Wednesday, January 7, 2015

Is Meat Unhealthy? Part VI

In this post, I'll examine the possible relationship between meat consumption and cancer risk.

Is cancer risk even modifiable?

Cancer is caused by the uncontrolled division of a population of rogue cells in the body.  These cells essentially evolve by natural selection to escape the body's multiple anti-cancer mechanisms.  

To a large extent, cancer appears to be a numbers game.  The human body contains about 37 trillion cells.  To get cancer, all you need is one cell that develops key mutations that allow it to shed its built-in restrictions on cell division.  The older you are, the more time you have to accumulate mutations, explaining why cancer risk rises sharply with age.

Unlike other common non-communicable diseases, we don't know to what extent cancer is caused by modifiable diet and lifestyle factors vs. bad luck that's completely outside our control.  Some cancers, such as lung cancer, are typically linked to lifestyle factors like cigarette smoking-- yet the majority of cancers aren't so easily understood.

There is an ongoing scientific debate about how much of cancer risk is modifiable.  Although there is clearly a certain amount of luck involved in cancer risk, the various stages of cancer development could theoretically be influenced by diet and lifestyle factors-- and this has often been supported by research.  Observational studies have suggested that at least 35-40 percent of cancers are preventable, although these estimates rely on major assumptions (1, 2).  In the end, I doubt there is any diet or lifestyle that can eliminate cancer risk, but overall cancer risk is probably modifiable enough that it's worth trying (particularly for the obvious risk factors like cigarette smoking).

Non-industrial cultures

A number of field physicians have reported that cancer is rare among traditionally-living cultures (Cancer: Disease of Civilization? Stefansson. 1960).  However, cancer rates are difficult to measure accurately in these cultures, due to their shorter mean lifespans, and the fact that many cancers are internal.  These reports are intriguing, but it's difficult to draw firm conclusions from them.

We do know that cancer existed in ancient times, because we can occasionally observe cancerous lesions in bones that are thousands of years old (3).  It's difficult to know what the age-specific cancer risk might have been among our distant ancestors, but we do know that their absolute cancer incidence would have been low simply because few of them survived to old age.

If we look at cancer incidence in different parts of the world (adjusted for age of course), the rates tend to be lower in less industrially developed areas such as West Africa (4).  Cancer mortality rates are lower as well, although the difference is less striking than the difference in incidence.  While some of these differences could be due to differences in diagnosis, these figures are at least consistent with the idea that cancer risk is modifiable by diet and/or lifestyle.

The risk of specific cancers can vary dramatically between cultures.  In particular, industrialization and affluence are strongly associated with a higher risk of colon/rectal, breast, lung, and prostate cancer (Western Diseases. Trowell and Burkitt. 1981).  This is thought to relate to changes in reproductive patterns, tobacco use, and diet.

Observational studies

Let's start with the Adventist Health Study, which examined the diet, lifestyle, and health of a religious vegetarian community in California.  Lacto-ovo vegetarian Seventh-Day Adventists (SDAs) in this study had a cancer risk similar to their omnivorous peers, while vegans had a slightly lower risk (5).

There are a number of other observational studies that have compared the cancer risk of vegetarians to omnivores-- too many for me to discuss here-- so I'll rely on meta-analyses (studies of studies).  The results are mixed, although the most recent one I could find did report an 18 percent lower risk among vegetarians (6, 7).  It's a small difference, but it was statistically significant.  

How about specific types of meat?  In general, poultry and fish consumption are associated with neutral or lower risk of common cancers such as breast, prostate, and colon/rectal cancer (8, 9, 10, 11, 12, 13, 14, 15, 16).  However, there may be an association between poultry intake and kidney cancer (17).

In contrast, red meat and processed meat are often associated with a small but statistically significant increase in total cancer risk (18, 19, 20), and fairly consistently associated with a larger increase of colon/rectal cancer risk specifically (21, 22, 23, 24, 25, 26, 27, 28).

It's worth keeping in mind the usual limitations of observational studies, such as mediocre diet assessment methods, and possible confounding by unexpected or unmeasured factors.  Sadly, we don't have any human randomized controlled trials to back up these hypotheses, and we probably never will.

What are processed and red meats?

Reijo Laatikainen and others suggested that I define what I mean by processed and red meats in this series, which is an excellent idea.  

For our purposes, the most useful definitions of processed and red meat are the ones that are most similar to the definitions used in the studies I cite.  In general, processed meats are those that have been preserved in some way to extend their shelf life, for example, hot dogs, bacon, sausage, ham, and cold cuts.  

Unprocessed red meats are those that are no more protected from spoilage than fresh red meat, such as all fresh whole cuts of beef and lamb, and ground meats.  Pork is also typically considered a red meat, despite being similar in color to chicken, probably because it has some nutritional similarities to beef.

Possible mechanisms

There are several known mechanisms by which red and processed meat might increase cancer risk-- buttressing the case made by observational studies.

When meat is cooked at high temperature, such as by grilling or frying, it creates potent carcinogens including heterocyclic amines (HCAs; 29).  HCAs promote the development of multiple cancer types in animal models, including the types of cancer that are most common in humans (29). Consistent with the animal studies, human observational studies report an association between the consumption of high-heat-cooked meat and several cancers including colon/rectal and breast cancer (29, 30).  This applies to all meat, not just red and processed meat.  It may be best to limit high-heat cooked food, and instead focus on lower-heat cooking methods such as steaming, pressure cooking*, poaching, and boiling.

As I discussed in the post on meat and diabetes risk, free (unbound) iron is a powerful driver of free radical reactions, and red meat is a rich source of loosely bound (heme) iron.  The potential resulting damage to the gut's epithelium could in theory contribute to an increased risk of colon/rectal cancer-- and this is supported by both animal and human studies (31, 32, 33).

Insulin-like growth factor 1 (IGF-1) is a hormone related to insulin that has received attention as a possible contributor to cancer risk.  IGF-1 is a growth factor, meaning that it instructs tissues to grow by increasing cell division.  IGF-1 levels are increased by high-quality protein, such as that provided by animal foods, and dairy seems particularly effective at increasing it (34, 35).  Animal foods seem to put the body into more of an anabolic (building up rather than taking down) state, which we'll come back to in later posts.  Theoretically, this could increase the rate of cell division of cancerous cells.  

Vegans have slightly lower IGF-1 levels than omnivores and vegetarians (36).  However, human studies have found inconsistent associations between IGF-1 levels and overall cancer risk, with the exception of pre-menopausal breast cancer and prostate cancer (37).  The association between circulating IGF-1 and prostate cancer risk is consistent with the (small but significant) association between dairy consumption and prostate cancer risk (38).  The meat-IGF-1 hypothesis is definitely intriguing, and it could be involved in specific cancers, but the link with overall cancer risk remains unclear to me.

Processed meat is often preserved using sodium nitrite to prevent spoilage.  Although nitrites and nitrates are a healthful component of many vegetables, nitrite can form potent carcinogens called nitrosamines when heated in the presence of protein such as meat.  Nitrosamine intake has been linked to digestive cancers in observational studies (39, 40).  Even processed meats that say "nitrite/nitrate-free" typically contain celery juice or another "natural" source of nitrite/nitrate.  

The newest arrival onto the scene is a sugar called Neu5Gc.  Unlike the energy-yielding roles of the sugars glucose and fructose, Neu5Gc plays a role in cell signaling as part of the complex sugar chains on the exterior of cells.  It's part of a family of such sugars called sialic acids.  During our evolutionary history, humans lost the ability to make Neu5Gc, but most other mammals still make it and their tissues contain it.  When we eat the flesh of mammals such as cows, sheep, and pigs, we absorb Neu5Gc and incorporate it into our tissues.  Since it's a foreign molecule however, our tissues mount an immune response against Neu5Gc, producing antibodies and possibly activating an inflammatory response.  A previous paper that developed this mechanism suggested that this inflammatory response could be involved in cancer risk (41).

Until recently, there was little evidence to support the hypothesis that Neu5Gc increases cancer risk.  However, a very recent paper has moved the needle somewhat toward plausibility (42).  First, they measured the Neu5Gc content of a variety of foods, showing that it's moderate to high in beef, lamb, pork, cheese, and caviar, but very low in poultry, fish, eggs, milk, and vegetables.  Then, starting with a strain of mice that is naturally susceptible to liver cancers, they knocked out a protein that is required for Neu5Gc synthesis, making the mice similar to humans in that regard.  They subsequently immunized the mice against Neu5Gc so that they would mount an immune response to it, similar to what is observed in humans.  Then, they fed the mice Neu5Gc, and found that it caused a large increase in the development of liver cancer, suggesting that the human-like immune response mounted by the mice increases cancer risk.

This study needs to be interpreted in the proper context.  First, it was conducted in mice.  Second, the amount of Neu5Gc in the diet was equivalent to a diet composed entirely of beef-- and not just any beef, but the highest-Neu5Gc beef measured in the study (beef Neu5Gc ranges 10-fold).  The exposure to dietary Neu5Gc was therefore some 40-fold higher than what most red meat eaters would experience.  Still, the study outlines a plausible mechanism for a link between red meat and cancer, and that helps increase our confidence in the observational findings.  Hopefully, follow-up studies in humans will paint a clearer picture of the importance of this mechanism to human health.
Synthesis and conclusions

Vegetarians and vegans have a modestly reduced overall risk of cancer relative to omnivores, although we don't know how much of that relates to meat avoidance specifically.  

There is little evidence that poultry or seafood intake contribute to cancer risk, however, I'm fairly convinced that red and processed meat contribute to cancers of the digestive tract such as stomach, colon, and rectal cancers (and possibly at other sites as well).  The observational studies, animal studies, and mechanisms are relatively consistent with that hypothesis.  We will probably never have randomized controlled trials in humans to test it.

Red meat is a highly nutritious food that our ancestors have been eating for millions of years.  I don't think we need to stop eating it entirely.  Still, from a cancer standpoint it's probably best to favor poultry and fish, and when we do eat red meat, to cook it gently.

* Pressure cooking involves somewhat higher temperatures than boiling, but the temperatures are still much lower than frying, grilling, and roasting.


Ash Simmonds said...

Another (huge) confounder to add to the red/processed meat merry go round is that most people and restaurants cook in industrial seed oils, so yet again the meat is likely getting the blame in observational data because it delivers the stuff that's killing us, not providing it.

Dan said...

Japanese (and Asians in general) have much higher incidence of digestive tract cancers than Westerners despite eating much less red meat. What explains the difference?

George Henderson said...

I have (at least) 2 problems with the neu5Gc theory.
1) if anything, beef prevents liver cancer in humans (albeit through the SFA + alcohol mechanism. Where are the cancers supposed to be associated with meat in this model?
2) doesn't this mean that any food or pathogen or pollutant to which humans form antibodies can be a carcinogen?

Reijo said...

Even if we might not witness a randomized trial on red meat and colorectal cancer, there is surrogate marker data available in humans. In these two trials red meat (dose 240-600 g/d) increased N-Nitroso compounds more than same dose of poultry, or low red meat diet. Processed meat seem to be even worse than red meat.

In other words, evidence against red meat does not only come from animal and cohort studies, but also from randomized controlled trials in humas with surrogate end points (like NOCs).

Lunn et al. Carcinogenesis. 2007 Mar;28(3):685-90

Bingham et al. J Nutr. 2002 Nov;132(11 Suppl):3522S-3525S

On top of what you have presented, colonic bacterial fermentation of unabsorbed protein might be one additional mechanism on how red might cause bowel cancer. Some 5-15 grams of modified protein is unabsorbed daily. This is typically meat protein which has been changed due to thermal processing (Maillard reaction). Protein fermentation takes place in distal colon. Lack of fermentable fiber may accelerates the process. Fermentation of protein increases pH (not good) and amount of toxic compounds like amines and phenols. It seems to have negative impact on microbiota as well.

Tuohy et al. Mol Nutr Food Res. 2006 Sep;50(9):847-57.

Scott etl al. Pharmacol Res. 2013 Mar;69(1):52-60

Kim E, et al. Nutr Res. 2013;33:983-94

In my opinion, World Cancer Research Fund produces the most comprehensive analyses both in humans and animals regarding diet and cancer. In the most recent update (“CUP”) on colorectal cancer, it concludes:

“Substantial amount of data from cohort studies showed a dose-response relationship, supported by evidence for plausible mechanisms operating in humans. The CUP Panel agreed that the recent evidence was consistent with the conclusion of the SER [second expert report 2007]; red meat is a convincing cause of colorectal cancer”

Update (CUP):


elbatrofmoc said...

Which of the observational studies you mention involved high intake of fresh red meat (rather than processed meat)? Could you please, if it's possible, list the numbers corresponding to your references? Also, are there any studies indicating the relation between cancer and red meat consumption in which preparation methods were controlled for (i.e., I'm interested if red meat prepared in relatively low temperatures is still shown to increase cancer risk)?Thanks!

I eat red meat only occasionally (about twice a week) and I've never really worried about it. Now I sort of don't know what to think. Do you completely abstain from eating red meat yourself? (just curious)

JR said...

This is the first time I recall reading that roasting can produce carcinogens. As the argument is based on roasting as a high-temperature cooking method, I wonder if you can define high temperature. Is there a temperature beyond which roasting is dangerous, and below which roasting is safe?

For example, when I look at roast chicken recipes, I see recommendations for roasting at anywhere from 325 degrees to 450 degrees. If I roast my chicken at 325 degrees is it likely to be safe to eat compared to a chicken I roast at 450 degrees? Will both temperatures produce carcinogens?

If I cover the chickens with foil to inhibit crisping and keep moisture in the roasting pan, will the roasting process produce fewer carcinogens?

Or, am I best off giving up roasted chickens entirely, as their carcinogens may be dangerous to my health, and eating only chickens I have cooked at low heat by other methods?

alexi de sadesky said...


Great series.

I'm wondering if you are familiar with Paul Ewald's work. He, with the help of Greg Cochran, came up with a brilliant theory for the causation of disease. The brief layman's summary of it is, infectious disease + genetics may be at the heart of various types of cancer and heart disease.

I'm not really them justice with that synopsis but, I'd be curious to hear what you think of his work.


Justin said...

Thanks for the nuanced post. Question for you since you turned me onto the Instant Pot but I'm still learning the ropes -- do you have any good roast-like ways to cook a cut of beef (like eye of round) in the Instant Pot?

Meanwhile, any ideas which cuts of beef are higher in Neu5Gc?

Gretchen said...

It would be interesting to do a study of cooking methods in various cultures vs diseases like cancer, diabetes, etc. In other words, focus on How instead of What.

Don't a lot of traditional societies eat a lot of stews or baking on hot coals as opposed to sauted or grilled? I'm just guessing.

Newbie said...

Hi Stephen, the iron issue is again up for discussion {....As I discussed in the post on meat and diabetes risk, free (unbound) iron is a powerful driver of free radical reactions ...} and I wonder whether you were able to find any more information on my previous query...
.... is it the elevation of ferritin per se, even in the face of normal iron studies, that predicts an elevated risk of progression to T2dm?

Stephan Guyenet said...

Hi Dan,

Japanese and some other Asians tend to eat a lot of processed fish and meat products. That might be a reason. Also, they probably have high infection rates with H pylori.

Hi Reijo,

I agree with your point about surrogate marker studies, and I cited some of those studies in my post, either directly or indirectly via review papers. Thanks for the additional references.

Also, thanks for sharing the excess protein fermentation hypothesis. Sounds like that is at least partially related to high-heat cooking. Although it brings up another question. Plant proteins generally tend to be less well absorbed than animal proteins, so wouldn't foods like beans leave a greater quantity of residual protein in the colon?

I'd also like to note that when gold standard measurement techniques are used, bakery products are the most concentrated source of dietary Maillard products.

Hi JR,

I don't know the answer to your question, however the "browning" of foods corresponds to the formation of Maillard reaction products so you could use that as a guide.

Hi Alexi,

I'm not familiar with Paul Ewald's work. Infectious agents are clearly involved in specific cancers such as stomach, cervix, and certain head/neck cancers. I'd be surprised if they were involved in all cancers.

Hi Justin,

My favorite way to cook a beef roast in the instant pot is to slow cook it, pot roast style. You can pressure cook it, but it doesn't turn out as well. The rapid heating makes it shrink and get tough, and then you have to cook it for a while to get it to become tender again. The texture never ends up as good as with the slow cooking.

The authors didn't report which cuts were higher in Neu5Gc, unfortunately.

Hi Newbie,

The ferritin issue is a legitimate one, since it's also increased by inflammation. However, the fact that phlebotomy increases insulin sensitivity, rodent studies show that iron feeding modifies insulin sensitivity, and human disorders of excess iron storage cause insulin resistance, increase my confidence level that iron itself is playing a causal role.

Stephan Guyenet said...

Hi elbatrofmoc,

I still eat red meat on occasion. I do a lot of things occasionally that I don't think are optimal from a health standpoint. I eat meat maybe every other day, usually poultry or seafood.

Reijo said...


It seems that supplemented fiber, especially fermentable carbohydrates such as resistant starch and fructans, can decrease the formation of NOCs during high consumption red meat. Beans, whole grains and soy are naturally high in fermentable carbs. Might that play a role?

I'm not aware of head to head trials beans against red meat.

alexi de sadesky said...

"I'm not familiar with Paul Ewald's work. Infectious agents are clearly involved in specific cancers such as stomach, cervix, and certain head/neck cancers. I'd be surprised if they were involved in all cancers."

Right. Ewald says this himself. However, he presents evidence that there are more infectious diseases responsible for cancer than we currently give credit for. His book Plague Time is a quick read. He also co-authored an ebook with his wife fairly recently specifically addressing cancer.

He has some really great talks available on youtube. One that he gave for a breast cancer group is probably most recent.

Anyway, just thought it'd be something that would interest you.

Thanks for all your diligent work, Stephan.

Ned Clack said...

What about Argentina? WHO Globocan shows Argentina way down the list for colorectal cancer incidence yet they eat a prodigious amount of red meat, much of it flame-grilled. Of beef alone they currently average about 1 Kg per head per week, but the people who are now not developing bowel cancer grew up when the average consumption was 2Kg per head per week. If red meat really is a risk factor, it seems to me there must be much bigger ones to worry about.

George Henderson said...

Why do we worry about small correlations?
Even assuming that these are "true" and not some "healthy user" effect, how many of us would need to eat a certain way to prevent one cancer in one of us?
Assuming too that the unusual dietary patterns followed by your readers, which are not those represented in the literature, don't change everything.
Epidemiology can't tell us who had the happiest love life or the most positive influence on culture or the happiest children. Should we be managing the perceptions of tiny risks? Is that the real meaning of Public Health?

Daniel said...

What are your views regarding the role of polyunsaturated fat in cancer incidence and progression?

The only two studies of which I am aware which come close to being RCTs in humans are the Lyon Diet Heart Trial and the Veterans Trial, both of which found that cancer is significantly increased in subjects consuming more polyunsaturated fats.

Animal trials are largely consistent.

raphi said...

You definition of cancer, much like you definition(s) of obesity, restate the problem - they're merely descriptive: "Cancer is caused by the uncontrolled division of a population of rogue cells in the body". Removing the word 'caused' would at least recognize we still don't actually know what cancer is caused by, ultimately. After all, the Genetic theory of cancer is no more proven than the Metabolic one.

Using 'significant' when discussing epidemiology is missing the key point about data randomization. Confidence intervals are much more appropriate. See here: "Note that all statistical tests of significance assume that the treatments have been allocated at random. This means that application of significance tests to observational data, e.g.epidemiological surveys of diet and health, is not valid. You cannot expect to get the right answer [...]
— Never, ever, use the word ‘significant’ in a paper. It is arbitrary, and, as we have seen, deeply misleading. Still less should you use ‘almost significant’, ‘tendency to significant’ or any of the hundreds of similar circumlocutions listed by Matthew Hankins [17]on his Still not Significant blog" [David Colquhoun]

raphi said...

"Cancer and ageing in mice and men" (aka Peto's Paradox)

A layman's version is available at:

This quaint example using blue whales is helpful to understand why thinking of cancer as lottery, anymore than we do with other diseases, is not of much help:

"To some extent, cancer is a lottery, and a 100-foot blue whale has a lot more tickets than we do.[...] If blue whales really did get cancer as fast as the models would suggest, they ought to be extinct. The failure of the model means that blue whales must have some secrets for fighting cancer." ==> and we're back to asking what causes cancer rather than throwing most of the causality back to pure luck.

Stephan Guyenet said...

Hi raphi,

Lifespan is highly plastic over evolutionary timescales. Our ancestors likely doubled their lifespans over less than half a million years. Long-lived species have evolved more effective anti-cancer strategies than short-lived species, because they have to or else they wouldn't exist.

Cancer is theoretically preventable over a human lifespan, if you have the genome of a blue whale. But we don't have the genome of a blue whale, so we're stuck with our human cancer protection mechanisms, which leave us somewhat at the mercy of bad luck over the course of our lifetimes.

Marc Brazeau said...

I love these series, but it would be really helpful if the posts contained links to the rest of the series, or at least links to the 'previous' and 'next' posts. Or perhaps they are there and I'm not seeing them. In that case, carry on.

raphi said...

Hi Stephan,

We have good clues cancer isn’t mostly down to a genetic roulette precisely because lifespans are plastic and the longer lived organisms don’t die of cancer more often, or linearly.

For the sake of clarity - the statistical occurrence of mutations in organisms is distinct from cancer rates in populations.

We don’t need the genome of a blue whale but that of a human, thankfully. [ By the way, 91% protein coding sequence conservation between blue whales & cows ain’t bad eh?] Neither do we really need to "prevent cancer”. Keeping it to low enough levels with reproductive success in mind is sufficient. We result from mutations and the corrections of those mutations. This truly dynamic equilibrium is achieved, for e.g., anytime a feature is evolved. Preventing cancer (although pretty fundamental), is but one feature amongst many.

In my experience, the idea that humans are somehow exempt from the same biological forces surrounding cancer as are other organisms is based more on puritanical notions of humans as distinct from animals than any genetic, anthropological, metabolic or physiological rationales.

We agree on their being an anti-cancer strategy; yet I take it to mean that luck has little to do with such mechanisms. Principles of evolution aren’t down to dumb luck, but to the interplay of it with emergent selective pressures.

Stella B. said...

In the previous part of your series, you talked about heme iron in the context of dairy fat and diabetes. I was just looking at the map of worldwide leading causes of death today. Heart disease is, of course, the leader in Europe, North America and Australia. Hemachromatosis genes are actually pretty common in Northern Europeans and in those areas where they have spread. Heteozygous individuals, while not at risk for iron overload, still have iron stores elevated within "normal" ranges -- those normal ranges being based on ... Northern European populations. I did 23 and Me and was surprised to find that I'm heterozygous for both the major and one of the minor forms, so I stopped eating beef and lamb.

I hope you post a lot in the coming weeks so that I no longer have to look at the croissant picture. Most of the food reward Friday pictures are not so alluring, but that one calls to me.

M doc said...

The confounders with vegetarians and Western diets in general still leaves me with too much skepticism to indict red meat as somehow carcinogenic. The diets of Seventh Day Adventists have been associated with some slightly lower risks of heart disease and cancer, even though some do eat meat, but their health benefits are no better than Mormons, who do eat meat, suggesting that other factors, such as higher standard of living, a stronger sense of community support and well being, along with other healthier behaviours might equally account for these small differences. Check out the Roseto Effect.

It is worth remembering some of those traditional diets cited as having lower cancer risks are, in some cases, heavy red meat eaters--the Masai, the traditional Innuit,etc, so is there something different about the meat eaten by Westerners?

And finally, where is your mention of the carcinogens created by the breakdown of various vegetable seed oils with heating, which continue to be somehow assumed to be healthful, despite barely 100 years of experience with them? It would have been useful to put the risks of red meat and these oils in context.

Unknown said...

You mention the 18% lower risk for one of the studies. I assume that is a 'relative risk' statement. In a study with 10,000 population, that could mean instead of the expected 1 person out of 10,000 having cancer, the meat eaters suffered a 1.18 incidence.

Of course, the 18% increase sounds a lot more dramatic than a 0.18 person increase.

It's too bad that peer reviewed journals do not insist that researchers always include the absolute risk figures in the abstract when relative risk figures are in the abstract.

Imagine how many people have been freaked out by the reported relative '18%' risk (danger, danger!) figure and decided to needlessly forego all red meat as a result?

aaron blaisdell said...

"During our evolutionary history, humans lost the ability to make Neu5Gc, but most other mammals still make it and their tissues contain it."

This is fascinating! Whenever a species evolves a loss of function phenotype, it is a strong likelihood that there was an adaptive reason for it rather than being due to a random walk process or the like. In this case, we know hominids increased their consumption of animal foods during the origin and evolution of the genus Homo. We also know that by at least 500kya, Homo (e.g., erectus) was regularly using fire, and all modern human groups cook meat and other foods (usually starchy tubers and corms). This suggests the hypothesis that humans lost the ability to produce signaling molecule Neu5Gc because we were getting sufficient amounts from diet. This is similar to the hypothesis that the reason higher primates (monkeys and apes) had lost the ability for the endogenous production of Vitamin C was because their common ancestor became a frugivore (fruit eater) and was able to obtain enough from diet that it no longer needed to produce it endogenously. Now we're stuck with diseases like scurvy when our dietary source of Vitamin C is insufficient. Could a similar prediction be made about vegans, that they might be at risk for a disease due to insufficient Neu5Gc?

Amy Berger said...

I have been running a very detailed (but still layperson friendly!) series exploring the metabolic origins of cancer on my blog. I invite anyone who's interested in this topic to come check it out. Really fascinating stuff.

Several posts are already up, and there a few more to come. Here's the start:

David Pier said...

Is Neu5Gc incorporated in to fetal tissues? If so, wouldn't it then be recognized as self, thereby eliminating any worry?

Stylooke said...

Hi Stephan,

Thanks for your work. I still feel as though red meat in and by itself is not particularly harmful, but when it's not balanced out with organ meats / collagen / skin / bones that the amino acids and nutrient profiles are off (e.g. high methionine : glycine ratio and high iron), causing problems.

You seem to focus exclusively on red meat and risks, is there any literature about protective effects of collagen or broths?

Aaron, I believe Neu5Gc was lost as an adaptation to malaria, which has a preference for binding to Neu5Gc erythrocytes. Sadly for us the current strain of malaria binds to Neu5Ac instead. So it is unlikely there was any other adaptive benefit, altough it could be possible.

Anna Friebe said...

aaron blaisdell,

The most likely explanation for the success of human ancestors without Neu5Gc is that they were protected from the chimpanzee version of malaria.

Marwan Daar said...

Perhaps this would be a good time to start thinking about a longitudinal study comparing those who identify as "paleo/primal/ancestral" with those who identify as vegetarian. Presumably, these are identities that are sufficiently established that there are a large number of people who will adhere to them throughout the majority of their lifespan.

Granted, there are a number of potential confounds (in particular selection effects), but it may provide some valuable data.

At the very least, it may avoid the problems associated with the healthy observer effect, whereby, due to the stigma associated with meat intake, there are a large number of lifestyle confounds associated with observational meat intake studies. Here, we'd have a cohort that is largely wheat free, processed food free, and perhaps is more focused on pasture centered animal products.

Chuck Steak said...

@Dan: the reason is believed to be the high consumption of fermented foods by Asians. Small amounts are good (probiotics...), but higher amounts seem to correlate with higher digestive tract cancers. Also, in poverty stricken areas, like rural China, people tend to use "night soil" (human feces) as fertilizer, which leads to contaminated vegetables.

@JR: 350 Fahrenheit and above will form carcinogens in both protein and starches, heterocyclic amines in the former and advanced glycation end products in the latter. You also start destroying micro-nutrients at that level. Around 212 degrees, the temperature of boiling water, seems best, so boiling and steaming, the first cooking methods of homo sapiens. Also, the shorter the better when it comes to cooking time.

@ Stephan: What about methionine? Aren't there clear links between high methionine production and cancer?

Blue Wren said...

the Health Correlator guy has an interesting post:

and he shows the statistical correlation that as animal protein increases, colorectal cancers decrease and that as plant proteins increase, colorectal cancers increase significantly.

Also the Hyperlipid guy has a few posts about fruit and vegetables changing the DNA and causing cancers.

Could it be that the ingestion of plant proteins plus their antioxidants be the event that compromises a human's gut health, eventually resulting in the inability for a damaged gut tissue to deal with neu5Gc properly?

Chris Wilson said...

Hi Blue Wren,
Looking at that post I'm not sure it's fair to conclude that plant protein is positively associated with colorectal cancer. For one thing, Ned Kock doesn't provide the shape of the association, as he does with total cholesterol and cancer (which was quite helpful). Looking at the graph in that case makes me suspicious of the entire methodology employed, as it's obviously a flat relationship with a single outlier point leading the algorithmic software to spit out a non-linear fit and then report a spuriously small p-value (=0.01). In general, when you have an algorithmic approach that is tacitly making multiple comparisons, and on top of that deciding the shape of relationships to optimize model fit, you cannot take the p-values it reports at face value, and it's never correct to translate them into probabilities of your alternative hypothesis being correct. Granted I don't think Ned Kock was trying to do a thorough analysis here, I'm just saying that I wouldn't go around saying that "the China Study data show that plant protein increases colorectal cancer" based on this. It looks like a preliminary jab, nothing more or less.