Thursday, February 20, 2014

The human's guide to being human: Evidence against the Western lifestyle

Over the course of the past 5 blogs, we have gone over how organisms on the planet interact with the environment and how this interaction leads to adaptability of the individual as well as evolution of the species through gene/environment interactions.  It is important to note that our ability to adapt to different environments has allowed humans to populate every continent on the planet except for Antarctica, something no other animal has done.  However, our ability to adapt is constrained by the genome that was developed over millions of years of evolution.  Furthermore, as the environment changes, traits that were once beneficial to our ancestors can become detrimental to us.  Since there are still pockets of people living in the same basic conditions our species evolved in, we can look at the difference between attributes of their lifestyle and compare it to ours to see if some of the diseases that we experience are products of a bad gene/environment interaction.  With advances in medical technology, we can also look at how different lifestyle factors change gene expression in a way that can lead to poor health.

Comparing Western lifestyles to modern day hunter gatherers

When we take a look at the health of modern day hunter gatherers, one thing is abundantly clear; they die in different ways.  While people living a western lifestyle are likely to die of Cancer or Heart Disease, modern hunter gatherers are likely to die of infection or from a violent cause.  Modern medicine has afforded people in the west the ability to avoid dying of infection and societal norms dramatically reduce the risk that you will die of a violent cause.  However, the notion that western people die of chronic diseases such as Cancer, Type 2 Diabetes or Heart Disease because they live for much longer aren't entirely true.  In fact, in modern day hunter gatherer societies, these diseases are quite rare even in those who live to older ages.  There is some evidence that the chronic diseases of aging are a product of our ancient genes interacting with our modern environment.

In 1984, Kerin O'Dea published a landmark paper that showed that when Australian Aboriginals who had developed Type 2 Diabetes while living a western lifestyle were reverted back to their traditional lifestyle, their insulin resistance improved dramatically in 7 weeks(1).  This is a big deal because Type 2 Diabetes increases your risk of both cancer and heart disease, among other things.  Many other factors associated with cardiovascular disease such as high blood pressure, high triglycerides, and high BMI also improved.  When you look at the environment these factors create within the human body and how the body responds to these factors, you can get a clear idea of how a western lifestyle can contribute to chronic disease.

Three conditions associated with chronic disease

When you look at Cancer, Type 2 Diabetes, and Heart Disease, there are 3 conditions within the body that are prevalent in all 3.  High levels of inflammation, blood glucose, and oxidative stress coupled with mitochondrial dysfunction are prevalent environmental conditions within the body in all 3 diseases.  In addition, people with Diabetes are far more likely to develop Cancer or Heart Disease.  Since Diabetes is a disease whose primary symptom is high blood glucose levels, and high blood glucose levels increase levels of inflammation and oxidative stress, this makes sense.  But what are these three conditions and how does the western lifestyle promote them?

Inflammation is part of the vascular system's response to harmful stimuli such as foreign invaders and damaged cells.  When you jam your toe against the wall, or a pathogen enters your bloodstream, the body responds by increasing inflammation, a vital part of the repair process.  In the example just mentioned, inflammation is acute and subsides in a relatively short period of time.  The inflammation associated with Cancer, Type 2 Diabetes, and Heart Disease is not acute, it's chronic and contributes to many negative processes within the body including arthritis, plaque accumulation on blood vessel walls, allergies, and is a central regulator of the environment around cancerous cells.  In other words, chronic inflammation is very bad.

Oxidative stress occurs when free radicals react with healthy tissues in your body.  Free radicals are unstable molecules that have an unpaired electron in their outer shell.  To remedy the situation, they go around to healthy, stable molecules and steal electrons from them, causing them to become free radicals.  Oxidative stress is when free radicals build up and overwhelm your body's ability to remove them.  As a result, parts of your cells become damaged and malfunction.  Organelles found within your cells called mitochondria are especially at risk for damage because many free radicals are produced as a natural byproduct of metabolism within the mitochondria.  This does not mean free radicals are bad, they are necessary for proper cell function.  But when too many of them build up and react with mitochondrial DNA, this causes bad mitochondria to be produced which causes more free radicals to be produced.  This process is called mitochondrial dysfunction and is discussed in more depth here.  Needless to say, having high levels of oxidative stress is a terrible state for your cells to be in.

Consistently high blood glucose is a hallmark of Type 2 Diabetes and is likely how many of the symptoms and co-morbidities associated with Type 2 Diabetes occur.  The process is quite simple.  High blood glucose levels cause your pancreas to secrete the hormone insulin which causes cells to take in glucose from the blood.  Eventually, your cells cannot take anymore so they begin to ignore insulin.  This process is termed insulin resistance.  Since blood glucose levels remain high, more insulin is secreted which leads to a state of high insulin levels, which is inflammatory.  In addition, high levels of blood glucose induce oxidative stress(2), particularly in the eye, kidney and blood vessels.  Finally, another hormone called leptin, which is key in the regulation of appetite, begins to climb as the brain becomes resistant to it.  Unfortunately, leptin is a highly inflammatory hormone.

Through this process, you are creating an environment that is extremely bad for your cells.  Perhaps the chronic diseases that are typical of the western lifestyle are simply how human cells adapt to an environment with excessive inflammation, high levels of oxidative stress, and high blood glucose levels.  Through the study in Australian Aboriginals, we can see that the reversal of Type 2 Diabetes in Aboriginals who went from a western lifestyle to the more traditional hunter gatherer lifestyle points to Type 2 Diabetes as being a disease caused by poor gene/environment interaction.  In hunter gatherers, the absence of the chronic diseases that are prevalent in western society provides further support that the chronic diseases of aging are not diseases caused by aging, they are merely diseases associated with aging.  However, we need to pinpoint the aspects of the hunter gatherer lifestyle that are different from those of people in the west and that are important to health.  While there are many aspects of these lifestyles that are different, three stick out like a sore thumb.  These 3 factors are sedentary time, altered circadian rhythm, and diet.

Lifestyle and genetic expression

When you look at the life of hunter gatherers compared to western people, it is readily apparent that hunter gatherers sit for far less time.  On top of getting food every day, hunter gatherers also don't have Barcaloungers to sit on.  While they may sit from time to time, they don't tend to sit for 8 or more hours a day like we do.  High levels of sedentary time are associated with high insulin levels, high blood glucose levels, and poor fatty acid metabolism.  Furthermore, many genes related to antioxidant and anti-inflammatory pathways as well as glucose metabolism are downregulated during periods of sedentary time but are upregulated when these periods of sedentary time are broken up with periods of activity(I blogged about this here).  If you are looking for an easy way to reduce inflammation, oxidative stress, and blood glucose levels, reducing the amount of time you spend sitting each day is as good as any.

Sleep is another lifestyle factor that is quite different between hunter gatherers and people in western societies.  Sleep as well as light and dark cycles set the stage for proper circadian rhythm.  When compared to hunter gatherer cultures, most of us in western cultures are severely sleep deprived.  This sets the stage for poor health by influencing the expression of hundreds of genes associated with health.  A study that compared 1 week of sleep deprivation(5.7 hrs per night) to 1 week of adequate sleep(8.5 hrs per night) found that sleep deprivation causes a downregulation of genes associated with anti-inflammatory and antioxidant pathways as well glucose metabolism when compared to adequate sleep.  In addition, many genes that are associated with circadian rhythm were also disrupted(3).  In total, the expression of 711 genes was altered when people were sleep deprived.  Getting adequate sleep is another easy way to improve the environment your cells are in, potentially reducing your risk for the chronic diseases of aging.

Of the 3 lifestyle factors that are obviously different between hunter gatherer and western cultures, diet is the most tricky because it is the most complex.  Is it the carbs?  Is it the fat?  Is it the calories?  While most of us seem to be preoccupied with these 3 questions, a case cannot be made for any of them.  Hunter gatherers live on many different ratios of carbs to fats and calorie intakes will fluctuate based on the availability of food.  The only thing we know for sure that is different between what hunter gatherers and western people eat is that hunter gatherers don't eat heavily processed foods.  Sure, they ferment, cook, chop, and soak many of their foods, but they aren't eating bread, pasta, cereal, or other foods that come in a box because they simply lack the technology to do so.

Remember, your genes aren't the only genes

We also know that the microbiome of hunter gatherers is vastly different from ours, but there is likely a large variability between the microbiome of different hunter gatherer cultures based on what they eat.  One thing we do know for sure is that hunter gatherers likely have a much more diverse microbiome because their diets are much more diverse than ours.  If you look  at the diets of most western cultures, they are mostly wheat, meat, dairy, and a few different types of fruit and vegetables.  I don't know for sure, but I believe one of the primary issues with our diet is that it's not diverse at all and contains many processed foods that can have a negative affect on our microbiome.  I believe this manifests itself in the form of Celiac disease and other forms of IBD which are all but nonexistent in modern hunter gatherer cultures but seem to be on the rise in the west.  (I have no direct evidence of this, but I have sound theory that I will expand upon in next Thursday's blog)  Remember, a change in the microbiome is effectively a change in the genome since there is more genetic material there performing biological functions for us than in our own cells.  The simple fix is to avoid or limit processed foods and eat a diverse diet.

Conclusion

Overall, using the evolutionary template as well as the way in which our bodies work provides compelling evidence that many of our health problems are related to a mismatch between our genes and the environment they are currently in.  When you look at other cultures who still live in a way very similar to the way our species evolved, they simply do not suffer from the chronic diseases of aging that are prevalent in western civilizations.  I am not suggesting that we abandon all we have gained over the past few thousand years.  On the contrary, I believe a combination of the advances we have seen in medicine and the knowledge that can be gained through an evolutionary perspective on lifestyle can lead us to even greater longevity than we see today.  This doesn't mean that everyone who applies these principles will live to 100, but it does means that you can maximize both your time and quality of life by living in a way that is congruous with how our species developed.

That about does it for the background information on how humans function.  From time to time I will tackle specific aspects about our lifestyle and health and how they fit in to this framework.  Next Thursday I will tackle gluten and the primary issue with it's consumption as well how it is able to create a bad environment for those who overconsume it.  Using the Human's guide framework, we'll take a look at why you can consume it for so long before acquiring symptoms of sensitivity.

Previous: Evolution and adaptation                                                                   Next: The problem with gluten