Saturday, 14 January 2012

The carnivore connection hypothesis

I just came across this article [1] and found that it's really quite interesting. It's about why we are insulin resistant. Even though the term "insulin resistance" is mostly used to describe a pathological condition, all tissues that can respond to insulin are, to some extent, insulin resistant and so we are all displaying various degrees of insulin resistance in various tissues all the time. Insulin resistance is simply when a tissue do not respond to insulin or responds poorly. So when muscles, for example, become insulin resistant, they do not take up as much glucose from the blood despite high blood insulin level. And they will keep burning a larger proportion of fat despite insulin trying to make them burn sugar. 

"Certain metabolic adaptations were necessary to accommodate low carbohydrate intake because the brain and reproductive tissues had evolved a specific requirement for glucose as a source of fuel."  

"The amount of carbohydrate may have ranged from as little as 10 g up to 125 g a day, much lower than the typical 250 to 400 g per day consumed in modern diets."

Brand-Miller, Griffin and Colagiuri looks at insulin resistance from an evolutionary perspective. The basis for the article is that the last 2 million years of human evolution was dominated by a low carbohydrate intake. This may have caused a selective pressure for insulin resistance. In addition, environmental pressures such as geographic isolation and/or starvation may have further increased the prevalence of insulin resistance genes in certain populations. The reason is that when carbohydrate intake is low it is important that the tissues that do not need to burn glucose and can burn fat become insulin resistant, thus freeing glucose for the tissues that need glucose and cannot burn fat. 

"With the first severe Ice Age, global temperatures fell dramatically and resulted in moist African forest becoming dry, open woodland and savannah. Hominids that were unable to utilize grasslands became increasingly carnivorous.

"In Africa and Eurasia, hunted animals displaced gathered plant foods as the principal source of food, leading to a diet low in carbohydrate and high in protein for most of the year. Increased meat intake from wild terrestrial and marine animals would have also provided greater amounts of omega-3 fatty acids such as docosahexaenoic acid essential for brain development, facilitating the larger brain size of H. sapien."

The authors further hypothesize that the selective pressure for insulin resistance was relaxed with the advent of agriculture and the increasing amounts of carbohydrate in the human diet. Domestication of cereal grains first began in the Middle east, some 12 000 years ago, and spread across to Europe and East Asia. The logic thus goes that populations that only recently have adopted agriculture are more likely to become insulin resistant, overweight and at ill health than those populations longer exposed.

As examples of such cultures the authors mention the Pima Indians, Nauruans, and Australian Aboriginals. The Pima only adopted agriculture some 5000 years ago, about the same time as us Norwegians.

According to the authors the carnivore connection hypothesis hinges on five lines of evidence:

(1) During the last two million years of evolution, humans were increasingly carnivorous, that is, consumed a low-carbohydrate, high-protein diet.

(2) A low-carbohydrate, high-protein diet requires profound insulin resistance to maintain glucose homeostasis, particularly during reproduction.

(3) Genetic differences in insulin resistance and predisposition to type 2 diabetes can be explained by differences in exposure to carbohydrate during the past 12,000 years.

(4) Changes in the quality of carbohydrate can explain the higher prevalence of type 2 diabetes in susceptible populations.

(5) Habitual consumption of a high-glycemic-load diet worsens insulin resistance and contributes to the obesity and type 2 diabetes in all populations.


Food
As there are some tissues that are in great need of glucose, mostly those with few or no mitochondria, insulin resistance is a key mechanism by which these tissues are properly fed. But now a days insulin resistance occurs in combination with a high carbohydrate diet and is a sign of something being very wrong - the reason being that when carbohydrate intake is high, insulin sensitivity needs to be high in order to keep us from being sugar poisoned. Usually when we talk of insulin resistance we are referring to liver insulin resistance. Glucose is an important fuel for fetal growth and insulin resistance thus ensures enough glucose is directed at this process. Pregnant women naturally become more insulin resistant, but if you are already insulin resistant this may develop into gestational diabetes, a form of diabetes that normally improves after pregnancy. Women with polycystic ovarian syndrome are insulin resistant and PCOS can be seen as just another manifestation of the metabolic syndrome in women. Brand-Miller and coworkers believe that these women may represent a group that was highly fertile in a low carbohydrate environment. There is much indicating that insulin resistant mothers have insulin resistant babies and that each new generation is more metabolically challenged that the former. So in individuals well adapted to low carbohydrate living, increasing insulin resistance is caused by continuous high carbohydrate dieting.

"We propose that the selection pressure for insulin resistance was relaxed first in Europeans when dietary carbohydrate increased 12,000 years ago with the advent of agriculture. In accordance with this long-term exposure, Europeans have experienced a lower prevalence of diabetes, even when overweight and obese (see Section 6), compared to other population groups."  

One aspect of this article I particularly liked, was that they did not adhere to a common misconception of food availability. They mention Neel’s thrifty gene hypothesis which suggests that cycles of "feast and famine selected for a quick insulin trigger." They also mention Gerald Raven's similar hypothesis that suggests that "muscle insulin resistance was the key to survival during food scarcity because it conserved glucose by minimizing gluconeogenesis and preserving lean body mass." Both of these hypotheses are based on an assumption that food must have been hard to come by during our recent evolution. To me this is a serious underestimation of humans and suggests that those doing the hypothesizing have themselves not spent much time outdoors. Luckily, Brand- Miller and coworkers are aware of the shortcomings of these hypotheses and write: "However, this is not supported by the scientific literature. While hunter gatherers would have been exposed to seasonal and geographical changes in food supply, severe food shortages or starvation were rare and more likely to occur after the transition to agriculture (preindustrialization)."

The authors also spend some time discussing types of carbohydrate and the transition from complex unrefined to refined easily digestible and the concomitant change in glycemic index. This might have further enhanced the insulin resistance promoting effects of our high carbohydrate diet.

Humans are well adapted low carbohydrate intakes, but it seems this ability might have come at a cost. Anyway, it seems many of us are fighting our genetic disposition by stuffing ourselves with carbohydrates. All in all a really interesting article and well worth a read.


1. Brand-Miller JC, Griffin HJ, Colagiuri S: The carnivore connection hypothesis: revisited. J Obes 2012, 2012: 258624.

17 comments:

  1. the most illuminating discussion on this subject i've ever seen -- thanks!

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  2. "So in individuals well adapted to low carbohydrate living, increasing insulin resistance is caused by continuous high carbohydrate dieting."

    As there are populations who are lean and insulin-sensitive on continuous high carbohydrate diets (from roots, tubers and/or rice), I think that it's more accurate to say "So in individuals well adapted to low carbohydrate living, increasing insulin resistance is caused by a continuous excess of energy from moreish, manufactured carbohydrate-based foods."

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    1. It's a valid point Nigel.Your rewrite makes more sense. Carbs alone aren't enough. I just did't bother going into all the other factors this time and resorted to an oversimplification.

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    2. Interestingly, the Pima's traditional diet (after adoption of agriculture but before adoption of the SAD) on which they were lean and insulin-sensitive was high (70–80%) in carbohydrate and low (8–12%) in fat. See The Traditional Pima Indian Diet: Composition and adaptation for use in a dietary intervention study

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    3. You wouldn't happen to have the full text?

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  3. This was a rewarding read, As you have written agriculture was a relative late-comer here in Northern Europe, why would we not expect to see Diabetes 2 rates at a comparable level to Pima indians? (I realise the study doesn't say that but Europeans are dealt with as a homogenous population)
    Should we see differences in diabetes 2 rates among Highland Scots pastoralist fishers or the Icelandic population which ate low carbohydrate during the colder centuries of the last millenium?

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    1. Thanks N. I know it doesn't all ad up, i.e. with Pima and other populations experiencing ill health because they adopted agriculture so late, while other cultures, who were equally late, seem to do fine. It might have to do with northern Europeans having a more mixed genetic background while the Pima f.ex. have not. Or it might just be that the hypothesis only explains part of the problem.

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    2. Thanks Pal, (my keyboard can't make accents, sorry) a possible mechanism might be greater evolutionary pressure in Northern Europe selecting for a compatibility with the novel foods. For example; marine resources appear to have been completely, even deliberately, ignored in neolithic Britain this could have created a greater reliance on Neolithic forms of calories.
      Neal

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  4. Does this suggest that in a low-carb weight-loss diet, for example, carb content should be kept high enough to preserve insulin sensitivity, at least for those who process glucose normally?

    (I'm thinking of anecdotal reports of increasing the rate of fat loss by slightly increasing carbs and of elevated blood sugar in long-term VLC diets.)

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  5. Hi Pal, nice post. I agree with you that sapiens is just too smart a species to go be going hungry all the time. However, one single week-long starvation period in a lifetime is enough to apply significant selective pressure on a population. Have a few of those, on different generations, and you’ll have clear signs of selection showing in the population after a few hundred years.

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  6. The amount of carbohydrate may have ranged from as little as 10 g up to 125 g a day, much lower than the typical 250 to 400 g per day consumed in modern diets
    Its not just about amount but also about concentration.
    Its not the same to consume 125g whole day, and in one meal. The first one is not harmful, while the second one may even harm you more then higher carb diet.

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  7. I'm currently reading the excellent book 'Survival of the Sickest' by Sharon Moalem in which he mentions that insulin resistance might've helped populations to cope in extremely cold environments. He explains that glucose lowers the freezing point of liquids (in this case, blood), thus reducing the formation of ice crystals.

    I don't have the book with me right now but he gives some compelling arguments to back up this hypothesis.

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    1. That sounded a bit extreme. It's pretty cold when you have to worry about ice crystals forming in your blood. You'd think gangrene was a given long before ice crystals form. But then again, this is not my area of expertise.

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  8. I disagree about the frequency of starvation. Consider the Last Glacial Maximum around 15,000 years ago. The population of humans in Europe was contracted to a much, much smaller number in just the southern Iberian peninsula. Also, Jared Diamond makes the assertion in one of his books that we all have antibodies to prions, which he then reasons is clearly indicative of the widespread occurrence of cannibalism. I would hypothesize that early humans had no abstract concept of "humanity". Another tribe was just another herd of prey (or predators). When all the large fauna had fled or been wiped out by the advancing cold and ice sheets, what else was there to hunt but the guys in the next valley south? As they were tougher to kill that beasts, it adds up to frequent days and nights of nothing to eat. Heavy selection pressure for our ancestors who toughed it out, IMO.

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  9. It's interesting that one of the authors of the carnivore-connection paper has written another paper that appears to be an example of academic incompetence morphing into misconduct. I am arguing near and far for the correction or retraction of the deeply flawed Australian Paradox paper. Check out the dispute in the following slideshow, and let me know what you think. Here it is: http://www.australianparadox.com/pdf/AUSTRALIAN-PARADOX-101-AUGUST.pdf or try #18 on LHS of http://www.australianparadox.com

    Regards,
    Rory Robertson

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    1. I haven't checked all the details, but as far as I can see this is standard sloppy science and your points are valid. If one should ever try to imply causation from such a correlation (which you really can't do) you need damn good data and you need to control for a lot of variables, and more importantly the correct variables. In theory it is possible that sugar consumption can drop as obesity rises, but the Australian paradox study in now way proves this with any certainty.

      Good luck with getting your message out there!

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