Do Type 1 and Type 2 Diabetes share a common cause?

A new study recently published in the journal FASEB provides evidence that both Type 1 and Type 2 diabetes share a similar cause that differs only in the rate at which either disease occurs.  In the study, researchers found that human amylin, a hormone long associated with Type 2 diabetes, accumulates in toxic clumps that destroy the beta cells of the pancreas responsible for producing insulin.  This causes progressively worse pancreas function, leading to failure, that ultimately culminates in either form of diabetes(1).  Let's take a closer look at the findings.

When you eat a meal, insulin is secreted to help control the level of glucose in the blood by making cells in the body take in glucose.  At the same time, the hormone amylin is also secreted to help insulin regulate blood glucose by slowing gastric emptying, reducing digestive enzymes, and causing you to feel full.  When a person secretes more amylin than they can break down, clumps of the protein form on the pancreas negatively impacting beta cell function and causing cell death, thus decreasing insulin production.

In this study, researchers took mice and inserted copies of the human amylin gene, making them either homozygous or hemizygous.  Mice who were homozygous for human amylin received two copies of the gene while mice who were hemizygous only received one copy.  Mice who had two copies of the gene experienced higher levels of amylin, rapid destruction of the pancreas, high levels of insulin, a shortened stage of prediabetes, and juvenile-onset, or Type 1, diabetes.  The mice that had one copy of the gene experienced lower levels of amylin and a more prolonged period of prediabetes, which led to adult-onset, or Type 2, diabetes.

If we look at this in concert with the research on leptin resistance that shows it to precede insulin resistance, we get an interesting picture.  Leptin is another hormone that signals you to stop eating and is secreted by fat cells.  People with leptin resistance produce a lot of leptin, but the cells in the hypothalamus that help regulate food intake don't respond to it.  As a result, people with leptin resistance don't get the "full" signal and continue to eat when they don't need to.  At some point, this may cause them to overproduce amylin causing the toxic clumps associated with Diabetes.  Of course, this is an extreme simplification of a complex topic that needs further study, but it does paint a picture that both could be prevented or reversed. In addition, this study was done in mice so further studies in humans are needed.

Bonus nerd info:  Interestingly enough, amylin shares a common effect on cells with amyloid beta, the protein associated with Alzheimer's disease.  Both cause dysfunction of the mitochondria and an increase in free radical production due to interference in the activity of complex IV in the mitochondria.  The end result of high free radical production...cell death.  These mechanisms only differ in where the cells they affect are found, amyloid beta in the brain and amylin in the pancreas(2).

Dietary resistant starch may reverse damage of a high meat diet

A recent study on the effect of resistant starch consumption on the risk for colorectal cancer found that consuming 40g of resistant starch with a diet high in red meat can reduce the risk of colorectal cancer associated with a diet high in red meat(1).  The researchers took 23 subjects and had them follow either a high meat diet or a high meat diet coupled with 40g of resistant starch for 4 weeks.  They then measured the expression of colorectal cancer promoting genes.  When the subjects consumed a high red meat diet, expression levels of the genes increased by 30%.  When the subjects consumed 40g of resistant starch with a high meat diet, expression levels of the genes went back to normal.

The researchers believe the improved effect of resistant starch is due to the presence of butyrate in the colons of people consuming resistant starch.  Resistant starch is a form of fiber that escapes human digestion and becomes available to bacteria in the colon.  Butyrate is a byproduct of the fermentation of resistant starch by resident bacteria.  While high consumption of meat increases expression of the genes associated with colorectal cancer, consuming resistant starch effectively reversed this expression, possibly by increasing levels of butyrate and other beneficial short chain fatty acids(SCFAs).

Good sources of resistant starch are under-ripe/green bananas and plantains, cooked and cooled potatoes(at least 24 hours), and chemically altered food products such as Hi-maize, a modified cornstarch currently used as a substitute for flour in home baking.  Bob's Red Mill Unmodified Potato Starch is also a good source of resistant starch at 8g/tablespoon.  While many have taken to huge servings of a single source, getting multiple types of fiber/resistant starch is likely a better option as different bacteria in different areas of the digestive tract ferment different types of fiber in to butyrate and other SCFAs.

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.

The Human's guide to being Human: How your cells work

Light energy from the Sun interacts with chlorophyll pigments found in plants to convert light energy in to usable chemical energy to power the plants' activities.  In humans, excess energy from food that is not used for daily energy needs is converted in to fat and stored for later use.  Approximately 85 million years ago, primates diverged from other mammals on the tree of life, eventually giving rise to what would become modern humans.  In 1928, Scottish scientist Alexander Fleming showed that if grown in the proper environment, the fungus Penicillium notatum would secrete a substance with antibiotic properties that he called Penicillin.

While there doesn't appear to be much similarity between the four examples listed in the above paragraph, they are all considered biological functions.  There are countless biological functions that occur within the human body on a daily basis, and when you expand that to include all of the biological functions from all life on the planet since life began, you would think it would be difficult to find something in common with all of them.  The thing is, it's actually not that difficult at all. Every biological function, whether it be from bacteria, insects, fish, birds, humans, or plants; or whether it takes place over the course of milliseconds, minutes, hours, or millions of years; is the product of a gene/environment interaction.  

Gene/environment interactions

There are many examples of how we have used the understanding of gene/environment interactions to better our lives.  In the example of penicillin, you may be surprised to learn that there is a completely logical reason that an antibiotic would be secreted by a fungus given the proper environmental conditions.  While the discovery of penicillin was accidental, the presence of an antibiotic can easily be explained by gene/environment interaction.

When Dr. Fleming picked up a petri dish that contained Staphylococcus aureus and had been contaminated with Penicillium notatum, he noticed that a mold had grown that killed the staphylococcus.  In an epic battle for supremacy, both the Staphylococcus aureus and Penicillium notatum were fighting for the limited food resources found in the petri dish.  However, when Penicillium notatum growth is limited by stress(In this case, competing for resources with another organism), it secretes an antibiotic that increases it's chance of survival and decreases the chance of it's competition's survival.  Using a finishing move contained within it's genome, the Penicillium dispensed of the Staphylococcus, won the battle, and became champion of that petri dish.


An infinite number of biological functions such as this take place every day.  As products of  gene/environment interactions, these functions are dependent on the presence of a gene and an environmental trigger that causes the gene to be expressed.  In the instance above, if Penicillium notatum didn't have the gene to secrete the antibiotic, or if the stress due to competition was not there, it would have never secreted it and the Staphylococcus would still be there.  Grown against a different foe with a more forgiving genome, or in an environment with ample food and space for both organisms, the staphylococcus may have stood a chance.  This is survival of the fittest, this is how natural selection, and biology as a whole, work.  In order to to understand biological functions and evolution, you first need to understand what genes are.

Genes and epigenetics

Genes, or DNA, are essentially a blueprint for you, a set of instructions contained within the nucleus of every one of your cells.  Your entire set of genes is referred to as your genome, and the vast majority of your genome is located within the nucleus of your cells and protected by a membrane.  A small portion of your genome is located within the mitochondria, or power plants of the cell, but those genes only code for parts found within the mitochondria.  Genes are often referred to as coding DNA because they are responsible for making proteins, and the part of your genome that consists of coding DNA is fixed from birth and identical in every cell of your body.  A perfect example of coding DNA in Penicillium notatum is the gene that makes pencillin, an antibiotic protein.  Another one found in humans is the gene that codes for insulin, a protein that helps the body store sugar.  The more complex the organism, the more complex the genome...or so we thought.

You may have heard that humans and chimpanzees are 98% similar from a genetic standpoint.  While it is true that our coding DNA is approximately 98% the same, the coding DNA is not the entire story.  Even a banana tree shares approximately 50% of it's coding DNA with humans.  This is because most living organisms are made up of the same types of cells with the same basic machinery in the form of organelles.

Organelles are the cell equivalent of organs, hence the name.  Interestingly enough, an organs' cells contain organelles that perform the function of that organ.  For example, the liver is a detox organ and the cells within the liver contain organelles that make detoxification enzymes, among other things.  These organelles are made in these cells because the DNA contains the instructions to make them and the environment the cell is in tells the cell to make these organelles.  This is how cells know what to do and why skin cells aren't actively making things like insulin, that set of instructions is read in the cells of the pancreas.  The environment communicates to the cell what to become, and the genes put that order in to action.

Taken a step further, your cells become what they become because the environment tells them what to become.  Many people don't realize that the blueprint in every one of your cells is identical.  So how does a skin cell become a skin cell and a liver cell become a liver cell if the instructions are the same?  In his book The Biology of Belief, Dr. Bruce Lipton discusses his work in cellular biology 50 years ago.  When he would take stem cells and put them in a petri dish under certain environmental conditions, they would become muscle cells.  The same stem cells placed in a different petri dish with different environmental conditions would become bone cells.  He explains that the environment interacts with the membrane of the cell and causes certain parts of the DNA to be read, or expressed, and other parts to be ignored.  This is called epigenetics and it is an aspect of genetics that was mostly ignored until recently.

Maybe that junk isn't actually junk

When scientists undertook the Human Genome Project, they expected to find at least 100,000 genes in humans given what they had found in other creatures.  Simple creatures such as C. elegans, a worm, has 20,000 coding genes, certainly a far more complex creature like humans will have more, right?  Not so much.  When the Human Genome Project was completed, it determined that humans had a total of between 20,000-30,000 genes.  What makes this even more shocking is that rice contains between 35,000-56,000 genes.  The problem isn't that we have so few genes, it's that a portion of the genome called "Junk DNA" that we disregarded happens to have a much larger effect on our complexity than the coding genes do.  In other words, what we called junk wasn't junk at all.

Since the "Junk DNA" didn't code for actual proteins, it sort of got thrown out with the trash, so to speak.  It certainly doesn't make sense that it's worthless considering it makes up about 98% of the genome.  However, since it didn't make anything quantifiable, researchers figured it was of minimal significance.  This portion of the genome is something we now call the epigenome, and it's significance is anything but minimal.  While the epigenome doesn't really make anything, it's significance is huge because it tells the coding genes what to do.  While the coding genes make insulin or organelles, the epigenome identifies the environmental condition and activates or suppresses all of the genes that are affected by that particular environmental condition.  If you look at the coding genes as the blueprint, the epigenome is the general contractor that reads the blueprint and puts it in to action. 

The epigenetics of animal development

From the day you are conceived, cells divide and replicate, passing along the genes that are contained within.  As you develop in to an embryo and beyond, HOX genes help guide your development by making HOX proteins that either repress or activate other genes.  In this way, the HOX proteins are a set of orders given out by the HOX genes that say, "Put the thorax here, put the eyes there, put ears here" and so on.  Embryonic development is a great example of epigenetics at play.  You may be surprised to learn that at one point you had a tail.  While you were but a wee embryo in your Mother's womb, you had a tail that eventually disappeared.  It disappeared because you are a human in a human uterus and human's don't have tails.  At some point during the developmental process, an environmental cue came that initiated apoptosis, or cell death, that lead to the removal of the tail.  The same thing happens with the spaces between your fingers and toes, the epigenome received a signal and the cells that made up the webbing between the hands and toes committed apoptosis and you were left with separate fingers and toes. In people with webbed hands or feet, or those born with a tail, the presence of these structures is an example of the epigenome not activating the proper sequence at the proper time. 

The power of the HOX genes also gives us an idea as to how all life on the planet is forever linked.  You may have noticed that all animals have a similar body plan.  While some may have wings, some paws, and others arms, the basic body plan is the same.  In the picture below, you can see how 2 seemingly uncommon creatures such as a fruit fly and a mouse share a similar blueprint for a similar overall body plan.

As you can see, there are similar structures and a similar basic body plan between a fruit fly and a mouse.  This is why we don't see animals that have 3 heads or an odd number of legs unless they are genetic defects.  There are only a few body plans that we see and all are similar because many of the instructions are similar because we share quite a few coding genes.  What makes this even more interesting, and the primary reason I used a fruit fly and a mouse, is that in 1994, research was done where the gene from a mouse that codes for the eye was placed in a fruit fly.  The result...the fruit fly grew a normal fruit fly eye.  This is because the genes are the same, it's not a difference in the specific gene, it's a difference in how and when the gene is activated that determines what type of eye is made, and that determination is made by the environment the cells are in.

Epigenetics and adaptation

So what does all of this have to do with being human and how we work?  Embryonic development is a great example of how epigenetics works, but epigenetics reaches well beyond embryonic development.  All biological functions are products of gene/environment interactions.   Your cells are attempting to put you in a position that is most advantageous to the environment you are in given what they can do, and when the environment remains consistent over time, patterns of gene expression are remembered and passed on to future cells.  Over time, your cells begin to "memorize" the environment by using epigenetic tags that get passed on to daughter cells, giving them a leg up.  When the environment changes for a significant amount of time, these tags are removed and different tags are laid down provided the environment remains constant for a time.

In much the same way, your genome has been shaped to make you better at things that your ancestors were good at.  While the epigenome can change in an individual, the coding genes do not, they are simply shaped in a population over the course of many generations as genes that put certain individuals at an advantage over others get passed on when people with those genes reproduce and have more children than those without the gene.  In addition, genes that put people at a disadvantage and also impact their ability to reproduce decrease or become removed from the population.  So in an individual, coding genes do not change they change in a population over long periods of time.

For example, the environment our ancestors were adapted to was low in food so being able to store fat efficiently is a beneficial trait to have.  Humans who were successful at passing on their genes to offspring were more likely to do this well so we are more likely to see people with genes that are efficient at storing fat.  In the same way, craving sugar and acting on that craving is something that is also advantageous when food can come and go in the blink of an eye, which is why most of us tend to crave fat, sugar, and carbohydrates.  

For most of our existence, food hasn't been that easy to come by.  Being able to store more energy for later use is in the best interest of humans because for most of our existence we have also needed to expend large amounts of energy to procure food.  Now, not so much.  When an organism's genes become adept at operating in a certain type of environment and that environment changes quickly, bad things can happen if there is a mismatch between what their genes are good at and what the environment requires for survival.  Since your genes are passed down to you by your parents, and theirs from their parents, your genes are well suited to an environment similar to theirs as well as their predecessors.  If your genes don't work well with the environment they are in because that environment changes on a dime, a mismatch occurs.  This mismatch between what our genes are good at and the environment they are currently in is likely the impetus for most of the chronic diseases we see today.

All is not lost, however.  The epigenome does allow us some flexibility to adapt to different environments, but there needs to be a willingness to do so in the face of such a drive to eat and be efficient with the amount of energy we use to get food.  In other words, personal responsibility is likely the first step until your body, and cells, adjust to the new environment.  Changing the environment you experience through diet and physical activity should begin to improve your health since it is the environment your genome was optimized for.  If your blueprint, or DNA, is fixed, why would things start to go bad if they've run smoothly for 50 or 60 years?  The likely answer lies with epigenetics.

Your genes are not your destiny

When people do genetic tests to find out if they have the gene or genes that are associated with a disease, what they are finding out is whether or not there is the possibility that a disease is in their future.  They are not finding out with 100% certainty that they will get a disease, that is dependent on if and/or when the gene(s) are expressed, and for how long.  There are people with genes associated with any number of diseases that may never get them.  Identical twins, while they contain the exact same DNA, often die of different causes.  That is because from the time they are born until the time they are married with children and have a career, their environments diverge from one another.  There are even identical twins where one is obese and the other is lean.  This is because the same blueprint has been put under different environmental conditions that have led to different patterns of gene expression.  The result...two different outcomes based on how genes are turned on and off by the lifestyle decisions each has made.

So why does the same plan lead to different outcomes based on specific aspects of the environment?  Why do biological functions occur?  And why may epigenetics help solve some of life's greatest questions?  The answers to these questions can be found by looking at evolution, but first we have to take a look at one more aspect of our genome that we didn't cover.  In the next blog we will go over the zoo of bacteria in your gut often referred to as your microbiome.

Next: Your microbiome

Why counting calories doesn't work

The food issue of Scientific American came out yesterday and they have a pretty cool spread on how and why counting calories doesn't work.  Below is a video going over some of the very basic science.

Why Calorie Counts are Wrong

As a strength and wellness coach I have seen the argument, time and time again, that in order to lose weight people need to eat less and exercise more.  This quantitative approach fails on so many levels that I thought it prudent to write a blog article on why it fails.  Before we delve in to the specific reasons why, I think it's important to first set down a framework for how the human body works.  From there I will go over why counting calories doesn't work and what you should focus on to lose weight effectively.

From hormones to genes to environmental signals

When you look at how the body works, you can see fairly easily how counting calories and focusing on burning them fails.  Systems within your body talk to one another via hormones, also known as chemical messengers.  For example, when you consume a meal, nutrients get digested and eventually enter your bloodstream.  These nutrients, in turn, cause the secretion of hormones to help utilize and store these nutrients.  When you exercise, hormones are also released that help dictate the fuel you use.  In fact, there isn't a time in the day when you are not secreting some level of many hormones.  However, while your hormones are affecting how you feel, how much energy you have, and whether you are actively using energy or storing it for later use; what you do throughout the day will also affect those hormones.

We do not need to discuss the biology of this in great depth to grasp a very simple concept.  What causes the secretion of hormones is genes.  In fact, every biological process occurs via genes.  A perfect example is alcohol.  In order to make alcohol you need water, sugar, and yeast.  The water is the medium in which the yeast convert sugar in to alcohol.  The yeast do this because they contain genes that direct the processes that cause the fermentation of sugar in to alcohol and water is required for this process.  If the genes weren't there, the yeast would do nothing.  If the water and sugar weren't there, the genes would do nothing.  If you put the yeast in a pail of gasoline and oil it would do nothing.  Genes are a set of instruction for what an organism will do under certain environmental conditions, or signals.  If the proper signals are not sent to the genes, they do nothing.

In much the same way, you burn fat under the proper environmental signals.  This is largely dictated by the hormonal environment within your body.  Making it an even more complex situation, we burn fat and glucose through separate, intertwined processes.  At no time are you ever burning 100% fat or 100% carbohydrate.  Even if you ate no carbohydrates, your body can still make glucose which is how carbohdyrates enter the glycolytic(carbohydrate burning) energy systems anyway.   If you ate no fat you would simply use body fat to fuel fat dependent energy systems.

The energy system that is predominantly used is largely dependent on the environmental signals you send, which are dictated by lifestyle factors including sleep, stress, exercise, diet, and how each affects your hormonal profile.  Ignore these factors and not only will you not burn fat, you will set yourself up for failure by producing a hormonal environment primed to drive your appetite through the roof and store as much of the energy you consume as possible.  So while you are essentially a machine, you are far too complex of a machine to be broken down in to a simple, archaic energy in/energy out system.

A good analogy for this is a hybrid car.  The calories in vs calories out mentality is that if the car won't move, all you need to do is put more fuel in to it, regardless of type.  However, if the car won't move because it is out of gasoline, you cannot pour electricity in to the gasoline motor because it cannot use electricity as it's energy source.

Appetite and food reward

Another reason that calories in vs calories out doesn't work is because it fails to address appetite.  Appetite is dictated by hormones as well as something called food reward which directly impacts hormone secretion.  The food reward system is very complex but involves the same processes and areas of the brain that drug addiction affects.  Basically, certain foods hit the reward center of your brain hard and generate a sense of pleasure we like.  This means that, over time, we will actively seek out these foods, especially when we are hungry.

Removing these foods for an extended period of time not only reduces your craving for them, it helps put you in a better hormonal environment to burn fat.  Frequent consumption of these foods wrecks your metabolism by negatively affecting your cells' sensitivity to insulin and leptin, two very important hormones.  If it were simply a matter of calories this shouldn't be an issue, but it's a big one.  It's also why once you pop you can't stop and the primary reason you can't eat only one.

It's all in the genes, and most of them aren't yours

Now that we have a thorough understanding behind the general concepts of how genes impact biology, it becomes important to realize that most of the genes responsible for the biology going on in your body right now do not belong to you.  Most people have heard of their gut bacteria, but I don't think they truly understand the scope of how important these little guys are.  From a shear numbers standpoint, the bacteria in your gut outnumber the cells of your body 10 to 1.  This not only means we are only 10% human, it also means that the amount of genetic material contained within the bacteria in our gut outnumbers that within our cells by a factor of 300(1).

If you buy in to the importance of genes for human health, it isn't too far of a stretch to realize that our gut bacteria should be a main concern.  These bacteria help us in many ways by helping train and control the immune system, manufacturing nutrients, transporting ions, helping heal intestinal damage, and this is merely the tip of the iceberg.  There also appears to be a line of communication between the brain and the gut.  This is a 2 way line of communication that appears to be through the vagus nerve(2), a part of the autonomic nervous system which regulates minor things like respiration, heart rate, and blood pressure. 

Changes in gut bacteria have been attributed to so many diseases that one may be suspicious of all the things healing the gut could potentially help.  People with autism, adhd, anxiety/depression, Type 2 diabetes, heart disease, you name it.  With regard to obesity, there is a clear relationship.  While there are more than 10,000 different strains of bacteria in your gut, most of that bacteria belongs to 10 species.  Of those 10 species, the ones that appear to be the most important to human health are bacteroidetes, firmicutes, and bifidobateria.

Specifically, with regard to obesity, there appears to be two strains of bacteria that are consistently different between obese and lean people, bacteroidetes and firmicutes.  Obese people tend to have fewer bacteroidetes and more firmicutes than lean individuals.  This relationship is so powerful that in mice, when mice with sterile guts are given the bacteria from lean humans they remain lean and when they are given the bacteria from obese humans they become obese.  If you place these mice together in cages and give them the proper diet the obese mice become lean(3) because the obese mice eat the lean mice's bacteria(aka poo).

Many other studies have shown that swapping the gut bacteria between lean and obese mice causes the mice to take on the form of the mouse whose gut bacteria they were given.  In all of these experiments, calories were kept exactly the same.  One of the primary factors noted for this phenomenon is that the gut bacteria in obese mice extract more energy from food which provides an energy surplus to the host.  This means that while the calorie count is the same, the gut bacteria liberate more energy for the host which in turn causes more calories to be absorbed.

Building a proper microbiome

For the most part, the types of bacteria found in your gut are determined in your first few years.  Whether you were born vaginally or via C-section, whether you were breast or formula fed, and whether you were kept in a completely sterile environment or had frequent exposure to dirt and bacteria when you were a baby will dictate the types of bacteria in your gut.  Once your gut is populated, the proportion of each strain of bacteria is largely dictated by diet.  In the study on mice that were given human gut bacteria, a diet high in fruits and vegetables and low in saturated fat led to the more desirable lean gut bacteria while a diet low in fruits and vegetables and high in saturated fat led to the obese gut bacteria.  From the research it appears that the more desirable gut bacteria tend to feast on the fiber and polyphenols found in fruits and veggies(4, 5).

I have not seen any evidence that suggests that saturated fat is implicated in altering the gut bacteria in obese people.  While it is true that obese people tend to eat more saturated fat, they also tend to eat more processed foods high in sugar and avoid fruits and vegetables.  One of the more troubling developments over the past 40 years is that people avoided saturated fat and swapped in processed, high sugar foods which do have a damaging impact on gut bacteria composition.  This scenario has played out the way it would in a petri dish as bad bacteria crowd out good ones because the bad ones are fed and the good ones starved.

Conclusion

The video posted above goes over why calorie counts are wrong, but that is besides the point.  Even if they were accurate, focusing on calories in vs calories out will never be a successful way for people to deal with weight loss.  If more people focused on what they should eat rather than how much, they would be in a much better place right now in terms of health as well as proper weight maintenance.  The research has been pointing in this direction for quite some time now, but by the time it reaches clinics and fitness professionals it may be too late for some.

Being a fitness professional, I should be towing this line if I was doing what's right for my pocket book.  If I want to do what's right for my clients, I will help them alter their lifestyle in a way that will foster genetic expression that is optimal for weight loss.  This doesn't involve buying supplements, starving yourself, and exercising with me 6 days a week.  It involves eating the proper foods and staying off their butts more than sitting on them, something I discuss here.  Exercise is merely icing on the cake.

Healthy mitochondria: The key to optimal health and wellbeing

While most people tend to look at human beings as an individual unit composed of organs and tissues with regard to health, it is important to realize that the health of individual cells will dictate how healthy your organs and tissues, and thus you, are.  Of course all parts of the cell serve a vital purpose to our survival, but one organelle appears to be particularly important for your health: The mitochondria.  Your mitochondria serve many roles in your cells that are critical to proper function including generating the bulk of ATP(Energy), cell specialization, apoptosis, control of the cell cycle, and cell growth.  The role of the mitochondria is so important to health that mitochondrial dysfunction is found in many of the chronic diseases people experience today including Cancer, Diabetes, Alzheimer's, Parkinson's and a host of others.  Let's take a look at the mitochondria and their impact on health.

A look at a single mitochondrion through a microscope

An interesting tidbit on the mitochondria

The mitochondria are interesting little organelles found within our cells.  Organelles are little structures within our cells that carry out tasks.  Each cell within in an organ has organelles that perform the function of that organ.  For example, one of the functions of your liver is detoxification and many of the cells within the liver contain organelles that do just that.  The mitochondria, which along with energy generation have many functions critical to survival, can be found in just about any cell within a multicellular organism.  The predominant theory on how mitochondria came to be in our cells is referred to as endosymbiosis.

Endosymbiosis is the theory that many of the organelles within our cells came to be there due to a mutually beneficial relationship with the host cell.  In the case of the mitochondria, the theory goes that the mitochondria were bacteria that were engulfed by a separate single celled organism.  There is plenty of evidence for this, and the fact that mitochondria contain their own DNA in the shape of a circle, something primarily found in viruses and bacteria, lends support to this theory.  Over time, the mitochondria became organelles within the cell and lost some of their DNA to the nucleus.  However, to this day, the mitochondria still contain some DNA that cannot be found in the nucleus of the cell.  This DNA primarily codes for proteins found in the electron transport chain, something we will discuss a little later.

What do the mitochondria do?

While the mitochondria within your cells do quite a few things, the role they are most famous for is generating most of the ATP.  ATP, or adenosine triphosphate, is the form of energy your cells use to accomplish the many tasks they perform.  Some cells create hormones, some cells create movement, some cells transmit nerve impulses, and some cells relay information within the body.  Any cell that requires energy to power it's processes uses ATP to do so.  Most cells have many mitochondria, and the number of mitochondria within the cell is in proportion to the energy needs of the cell.  In addition to generating energy for cells, mitochondria also have a prominent role in apoptosis, or cell suicide.

While the concept of cell suicide may sound bleak, apoptosis is a critical process that begins when you are developing as a fetus.  The formation of fingers and toes is accomplished by apoptosis of the cells between the fingers and the toes.  In people with webbed feet or hands, this process did not operate efficiently when they were in the womb.  Apoptosis helps remove unwanted or unhealthy cells before they become a problem.  When apoptosis doesn't occur, bad things happen.  Cancerous cells somehow override apoptosis which is how they proliferate and become tumors.  As long as apoptosis is working properly, irregular cells are terminated.  In fact, thousands of cancer cells develop and go through apoptosis ever day.  It's when apoptosis doesn't work smoothly that cancerous cells proliferate and become tumorous.

As you can see, healthy mitochondria are important for health.  By eating the proper foods and getting regular physical activity, you can keep your mitochondria working smoothly.  Let's take a look at the foods you should be eating and things you should be doing to maintain healthy mitochondria.

Foods for healthy mitochondria

Many foods are beneficial to healthy mitochondria, chief among them are vegetables high in sulforaphane.  Sulforaphane is a molecule found in cruciferous vegetables that helps to increase intracellular glutathione levels.  Glutathione is your body's master antioxidant.  One of the ways your mitochondria makes ATP is the electron transport chain(ETC).  The ETC generates energy by passing electrons between molecules in the mitochondria which creates an electrochemical gradient.  It's not important to understand the specifics of this energy generating process, but it is important to understand that this process generates free radicals as a natural byproduct of making ATP.

Free radicals are unstable substances with an unpaired electron in their outer shell that react with healthy components of your cells.  It is important to limit free radicals because they can interfere with proper functioning of the cell.  Antioxidants donate electrons to free radicals but become weaker free radicals in the process.  Glutathione, being the master antioxidant, donates electrons to free radicals as well as antioxidants that have become free radicals.  Having high glutathione levels, then, can allow you to limit free radical production and limit the amount of damage free radicals can do to your mitochondria.  This is important because most of the antioxidants you eat cannot enter the mitochondria and since the mitochondria has DNA that codes for the proteins in the ETC, damage to that DNA can accelerate free radical production.

Eating cruciferous vegetables such as broccoli, cauliflower, cabbage, asparagus, and kale is important to help keep your glutathione levels high.  Studies have shown the sulforaphane found in these vegetables helps induce cell apoptosis in cancer cells(1).  However, since these vegetables are also goitrogenic meaning they can interfere with thyroid function, you want to limit consumption of these foods to five or six servings a week.  Cruciferous vegetables are not the only foods found to increase glutathione levels, whey protein(2) and blueberries(3) both contain compounds that increase glutathione levels as well.

Supplements for healthy mitochondria

While keeping glutathione levels high should be one of your goals, supplemental glutathione won't work because it is destroyed by stomach acid.  N-Acetylcysteine does appear to work very well at keeping glutathione levels high(4).  However, when looking at maintaining good mitochondrial health and a healthy number of mitochondria in your cells, there is more to it than just increasing glutathione levels.

Magnesium deficiency has been shown to lead to fewer mitochondria in cells(5), so getting sufficient levels of magnesium is important to generating many mitochondria.  Iodine is another important nutrient to make sure you are getting enough of to support healthy mitochondria.  In addition to it's role as a component of thyroid hormone which regulates metabolism throughout the body, iodine also has an important role to play in cell apoptosis(6) which it apparently mediates through mitochondrial mechanisms(7, 8).  In one study, iodine was shown to induce apoptosis in human breast cancer cells but not in healthy cells that surround the cancerous cells(7).  In another, iodine helped induce apoptosis in 4 out of 5 breast cancer cell lines.  For the most part, people tend to be deficient in iodine unless they consume large amounts of fish or low to moderate amounts of seaweed.  Table salt is iodized but few people use iodized salt and the iodine tends to evaporate out of the salt over time.

Lifestyle factors for healthy mitochondria

Given what we've discussed thus far about mitochondria, you may be able to figure out the things you should be doing to have many, healthy mitochondria.  Calorie restriction has been shown to boost the health of mitochondria which makes sense.  Fewer calories going through the mitochondria means fewer free radicals that can potentially react with healthy parts of the cell.  Ketogneic diets tend to lead to healthy mitochondria, potentially via an increase in glutathione levels(9).  It is important to note that one should not randomly undertake a long term ketogenic diet as these types of diets require modulating the intake of other nutrients for safe implementation.

Another thing people can do to maintain healthy mitochondria is exercise.  Daily physical activity is important to signal cells to keep many mitochondria on hand.  There is probably a sweet spot you should shoot for as excessive exercise should, in theory, lead to greater free radicals via increased mitochondrial free radical production.  If I were to ballpark it I would say running for 3-5 miles per day is probably ok but anything above that would provide no added benefit with potential negative consequences, but there are no studies to back up this assertion.  As far as strength training, a normal strength training program is probably fine but bootcamp or circuit style training could potentially cause problems in excess.  Regardless, any situation where you are calling on your body to produce lots of energy will create lots of free radicals that you should attempt to keep in check by keeping glutathione levels high and eating foods high in antioxidants(fruits and veggies).

Conclusion

Keeping healthy cells is important to maintaining your health.  While all components of your cells are important, the mitochondria are crucial for energy generation and proper cell functioning.  There are many things you can do to keep many, healthy mitochondria.  Eating foods that boost glutathione levels as well as making sure you are getting enough magnesium and iodine are nutritional strategies everyone should utilize.  In addition, regular physical activity that is not excessive can signal your cells to increase production of mitochondria without the netative side effect of creating too many free radicals.

Feel fat, depressed and unhealthy? Get off your tookus!

If you're like most people, you spend your entire day at a desk and 3-4 hours a week at a gym trying to combat the negative effects associated with sitting at that desk.  As time has gone on, you've probably also noticed a reduced ability to maintain your body weight as well as increased risk markers for cardiovascular disease and other chronic diseases.  Even when you double up the amount of time you exercise per week for your New Years' resolution your results get worse each year, leading to year over year increases in fat mass.  The reason this happens is not because you don't exercise enough, it's because you spend too much time sitting.  Sedentary behavior leads to modified genetic expression that promotes fat gain and cardiovascular disease, and no amount of exercise at a gym will prevent that.  When you look at the grand scheme of things, even if you exercise intensely for 16 hours a week that still leaves 152 hours per week where the wrong genes are turned on.  Don't believe it?  Let's take a look at some of the research.

High levels of sedentary behavior are associated with the metabolic syndrome, independent of other factors related to the metabolic syndrome including moderate to vigorous physical activity(Alcohol intake, smoking status, age, gender, diabetes and heart disease)(1, 2).  This means that getting physical activity via exercise did not compensate for the amount of time spent being sedentary.  The amount of sedentary time also has a strong positive relationship with triglyceride levels as well as waist circumference and waist to hip ratio.  High levels of sedentary time also lead to higher circulating levels of insulin(3, 4, 5, 6, 7, 8), impaired glucose clearance(3, 7, 8)  and impaired fatty acid metabolism(5, 7, 8).  While a couple of these studies were done with people on multiple days of bed rest and therefore not directly comparable to people sitting at a desk day in and day out, most of these changes with insulin action and glucose appear to be a result of changes in localized gene expression due to a lack of muscular contraction(7).  In fact, as discussed in Part 2a of my 3 part series "Myths, Metabolism, and Appetite" (Part 2a), it may actually be whether or not the leg is loaded, regardless of muscular contraction.  Unloading one leg while still allowing movement of that leg for 48 hours leads to altered genetic expression that increases protein breakdown and anti-oxidant pathways (Indicating increased oxidative stress) while reducing mitochondrial metabolism with no change in gene expression in the other leg(9).  This reduction is mitochondrial metabolism is probably the mechanism by which fatty acid metabolism is reduced during sedentary periods.  These changes persisted even after 24 hours of reloading the leg.

When we look at who is most affected negatively by sedentary behavior from an insulin sensitivity perspective, it appears that healthy people are more negatively impacted than people prone to Type 2 Diabetes (T2D).  In a study that looked at bed rest and changes in insulin sensitivity with healthy people as well as people with first degree relatives with T2D (FDR)and those with low birth weight, two risk factors for T2D, the healthy subjects experienced a greater drop in insulin sensitivity (5).  The authors hypothesize that this effect is due to the other two groups already having some degree of insulin resistance. In another study comparing insulin sensitivity changes in healthy subjects to FDR, whole body insulin sensitivity declined in both groups but hepatic (Liver) insulin sensitivity declined only in the FDR group.  This is interesting because as discussed in "Myths, Metabolism, and Appetite", people who are prone to T2D and FDR of T2D have fewer type I fibers and a higher proportion of type IIx muscle fibers.  This is, in part, a gene environment interaction.

While the more oxidative (Fat burning) type I fibers have not been shown to convert to other fiber types, the more glycolytic (Glucose burning) type IIa and IIx fibers tend to convert back and forth based on recruitment of said fibers.  Lack of use causes IIa fibers to convert to IIx fibers which are more insulin resistant while regular recruitment of IIx fibers causes them to convert to IIa fibers.  In people with a higher percentage of type II vs. type I muscle fiber types that also do not recruit these fibers regularly, most will become insulin resistant as more of their musculature converts to the insulin resistant type IIx fibers.  People with this genotype probably have to participate in regular strength training to recruit the insulin resistant IIx fibers enough so that they convert to the less insulin resistant IIa fibers, particularly if they intend to consume a high carbohydrate diet.  Coincidentally, converting IIx fibers to IIa fibers allows these people to store more muscle glycogen.  Emptying out these glycogen stores with regular, intense strength training will provide a larger storage compartment for ingested carbohydrate and delay hepatic insulin resistance.  Ironically enough, people with this genotype tend to be the better power sport athletes so it seems that modern life is just not compatible with this genotype.  My guess is they would also have been the best hunters which could indicate why such a high percentage of the population is prone to T2D from an evolutionary perspective.

Another interesting aspect of sedentary behavior is it's effects on lipoprotein lipase(LPL) activity.  LPL is an enzyme responsible for triglyceride breakdown.  Reduced LPL activity leads to higher blood triglycerides via a reduced ability to metabolize fat.  Obviously conditions that lead to a reduction in LPL activity are not ideal, especially if one of your goals is to reduce body fat.  Sedentary behavior has been shown to dramatically lower LPL activity (6, 7) in the muscles of the leg and reducing sedentary behavior has been shown to have a greater effect on increasing LPL activity than does adding vigorous physical activity (7).  This increase in LPL activity makes sense because the muscle fiber type associated with physical activity of lower intensities is the type I fibers that tend to rely more on fat as a substrate.  As the intensity of your exercise increases, so does the utilization of glucose as fuel to power the type II fiber types during that activity.  During both active and passive recovery there appears to be a switch to the type I fibers and a greater reliance on fat as fuel, perhaps to spare glucose for future intense activity.

Other genes and pathways associated with health are positively affected by breaking up periods of inactivity.  One study identified 75 different genes differentially expressed during periods of inactivity vs. periods of activity used to break up inactive periods (8).  Many of these genes are involved in processes that are known risk factors for cardiovascular disease.  Breaking up periods of inactivity with periods of physical activity for 2 minutes every 20 minutes positively affected the expression of genes associated with carbohydrate metabolism, antioxidant pathways and anti-inflammatory pathways.  Another study found breaking up periods of inactivity improved postprandial insulin and glucose concentrations when compared to a completely sedentary condition(9).  While we have focused much of our attention on the localized effect of sedentary behavior on muscles and to a lesser extent the liver, there also appears to be a significant negative impact on the brain.

Increased sympathetic nervous system activity is a widely known symptom of obesity and T2D.  The autonomic nervous system is in charge of regulating mostly involuntary processes and has two branches.  The parasympathetic branch is responsible for rest and digest while the sympathetic nervous system is responsible for the fight or flight response.  People with increased sympathetic nervous system activity have a problem getting out of stress mode, in other words they are in a constant state of stress.  Research indicates that this increased sympathetic activity may be mediated by dysfunction in a part of the brain called the rostral ventrolateral medulla (RVLM)(10).  The RVLM is the primary part of the brain involved in regulating sympathetic nervous system activity.  Physical inactivity may have wide-ranging negative effects on the RVLM and this could explain the detrimental effects of sedentary behavior on measures of cardiovascular disease regulated by the autonomic nervous system such as hypertension.  It is not known at this point if the difference between sedentary and active people is due to a negative effect of being sedentary, a positive effect of being active, or a combined effect of the two.

As you can see, being in a seated position for prolonged periods is a significant factor in poor health and an inability to metabolize fat.  While insulin sensitivity and blood glucose utilization are two big factors impacting both, these are not the only considerations.  The data suggests that sitting for long periods of time is terrible for your health and no amount of exercise at the gym can attenuate the bad effects of sitting.  These effects may expand beyond the physical changes happening in the muscles and more than likely has deleterious effects on the brain.


EDIT: After I wrote this I found a new randomized clinical trial that looked at 3 groups (sedentary, sedentary+1 hour of intense exercise, and a group that spent half the time being sedentary and the other half standing or doing low intensity activity).  Guess who "won".  :)

Check it out.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0055542

Hardwired for failure...

http://www.sciencedaily.com/releases/2012/06/120612115812.htm

http://www.newstrackindia.com/newsdetails/2012/12/20/205-Gut-bacteria-may-be-making-you-hungry.html

The articles above illustrate something I try to get clients to understand every day.  While they are busy concerning themselves with how many calories they consume and trying to burn as many as possible, something I tell them not to do, they ignore the fact that what they choose to eat is actually changing their operating system.  The reason I recommend a paleo diet is that the paleo diet actually repairs this operating system.  It's not only the software our systems have run on forever, it's the software our systems are optimized for.

When you choose to follow the diet for a couple of days and then go off the rails and eat something you shouldn't, you undo a significant amount of the progress you made because you begin to re-feed the bacteria you have been trying to do away with for the last couple of days.  Think of it as sending supplies to the enemies you are at war with, why would you do that?  Obviously if you are further along on the diet and have re-established your operating system you have a lot more leeway than someone who has been on the diet for a little while.

One of the hardest things to do is to get someone to change their diet.  I can't tell you how many clients who I've told to eliminate grains, legumes, and dairy who tell me they have done just that only to find out they are eating greek yogurt and granola for breakfast.  Granola has grain in the first 4 letters and who doesn't understand yogurt is dairy?  It's not that they are stupid people, it's that in a metabolically deranged individual they will always look for workarounds, it's what their body tells them to do.  Given the multiple body systems, and non-body systems in the instance of gut bugs, involved in driving them towards what they eventually end up eating, stupid isn't the proper term. I prefer the term hardwired for failure, and until they fix this issue that's what they'll continue to be.  While they may be able to lose a little weight here and there and maintain it for a few months, they will always go back to the status quo because they never fix the problem.  Eating the way a standard American eats changes the operating system, changes appetite, and drives people to make poor food choices.  It is also one of the primary drivers of the obesity and heart disease epidemics.

Epigenetics:Why you should care about sleep, physical activity, and what you eat.

Suppose you are sitting on a train, on a bus, on a plane, or on a park bench in between 2 other people.  Look to your left…Look to you right…Look in to your own hands…Now, realize a harsh reality…Two of you are going to die of cancer, diabetes, or heart disease; largely preventable diseases that have a deeper root in the way you live your life than in the genetic hand you were dealt. 

It may come as a surprise to you that you have a hand in preventing these diseases.  Twenty years ago it was thought that you were dealt your “hand” and you had to live with it.  The human genome project was undertaken to identify these genes so that pharmaceutical companies could target them and provide us with personalized therapies for what ailed us.  It was theorized that human complexity was determined by a large number of genes and once we mapped this genome we would be able to use the power of pharmaceutical medicine to completely revolutionize the way we practice medicine.  The fruit fly has about 12,000 genes, a piece of rice…40,000.  With such simple organisms having such a large number of genes, it was assumed that humans would have in excess of 100,000.

When the human genome project finished mapping the human genome, there was a bit of disappointment.  Not only do humans not have more than 100,000 genes, it turns out we barely have 20,000.  In addition, we share about 60% of our genes with the fruit fly.  To add insult to injury, we share 50% with a banana.  So, in the grand scheme of things, we really aren’t that exceptional.  That is, until, you look in to a little part of the DNA sequence that was once referred to as junk DNA.

The human genome project looked at what are called protein-coding genes.  Protein-coding genes make proteins in the body that ultimately make up you.  At the time, it was thought that the rest of the DNA outside of the protein-coding genes was junk and performed no real purpose.  Once it was found that the amount of our protein-coding genes was so low, scientists realized human complexity couldn’t be explained by protein-coding genes.  They decided to take a second look at the junk DNA and, lo and behold, they found something.

The original line of thinking that lead scientists to name this portion of DNA junk was that if a gene doesn’t make anything, it couldn’t have any relevance to human complexity or health.  When they realized the solution couldn’t come from the protein-coding genes, they needed to change their line of thinking.  By looking deeper in to the “junk DNA”, they realized that it wasn’t junk at all.  In fact, the junk DNA is running the show.  While the junk DNA doesn’t make anything, it basically gives the orders to the protein-coding genes to, “Make it happen!”  Rather than making insulin, or cortisol, or forming muscle tissue; the junk DNA acts as a switch and causes a number of genes to be expressed, calling in to action the appropriate gene sequence based on what you tell it to do.  But how do you tell it what to do and how does that impact your health?

There are 3 primary modifiable ways your body communicates with the environment; your diet, your lifestyle, and physical activity.  It is this communication with the environment that tells your body what to do.  In other words, this communication drives evolution by natural selection.  It does this via the hormones you produce in response to this communication.

It is well known that a lack of sleep will cause excess cortisol secretion, one of the primary hormones of your stress response.  Excess cortisol in the long term negatively impacts blood glucose, both by causing your blood glucose to rise directly as well as increasing your appetite for carbohydrate containing foods. This in turn may eventually lead to a malfunction in the hormone insulin, leading to constantly elevated blood glucose and Type 2 Diabetes (T2D).  Type 2 Diabetes is a major factor for many chronic diseases such as heart disease, Alzheimer’s disease, and cancer. 

Most of the recent research on Alzheimer’s disease has identified insulin resistance as a major predisposing factor.  In fact, this relationship is so strong that most researchers are referring to Alzheimer’s disease as Type 3 Diabetes, or insulin resistance of the brain.  Furthermore, a relationship has been established between Alzheimer’s/Dementia and lack of sleep, with sleep troubles being an indicator of future disease progression.  Given the relationship between sleep and cortisol as well as cortisol and insulin resistance it would seem that the answer to a cure for this disease may reside in the switches, not the coding DNA.  In other words your destiny isn’t written for you, a significant amount of it lies in your hands.

When you look at the cellular changes that occur in cancer, insulin and glucose are front and center.  Not only do most cancer cells primarily use glucose for fuel, cancer cells have 6 times more insulin receptors on their cell membranes than healthy cells.  This sounds like a pretty good adaptation to an environment that is high in both glucose and insulin.  Even better, the research on junk DNA identified that most of the thousands of changes seen in cancer don’t happen in the coding DNA, they happen in the switches.  Since they are happening in the switches, we have some control over them.  If you flip the switch on you get problems, if the switch stays off the problems are kept at bay.  This isn’t to say that once you have established cancer that you can reverse or remove it by changing your lifestyle, only that having the gene isn’t necessarily a death sentence provided you do your best to provide the proper information to the switches.  To the best of our knowledge, the best way to do that is get 8 hours of sleep a day, get regular physical activity, and eat a mostly whole foods diet while avoiding processed foods.