Fasting pertains to the act of refraining from consuming and a metabolic state that occurs after complete digestion and absorption of consumed food. Some medical interventions require a diagnostic fast to help diagnose a health issue or as part of preparation for a medical examination and certain medical procedures.
Moreover, aside from religious and cultural practices, fasting has become popular among health enthusiasts because of its purported benefits and applications like in weight loss and management and reducing risk of certain diseases. There are also different approaches to fasting. These include intermittent fasting and alternate-day fasting. Some focus on consuming specific food like water or liquid and plant-based meals.
There is emerging evidence confirming some of the potential benefits of fasting. Research has uncovered what happens to the body while it is deprived of nourishment for an extended period or once digestion and absorption are completed. However, in extreme cases, prolonged fasting also has a negative impact on the body.
What Happens to Your Body When You Fast: A Timeline of Different Biological Processes Occurring While Fasting
0 to 4 Hours: The Fed or Absorptive State and Anabolic Phase
The fed state is a metabolic condition of the body after consuming food and while food is being digested and nutrients are absorbed. This begins after a meal and lasts up to 4 hours. The fed state is also primarily an anabolic state. This means that the body is focused on building and storing. Below are important biological processes under this state and phase:
• Digestion and Absorption: The digestive system of the body is active under the fed state because it is on the process of digesting and absorbing nutrients from the last meal. This involves breaking down food into its smallest usable components then taking them from the digestive tract into the bloodstream or lymphatic system.
• Glucose Spike and Insulin: Glucose in the blood rises due to the rapid influx of glucose from consumed carbohydrates. This process is called postprandial hyperglycemia. The pancreas then secretes insulin to assist in transporting glucose into cells either for energy or storage. Glycogen synthesis occurs in the liver and muscles.
• Critical Hormonal Shifts: The levels of the hunger hormone called ghrelin fall while the satiety hormone called leptin rises. Ghrelin is produced by specialized cells in the stomach when it is empty. Leptin is primarily produced by adipose tissue or fat cells and it acts on the brain to signal that the body has sufficient energy stores.
4 to 12 Hours: Early Fasting and Post-Absorptive or Catabolic Phase
The period between 4 and 12 hours after the last meal marks an important transition to the energy metabolism of the body. This period is often referred to as early fasting or the post-absorptive state and is characterized further by the commencement of the catabolic phase and glycogen depletion. The following are the critical processes under this stage of fasting:
• Glucose and Insulin Decline: Both glucose and insulin levels begin to drop as absorbed nutrients are used up. The body then starts to tap into its stored glycogen reserves in the liver and muscles in a process called glycogenolysis. The pancreas releases more glucagon to signal the liver to break down glycogen into glucose.
• Early Gluconeogenesis: Note that glycogenolysis is the main mechanism for maintaining blood glucose. However, to maximize energy reserves, the liver also starts to perform a small amount of gluconeogenesis in which new glucose is synthesized from other non-carbohydrate sources like amino acids and glycerol.
• Initial Fat Mobilization: The glycogen stores dwindle down further as it breaks down into glucose. The body then slowly begins to mobilize stored fat for energy through a process called lipolysis in which triglycerides are broken down into fatty acids.
• Notable Hormonal Changes: The level of the human growth hormone may start to rise in this phase to preserve muscle protein. The hormone ghrelin may start to rise again towards the later part of this 4-12 hour window to signal that the body needs to consume food to replenish depleted nutrients and short-term energy reserves.
It is important to note that the biological processes in this phase of fasting can differ from person to person. The goal of the body during this period is to maintain blood sugar levels. Remember that this phase involves catabolism. This is a metabolic process in which the body shifts from storing energy to breaking down its short-term energy reserves.
This phase is also marked by glycogen depletion. The depletion rate depends on factors like initial glycogen stores from the amount of carbs consumed, level of physical activity, and individual metabolic rate. Liver glycogen is the most readily available. Muscle glycogen is also tapped but it can only be used for energy by the muscle cells themselves.
12 to 24 Hours: Actual Fasting State and Fat Burning Phase
The glycogen reserve of the body becomes depleted or is nearing complete depletion in the 12th hour of fasting. A complete depletion results in fat burning. This is the core biological process of this phase. Fat is the largest energy reserve of the body and it stores significantly more energy per gram than carbohydrates or protein. Below are the processes:
• Further Glycogen Depletion: The glycogen stored in the liver depletes around 18 to 24 hours into fasting. This means the body can no longer rely on glycogenolysis to maintain blood sugar levels and fuel itself. This depletion is a critical metabolic signal that forces the body to seek alternative and more abundant energy sources.
• Metabolic Switch To Lipolysis: Fat becomes the main fuel source. Hormones such as glucagon, norepinephrine, and epinephrine stimulate lipolysis in which adipose tissues break down stored triglycerides into free fatty acids and glycerol. These free fatty acids are released into the bloodstream and delivered to most tissues.
• Initial Ketone Production: The liver converts fatty acids into ketone bodies via a process called ketogenesis. Ketones can be used by the brain and other organs for energy. Note that many tissues can directly use free fatty acids for energy. The brain primarily depends on glucose and red blood cells lack mitochondria to use free fatty acids.
• Further Gluconeogenesis: Remember that gluconeogenesis is a process in which the liver synthesizes new glucose from non-carbohydrate sources. These sources include glycerol from triglycerides, lactate produced by red blood cells and exercising muscles, amino acids derived from consumer or internal protein breakdown, and some ketones.
• Possible Reduced Hunger Pangs: The body adapts to fat burning with the rise in ketone levels. Hunger pangs may subside because ketone bodies have appetite-suppressing effects and the efficient production of glucose via gluconeogenesis results in a more stable blood sugar level which prevents triggering intense hunger.
Remember that the 12th-hour to 24th-hour mark into fasting is a significant transition to the fasting state where the body undergoes substantial metabolic shifts because it has exhausted its readily available short-term glucose stores and must now rely heavily on its fat reserves. This is not a hard and immediate shift at the 12th hour because it is a continuous process.
Several factors influence the exact timing and characteristics of the actual fasting state. The most important one is the level of initial glycogen stores. The level of liver glycogen liver would be higher if the last meal was high in carbohydrates and it will take longer to deplete. A lower-carb diet or light meal will lead to faster glycogen depletion.
Another factor that affects the onset of the actual fasting state is prior physical activity. An intense physical activity before fasting can significantly deplete muscle and liver glycogen stores and lead to an earlier shift to fat burning. A higher basal metabolic rate or BMR can also influence the onset of the fasting state because it translates to faster energy utilization.
It is also important to underscore that the body starts increasing fat burning well before it enters significant ketosis. To be specific, while fat burning ramps up around 12 hours, detectable ketone levels, which indicate initial ketosis, often become more prominent around 18-24 hours and it will continue to rise with longer fasting durations.
24-72 Hours: Deep Fasting State, Ketogenesis, and Cellular Repair
The period between 24 and 72 hours of fasting is often referred to as the deep fasting state. This is when gluconeogenesis becomes the main source of blood sugar level from 24 to 48 hours while a more heightened ketogenesis transpires after 48 hours to fuel the brain and other organs. Cellular repair also commences. Below are the biological processes under this state:
• Initial Gluconeogenesis Dominance: The liver continues to perform gluconeogenesis by using glycerol and lactate. This process becomes the dominant source of blood sugar levels from about 24 to 48 hours despite fat burning ramping up further. The role of this process becomes lesser as the whole fasting timeframe goes deeper.
• Heightened Ketone Body Production: Note that ketogenesis or the production of ketone bodies increases further in the 24th-hour mark. The body enters deep ketosis around the 48th-hour mark in which ketone production levels reach nutritional ketosis to fuel 60 to 70 percent of the energy requirement of the brain and spar muscle protein.
• Cellular Cleanup and Recycling Process: The cellular process called autophagy begins around 36072 hours into fasting and it involves cells breaking down and recycling old and damaged cellular components. The activation of autophagy is signaled by energy stress low nutrient availability or low insulin and high glucagon levels.
• Important Hormonal Changes: Human growth hormone or HGH levels may rise from the 24th-hour mark to help preserve muscle mass and further promote fat burning. The low levels of insulin and glucose contribute to improved insulin sensitivity. The level of IGF-1 decreases. IGF-1 is a growth factor involved in growth and development.
Autophagy is one of the most sought-after benefits of fasting. Fasting triggers this fundamental cellular self-eating and recycling process because it creates a state of nutrient deprivation and energy stress within the cells. The cell senses this lack of external resources and adapts by turning on internal recycling mechanisms to survive and maintain function.
The levels of human growth hormone or somatotropin also increase because it is a crucial adaptive response in the absence of incoming nutrients. An inverse relationship exists between somatotropin and insulin. Low insulin level signals hunger and the body will resort to releasing somatotropin in the absence of nutrients to promote fat mobilization and preserve protein from muscles.
72 Hours and Beyond: Prolonged Fasting and Sustained Ketosis
The prolonged fasting state happens around 72 hours and beyond. There are some benefits and costs associated with this period. Most of the benefits transpire in the earlier hours of the 72nd-hour mark but costs or health-related risks and dangers emerge in the later hours. The following are the critical biological processes occurring during this state and phase:
• Sustained and Deeper Ketosis: Blood ketone levels are high and stable during this fasting state. Ketones become the primary fuel source for the brain and a substantial energy source for many other tissues. The body becomes an effective fat-burning machine at this point while still trying to prevent using protein from muscles.
• Important Hormonal Adaptions: IGF-1 is kept low and further keeps autophagy. Cortisol levels remain stable or show fluctuations. There might be a slight reduction in thyroid hormone activity to reduce basal metabolic rate and conserve energy and a slight elevation in adrenaline or norepinephrine to support energy mobilization.
• Notable Weight Loss Factors: The body losses long-term weight during this period. This comes from continued fat loss due to the metabolization of adipose tissue. There is a risk of losing muscle mass under a more prolonged fasting state because the body would resort to using protein for energy in albescence of fat stores.
• Important Electrolyte Changes: Prolonged fasting can disrupt the electrolyte balance in the body. Sodium is lost in urine and potassium can be lost during muscle breakdown. Note that electrolyte imbalances can lead to serious complications including fatigue, muscle cramps, heart arrhythmias, seizures, and even death.
Pointers and Reminders: Important Considerations of the Different Timing or Onset of Biological Processes While Fasting
It is important to reiterate and underscore the fact that the exact timing and extent of the different biological processes and physiological changes discussed above can vary depending on individual metabolism, physical activity level, the composition of the last meal, health condition, and overall body composition. The timeframe above is an estimate.
Prolonged fasting, particularly for more than 24 to 48 hours, should be undertaken with medical supervision, especially for individuals with underlying health conditions. Staying well-hydrated with water is crucial during any fast to avoid dehydration and associated health risks. Electrolyte supplementation should also be considered for longer fasts.
Moreover, after prolonged fasting, it is essential to reintroduce food carefully to avoid refeeding syndrome. This is a potentially fatal metabolic complication due to a sudden insulin surge that can occur when nutrition is reintroduced too quickly or inappropriately via food consumption after a period of significant malnutrition or prolonged fasting.
FURTHER READINGS AND REFERENCES
- Imada, S., Khawaled, S., Shin, H., Meckelmann, S. W., Whittaker, C. A., Corrêa, R. O., Alquati, C., Lu, Y., Tie, G., Pradhan, D., Calibasi-Kocal, G., Nascentes Melo, L. M., Allies, G., Rösler, J., Wittenhofer, P., Krystkiewicz, J., Schmitz, O. J., Roper, J., Vinolo, M. A. R., … Yilmaz, Ö. H. 2024. “Short-Term Post-Fast Refeeding Enhances Intestinal Stemness via Polyamines. Nature. 633(8031): 895-904. DOI: 1038/s41586-024-07840-z
- Longo, V. D., and Mattson, M. P. 2014. “Fasting: Molecular Mechanisms and Clinical Applications.” Cell Metabolism. 19(2): 181-192. DOI: 1016/j.cmet.2013.12.008
- Wang, Y., and Wu, R. 2022. “The Effect of Fasting on Human Metabolism and Psychological Health. Disease Markers” 2022: 1-7. DOI: 1155/2022/5653739