Think fast: a review of research on intermittent fasting

Recommendation: Once you’ve balanced your diet, sleep schedule, and exercise/movement, consult your doctor to see if fasting is safe for you. If your doctor has no concerns for you adopting a light fasting regimen, see if you can comfortably adopt one of these two methods (alternatives are discussed below):

1. Fast one day per week for 20 hours (including 7-9 hours sleeping). If you handle it well, consider increasing the number of fasting days to every other day for up to one month at a time (then go back to one day/week). Negative effects have been seen from long-term alternate-day fasting regimens (6, 8 months)1 2 , so I don’t feel comfortable following this method for longer than 4 weeks even though these results are uncommon.

–OR–

2. Adopt a 12/12 eating schedule each day. Don’t worry which hours you eat, but make sure to only eat within a 12-hour window of time. This could be not eating after 10pm, sleeping 12-7am, and fasting until 10am. Water, plain tea, and plain coffee are probably fine during fasting hours, though studies haven’t tested the effects of tea/coffee on fasting.

Major assumption: this assumes healthy food is being eaten. Whatever benefits fasting provides are assumed limited to the nutritional value of whatever food is eaten. Also, because the effects are seen all over the body there are too many mechanisms involved for us to totally understand how dietary restriction might work to benefit us until we study it further (though at least two mechanisms are known–reduced oxidative damage and increased cellular stress resistance).3 Still, several pathways, proteins, genes, etc. have been identified specifically and are the targets of ongoing research.

Why should anyone consider this?

In 2014, after reviewing over 100 studies on intermittent fasting (IF), doctors at USC, Johns Hopkins, and the National Institutes of Health had this to say:

“Based on the existing evidence from animal and human studies described, we conclude that there is great potential for lifestyles that incorporate IF during adult life to promote optimal health and reduce the risk of many chronic diseases, particularly for those who are overweight and sedentary.”4

To prevent over-excitement, heart doctors at the University of Utah reviewed research up to January 2015 seeking randomized controlled clinical trials which supported the growing interest in fasting as a health intervention. They had this to say:

“Whereas the few randomized controlled trials and observational clinical outcomes studies support the existence of a health benefit from fasting, substantial further research in humans is needed before the use of fasting as a health intervention can be recommended.”5

Still, an August 2015 review of 69 intermittent fasting studies (all species) commented:

“In healthy, normal weight, overweight, or obese adults, there is little evidence that intermittent fasting regimens are harmful physically or mentally (ie, in terms of mood).”6

What I took away from these quotes and the research presented here is that doctors are very interested in the practice of strategic, deliberate fasting as a way to encourage health. But like with all medicine, a doctor cannot recommend fasting as a promoter of health without ample data–meaning clinical results of well-designed, valid, and peer-reviewed studies. This leaves us, as owners of our health, to determine how we can incorporate this promising concept of fasting for ourselves, understanding that medical experts aren’t yet able to fully and “openly” support its wide-spread adoption.

Research has long suggested there may be benefits from a restricted diet (anywhere from 10-40% reduction in daily calories). Published results include up to 50% increased average and max life span in yeast, roundworms, rodents, and monkeys (human diets are harder to restrict in a lab and live way too long).7 In humans, Alzheimer’s risk may be reduced by caloric restriction.8 This is even a lifestyle now adopted by many people expecting to extend their lives up to 1/3. The goal is not only to increase quantity of life, but also quality of life in later years.

“Caloric restriction (CR) is the most effective antiaging therapy to date. A reduction of 10–40% in food consumption while maintaining adequate nutrients increases the average and maximum lifespan in many experimental model organisms. The exact mechanisms of CR have yet to be elucidated, but they appear to involve highly conserved mechanisms of stress response.”9

Several major health journals recognize accelerating amounts of research across species showing beneficial physiological effects of CR and IF on health span. The Journal of Nutritional Biochemistry is among those publishing the range of documented effects:

“Prominent among these are the following: increased insulin sensitivity that results in reduced plasma glucose and insulin concentrations and improved glucose tolerance; reduced levels of oxidative stress as indicated by decreased oxidative damage to proteins, lipids and DNA; increased resistance to various types of stress including heat, oxidative and metabolic stresses; and enhanced immune function.”10

Definition and variations

“Intermittent fasting” (IF) is any regimen which requires partial or complete fasting on a repeating cycle. An example is eating one day, fasting the next, and repeating that cycle indefinitely. “IF” is different than, but related to “calorie restriction”, which is a sustained significant reduction in total calorie intake over time regardless of any eating schedule. An example would be simply eating 60% of the calories you normally would each day, indefinitely. Calorie restriction (CR) is uniformly accepted as a way to extend life, mostly by leading to reductions in known disease risk-factors. Support for 1 day/wk fasting (a form of IF), comes from several studies, but as one put it, “achieving a moderate reduction in energy intake in middle-aged adults, such as through a 1 day/week fasting regimen, could be a much less daunting task than a 40% reduction in intake from adolescence onward.”11 Thus, CR and IF are both in the category of “having enough evidence to warrant changing behavior” in my opinion (as well as the opinion of many doctors, researchers, dieticians, and especially “bio-hackers”). In reality, many IF regimens lead to calorie restriction, since extra calories aren’t always consumed on the non-fasting periods. Alternatively, you could eat extra calories during non-fasting periods to make up for lost calories during fasts. Surprisingly, benefits have been seen with this, too.

Many different diets fall into these two categories (IF and CR). Each of them involves some kind of significant restriction–either cyclical, total starvation periods (i.e. intermittent fasting) or daily reduced caloric intake (often about 60% of the amount you would eat, otherwise). An example of non-intermittent caloric restriction would be the regimen of eating 60% of ad libitum calories daily. However, it is again important to note these diets are supplemented with vitamins and minerals, so eating healthy when you do eat is key.12 As one publication describes, IF regimens vary in research:

“The number of Energy Restricted(ER)-days per week and degree of (Restriction) of partial Intermittent ER protocols has varied between studies, but ultimately this approach entails intermittent periods of very low energy intake, ranging between 15-50% of energy requirements. Individuals are then asked to consume an ad libitum or euenergetic intake on non-restricted days.”13

The focus here is “true” fasting

Though IF diets allowing some calories during fasting periods are shown beneficial, my biggest interest is in research regarding total fasting (0 calories) during certain windows of time throughout the day or week. For example, a 16/8 eating schedule means you only eat within a window of 8 hours each day (e.g. noon to 8pm) and totally fast for 16 hours (about 8 of which are sleeping, usually). IF, for me, is any repeated cycle of full-fasting and non-fasting periods, regardless of how many total calories are consumed over time. As with the 16/8 regimen, this article will cover protocols which call for periods of complete (0 calorie) fasting periods, even if they’re not full-day fasts.

Examples:
– Alternate Day Fasting “ADF” or Every Other Day Fasting “EODF” cycle: eat what you want for 24hrs, then 0 calories the next day.14 15
– Time-Restricted Fasting “tRF” e.g. 12/12 and 16/8: eat ad-libitum for a certain number of hours each day (an “eating window”), then fast the rest of the day.16 17 18
– 2 fasting days per week19
– 48 hour fasting:20
– 1 day/wk full fast:21 22

"DR"= (Dietary Restriction) "IF" =(Intermittent Fasting)
“DR”= (Dietary Restriction) “IF” =(Intermittent Fasting)

A significant range of benefits have been seen by these diets. Obese (note: not healthy) mice eating 20%-50% of their caloric requirement every other day showed benefits in as little as two weeks noted by reductions in: insulin resistance, asthma, seasonal allergies, infectious diseases of viral, bacterial and fungal origin, arthritis, symptoms due to CNS inflammatory lesions cardiac arrhythmias (PVCs, atrial fibrillation), and menopause related hot flashes.23 Although that study represents an “intermittent” cycle of eating less, it’s also a calorie restriction regimen, and would not technically be considered “intermittent fasting” by some, though others refer to it as “modified” alternate day fasting (ADF).24

Fasting study results25

Observed Benefits of IF (all species)

Pivotal Roles of the Nervous and Endocrine Systems as Mediators of Adaptive Responses of Major Organ Systems to Intermittent Fasting
Pivotal Roles of the Nervous and Endocrine Systems as Mediators of Adaptive Responses of Major Organ Systems to Intermittent Fasting

– Increased resistance of neurons in the brain to excitotoxic stress, reduced risk of diabetes/better insulin activity.26 27
– Increased adiponectin.28
– Enhanced learning and memory29 30
– Improved risk factors for coronary artery disease and stroke including a reduction in blood pressure. 31 32
– Cardiovascular stress adaptation is improved and heart rate variability is increased33
– Increased autophagy (referred to as “cellular cleansing”) within the body and brain; and, specifically, within cortical neurons34

Studying short vs long-term IF regimens

As seen with most studies, 4, 12, and even 64 week studies of every other day fasting have all shown benefits.35 36 37 However, in obesity-prone mice, how long the rats were fed on an IF diet mattered. Short-term (4 weeks) calorie restriction and intermittent feeding presented similar benefits relative to glucose tolerance. Surprisingly, long-term (32 weeks) intermittent feeding promoted glucose intolerance (BAD), similar abdominal fat levels (unfortunate), and low serum adiponectin (no bueno), and significantly increased reactive oxygen species (ROS) release (ROS are a specific type of potentially damaging “free radical”).38

Final summary and outlook

We’re gathering significant data to support the benefits of short-term fasting–benefits which may even surpass those of caloric restriction (reduced serum glucose and insulin levels and increased resistance of neurons in the brain to excitotoxic stress (overstimulation)). Though most of my research led to studies of “Every-Other-Day” fasting39 40 41 , various lengths of fasts have been studied. Also, short-term fasting is shown to provide benefits even while maintaining body weight and caloric intake. Again, this would suggest eating 2,000 calories daily may not be as healthy as 4,000 every other day. “The mechanism remains unknown, but the need for a long-term reduction in caloric intake to achieve these benefits has been assumed”.42 The phrase “long-term” simply means the benefits from these diets might only come if you start early in life and that they compound over time. That concern has been reduced with further research, but in general the earlier fasting is started the more significant its effects–good or bad–are. Overall, it seems this will continue to be a key area of nutrition and medicine research going forward. Because of that fact and its probable health benefits it is more than reasonable to spend a little effort determining if you can incorporate fasting comfortably!


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