogens, grains and legumes contain phytic acid, digestive enzyme inhibitors, and tannins, tomatoes and potatoes contain glycoalkaloids that can be quite toxic under certain circumstances, etc etc. I would not say any of those foods are inherently unhealthy though. The question is, in the context of a typical dietary pattern, what foods will decrease overall health and what foods will increase it in most people?

There is really no evidence that poultry or seafood are harmful, if properly consumed (in fact most of the evidence suggests seafood is protective, with the possible exception of highly contaminated species of fish). There is conflicting evidence that red meat could be harmful. However, most of it comes from epidemiological studies that I don't find very convincing. The first reason is that the food frequency questionnaire is quite a poor measurement tool for red meat intake (typically less than 25% of the variability in intake between individuals is accounted for), and different types of people are likely to over- or under-report it, introducing systematic biases into the data. The second reason is that people who eat red meat tend to have a suite of unhealthy diet/lifestyle behaviors, and I don't believe observational methods are able to fully correct for these mathematically.

Controlled feeding trials show that when fat content is controlled, serum lipids are the same whether you eat white meat or red meat:
www.ncbi.nlm.nih.gov/pubmed/21902857

Controlled "paleolithic diet" trials including red meat have shown that it is compatible with substantial fat loss and improvements in glucose tolerance and estimated insulin sensitivity.

Personally, I think the most plausible mechanism by which fresh red meat could be harmful is iron overload. Serum ferritin, although not generally associated with CHD risk or total mortality, is strongly associated with diabetes risk. People with high ferritin are probably better off avoiding red meat, or donating blood. However, for premenopausal women this same property will often be helpful because they're frequently anemic.

We'll see where the evidence leads, however for the time being I'm not convinced that gently cooked good quality fresh red meat is harmful. I do not think it's irrational to believe that red meat is harmful, because there is some evidence that's consistent with that view. I say if you want to avoid red meat, go ahead and avoid it. Same for saturated fat.

Regarding parasites, it is possible that they're part of the reason why high-meat HGs have low cholesterol, although I find that explanation to be rather ad hoc since it has never been experimentally demonstrated. I think leanness and energy balance is an explanation that rests on a more solid footing. Regardless, every non-industrial culture has parasites, so this same line of reasoning also applies to the Tarahumara, Bantu, New Guinea highlanders, and all the other plant based cultures with low cholesterol.

Unknown said...

Frank,

I think Stephan addressed the main biologically-plausible issue with red meat consumption: iron-storage overload.

Ron Krauss is actually working on this hypothesis presently, and should have some interesting data soon.

“Ron Krauss: Saturated Fat and Red Meat? It Depends.” How On Earth - The KGNU Science Show, n.d. http://howonearthradio.org/archives/1894.

Within the boundaries of real foods and a non-extreme diet, there is no problem with SFA and cholesterol consumption. Although there is always conflicting evidence, I think the balance, carefully interpreted (but not too carefully I hope! ;)) shows that SFA consumption is in fact protective, at least up to a certain level.

{For a powerful demonstration of a dose-response *protective* effect of SFA consumption:
Mozaffarian, Dariush, Eric B. Rimm, and David M. Herrington. “Dietary Fats, Carbohydrate, and Progression of Coronary Atherosclerosis in Postmenopausal Women.” The American Journal of Clinical Nutrition 80, no. 5 (November 1, 2004): 1175–1184.}

Why Mozaffarian (and Willet and the other Harvard boys) continues to advocate vegetable oil consumption is, however, beyond me! From the first principles reasoning I articulated earlier in this series of posts- there is reason to expect SFA's to be protective relative to PUFA's with regards to actual infiltration of LDL into arteries. Ron Krauss also says as much in the interview I linked to above- and his group has demonstrated the pattern shifts that are probably involved.

This is also consistent with the early PUFA-oil trials (e.g. Rose Corn Oil, and Anti-Coronary Club) although admittedly not with some of the later trials. The best explanation I've seen for the difference is that the later trials were not *displacing* a low-PUFA intake (as was the baseline in the early days when people were getting a lot of animal fat and little vegetable oil). Also, I think there was an obvious problem with some researchers thinking that a lowered TC or LDL (mass) measurement, was, in itself, protective. But I'm not sure that's the whole story...

Anyhow, it seems to me that displacing SFA's with PUFA's is dangerous. MUFA's are probably a fine, and I think the body's endogenous production of a mix of SFA's and MUFA's from carbohydrate is a signal that some kind of balance between saturated and unsaturated (mostly MUFA) fats is desirable, especially if they constitute more than a trivial amount of total energy intake.

I'm sorry, but I don't think there is a good argument in 2012 for the vegan diet, outside of an ethical belief system...I don't even think it's a productive conversation to have, and I would much rather that those of us in opposition to SAD and unsustainable agriculture move beyond it once for all into other more important issues...


Chris

Frank said...

Hi Stephan.

Before going any further, I just wan't to make clear i'm not really debating this up with you or anyone as i'm far from being sure about what dietary pattern should be followed (if any, as what comes out of all of this is that humans are opportunistic creatures that can do well on a large variety of dietary patterns - but obviously we are looking for the optimal one, if that can be found) but I'm just giving my point of view away, the things that make me consider lowering meat, which tends to change a lot on a day to day basis. That being said...

Yes, there are biological mechanisms even for vegetable products, but they are not observed in large scale observationnal human studies, unlike meat. If we had only mechanisticals study for meat I would not give it too much attention, but as I said, when we have multiple lines of evidences that are consistent (fundamentals, animals, epidemiological in human) it starts to add up. Like lectins could theorically brings up problems, but when you look at population eating huge amount of lectins-containing food, they don't have these theorical problems.

As for epidemiological studies, again, on their own, they don't tell us much, but my reasonning is the same : there is multiple, consistent line of evidences that indicate that meat could increase diseases risks, so it adds up.

In the latest EPIC study, they compared healthy omnivores (not smoking, eating fruits and veg, etc, etc) to healthy vegetarian, and vegetarian still did better than the healthy omnivores, in regards to cancer.

http://nutritionfacts.org/video/vegetarians-versus-healthy-omnivores/

Iron overload is one of the most studied mechanisms, but i'm still concerned about the high AGEs content of meat, the effect of SFAs & cholesterol on insulin sensitivity (especially in the lean, insulin-sensitive individuals), the effect of animal protein on IGF-1 and the link between IGF-1 and cancer (far from proven) the amines formed in meat while cooking, the effect of SFAs on LDL. On the top of my head this is what I can remember that could be harmful with meat.

Well, as you said, we'll see where the evidence will lead us, and again, I'm pretty sure i'm fully in agreement with your general dietary patterns recommandations, so i'm not really debating anything here.

Stephan, you are one of the most open minded bloggers that i've read, i'm thanking you for this.

Cheers!

Frank said...

Hi Chris

Reading your post had my remember this post from Michael Rae

http://www.mprize.org/blogs/archives/2010/01/hi_dr_feinman_a.html

I think it adresses some of what you says.

And again, i'm not pushing nor is Plant Positive pushing a vegan diet. Plant-based with occasionnal animal food consumption is not vegan. But it is still very different than what the paleo diet recommend (high in meat, SFAs, cholesterol, avoidance of legumes and grains) - which, btw, isn't what I think Stephan recommend.

Frank said...

Chris

If we are to assume that LDL infiltration is problematic, why would we accept to have higher LDL level in the first place?

There was a review paper arguing that the size of LDL particule don't matter, in the end it is still about Total LDL level.. I can't find the review paper right now, I'll keep looking and post it back.

Frank said...

ref:

LDL PARTICLE SIZE: DOES IT MATTER?

http://www.athero.org/commentaries/comm564.pdf

Robert Andrew Brown said...

Hi Frank

By nuanced I meant less aggressive and responding to some of the more complex arguments raised.

The primitive nutrition series does refer to some fascinating material but many of the arguments are open to interpretation and some I respectfully suggest are prematurely drawn and flawed, for example the much discussed cholesterol argument is just not as simple as vegetarianism = low cholesterol = heart health.

A host of other reasons apart from meat and 'fat' may also contribute to explaining the positive health outcomes seen in those moving from the standard American diet onto vegetarian diets.

Eskimos demonstrate that people can be healthy eating a lot of fat, but the fat the ate was mainly marine (so high in Omega 3s rather than 6s) and probably largely uncooked.

Interestingly in this video Dr Barnard' vegetarian diet excludes all vegetable oils, (Eg see 14.30 and 21.50 which recognises the importance of the Omega 6 derivatives the prostaglandins in inflammation pain and hormone production - an issue I also raised a while ago in an interesting but poorly written book) From his lectures it looks as if junk food is off the vegetarian menu as well as providing some supplementation. He does not differentiate between meat types, processed meat, fish, cooking methods etc.

I very much recognise that Dr Barnard is working hard on a non profit basis to try and achieve better health, and commend him for it.

There are populations that lived on very high carb diets and did not suffer from western conditions, albeit it is clear every diet has it benefits and detriments.

There are some very healthy vegetarians, and many that are definitely not so healthy, which raises important long term questions.

Our gut suggests we are designed for more nutrient dense foods, and cooking may be a factor in accommodating vegetable material to the human gut, but it also suggests that animal matter formed an important part of our diet.

If the premis was you can be healthy on a vegetarian diet conditional on defined nutritional requirements, and they believe it is a better way forward to human health, I would accept that would be a reasonable corner to fight. I would be interested in looking at the evidence they offered as to the long term health effects of a vegan diet etc.

I do not think many would dispute removing junk (most 'processed')food from their diet, including plant fiber, removing vegetable oils, and taking some supplements of essential nutrients would improve the health of most people on the average 'Western' diet.

The question is not will less junk food and vegetable oils improve long term health, but how do we achieve optimum nutrition, and how do we logically account for the inconsistencies that are seen in historic tribal diets in the fats v carbs arguments.

Stephan is doing a great job in helping us tease out these arguments and is not afraid to amend his position in the light of new evidence.

Robert Andrew Brown said...

I forgot the reference. Here it is

http://www.youtube.com/watch?v=TDgA3T_JF2A&feature=related

Apologies

Robert Andrew Brown said...

"In the latest EPIC study, they compared healthy omnivores (not smoking, eating fruits and veg, etc, etc) to healthy vegetarian, and vegetarian still did better than the healthy omnivores, in regards to cancer.

http://nutritionfacts.org/video/vegetarians-versus-healthy-omnivores/"


Thanks for the very interesting reference.

The conclusion was

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699384/?tool=pubmed

"Results:
There was significant heterogeneity in cancer risk between groups for the following four cancer sites: stomach cancer, RRs (compared with meat eaters) of 0.29 (95% CI: 0.07–1.20) in fish eaters and 0.36 (0.16–0.78) in vegetarians, P for heterogeneity=0.007; ovarian cancer, RRs of 0.37 (0.18–0.77) in fish eaters and 0.69 (0.45–1.07) in vegetarians, P for heterogeneity=0.007; bladder cancer, RRs of 0.81 (0.36–1.81) in fish eaters and 0.47 (0.25–0.89) in vegetarians, P for heterogeneity=0.05; and cancers of the lymphatic and haematopoietic tissues, RRs of 0.85 (0.56–1.29) in fish eaters and 0.55 (0.39–0.78) in vegetarians, P for heterogeneity=0.002. The RRs for all malignant neoplasms were 0.82 (0.73–0.93) in fish eaters and 0.88 (0.81–0.96) in vegetarians (P for heterogeneity=0.001).
Conclusion:
The incidence of some cancers may be lower in fish eaters and vegetarians than in meat eaters."

Fish eating also appears to confer a possible advantage in some cancers - I suggest we are still back to ferreting out the detail.

Robert Andrew Brown said...

Dr Barnard with his vegetarian diet also recommends vitamin D supplementation.

http://www.youtube.com/watch?feature=endscreen&NR=1&v=aWLnlhLNa28

Hopefully not many readers will dispute that many in the population are vitamin D insufficient and a long way below the suggested optimum.

A whole food, high plant fiber, low vegetable oil fat, no junk food vegetarian diet, plus B12, Vit D, a multi vitamin (which will include some minerals) has to be an improvement on the Standard American Diet.

Unknown said...

Frank,

Thank you for the review paper. I'll look it over for sure. I agree for various reasons that the particle size framework is fundamentally limited right now. Let me quote from a post that Chris Masterjohn wrote in response to a podcast interview {I think a lot of Masterjohn, and since this area isn't my specialty I tend to defer to those with greater expertise who I trust for various reasons}:

"I think this is possible, but again, the importance of particle number and size is in its infancy right now. I think the best evidence is behind promoting rapid clearance of lipoproteins and preventing oxidation by supporting antioxidant defense, proper endocrine signaling, and minimizing inflammation. Whether particle number or size is an independent contributor to the process rather than just an indicator that these other things have gone wrong is not at all clear to me at this point."

(http://chriskresser.com/episode-16-chris-masterjohn-on-cholesterol-heart-disease-part-2)

I think rate of clearance is the key point here. If LDL is higher with a faster rate of clearance, you are more protected than if LDL is lower with a lower rate of clearance. Particle size may be a proxy for this, but hasn't proved superior to TC/HDL, for instance, and may have significant methodological shortcomings still.

My point is that we have a theoretical basis implicating excessive PUFAs, supporting a protective role for SFAs (as demonstrated in the Mozaffarian study, which was far larger than, say, the Ornish trials), and complicating the significance of LDL magnitude within a reasonably normal range.

Chris

Frank said...

Hi Robert

I don't think I would classify Eskimos has a model of health

Again...

http://www.youtube.com/watch?v=x6j75BDq6DQ

You say a high-fat diet, but I think it's important not to lose sight of what really was the Eskimos diet : They were eating a lot of raw meat, organs (including brain) and even the feces of the animal corpse, to get fibers. Are we going to tell people to eat this way if we want to emulate their diet?

The Eskimos had early evidence of atherosclerosis and evidences of osteoporosis (most likely from a high protein, low calcium diet) and parasite infections.

Yes, there are healthy vegans and non-healthy; let's not forget that 1) it's still possible to have a crappy diet even if you're a vegetarian, especially if it was not really your choice and you don't have a good understanding of nutrition and 2) nutrition is far from the only important aspect of health. I would not say this is a proof of anything.

Everything is better than the SAD diet, this is a big problem with western, recent diet studies. Most participant at baseline have atrocious diet, so anything is actually better, that's why everything always improve in these studies. Even the Paleo diet is better than the SAD. Again, that don't prove much.

I'm up to a point where I really think that the evidences as a whole (that point is very important, as a whole) tell us that it's not a bad idea to rely less on animal food product. But that's just me. And i'm open to any new evidences.

Thanks for the discussion!

Frank said...

Hi Chris.

My understanding of the issue is also limited to what I can read in the published litterature (btw, it was more like a commentary than a review paper, but she still explain a few important things, such as the methodology limitation of old technique) so I don't know much more than that.

I guess the clearance speed must be important, but it remains that if your LDL are low, you're less likely to have problem, whatever the problem might be, although this is certainly not bullet proof.

The thing is that, given a minimum to get B12 and carninutrients, and I don't see any good reason to rely more than that on meat, and a few reasons not to, so my choice is not quite hard.

Thanks for sharing your thoughts with me!

Cheers!

Asim said...

http://anthonycolpo.com/?p=3550

Anthony Colpo on Plant Positive...

Asim said...

http://www.nature.com/nature/journal/v472/n7341/full/nature09922.html

http://www.cleveland.com/healthfit/index.ssf/2011/04/cleveland_clinic_researchers_f_2.html

"A study by the researchers, published Wednesday, showed that people who eat high animal-fat diets are not predisposed to heart disease based on genetics alone but also on the composition of their gut bacteria and how these bacteria aid in the digestion of their food."

Peter said...

"Regarding parasites, it is possible that they're part of the reason why high-meat HGs have low cholesterol, although I find that explanation to be rather ad hoc since it has never been experimentally demonstrated"

The mechanism how parasites affect serum lipids is quite well understood.

Role of cholesterol in parasitic infections
http://www.ncbi.nlm.nih.gov/pubmed/15882457

I don't have any data on the lipid-profiles of modern paleo-dieters. Anecdotally I can only tell what Kurth Harris has disclosed. Apparently he receives plenty of emails from people claiming to have their cholesterol shot through the the roof after adhering to his dietary principles.

"I don't think any person on the planet needs to have any of their lipoproteins or cholesterol tested ever. I think it's all worse than useless because, what happens is - and I get these emails all the time - you know, eating Paleo, feeling great, blood pressure decreased, no longer on medication, no longer have diabetes... bench press 250, and then they say, but, but, my total cholesterol is now 290 or 300 ...

My answer to that is, well, you were doing fine until you got your cholesterol measured."

--Kurt Harris, MD

According to Caldwell Esselstyn, his patients typically see their total serum cholesterol going under 150mg/dl in 14 days.

Peter said...

Very good source for references from PlantPositive/PrimitiveNutrition

The Futility of Cholesterol Denialism, Part 2: Cholesterol in Populations

http://www.youtube.com/watch?v=qGt97ojn5zs&list=PLDBBB98ACA18EF67C&index=3&feature=plpp_video

Asim said...

Again, how does cholesterol levels in the blood rising equate to higher CVD risk?

As the paper of Stephen Hazen references above, which was published just last year, and is critically recognized through scholarly award, the TMAO is a much better prognosticator of CVD risk than cholesterol, by ten times, and the TMAO levels are directly correlated to the gut flora.

Even when speaking about cholesterol, Hazen has clearly stated at another time:

"Most of us get over half of our cholesterol from what we make, not what we eat. Going on a strict low-cholesterol diet — while it's important and we recommend it — it won't have a significant effect on their cholesterol," says Hazen of people who produce too much cholesterol. Those people will benefit more from medication as their primary cholesterol treatment.

http://www.everydayhealth.com/heart-disease/cholesterol/taking-an-individual-approach.aspx

Asim said...

Even the following paper recognizes the variation in levels of LDL leading to heart disease:

http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/liu/ldloxida.pdf

"Numerous studies have shown that elevated serum low-density lipoprotein (LDL) cholesterol is
the crucial factor for the initiation and progression of atherosclerosis, and lowering LDL
cholesterol can largely reduce the incidence and mortality of cardio- and cerebro-vascular
diseases [1-3]. However, there is great variability in the incidence of coronary artery disease
(CAD) at any given level of plasma LDL cholesterol [4].
"

Asim said...

Further, the idea that changes in blood levels of a particular 'ingredient' through diet, such as cholesterol, necessitates a necessary evil is just not substantiated.

For example, oxidative stress increases during aerobic exercise. Does that mean one shouldn't run, because it would negatively impact the heart? The body most likely adapts, which is indicated by anti-oxidant defenses being triggered. Anti-oxidant levels go up as well.

It's hormesis.

Peter said...

Asim,

What I coincidence. I am just watching this video from Primitivenutrition and thinking that it would answer to many of your questions.

The Futility of Cholesterol Denialism, Part 3: A Process of Elimination

http://www.youtube.com/watch?v=SD48EGuP0QY&feature=autoplay&list=PLDBBB98ACA18EF67C&playnext=1

I am not in position to take a stance in this, but again anecdotally, I've heard several vegans getting their cholesterol from circa 200 to 120 in few weeks after ditching vegetable oils. Some people indeed have a problem with the liver. However, I don't think the doctor you referenced is fully aware of the results people get with aggressive dietary interventions. I am talking about the Ornish-Esselstyn-Pritikin style approach.

Asim said...

Considering Stephan HAzen is the head of the Preventive Cardiology at the Cleveland Center, and has just been awarded with a Top 10 Clinical Research Achievement Award for the paper I just referenced above, I'm quite sure he's aware of what you claim he is not aware of.

Asim said...

As an aside, cholesterol levels lowering as a result of the abandonment of vegetable oils can actually be indicative of the fact that cholesterol levels went up to protect against the damage the vegetable oils were causing.

It's circular reasoning yet again... Cholesterol is the negative effect because of vegetable oils.

Just to give you another example... It is now known that those people will higher levels of LDL normally put on more muscle mass. Your cells need cholesterol for the repairing.

http://tamunews.tamu.edu/2011/05/04/%E2%80%98bad%E2%80%99-cholesterol-not-as-bad-as-people-think-shows-texas-am-study/

Asim said...

Wiki will tell you 80 to 90% of all cells create and control cholesterol production in the body. Liver just produces a slightly greater relative amount.

Arguing that higher LDL levels are a problem of the liver is a rather huge leap of faith,

nothing91 said...

LOL, so Bog gets kicked out and now two of his meat-is-evil friends (Frank and Peter) show up. What an incredible coincidence! I'm sure Bog didn't contact them elsewhere and tell them to start posting here now that he cannot. Not a chance that happened, right? :-)

Stephan Guyenet said...

Let's not pick on Frank and Peter please. They're sharing their views in a respectful manner.

Stephan Guyenet said...

Hi Peter and Frank,

Just a quick couple of responses to some of the issues you raised. Regarding parasites, I do think it's plausible that they're a reason for low serum lipids in non-industrial cultures, however since parasite load has not been measured and related to serum lipids in the populations in question, it remains speculative. According to the paper Peter cited "The mechanisms involved in lipid changes related to parasite infections remain uncertain". The effects of parasite infection on CHD risk also remain uncertain, but I think you could hypothesize based on the lipid effects that they would be protective. In any case, a quick Google search reveals that populations such as the Tarahumara, Bantu and NG highlanders are riddled with several species of parasites, so applying the argument consistently, you can't attribute their low cholesterol to avoiding SFA and cholesterol either.

In addition, the Tarahumara have very high rates of iron deficiency anemia (common in cultures with heavily grain-based diets), iodine deficiency goiter is common, and they have high mortality rates in general. The point is that you can't point out the negatives about the Masai and Inuit (which I don't dispute) without acknowledging the negatives of more plant-based cultures.

Serum cholesterol will drop on almost any whole food diet that involves significant fat loss, particularly if it's high in fiber. Going vegan, even if the diet is well composed, will not get most peoples' total cholesterol under 150 mg/dL. Caldwell Esselstyn showed this in his CHD trial. He had to use a combination of diet and drugs to get the TC of coronary patients below 150 mg/dL.
http://www.ncbi.nlm.nih.gov/pubmed/7500065

The diet was extreme: a fat-free, whole food, nearly vegan diet. To his credit, the drug and diet combo apparently had a strong protective effect on CHD risk in that group. However, there's no evidence the effect was related to meat avoidance per se. His diet was super low in palatability, meaning they probably lost a considerable amount of fat and returned to energy balance. In addition, it eliminated junk foods, sweetened beverages, and was based on whole foods rich in essential nutrients, polyphenols and other protective phytochemicals. Not very surprising that it improved their cardiovascular health.

Regarding the high AGE content of meat, the highest quality evidence available indicates that this is a misconception. The idea originates from Dr. Helen Vlassara's research, which used ELISA to measure AGEs. Yet, a number of her findings were biochemically implausible, and the gold standard technique, GC-MS, found that cooked meat is considerably lower in AGE than bread crust for example. Butter contains a negligible quantity of AGE as expected, also in contrast to Dr. Vlassara's data.
http://www.ncbi.nlm.nih.gov/pubmed/18389168

That being said, I think ideally all plant and animal foods should be cooked gently.

Another point is that while low cholesterol is associated with lower CHD mortality, cholesterol below 140 mg/dL is associated with a substantially elevated risk of total mortality. Some people will have you believe this is because the cholesterol of old people declines as they are dying, but the same thing was observed in the massive MRFIT study, which looked at men from 35-57 years old.
http://wholehealthsource.blogspot.com/2009/07/mrfit-mortality.html

Whether this reflects cause-and-effect is open to question, but it certainly does raise some concerns about the overall effects on health of extreme cholesterol reduction in the context of a Western diet/lifestyle.

Cheers guys

AgingHippie said...

Have you seen this documentary

Did Cooking Make Us Human?

http://veehd.com/video/4565756_Did-Cooking-Make-Us-Human

Peter said...

Stephen,

I think primitivenutrition video serie covers the data on the identified parasites among modern hunter-gathers. Not sure though, since it's a while since I watched his initial serie. However, his material covers atleast very illustrative rotend study. The parasites could alone reverse the heart-disease of the mouse after it had been exposed to atherogenic diet. And, the definition of atherogenic diet in that study was not a diet of lectins, wheat and sugar.

In the Western people mortality risk has been associated with both lowered cholesterol synthesis and lowered cholesterol absorption which lead to lower serum cholesterol levels. In Western cultures sudden drop in cholesterol among elderly people rarely conveys any good news. Yet, it happens all the time. Chemotherapy, f.ex is very efficient tool in lowering serum lipids.

With all the data available, I don't think it's hard to reduce your cholesterol under the 150mg/dl treshold at all. In fact, everyone can try it for themselves. I don't think it's an issue whether plant-based cultures had parasites or not. They probably had them at much lesser rate compared to hunter-gatherers since they (plant-based cultures) were agriculturalists who had atleast primitive levels of sanitation sorted out. Ornish did not have any problems with his cholesterol targets for his patients, and he didn't use statins. Esselstyn opted statins only because of the time issue. There wasn't any. His patients were very, so sick there wasn't even chances for them to go through another mechanical procedure. That's why they were being allocated to Esselstyns care in the first place. No one had nothing to loose.

Esselstyn makes the point that virtually everyone can reduce their cholesterol under the 150mg/dl target in weeks. According to him, there's only small minority who do not succeed with this with diet alone, usually these people end up in the 155-165 range. I think that those people who cannot reduce their cholesterol simple do not go far enough with their diet.

Okinawa people are known to suffer from deficiencies, yet they are almost completely free from any chronic diseases, and have a nice life-span. IMO a valid point.

Peter said...

I might further add that we have plenty of data about the people who have exceptionally low serum cholesterol thanks to their genetic make-up. Some of these people have their LDL just 20mg/dl. Health-wise these people do just fine. Given this and the fact that Okinawa-folk have the longest life-span recorded (they surely had traditionally their cholesterol under 150mg/dl), IMO the whole notion of low-cholesterol being inherently dangerous is not well justified. We have many studies which have controlled the correct co-founders and found out that the lower the LDL, the better.

Anyway, I was surprised that even NCEP (national cholesterol education program) recognizes this:

"Only populations that maintain very low levels of serum cholesterol, eg. total cholesterol below 150mg/dl (or LDL cholesterol under 100mg/dl) throughout the life do we see a near-absence of clinical CHD".

Very low serum cholesterol maintained thoughout the life through lifestyle factors most likely have a favourable influence on life-span, atleast given that you have an access to a well sanitised toilet and antibiotics.

Ornish et al. demonstrated in an intervention trial that lowering LDL was associated with increased telomerase activity, which in turn is associated with longevity.

http://www.ucsf.edu/media/pdf/nobel/blackburn_and_ornish_lancet_2008.pdf

Relationship of baseline serum cholesterol levels in 3 large cohorts of younger men to long-term coronary, cardiovascular, and all-cause mortality and to longevity.

“These results demonstrate a continuous, graded relationship of serum cholesterol level to long-term risk of CHD, CVD, and all-cause mortality, substantial absolute risk and absolute excess risk of CHD and CVD death for younger men with elevated serum cholesterol levels, and longer estimated life expectancy for younger men with favorable serum cholesterol levels”.

http://www.ncbi.nlm.nih.gov/pubmed/10891962

I am glad I participated in this interesting debate. Unfortunately, I have to step aside.

Best regards,

Peter

Peter said...

Forgot this (important for all-cause mortality):

A meta-analysis of 108 randomized controlled trials of various lipid modifying interventions found that lowering LDL cholesterol significantly decreased the risk of coronary heart disease and all-cause mortality, whereas modifying HDL provided no benefit after controlling for LDL cholesterol.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645847/pdf/bmj.b92.pdf

Robert Andrew Brown said...

DO NOT download the software to view the link suggested by ageinghippy it is corrupted with a virus

Frank said...

Hi Nothing

I'm a long time reader of this blog, i've posted here before. Why do you seem to imply that I am dogmatic about my view on meat? I would say that my concerns in regards of meat are quite reasonnable and justified. I don't see how anyone who truely care about his health could easily brush away with the back of his hand so much evidences in favor of reducing meat and so much evidence in favors of whole grains and legumes.

After all, these are the official recommendation, it's not like I was holding a controversial point of view, unlike the paleo diet.

Hi Stephan

Thanks you for the AGEs datas, I was unaware of this. I was still using Vlassara's data. I'll have a look.

Just as Peter, i'm not here to debate or confront anyone on their take of the current evidences, so I was glad to share my point of view with intelligent and open-minded individuals here, and i'm gonna keep going forward,

Kind regards,

Arska said...

High cholesterol is good for women according to this latest Norwegian study: http://t.co/PPKzGI2w

Jane said...

'..the Tarahumara have very high rates of iron deficiency anemia (common in cultures with heavily grain-based diets)..'

The paper about this tells us the following.
'Iron deficiency is the most common nutritional disorder in the world. ..The normal physiologic iron losses among menstruating women and the substantial increase in iron requirements during the second/third trimesters of pregnancy make it inevitable for many women to develop anemia if they do not receive supplemental iron.'
http://global-breastfeeding.org/pdf/monarrez_anemia.pdf

Some people would not agree with this. Here's what Ray Peat says.
'Anemia in women is caused most often by a thyroid deficiency or by various nutritional deficiencies. ..Iron deficiency anemia does exist, in laboratory situations and in some cases of chronic bleeding, but I believe it should be the last-suspected cause of anemia, instead of the first.'
http://raypeat.com/articles/articles/iron-dangers.shtml

There are even scientists who believe 'iron stores' are abnormal and we shouldn't really have any. After all, practically everything we eat has iron, and if we have 'depleted iron stores' we can increase iron absorption many fold. Iron can be released from its intracellular storage protein ferritin by reactive oxygen species, meaning that all iron stores are potentially toxic.

So might the Tarahumara have other deficiencies? According to the National Geographic, they 'eat a lot of Maruchan, the Japanese instant noodles that come in plastic-foam tubs. Foil-wrapped potato chips, too, and plastic liters of Coca-Cola, and Tecate beer in pop-top cans..'
http://ngm.nationalgeographic.com/2008/11/tarahumara-people/gorney-text

Peter said...

Unlike planned, I have a free evening...nice:)

"High cholesterol is good for women according to this latest Norwegian study"

@Arska,

the study is an excellent reminder that science is not a democracy, not all studies are made to be equal. To understand why you might have a hard time convincing people to take that study seriously, you may want to view primitivenutrition's view:

RaCCG7: Norway, Women, and Cholesterol
http://www.youtube.com/watch?v=xiNvQ-g1XGs&list=PLDBBB98ACA18EF67C&index=19&feature=plpp_video

Basically the scholars behind the study did not even adjust the data for statin usage. The red flags of the study are numerous. A Finnish study that came out the same time was of much more higher quality. They observed the same what the Norwegians did, but adjusted for appropriate co-founders, the result, the lower the LDL, the better.

Joint effect of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol on the risk of coronary heart disease.

http://www.ncbi.nlm.nih.gov/pubmed/22023802

Anyway, I am bit perplexed over Stephens views of the impact of diet on serum lipids. I recall Stephen even did a blog post about the potato lobbyist who went to a high-carb vegan diet for 60 days and dropped his serum cholesterol by 60points all the way to the 140 range.

One of Esselstyns patients in his study was cardiologist from the same clinic. He was in his 40s, lean and fit had serum cholesterol 156 and was diagnosed with well progressed coronary heart disease. However, he was not in imminent threat and hence did not take statins. With diet alone he went from 156 to 89 in few weeks and saw a complete reversal of his coronary heart disease. The other patients were very ill, many of them had to sit while sleeping due to heavy angina. The men were all impotents who could barely walk 200yards without chest pain. Esselstyn though it was good idea to start with statins eventhough at the same Ornish was doing the complete drug-free trial and got each of his patients under the 150 treshold.

Stephan Guyenet said...

One thing I'd like to see more of a discussion on is serum cholesterol distribution in lipoproteins. Just as LDL (perhaps oxidized) is a causal factor in CHD, HDL is a protective factor and this is also causal. Total cholesterol is an outdated marker of heart attack risk, and is surpassed in predictive ability by the ratio of LDL to HDL (or TC:HDL or non-HDL:HDL). You can lower TC by lowering LDL, HDL or both. If the ratio doesn't improve, you have presumably not lowered CHD risk.

Here's an application of this idea. Last time I got my TC tested a few years ago, it was ~250 mg/dL. High risk, right? Except my HDL was 111 mg/dL (if I recall), and my LDL:HDL ratio was 1.2, placing me in an extremely low-risk category. Would I benefit from attempting to lower my TC to 150 mg/dL? Likely not. My cholesterol has probably changed since then though since my diet has changed.

Saturated fat, in short-term feeding studies, elevates both LDL and HDL, and according to Dr. Krauss's research, the increase in LDL may be due to an increase in particle size rather than number (and this implies no increase in risk from LDL). This may be why observational studies almost always find that saturated fat intake is not related to heart attack risk. Another reason may be that they typically find no relationship between SFA intake and circulating cholesterol level, so SFA may have only a minimal effect in the long term. The idea that SFA increase circulating cholesterol is based almost entirely on controlled studies lasting less than 3 months.

The point is that total cholesterol is not the best predictor of risk, so why focus on it? Using more modern and more accurate risk prediction methods including HDL allows us to be more flexible and achieve a more sophisticated understanding of the relationship between diet and CHD risk. Why eat an extreme diet to achieve extreme cholesterol values when you can get the same degree of risk reduction without it?

Regarding Dr. Ornish's claim that he can get people's TC to below 150 mg/dL with diet alone, I'd like to see some peer-reviewed evidence for that please.

Regarding intestinal parasites, all non-industrial cultures have them, and I'm not aware of any evidence that plant-eating cultures have fewer than animal-eating cultures. It's doesn't take a whole lot of digging to find evidence of widespread infection among the Tarahumara and other mostly plant-based cultures.
http://www.ncbi.nlm.nih.gov/pubmed/22069065
http://www.ncbi.nlm.nih.gov/pubmed/14950359
http://www.springerlink.com/content/71dff20dk4urayla/

Here's a study of horticultural New Guinea highlanders from 1970:

"Intestinal parasites were exceptionally frequent, especially Ascaris and hookworm (probably both Ancylostoma duodenale and Necator americanus), and a most notable feature (to the reviewer) was that one-third of all babies under 1 year old examined had hookworm. [This must be some sort of world record, but, surprisingly, the author makes no comment on it.] Entamoeba histolytica-like cysts were found in over 13%."
http://www.cabdirect.org/abstracts/19712700359.html;jsessionid=A7BD35159D6726ACCA80550DA362297F

Stephan Guyenet said...

One last thing I'd like to add briefly. One of the reasons the Paleo movement exists is that there are many people who have not been served well by the low-fat plant-based diet recommendation. Some people find that it's hard on their digestion, leaves them fatigued, and/or does not help their body weight or blood lipid profile. If someone goes Paleo and they feel better, plus their lipid profile improves (which is often but not always the case), and their glucose homeostasis improves dramatically (which is typical for people with pre-diabetes, see Dr. Lindeberg's trial for example http://www.ncbi.nlm.nih.gov/pubmed/17583796), it seems odd to me to tell them not to do it because it will ruin their health.

There's individual variability and what works for one won't necessarily work for another.

François Létourneau said...
This comment has been removed by the author.
Frank said...

Hi Stephan

What do you think of the meta-analysis that Peter posted just above which found LDL to be the greatest predictor of CHD?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645847/pdf/bmj.b92.pdf

Peter said...

Stephen,

what I meant was that the parasites and plant-based cultures is irrelevant in the sense that I believe everyone can get their serum cholesterol in the healthy 150mg/dl range in few weeks after adhering to Tarahumara-Ornish-Chris Voigh-style food patterns. You can start by with Ornish's classic study (Lancet 1990).

I'd say no one in the Paleo sphere have ever adhered to the kind of low-fat diet that 3/4 of the world still understood it few decades ago. Over 70% calories from unprocessed starch foods, low-protein, mostly plant-based diet, that is.

The american "low-fat" is diametrically opposite to Tarahumara-Okinawa food patterns, they have generally nothing in common. Apart from Pritikin's patients, virtually no one has consumed that kind of diet in the West. The american "low-fat" is epitomized in the WHI-trial. It's a diet laden with cholesterol and animal protein together with very low-fiber intake (only 16g), most likely it's only low-fat because sugary drinks (coke) dillute the high fat intake.

I personally think at this point that it's rather clear that most of the focus should be in lowering the LDL, and that is exactly what most of cardiologist are doing.

'Good' HDL Cholesterol Can Also Be 'Bad' (2012)

"the HDL amplified inflammatory reactions several times over and could explain the latent chronic inflammation that is associated with high cardiovascular risk,"

"Lowering the LDL level is therefore still even more important than raising the HDL level."

http://www.sciencedaily.com/releases/2012/01/120113210207.htm

Some HDL, or "Good" Cholesterol, May Not Protect Against Heart Disease (2012)

http://www.hsph.harvard.edu/news/press-releases/2012-releases/hdl-cholesterol-heart-disease.html

HDL Not Always the Good Cholesterol We Think Says University of Chicago Study (2008)

http://seniorjournal.com/NEWS/Health/2008/20081201-HDLNotAlwaysTheGood.htm

It can be long road for paleo-advocates to push their views to the mainstream, after all, there's not a single paleo-advocate who would have a background in modern lipid-research.

Peter said...

"after all, there's not a single paleo-advocate who would have a background in modern lipid-research".

this can ofcourse change someday.

Asim said...

Actual Okinawan diet:

http://www.okinawa-information.com/content/food-diet-okinawa-islands

Asim said...

Demonstrating that defective HDL can lead to a higher inflammatory state, which can promote CVD risk does not establish, logically, that higher LDL levels lead to higher CVD risk. It simply means that defective HDL levels can increase CVD risk, when the HDL isn't functioning properly.

It's essentially saying the same thing as somebody who argues that the quantity of LDL doesn't increase heart risk, but the QUALITY, i.e. oxidized LDL, which does.

Asim said...

Again, the assumption that LDL is what causes heart risks is presumed as a fundamental truth in essentially all the articles references, when this is the very basis of contention.

http://medicine.osu.edu/research/news/archive/2012/01/25/osu-wins-nih-funds-for-statin-focused-pgx-study.aspx

It just shows how much money is being pumped in to the promotion of statins.

"Specifically, he wants to develop MULTI-GENE models for use in patient-selection strategies for improving the efficacy and cost-effectiveness of statins and to reduce the incidence of adverse effects."

Are you kidding me, multi-gene models...

Stephan Guyenet said...

Hi Peter,

Wait a minute, are you arguing that HDL isn't important for CHD risk, or that it could even be harmful? That is a rather bizarre perspective, considering we have very solid and consistent evidence showing an inverse relationship between HDL level and CHD risk, and that there are quite well established mechanistic reasons for this. HDL is anti-inflammatory and transports cholesterol from foam cells to the liver. People in my department do reverse cholesterol transport experiments with HDL on a weekly basis.

The NCEP recommends screening for low HDL to identify those at high risk of CHD.

High HDL is associated with low CHD risk, and the ratio between non-HDL and HDL provides better risk prediction than non-HDL alone. This is supported by a meta-analysis involving 900,000 people with 55,000 vascular deaths:
http://www.ncbi.nlm.nih.gov/pubmed/18061058

Frank, the review article Peter posted was specifically looking at treatment-induced changes in LDL and HDL, which is not the question we're debating here. That meta-analysis mostly concerned drug studies. Yes, statins reduce CHD risk (at least in high-risk groups) and that is probably related at least in part to LDL reduction. We don't yet have any drugs that are capable of increasing the functional capacity of HDL. Key phrase = functional capacity. CETP inhibitors like torcetrapib increase HDL cholesterol but do not increase HDL functional capacity, in fact they likely reduce it because all they do is pack the existing particles with more cholesterol esters.

Peter, I did look up Ornish's 1990 Lancet paper, and that's exactly why I said his diet doesn't reduce TC to under 150 mg/dL. He combined diet, exercise and stress reduction, and TC went down to ~177 if I recall.

I agree that the diet of plant-heavy non-industrial agriculturalists is not the same as the modern low-fat diet. Following the same logic, the diet of non-industrial cultures with a higher meat intake was not like the average American diet either.

What do you think about the low-carb studies in which meat and SFA intake went up, and estimated lipoprotein atherogenicity went down?

www.ncbi.nlm.nih.gov/pubmed/15148063
www.ncbi.nlm.nih.gov/pubmed/18635428

Or the 2-year study in which a high saturated fat LC diet cause regression of carotid atherosclerosis, comparable to low-fat and Mediterranean control diets?
www.ncbi.nlm.nih.gov/pubmed/20194883

I find all this rather hard to reconcile with the idea that meat and SFA are harmful in the context of a well planned diet.

nothing91 said...

Frank,

"Why do you seem to imply that I am dogmatic about my view on meat?"

For the same reason I say the Earth is round. :-)

"I don't see how anyone who truely care about his health could easily brush away with the back of his hand so much evidences in favor of reducing meat"

Like all those AGEs!

allison said...

I'd like to know who funded those studies purporting to show a relationship between cholesterol intake and inflammation. I'd bet it was pharmaceutical industry funded. The industry has been an pains to explain the fact that statins, while engineered to lower serum cholesterol, produce an unintended antinflammatory effect. The "cholesterol causes inflammation/oxidation theory" seems like a desperate attempt to square the circle.

Robert Andrew Brown said...

A thought provoking link on long lived peoples

http://www.beyondveg.com/tu-j-l/raw-cooked/raw-cooked-3i.shtml


Wikipedia on the Okinawan diet

http://en.wikipedia.org/wiki/Okinawa_diet

"Indigenous islanders' diet

People from the Ryukyu Islands (of which Okinawa is the largest) have a life expectancy among the highest in the world.,[2] although their life expectancy rank among Japanese prefectures has plummeted in recent years.[3] Their unusual longevity has been attributed in part to the traditional local diet, but also to genetic inheritance, lifestyle, and environmental factors.

Generally, the traditional diet of the islanders was 20% lower in calories than the Japanese average and contained 300% of the green/yellow vegetables. Although the traditional Japanese diet included large quantities of rice, in Okinawa, rice was consumed in smaller amounts and the staple was instead the sweet potato. The Okinawan diet has only 25% of the sugar and 75% of the grains of the average Japanese dietary intake.[1] The traditional diet also includes a relatively small amount of fish (less than half a serving per day) and somewhat more in the way of soy and other legumes (6% of total caloric intake). Pork was highly valued, and every part of the pig was eaten, including internal organs. However, pork and fish were primarily eaten on holidays, and the everyday diet was almost exclusively plant based.[4] Cooking was sometimes done with lard. Their overall traditional diet would be considered a very-high-carbohydrate by modern standards, with carbohydrates, protein, and fat providing 85%, 9% and 6% of total calories respectively.[5] The consumption of pork in Okinawa in 1979 was 7.9 kg (17.4 lbs) per person per year.[6] This may be contrasted with the average consumption of meat in the United States, which, by 2005, included 62.4 lbs of beef, 46.5 lbs of pork, and 73.6 lbs of poultry per person per year.[7] Virtually no eggs or dairy products were consumed.[8]

An Okinawan reaching 110 years of age has typically had a diet consistently averaging no more than one calorie per gram of food and has a BMI of 20.4.[citation needed]

In addition to their high life expectancy, islanders are noted for their low mortality from cardiovascular disease and certain types of cancers. Willcox (2007) compared age-adjusted mortality of Okinawans versus Americans and found that, during 1995, an average Okinawan was 8 times less likely to die from coronary heart disease, 7 times less likely to die from prostate cancer, 6.5 times less likely to die from breast cancer, and 2.5 times less likely to die from colon cancer than an average American of the same age.[8]

The traditional Okinawa diet as described above has been practiced on the islands till the end of the World War II. Since then, dietary practices have been shifting towards Western and Japanese patterns, with fat intake rising to 27% of total caloric intake and the sweet potato being supplanted with rice and bread. [5]"

Robert Andrew Brown said...

Following up on Stephan's references another trial which suggests that weight loss at least in the short to medium term is more important than whether the diet is high or low carb.

Effects of a 2-y dietary weight-loss intervention on cholesterol
metabolism in moderately obese men

"Conclusions: Long-term weight loss is related to a characteristic
response suggestive of altered cholesterol and apolipoprotein metabolism.
Various diets have a similar effect on these effects."

http://www.ajcn.org/content/94/5/1189.full.pdf+html

Frank said...

Nothing91

Why do you even comments if you're obviously not interested in having a proper discussion? Your comments are always filled with sarcasm and/or arrogance. Why do you even lose your time adressing me if you think i'm a crackpot pushing a particuliar agenda? You have better things to do, don't you?

The AGE paper that Stephan referenced measured only one AGE, CML. There are various AGEs, and this paper certainly isn't a conclusion in itself as to what food is high in the various form of AGEs. And AGEs is only one of the concern i've raised, and i've already said that i'm not anti-meat, i'm looking for the optimal quantity of meat. I personnally care enough about my health that i'm not ready to brush away 50 years of science in the name of a fad diet. My mind remains open, tho'.

So, unless you have something interesting to say in regard to what I said, I'm just going to ignore you as I don't feel talking with you will be of any good.

Thanks Stephan for your take on the meta.

Stephan Guyenet said...

No problem Frank. By the way, I have nothing at all against a low-meat diet. My own diet isn't particularly high in meat at this point. I conceptualize my diet as a sort of cross between a Paleo diet and a non-industrial agriculturalist diet. I eat a modest portion of meat on most days, but many of my meals are vegetarian and sometimes even vegan, heaven forbid! Haha. I don't worry about using butter, red palm oil, and virgin coconut oil when I want to though.

Josh said...

I have enjoyed reading this discussion. Thanks Stephan for participating in the comments as it is obviously a time consuming and frustrating task at times. When you answer a question it not only helps the person who asked it, but also many others who read the comments.

Another study to toss into the mix - Meta-analysis of statins as primary prevention treatment for high-risk individuals shows no benefits in all cause mortality -http://www.ncbi.nlm.nih.gov/pubmed/20585067

Peter said...

Stephen,

"...Following the same logic, the diet of non-industrial cultures with a higher meat intake was not like the average American diet either".

You have a point. The problem is just that most of those who try to mimmick the meat-rich paleo-diet in their own eco-niche (and in isocaloric context) end up having their serum lipids very high. Some of them end so high that IMO it is justified to ask whether their new paleo diet brought any actual improvements to their baseline, SAD diet.

Like the up-to-date, lipid-research has established in recent years, I think it's more important to pay attention to LDL and in the end, total cholesterol. The story of HDL as "good cholesterol" has become more nuanced during the last years. A healthy diet should not raise your LDL nor HDL cholesterol.

I cannnot access to Ornish paper, right now. You might have a point. I was probably wrong about the exact serum cholesterol values his patients ended-up with during the year long trial. For really high-risk patients the expected drop in serum cholesterol is just an issue of weeks as it might appeared in my writings. However, I am not incorrect given the big picture.

Effectiveness of altering serum cholesterol levels without drugs

"Low-fat diets as commonly prescribed rarely produce significant LDL declines....One exception to this, however, is the Dean Ornish–style diet.....On average, Ornish's patients lost 24 lbs in a year and had a 37% reduction in LDL cholesterol levels (HDL cholesterol levels were unchanged)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1312230/

In essence the author concluded that the kind of "low-fat diet" we understand it in Western cultures does not work, but once we adhere to the kind of low-fat, plant-based diet that wasn't too far from the norm in 3/4 of the world few decades ago works pretty well.

Peter said...

Continue....

I think the studies where the Atkins crew is involved (Westman, Phinney, Volek, etc) have always too many red flags on them.

Usually their patients are put to a very low-calory diet and have their control group on a diet which they refer as "low-fat". When we look at the fiber-intake, we can usually grasp what is going on. IMO fiber intake is the best proxy to quickly assess whether the diet is junk food diet or not (16g fiber is a junk food diet). Ironically, in many of their studies, the high-fat group shows an elevated LDL compared to their "low-fat group" even despite of heavy calory restriction:

“Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet” (Volek et al.)

I know I am being a poor debator here, but again, primitivenutrition have covered most of these studies in detail. I can see why they do not really gain popularity outside the low-carb/paleo movement.

In regards to the Shai et al., 2010 study (it really is a funny story):

Primitive Nutrition 53: The Best Low Carb Research (Money Can Buy), Part II

http://www.youtube.com/watch?v=sZAP47e-NPc&list=PLCC2CA9893F2503B5&index=53&feature=plpp_video

I think, you Stephen had pretty spot on, when you wrote in one of your earlier post that extraordinary claims require extraordinary evidence. In the paper by Shai et al. we do not saw any such evidence. And, as Ornish pointed out, it doesn't help the "SFA is harmless" -case that the patients under Shai's 1200kcals/per day diet scheme were told to choose vegetable fats over animal sources. Their intake of saturated fat was very low, as was the intake of all nutrients. "Are the Atkins people now advocates for vegeterianism now" asked D. Ornish with a hint of irony in his respond letter.

Also, a valid point is to ask whether carotid intima thickness regression is good indicator of cardiovascular risk in the first place:

Does carotid intima-media thickness regression predict reduction of cardiovascular events? A meta-analysis of 41 randomized trials

http://www.ncbi.nlm.nih.gov/pubmed/21126642

I think it's clear that Shai, Westman, Phinney, etc are not even trying to persuade the science world on their side. IMO they are interest in making headlines in media and blogosphere and fill the Atkins books they sell with serious-sounding references.

Last words in regards to serum cholesterol;

I have myself lower serum cholesterol compared to Tarahumara-folk (who are in the 134 range) and I do not have any parasites. My diet is even healthier than the diet of Tarahumara; I have more variability, and most importantly more dark green leafs. Unlike the Tarahumara, I also skip the two eggs per week.

Best regards,

Pete

Josh said...

Peter, if you have TC < 134, take a look at where you are on the MRFIT all cause mortality graph in this post - http://wholehealthsource.blogspot.co.nz/2011/01/does-dietary-saturated-fat-increase.html

Josh said...

... or on an even fancier graph - http://perfecthealthdiet.com/wp/wp-content/uploads/2011/06/O-Primitivo-Cholesterol.jpg

Unknown said...

The graph Josh linked to is fascinating. Y'all should have a look at it.

I'm a little skeptical of the fit curve for CHD. One thing that appears in the trough is the highest variability. Both the lowest and highest CHD mortality occurs in the same range of TC (roughly 195-215).

This suggests to me that TC is not a very good marker for CHD risk, as Stephan and many others (including myself) have been saying. It's also consistent with why, for instance, the Lyon diet trial, which showed the largest reduction in CHD risk of any controlled longer-term study to date, demonstrated substantial risk reduction without a significant TC trend either way.

I'm sorry, but the position that TC or LDL alone (particularly their reduction) is the primary risk factor to target (or the causative basis of CHD) is simply not tenable any more. That's a decades old supposition that I don't think is going to be around once much longer-- although it will take some more retirements from the old guard to allow the paradigm shift to proceed. It may well be, as some have suggested, that it's lifespan is also being prolonged by pharmaceutical influence (anyone that doubts the significance of their lobbying/funding is seriously deluding themselves).

As Stephan says, there's no problem with a low-meat diet. As I've been acknowledging, I don't think the "plant-based/low-fat" diet cannot work- it clearly can. I just don't think it's the single optimal strategy to promote for several reasons- and it seems it's advocates rely on an outmoded version of the lipid hypothesis to explain it's efficacy...

Chris

Stephan Guyenet said...

Hi Peter,

You said "The problem is just that most of those who try to mimmick the meat-rich paleo-diet in their own eco-niche (and in isocaloric context) end up having their serum lipids very high. Some of them end so high that IMO it is justified to ask whether their new paleo diet brought any actual improvements to their baseline, SAD diet."

I agree with this. If the paleo diet makes your LDL go through the roof, then IMO it's not for you. However, that's not the typical lipid response for either paleo or low carb. There have been several controlled trials on the paleo diet at this point, and many on LC diets, and neither one typically raises LDL (e.g. Shai et al), and the overall effect on lipids appears favorable, although if you look hard enough you can find a few LC studies where LDL increased. Most of the LC diet studies were not calorie restricted, although a few were.

At the same time that I recognize that the Paleo diet (particularly high-meat high-fat low-carb incarnations) don't work for everyone, I think we all have to recognize that the Paleo diet has shown exceptional promise in controlled trials for treating glucose intolerance and early diabetes. Blood glucose control as I'm sure you know is one of the main contributors to CHD risk, on par with lipids. I think it would be rash to overlook a diet that's so effective at rapidly restoring glucose homeostasis and producing fat loss.
www.ncbi.nlm.nih.gov/pubmed/17583796

I've never seen any vegetarian or vegan diet that produces comparable improvements in glucose homeostasis in clinical trials.

I'm not surprised that this Primitive Nutrition guy pointed out that in the Shai et al study I referenced, the LC group was instructed to favor vegetarian sources of food. However, there's a hitch that he may not have told you about: the participants didn't listen. Total intake of saturated fat and cholesterol increased from baseline, particularly as a percentage of calories (12.3% by the end-- no one would call this a low SFA diet). Despite the fact that SFA and cholesterol increased, carotid atherosclerosis regressed the most in that group, consistent with the fact that their TC:HDL ratio improved the most. I don't see any way to explain away this result, and the investigators certainly accepted it at face value.

Shai et al IMO was the best LC diet trial to date due to its long duration (2y) and exceptional diet adherence. I think this Primitive Nutrition guy is trying a little too hard to find flaws. However, I do take your point that carotid IMT may not be the best marker for coronary events. This is a controversial subject however, and the authors obviously would not have bothered to measure it if they thought it was meaningless.

Btw, I just re-checked the Ornish paper we were discussing, and I have to correct myself; the participants got down to 167 mg/dL rather than 177 as I had written previously. He reported HDL and LDL, and the intervention reduced LDL without having much effect on HDL. As I think I said before, I have no doubt that his diet/lifestyle/weight loss/smoking cessation program reduces the risk of having a heart attack. However, there's no evidence that avoiding meat specifically is one of the reasons it works.

Peter said...

@Stephen,

I appreciated your input, however, I am quite cynical about these papers produced by the Atkins crew.

The fact is that the calory intake of the low-carb crew in Shai's study was 1250/per day, that's severe calory restriction and IMO much more important factor to consider than any nutrient make-up of the diet. In other words, with the that calory intake, it's irrelevant whether one increase their cholesterol and SFA intake from the baseline, the increase could not have been much in absolute terms anyway. IMO this study was about the power of calory restriction, not about the impact of lipids to carotid thickness.

Moreover, as the PrimitiveNutrition chap pointed out the study was not even randomized, meaning that those in the LC group had the highest rates of carotid thickness to begin with. It works the same way than it does with weight-loss: those who have most to loose, usually loose it the most. I wouldn't fair well in a weight-loss competetion, does it mean my diet sucks?

The control groups had names such as "low-fat" or "mediterranian" but in reality, apart from semantics, the diet had nothing to do with these labels. Shai did not either report the LDL of the low-carbers, why? Because it most likely went up even despite the 1250 calories consumed daily.

What do you think Shai's data would have looked like in comparison if you had Chris Voight as a reference group f.ex?

In the Volek study I linked to you the "The low-fat" group lowered their fiber intake and simultaneously relative fat intake. This effect was most likely achieved by adding sugary drinks to the diet. The "low-fat" group did not even manage to get fiber worth of two big pears. Yet, the low-carb crew showed higher LDL in the end. Amazing.

Are there any other whole-food vegan diet trials besides Barnards trial? I think his intervention participants did well, especially if you consider that it was the first diabetes trial ever that did not impose calory restriction to the intervention group. They were free to eat all they wanted.

Peter said...

Continues..

Unlike in the drug-free Ornish study, 26% of Shai's partcipants were on lipid-lowering therapy and another 31% on a blood-pressure lowering medication throughout the trial. There's a valid point to be made that it took only the lowered blood pressure and weight-loss to induce the regression in carotid thickness.

We've seen regression in carotid thickness even in plain blood-pressure-lowering drug trials:

Carotid intima-media thickness and plaque volume changes following 2-year angiotensin II-receptor blockade. The Multicentre Olmesartan atherosclerosis Regression Evaluation (MORE) study

http://www.ncbi.nlm.nih.gov/pubmed/19124398

Moreover, Ornish study, f.ex did not just look carotid thickess but also cardiadic events, and that is what ultimately counts.

I also wonder why did Shai stick only in measurements of artery walls? At this point we know that measurements of aortic valve calcification are more important

I have to say that I am not too convinced about the scientific integrity of the Atkins folk and I have no difficulties understanding Westman's frustration over the fact that very few people are interested in these studies. IMO they are simple not convincing. I think it's clear that these studies provide us very little which would lead us to give a second thought on the role of animal lipids in the etiology of heart disease.

Peter said...

"I think we all have to recognize that the Paleo diet has shown exceptional promise in controlled trials for treating glucose intolerance and early diabetes"

Sorry, I forgot this.

A Palaeolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease.
http://www.ncbi.nlm.nih.gov/pubmed/17583796

For the millionth time :)

Primitive Nutrition 15: Define "Healthful"?, Part II

http://www.youtube.com/watch?v=EDbguStz4F4&list=PLCC2CA9893F2503B5&index=15&feature=plpp_video

I don't think we need any paleo-hypothesis to explain this. I think it was even slightly bizarrre that the scholars enunciated this. The intervention group just ate more fruits, more solid foods and less calories and less saturated fat compared to the control group. Both groups were high on cholesterol. The control group ate more fiberless liquid carbs and thus showed 17% more higher carbohydrate intake but only 5 grams higher fiber intake. Again, the diet they fed to control group borne mediterranian diet only in its name. Mediterranian diet is low in cholesterol and high in fiber and obviously high in fiber-rich whole-foods. I think, neither of the diets were particularly healthy for a diabetic.

Anyways, I had much good time debating. Now I have to seriously step aside, I leave the last words for you Stephen.

Peter said...

Sorry,

the Shai study was indeed randomized but it didn't help that proportionately the indidences of thickest carotid arteries were in the LC group.

Robert Andrew Brown said...

Today's news

"Interpretation
In individuals with 5-year risk of major vascular events lower than 10%, each 1 mmol/L reduction in LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1000 over 5 years. This benefit greatly exceeds any known hazards of statin therapy. Under present guidelines, such individuals would not typically be regarded as suitable for LDL-lowering statin therapy. The present report suggests, therefore, that these guidelines might need to be reconsidered."

The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2960367-5/fulltext


Nobody on the news is talking about the fact that cardiac diseases and hypertension were extremely low in populations on pre western diets, and debating if we should in hte alternative be looking more seriously at what we have done to the diet, rather than the prospect of mass long term 'medication'.

Robert Andrew Brown said...
This comment has been removed by the author.
Robert Andrew Brown said...

Re Primitve nutrition links

I have been trying to watch some of the Primitive Nutrition videos, but keep finding my self sufficiently exasperated at what I am hearing to make very trenchant comments out loud at the computer.

These links contain some great references and thought provoking material, but for me the material gives a strong sense the author/s are motivated at least in part by a strong animosity towards proponents of low carb diets, which for me clouds the authors judgment and objectivity in considering the issues raised, and in the conclusions they reach

Josh said...

The meta-analysis of statins that Robert quoted claiming lower cardiovascular events and all cause mortality is interesting. So we have one meta-analysis showing that statins don't have any positive effect on all cause mortality even in high risk patients and another meta-analysis saying that even in people with low risk that they improve all cause mortality. How is the average person supposed to navigate this scientific minefield? Are statins really great drugs with a huge amount of evidence behind them? Can we trust that these studies are neutral when a multi-billion dollar industry depends on positive results? Are there major conflicts of interest - http://wholehealthsource.blogspot.co.nz/2008/08/conflict-of-interest.html ?

Jane said...

I've been watching the Primitive Nutrition series too. I'm finding it very interesting. He occasionally rubbishes people, like Stephan and Denise Minger, but he really can't be taken seriously when he does that. He even calls Stephan 'Goyenet'.

Peter said...

Phew....

this will definitely be my last for now on, promised. Ban me stephen, if it isn't :)


@Robert,

Great study about statins in a low-risk people. I think it gradually all comes to what the editor in chief of American Journal of Cardiology has told us for years,

Evaluating lipid-lowering trials in the twenty-first century.

“…Only pure vegetarians for practical purposes do not need statins, most of the rest of us do”

http://www.ncbi.nlm.nih.gov/pubmed/19406281

In his landmark article, The cause of atherosclerosis, he went even further:

"Because humans get atherosclerosis, and atherosclerosis is a disease only of herbivores, humans also must be herbivores”

http://ncp.sagepub.com/content/23/5/464.full

NY times yesterday (may 16th)
Doubt Cast on the ‘Good’ in ‘Good Cholesterol’

"I’d say the HDL hypothesis is on the ropes right now,” said Dr. James A. de Lemos, a professor at the University of Texas Southwestern Medical Center.."

"The current study tells us that when it comes to HDL we should seriously consider going back to the drawing board, in this case meaning back to the laboratory,” said Dr. Lauer, who also was not connected to the research. “We need to encourage basic laboratory scientists to figure out where HDL fits in the puzzle — just what exactly is it a marker for.”

http://www.nytimes.com/2012/05/17/health/research/hdl-good-cholesterol-found-not-to-cut-heart-risk.html?_r=2&hp

Jane said...

Statins work because they do what magnesium does and most people have magnesium deficiency.

'Since Mg(2+)-ATP is the controlling factor for the rate-limiting enzyme in the cholesterol biosynthesis sequence that is targeted by the statin pharmaceutical drugs, comparison of the effects of Mg(2+) on lipoproteins with those of the statin drugs is warranted. Formation of cholesterol in blood, as well as of cholesterol required in hormone synthesis, and membrane maintenance, is achieved in a series of enzymatic reactions that convert HMG-CoA to cholesterol. The rate-limiting reaction of this pathway is the enzymatic conversion of HMG CoA to mevalonate via HMG CoA. The statins and Mg inhibit that enzyme. Large trials have consistently shown that statins, taken by subjects with high LDL-cholesterol (LDL-C) values, lower its blood levels 35 to 65%. They also reduce the incidence of heart attacks, angina and other nonfatal cardiac events, as well as cardiac, stroke, and total mortality. These effects of statins derive less from their lowering of LDL-C than from their reduction of mevalonate formation which improves endothelial function, inhibits proliferation and migration of vascular smooth muscle cells and macrophages, promotes plaque stabilization and regression, and reduces inflammation. Mg has effects that parallel those of statins. For example, the enzyme that deactivates HMG-CoA Reductase requires Mg, making Mg a Reductase controller rather than inhibitor. Mg is also necessary for the activity of lecithin cholesterol acyl transferase (LCAT), which lowers LDL-C and triglyceride levels and raises HDL-C levels. Desaturase is another Mg-dependent enzyme involved in lipid metabolism which statins do not directly affect. Desaturase catalyzes the first step in conversion of essential fatty acids (omega-3 linoleic acid and omega-6 linolenic acid) into prostaglandins, important in cardiovascular and overall health. Mg at optimal cellular concentration is well accepted as a natural calcium channel blocker. More recent work shows that Mg also acts as a statin.'
http://www.ncbi.nlm.nih.gov/pubmed/15466951

Jane said...

'..I think we all have to recognize that the Paleo diet has shown exceptional promise in controlled trials for treating glucose intolerance and early diabetes.'

Do we have a study comparing a whole-food Paleo diet with a whole-food Mediterranean-style diet? Lindeberg's trial did not do this. His Mediterranean subjects were eating low-fat dairy, refined oils, and an unknown amount of refined carbs. The Paleo subjects on the other hand were eating nothing that was refined.

Robert Andrew Brown said...

Jane - Thanks for the magnesium / statin information. It is fascinating.

Peter - studies on populations on pre western diets in 1930 - 1950 remarked that high blood pressure was almost unknown and heart disease was rare. These populations ate a variety of diets, and I am not aware of one that was exclusively vegetarian, and granted neither did they eat steak every day.

Your arguments and links have been thought provoking.

Asim said...

I can only laugh when I hear such ridiculous nonsense as the above:

"Because humans get atherosclerosis, and atherosclerosis is a disease only of herbivores, humans also must be herbivores”

So Baboons are herbivores? First your told, humans only get astherosclerosis. Then your told, only herbivores get astherosclerosis....

What 'fact' are they going to spew forth next?

Asim said...
This comment has been removed by the author.
Asim said...

BTW, a human being is not a carnivore and not a herbivore. It's an omnivore, like a baboon.

Unknown said...

Hi Peter,

I also shouldn't be spending this much time on this, but it's an important issue, so what the heck. I find most of your points and references to be mainly nitpicking around the corners- no offense personally intended.

Here's the big picture, to recap:

1) The effect of feeding SFA/cholesterol is not consistent and is of low magnitude except in "hyper-responders"
2) There are plenty of good studies showing the protective effects of animal-derived nutrition
2) TC is not a good marker of heart disease risk, being super-ceded by TC/HDL and particle size (possibly, but they appear to both be proxies for an underlying process)
3) The lipid hypothesis in it's modern form is about LDL receptor activity and the degeneration/modification of LDL molecules, not the absolute concentration of LDL
4) Substitution of PUFA's for SFA's has been tested and found wanting in controlled intervention studies, and the substitution of carbohydrates is neutral in those without metabolic syndrome (because the body will just make SFAs and MUFA's out of carbs anyways...)

You will find all of those points substantiated by myself or Stephan in previous comments in this thread.

I find it incredible that you cite the case of someone with a TC of 156 developing advanced atherosclerosis. Isn't this close to Bog's imaginary magical immunity threshold? How low is low enough?

Your position requires that lipoproteins are basically and essentially bad- they evolved to assassinate us in the course of their presumably necessary duties, and that the best diet is void of animal products contributing SFAs and cholesterol, and letting the body synthesize these compounds entirely by itself (out of excess carbs and other precursors). Because somehow, when the body makes SFA's and cholesterol, and packages them into lipoproteins like LDL, it is not bad, but when the body packages SFA's and cholesterol from food into lipoproteins they are bad? Is all LDL bad? Even HDL?

So we're back to Bog's all-or-nothing position. Like I said before, this cannot be refuted until a really good, randomized intervention study pits these competing dietary strategies against each other (in both a metabolic ward, and a longer-term follow-up setting).


Chris

nothing91 said...

Josh,

"... or on an even fancier graph - http://perfecthealthdiet.com/wp/wp-content/uploads/2011/06/O-Primitivo-Cholesterol.jpg"

Great stuff, thanks for posting it.

I'm really shocked that neither Peter or Frank had anything to say about it. Truly, undeniably shocked.

Frank said...

Not quite impressed by this graph as it has been discussed by Plant Positive in his series.

(first, you need to know what he was saying of another graph)

"Here is an example of the use of misleading graphs in the cholesterol games. This comes from a website called Perfect Health Diet. This graph purports to show the relationship between healthy life expectancy on the y-axis along the left, and the ratio of animal to vegetable foods consumed on the x-axis at the bottom, with each point on the graph representing a country. It appears that in countries that eat more animal foods people live longer, with Iceland all the way to the top right. The Perfect Health Diet people think this is pretty powerful stuff. "Take that, vegetarians!," they say.

This graph is misleading, partly because it basically represents the food ladder, where wealthier countries eat more animal foods because they can afford to.

Look at the countries with the shortest life spans down at the bottom left and you'll see countries afflicted with poverty and infectious disease like Angola, Mozambique, and Swaziland. At the other end of the spectrum you'll see industrialized nations with top health care systems like France, Sweden, and Denmark. I guess the very smart people at this site think the only difference between Lesotho, with its rampant HIV epidemic, and Iceland, with its complete universal health care system, is the amount of saturated fat they eat. Yes, I'm sure the vegetarians find this graph absolutely devastating. Good job, Perfect Health people!

"

And here's the critio he made of the graph Josh posted :

"Here's another graph they liked on that site. This one shows all-cause mortality along the left and total blood cholesterol along the bottom. As you might expect, what's happening here becomes obvious when you again look closely at the countries. The countries with the highest mortality to the top left are places like Barundi, Mali, and Guinea. The countries with the lowest mortality at the bottom of the curve are places like Germany, France, and Belgium. Mortality rises again with cholesterol at the bottom right with places like Colombia, Uruguay, and Belarus. You see the same phenomenon is at work.

There is more to this, though. Look closely and you can see the creator of this graph chose to plot infectious and parasitic diseases separately. It doesn't follow a U-shape like all-cause mortality does. It starts high at around the 1000 mark on the left and then just plunges to zero near the middle. This effect is behind claims you may see online that high cholesterol protects against infectious disease. If you buy into that belief then would have to believe that people with high cholesterol don't get sick much. That's an argument I'd love to hear a cholesterol confusionists make.

Especially when evidence suggests lower cholesterol enhances immune function."

Frank said...

http://plantpositive.squarespace.com/blog/2012/3/25/tpns-40-41-playing-games-with-your-heart.html

Hope you don't mind Stephan if i'm linking directly to his website.

Robert Andrew Brown said...

Frank you quoted

"Especially when evidence suggests lower cholesterol enhances immune function"

I would be very grateful for papers that support this statement.

Here is one that from the summary does not:

http://www.annclinlabsci.org/content/37/4/343.full

Low Serum LDL Cholesterol Levels and the Risk of Fever, Sepsis, and Malignancy


"Each 1 mg/dl increase in LDL was associated with a relative reduction of 2.4% in the odds of hematological cancer (OR 0.976, 95% CI 0.956–0.997, p = 0.026). Low LDL levels also increased the odds of fever and sepsis between the groups (OR 5.3, 95% CI 1.8–15.7, p = 0.02). In summary, low serum LDL cholesterol level was associated with increased risks of hematological cancer, fever, and sepsis. "

In the body of the text it says
"Moreover, during the past few years large scale randomized trials and observational studies of lipid lowering agents suggested uncertainty about their beneficial effects with respect to noncardiac mortality and major morbidity [3–10]. The explanation for an increased non-cardiac mortality rate is not clear."

Josh said...
This comment has been removed by the author.
Josh said...

I agree with the criticism of the cholesterol graph plotted by country. There are far too many confounding factors to draw any conclusions. The MRFIT graph is much better, n=350,000. All cause mortalitly is lowest between TC 160 - 220 with risk increasing at lower and higher levels.

BB said...

One adaptation that is counter intuitive, is the selection for small heads. Loren Cordain pointed this out years ago perhaps in not quite the same words.
The Neolithic diet/lifestyle leads to a smaller pelvis, hence difficulty in birth. Hence increased maternal and infant mortality. This is very expensive to the tribe, and is one of the most powerful inflexion points for natural selection.
Infants with smaller heads will have a safer passage through the birth canal.
Natural selection can favour that even if it means reduced intelligence. Better small head than dead.
The mathematics of selection you allude to basically fit in with classical evolution/population theory as espoused in the Logistic Function from the 1800's which is quite different to logistic regression. It was intended as a mathematical expression of Darwinian selection and still looks good today.

Pranay said...

Hey Stephan,

I have always been interested in analyzing the diets of traditional Indians from India. I don't necessarily mean indigenous populations (though that would be cool too!), but just ancient cultures, either pre- or post-agriculture. Specifically, I wanted to see how healthy the traditional Indian cuisine (probably not what the Indigenous had) is compared to other diets. Indian cuisine is probably the most versatile when it comes to vegetarian options (still including dairy) and I was wondering what a breakdown of its macro and micro nutrients would look like. Do you have anything like that or know where I might be able to access such information? Thanks!

shaista said...

Very well done sir .