Intermittent Fasting

Periods of voluntary abstinence from food and drink (i.e., intermittent fasting) has been practiced since earliest antiquity by peoples around the globe.

The major mechanisms to link fasting regimens with human health: (1) circadian biology, (2) the gastrointestinal microbiota, and (3) modifiable lifestyle behaviors such as diet, activity, and sleep.

Alternate Day Fasting

Alternate day fasting involves “fasting days” in which no energy-containing foods or beverages are consumed alternating with days where foods and beverages are consumed ad libitum. In 2007, Varady and Hellerstein reviewed alternate day fasting studies in animals and concluded that this fasting regimen was as effective as simple caloric restriction in decreasing fasting insulin and glucose concentrations. Alternate day fasting in animals also reduced total plasma cholesterol and triglyceride (TG) concentrations, and had beneficial effects on cancer risk factors such as cell proliferation.

Modified Fasting Regimens

Modified fasting regimens generally allow for the consumption of 20-25% of energy needs on regularly scheduled “fasting” days. In these studies, the term fasting describes periods of severely limited energy intake rather than no energy intake. This regimen is the basis for the popular 5:2 diet, which involves energy restriction for 2 non-consecutive days a week and usual eating the other 5 days.

Time-Restricted Feeding

Rothschild et al recently reviewed the animal literature on time-restricted feeding. Twelve studies were identified with daily fasting intervals ranging from 12 to 20 hours, in numerous mouse models, with variability in coordination with light/dark phases and composition of chow.
In spite of the heterogeneity of these studies, the authors concluded that in mice, time-restricted feeding was associated with reductions in body weight, total cholesterol, TGS, glucose, insulin, interleukin-6 (IL-6), and TNF-a, as well as improvements in insulin sensitivity.
It is notable that these health outcomes occurred despite variable effects of intermittent fasting on weight loss.

Ramadan Fasting

One of the five pillars of Islam is that healthy adult Muslims must fast from dawn to sunset during the holy month of Ramadan. In addition, fluid intake, cigarette smoking, and medications are forbidden.

Depending on the season and the geographical location of the country, day fasting can vary from 11 to 22 hours. Islamic fasting during Ramadan does not require energy restriction; however, as intake of food and fluid becomes less frequent, changes in body weight may ocures

Other Religious Fasts

A study of 448 patients from hospitals in Utah found that Church of the Latter Day Saints followers who reported routine fasting (29%) exhibited significantly lower weight and lower fasting glucose as well as lower prevalence of diabetes (OR 0.41; 95% CI 0.17, 0.99) and coronary stenosis (0.42, 95% CI 0.21, 0.84). Seventh-day Adventists emphasize a healthy diet and lifestyle as important expressions of their faith and live approximately 7.3 years longer than other white adults. This increase in life expectancy has been primarily attributed to healthful lifestyles including not smoking, eating a plant-based diet, and regular exercise. Seventh-day Adventists often consume their last of two daily meals in the afternoon, which results in a long nighttime fasting period that may be biologically important.

Circadian Biology

Intermittent fasting regimens that limit food consumption to daytime may leverage circadian biology to improve metabolic health, Organisms evolved to restrict their activity to the night or day by developing an endogenous circadian clock to ensure that physiological processes are performed at the optimal times. Time of day plays a major role in the integration of metabolism and energetics as well as physiologic indices such as hormonal secretion patterns, physical coordination, and sleep. In mammals, the master biologic clock is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and is entrained to light and dark stimuli. Similar clock oscillators have been found in peripheral tissues such as the liver; with feeding as the dominant timing cue (i.e., zeitgeber).

Gastrointestinal (Gut) Microbiota

Many functions of the gastrointestinal tract exhibit robust circadian or sleep-wake rhythms. For example, gastric emptying and blood flow are greater during the daytime than at night and metabolic responses to a glucose load are slower in the evening than in the morning. Therefore, it is plausible that a chronically disturbed circadian profile may affect gastrointestinal function and impair metabolism and health.

Intermittent fasting may directly influence the gut microbiota, which is the complex, diverse, and vast microbial community that resides in the intestinal tract. Studies suggest that changes in composition and metabolic function of the gut microbiota in obese individuals may enable an “obese microbiota” to harvest more energy from the diet than a “lean microbiota” and thereby influence net energy absorption, expenditure, and storage.

Modifiable Lifestyle Behaviors


Metabolic unit studies of alternate and modified day fasting have documented decreased energy consumption. However, studies of fasting regimens in free-living adults are dependent on self-reported energy intake, which correlates poorly with objective markers of energy intake. Weight change offers an indirect assessment of the impact of intermittent fasting on energy intake and as shown in statistically significant weight reduction was observed in 85% of intermittent fasting trials. Most fasting regimens reduce the total number of hours available for eating and thereby may reduce overall energy intake and risk of obesity. In addition, research in shift and night workers has demonstrated alterations in appetite-regulating hormones (leptin, ghrelin, xenin) that may lead to increases in total energy intake.


It is well known that in humans, even a single fasting interval (e.g., overnight) can reduce basal concentrations of metabolic biomarkers associated with chronic disease such as insulin and glucose. For example, patients are required to fast for 8-12 hours before blood draws to achieve steady-state fasting levels for many metabolic substrates. Therefore the important clinical and scientific question is whether adoption of a regular intermittent fasting regimen is a feasible and sustainable population-based strategy for promoting metabolic health. In addition, research is needed to test whether these regimens can complement or replace energy restriction and if so, whether they support long-term weight management. Below, we briefly summarize the major conclusions that can be drawn based on the current evidence.
Studies in rodents and other nocturnal mammals support the hypothesis that intermittent fasting and restricting the availability of chow to the normal nighttime feeding cycle improves metabolic profiles and reduces the risk of obesity, obesity-related conditions such as non-alcoholic fatty liver disease, and chronic diseases such as diabetes and cancer.
In healthy, normal weight, overweight, or obese adults, there is little evidence that intermittent fasting regimens are harmful physically or mentally (i.e., in terms of mood).
It appears that almost any intermittent fasting regimen can result in some weight loss. Among the 13 intervention trials included in this review, 11 (84.6%) reported statistically significant weight loss ranging from 1.3% in a cross-over trial with a 2 week intervention 23 to 8.0% in a 1-arm trial of 8 weeks duration
Based on only 3 studies, alternate day fasting appears to result in weight loss as well as reductions in glucose and insulin concentrations. However, this pattern may not be practical because of intense hunger on fasting days.
Modified alternate day fasting regimens result in reduced weight, ranging from 3.2% in comparison to a control group 16 over a 12 week period to 8.0% in a one-arm trial over an 8 week period. 13 There was limited and mixed evidence for reductions in insulin concentrations, improvements in lipids or reductions in inflammatory factors.
Research to date has not demonstrated that alternate day fasting regimens produce superior weight loss in comparison to standard, continuous calorie restriction weight loss plans.
There are limited data from human studies to support the robust rodent data regarding the positive impacts of time-restricted feeding (i.e., eating patterns aligned with normal circadian rhythms) on weight or metabolic health.
There are considerable observational data on various forms of religious fasting, most of which suggests that these regimes result in transitory weight loss with mixed impacts on other biomarkers.
Data are lacking regarding the impacts of intermittent fasting on other health behaviors such as diet, sleep, and physical activity.
There are little or no published data linking intermittent fasting regimens with clinical outcomes such as diabetes, cardiovascular disease, cancer, or other chronic diseases such as Alzheimer’s.