Human metabolism
If there was such a thing as a car that could seamlessly switch between using petrol and diesel for fuel, it would not be nearly as sophisticated as human metabolism. When we are healthy, we can use different fuels in a way that can’t be done with even the most modern technology.
Our metabolism is the result of two million years of evolution during which we survived seasonal and multi-year ups and downs in different types of food from animals and plants. However, to fully take advantage of the metabolic sophistication we are each capable of, we must eat in a way that keeps us healthy, and by that, I mean metabolically flexible. At all costs, we must avoid a condition called insulin resistance. For perspective, I believe that I once ate things that caused me to become insulin resistant, and that led to my heart disease.
“...to fully take advantage of the metabolic sophistication we are each capable of, we must eat in a way that keeps us healthy…metabolically flexible.”
Understanding how our metabolism works is important because it explains why an outwardly healthy athlete following conventional dietary and medical advice (me) can still contract a serious chronic disease. As I discovered, our metabolic fate is determined predominantly by the types of nutrients in our food. The balance of calories in versus calories out can be quite unimportant.
In this paper I’ve tried to describe how our metabolism works, what to eat to stay healthy, and what can happen when we don’t.
Note that I’m describing only the nutrition that is derived directly from our food. Microbiome accessible carbohydrates, fibre, and the ways in which we derive energy from our microbiome have been described previously.
What is human metabolism?
Metabolism is the conversion of nutrition into energy for the purpose of fueling the things our body needs.
Healthy – metabolic flexibility (insulin sensitivity)
Three major (macro) nutrients in our food are used as starting materials for fuel, namely carbohydrates, fats, and proteins.
Our bodies preferentially use carbohydrates and turn them into blood glucose
Blood glucose is kept not too high and not too low by the hormone insulin which sends glucose to the parts of the body where it is needed (brain, muscles, etc.)
When we eat more carbohydrates than we need immediately, our liver turns them into fat for storage and later use
When carbohydrates are not available, our bodies will use stored fat for fuel. In extreme conditions, stored protein (muscle) will be used for fuel
Unhealthy – insulin resistance
When we consume too much carbohydrate, we produce too much insulin and our body (brain, muscles, fat stores, etc.) become “numb” to its messages and stop absorbing glucose from our blood. This is called insulin resistance
Insulin resistance leads to even more insulin production. In this state, blood sugar and insulin remain long-term at unhealthy levels leading to disease
Considering bioavailability
There’s nothing complicated here. Things in our food are considered bioavailable if we can absorb them from our intestine. In other words, they are biologically available to our bodies. Processed carbohydrates contain many sugars and starches that have been changed from natural whole food into simple processed components which are absorbed by our bodies very quickly.
Understanding macro-nutrients
Our energy comes from bioavailable carbohydrates, fats, and proteins in the food that we eat, from fat we have stored, and occasionally from protein stores (muscle).
I try not to eat any highly processed food (carbohydrates and seed oils especially) because many of them promote insulin resistance and other forms of poor health.
Carbohydrates
When we do eat carbohydrates, our body will use those before fats and proteins for energy. This means that the carbohydrates we eat are likely to determine whether we remain metabolically flexible or are likely to develop insulin resistance and ensuing ill-health. The key to staying healthy, is to consume natural whole foods that are low in processed sugars and starches.
Fats
Fats are unlikely to affect metabolic flexibility. However, artificial fats can cause long-term (chronic) inflammation which is also unhealthy. We’ll discuss that another day.
Proteins
Like fat, proteins are unlikely to affect metabolic flexibility. However, we do need to be aware of proteins combined with sugar, seed oils and grain-based pastries. I also avoid grain-fed meats and farmed fish because their feed causes them to accumulate unhealthy fats.
Healthy metabolism –
switching between types of fuel
The most important thing to remember is that our use of macronutrients is prioritised in favor of carbohydrates first, then fats, then proteins (Figure 1).
Figure 1. Healthy macronutrient prioritisation. The hormone insulin acts like an interactive traffic light to ensure that we use available macronutrients in a metabolically flexible way. Our liver acts in tandem with insulin to provide energy in the form we can use
Sugars and starches are broken down into glucose which is the most common carbohydrate starting material in human metabolism. Any glucose not used for fuel may be stored as another carbohydrate called glycogen (see glossary) or converted to fat. We use glycogen as a short-term carbohydrate store for quick use and fat reserves as a longer-term energy store.
If glucose isn’t available, either because we didn’t eat carbohydrates or we have exhausted our glycogen store, we will switch to metabolise fats.
Protein is a little different from carbohydrates and fats in that it is not typically a primary source of metabolic energy, and is instead typically used for things like cell building and repair. There are exceptions to this, particularly for those of us on a so-called carnivore diet (only meat) or at times of prolonged absence of carbohydrates and fats in the food we eat.
Our livers act as the chemistry factory where different fuel sources are converted as needed. An example is the conversion of excess carbohydrates from our food being converted into fat for storage and future use.
“Insulin is the main hormone involved in human metabolism and may determine whether we are healthy or not.”
Healthy metabolism - how do we switch between types of fuel?
You may have heard of the hormone insulin because of its role in treating diabetic patients control their blood glucose. Insulin is the main hormone involved in human metabolism, and may determine whether we are healthy or not.
Insulin has two main roles. Firstly, it keeps our blood glucose level within a safe range, ensuring that we have enough for our energy needs and that it does not become dangerously high. Insulin’s second role is analogous to a very dynamic and interactive traffic light essentially ensuring that the macronutrients available are used for energy as summarized in Figure 1.
Insulin responds to the levels of glucose in our blood and signals appropriately to our organs to keep blood glucose at a steady and healthy level, irrespective of what we are eating.
Unhealthy metabolism - insulin resistance
When we eat large amounts of bioavailable carbohydrates, especially those extracted from natural food and turned into highly processed products, over a long time, our blood glucose levels remain high, and our body responds by producing more and more insulin as it tries to keep our blood glucose within a safe range. This causes our blood insulin level to remain constantly high rather than go up and down as it does in a healthy state of metabolic flexibility.
“Insulin resistance represents a disintegration of the glucose-insulin signaling mechanism at the centre of healthy metabolic flexibility and it is associated with a range of so-called chronic diseases...”
Constantly high levels of insulin means that our cells are always being signaled to take up more glucose for energy. It also means a constant signal to our liver to create fat for long-term storage. Our body fat cells eventually stop responding to the insulin signal at which point fat may be stored in our livers. This process of ever-higher insulin being ignored by our cells becomes the vicious cycle that is insulin resistance.
Insulin resistance represents a disintegration of the glucose-insulin signaling mechanism at the centre of healthy metabolic flexibility and it is associated with a range of so-called chronic diseases (e.g., obesity, type-2 diabetes, poly-cystic ovarian syndrome, hypertension, dementia, cancer, and non-alcoholic fatty liver disease), including heart disease. In essence, when our cells become resistant to its signal, insulin changes from our most important metabolic hormone to one of the most harmful to human health.
“…there is no One True Diet that works for all.”
Metabolism is personal
Too much bioavailable carbohydrate in our diet is unhealthy. However, it is also true that we all respond differently to the things we eat and the variation from person to person is large. This means that some people will be able to eat more bioavailable carbohydrates than others without developing insulin resistance. Individual variation is a phenomenon I’ve encountered repeatedly in my nutrition research, and I can’t make the case more clearly than Tim Spector:
“…if you want to find foods that work best with your metabolism, then you need to know your personal nutritional response – something that can’t be predicted from simple online genetic tests. We all have our own personal tastes and preferences when it comes to food, so it makes intuitive sense to think that our personal metabolisms and responses to the foods we eat should be different too. But scientific research is only just catching up with this gut feeling, proving that everyone is unique and that there is no One True Diet that works for all.”
What’s worth remembering?
I am an example of someone who followed the rules and looked healthy on the outside but was quite sick inside.
As I discovered, our metabolic fate is determined by the types of nutrients we consume. The balance of calories in versus calories out is a secondary consideration and may be quite unimportant. We evolved to eat a range of natural whole food types and cannot remain healthy under a constant river of bioavailable carbohydrates from processed dietary products. However, we all respond uniquely to what we eat, to levels of insulin in our blood, and to insulin resistance if it develops. I encourage you to understand your own metabolism and eat what you think makes sense for you.
Bibliography
Bikman, B. (2020) Why We Get Sick. Dallas: BenBella Books
Feinman, R.D. (2019) Nutrition in crisis: Flawed studies, misleading advice, and the real science of human metabolism. 2nd ed. White River Junction: Chelsea Green Publishing
James, W.P.T. et al (2019) Nutrition and its role in human evolution, J Int Med, 533-549
Kendrick, M. (2021) The clot thickens: The enduring mystery of heart disease. London: Columbus Publishing
Lustig, R. (2021) Metabolical: The truth about processed food and how it poisons people and the planet. London: Hodder and Soughton
Pontzer, H. (2021) Burn: The Misunderstood Science of Metabolism. London: Penguin Random House
Spector, T. (2022) Food for Life: The New Science of Eating Well. London: Penguin Random House
Taubes, G (2020) The case for Keto: The truth about low-carb, high-fat eating. London: Granta Publications
Glossary
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A complicated molecule derived from the metabolism of macronutrients and acts as the main fuel used by all human cells
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The simplest and most common carbohydrate used as a starting material for human metabolism and energy production
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A complex carbohydrate (highly branched polymer of glucose) that serves as a storage for excess glucose. Glycogen is stored in the liver and in muscles. We typically store only 2,000 calories worth of energy (500 in the liver and 1,500 in our muscles) so it’s only for short-term use. Our fat reserves contain much more energy and are used for longer-term storage.
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The most important hormone controlling the major events in metabolism—storing fat and carbohydrate as glycogen, encouraging protein synthesis. Levels of insulin in our blood are controlled by glucose in our blood
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Reduced response of our cells to insulin which causes our body to produce even more insulin to keep blood glucose at a safe level. This can occur when we eat large amounts of carbohydrate over long periods of time. When our cells become insulin resistant, we need to have high levels of insulin in our blood at all times to make our metabolism work. Those high levels of insulin can lead to things like heart disease, obesity, type-2 diabetes, poly-cystic ovarian syndrome, hypertension, dementia, cancer, and non-alcoholic fatty liver disease, amongst others.
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The most important chemical reaction centre in the human body and an important glycogen store for quick release to maintain blood glucose levels. The place where proteins and fats are converted for use in metabolism at times when carbohydrates from food are low
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The ability to switch between using carbohydrates, fats, and proteins for energy
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A constellation of disorders caused by insulin resistance Metabolism – the way our cells use and expend energy. Can be modified by many factors including sex, age, exercise, illness, body weight, and nutrition