Evolution, diabetes, and blood glucose regulation

When practiced appropriately, science can shed a lot of light on some pretty powerful concepts in human health.  To date we have unlocked the human genome, developed some novel pharmaceutical interventions for diseases that were once taking a large toll on society, and begun to understand that we are carrying along an exponentially larger number of bacteria that have a dramatic impact on the way we function.  However, many of the health concerns we see today are not being addressed in the appropriate manner.  Comparing the use of a pharmaceutical drug to no treatment, or placebo, makes perfect sense when you are dealing with a bacterial or viral pathogen, but does it really make sense when the true problem is a poor lifestyle?

When performing science, you are not really trying to prove anything, you are trying to disprove the null hypothesis.  The null hypothesis is the default position, and in the instance of a pharmaceutical intervention against a pathogen it typically means giving some of the subjects a placebo pill to simulate not doing anything.  The problem is, at this point, there is a very large lifestyle component to the vast majority of diseases we are seeing today.  This includes cardiovascular disease, some types of cancer, Alzheimer's, and the topic of this blog, Type 2 diabetes.  If we know that a poor lifestyle largely contributes to these diseases, should the default position be taking a placebo pill and calling it a day, or would it make more sense to have the default condition be changing those lifestyle habits that cause the disease?  I suppose that depends on how you look at what the pharmaceutical intervention is trying to accomplish.

Let's be honest, I've worked in the health and wellness field for 18 years.  When someone is told they need to change their lifestyle or a disease they have is going to progress and they choose not to, they really aren't looking for a solution.  What they are looking for is something that will allow them to continue their poor lifestyle while preventing the damage that their lifestyle causes.  If this is what we are testing for with pharmaceutical interventions for these lifestyle diseases, it only makes sense to have the null hypothesis be the condition where the damage stops.  In other words, the null hypothesis should be the lifestyle that causes no more damage.  That way, when we compare the pharmaceutical intervention to the proper lifestyle group, we have an idea to what extent the drug is actually subsidizing the poor behavior.  When you compare the pharmaceutical drug to doing absolutely nothing other than taking a sugar pill, what would you expect to happen?  The drug will come out looking like it's the cure for something that it's not, which gives the false impression that the person has nothing to worry about.

So what lifestyle should be this default position?  Since these lifestyle diseases are prevalent in Western society, it makes no sense to have the null hypothesis be based on the lifestyle of Westerners.  However, these diseases are not at all prevalent in modern day hunter gatherers who live a lifestyle more in line with the one we spent most of our time evolving under.  This has led many to believe that the null hypothesis, the default lifestyle condition to test against, should be identical to the one we evolved under.

This poses a major problem.  The vast majority of our science has been conducted during a time when the Western lifestyle has been the default condition because that has been the default condition since clinical research has become prominent.  An easy way to understand this is that we have come up with RDAs for nutrients in human health, but these RDAs are only relevant under a Western lifestyle because a Western lifestyle is the condition under which they were tested.  So it is improper to say that the RDA for Vitamin C is the amount of Vitamin C one needs to prevent scurvy.  The proper way to phrase what the science actually shows is that the RDA for Vitamin C is the amount of Vitamin C one living a Western lifestyle during the time of testing needs to prevent scurvy.

Assuming the way we currently do things as it pertains to lifestyle is the default condition can also lead us down the wrong path when we are looking at how our body works.  It has been assumed that the liver is the primary site of blood glucose regulation.  However, this may not actually be the case, it could be that the liver is the primary site of blood glucose regulation in those living a Western lifestyle.  A study looking at blood glucose regulation in mice has shed some light on why this may be the case.

In order to better understand how blood glucose is regulated, researchers studied mice who were unable to regulate blood glucose via the liver.  The liver is considered to be critical in blood glucose regulation, without it we cannot stabilize blood glucose.  As the story goes, we eat carbohydrates that turn in to glucose, the liver stores that glucose and releases it during fasting, and when we are completely fasted, the liver makes glucose from non-carbohydrate food sources.

In the fed state during the study, blood glucose levels were identical between normal mice and mice that were unable to use their liver to regulate blood glucose.  During the fasted state, blood glucose levels dropped initially and ketones went up, but within 30 hours both groups of mice had the same blood glucose level as genetic expression changed in the kidneys and intestine to favor blood glucose regulation by those organs in the absence of the liver(1).  It is important to note that while blood glucose levels were lower in the mice who relied on the kidneys and intestines for glucose production, blood glucose never reached a critical state as the kidneys and intestines utilized ketones for approximately 50% of their energy and were able to provide enough glucose for survival.  In addition, this study found that the kidneys and intestine make glucose out of the amino acid glutamine while the liver uses alanine and lactate.

While it may not seem like this study has any real world relevance since most humans have functioning livers, it does highlight that the liver is not absolutely necessary for blood glucose regulation.  The liver is certainly a large player in blood glucose regulation as it can store approximately 100g of glucose and is capable of making glucose from other sources, but the assumption that the optimal way to regulate blood glucose is through consumption of carbohydrate and storage in the liver is flawed.  At this point we really don't know for sure how to optimally regulate blood glucose, but if we look at some key aspects of the ancestral diet some doubt creeps in.

In my next blog we'll take a look at how blood glucose may have been regulated by ancestral humans and how the drastic change in the way we regulate blood glucose now may be contributing to the increased prevalence of Type 2 diabetes.

Part 2

Evolution, physical activity, and human health

The chronic diseases we see today are often the result of poor lifestyle choices.  Cardiovascular disease, Type 2 diabetes, obesity, cancer, arthritis, depression, and Alzheimer's disease are all considered normal parts of the aging process and are often called diseases of aging.  The problem is, when you look at "less civilized" cultures, particularly modern day hunter gatherers, these diseases either don't exist or are insignificant even in older members.  This has caused many to postulate that the Western lifestyle may be a significant factor in the prevalence of these diseases.

In 2002, Booth wrote a paper going over exercise and gene expression(1).  This paper is a classic in the evolutionary medicine arena because it shined a light on the effect of exercise on gene expression and proposed the theory that genes expressed as a result of physical activity would promote disease in a person who doesn't meet the necessary threshold to activate these genes.  In other words, the lifestyle diseases that are often attributed to aging may be, at least partially, from a deficiency in physical activity.

 

Booth's primary focus was on the notion that physical activity increased muscle mass and fuel utilization, improved cardiovascular function, and improved cellular insulin sensitivity while physical inactivity did the opposite.  Given that lower muscle mass, poor cardiovascular function, and poor insulin sensitivity are either seen in or associated with most of the lifestyle diseases seen in Western culture, it is fair to say that all of these factors may play a role in the relationship between Western disease and physical inactivity.  However, current research adds more to the story.

A review from 2010 discussed the relationship between inactivity and an overly sensitive stress response(2).  Recently, the author of that study was able to identify the physiological change in the brain that come with high levels of physical inactivity.  He found that physical inactivity causes a re-wiring in the rat brain.  Specifically, it causes a more dispersive branching of neurons in the rostral ventrolateral medulla(RVLM), an area of the brain that helps control the stress response(3).  The researchers believe this increased branching is what causes the neurons in the RVLM to be more responsive to stress in physically inactive rats.  While this study has not been repeated in humans, it bears to note that increased sensitivity of the stress response, also called increased sympathetic tone, is also found in many of the lifestyle diseases mentioned above and sedentary behavior is also strongly associated with these diseases(4, 5, 6, 7) and the low grade inflammation that accompanies them(8, 9).

There are other avenues within inactivity physiology that apply to health and are worth mentioning.  During aerobic metabolism, reactive oxygen species(ROS), or free radicals, are continuously generated(10).  Free radicals are molecules with an unpaired electron that serve vital roles in cellular function, but react with healthy molecules within the body and cause oxidative stress when not held in check.  Oxidative stress occurs when free radical generation outpaces the ability of the body's antioxidant defense systems to deal with free radicals.  The body's antioxidant pathways donate electrons to free radicals and help keep free radicals at a healthy level.  As I mentioned in this previous blog, prolonged sitting causes changes in genetic expression that reduce antioxidant and anti-inflammatory pathways and reduce insulin sensitivity.  This would increase oxidative stress which is another physiological factor associated with lifestyle diseases.  In addition, increased oxidative stress leads to higher levels of inflammation which are also associated with these diseases.

Some people attempt to head off oxidative stress by taking antioxidants supplements.  The problem with this is that when supplemental antioxidants are taken and they meet up with a free radical, they donate an electron to the free radical which makes the former antioxidant a free radical, albeit a weaker one.  The antioxidants generated by the body's antioxidant defense system, particularly glutathione, are able to donate electrons to free radicals as well as recharge antioxidants that become free radicals as a result of donating an electron.  This makes the body's antioxidant defense system far more powerful than any antioxidant you can take orally.

What makes this avenue of inactivity physiology particularly interesting is that recent evidence has shown that the average daily energy expenditure of Hadza hunter gatherers is the same as Westerners when controlled for body size despite the physical activity level of the Hadza being greater(11).  Since a person at rest is primarily utilizing aerobic metabolism, it is safe to assume that both groups are either generating the same number of free radicals or the Westerners are generating more based on their larger size alone.  On top of this, the increased level of sedentary behavior associated with the Western lifestyle could potentially induce higher levels of oxidative stress through a reduction in antioxidant gene expression while the physically active lifestyle of the Hadza may promote health by keeping free radical levels at an appropriate level.  Since the Western lifestyle diseases discussed earlier are also associated with high levels of oxidative stress and hunter gatherers like the Hadza rarely experience them, it makes you wonder if shutting down these pathways contributes to the Western lifestyle diseases.  In other words, a deficiency in physical activity may in fact be a strong contributor to the lifestyle diseases that are prevalent in Western cultures for many physiological reasons.

The bacteria in your gut: Your "flexible" genes

Your microbiome, the community of bacteria that live within and on you, has become a hot area of research recently.  This bacteria lives on your skin, in your mouth, all throughout your digestive tract, and basically in any nook or cranny you have.  The bacteria that reside in the digestive tract perform a host of functions for their...well...host.  They help train the immune system, help with mineral absorption, help breakdown things we cannot break down, and make short-chained fatty acids that help keep our digestive tract in tip-top shape.  Many health problems are associated with the composition of bacteria you have in your gut including obesity, Type 2 diabetes, arthritis, IBS/IBD, Crohn's disease, Celiac disease, anxiety/depression, autism, and many others.  This has led researchers to seek out what a healthy microbiome is so that we can manipulate it to promote health.

 

The many ecosystems that make up your microbiome

The Human Microbiome Project was undertaken to take a glimpse at the microbiome of those in Western society while researchers are also taking a look at modern day hunter gatherers to get a glimpse at how our microbiome may have evolved with us.  One of the more notable findings in hunter gatherers is that they tend to have a much more diverse microbiome than those of us in Western society.  Over the course of the last month, more information has been uncovered looking at both the Western population as well a modern day hunter gatherers.

Researchers from the Human Microbiome Project have analyzed microbiome samples from 300 people and determined that, based on current data, there is no single healthy microbiome.  Based on all of the data to date, healthy people can have a wide range of different microbiomes(1).  Several lifestyle factors such as if you were born by C-section, whether you were breast fed, or past antibiotic usage can impact the microbiome in your GI tract while gender can affect the microbiome in different body sites.  Each person has a signature microbiome that is representative of the environment they grew up in and the lifestyle that they have lived.  In fact, lifestyle has a huge impact on the make up of your microbiome, as seen by a recent study looking at Hadza hunter-gatherers.

In the study, researchers found that even people who live in the same environment, which essentially means they are exposed to the same types of bacteria, have different communities that live alongside, and inside, them.  Hadza men and women differ greatly in the composition of their microbiome, due primarily to the fact that men tend to hunt game and collect honey while the women gather primarily plant foods(2).  While the food is shared, the men tend to snack on more of the foods that they collect while the women tend to snack on more of the foods that they collect.  So despite eating the same foods, even just a small change in the percentage of the foods consumed can significantly change the microbiome.  This makes sense because they eat what you eat but don't absorb.  Plant materials, high in fibrous material that humans cannot digest, provide substrate for bacteria living in the colon.  The colon harbors the largest percentage of bacteria in the digestive tract by far.

Hadza chicks, scarfing fries and discussing the latest Real Housewives of Tanzania episode

One interesting aspect of this study is that the Hadza had a large number of bacterial species that are associated with disease in Western populations and low levels of bacteria that are associated with health. Despite having what one would consider a less than ideal microbiome based on what our research shows, the Hadza don't experience IBS/IBD like we do.  This reinforces the notion that there is not a single healthy microbiome, and points to the total collection of bacterial species that make up your microbiome as being important, not the presence of specific species.

A third study followed a group of people called Hutterites for a year.  Hutterites more closely resemble the Amish in that they are exposed to technology such as medical care, exposure to vehicle exhaust, and electricity.  The Hutterite share a communal lifestyle so they have a very similar microbiome between members.  While this similarity between the microbiome of members of the group remains stable throughout the year, the microbiome of the entire tribe changes with the seasons as the availability of food changes(3).  As the seasons change, so does the microbiome of the tribe as the types of foods they consume changes with their availability.

This study, coupled with this other study(4) that showed that extreme shifts in diet can begin drastically changing the microbiome within hours, paints the microbiome as a shiftable genome that helps the host adapt to the changing environment.  In fact, the number of genes within the microbiome of an individual outnumbers the number of genes that they possess in your cells by an order of 100 to 1, maybe even more.  Western medicine has placed such a large emphasis on how strongly genetic factors play in the many diseases we see, yet until recently has ignored the fact that most of the genes that will have an impact on the many biological functions that go on within the human body are directly influenced by diet and lifestyle. 

While research in the microbiome is in it's infancy, it's great that we are directing so much attention towards it.  Studying the microbiome will likely be the next big step in understanding human health and function.  It is also likely necessary to undo some of the damage we may have done with some of our current medical(Antibiotics) and social(extreme hygiene) practices.  This is not to say that these practices aren't necessary or are bad, merely that understanding them and the way they impact our microbiome more thoroughly will only improve their effectiveness.

Introductory Stretching Video

In my last video blog I illustrated how I foam roll at the beginning of my workouts or when I feel my muscles feel like they are getting tight.  In this second video, I go over my stretching routine that follows the foam rolling routine.  For someone who hasn't exercised in a long time, or someone who has lived a sedentary life where they haven't exercised before, this 3 part program is likely where you will start.  The purpose of the entire program is to physically prepare your body for a more active lifestyle and to prevent some of the injuries that often occur in people who have never exercised before that begin an exercise program.

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Next Thursday I will go over the activation and mobility portion of my program.

Olestra may have some clinical value...

I remember eating chips made with Olestra back in college. I remember the warnings of anal leakage, but I also remember thinking that they tasted pretty good.  Well, a news study provides evidence that Olestra may help people reduce PCB levels in the blood.

Earlier studies in animals showed that olestra would bind PCBs in the digestive tract, preventing them from being absorbed.  Researchers theorized they would see the same effect in humans, and a small trial recently conducted showed that people who ate chips with Olestra saw a reduction in PCBs in the blood(1).  PCBs are an environmental toxin associated with cancer, hypertension and diabetes as well as skin conditions.

One of the concerns with Olestra is that it may do the same thing with fat soluble vitamins.  The whole anal leakage thing is also still a little concerning, but it will be interesting to see this thing play out. If anything, this does shine a little light on the fact that we are far too lax in letting items enter our food supply. Despite this being a positive finding, we shouldn't be adding things like this to the food supply without researching them well enough to determine exactly what they do.

Introductory foam rolling video

In this video, I go over my introductory foam rolling program.  I also go over why one would want to foam roll and the benefits you can expect from regular foam rolling. 

Note: In this video I roll one side of my body to show you how you can determine how restricted your fascia is.  Obviously you should do the other side once you've determined done this.  Next week Thursday I will go over my stretching/activation/mobility program.  For best results, you want to foam roll and stretch at least 3x per week initially and then continue at least 2 more times per week.  I like to do it prior to workouts as a part of my warm up, but you can also just have a foam rolling/stretching program if you get exercise through methods other than lifting weights.

Product Review: Veggetti

When I began removing processed food from my diet, I began to realize how much my diet relied on pasta, bread, and cereal.  Removing these foods initially was a daunting task, but then I learned about things like lettuce wrapping hamburgers, spaghetti squash, making plantain chips with a mandolin slicer, and turning zucchini in to "pasta" with a julienne slicer.  Over the years, my kitchen gadget collection increased from a few knives and a cutting board to about 20 different tools I use on a weekly basis.  When a client recommended I give the Veggetti a shot, I thought, "Why not?"  I'm glad I did.

Now, I'm not an infomercial guy.  I'm typically asleep by the time they come on at night and when I wake up in the morning I like to get work done before making breakfast, so the various tools that find their way in to infomercials rarely come to my attention until they make it to Bed Bath and Beyond.  I was training a client one day and she remarked that she missed pasta.  I recommended spaghetti squash or julienne slicing a zucchini, and she said she ordered a Veggetti from TV but was waiting for it.  After figuring out what the hell a Veggetti was, I went to Bed Bath and Beyond and bought one.  I have 3 issues with using a Julienne slicer to make zucchini pasta; it 's time consuming, the seeded center just shreds and your left with a square core of waste, and I often cut my fingers with the slicer when the zucchini gets small.  The Veggetti eliminates these issues.

The Veggetti is built fairly well, it's sturdy and can be used to make thin pasta or thick pasta depending on which side you use.  The package says you can use it for most types of vegetables, to date I have only used it for zucchini pasta and "spiraly" cut sweet potato strings and it worked well for both.  It comes with a cap you can use to hold the veggies, but I had no problem holding the zucchini by the stem and the sweet potato by the tip.  I could see someone who's not paying attention cutting a chunk out of their finger if they're in a rush, though.  Even if you're not in a rush, this thing works so much faster than a julienne slicer at making zucchini pasta.  While there is still a small spirally core that is left over, it resembles a long piece of rotini I just threw it in with the pasta and didn't notice. At $15 before a 20% off coupon, it's well worth the investment.  Clean up was easy, the only drawback was that you get extremely long "pasta" so you will need to cut it up a bit if you don't want to slop pasta sauce everywhere.

Logical fallacies aganst a Paleo diet

At this point in time, there is not likely a more controversial diet than the Paleo diet.  Advocates tout how much better the vast majority of people who undertake it feel as well as the numerous health improvements, primarily autoimmune diseases that go in to remission, that people see under a Paleo diet.  Critics argue that there wasn't a single Paleo diet, per se, and that grains, legumes and dairy have been a major part of a healthy diet for many years.  The question then becomes, "So who is right?"  Therein lies the problem, the argument between the advocates and critics really isn't about who is right, it's about whether or not the science supports the Paleo diet or not.  The problem here, in my opinion, is that those criticizing the diet set the bar at a level that won't likely be met for some time, but that doesn't mean the supporters of Paleo are wrong.

I've been in many discussions with people who basically believe the Paleo diet is poppycock.  I've argued with trolls on the internet, I've had physicians tell me it's complete BS, and I've read Paleofantasy in utter surprise that a higher level scientist would make several errors in logic in a published piece.  I will spare you the arguments on straw men such as the Paleo diet is low carb or that it's basically a bacon orgy.  I will focus on the basic assumption that the Paleo diet views grains, legumes, and dairy as foods that are likely to be problematic for more people than they are healthful.

The first error in logic that comes up in a typical argument is that the onus of proof is on the person making the claim.  This is a typical argument from a person who is a contrarian and just likes to argue.  If I say I don't believe those 3 groups of food are healthy for people to consume and you say that I'm wrong, it seems to me that both of us has made a claim that needs backing up.  At this point, both should provide their reasoning behind their claim, this is how science works.

This isn't typically how it goes, however, and when they ask for evidence they go straight for the gold standard.  They say you must provide a randomized controlled clinical trial(RCT) in order for them to take your claim seriously, which is setting the bar higher than they should because, as far as I am aware, there exists no such study that backs up either side of the argument.  They then point to a few epidemiological studies or studies comparing whole grain consumption to refined grain consumption to show that grains are perfectly fine to consume.  None of them actually show this because epidemiological studies can't show causation and comparing whole grain consumption to refined grain consumption shows nothing about whether grains are a healthy food choice, only that whole grains are better than refined grains.

This brings up a couple of important points about applying logic.  First, just because there is no evidence that something exists doesn't mean it doesn't, especially if it hasn't been studied in depth.  At some point I'm sure there was scant evidence that the Earth was round or that bloodletting was a stupid idea, but both ended up being true anyway.  There was likely anecdotal evidence for both long before there was an RCT, that's how science works, observation followed by testing.  Nevertheless, I'm sure the countless people who died or whose illness was prolonged from bloodletting would have loved to know that there was an argument to be made against it.  About 10% of our entire medical system is based on RCTs, the rest is based on anecdotal evidence, epidemiological studies, and other forms of evidence that would not suffice critics of the Paleo diet unless they were using it to argue against the diet, but who have likely benefited from medical care that was based on that inferior data.

Another point about logic is that it should be applied universally.  Many critics of Paleo like to point out that just because something wasn't eaten in Paleolithic times doesn't mean that it's bad for you, which is actually true.  In the same sense, just because we have been eating something for 10,000 or even 50,000 years and it hasn't killed us before we've reproduced doesn't mean it's good for us, only that it doesn't affect reproduction and therefore won't place selective pressure on our species.  This means it won't thin out the herd and force a change in our species, it may simply become a nuisance that people have to deal with as they get older and damage accumulates.  Arthritis doesn't kill you, but I imagine anyone who has lived with it for decades would be happy if they didn't have to live the rest of their lives with it.

My final point is about arbitrary points in time.  It is not logical to assume that anything that happened prior to the RCT is BS or that anything we are eating now that doesn't cause an immediate cardiac arrest is healthy.  There weren't RCTs in ancient Greece when modern humans began to realize that the Earth wasn't flat, but it turned out to be true anyway.  Most people aren't interested in finding out exactly what the science says, most are interested in what is most likely the truth and this sometimes requires going outside of what the science specifically says and extrapolating from other areas of science to fill in the holes.  In the same way that not all foods that we eat now are healthy, not all new foods are bad just because we didn't eat them at some arbitrary point in time.  We are constantly changing and some new foods that weren't available in the Paleolithic such as olive oil and broccoli have turned out to be quite healthy for us.

So why do I follow a Paleo diet?  I don't really follow a Paleo diet, I follow a Paleo template.  I limit grains, legumes and dairy because I feel there is enough evidence that those foods contain proteins that are not digested well by us that make their way in to our colon and mess with our microbiome.  This is likely a dose dependent issue and genetic variability as well as epigenetic factors likely play a role so certain foods may be perfectly fine for some people and not so fine for others.  Until there is a way to tell for sure, I will limit those foods, but I still eat them on occasion.  You can hedge your bets by eating a diet high in vegetable matter, moderate in meat, and high in fermentable fibers that the healthy bacteria in your gut use to sustain themselves.  This should, in theory, also allow you to get away with eating things that are not necessarily healthy for your microbiome as it bolsters the good guys so that the bad guys don't take hold.  At least that is what I have come up with based on the evidence, if any new evidence comes to light I will certainly take it in to consideration.