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Fasting – the voluntary abstinence from food and drink – is an ancient tradition, long believed to be vital to humans’ physical and spiritual health. Practiced for millennia by various cultures and religious groups, fasting is now widely appreciated for its beneficial effects on human metabolism and healthspan.^{[1] [2] [3]}

A growing body of evidence suggests that in the absence of ready supplies of glucose and fats from meals, fasting flips a metabolic “switch,” liberating fat stores via fatty acid oxidation and ketone production while prioritizing the safeguarding of lean muscle mass and function.^{[4] [5]} As such, fasting provides a mechanism that not only improves overall body composition but also triggers the activation of biochemical processes and signaling pathways that optimize human performance and physiological function, possibly slowing the processes of aging and disease.^[6]

Fasting also stimulates hormesis, a compensatory defense response following exposure to a mild stressor (short-term food deprivation) that is disproportionate to the magnitude of the stressor.^{[7] [8]} Hormesis triggers a vast array of protective mechanisms that not only repair cell damage but also provide protection from subsequent exposure to more devastating stressors.^[9]

The term “fasting” is a broad one, comprising multiple types and subtypes of the practice, including intermittent, alternate-day, periodic, and others, and ranging in duration and degree of restrictiveness.

Common types of fasting

Intermittent fasting means different things to different people, even among the research community. This lack of specificity has been a source of consternation for experts in the field of fasting, with some advocating that the phrase be retired. Often, when someone uses this phrase they may actually mean one of the following:

• Time-restricted eating
• Alternate-day fasting
• Periodic or prolonged fasting (multi-day), sometimes referred to as intermittent

Time-restricted Eating

Time-restricted eating or time-restricted feeding refers to limiting food intake to certain hours of the day, without an overt attempt to reduce caloric intake. More often than not, this is what a person is referring to when they talk about intermittent fasting. The most common version of time-restricted eating is so-called “16:8” fasting where all of the day's calories are consumed within an eight-hour window, leaving 16 hours for fasting, including the hours during which a person is asleep.^[10]

Time-restricted eating exploits the body’s innate 24-hour patterns – the genetically encoded molecular clocks present in every cell, from the complex (liver cells) to the simple (hair follicles) – and provides the body an essential downtime where it can focus on DNA and cellular repair and restoration rather than digestion.^[11] As such, time-restricted eating may trigger some beneficial health effects, such as reduced fat mass, increased lean muscle mass, reduced inflammation, improved heart function with age, increased mitochondrial volume, ketone body production, improved repair processes, and enhanced aerobic endurance.^{[12] [13] [14]}

Interviews focusing on same-day fasting (time-restricted eating):

• Dr. Satchin Panda on Time-Restricted Feeding and Its Effects on Obesity, Muscle Mass & Heart Health
• Dr. Satchin Panda on Practical Implementation of Time-Restricted Eating & Shift Work Strategies

Alternate-day fasting

As the name implies, alternate-day fasting involves fasting every other day, while eating normally on non-fasting days. In a modified version of the alternate-day fast, participants can consume a small amount of food – approximately one-fourth of their optimal intake – on fast days. Alternate-day fasting appears to have the same effects as other variants of fasting and may be beneficial for weight loss due to its greater sustainability.^{[15] [16] [17]}

Prolonged Fasting

Prolonged fasting, sometimes referred to as periodic fasting, typically exceeds 48 hours. This type of long-term food deprivation can set off a unique set of metabolic events, such as deeper ketosis as glycogen stores are depleted, which may promote cellular and systemic clean-up through programs such as apoptosis and autophagy. A typical periodic fast in the research setting lasts between 48 and 96 hours.

While most people can safely practice time-restricted eating, periodic fasting may be more appropriate to do under the guidance of a physician. As a safer alternative, one approach appears to recapitulate many of the same effects of prolonged fasting with a hyper-low calorie, low protein, higher fat diet stretched out over a longer interval of five days – a diet called the fasting-mimicking diet. Fasting-mimicking recapitulates humans’ ancient patterns of exposure and response to famine and feast, providing a means of cellular renewal and disease protection.^[18]

Interviews covering prolonged fasting and fasting-mimicking:

• Valter Longo, Ph.D. on Fasting-Mimicking Diet & Fasting for Longevity, Cancer & Multiple Sclerosis
• Dr. Valter Longo on Resetting Autoimmunity and Rejuvenating Systems with Prolonged Fasting & the FMD

Interview discussing the cellular clean-up program autophagy:

• Dr. Guido Kroemer on Autophagy, Caloric Restriction Mimetics, Fasting & Protein Acetylation

Fasting concerns

Some evidence from epidemiological studies suggests that long overnight fasts are detrimental to health.

One study evaluated dietary factors that increased a person's risk for being hospitalized with gallstones. The study involved more than 4,700 women between the ages of 25 and 74 years who were enrolled in the first National Health and Nutrition Examination Survey (NHANES). Analysis of the women's dietary recalls and medical histories revealed that a long overnight fasting period and dieting were the two most important dietary risk factors for hospitalization with gallstone disease. Compared to eight hours of fasting, nine hours of fasting was associated with approximately 30 percent increased risk of gallstones; 15 hours of fasting was associated with a 100 percent increased risk of gallstones, even after adjusting for other risk factors.^[19]

Another study based on NHANES data investigated associations between skipping breakfast (in effect, creating a long overnight fast) and increased risk for developing cardiovascular disease. The study involved more than 6,500 adults between the ages of 40 and 75 years. Participants reported their breakfast eating habits as follows: 5.1 percent never consumed breakfast. 10.9 percent rarely consumed breakfast, 25.0 percent consumed breakfast some days, and 59.0 percent consumed breakfast every day.

Participants who never consumed breakfast were 87 percent more likely to die from cardiovascular disease-related deaths and were 19 percent more likely to die from all causes of premature death compared with those who ate breakfast every day. However, there was either a null or a protective effect for those who ate breakfast sometimes or rarely, implying that never eating breakfast is simply a biomarker for other unhealthy habits that confound interpreting the data. After adjusting for known confounding factors, the results from the group that never ate breakfast remained significant but results from the group that ate breakfast sometimes or rarely also remained null or protective. This implies that there are other confounding factors that were not accounted for.

The major weakness of epidemiologic studies such as these is their inability to experimentally establish cause and effect. The association between long fasting periods and increased risk for disease or death may be related to factors other than the fasting itself. It is noteworthy that fasts of approximately 12 hours in duration have shown no harmful effects.^[20]

Transformative effects of fasting

Most people who practice fasting report feeling energized and more alert at the end of their fast, which may represent a “resetting” of their body’s natural metabolic rhythms. This transformative effect of fasting appears to be linked to certain aspects of repair and rejuvenation that are integral to fasting physiology and may provide critical elements in optimizing lifespan and healthspan.