Fasting - A Scientific Explanation

Fasting has been around for generations as part of cultural spiritual practices. Today it is used for proper weight maintenance, healing from disease and prevention. Humans are metabolically flexible.  We are able to change the source of energy that we use to power our cells depending on the available resources. Ultimately it is the production of ketones that generates the healing ability of a fast, disease prevention and increased longevity.

What is fasting

Fasting, as its commonly practiced today, is the refrain from food and most drinks for a varying period of time depending on the intended goal. There are many fasting practices from eating just one meal a day, to limiting food intake to 8 hours daily, to caloric reduction two days of the week, to a weekly 24 hour fast. These processes are termed intermittent fasting.  Although each method is different the benefits are conserved. Fasting can also be taken a step further to the intake of water for an extended period of time called a water fast. The benefits of an extended water fast exceed intermittent fasting in its ability to heal the body from many common illnesses such as hypertension (high blood pressure), hypercholesterolemia (high cholesterol), diabetes, arthritis, lupus, fibroids, chronic pain and asthma permanently.

We always exist in two states: the fed state where we are energy storing, and the fasting state where we are energy burning. The fed state is characterized as the time when we are actively eating and storing food. In the fed state we are burning the glucose we acquire through eating for energy and storing the excess amounts as glycogen in the liver and muscles.  The fasting state begins when we stop consuming calories. Our body initially goes into a process of creating glucose from glycogen, and once those stores are exhausted, ketones from fat.

What is Glycogen?

Glycogen is the storage form of glucose. It is stored in the muscles and liver of human beings and used during times of glucose depletion.  Everyone has around 24 hours of glucose available for use from the everyday eating habits we are accustomed to. Once a fast starts, glucose is not replenished and the body begins breaking down glycogen for energy. The body changes from fed state to fasting state. The process of breaking glycogen down to glucose for use is called Glycogenolysis. From there, the glucose is further broken down to a molecule called pyruvate, which used in a process known as the Kreb’s cycle or the Citric acid cycle (TCA), located in the powerhouse organelle of each cell, the mitochondria. This series of biochemical reactions transforms pyruvate into adenosine triphosphate (ATP), the energy currency of the cell.  ATP is required to power the billions of biochemical reactions happening in each cell, each second. It is constantly being generated and consumed in an on-going process as long as a cell is alive. Our energy requirements are constant. After 48 hours for women, and 72 hours for men, all the glycogen stores have been converted to glucose and the body switches its fuel source again.

Ketosis

This is the last source of energy the body can use during times of fasting. It is the process of breaking down fats into ketone molecules so they too can enter the Kreb’s cycle and become energy for the cells. Fat, or triglyceride, breakdown into ketones happens in the liver, Ketones then enter the blood stream where they are taken up by other organs and muscle tissue. Ketolysis is the conversation of ketones into energy and also happens in the mitochondria of human cells. This process of ketone breakdown is known as beta-oxidation.

Ketones are particularly important for the brain which cannot use fatty acids for energy when blood glucose levels become compromised. Ketone bodies provide the brain with an alternative source of energy, amounting to nearly 2/3 of the brain's energy needs during periods of prolonged fasting and starvation. Ketone bodies are always present in the blood and their levels are increased during fasting and prolonged exercise. After an over-night fast, ketone bodies supply 2–6% of the body's energy requirements, while they supply 30–40% of the energy needs after a 3-day fast. In healthy adults, the liver is capable of producing up to 185g of ketone bodies per day. When ketones progressively build up in the blood as fasting continues, they spill over into the urine. The presence of elevated ketone bodies in the blood is what is known as ketosis. Their presence and concentration in the urine makes the level of ketosis particularly easy to test using a urine ketone test strip.

The liver generates 3 types of ketones from fat. And they are: Beta-Hydroxybutyrate (BHB) (78%) structurally not a true ketone, Acetoacetate (20%) and Acetone (2%). The benefits of a fast are primarily due to BHB and acetoacetate which can be converted to Acetyl-CoA and used in the Kreb’s cycle to produce ATP.  Whereas acetone, unable to convert to Acetyl-CoA, is released from the body through the lungs (1).

Why are ketones such an efficient fuel?

As mentioned, each one of cells requires energy to function. Cells make up tissues and tissues make up organs such as our internal organs (liver, kidney, heart, brain) as well as external organs like the skin and other tissues such as bone, connective tissue and hair. Each organ and their cells require energy to function. That energy can be produced by glucose or ketones in the  mitochondria. But to get each molecule ready for the mitochondrial Kreb’s cycle requires breaking it down to a size and structure that can enter the cycle, and this is where ketones have the advantage. Each fuel has to be broken down to Acetyl-CoA to enter into the Kreb’s cycle. To break a ketone down to a acetyl-CoA to enter the takes 3 steps, whereas glucose takes 10 steps. Breaking chemical bonds take energy. The less bonds that need to be broken, the easier it is to extract the fuel and obtain energy. By being less energetically expensive to breakdown, ketones are more easily and rapidly converted into ATP than glucose. It is less energetically expensive and more efficienct to power the body with ketones rather than glucose.

Benefits of Ketosis

After 12 hours of fasting BHB levels rise above 0.6 mmol/L. During nutritional ketosis, or ketongenic diet, BHB levels can reach from 0.6 - < 3 mmol/L. The body’s metabolism of BHB activates autophagy, the cleaning up of old cells. Apoptosis is known as cell death and is a natural process initiated in each cell at the end of the cell cycle. Removing old cells from the body positively influences longevity and lifespan. Retaining only optimally functioning cells in the body and removing old, less functioning cells from the body improves tissue and organ function and overall health as a whole. After a 3 days of a water fast all of the white blood cells in the body have been destroyed and replaced by new ones. This is a considerable immune system upgrade.

The blood brain barrier functions to preserve, nourish and maintain the health of the sensitive brain tissue. During ketosis this barrier has an enhanced ability to preserve brain cells, known as neurons and their synaptic connections. As a result the brain experiences improved cognitive function, stress resistance and reduced inflammation from the reduction in free radicals and their damage. People with Parkinson's disease see a reduction in symptoms. BHB use improves the cognition of people with dementia, Alzheimer’s and Parkinson’s diseases. Children with epilepsy see a reduction in symptoms and improvement in brain activity. The heart experiences a lowered heart rate & blood pressure as well as increased stress resistance. Fat cells are reduced as they are being consumed for energy. Muscle cells experience an increase in insulin sensitivity, efficiency, and reduced inflammation. There is a reduction in inflammatory mediators in the blood and leptin hormone.  The liver has an increased insulin sensitivity, ketone production and decrease in inflammatory mediators. The intestines have a reduced energy uptake and inflammation and undergo extensive cell proliferation, or regeneration if tissue (2).

During exercise BHB helps to reduce oxidative stress, and improving recovery. By reducing oxidative stress it protects the brain and cardiovascular system during exercise. BHB helps to prevent bone deterioration. It can slow brain tumor growth, and stop the spread of metastatic tumors. Fasting can kill pancreatic cancer cells and reduce cachexia (muscle wasting) in late stage cancer patients. Fasting slows the growth of neuroblastomas (cancer in nerve tissues (3). Consuming ketones has remarkable determinants for the prevention of other disease development including dementia, depression and mood disorders and breast cancer (4). On a more technical level, fasting blocks inflammation via NLRP3 thereby preventing the development of: neuroinflammation, cancer, insulin resistance, bone diseases, Alzheimer’s disease, metabolic syndrome and diabetes type 2 (5).

Insulin resistance and type 2 diabetes can be cured and prevented with fasting because it reduces insulin in the cells thereby increasing the cells sensitivity to insulin when it returns. Increasing the cell’s insulin sensitivity means that less glucose is required in the blood stream to meet the energy requirements of the cells as the detection and update of glucose happens efficiently. During insulin resistance, the receptors have been downgraded (removed) because there is an overabundance of glucose in the blood. As a result the cells don’t achieve glucose satiety with the same glucose levels and require more to experience the same effects, often exceeding the upper tolerable limits of blood glucose concentration. Insulin resistance leads to excessive inflammation and tissue damage in the long term or triggering in a diabetic crisis and comma acutely.  Keeping our cells insulin sensitive prevents the development of type 2 diabetes.

Conclusion

Fasting has been around since the early days of man. The brilliance of water fasting has to do with our body’s metabolic flexibility to transition from one energy source to another. Ketones have enormous benefit on the organ systems of the body for the prevention and healing of disease. Fasting reduces negative processes in the body and positively impacts our longevity and quality of life throughout.