Sunday, February 3, 2013

The Carnivore Connection Hypothesis: Part 2

Read part 1 here

Chris Masterjohn’s AHS 2012 Presentation 

Chris Masterjohn’s AHS 2012 presentation is excellent on so many levels.  It’s highly relevant to this post and I consider it to be required viewing.  He makes the following points: 

  • Most humans (>95%) have many duplications of the salivary amylase (SA) gene, whereas chimpanzees have no duplications
  • Populations consuming a higher starch diet tend to have more copies of the SA gene on average (7 copies) than populations consuming a low starch diet (5 copies), but both groups have more copies than chimpanzees (2 copies)
  • The number of copies of the SA gene correlates with SA activity.  Humans have ~4 times more SA activity than gorillas and ~10+ times more SA activity than other primates
  • During a ‘starch tolerance test’ people with high SA activity have a lower AUC for blood glucose and insulin due to a greater pre-absorptive insulin release
  • But during a glucose tolerance test there is no significant difference between people with high SA activity and people with low SA activity
  • Insulin resistance can be caused by energy overload and oxidative stress 

This suggests: 

  • Humans are adapted to eating carbohydrate, specifically starch (somewhat countering the first line of evidence)
  • While there are people who have less adaptation to starch, these people don’t perform significantly worse on glucose tolerance tests, which is a marker of insulin resistance used to diagnose IR/T2D (a very strong counter to the third line of evidence)
  • Insulin resistance can be caused by an underlying pathology 

Underlying Pathologies of IR and T2D 

The carnivore connection hypothesis doesn’t account for the underlying pathologies behind IR and T2D.  To their way of thinking it’s pretty much all about GL, but increasing carbohydrate consumption increases insulin sensitivity, not the other way around [1].  Underlying pathologies of insulin resistance include chronic inflammation and mitochondrial dysfunction, which can be caused by energy overload and other mechanisms* [2]. 

IR and T2D are clinically considered to be on the same continuum, with T2D being diagnosed as a more severe form of insulin resistance, as indicated by elevated fasting blood glucose and impaired glucose tolerance*.  But T2D isn’t just more IR, it requires a reduced insulin release from the pancreas as well.  At least the authors make the distinction between IR and T2D, but they propose that high GL diets cause T2D by exhausting the beta-cells of the pancreas.  If T2D is due to beta cell exhaustion then an animal model like the LIRKO mice (who lack insulin receptors in the liver, have insulin resistance and hyperinsulinemia) would exhaust their beta cells and develop T2D. 

The problem is LIRKO mice don’t develop T2D because they compensate for liver insulin resistance by increasing beta cells, which is mediated by insulin signalling [3].  LIRKO mice who also lack insulin receptors in the beta-cells (βIRKO) don't compensate and develop T2D [4].

This suggests that physiological adaptations to higher carb diets would involve both an increase in insulin sensitivity and beta-cell mass, and that you need an underlying pathology, like mitochondrial dysfunction [5] [6], to impair homeostatic regulation

Seeing as beta cell exhaustion doesn’t occur and those who eat a higher GL diet have a greater physiological adaptation that promotes insulin sensitivity and insulin release, people who eat a high GL diet should do better on standardised tests such as the oral glucose tolerance test 

* Under these circumstances IR can be viewed as a physiological adaptation to energy overload.  But remember that physiological adaptation and evolutionary adaptation are not the same.


Remember the four lines of evidence: 

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.” 

The first line of evidence is fairly accurate.  Hunter-gatherers (HGs) generally eat fewer carbohydrates than we do now (~22-40% vs ~50-55%) although this varies widely between HG groups and some eat more carbohydrate than we do.  Though that doesn’t refute the third line of evidence so long as the high carb HGs are less vulnerable to IR/T2D than those of European descent and the low carb HGs are more vulnerable.  The problem is that some high carb HGs/TCs are among the most vulnerable to IR/T2D (Pima, Hawaiians). 

No issue with the second line of evidence.

Even though I have often recently said 'physiological adaptation is not the same as evolutionary adaptation', the third line of evidence is very believable.  I actually thought there would be an effect, just as not large as what the authors were making out.  However, the fact that people with less adaptation to starch perform equally as well on glucose tolerance tests and the Pima/Hawaiians being among the vulnerable to IR/T2D is a strong refutation of the third line of evidence 

The fourth line of evidence suggests high GI/GL diets cause IR and beta-cell exhaustion (in those genetically vulnerable), therefore T2D.  However the opposite is true: carbohydrate consumption correlates with insulin sensitivity, beta cell exhaustion doesn’t occur and insulin promotes beta cell growth/regeneration 

The two main points about the CCH is that vulnerability to IR/T2D can be explained by ancestral carbohydrate consumption and high GI/GL diets cause IR/T2D.  Both points have strong counter evidence against them

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