It’s taking me awhile to “digest” all the information (hehe), but I found the seminar fascinating and wanted to summarize some main points. Lots of open questions remain, but John Pepper of National Cancer Institute really shows how examination of any health problem needs to focus not only on proximate causes, but the ultimate or evolutionary causes.
So.. Pepper asks- why is mammal meat bad for humans, specifically?
In humans, red meat (he refers to it just as mammal meat) is linked to inflammatory diseases (cardiovascular, alzheimer’s, arthritis). What’s the mechanism behind this?
The inflammation from mammal meat has to do with our antibodies attacking something coming from other species.. When we eat mammal meat, we in fact incorporate something non-human from the diet- sialic acid.
Both human and other mammals have sialic acid in their tissues, actually, but humans have a unique mutation that replaces the form found in other mammals (ancestral form- Neu5Gc) with a different one- uniquely human (Neu5Ac).
So.. if we eat meat we get the new aquired ancestral sialic acid, it becomes part of our cells, and the small structural differences in the two get recognized by the immune system.. which responds with a defense- inflammation!
Chimpanzees are humans’ closest evolutionary relatives, sharing a common ancestor 6–7 million years ago..
WHY does human sialic acid differ uniquely? The “Malaria hypothesis” (see Martin&Rayner, 2005) proposes that in Africa, early humans escaped from the ancestral pathogen they shared with chimpanzees. They managed to do so by replacing the pathogen’s binding target (ancestral sialic acid Neu5Gc) with novel Neu5Ac. With time, a population of that old evaded pathogen evolved to infect humans again by recognizing the new Neu5Ac..leading to the origin of malaria.
If the Malaria Hypothesis explains why the initial change in humans happened.. why has it remained the same to this day? I mean, it’s been some several million years now- has this mutation been advantageous this whole time? It’s an important question because this sialic acid mutation poses a COST on our health: this trait causes chronic inflammation in people who eat mammal-derived foods + it also now causes vulnerability to malaria.
The hypothesis for why the human sialic acid modification is still around is that it
provides benefits- specifically, protection from parasites and pathogens via increased inflammation. This is relevant because of what humans have been doing for the last ~15,000 years. Animal domestication!
Humans are more vulnerable to shared pathogens from other mammals (than from non-mammals). So being around cattle, for example, carries a risk of catching pathogens from which that cattle suffers. Such animal pathogens impose a strong selective pressures on humans.. Pepper suggests that the uniquely human sialic acid (Neu5Ac) allows our diet to adapt us to the issue of animal pathogens by adjusting our inflammatory tone (how much inflammation we are experiencing): “those human populations that are exposed to domesticated food-mammals and their pathogens are also eating mammal-derived foods that are pro-inflammatory (both meat and dairy).”
Inflammation is a great example of a trade-off. It both has benefits (protection from parasites & infections) and costs (chronic disease, metabolic expense of mounting an immune response). The optimal balance for this trade-off would depend on how strong of a pathogen pressure you’re experiencing.
This increases inflammatory PROTECTION only where it’s most needed (like around animals). So this auto-immune inflammation from mammal foods in the diet not only increases likelihood of chronic disease, but protects against shared mammalian pathogens.
….. …… ……
It got me thinking about human culture and our ability to modify our environment in all sorts of ways- an example of “maladaptation” to modern times! Living in cities, not exposed to higher pathogen load from being around domesticated animals..yet having access to all the mammal meat we can buy = all put you in a situation where the good old sialic acid mutation might do more harm than good. Should people go vegan? Should they simply cut down on red meat? There was no discussion on the effect size of mammal meat eating and chronic disease, so I wouldn’t necessarily jump onto any lifestyle changes based on this talk. Yet the process of understanding this health concern through the lens of evolutionary medicine is quite fascinating!
P.S. I’m not an expert on this topic. If you have something to correct or add, please comment 🙂
Got it- to FAST? 😀
The past week has been a treat in terms of great talks on campus. At ASU we are super-lucky to have the Center for Evolution & Medicine, which holds weekly talks by amazing speakers.
When I saw that the upcoming seminar was related to diet and eating..or more specifically NOT eating or “dietary restriction”, I of course RSVPd in a heartbeat.
“Eat breakfast yourself, share dinner with a friend, give the supper to your enemy”- Russian Proverb
I’ve been in fact fascinated with caloric restriction for years now (I wrote a whole research paper on it in the first year of my master’s degree). You might have heard of intermittent fasting (e.g. popular in the CrossFit world), or the CR Society ( http://www.crsociety.org/ )- all are related to the concept that restricting food intake results in health benefits (from extending life to preventing and reversing disease).
I’m sure you can Google caloric restriction and find a bunch of information on its reported benefits..you would see this chart at the CR society website- the lifespan of calorie-restricted (CR) mice vs non-CR mice. You can see that those whose food intake was restricted by more & more % lived longer. Why do many animals (and perhaps humans) appear to be so well-adapted to eating less? The traditional interpretation of this CR phenomenon is that the dietary restriction effect “has evolved as a way to enhance survival & preserve reproduction during periods of naturally occurring food shortage”. In other words- being adapted to do well on restricted food intake during rough times would have helped our ancestors survive them & stay healthy to have kids later when the food situation improves.
The traditional interpretation of this CR phenomenon is that the dietary restriction effect “has evolved as a way to enhance survival & preserve reproduction during periods of naturally occurring food shortage”.
Experimental evidence with animals, however…supports a different hypothesis- the one Dr. Austad (Professor & Chair of the Department of Biology at the University of Alabama) presented to us last week. Again, I wouldn’t be able to cover everything he discussed during the seminar, but I do want to highlight a couple of main points!
I. First, even though the first book on dietary restriction (DR) dates back to the late 16th century, we still do not know the mechanism behind why DR seems to extend life and vigor in animals + delay disease such as cancers. METABOLISM was the original suspect, as metabolic rate goes down with fasting.. however, metabolic rate drops initially yet gradually goes back UP (takes 6-8 weeks to happen).. Since DR changes an unbelievable amount of physiological parameters (see screenshot ->) it is very hard to determine its mechanism.
II. Second, while many sources cite mice experiments showing life extension with caloric restriction.. those experiments are done with lab mice. When DR studies are done with wild mice, DR has no effect on longevity. WHAAAT!! I’ve never heard this before- in fact i was under the impression that CR/DR extends life in animals, period. Well, NO STUDY has ever found that DR extends life or improves health in nature (or even “nature-like” conditions). Mice in the wild actually do not have enough fat stores to reduce feeding except very briefly (wild mice has about 4% fat while a regular lab mice has 15%; also lab mice do not reproduce). In fact, mice in nature simply do not live long enough for the survival benefits of DR to be important. Another challenge to the original hypothesis that adaptation to dietary restriction enhances survival, is that DR increases mortality from some infections. Lastly, DR increases cold sensitivity (and cold is a major source of death in wild mice) and slows down wound healing.
Sounds like animals in the wild would not benefit from adaptation to dietary restriction… yet why is the positive DR effect observed in so many studies so common?
III. Well, even though wild mice do not live longer with restricted diets, DR still results in cancer protection for them. But even more importantly, DR has been found to protect against acute effects of many many toxins! Dr. Austad talks about this discovery in the following way:
.. if animals can not afford to wait to reproduce..and they have to do it even when food conditions are poor, what they will do is broaden their diet. This means they might be ingesting a lot of toxins they are not normally exposed to (foods infected with fungi, new seed types that are well defended by the chemicals they wouldn’t normally encounter). So the hypothesis is that DR acutely induces broad defense mechanisms from a broad range of toxins
Toxicology studies have shown that mice that are calorically restricted survive a wide range of toxins. DR also acts as an acute (vs. chronic) protectant against other problems (see slide below). Renal ischaemia reperfusion injury (IRI) is a common cause of acute kidney injury and we can see that while ad libitum mice are dying steeply by day 7, those on DR of various proportions survive (30% DR is only 70% of normal food intake; ad libitum stands for eating as much as one wants). This is quite impressive!!!
These acute benefits of DR have very important implications. We can think about these effects actually protecting the body against the toxins it itself produces (like free radicals).. it also has clinically relevant advantages- e.g. patients on very strong drug cocktails fasting to avoid harsh side-effects. This suggests that the protective effects of DR could have clinical relevance unrelated to chronic benefits like life extension.
The new hypothesis explaining the evolutionary advantage of this paradoxical effect is that dietary restriction arose as a defense against novel exposure to toxins during food shortage.
So in conclusion.. we saw evidence suggesting that dietary restriction would NOT enhance survival in nature. Yet research has shown that DR increases health and life in a diversity of species. The new hypothesis explaining the evolutionary advantage of this paradoxical effect is that dietary restriction arose as a defense against novel exposure to toxins during food shortage.
My conclusion? I’m still excited about this topic- more than ever before!!! There is a lot of work done now on the timing of food intake as well (not just restricting the amount, but restricting the timing of eating and human health) and I can’t wait to post more about this (after I collect some necessary data though :). Watch out for early May as I’ll be sharing some more info!
One fascinating topic is why we humans are susceptible to disease. If natural selection*** shapes successful traits, then why do we catch and develop so many diseases??
Evolutionary medicine is the field that tries to figure out why natural selection has left us so susceptible to illness (physical and mental). Here are some ways to explain our vulnerability to getting sick:
Reproduction vs. Health
I feel it is a common misconception that evolution wants us to live longer healthier lives (e.g. when people say that we’ve evolved to eat a certain way that allows us to live long and be disease-free).. and it is disturbing and heartbreaking for some to find out that evolution pretty much doesn’t care about your happiness, health, or longevity. 😦 Natural selection does not shape organisms to increase all those things, it shapes them to improve our fitness (Fitness NOT meaning long healthy lives [and with a six pack, preferably], but having more healthy children). So a trait that actually harms health will still get inherited if it increases reproduction!
One example I have heard of is having attractive female proportions (waist to hip ratio and all): it increases the chances that you will have more children by making a female desirable by men, but it is associated with higher risk of some diseases in old age.Another interesting example is higher mortality of males in adulthood- natural selection can favor such traits as risk taking, (which is important in attracting females as males compete for female attention), though it can decrease the lifespan of people whose personalities allow for increased risk taking.
I’ve seen that some paleo diet followers discuss evolution as a benevolent force that has figured out a way for humans to live long and prosper, and while that’s not true on the level of the individual (it technically “cares” that the species prospers by spreading), it doesn’t mean that you can’t use evolutionary theory to personally get healthier.
Our genes don’t match the environment!
Humans have created quite amazing conditions for ourselves- sanitation, roads, safe desktop jobs, public transit, etc. Things that make life comfortable and pleasant. And technologically advanced societies see higher rates of various disorders- autoimmune disease, obesity, drug abuse and so on. Many versions of certain genes are only problematic in modern environments. Proponents of all sorts of paleo-related diets, for example, claim our evolved preference for sugar and salt is dangerous in the world where processed foods are cheap and omnipresent (though adaptive in the wild as sugary ripe fruit are nutrient & calorie-rich). Another example is nearsightedness– it’s a problem in societies where kids begin reading early and is not a problem in populations that hunt & gather.
Other explanations are:
Pathogens simply evolve faster than their hosts (ourselves) so we will never have an immune system that is not vulnerable to some disease.
There are also tradeoffs: a certain trait can have great benefit in one way, yet it may have negative effect in other respects (again- being a seductive mess on a motorcycle might make females go crazy over you & want to reproduce, but it also makes one susceptible to dying from unsafe choices).
Once again, here is a GREAT read on EVOLUTION AND THE ORIGINS OF DISEASEby Dr. Nesse (MY INSTRUCTOR!) and Dr. Williams with MUCH more comprehensive explanations AND more interesting examples than I have in this blog entry. 😉
Evolution: change in genetic makeup of a population over generations; it requires genetic variation. The variation in genes arises from mutations and recombination.
Natural selection favors traits that allow an organism to produce more offspring [that is healthy enough to produce its own]
Fitness does not mean personal health & longevity. Fitness means how good you are at leaving a successful offspring.
Inclusive Fitness: unlike previously thought, evolution doesn’t work on the level of groups/species but on the level of individuals (so traits that aren’t “good” for the whole species but are good for this individual having more kids are going to be selected for). E.g. genes that make one aggressive to others will still pass on if it leads to this individual reproducing successfully.
HOWEVER, nice helpful personality traits are successful & are passed on (humans are incredibly altruistic vs. other animals) as it makes one do nice things for close relatives. Since you share genetic material (50% with each parent and siblings, 25% with cousins), the individual’s reproductive success actually includes not only how many healthy kids you produce, but how many your closest relatives do also!
There are no traits/genes that are awesome universally. The benefit of a certain trait is always in the context of the environment. E.g. sodium retention is prevalent in people that evolved around the equator since it gave them a selective advantage (salt is necessary to your body but is lost via sweat and urine.. you’d sweat way more in the hot climates).
[***Natural selection: imagine a group of people/dolphins/bugs. If this group’s members differ in some way that influences the likelihood that they’ll be part of the group in the future, this group will end up changing with time. So if some members have a genetic variation that influences how many kids they’ll have, in time this group will change and have more of the genetic trait that resulted in more kids!
A popular example is trees that once had light barks but got covered in black soot. The group of moths that used to hang out by the tree had variation in color- some white, some black.. The white ones will end up being eaten up by birds simply because they are now super visible on the dark bark and, in time, majority of moths will be black (the group has changed!) . Thus, a genetic trait is only “successful” in a context of an environment. There is nothing beneficial to being a black moth other than you’re less visible on black bark and thus will end up having more offspring than the white moths in the group.]