Isabel Azevedo
Porto, Portugal

Having struggled with the obesity epidemic for decades,^1,2 the scientific and health care communities are now giving attention to the effects of fasting for preventing and treating this important health problem. Appearing at first sight to be a simple issue of energetic balance, obesity has been shown instead to be a complex disease with genetic, behavioral, socioeconomic, and sociocultural determinants. It is moreover entangled with insulin resistance, hypertension, and dyslipidemia as part of the metabolic syndrome, a major cause of type 2 diabetes and cardiovascular disease.³

As expected, calorie restriction reduces body weight.^4,5,6 Most humans, however, have been shown to be incapable of voluntarily restricting calorie intake for long periods of time.⁷ By contrast, intermittent fasting also decreases body weight and appears much more feasible.⁸ As a matter of fact, humans have practiced intermittent fasting for millennia—for environmental, medical, or religious reasons.

Intermittent fasting is a dietary approach in which no or few calories are consumed for periods ranging from twelve hours to one or more days, in a recurrent pattern. There is an extensive and solid amount of research work in animals and some studies in humans demonstrating the striking effects of fasting. As previously described for calorie restriction, fasting decreases body weight and improves metabolic parameters associated with type 2 diabetes, cardiovascular disease, and cancer.^9-12 Intermittent fasting has additional health benefits when compared to calorie restriction in that it favorably interacts with circadian biology, gut microbiota, and motor activity.^9-11,13,14 It also spares lean mass, a most important point, especially in the context of aging.⁸

The metabolic consequences of fasting were first published in the nineteenth century. The biochemistry and physiology of the feed-fast cycle, with the metabolic switch between glucose oxidation and fat oxidation/ketogenesis, along with the ratio insulin/glucagon hormones, have been studied for many decades. It is well known that to remove fat acquired in times of plenty, it is necessary to fast for long enough to deplete liver glycogen, revert the insulin/glucagon ratio, and shift metabolism from lipid synthesis to fat mobilization through fatty acid oxidation and production of ketones. It is thus intriguing that attention to fasting as therapy for obesity has taken such a long time.

More recent is the discovery of orexins, neuropeptides produced in the hypothalamus during fasting. They increase appetite and increase vigilance, exploration, and locomotor activity.^15-18 Dietary regimens that include significant periods of fasting facilitate motor activity, in contrast to feast periods, when the body demands rest. This is probably a further mechanism by which fasting benefits health.

Although ketones were shown more than fifty years ago to be the primary fuel for the brain during starvation, they were thought of being mere metabolic fuel.¹⁹ Recent research, however, has been showing a growing number of pleiotropic effects of ketones at the central nervous system. Beyond prevailing interest in the treatment of epilepsy,²⁰ ketones may be useful in the treatment of Alzheimer’s disease,^21,22 and may be responsible for the improvement in various cognition parameters observed during fasting.¹¹

It can be concluded that intermittent fasting regimens promote weight loss and may improve metabolic health. They also induce metabolic and signaling pathways that optimize performance, slowing aging and disease processes.

A variety of intermittent fasting regimens have been studied.^10,11 In “time-restricted eating” a minimum of twelve hours of nightly fast is recommended, sixteen hours being better.^11,23 An interesting regimen is one called “5:2” (severe energy restriction for two non-consecutive days per week and ad libitum eating for the other five days). It mirrors the traditional religious fasting of Jews and Christians.²⁴ Christians, however, dropped one of the weekly fasting days,* and currently obligatory fast is reduced to two days per year (Ash Wednesday and Good Friday in Lent).²⁴

Most religions recommend periodic fasting, presumably to enhance spirituality. The impact of fasting on resting state brain networks²⁵ or on the activation of dopaminergic activity by orexin,²⁶ are indeed compatible with an ego dissolution effect, as described for mindfulness ²⁷ or some drugs.²⁸ But prescription of fasting by religious authorities also seemed to include a hygienic aim, as in St. Paul’s Letter to the Philippians, or in St. Anthony’s (1195 –1231, born in Lisbon, died in Padua) sermon. St. Anthony considered that gluttony had several forms: eating ravenously, too much, or too soon. This instruction from hundreds of years ago is now receiving support from modern science: time-restricted eating is a powerful cue to synchronize body and brain clocks, leading to marked health benefits.^9,23,30

Editorial note

* For Catholics, traditional abstinence from meat on Fridays was modified in 1966 to allow other penitential acts in substitution. See https://www.usccb.org/prayer-and-worship/liturgical-year-and-calendar/lent/us-bishops-pastoral-statement-on-penance-and-abstinence

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