Some things seem so obvious no amount of research or inquiry should be necessary to establish veracity. Things Simply ARE. The notion that fat makes one fat is a prime example. Consider the balanced chemical equation for the formation of water from hydrogen and oxygen:
H2 + 1/2O2= H2O, hydrogen and oxygen on one side, same thing on the other. Linear, first order logic like this permeates our world and serves us sufficiently in most situations…but not all. Consider the notion that fat makes you fat. Fat+People=FatPeople. It makes sense…fat on one side of the equation (food)= fat on the other side of the equation (people). Unless you’ve had your head at the bottom of a bag of Heart Healthy SnackWells you likely know better than that…but it makes SO MUCH sense!
In the 1960’s a theory was put forward to explain our tendency to get fat and this theory has elements of the flawed first order thinking described above. In fact many interrelated topics concerning fat gain and health fall down because of this reasoning. The catchy name was “The Thrifty Gene” Hypothesis. In this scenario, the collective “WE” are the unwitting victims of gremlin like genes that curse us with a tendency towards the cherubic because our ancestors had access to sporadic food sources and thus the folks who could gorge when the gett’n was good faired better when victuals were scarce. Why? Because, some could STORE fat more effectively than others, or so the theory goes. In more carnal terms, some folks were chubby enough to survive long enough to procreate. At first blush this makes a lot of sense and certainly we have the capacity to store energy in the forms of glycogen, protein and fat but is this Thrifty Gene notion TRUE? Well…no. Before I get into why it’s not true I just want to make clear that the thrifty gene hypothesis is predicated on the notion that periodic starvation and LACK of food is the reason why our affluent (most “authorities” point to fat as the problem) lifestyle leads us to our chubby condition.
Thrifty Gene Debunking Part 1-Cordain Speaks!
Prof. Loren Cordain wrote a communication to DR. Gerald M. Reaven MD regarding details of the mechanisms underlying insulin resistance and it’s evolutionary significance. You can read that full exchange here but I’d mainly like to illustrate Cordain’s point that starvation was rare in hunter gatherers was and continues to be largely ignored. Prof. Cordain makes the point that the archeological evidence and ethnographic records suggest that hunter-gatherers experienced little starvation, especially as compared to agriculturalists. Now this is a central feature of the Thrifty Gene hypothesis which is a guiding principle of modern metabolism research…and Dr. Reaven felt that debate on the DETAILS of why insulin resistance exists (mechanisms) was unimportant compared to simply agreeing that insulin resistance was “Once evolutionary useful…” Dr. Reaven is a hell of a researcher but the WHOLE premise of the Thrifty Gene hypothesis is that our ancestors faced frequent starvation and the only people to survive were those who had the most energy efficient genes. If the premise of frequent starvation is WRONG then our researchers are trying to interpret data and make sense of metabolic derangement with a broken model. This is a painfully common theme in research concerning why we get fat. Speaking of which:
Thrifty Gene Debunking Part 2-Devany tells us why we get fat.
Prof. Arthur Devany wrote a BEEFY paper some time ago with the provocative title: Why We Get Fat. It’s a great paper but it’s thick and fairly technical…muscle through it and get what you can from it anyway. What I want to highlight from the paper are the models of energy consumption and expenditure that show humans are wired to live at caloric excess. There were certainly periods of hunger, however these periods are relatively short and the energy reserves necessary to carry humans through lean times is achieved by the 9-13% body fat typical of hunter-gatherers.
Thrifty Gene Debunking Part 3-Dr. Michael Eades
Just a few days ago the always right on Dr. Michael Eades posted a fantastic piece comparing the Ansel Keys starvation study to the Yudkin low Carb study. The reason for this post was to make firm his position that “A calorie is not a calorie”. Apparently Dr. Eades has taken some heat from folks who contend total calories are the most important component of fat gain and health issues, while the good Dr. contends food quality is of greater importance. In this comparison Dr. Eades drew upon two historically significant studies that compared the effects of approximately isocaloric diets with VASTLY different macronutrient ratios. Both contained similar amounts of protein but one had the bulk of calories coming from carbs, the other from fat. If, as some of Dr. Eades detractors put forward, a calorie is just a calorie, the health, energy and vitality of the subjects in the two tests should have been identical. Oh, But they are not equal! Calories matter however it appears composition matters more…but why? On a mechanistic level it is obvious that insulin plays a remarkable role in hunger, nutrient partitioning and general health. It is a bit off topic but interesting to note that the high carb group displayed symptoms consistent with nutrient deficiencies including essential fatty acids and vitamins. We observe no such problems in the low carb group. Recent research has demonstrated that low carb diets decrease the need for various nutrients including folate and omega 3 fatty acids as compared to a standard high carb diet. Interesting no? One might even make the case that the junkier the diet (higher in carbs) the more vitamins are necessary…and this is indeed what we observe.
Dr. Eades offers a phenomenal analysis of the two studies but I think it’s worth noting the low carb group is allowed ad-libitum access to food, yet theses folks consumed what is essentially a caloric restricted diet…but with none of the problems experienced by the high carb group. According to the Thrifty Gene hypothesis, if humans are given access to unrestricted food they SHOULD gorge well above maintenance levels because this is the only way our ancestors could have survived. What we observe however is if carbohydrate levels are relatively low while protein is moderate and fat intake is high satiety precludes weight gain. Said another way: It’s hard as hell to get fat on a low carb diet. Carbohydrate consumption is the underpinning of metabolic derangement which fuels additional hunger…. that leads to the vicious cycle of additional carb consumption.
Evolutionary biology is important for a framework to postulate questions and assess data relating to human health but what if we have our model wrong? A calorie is just a calorie and our genes are suspiciously thrifty…and the real reasons for disease go ignored because they do not fit our expectations. It’s time to either rethink our models or actually pay attention to our evidence!
Regarding the Eades post, you can’t compare a strictly provided and monitored 24 week starvation diet with a self reported (from my reading of Eades’ description of the low carb study) 2 week study.
He writes “I know that I’m not truly comparing apples to apples with these studies” and then proceeds to extol the comparison.
Don’t get me wrong, I think the whole “a calorie is a calorie” saying is complete garbage. However, using those two studies as a comparison is fundamentally flawed…
-S
PS. More Posts! =)
Sameer-
You are right on of course. Dr. Eades intentionally or unintentionally ads a bit of weight to his case with his followup post looking at his own caloric intake. Still not exactly apples and apples but it’s compelling. There may be more in the literature that supports this. I wonder what the diets of kids on ketogenic diets for epilepsy look like calorie wise?
Thanks for stopping in!
Robb
Hey Robb,
Awesome article… I like what you’re doing with the blog.
I noticed that one of your categories was CrossFit. Interesting choice for a name…
Thanks Robert!
Life is interesting sometimes…looks like I’ll be re-affiliating with CrossFit. I’ll be spending the bulk of my time developing the blog and our local gym but I’m hoping to get to some of the certifications again soon.
Robb
Great post Robb! “Check your premises” is a phrase I like to use when people think some result is odd.
Scott Kustes
Thanks Scott!
Nicki uses a more direct approach when my premise is questionable: “Robb…you are an idiot…” Very…effective!
Robb
Robb,
Big fan of your posts on Performance Menu and Crossfit (I am a lurker).
Take a gander at this article in Time Magazine about low carb and cancer:
http://www.time.com/time/health/article/0,8599,1662484,00.html
Sully-
It’s a great article…I’m going to expand on this in another post. THANK YOU for the link!
Robb
Hey Robb–
Nice post.
I don’t know if you’re aware or not, but Neel rejected his own ‘thrify gene’ hypothesis in a paper (actually a book chapter) that is much less frequently read and quoted than his original musings from 1962.
Neel JV. (1982) The Thrifty Genotype Revisited. In The Genetics of Diabetes Mellitus, ed. J. Kobberling and R. Tattersal. New York: Academic Press, 283-93.
Cheers–
Mike
Doc-
I was TOTALLY unaware, thank you! It’s interesting that the original proposition has had such “stickiness” in the research community and beyond. Your blog continues to crush BTW! Always phenomenal material.
Robb
Nice review and synopsis of the material Robb.
*looks around guiltily and leaves*
Thanks Shaf!
Robb
Great post with the followup on Eades own intake. Keep posting Robb! And I think its great you’re back on CF. We need you there.
Thanks Jonas! Hej! Swedes need to stick together!
Robb
Hi Robb,
Interesting blog…albeit I’m 3 years late!!! 🙂 But hopefully you’re still monitoring because “I’m bringing thrifty back…”
I completely disagree with all the theories that debunk thrifty gene – including Neel himself. I think we need to revisit this very likely phenomenon.
Funny enough, you began your blog with this line, “Some things seem so obvious no amount of research or inquiry should be necessary to establish veracity. Things Simply ARE.” – well, that is how I feel about thrifty gene.
Here are my few points of contention:
1. We can’t compare how our brains are “wired” based on whole grains. Back in the bush, we likely sought after calorically dense foods that were necessary for our survival… notably GLUCOSE (fuel for the brain, body and then stored). What we didn’t bargain for was FRUCTOSE … the unfortunate byproduct of the sucrose molecule found in fruit. But this was okay too… because as we all know, fructose replenishes the glucagon stores in the liver and then is converted to triglycerrides and stored as FAT. So, a definite “two-fer” …
2. Part of Neel’s own argument against his theory was natural selection, and “why would we select a gene/process that resulted in a disease, such as diabetes?” Well … I have the answer for that as well. First off, we have to be realistic… how much obesity does one really believe a hunter/gatherer was capable of creating? Furthermore, any endocrinologist will tell you that the quickest way of reversing T2DM is through exercise… and who better to demonstrate this than our prehistoric ancestors, who had no choice but to walk… lift…. carry…. push…. pull…. – well, you get my point. In other words, save for Type 1 DM, I don’t believe there was an epidemic of T2DM back in the cave.
My theory on “Thrifty Gene Gone Haywire” is the combination of a few things:
1. Our natural “hunt” and “gathering” of palatable foods that are sweet, high fat or salty has become an absolute disaster in our current super-sized food environment. Not only is a neurochemical cascade set forth at the sight of the golden arches, but we are literally defenseless against self-control. Why? Likely because of the ubiquitous presence of fructose… the sugar that interferes with our glucose/leptin system… and therefore impedes satiety cues.
Ok I know this post is ages old and my comment will never reach the Great Robb’s eyes but…just for s#@ts and giggles. First, i’m a pharm.d. (for what it’s worth) and I love the blog and podcast.
I’m not arguing for the “thrify gene” hypothesis here, but I would have to say that arguing that starvation was rare in hunter gatherers does not seem like a relevant point to make. And if proponents of the theory argue that the thrifty gene was important because starvation was common then they are only weakening their position and openning themselves up to refutation by evidense that starvation was in fact rare. Even if starvation was rare…say it was only significant or life-threatenting one time every few generations, or even longer, it would seem that would place a tremendous amount of selective pressure favoring individuals who could survive the longest without food. In fact, you could make the arguement that even a single mass starvation event and subsequent evolutionary bottle neck could, at least in theory, lead to a predominance of such a thrifty gene. Sort of like exposing bacteria to an antibiotic will immediately favor resistant strains, even after a single exposure. And I would imagine that resistance could be observed for many generations thereafter. So I think your point weakens your argument only because, if one so wished, they could retort, “sure starvation wasn’t common, but those rare starvation events had a huge effect on human evolution none-the-less.” There you go…that’s all my arm-chair evolutionary biology has for ya. Keep up the awesome work and thanks for everything.
You seem to like to argue in circles, but are not providing an support for what you are saying. If you read the literature on TG hypothesis it was put forward that we experienced significant periods of starvation and this forged our genome. Now you are saying that highly irregular events are a shaper of the human genome, yet there is NO mechanism to support this. NONE. You are not considering genetic reaction norms or the other factors commonly attributed to a stress that is sufficient to cause adaptation. This TG idea still pervade science and it’d god damn wrong. It states that calories are the ultimate governor of metabolism when clearly mocronutrients and a host of other issues are front and center and offer more impact on gene expression. Get off your armchair and go lear Pharm-D ;0)
Yikes! Thanks for the reply? The only point that I (apparently rather poorly) attempted to make, was that it doesn’t seem that a selective pressure would need to occur frequently in order to have a significant effect. So making the point that “starvation was rare” does not seem like a useful argument to make. If, hypothetically speaking, there were a starvation event where a significant fraction of the species who was the least equiped go long periods of time without food died, and left alive only those who could, by chance, survive for longer periods of time without food, then a greater fraction of the species after the event would be better equiped to handle starvation. I just wouldn’t think such events, if they do occur, would need to occur often in order to leave their mark.