Sunday, January 27, 2013

The Carnivore Connection Hypothesis: Part 1

The carnivore connection hypothesis (CCH) proposes that insulin resistance is an evolutionary adaptation to a low carbohydrate diet, which is based on four lines of evidence [1] [2] [3]. 

1.      “That during the last two million years of evolution, humans were primarily carnivorous, i.e., flesh-eating hunters consuming a low-carbohydrate, high-protein diet”
2.      “That a low-carbohydrate, high-protein diet requires profound insulin resistance to maintain glucose homeostasis, particularly during reproduction”
3.      “That genetic differences in insulin resistance and predisposition to NIDDM can be explained by differences in exposure to carbohydrate during the past 10,000 years”
4.      “That changes in the quality of carbohydrate can explain the recent epidemic of NIDDM in susceptible populations.” 

Carbohydrates in Traditional Diets 

The third line of evidence is an attempt to explain the differences in IR and T2D between populations - how the Pima and Nauruans have some of the highest rates of T2D and how Australian Aborigines and Eskimos have higher rates of T2D than Australians/Canadians of European descent. 

The differences are based on the first line of evidence, which suggests that hunter-gatherers are mostly carnivorous.  The CCH papers (1994, 2002 and 2011) cite 1977 book by Eaton and Konner to suggest hunter-gatherers ate between 10-125 grams of carbohydrate a day, but in their Paleolithic Nutrition paper (1985) they estimated an average macronutrient ratio of 34:21:45 (P:F:C), which they later (1997) updated to 37:22:41 [4]. 

Cordain, et al (2000) found a problem with previous estimates and instead suggests on average hunter-gatherers got 19-35% of their calories from protein, 28-58% from fat and 22-40% from carbohydrate [4].  So although on average, hunter-gatherers consumed less carbohydrate that we currently do, the average wasn’t as low as 10-125 grams (at 2,000 calories 22-40% carbohydrate is 110-200 grams, at 3,000 calories it’s 165-300 grams) 

Jenny Brand-Miller*, one of the co-authors of the CCH papers should be aware of this as she is also a co-author of [4].  But that’s ok, it doesn’t necessarily refute the CCH, though one could speculate at the possibility of any selection bias.  What may somewhat refute the CCH are cultures that have historically eaten high carb diets, yet are vulnerable to IR/T2D 

The CCH uses the Pima, Nauruans, Australian Aborigines and Eskimos as examples of cultures who have historically eaten low carb diets and are vulnerable to IR/T2D.  The traditional Nauruan diet seems to be mainly fish and coconut, the traditional Aboriginal diet may have been high carb [5], but would have depended on location and season, and the traditional Eskimo diet was likely ketogenic.  But the Pima traditionally ate a very high carb diet** [6]. 

Due of their high carb diet, the CCH would predict the Pima to be quite carbohydrate tolerant and resistant to IR/T2D, yet they have among the highest rates of IR/T2D in the world. 

The CCH also can’t explain how other high carb eating HGs/TCs are vulnerable to IR/T2D.  For example, native Hawaiians have higher rates of T2D than Caucasians living in Hawaii (14% vs 3%) [7] and the traditional Hawaiian diet was likely very high in carbohydrates [8].  There are bound to be other examples. 

The alternative explanation, which I mentioned in the thrifty gene hypothesis (which is actually kind of similar to the CCH) is that HGs/TCs have had less adaptation to western foods whether it’s alcohol, milk, fruit, seeds, refined sugar, nutrient poor foods, etc. 

* For those who like gossip: Jennie Brand-Miller’s professional career is devoted to GI, many of her published works are on the benefits of low GI diets.  She is a co-author of “The Australian Paradox: A Substantial Decline in Sugars Intake over the Same Timeframe that Overweight and Obesity Have Increased[9] (there’s an entire website to rebut the Australian Paradox paper), the Paleo related paper I mentioned above, and has argued that it’s high GI foods, but not sugar, that has caused increases in obesity and T2D 

** Gary Taubes tells us the Pima got fat and diabetic because they increased their carbs and Jennie Brand-Miller tells us the Pima got diabetic because they were previously eating low carb.

This blog post is in two parts.  Read part 2 here

Monday, January 21, 2013

Bad Evolutionary Theories of Disease

“Just because your hypothesis relies on ‘evolution’ doesn’t make you anymore right than anyone else” - Mat Lalonde 

Some in the ancestral/alternative health community may be attracted to evolutionary theories of disease, and agree with them even when the evidence doesn’t support the arguments or the conclusion*. 

I’ve discussed the thriftygene hypothesis**, which proposes obesity, a chronic disease, is evolutionarily adaptive***.  While the observations are correct, the explanations have a lot of counter-evidence against them and alternative explanations seem more accurate. 

There are other evolutionary theories of disease that propose a particular chronic disease is evolutionarily adaptive.  For example: 

* Some may also automatically consider Paleo to be the right approach to eating just because it uses evolution.  Even if it’s true, the argument is invalid 

** The thrifty gene hypothesis suggests some people have thrifty genes that promote overeating and weight gain during times of plenty to prepare them for famines, and that because famines no longer occur these people gain weight 

*** Weight gain could be a physiological adaptation to energy overload mediated by low level mitochondrial dysfunction, ER stress, PTP1B, therefore minor leptin resistance to enable excess calories to be stored as fat.  But physiological adaptation is different to evolutionary adaptation. 


“…adolescent acne is a normal physiological process - a high-order psychoneuroimmune interaction - that functions to ward off potential mates until the afflicted individual is some years past the age of reproductive maturity, and thus emotionally, intellectually, and physically fit to be a parent.” [1] 

Acne shouldn’t be necessary for this function.  Cultural norms and other cues could ward of potential mates and the difference in appearance between 12-14 year olds and ~20 year olds is a signal of maturity.  There are some problems with this idea: 

  • No cases of acne have been found among hunter-gatherers and lower rates of acne are observed in rural, less westernised groups [2]
  • Acne affects young adults as well and can persist into middle age
  • Severe acne can cause semi-permanent scarring
  • (Not all adolescents are/have been affected by acne) 

Androgens for sebum production and bacteria both seem necessary for acne [3].  But plausible underlying pathologies of acne include: hypochloridia, leaky gut, dysbiosis, LPS, chronic stress, low Treg cells/IL-10 and inflammation.  These underlying pathologies are a more plausible explanation of acne and may explain the associations between acne and other chronic disease [3] [4], the absence of acne among hunter-gatherers and the prevalence among modern industrialised societies 

There are others like this which I’ll tackle in future posts 

A General Genetic Argument 

Below is a line of arguing that has been used to suggest depression is evolutionarily adaptive, but can also be used for any other highly heritable chronic disease 

  • Depression is highly heritable
  • Genes that predispose one to depression are still around
  • Therefore those genes have not been selected against
  • Therefore those genes have been selected for (are evolutionarily adaptive)
  • Therefore depression is evolutionarily adaptive 

The first conclusion is fine and is one of the points I made in my previouspost.  The second and third conclusion do not necessarily follow. 

Just because genes haven’t had selection pressures against them doesn’t mean they have had selection pressures for them.  Seeing as hunter-gatherers and traditional cultures have near population-wide freedom from chronic disease, genes that promote chronic disease only in the context of western diet and lifestyle haven’t had almost any selection pressure against them, at least in so far as the genes relate to chronic disease. 

Just because genes that are associated with chronic disease have been selected for, doesn’t mean the chronic disease has been selected for (that's a false dichotomy).  Genes produce proteins that have many effects on the body.  Some of these effects may have been beneficial among hunter-gatherers but promote disease in the context of a western diet and lifestyle.  A good example is the GG phenotype for myeloperoxidase (MPO), which increases the expression of the MPO gene, therefore generally more MPO.  The GG phenotype would have ideal for hunter-gatherers as it enhances immunity but is detrimental now as MPO products can oxidise LDL and HDL and promote atherosclerosis.  The argument above could conclude that atherosclerosis and CVD are evolutionarily adaptive.  The more likely explanation is that the GG phenotype has had positive selection for its immune effects without negative selection due to CVD.

Tuesday, January 15, 2013

An Evolutionary Approach to Chronic Disease

Most people don’t know what causes chronic disease.  In their eyes it ‘just happens’ and is due to genetics, for example: ‘I have breast cancer because my mother did’.  When you’re surrounded by so many who are overweight, diabetic, have had a heart attack, are aging poorly, etc, it can seem that chronic disease is normal.  When you combine normality with a lack of understanding, chronic disease seems inevitable and that there’s little you can do. 

Population-Wide Freedom of Chronic Disease 

However, many of the chronic diseases we suffer from are very rare among modern day hunter-gatherers (HGs) and the traditional cultures (TCs) visited by Weston A. Price. 

When HGs or TCs adopt a western diet they succumb to the same diseases as we do.  This suggests their diet, rather than their genes, protects against chronic disease, and that it’s possible to have near population-wide freedom from chronic disease. 

A counter argument is that those people didn’t live long enough to show signs of chronic disease.  But this counter argument lacks merit:

  • Average life expectancy at birth was quite low for HGs, which is due to high infant and childhood mortality.  Most who make it to 15 live to 45 and 45 year old HGs can expect to live another ~20-25 years [1]
  • Biomarkers of disease risk such as elevated fasting glucose, blood pressure, atherosclerosis are rare among HGs and common in age matched western populations [2]
  • Chronic disease can occur in early age: certain autoimmune diseases are more likely to begin in younger people, childhood obesity and diabetes is climbing and early signs of atherosclerosis can be seen in young people
  • Most of the increase in coronary heart disease in the early 20th century can’t be explained by changes in average lifespan [3] 

Where’s the Selection Pressure? 

There’s some further supporting evidence for low chronic disease among HGs and TCs. 

In Chris Masterjohn’s presentation for the Real Food Summit he makes an excellent point (in Part 1 at ~24:00) that among populations free of chronic disease the most vulnerable and the least vulnerable members are protected from chronic disease.  He described that and other details as a strength of Price’s work.  For this post I’ll take it in a different direction. 

Most people agree that chronic disease reduces fitness (evolutionary/natural selection fitness that is)*.  If a person’s genetics were such that they spontaneously developed obesity (ob-/ob-) for example, those genes would have strong selective pressures against them and go quickly out of the gene pool. 

Some genetic mutations, such as familial hypercholesterolemia (FH), and some polymorphisms, such as the GG phenotype of myeloperoxidase (MPO), are associated with a higher risk of disease (in both cases CVD).  (Other genetic mutations and polymorphisms would be associated with lower risk of disease.)  These are the kinds of things that are meant by genetic risk/vulnerability and is how family history can be predictive. 

But you’ve got to wonder how these and other ‘bad genes’ are around, seeing as they are seemingly so harmful now. 

If one were genetically susceptible to disease and in an environment that promoted disease, then those genes would have strong selection pressures against them.  Perhaps they would pass those genes to the next generation, but on a large scale those genes would become rarer over time. 

In an environment that doesn’t promote disease, there’s no selection pressure against ‘bad genes’ and so the ‘bad genes’ stay around.  This is important because it provides support for both chronic disease being previously rare and ‘bad genes’ not being a death sentence. 

Except for some pretty extreme gene mutations such as homozygous FH, chronic disease doesn’t have to run in the family and we should not become fatalistic. 

* Some theories are based on the idea that a vulnerability to chronic disease has been and can be adaptive.  These theories will be the focus of a future post. 

Paleo and WAPF 

The diet of HGs and TCs seems to be the main protective element against chronic disease and is a main starting point for the Paleo and WAPF approach to eating 

Without understanding the causes of chronic disease we can have reasonable guess that switching to a Paleo/WAPF approach to eating is probably to going to improve someone’s health and may even reverse their chronic disease.  We can make this guess and somewhat generalise to them based on:

But understanding the causes of chronic disease is important because simply recommending that one should eat Paleo/WAPF may not be as convincing or as helpful as the advice could be.  Valid questions that we could be asked include:

  • How does Paleo/WAPF help?
  • Are there any new foods that are helpful and any old foods that are harmful?
  • What about supplementation?
  • What about other lifestyle factors? 

Without much understanding we can’t properly answer those questions.

Sunday, January 6, 2013

Book Review: Perfect Health Diet

The new edition of Perfect Health Diet was released in December 2012 and the Australian edition is set to be released on the 7th of January.  Australian readers will appreciate the Australian edition as the measurements are in metric* and it has Australian statistics where possible. 

* The exception is the blood test measurement for vitamin D.  For vitamin D, to convert ng/ml to nmol/l, you will need to multiply by 2.5
Perfect Health Diet

For those unfamiliar with the previous edition, Perfect Health Diet (PHD) is about finding a diet for perfect health (fancy that).  Often you’ll hear you should ‘eat a healthy diet’.  But what is a healthy diet?  Simply recommending real food (or whole/unprocessed food) is ok, but carnivore and vegan diets can qualify as real food and some real food can be nutrient poor and/or toxin rich.  Most people have some vague ideas as to what a healthy diet is, which probably doesn’t come from synthesising research studies.  That’s where Paul and Shou-Ching Jaminet come in with PHD.  Similar to the previous edition, PHD is divided into five sections: 

  • Part 1 begins with a big picture perspective - looking to hunter-gatherer diets, other mammalian diets, human breast milk and body composition for clues.
  • Part 2 covers the macronutrients, the types of fats and carbohydrates, ideal protein, fat, carbohydrate intakes and macronutrient ratios
  • The Jaminets have come to the conclusion that chronic disease is largely caused by toxins, malnutrition and chronic infections.  Parts 3, 4 and 5 cover these topics

When I read the first edition about a year ago, I was quite sceptical of infectious causes of aging and disease were as prevalent as what the Jaminets were saying.  Over the course of 2012, I looked into the causes of chronic disease and found chronic bacterial and viral infections are quite widespread, are associated with many chronic diseases and seem to have a strong role in autoimmune diseases, depression and cancer.

To clear chronic infections the Jaminets primarily recommend measures to strengthen the immune system such as an 8 hour eating window to promote autophagy and vitamins A, D and K2.  One thing I noticed in my research is that while many people have chronic infections, those with a weak or poorly regulated immune system were the ones who were far more likely to develop chronic diseases from them.  So even if the measures in PHD don’t rid you of a chronic infection you will be far less likely to develop a chronic disease.

The New Edition

For those who have read the previous edition you’re probably wondering what’s different with the new edition.  It’s a longer book (~1.5x as many pages) with more content.  The recommendations have changed a little and there are new sections on weight loss, blood lipids and how to be in tune with our circadian rhythm.  Paul Jaminet has a two part series on what’s new in the new edition.

Weight Loss

In the weight loss section the Jaminets discuss the food reward hypothesis of obesity, which has been a hot topic in the blogosphere over the past two years.  They make the following points:

  • The cafeteria diet and the refined ‘high fat diet’, which are fed to rats and mice to induce obesity, are very palatable and rewarding yet also nutrient poor and toxin rich
  • Nutrient hunger is a plausible and logical explanation for overeating nutrient poor junk food and obesity
  • Obesity is a chronic disease.  We should be able to lose weight/maintain a healthy body weight by addressing the same things that underpin other chronic diseases - toxins, malnutrition and infections
  • ‘A healthy diet is a delicious and satisfying diet’ and ‘every meal should be delicious’ 

I agree with all these points and the last point is particularly important in a diet related book.  You wouldn’t want someone to eat some strawberries (for example) or a delicious meal, then feel guilty and anticipate weight gain just because they were delicious.

Reader Reports

Another new feature of the new edition are ‘reader reports’ - testimonials of readers from the blog who have experienced health improvements from eating a PHD style diet.  While testimonials are hardly gold standard scientific research, some of the reader reports in PHD are of people overcoming chronic health problems, which should be quite intriguing and motivating for someone new to all this.  After all, it was one of the things that first got me interested in nutrition and health.

Some of the reader reports are about the benefits of ketogenic diets, some are about coming out of very low carb diets by adding starches and a few are about lowering the number of carbohydrates from the standard australian/american diet (SAD).  I hope no one is confused about this, as it’s consistent with the overarching economical approach to nutrition in the book - be sufficient in every nutrient (including glucose) without excesses in any nutrient, while minimising toxins.  There seems to be two target audiences for PHD: people following a low carb or paleo diet and people eating the SAD or something similar.


At the moment PHD is the best book I've read on the subject of diet/health and is the book I would recommend to people interested in weight loss or in improving their health.  There is much to commend the book:

  • PHD is a well-researched book with more than 1,000 citations.  The scientific approach and the citations should be convincing to a sceptic and an excellent introduction for someone who wants to learn more
  • Even though PHD is scientific, the science is not impossibly academic and should be understood by the average person (although it may take a little longer to read or require a second read).  The layout makes the book really easy to read
  • The Jaminets approach the subject of nutrition in quite a unique way (such as breast milk, mammalian diets, the economical approach to nutrition, chronic infections, etc) and the arguments are often logical and intuitive as well as being supported by evidence
  • PHD covers a very broad topic yet manages to be thorough and quite specific in its recommendations
  • The economical approach to nutrition in the book makes it safe and easy to recommend to a wide audience.
  • A comment by George on Chris Kresser’s site described PHD as an ‘idiot-proof diet’.  Which I agree with, due to the specific recommendations and the safe economical approach to nutrition
  • On topics such as saturated fat, salt, etc, instead of going with political correctness or stirring up a controversy, the Jaminets just say it how it is
  • Recommending 1.35kg of plant food per day dispels the popular misconception that Paleo diets are all about eating meat 

I have a few minor problems with the book:

  • 75g of protein a day might be too low as a general recommendation.  Robb Wolf recommends 2.2g of protein per kilo of (lean) body weight, and other people recommend 1.4-1.5g per kilo of ideal body weight and a minimum of 90g.  Eating more protein would also improve nutrition if it comes from meats, eggs and other whole foods
  • White rice is a safe starch but not very nutritious.  People who are eating more calories can probably get away with more white rice, but those who eat <2,000 calories a day should eat less (perhaps <1-2% total calories per week).
  • The supplement recommendations could be more convincing.  Unlike the SAD, people eating a PHD should be getting enough selenium, B vitamins, vitamin C, zinc, copper and choline, etc.  Also, the trace mineral list at the end of the chapter had very little research to support the recommendations 

Rather than say you should or shouldn’t buy PHD I’ll say this: if you had to pick only one diet/health related book for yourself or for someone you know, Perfect Health Diet would be that book. 

You buy the book from Scribe here 

* Paul Jaminet sent me a review copy.  I had the previous edition and was planning to buy the new edition anyway.  I was already recommending the previous edition to those who were interested and now will recommend the new edition.  I won’t receive any money from this review