Intermittent Fasting: Health Benefits of Reaching a Fasted State

At any given moment, your body is either in a fasted state or fed state. Your body operates differently in a fasted state and, as a result, there are a slew of health benefits. Intermittent fasting is a method for timing your eating so your body can reach this fasted state and reap the benefits. This post outlines what is happening in your body in the two states, explains the health benefits of reaching the fasted state, and links to research and other scientific studies on intermittent fasting diets. For brevity's sake, I have left out certain biological details; I encourage you to explore the links in the References section below and further research anything that piques your interest. Let's get in to it!


Fed State vs. Fasted State

The fed state, also known as the post-absorptive state, is the state your body is in when you have recently had a meal (1). Food is digested in the intestinal tract and broken down into macromolecules, such as amino acids and glucose, to be used in cellular processes throughout the body. As glucose enters the bloodstream, your blood-sugar levels rise, which triggers beta cells in your pancreas to release insulin. Insulin is a hormone whose main job is to regulate your blood-sugar levels and ensure glucose is used and stored effectively within the body. It does this in a few ways (1):

  • Allows glucose, the human body's main source of energy, to enter cells and be used for various processes.
  • Helps store any glucose that is not immediately needed in the liver in the form of glycogen. This is considered short-term storage of glucose, which will be used when the level of glucose in the bloodstream drops.
  • Enables glucose to enter muscle tissue, where it is stored as glycogen. Insulin also enables glucose to enter adipose tissue. Adipose tissue is body fat and it uses glucose to synthesize triglycerides, which are the main component of body fat. Glycogen in muscle tissue and triglycerides in adipose tissue are both considered to be long-term storage of glucose.

A few hours after the meal, your blood-sugar levels will drop as the glucose you consumed has been used for cellular processes or stored. This decrease in blood-glucose triggers the alpha cells in the pancreas to release glucagon. Glucagon is a hormone that stimulates the liver to break down its stores of glycogen into glucose and release it to the bloodstream (1). As your body needs more and more fuel for cellular processes, these glycogen stores will run out. When this happens, typically about 10-12 hours after your last meal, your body reaches the fasted state. What does your body use as an energy source when blood-glucose levels are extremely low and glycogen stores have been depleted? Fat, which brings us to the first benefit of reaching a fasted state:

Increased Fat Burn

This occurs because glucagon will stimulate adipose tissue (body fat) to break down triglycerides, the long term storage of glucose mentioned above (1). The decomposition of triglycerides provides fatty acids and glycerol. Glycerol can be used by the liver to synthesize glucose, through a series of reactions known as gluconeogenesis (2). Fatty acids cannot be converted to glucose but alone can provide fuel for muscle tissue and other organs. Thus, body fat is literally broken down to provide energy for your body.

The fatty acids and glycerol from decomposed triglycerides can be used to create another energy source: ketones (1). Ketones, also referred to as ketone bodies or ketonic acids, provide fuel for the body when glucose is absent. Most importantly, the brain and the heart can use ketones in place of glucose to meet their energy needs (3). We have arrived at another benefit of reaching a fasted state:

Raised Production of Ketones

When your body relies primarily on ketones for energy, because blood-glucose levels are so low, you are in a state of ketosis (3). Ketosis has been linked to a few health benefits:

  • Reduced risk of cardiovascular disease, by improving the amount and quality of cholesterol in the blood (4)
  • Improved appetite control, by altering levels of hunger hormones such as ghrelin and leptin (4)
  • Lessened symptoms of epilepsy, by improving neurotransmitter activity in the brain; it's possible ketosis could prevent other neurodegenerative diseases such as Alzheimer's and Parkinson's (5)

The benefits of ketosis are why some people choose to practice a ketogenic diet, which is high-fat, adequate-protein, and low-carbohydrate (6). Ketosis is not to be confused with ketoacidosis, which is a metabolic condition where the blood becomes too acidic; it is most often linked to uncontrolled type 1 diabetes and can be fatal if left untreated (4).

Some other health benefits linked to reaching a fasted state, discovered through scientific studies of fasting diets, include: 

Reduced risk of type 2 diabetes and obesity (thanks to amplified insulin sensitivity)

Insulin plays a key role in the body's ability to absorb glucose and use it for energy. It is critical that cells respond appropriately to the presence of insulin; the degree to which cells react to insulin is described in terms of insulin sensitivity/resistance. If someone is insulin sensitive, they require less insulin for their cells to absorb glucose and lower blood sugar levels, as compared to someone who is insulin resistant. The pancreas compensates for insulin resistance by producing more insulin. This increases the amount of insulin in the bloodstream (hyperinsulinemia) and, over time, can lead to type 2 diabetes, obesity, and other issues. A study conducted on eight healthy young Caucasian men showed that intermittent fasting increased insulin sensitivity. The subjects fasted for 20 hours every other day for 14 days. They were instructed to maintain their usual caloric intake and activity levels, and the fasting period would last from 10 pm until 6 pm the following day. Although they were not able to conclude why intermittent fasting contributed to increased insulin sensitivity, the researchers hypothesized that it could be caused by increased levels of adiponectin - a protein secreted by adipose tissue cells (7).

Decreased body fat and waist size, maintained muscle mass

Researchers from the Longevity Institute and the University of Southern California performed a study of the impacts of a fasting-mimicking diet (FMD) on seventy men and women. The subjects were of relatively equivalent health before the study. A control group of the subjects maintained their usual diet for three months and one group practiced FMD for three months. The fasting-mimicking diet involved following usual diet for all but five days of each month, during which the subjects consumed much lower calories to mimic a fasting diet. The study found that FMD subjects lost body fat and decreased their waist size (8). This can most likely be explained by the increased fat burn that occurs while in a fasted state, as outlined above. Furthermore, lean muscle mass maintained in both sets of subjects (8). Even though fasting can cause the body to break down muscle as an energy source, fasting has also been shown to increase human growth hormone production (9).

Reduced inflammation

The study discussed in the previous point found that FMD subjects had lower levels of inflammation at the end of the three months than the control groups (8). Inflammation is one of the body's main protective responses to infection or damaged cells. Inflammation, however, can lead to and/or exacerbate disorders such as acne, asthma, bowel diseases, depression, HIV/AIDS, and cancerous behavior of cells (10). The reduction in inflammation was determined by measuring levels of C-reactive protein in the subjects' blood; levels of C-reactive protein are primarily impacted by inflammation, therefore, it is regarded as a main indicator of inflammation (11). The study found that the amount of C-reactive protein in the blood decreased in FMD subjects. Thus, it can be safely assumed that the FMD reduced inflammation.

Reduced risk of cardiovascular disease

Cardiovascular disease is the leading cause of death in America (12). The main factors that lead to CVD are high blood pressure and high levels of cholesterol, specifically low-density lipoprotein (LDL) cholesterol - the "bad" cholesterol (13). Regular exercise, balanced diet, and plenty of sleep throughout one's life is enough to mitigate these risk factors. The same study referenced twice above found that FMD subjects ended up with a lowered blood pressure and lowered levels of LDL cholesterol than those of the control group (8). Thus, intermittent fasting paired with the healthy habits mentioned above can further eliminate your chances of heart disease. 


The body is a fascinating piece of machinery. The research I did for this post gave me a deeper understanding of what is happening biologically when I fast. Learning how something works is a critical first step, of course, but knowledge can only become practice if you experiment! The best way to experiment is to conduct a "study of one" - try it out on yourself, monitor how you feel, and track any physical changes. Not sure how to begin intermittent fasting? My getting started guide breaks it down; check it out here.

Thanks for reading!


References

(1)  Berg, J., Tymoczko, J., Stryer, L. (2002). Biochemistry. 5th edition. Section 30.3, Food Intake and Starvation Induce Metabolic Changes. New York: W H Freeman. https://www.ncbi.nlm.nih.gov/books/NBK22414/

(2)  Gluconeogenesis. (2017, January 15). Wikipedia, The Free Encyclopedia. Web. Retrieved March 22, 2017. https://en.wikipedia.org/w/index.php?title=Gluconeogenesis&oldid=760169843

(3)  Ketone bodies. (2017, March 1). Wikipedia, The Free Encyclopedia. Web. Retrieved March 22, 2017. https://en.wikipedia.org/w/index.php?title=Ketone_bodies&oldid=768037404

(4)  Paoli, A., Rubini, A., Volek, J. S., & Grimaldi, K. A. (2013). Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. European Journal of Clinical Nutrition, 67(8), 789–796. http://doi.org/10.1038/ejcn.2013.116

(5)  Hartman, A. L., Gasior, M., Vining, E. P. G., & Rogawski, M. A. (2007). The Neuropharmacology of the Ketogenic Diet. Pediatric Neurology, 36(5), 281–292. http://doi.org/10.1016/j.pediatrneurol.2007.02.008

(6)  Ketogenic diet. (2017, March 8). Wikipedia, The Free Encyclopedia. Web. Retrieved March 22, 2017. https://en.wikipedia.org/w/index.php?title=Ketogenic_diet&oldid=769344465

(7) Halberg, N., Henriksen,M., Soderhamn, N., Stallknecht, B., Ploug, T., Schjerling, P., Dela, F. (Dec 2005). Effect of intermittent fasting and refeeding on insulin action in healthy men. Journal of Applied Psychology, 99 (6), 2128-2136. http://jap.physiology.org/content/99/6/2128

(8) Wei. M., Brandhorst, S., Shelehchi, M., Mirzaei, H., Cheng, C., Budniak, J., Groshen, S., Mack, W., Guen, E., Di Biase, S., Cohen, P., Morgan, T., Dorff, T., Hong, K., Michalsen, A., Laviano, A., Longo, V. (2017). Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Science Translational Medicine, 9 (377). https://www.dropbox.com/s/ajmrgno9b38ncgi/2017-wei.pdf

(9)  Ho, K., Veldhuls, J., Johnson, M., Furlanetto, R., Evans, W., Alberti, K., and Thomer, M. (1987). Fasting Enhances Growth Hormone Secretion and Amplifies the Complex Rhythms of Growth Hormone Secretion in Man. The American Society for Clinical Investigation, Inc., 81, 968-975. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC329619/pdf/jcinvest00482-0014.pdf

(10)  Inflammation. (2017, March 9). Wikipedia, The Free Encyclopedia. Web. Retrieved March 22, 2017. https://en.wikipedia.org/w/index.php?title=Inflammation&oldid=769507037

(11)  C-reactive protein. (2017, March 4). Wikipedia, The Free Encyclopedia. Web. Retrieved March 22, 2017. https://en.wikipedia.org/w/index.php?title=C-reactive_protein&oldid=768610329

(12) Heart Disease Statistics & Maps. (2015, August 10). Cdc.gov. Web. Retrieved March 22, 2017. https://www.cdc.gov/heartdisease/statistics_maps.htm

(13)  Conditions That Increase Risk for Heart Disease. (2015, August 10). Cdc.gov. Web. Retrieved March 22, 2017. https://www.cdc.gov/heartdisease/conditions.htm