Fasting is gaining increasing attention as a potential method to optimize weight and reverse insulin resistance. Can fasting be a helpful practice on the road to optimal health?

Here is a quick overview on fasting, types of fasting, and benefits.

Early Studies on Mechanism of Fasting

We owe much of our knowledge to what happens in the starvation state to George F. Cahill, who conducted studies in the 1960s and wrote an article about it entitled “Starvation in Man.” The dogma of the time was that the only source of fuel for the brain as glucose. However, things didn’t seem to add up. Their studies showed a different story.

Muscle tissue can provide glucose from the breakdown of amino acids. However, if one were to die from starvation, they would still have about 50% of their muscle tissue. This phenomenon suggests that there is a relative conservation of muscle tissue. Cahill determined through jugular venous samples of 3 obese subjects in a 6-week starvation trial that the brain’s energy source shifted away from glucose to B-hydroxy-butyrate (BHB) and acetoacetate. These substances are known as ketone bodies. There was a shift toward fat breakdown (catabolism), protecting muscle tissue. 

While it’s true that the body uses fuel preferentially in the form of glucose, it perseveres with ketone bodies in the starvation state. Metabolism begins with what comes in after eating, the body usually favoring glucose metabolism for energy, and continues with endogenous (internal) methods to maintain a basal fuel level. 

A high carbohydrate diet preferentially shifts the body to glucose use as the fuel source. Glucose requires insulin to metabolize it in the body. Insulin signals the liver and muscle tissues to store glucose in liver and muscle tissue as glycogen (glucose chains) and in fat cells as triacylglycerols. The process of storing glucose in the liver and muscle tissue is known as glycogenesis. 

When there is a change from a high carbohydrate to low carbohydrate intake, such as in a diet or fasting state, insulin secretion decreases as glucose intake decreases. Another hormone, glucagon, maintains a steady-state, allowing for the release of glycogen to glucose in the bloodstream. This process is known as gluconeogenesis. However, glycogen stores run out over approximately 24 hours.

Further glucose production can occur in the liver in prolonged starvation with the use of amino acids. Doctor Cahill and his colleague Dr. Owen determined that the kidneys contribute to the production of glucose during this period, as it transforms glutamine and alanine produced by muscle tissue into ammonium and glucose. 

There is a shift to ketone bodies and free fatty acids as a fuel source with a prolonged fast, as glucagon mobilizes fat stores. The liver accomplishes the bulk of the work of free fatty acid and ketone body generation. Ketone bodies form after free fatty acids are generated from adipose tissue and converted in the liver to acetyl CoA, which can cross the blood-brain barrier. Using BHB’s and acetoacetate as a fuel source, the brain spares using glucose from muscle catabolism.

The Types of Fasting

There are multiple approaches to fasting and ways to reduce long-term starvation risks and vitamin deficiencies. Essentially, these techniques call for some degree of Intermittent fasting, or spacing between meals. Examples of fasting include Alternate-Day Fasting, Modified Fasting, and Time-Restricted Feeding. Alternate-Day fasting is self explanatory, involving a day of regular consumption followed by a day of fasting. Modified fasting includes periods of time where there is a significant reduction of intake but not complete fasting. Time-Restricted feeding relates to eating for a shorter window of time, for example a period of 4 to 12 hours, while fasting for the difference.

The Health Benefits of Fasting

There have been many health claims to fasting. Advocates claim that the shift to fat stores improves the function of insulin in people with diabetes and obesity. There is a loss of water weight and a reduction in bloating. Health experts tout a cleansing process to prevent cancer tissues or autophagy. There is even some improvement in thought-processing and reduction of risk of cognitive impairment.

Studies show that these diets improve various markers, including fasting insulin and glucose levels, cholesterol, and inflammatory markers, IL-6 and TNF-alpha. There was also an improvement overall in mood and self-confidence with a reduction of tension and anger.

Overall, the starvation state, one that normally occurs from after dinner to breakfast, is a normal physiologic process where the body begins to consume adipose stores as a fuel source. Various type of fasting extend this period, accentuating the process. The body resorts to using more adipose stores, while insulin secretion drops and glucagon levels go up.

The pituitary gland is an important point of the hypothalamic-pituitary-adrenal (HPA) axis, the main regulating system of the body. Pituitary hormones follow a circadian rhythm, meaning that there is a change in production whether its daytime or nighttime. Accordingly, there may be a benefit in eating during certain hours of the day. In a recent review of 23 articles suggested a weight loss of 3% and loss of fat mass with time-restricted eating limited to the day. However, further studies are needed to clarify this effect.

Fasting: Summary and Recommendations

1. Periods of fasting improve metabolic functioning in the body, which provide a host of benefits
2. The body furnishes cellular requirements through processes such as breaking down glycogen and adipose stores.
3. The numerous benefits of fasting include improvements in fatty liver, diabetes, adipose stores, microbiome, and inflammation.
4. Consider adding intermittent fasting with the assistance of your primary physician or health coach.

Welcome to the Daily Apple, a new page on Your Health Forum that addresses questions that you may be curious about and likely come up in clinic visits. The goal is to answer questions in a helpful format to allow quick learning and application in an article about 500 words or less.

Bibliography

Adafer R, et al. Food Timing, Circadian Rhythm and Chrononutrition: A Systematic Review of Time-Restricted Eating’s Effects on Human Health. Nutrients. 2020. 12(12):3770. doi:10.3390/nu12123770.

Cahill G. Starvation in Man. Clinics in Endocrinol and Metabolism. 1976. 5(2): 397-415.

Patterson R, Sears D. Metabolic Effects of Intermittent Fasting. Annual Rev Nutrition. 2017. 37:371-393.