To maintain metabolic homeostasis and good health, the body communicates via innumerable signaling mechanisms and pathways, and with this complex network, the body does a great job of taking care of its needs. Unfortunately, this signaling network has the tendency to become dysfunctional as a result of novel environmental inputs sent into it by the modern, industrialized world.
Previously, I have discussed these dysfunctional signaling cascades at length to describe some of the pathways by which modern disease is, to a large extent, the product of dysregulated metabolic signaling pathways (i.e. energy dysregulation). When energy is sent down dangerous pathways (e.g. excess fat accumulation and/or irregular fat storage), the body can find itself in a state of hyperlipidemia and systemic inflammation, which is a strong internal signal that dysfunction is arising and that the body must take drastic action to attempt to fight off this danger. Downstream, this results in dangerous conditions, including insulin resistance, hyperinsulinemia, and hyperglycemia, a pathophysiologic state termed metabolic dysfunction.
By sending inputs into the body that result in dysfunctional signaling, the body loses its ability to properly regulate itself, allowing for a state of metabolic dysfunction and poor health to set in.
I have built up the Reprogrammed Systems Model describing this series of signals and pathways as its foundation. As it is these signals that are the primary driving force for modern disease, it is clear to see that it is towards these driving forces that we must put our attention if we want to effectively address the modern disease epidemic.
To counteract this pathophysiologic state, I have discussed at length how each individual can take action to avoid environmental inputs that send the body down these dangerous pathways of energy dysregulation. These actions comprise of dietary and lifestyle changes, including the avoidance of industrial foods (e.g. sugar, refined grains, and vegetable oil) and limiting of chronic stressors.
The avoidance of environmental inputs that drive these dangerous pathways will undoubtedly direct you down the road to good health. With an awareness of what you eat (and your stressful behaviors), you have the ability to largely control the pathways that sources of energy take through your body, thus helping to shift energy away from excessive and dangerous storage.
For most of you, this first perspective of the Reprogrammed Systems Model (we could think of this as the environmental inputs perspective, or as the energy in perspective) will be enough to make great strides forward, and may possibly even be enough the help you sail through a long, healthy life.
However, I would be doing a poor job if I left you believing that this energy in perspective is all you need to ward off poor health. As we know from the previous article on energy balance, energy enters the body, is shuttled around, and eventually leaves the body. To create a more effective approach to addressing modern disease, we must expand our perspective of this model to include an additional focus on what is happening from an energy out perspective.
With this expanded perspective of the Reprogramed Systems Model, my hope is that we gain a more thorough understanding of what really needs to happen to fully address energy dysregulation – that is, a shift of energy away from excessive and dangerous storage and instead towards oxidation.
Expanding the Reprogrammed Systems Model:
To do this we are going to think about the Reprogrammed Systems Model from two slightly varied perspectives.
- In the last article, I discussed how overall energy balance is an important concept to understand when it comes to addressing modern disease. With this article we will continue our work integrating energy balance with the signaling mechanisms forming the Reprogrammed Systems Model. To lose weight and improve health, a calorie deficit is necessary. However, the method used to reach this calorie deficit matters. Let us move forward continuing to build an effective method to create a calorie deficit.
- I have kept our focus on two main perspectives of the Reprogrammed Systems Model. We began by understanding the internal mechanisms which form particular pathways for energy to flow. I then added in how particular environmental inputs tie into these pathways. Now, let us think about the final perspective of this model: energy output.
The Reprogrammed Systems Model Meets Energy Balance
Energy balance is a tool that can be used to help us think about addressing the excess energy problem. Excess energy in circulation is a key factor contributing to the progression of modern disease, and thus it is necessary that we address the body’s hyperenergetic state, which means a calorie deficit must be created.
As we know from energy balance theory, to lose weight we must create a calorie deficit, which means more energy must be expended than is received. However, the method we use to do so matters, and the method is often not as simple as “eating less and exercising more.”
Rather, by using a method that is aligned with the design of the human body – a method that utilizes calorie balance while taking energy signaling into great consideration – we can work towards effectively addressing weight loss and modern disease.
By examining the Reprogrammed Systems Model from an energy balance perspective, we can easily notice a few things. First, the energy that enters the system can go down three primary pathways: storage, oxidation, or conversion. We already know some of the signals that send energy towards storage (e.g. irregular/excessive insulin secretion), and we additionally know how we can use this information to make better decisions that lead away from chronic and irregular fat storage (e.g. consume foods that do not spike insulin).
We also talked a bit about certain conversion pathways that ultimately lead to fat storage. For example, the consumption of sugar or refined carbohydrates can result in a large load of sugar sent into the bloodstream and to the liver, of which the liver simply converts to fat for storage.
Now, let us move forward by examining the last portion of this model in greater depth: Energy oxidation and energy output.
Energy Dysregulation Drives Fat Accumulation: The Energy Out Perspective
A healthy body is one that can properly store, release, convert, and burn energy. We’ve put a lot of work into understanding these first concepts. Now, let us finally turn our attention towards the last concept – understanding the signaling involved in the oxidation of energy.
As we have learned while discussing energy regulation pathways, the biology supporting the inputs into the human body is incredibly complex. Energy accumulation is so much more than simply eating too much – it also has to do with the form of that energy and how the body receives that particular form.
Similarly, energy out is so much more than simply burning more calories through exercise. Energy expenditure involves a number of mechanisms and pathways, most of which have nothing to do with how much an individual decides to exercise on any particular day.
Processes involved with Energy Out:
- Sleep
- Movement
- Cognitive Processes
- Metabolic Processes
To understand energy expenditure, I could walk you through the optimization of each of these energy-burning pathways. This method would involve picking apart the many pathways through which energy is burned and zooming in on each pathway to maximize the amount of energy that is utilized.
However, I am a strong believer that this linear approach is not the most effective way to solve the problem. In addition to it being time-consuming to understand each pathway, we also risk the strong possibility of these pathways being co-dependent and thus miss out on understanding the true complexity of the system.
Instead of taking you through each possible pathway of energy oxidation, I am going to take an approach that will help you understand how a healthy body, overall, is more efficient at burning more total energy (the systems approach).
Remember, it is energy dysregulation and metabolic dysfunction that results in the build-up of excess energy, and that this excess energy combines with other factors to result in modern disease. Let us now continue on with these same concepts using the Reprogrammed Systems Model to address the key mechanisms contributing to the far end of the energy regulation process: the halting of energy oxidation.
Refresher: Macro and micro signals
A number of complex signals drive energy regulation and metabolic pathways. To keep things simple, I categorized these signals into two types:
- Macro signals drive the bulk flow of energy
- Micro signals indirectly affect energy flow via their influence on the functioning of the components involved in the system.
Previously I have focused our attention on one primary example from each category:
- Insulin is the body’s primary macro signal. When insulin is elevated the body sends energy in the general direction of storage. Only when insulin is low can the body effectively burn energy.
- Inflammation is a primary micro signal. A pro-inflammatory state signals to the body that it needs help fixing a problem. Unfortunately, when it comes to metabolic dysfunction, the body’s response to this signal is often quite dangerous (e.g. insulin resistance).
Moving forward now, I am going to expand this knowledge with two new signals:
- Macro signal: Glucagon
- Micro signal: ROS
As we will see, with the basic knowledge of these four signals (macro: insulin & glucagon; micro: inflammation and ROS), we have the ability to make enhanced decisions leading us directly down the Road to Good Health.
Let me clarify a few concepts and some terminology.
- Remember, when we want to burn energy to address the excess energy accumulation problem, what we really mean is that we want to burn fat. Being more technical here, this means we want to oxidize fatty acids: it is the oxidation of fatty acids that results in fat leaving the body.
- When the mitochondria oxidize fuel for energy production, the molecule that is formed for use as energy by the body is ATP. A number of metabolites are also formed in the process, which will become relevant soon.
- The bulk of ATP synthesis, particularly speaking of fat oxidation, occurs at the site of the mitochondria.
- As always, remember that this is not a simple, passive process. There are an incredible number of regulatory mechanisms involved fatty acid metabolism, including the process of getting fatty acids into a cell, processed, and then sent into the mitochondria.
Based on the fact that fatty acid oxidation is what needs to occur to effectively address the excess fat accumulation problem, this discussion of energy burning will focus on fat oxidation, which will keep our attention at the site of the mitochondria.
Reprogramming the Body for Fatty Acid Oxidation
Remember back to a particularly useful diagram – when energy enters the body it can go in any number of directions.
If we want to lose weight by burning a large amount of fat, then we need to ensure that this system is programmed for these particular pathways:
- Fat storage –> oxidation
- Stored fat must be released, sent to mitochondria, and oxidized
- Proper glucose <–> glycogen conversion and usage
- glucose (the free form) and glycogen (the stored form) must be converted and used wisely. This form of energy is important for the body, but its overuse is the very thing we are aiming to avoid.
This means that it is not necessarily true that we need to burn off a whole bunch of energy (the calorie centered approach). Rather it means that we need to get the body programmed to send stored fat towards oxidation, while sparing energy from other forms (e.g. glycogen, muscle, and other tissues).
So how is this done? How do we get the body to direct the food we consume to avoid fat storage, and also to allow the fat stored in the body to go towards oxidation?
1. Think About Macro Signaling
First, we need to remember our macro signaling. You may remember that there is one particular signal that halts the flow of energy (more specifically, of fat) from going into the cell and into the mitochondria to be oxidized.
That signal is none other than insulin. When insulin is elevated, the cell becomes unable to burn fat for fuel. This means that, if an individual is trying to burn fat (as any healthy individual needs to do), then they will have a much more difficult time doing so when there is a strong insulin signal.
I cannot stress enough the role that insulin has to play in energy dysregulation and metabolic dysfunction. As the body’s primary energy storage hormone, its excess and irregular secretion, brought on by an industrial foods based diet, is arguably the most significant factor driving modern disease.
However, insulin is not the only important signal involved in this system. To get an even better understanding of how the body handles energy storage and oxidation, let me bring in the new hormone signal: glucagon.
You can think of glucagon, quite simply, as your energy release hormone. While insulin signals to cells to store energy, glucagon signals to cells to release energy into circulation so that it can be utilized for ATP synthesis. As the goal is to release large amounts of fat from storage, we need to make sure that glucagon is on our side.
We already know how to avoid the excessive and irregular release of insulin: Refined foods and high carbohydrate meals spike blood sugar, resulting in a spike in insulin. By avoiding these foods and instead consuming real, whole foods – foods that are high in fat and contain adequate amounts of protein – we can minimize the release of insulin.
The good news is that the same guidelines can, for the most part, be followed for glucagon secretion. Remember, if we want to release lots of fat for oxidation, glucagon needs to be elevated. This means that chronic inhibition of glucagon should be avoided.
To keep things simple, you can think about how your diet influences glucagon as macronutrient-based: Diets high in carbohydrate tend to result in inhibited glucagon secretion, while diets higher in fat and protein tend to elevate glucagon levels.
Overall, quite simply, you can think about the lowering of glucagon and elevation of insulin as driven by high carbohydrate meals. If you consume a high carbohydrate meal, insulin becomes elevated while glucagon release is inhibited, resulting in a high insulin to glucagon ratio, putting the body in fat storage mode. By consuming a lower amount of carbohydrate while consuming more fat and protein, the resulting low insulin-to-glucagon ratio allows for fat burning.
Be careful though, as it is not just the type of macronutrient that matters – quality is just as important. Consuming a load of plant-based foods that are high in fiber, polyphenols, and other nutrients will likely end up contributing to a better ratio. Consuming refined foods, even refined protein, is a sure way to send these hormones in the wrong direction, sending you down the road to fat storage and halted fat oxidation.
Although this is not so relevant to insulin and glucagon, the avoidance of refined fats, particularly refined polyunsaturated fat (i.e. vegetable oils), is also of utmost importance, albeit for different reasons. I bring this up here because it is common for people to hear the message to avoid processed carbohydrate, and to fill that void with refined fat. This is not a healthy way to do this. Consuming large quantities of refined vegetable oils may not set off insulin, but it will send you down other pathways towards poor health, which is missing the entire point.
Note – glucagon is incredibly interesting and relevant, but it doesn’t get the attention it deserves. I recommend checking out Dr. Ben Bikman, particularly his lectures on the topic of insulin:glucagon ratios.
The Finishing Touch: Micro Signaling in the Mitochondria
To finish things up, we have one more concept to understand. We now know how the foods we consume can lead to halted fat oxidation through the direct flow of energy, but now we have to understand how things are operating from a functional point of view. To do so, we need to understand micro signaling at the site of fat oxidation.
To take energy as we know it (as carbohydrate, fat, or protein), and then to convert it into ATP, the body has to go through many steps. That energy must be digested, sent around the body, potentially stored or converted to other forms, and then finally sent to the cell for oxidation. The final step in this process is completed with the help of an incredible biological machine: the mitochondria.
The mitochondrion is no simple machine. It continuously senses the energetic state of the cell, using this information to decide what to do with the energy it receives. That energy can come in a number of forms and is dealt with in a different manner depending on the form of energy, the energetic state, and the state of the machinery itself.
To put things into perspective, I want us to first think about the scale of the system we are discussing. There are hundreds of trillions of mitochondria in each human body. A cell can contain thousands of these little machines, which are continuously processing ATP. For reference, a common statistic tossed around is that the body produces its own weight in ATP every day.
In terms of what the mitochondria is actually processing – it is taking molecules consisting of several atoms and stripping away individual atoms (e.g. the removal /addition of hydrogen). Thus, when I speak of micro signals here, we are literally discussing atomic, or even subatomic processes.
Be careful here though – don’t be fooled by the microscopic size of this system, as its dysfunction has consequences that accumulate, feedforward, and emerge as dysfunction at the macroscopic, life-altering level.
Getting into these signals now, let us focus on what is arguably the most significant signal in this system: ROS, which stands for reactive oxidative species. As the mitochondria processes energy for ATP synthesis, electrons are passed down a chain of complexes embedded in the mitochondrial membrane (i.e. the electron transport chain). Each of these electrons is, ideally, destined for an oxygen molecule(which produces water). Of course, this process is not always perfect, which means that sometimes this process is incomplete, leaving an oxygen radical free to leave the complex with the potential to become a reactive oxygen species.
Mitochondria work as a balanced system. As they oxidize energy, oxygen species are naturally created. This isn’t inherently a bad thing because, as nature is designed, there are systems in place to balance the formation of these oxygen species. It is the job of antioxidants to gather up these free radicals before they can go on to cause trouble.
However, when a shift in this balance occurs (i.e. too many oxygen species and too few antioxidants), then the system becomes overloaded with oxygen species, putting the cell in a dangerous situation.
ROS tend to get a bad rep, as their presence tends to result in damage and/or dysfunction. For example, ROS are present at the scene of the crime for most pathophysiologic metabolic conditions (e.g. insulin resistance). However, I don’t like to judge ROS as an inherently bad thing – something that needs to be minimized as much as possible. Instead, I see ROS simply as a signaling mechanism – a signal that alerts the body that a potential problem has arisen and that it needs to respond. For example, the elevation of ROS can alert the cell that a mitochondrion is losing its ability to properly function and that it should be killed off (mitophagy) so that a new, healthy mitochondrion can take its place.
Overall, I will argue that ROS production is a beneficial signal because it alerts the cell that a response is needed to help the distressed mitochondria. Unfortunately, as is the case with many signals arising from a body living in an industrialized world, this signal is dealt with in a manner that can lead to further damage.
The elevation of ROS is a signal that the mitochondrion is in distress, and that the cell needs to do something. The responses to this misbalance are far and wide, but most significantly for this discussion is the resulting insulin resistance. ROS can form because too much glucose is being pushed through the mitochondria. The body responds, logically, by becoming insulin resistant, thus disallowing glucose to enter the mitochondria.
As we all know, insulin resistance is a primary condition driving metabolic dysfunction and modern disease. When cells lose the ability to respond to glucose, yet the body continues to receive large amounts of glucose, the system is on a clear path toward disease.
Also, note that this is a major site of cancer-based research – the inability to properly oxidize energy is tightly linked to cancer overall – see metabolic theory of cancer. Dr. Thomas Seyfried is a great source.
To counteract this dangerous phenomenon, it is not that ROS production needs to be shut down. Shutting down ROS production may help mitigate problems downstream, but it does not necessarily address the larger issue – that issue being the cell’s mitochondria in distress. Rather, the system needs to be put back into a healthy balance, as a healthy balance is a sign that the machinery is working properly and dealing with a healthy load of energy.
Based off of this logic, let us move forward with the Reprogrammed approach by focusing on simple, practical options that you have to better program your body for optimal mitochondrial functioning.
Reprogram your Body for Optimal Mitochondrial Functioning
Overall, it helps to think about the mitochondria found in the typical modern day body as under an incredible load. They work all day every day to handle the absurd load put on them by the incredible amount of energy sent through their ATP production lines. On top of this, these mitochondria are withdrawn from the proper resources they need, including the antioxidants naturally found in real food. Finally, to make matters worse, they are regularly exposed to dangerous toxins – foreign molecules that interfere with their ability to properly function.
To address the burden and distress the mitochondria, I suggest starting with the following:
- Stop consuming refined foods, particularly in the form of refined carbohydrates
- A high carbohydrate or refined foods based meal sends an overload of energy to the cell, putting the mitochondria in overdrive. Give the mitochondria a break by consuming real, whole foods – foods that release energy in a controlled fashion, a manner in which cells are designed to oxidize fuels.
- Give the mitochondria a break by eating less frequently
- Remember that point I made about ROS being a signal that the mitochondria need help. Remember the additional point I made about this signal becoming detrimental in today’s industrial food-based society. Here’s a problem: Mitochondria become overstressed due to the load put on them by an industrial foods based diet. However, when they try to signal for help (via ROS production), the cell is unable to help them out because the cell is under a constant load of incoming energy.
Instead of overloading your cells and mitochondria with a load of energy all day every day, allow them some time to take care of themselves by stopping the constant inflow of food.
Reprogramming your mitochondria for optimal fat oxidation begins with eating real, whole food – food consumed in 2 or 3 substantial meals. Preferably, these meals are consumed in a window of 10-12 hours or less. By consuming your food in 2-3 meals all within a 10-12 hour window, you give your cells and the mitochondria contained within the downtime they need to assess and respond to their own needs (note: see autophagy or mitophagy for more on this concept).
In the name of providing you with practical advice that you can focus on in the next few weeks, I am going to stop here. My belief is that this is the most important information you need to get started on your journey down your Road to Good Health. Down the road we can talk about how exercise or other techniques can be useful in this process.
Beginning Your Journey on The Road to Good Health
My hope is that, with this first piece of advice, you will be well on your way to Reprogramming your body for fat burning. By building up a strong force of healthy mitochondria and directing excess fat in their direction, the body is in great shape to begin burning off excess fat accumulation and to move towards a state of healthy energy regulation and metabolic function.
Of course, there is much more knowledge that can be useful when optimizing this process. For example, we haven’t even begun to discuss how exercise can be implemented, or how specific foods can be used or removed from your specific diet.
The thing is, all of this can become tricky when combined and put into practice. Instead of overwhelming ourselves with an overload of information, I instead want you to focus on step 1: just eat real, whole foods, and aim to do so in 2-3 meals without snacks.
Once this has been accomplished, then we can begin to discuss some of the other tools you can use to Reprogram Your Health.
If you’re interested I’ll lay out the full plan up next in one last article to this introduction series.