I want to talk today about a topic in science that can really help with the way we view nutrition day to day. This concept is taken from chemistry and is useful to describe the way that systems behave when exposed to varying concentrations of a substance. To make this topic make sense I need to explain a couple of important aspects on the topic.

 1.) Affinity: This term describes the level of attraction of one molecule to another molecule.
 Example: Hemoglobin has affinity for several substrates including oxygen. The affinity for oxygen is not as high as the affinity for carbon monoxide making carbon monoxide a toxic substance since oxygen cannot bind to hemoglobin when it is present resulting in suffocation.

 2.) Disassociation Constant (Kd): In scientific terms the affinity of a substance is measured by describing the concentration at which half of all the available substance is bound to a partner in solution. This is called the Kd, or the disassociation constant described in units of molarity or moles/liter denoted with a capital M. The Kd can vary depending on the pairs of molecules being described. This is important for things like neurotransmitters that have multiple binding partners but may prefer particular receptors over others.
 Example: A molecule that has high affinity will have a low Kd value since few molecules are needed to have half of them bind to its substrate.

 3.) Enzyme kinetics: This is a term that is used to describe how enzymes behave when they are exposed to a substrate. Enzymes are catalysts for reactions and their behavior is dictated by their intrinsic properties. When they are in solution with their substrate under the proper conditions they will exhibit a reaction that is related to their affinity for their substrate. Due to the constraints of their physical properties enzymes are limited at how fast they can react with their substrate to create a product (substrate+enzyme-> enzyme/substrate ->product+enzyme). This means that an enzyme has a maximum potential for the rate at which it can catalyze a reaction with the fastest enzymes limited only by diffusion (~10-9/Msec) with the rest falling below this limit. Each step of the process is subject to regulation making this process a lot more complicated.

 A long time ago in the beginning of biochemistry, scientists studied the rates and reactions of enzymes and discovered many properties of enzyme kinetics. There are many and may be too confusing to describe in detail here but there is an important lesson in all of this. Concentration matters!
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 Enzymes regulate vast and seemingly complicated processes by having different rates at which they catalyze reactions. These reactions are regulated not only by the enzymes themselves but by the reactants they use. This is how our body regulates everything inside the cell. If levels of a particular substrate rise too high then it can inhibit the enzyme that is upstream creating the substrate. Nucelotide synthesis is regulated in this way. DNA is comprised of four nucleotides, adenine, cytosine, thymine and guanine. Each is necessary in equal proportions to create DNA. When the enzyme the levels of one nucleotide rises it inhibits the enzymes that catalyze the reactions to create the other nucleotides resulting in a balance of available nucleotides in the cell.   
 These examples are useful because they can give us an idea about how the cell works autonomously. The cell's intelligence is based on the ability to react to changes in its environment. The way it does this is by creating a balancing act from the interplay between substrates, enzymes, cofactors and all of the other environmental stimuli it encounters. This interplay comes together at the level of the organism to provide us with robust responses to our environment. Here is a great example that relates to nutrition and everyday life.
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Credit: Human Metabolism Michael Palmer, MD, Department of Chemistry University of Waterloo Ontario Canada
(4.4-6 mM is average blood glucose of the blood)

This graph illustrates an important concept that actually can come in handy when thinking about carbohydrate metabolism. What is shown is three different versions of a molecule called the glucose transporter (GLUT). This protein comes in a variety of flavors and is denoted with a different number after GLUT. Each of the members of this family can transport glucose and some can transfer other sugars as well. What is shown on this graph is that there is difference in the rate at which these transporters will move glucose out of the bloodstream and into the cell. The brain is a glucose hungry organ and so its transporters have a high affinity for glucose to keep up with demands. The liver on the other hand only needs to soak up excess glucose that is circulating around in the bloodstream. The GLUT4 transporter lies in the middle of the two and is important since it is only called into action after high energetic demand created from keeping muscles under tension (i.e. weightlifting). This effort activates glycolytic pathways in muscle tissue quickly depleting the muscles stores of glycogen. Each transporter exists to serve a function of the body in order to preserve homeostasis.

"Sure, all this sounds good and dandy but how does this help me?"
 Great question! This topic is important because it relates directly back to health and nutrition. Our brains are like the glucose sponge of the body, it soaks up glucose all the time and its GLUT3 is quick to reach its maximum efficiency at relatively low concentrations. On the graph the GLUT3 line starts to max out at what is considered the "normal" blood glucose level. This makes sense because we want our brains to have all the energy it needs all the time. If we had to eat to get to optimal glucose levels for the brain then we may not survive all that long. Notice that as blood glucose levels rise the brain GLUT3 doesn't get any faster at transporting glucose from the bloodstream. This is an important fact and is analogous to a car in first gear. The GLUT3 protein trades its maximum velocity for a quick start. This means that once glucose levels go too high GLUT3 cant bring down blood glucose levels on its own at any significant rate. Excess glucose is toxic to cells beginning around 11mM and thus other systems are needed to keep blood sugar in an appropriate range.

 The bottom line of the graph depicts the liver transporter GLUT2. It is interesting to note because it is important for how fat deposition occurs. When blood sugar levels rise past the range at which they can be handled by the tissue GLUTs then insulin is released to help transport glucose into tissues. In addition to insulin the GLUT2 protein works to bring blood glucose levels down. GLUT2 is a slow transporter that gains velocity as concentration increases. The GLUT2 transporter is also found on the pancreatic islet cells that release insulin. It is the transport of glucose into these cells that causes them to release insulin in response to increased levels of glucose.

 Example: Say you were to consume a food item that was comprised mostly of simple sugars. Once digested, the quick release of sugars into the bloodstream will begin to overwhelm the mechanisms in place to keep blood sugar in its normal range. The rise in blood sugar causes the release of insulin along with the GLUT2 transporter in the liver soaking up blood glucose to turn into glycogen. Once glycogen levels are maximal then the excess transported glucose is turned into fatty acids.

 This is how the majority of weight gain occurs. When blood glucose levels rise the glucose needs to go somewhere and usually that somewhere doesn't help get my pants on. Adipose tissue is extremely sensitive to insulin and when there is excess glucose not only is glucose being turned into fat by the liver but it is also being stored in fat cells. This glucose storage needs water to occur which is where the bloating feeling and look of excess carbohydrates come from. Its about a 4:1 ratio of water to glucose storage that occurs in cells and is the first weight to be lost when adopting a lower carbohydrate eating regime.
 I want to end this discussion with a little bit of useful information.
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 Fact: Exercise can help us lose weight and control blood sugar levels.

 This may not be new or groundbreaking but it may make a lot more sense after all this information. Lets refer to the graph one more time and look at the GLUT4 line. This line shows that as blood glucose levels rise the GLUT4 transporter begins to pick up steam before the liver gets dibs on that blood glucose. This means that if timed properly we can eat carbohydrates and get them to the tissues that need them the most, our muscles. The GLUT4 transporter is tricky though, it only comes to the surface of cells in response to strenuous exercise. I repeat, STRENUOUS exercise. This doesn't mean running, walking, yoga or any other light to moderate exercise. While those activities will cause GLUT4 translocation it wont be to the levels the warrant massive carbohydrate repletion. Its translocation, or movement to the exterior of the muscle cell depends on the kind of exercise being done. Time under load is an important factor to consider when consuming carbohydrates for the intent to replete muscle glycogen. Choosing starchy carbohydrates allows the sugars to digest slowly whereas simple sugars will raise the blood glucose too high, too quickly to be useful for shuttling glucose exclusively into the muscle tissue since the liver will compete with the other transporters for glucose. Keeping glucose levels at the moderate range will allow more glucose to make it into the muscle cells over being deposited as fat. Gaining an understanding on how glucose is metabolized in our bodies can give us better insight into food choices and nutrient timing to achieve maximum results.  

The Paleo "diet" is plagued with a problem. Not one that arises from the actual recommendations made by its author Loren Cordain but rather from branding. The word Paleo is a reference to our common ancestors existing some 2.5 million-20 thousand years ago. The Paleo anachronism may bring to mind images of Flinstoneesque characters, pronounced brow ridges, protruding lower jaws and individuals adorned in leopard skin garbs living in rock homes (minus the pig trash compactor) . Continued explanation of Paleo can result in glazed over looks and the discussion may end with the listener missing the tenets of the diet or any of its guiding principles. The "diet" is actually the long-term application of habitual practice and lifestyle changes.

Some may be afraid of drinking the 'Paleo' Kool-Aid since it requires close examination of the way we live our lives. The food we eat, the ways we deal with stress, our interpersonal relationships, work, exercise, the way we sleep and for how long. All this change can sound daunting if one is living in discordance with what our human body was evolved to do. Changing a lifestyle can be difficult to impossible if the belief structure surrounding it doesn't change first. Believing that health is a priority and that the things that jeopardize it are not things that we are missing out on is essential to implement lasting changes. Putting health as the top priority makes all decisions easier. When we trade time to eat well, exercise and sleep sufficient hours, our levels of stress rise and we trade disease for health and well-being. Modern society does not promote human wellness as its top priority leaving the burden on the individual to create a healthy environment for themselves.

Regardless of our diets or lifestyles dogmatic views of the world will almost certainly lead to conflict. This results from an inability to change, to allow new information to add, subtract or modify our existing theories or worldview. This is the antithesis of the scientific method. Any eating regime or habitual practice unable to be modified is intrinsically flawed if new data cannot alter it. Allowing information to alter our ideas is essential to making informed and rational choices and is the heart of the scientific method. This can make a lot of people reticent to make a stand on any position since new information may lead them to retract their position or force them to adopt a new one. In an effort to save face many people will form alternate assumptions that ignore detrimental data in an effort to fit to their own worldview rather than to alter it.
There are people who want to make us believe that the Paleo diet is not viable because it discriminates against certain food groups or  labels a particular food as the root of all evil (baguette anyone?). This may be true in practice but is not what the underlying principles of Paleo are. Elimination of foods occurs from first principles derived from scientific data rather than on a purely subjective or ideological bias. The Paleo diet was created using primary scientific literature to form hypotheses, it makes testable assumptions and predictions along with being open to refinement through newly acquired data. Paleo is constantly changing as new information comes to light since it is rooted in the scientific method. This may make it seem sometimes that Paleo recommendations vacillate but like any theory it is open to refinement. Fad diets are constructed from anecdotes and suffer from individual variability and are generally not sustainable. They can also be loosely based on government recommendations for health which have been shown to be flawed and falsely modified to support corporate profit.

Paleo is More than Just Food
The Paleo diet was coined to describe a set of ideas about diet that would address issues with nutrition, metabolism and disease in modern society using anthropological and biochemical data. The use of the word "Paleo" belies the implications that it sets forth about the way that we view not only food but the way we live our lives. This diet can undergo modification to tailor individual sensitivities and genetics making it better to refer to the Paleo diet as the "Ancestral Template". The Ancestral Template makes a much clearer impression of what the aims of the diet/lifestyle are. It provides us with an evolutionary lens to examine the choices that we make in our lives and consequently our food choices.

The reason I prefer Ancestral Template is it points out the fact that its not just the common ancestors of all humans but also the ones that were evolving in disparate groups over the past few thousand years as well. This means taking into account not only how our common human relatives were adapted to their environments but also the variations in populations separated for thousands of years around the globe. Human beings exhibit adaptive radiation to the point where humans are found in all environments around the world. To say that everyone should follow Paleo canonically would be a poorly thought recommendation. Individual variation makes any global recommendations only a starting point with certain foods being more tolerated than others due to individual genetics and environment. This is why personal experimentation is so important to determine how Paleo fits into your life with your genetics.

The Ancestral Template makes assumptions about our optimal lifestyle through observing human behavior and understanding our common biology and physiological needs and constraints. The ideas promoted by the Ancestral Template are arguably all designed to make a person feel happy, adjusted and productive.
A short list of these practices: avoid anti-nutrients, reduce inflammation, exercise with movements that humans are mechanically designed for including sprinting/running/walking, reduce stress, sleep when it is dark, enjoy community and get adequate sunlight exposure.

The human experience is filled with choices with most of them made with partial information. Our health has been under investigation by humans possibly for as long as humans have cohabitated. Shamans and mystics were needed to heal humans when there was little information about the nature of disease as humans used their experiences to heal to the best of their ability. As more information came to light the use of medicinal plants and concoctions were applied to healing. Each discovery created new levels of health for humans. Science has given us the opportunity to evaluate and understand topics in depth to levels that no humans have ever had the ability to do. Antibiotics, vaccines and modern medicines are examples of how discovery can lead to new ways of understanding disease. Modern medicine  is our most powerful tool for cases of catastrophe but performs poorly in preventing disease. Applying the evolutionary lens to human health provides us with a set of practices to promote health before disease strikes.

Extending the ideas of the Ancestral Template to our relationships with the organisms we interact with adds another thread to a rich and vibrant tapestry of human health. Humans are animals and exist as part of an ecological web in which they evolved alongside all other organisms.

The Ecological Mindset: Beyond Paleo
The Ancestral Template attempts to look for the most ecological solution to the problem of understanding human health. This template is an extension of a greater principle at work I will term the ecological mindset; a way to view the world and our interactions with it to produce the most harmonious and sustainable outcomes. For instance, the ecology of our bodies consist of  a trillion of our own cells and a 10-fold greater number of other species' cells. These complex interactions create our metabolism, determine our mood, our sense of well-being and our overall health. Discord in the community we call self creates disease. When examining our choices in life we must examine the effects that our choices can have on this community called self along with the community of interactions outside of our self. Understanding what makes these communities operate at maximum efficiency will produce the best possible humans with healthy relationships. This is the goal of the ecological based mindset.

Adopting an ecological mindset is applicable to all areas of our life and has implications on our social, political and economic structures. Using a discriminate eye and thinking of ourselves as interconnected with the environment and within ourselves promotes a world filled with well-adjusted, energetic, friendly, healthy and happy people. Practicing the Ancestral Template and basing our life choices with an ecological mindset can be used to create a better world for all humans. It creates by working in harmony with our biology and ecology. Creating more efficient energy capture systems by promoting natural processes, using our environment to promote human health while creating self perpetuating systems underlies the ecological mindset. This mode of thinking puts emphasis on creating well-being in all systems  including our own local systems (i.e. our bodies, communities, cities). Ultimately the cost of this mentality is self examination, internal reflection and critical examination of all our actions and the impact they have on our ecology.
References:
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1. HarvardSchool of Pubic Health: the Nutrition Source,
Food Pyramids and Plates: What should you really eat? 2014
http://www.hsph.harvard.edu/nutritionsource/pyramid-full-story/
2. The Paleo Diet: Loren Cordain 2002