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):

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:

Interview discussing the cellular clean-up program autophagy:

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.

  1. ^ The effect of short-term fasting on liver and skeletal muscle lipid, glucose, and energy metabolism in healthy women and men Journal of Lipid Research 53, no. 3 (December 2011): 577–86. https://doi.org/10.1194/jlr.p020867.
  2. ^ A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan Cell Metabolism 22, no. 1 (July 2015): 86–99. https://doi.org/10.1016/j.cmet.2015.05.012.
  3. ^ Metabolic Flexibility: Interplay of Diet Composition and Intermittent Fasting on Healthspan (P08-053-19) Current Developments in Nutrition 3, no. Supplement_1 (June 2019). https://doi.org/10.1093/cdn/nzz044.p08-053-19.
  4. ^ Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice Endocrinology 157, no. 2 (December 2015): 679–91. https://doi.org/10.1210/en.2015-1622.
  5. ^ Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting Obesity 26, no. 2 (October 2017): 254–68. https://doi.org/10.1002/oby.22065.
  6. ^ Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans Cell Metabolism 30, no. 3 (September 2019): 462–76.e6. https://doi.org/10.1016/j.cmet.2019.07.016.
  7. ^ Beneficial Effects of Mild Stress (Hormetic Effects): Dietary Restriction and Health Journal of PHYSIOLOGICAL ANTHROPOLOGY 29, no. 4 (2010): 127–32. https://doi.org/10.2114/jpa2.29.127.
  8. ^ Dietary restriction, glycolysis, hormesis and ageing Biogerontology 8, no. 2 (September 2006): 221–24. https://doi.org/10.1007/s10522-006-9034-x.
  9. ^ Hormesis defined Ageing Research Reviews 7, no. 1 (January 2008): 1–7. doi:10.1016/j.arr.2007.08.007.
  10. ^ Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males Journal of Translational Medicine 14, no. 1 (October 2016). doi:10.1186/s12967-016-1044-0.
  11. ^ Time-restricted eating and circadian rhythms: the biological clock is ticking Critical Reviews in Food Science and Nutrition , July 2020, 1–13. https://doi.org/10.1080/10408398.2020.1789550.
  12. ^ Metabolic adaptations of liver mitochondria during restricted feeding schedules American Journal of Physiology-Gastrointestinal and Liver Physiology 289, no. 6 (December 2005): G1015–G1023. https://doi.org/10.1152/ajpgi.00488.2004.
  13. ^ Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans Nutrients 11, no. 6 (May 2019): 1234. https://doi.org/10.3390/nu11061234.
  14. ^ Metabolic and molecular framework for the enhancement of endurance by intermittent food deprivation The FASEB Journal 32, no. 7 (February 2018): 3844–58. https://doi.org/10.1096/fj.201701378rr.
  15. ^ Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and cardioprotection in obese adults The American Journal of Clinical Nutrition 90, no. 5 (September 2009): 1138–43. https://doi.org/10.3945/ajcn.2009.28380.
  16. ^ Weight-Loss Outcomes: A Systematic Review and Meta-Analysis of Intermittent Energy Restriction Trials Lasting a Minimum of 6 Months Nutrients 8, no. 6 (June 2016): 354. https://doi.org/10.3390/nu8060354.
  17. ^ Defining the Optimal Dietary Approach for Safe, Effective and Sustainable Weight Loss in Overweight and Obese Adults Healthcare 6, no. 3 (June 2018): 73. https://doi.org/10.3390/healthcare6030073.
  18. ^ Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease Science Translational Medicine 9, no. 377 (February 2017): eaai8700. https://doi.org/10.1126/scitranslmed.aai8700.
  19. ^ A prospective study of hospitalization with gallstone disease among women: role of dietary factors, fasting period, and dieting. American Journal of Public Health 81, no. 7 (July 1991): 880–84. https://doi.org/10.2105/ajph.81.7.880.
  20. ^ Intermittent and periodic fasting, longevity and disease Nature Aging 1, no. 1 (January 2021): 47–59. https://doi.org/10.1038/s43587-020-00013-3.

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