A new mice-with-an-engineered-human-genetic-deficiency study is out that promises to shed light on why humans are so darn diabetic and obese – and the cause is an evolutionary “mistake.” A deficiency that apparently slipped through the cracks without somehow leading to our species’ demise. You see, we’re missing a genetic component shared by pretty much all other mammals besides ourselves. While mammals generally produce two types of sialic acids, N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), thanks to a mutation in a gene called CMAH, humans produce only the former. We don’t have the enzyme necessary to convert Neu5Ac to Neu5Gc. Why is this important? Sialic acids act as “contact points” for our cells to interact with the environment and other cells, and the latest research indicates that mice with the humanesque CMAH mutation are more prone to diabetes, especially when they’re overweight.
Both mice with the genetic mutation and without grew obese and insulin resistant on the high-fat lab diet (I only have access to the abstract, so no details are given on the composition of the high-fat diet, but if it’s anything like the 14.4% trans-fat ketogenic rat diet, I wouldn’t read much into it), but only the mice with the mutation experienced pancreatic beta cell failure. As you may know, a healthy pancreas with successful beta cells secretes insulin as needed. Unhealthy pancreases whose beta cells are abject failures tend to be owned by diabetics. These mice showed all the hallmarks of human diabetes – obesity, insulin resistance, and a failing pancreas – while possessing the same genetic “defect” that humans have. Diabetes is increasingly prevalent among modern humans, all of whom possess the CMAH defect. Coincidence?
I can buy it. It seems like a reasonable hypothesis, but I wonder how relevant it really is to the situation. I have to wonder, for example, why we and our hominid ancestors were able to stay relatively healthy and free of a serious diabetes epidemic for 2.8 million years. We’ve (and by “we,” I mean homo sapiens sapiens and our immediate ancestors) never had the ability to make Neu5Gc – same as the mice with pancreatic failure – and yet it’s only in the last few decades that diabetes has grown to epidemic proportions. Maybe there’s something more to the epidemic? Perhaps major changes to our food, our activity, and our lifestyles that have taken place in the last hundred years are altering the way our genes interact with the environment? Just throwing it out there.
Anyway, how come Neu5Gc production was deactivated in hominids? Where’s the advantage? Three million years ago, malarial parasites found hosts by latching exclusively onto Neu5Gc sialic acids, so the Neu5Ac—>Neu5Gc deactivation mutation probably gave hominids resistance against malaria. They no longer carried Neu5Gc and the parasites had no entry point. Obviously, malarial parasites have since adapted and now frequently use our bodies as hosts through different pathways, but that’s the evolutionary “justification” for the CMAH mutation. There’s also speculation that total removal of Neu5Gc from hominids allowed the expansion of their – of our – brains in concert with our switch to a denser diet rich in animal foods.
To me, this just goes to show that there’s no grand design at work here. There’s no steady progression onward; rather, evolution is a series of fits, starts, momentary setbacks, and shortsighted adaptations. It’s fascinating, fun stuff.
What do you think about all this? Does it make you more resolute to wrest control of your environmental inputs, like diet, exercise, and stress?
Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.