The metabolic flexibility of the human body

Humans have evolved to have very efficient bio energy fuelling systems. We are a species that can withstand periods of food abundance and scarcity, largely due to our metabolic flexibility or hybrid systems. Our body’s ability to efficiently adapt our metabolism to different energy sources depending on demand and availability, maintains our energy homeostasis. In simplest terms, it is our cell’s capacity to switch between using stored glucose and internal fats.

Modern society, particularly western, has been geared to more a glucose-dominant state with caloric excess and a nutrient poor diet. This combined with a more sedentary lifestyle and decreased energy expenditure, an overall decrease in manual labor and over reliance on technology, can be identified as major contributory factors in our loss of metabolic flexibility.

Scientific research has shown that Insulin use and sensitivity is a key aspect to our overall metabolic health, ageing, vitality and longevity. When Insulin resistance happens, it can be linked to weight gain, obesity and metabolic disfunction and can often be a precursor to type-2 diabetes. Metabolic inflexibility not only gives rise to obesity and type-2 diabetes, but also most other NCD-like cardiovascular diseases, chronic inflammation, reduced immune function, and an increased risk for certain cancers. 

Metabolic flexibility can be optimised through proper meal timing, food choices and exercise. The saying “You can’t out run a bad diet” springs to mind and in this context has real meaning.

Mitochondria are central to our metabolism as they are the powerhouse of the cell; where energy from the food we eat is converted to cellular energy. The capacity of our mitochondria to adapt to different fuel sources namely Glycogen - sugar or FFA - Fats is essentially what defines metabolic flexibility on a cellular level, and thus mitochondrial function.

Metabolic flexibility involves nutrient responses, uptake, transport, and storage so as burning these nutrients is optimal for fuel. Our complex biochemical-electrical systems act in response to the type, timing totallity of Nutrients- Food we eat, don’t eat (intermittent fasting), meal composition (protein, carbs, and fat), exercise, temperature (e.g., cold exposure), and is influenced by numerous hormones.

The key message of this complex bio system is that chronically eating and always having a caloric surplus doesn’t help. It impedes our metabolic flexibility and promotes insulin resistance, with extra calories from sugar based foods leading to obesity and metabolic disfunction.

When it comes to the relationship between insulin resistance and metabolic flexibility, the main driver is the level of obesity and the amount of skeletal muscle mass. Skeletal muscle size and function is so important for metabolic flexibility because they account for the very large majority of glucose disposal, and therefore plays a main role in glycemic control and insulin sensitivity. It has been suggested that skeletal muscle mitochondrial dysfunction precedes insulin resistance, as mitochondrial adaptations in the skeletal muscle of type-2 diabetics. 

If you’re concerned about your metabolic flexibility look to all the key aspects mentioned above:

Food type, timing totality of Nutrients - Food we eat, don’t eat (intermittent fasting), meal composition (protein, carbs, and fat), exercise, temperature (e.g., cold exposure), and is influenced by numerous hormones. But also another key here is Muscle function based around activity, resistance training and EXERCISE!

Without a shadow of a doubt, a sedentary lifestyle year after year will do a major disservice to your metabolic flexibility. Whether you’re running, cycling, lifting weights, or simply working around the yard, regular exercise will help you to improve mitochondrial function and metabolic flexibility. Exercise increases the activation of AMPK, an important nutrient sensor involved in increasing mitochondrial quality and quantity through the expression of several transcription factors and co-activators. Through several complex pathways, mitochondria respond to exercise by replicating, growing, and building a stronger mitochondrial network (mitochondrial biogenesis). Combined with a caloric deficit (further increases AMPK), and thus weight loss. Regular exercise has been shown to improve insulin sensitivity, mitochondrial content, and metabolic flexibility in both normal and overweight participants. In addition, exercise stimulates insulin-independent glucose uptake, meaning glucose can enter your cells without the help of insulin (a major advantage!).

If you simply go for a 10-15 min walk after eating a meal (especially if it’s carbs) you will reduce the postprandial glucose spike and insulin secretion, which simultaneously stimulates glycogen replenishment and fat oxidation. The take home message is that exercise is the surest way to get those mitochondria firing, promote glucose disposal, insulin sensitivity, and improve metabolic flexibility.

But you can also eat less, eat better, Increase your metabolic flexability to help lose weight! It’s easy right, especially with the help of key Keto products such as those here at GloNua.

As highlighted already, being overweight and frequent feedings impedes metabolic flexibility. In contrast, eating in a caloric deficit helps the body breakdown stored fat in places we don’t want it stored (visceral fat) which is likely very important for restoring obesity-related metabolic inflexibility. In the study mentioned previously by Kelley et al., weight loss in previously obese participants improved insulin sensitivity and their response to insulin infusion, indicating improved metabolic flexibility.

Going extended periods without eating at all, as you would with intermittent fasting or prolonged fasting, allows the body to enter periods of low insulin and high glucagon, forcing the mitochondria of our cells to maximize fat oxidation. Intermittent fasting can be something you practice daily (e.g., 16/8 time-restricted feeding) or periodic multi-day fasts (e.g., 48-72 hour fasts). If you are starting at a place of poor metabolic flexibility, you may find it difficult to fast, and it is recommended that you start slow (~10-12-hour fasts) and work your way up to longer fasts.

How caloric restriction and intermittent fasting may work to improve metabolic flexibility is intuitively easy to understand. If we stop eating, we essentially force the body to burn its stored energy through lowering insulin and elevating glucagon. Since we only store minimal amounts of glucose as glycogen (relative to how much fat we can store), glucose can only sustain us for so long until we need to make the switch to fat. The resulting cascade of cellular events (e.g. activated AMPK, enhanced mitochondrial activity) ensures we have energy needs met, although the rate of transition may vary considerably between individuals.

Can you improve metabolic flexibility by removing carbohydrates from the diet independent of caloric intake or weight loss? Maybe!

We certainly need more research to help clarify because most studies using carbohydrate-restriction for improving disorders associated with metabolic inflexibility are often confounded by simply producing a calorie deficit (ie. subjects lost weight), so it’s hard to tease the two apart. That said, athletes who follow ketogenic diets show significantly greater capacity to burn fat, which is likely part of “training” the metabolism to use fat as fuel. Also, a study in obese men found significantly increased fat oxidation relative to glucose after a short term ketogenic diet, compared to an isocaloric balanced diet. Since a ketogenic diet mimics the fasting state in a lot of ways, it is very possible that periodic ketosis induced by a ketogenic diet can be used to improve metabolic flexibility on the fat-burning end of the spectrum. The increased fat oxidation is likely driven by the suppression of insulin signaling associated with a ketogenic diet. The potential caveat is that it may come at the cost of reduced capacity to burn glucose (e.g., suppressed insulin reduces PDH activity) if one sustains carb restriction for long periods of time. Whether that is an issue is not well-known, nor does it matter if you are using a ketogenic diet to manage a disease process, like epilepsy. However, by definition, metabolic flexibility is the ability to switch back and forth between glucose and fat, so if you are following a ketogenic diet for general wellness, periodically kicking yourself out of ketosis may actually be of benefit in terms of metabolic flexibility. The simple solution could be to simply couple a lower carb diet (like 100g/day) with time restricted feeding. Introducing small amounts of carbs in occasionally and keeping your body “hungry” for carbs (ie. keeping low fasting glucose levels) may allow you to increase insulin sensitivity while also enhancing carb tolerable and metabolic flexibility.

In summary, if the goal is to be as metabolically flexible and insulin sensitive as you can be, you want to have a high tolerance for carbohydrates, while also being a very efficient fat-burner. And it’s very unlikely that you will achieve this by eating all the time, being overweight, and not exercising. Depending upon personal preferences each individual will need to adjust dietary patterns, fasting and exercise selection to fit their lifestyle, but when these things are combined together that will maximize your metabolic flexibility.

Impaired mitochondrial function often results in excessive production of reactive oxygen species (ROS) and is involved in the etiology of many chronic diseases, including cardiovascular disease, diabetes, neurodegenerative disorders, and cancer. Moderate levels of mitochondrial ROS, however, can protect against chronic disease by inducing upregulation of mitochondrial capacity and endogenous antioxidant defense. This phenomenon, referred to as mitohormesis, is induced through increased reliance on mitochondrial respiration, which can occur through diet or exercise. Nutritional ketosis is a safe and physiological metabolic state induced through a ketogenic diet low in carbohydrate and moderate in protein. Such a diet increases reliance on mitochondrial respiration and may, therefore, induce mitohormesis. Furthermore, the ketone β-hydroxybutyrate (BHB), which is elevated post ingestion of MCT OIL POWDER or resulting from fasting, acts as a signaling molecule in addition to its traditionally known role as an energy substrate. BHB signaling induces adaptations similar to mitohormesis, thereby expanding the potential benefit of nutritional ketosis beyond carbohydrate restriction. This review describes the evidence supporting enhancement of mitochondrial function and endogenous antioxidant defense in response to nutritional ketosis, as well as the potential mechanisms leading to these adaptations.

The terms healthy diet, nutrition, nutrient density, lifestyle are center to achieving Better Metabolic Health:

Understanding the fundamentals of weight loss and regain could be a crucial part to your success, as knowing why you are making the changes you make become a physical and an emotional investment. If you need to lose weight to regain your health and you are serious about taking your health into your own hands, ignorance is not bliss. This is where sustained adherence or lifestyle choice are primary factors and key to achieving the goals.

GloNua believe the keto approch to eating is by far a very successful and a maintainable weight management strategy. Historically, the ketogenic diet was used as a treatment for specific conditions such as pediatric epilepsy, more recently attention has been given to its application in the treatment of cancer, type-2 diabetes, Alzheimer’s Disease, and more. Today, weight loss, often seen as a side effect of ketogenic therapies, is being explored as a single entity, and it is no secret that many people have experienced amazing success with the diet. That is also why we consider it a valid approach for body condition, brain health and weight loss. GloNua aim to aid you on your journey toward better health. Many scientific research studies now explore this in depth pointing toward the rationale for how the ketogenic diet can be used to create a more favourable metabolic state with less free radicals, ROS (reactive oxidative species), reduced inflammation and required calorie deficit needed for better internal health resulting also in meaningful weight loss.

GloNua BioHacking Tips:

What we eat and how we move, directly affects mood, function, body and all of the complex bio-chemical processes that go into make us who we are. Being aware of this is imperative in gaining the insight you require to take the initial steps towards a better you. As the founder of GloNua I feel it’s important to share some of these pillars and key aspects in a simple format to help you understand.

Diet
My regime is based on what I like to call M.E.A.L. (Meat, Eggs, Added oils, Leaves). I advise eating grass fed meats and non-farmed fish. Steaks are great, but there’s so many options when it comes to good quality meat. After a workout or pre bed sometimes I’ll have a protein shake. I don’t eat that many carbohydrates, but they are cycled in and out as they do contain fibre, and at times on Keto, science has found that we can get the benefits utilising such cyclical patterns. Everybody is slightly different, from gender, to age and daily routines, so see what works for you. I do occasionally enjoy a sweet treat after my main meal (I am human). Replace the highly processed industrial mono-cropped agriculture: refined grains, sugar and seed oils with our ancestral diet rich in animal meat, fish, fat and organs (Collagen/gelatine rich) foods.

Try to avoid a much as possible:
Sugar, Seed oils, High Fructose Corn Syrup, Trans fats, Refined carbs. These are all present in so many processed foods or packaged foods, just check the labels.

Intermittent Fasting
Practice Intermittent Fasting. I have implemented it in my life in various forms for years and it has delivered many benefits including better energy, better mood and better cognitive function (also covered in our blog page in depth).

GloNua Biohack Pillars:

• *Mind and body awareness

• Fast

• Eat real food = satiety

• Exercise - Build muscle (it burns fat), do weights and Hiit.

• Sleep well - 7-9 hours

• Sunlight - AM & PM, it has numerous body benefits.

• Meditate - practice correct breathing& presence even 5-10mins.

• Engage with people - Social Contact.

• Get out in nature - Positive to Negative balance

GloNua believe the keto approch to eating is by far the most successful and maintainable weight management strategy. Historically, the ketogenic diet was used as a treatment for specific conditions such as pediatric epilepsy, more recently attention has been given to its application in the treatment of cancer, type-2 diabetes, Alzheimer’s Disease, and more. Today, weight loss, often seen as a side effect of ketogenic therapies, is being explored as a single entity, and it is no secret that many people have experienced amazing success with the diet. That is also why we consider it a valid approach for body condition, brain health and weight loss. GloNua aim to aid you on your journey toward better health and Wellness. Many scientific research studies now explore this area of Health in depth pointing toward the rationale for how the ketogenic diet can be used to create a more favourable metabolic state, less ree radicals, reduced inflammation and required calorie deficit with key Nutrients all needed for meaningful Health, wellbeing.

For individuals needing to lose weight for the sake of their health and wellbeing, finding a strategy that works for you can be extremely liberating. Not only is weight loss accompanied with a decreased risk of several major chronic diseases, but it can increase your quality of life. There is no doubt that there is an emotional component to one’s weight loss journey, and we strongly believe the information in our Blog can set you on the path to better health.