Intermittent fasting’s current popularity has been sparked by promising research on caloric restriction and circadian rhythms. Caloric restriction is the practice of chronically restricting calories by 20-40% without inducing nutrient deficiencies. It has been shown to extend lifespan in a variety of animal models of aging, yet its effects on humans are still not clear. Looking for a more pleasant way to reap the benefits of caloric restriction, IF was proposed as an alternative, and it appears that many of the mechanisms behind the benefits of caloric restriction overlap with those of IF.¹ Circadian rhythm research suggests that nearly every tissue and physiological function experiences 24-hour oscillations. Cortisol, thyroid hormones, insulin levels, and even gut microbiota all exhibit diurnal rhythms and, along with light/dark cycles, food is a major driver of these rhythms. By purposely separating incompatible processes (such as digesting food and metabolic maintenance activities) we can set our daily rhythms to optimize physiology.² IF is an excellent way to synchronize the circadian rhythms that drive metabolism. The contemporary nutrition recommendation to eat frequently throughout the day and the constant availability of highly palatable foods has led the majority of Americans to eat for nearly 15 hours a day.³ Might it be that when we eat is as important as what we eat?

Benefits of Intermittent Fasting

Much of what we know about the potential benefits of IF comes from animal studies. From this research it has been hypothesized that IF may influence many biological functions that have wide-reaching effects throughout the body, including…

• reducing oxidative stress and the damage it causes.^{4 5} Oxidative stress is an imbalance between the production of free radicals (a.k.a. reactive oxygen species) and the body’s antioxidant defenses against them and its ability to repair the damage they cause. Oxidative stress is believed to be involved in the development of numerous diseases and conditions;
• increasing cellular resistance to stress, which makes cells better able to withstand metabolic and toxic insults;⁶
• helping to sync the circadian rhythms that control many metabolic pathways;⁷
• improving autophagy, the process by which the body recycles damaged and worn out cells to maintain homeostasis.^{8 9} Autophagy is important in maintaining muscle mass and a healthy immune response, for removing toxic compounds, such as the beta amyloid that accumulates in the brains of Alzheimer’s patients, and for protecting the structure and function of cells, such as the insulin-producing pancreatic beta cells.¹⁰ A reduction in autophagy is believed to be a major contributor to aging;
• modulating inflammation in the body and brain;^{11 12 13}
• increasing DNA repair;¹⁴
• improving mitochondrial health.^{15 16} Mitochondria are the energy producing structures found in most cells of the body. Mitochondria produce the energy, as ATP, that is required to fuel nearly every function and biochemical process in the body.

These mechanisms have broad reaching impacts and support longevity and optimal metabolic function. IF might be beneficial in the following specific instances:

Aging

In addition to IF’s possible longevity benefits, it may also improve how we age. Middle-aged mice that were intermittently fasted for 12 weeks had improved motor coordination and learning response and decreased inflammatory markers.¹⁷ And in a small study of men, fasting increased growth hormone levels.¹⁸ It should be noted however, that not all research on IF and aging has been positive.  In one study, mice started on IF at 10 months (the equivalent of middle-age) actually had a decreased lifespan compared to mice started on IF earlier in life.¹⁹ Another study of mice found that although alternate-day fasting did extend lifespan in male mice, it did not positively affect many other markers of aging, suggesting that it extended life without slowing the aging process.²⁰

Blood Sugar Regulation

In animals, IF leads to improvements in fasting insulin, insulin resistance, and insulin sensitivity, and several small human studies support this effect in humans as well.^{21 22 23 24 25} In both rodent models and some small human studies, IF improved several markers of type II diabetes, although not all human research has corroborated this.^{26 27 28 29 30 31}

Brain Function

In animals, IF appears to protect and preserve brain function by modulating brain inflammation, stimulating production of proteins that enhance the brain’s resistance to oxidative stress and metabolic insults, and by stimulating autophagy and DNA repair.^{32 33 34} In animal models of neurodegenerative diseases like Alzheimer’s, Parkinson’s and Huntington’s, IF-fed mice perform better and show fewer symptoms than control mice.^{35 36 37} The benefits of IF may extend to other brain insults, like stroke, as well.^{38 39 40} It should be noted that most of the research in this area used IF prior to the brain insult or from a young age as a preventative measure, and while there is some research to indicate that taking up IF after a stroke or once a neurodegenerative disease has already begun may be helpful, results have been mixed and more research is needed to understand its full potential and limitations.^{41 42}

Cancer

In mice and rats, alternate-day fasting and time-restricted feeding appear to be protective against some types of cancer. However, two reviews of the available animal and human research concluded that we don’t yet have strong enough evidence to recommend IF as a cancer preventative.^{43 44 45 46} Another area where IF shows promise is in mitigating many of the side effects of conventional cancer treatments and even making conventional cancer treatments more effective against cancer cells while protecting healthy cells from damage.^{47 48 49 50} Talk to your doctor if you have cancer and want to know whether some form of fasting would be right for you.

Cardiovascular Health

In both animal and human studies, IF appears to lower LDL cholesterol and triglycerides without affecting HDL.^{51 52 53} Perhaps more importantly, it increases LDL particle size while decreasing the proportion of small dense LDL particles.^{54 55} Large, “fluffy” LDL particles are believed to be less atherogenic than small dense LDL particles. IF may also lower blood pressure.^{56 57} Middle-aged rats that had been fed an IF diet for three months had significantly less inflammation and damage after a heart attack than those that had been fed ad lib.⁵⁸ This same study found that animals on the IF diet had significantly higher levels of adiponectin, a hormone involved in regulating glucose levels and fatty acid breakdown, which may be cardioprotective.

Digestion

You may be familiar with peristalsis, the wave-like muscle contractions of the intestines that move food through the digestive tract, but you might not be familiar with migrating motor complex (MMC), rhythmic intestinal muscle contractions that are active between meals when the body is not actively digesting food. MMC plays a housekeeping role by sweeping undigested material through the digestive tract.⁵⁹ Disruption in MMC predisposes individuals to Small Intestinal Bowel Overgrowth (SIBO) and has been associated with IBS, functional dyspepsia, diabetes gastroparesis, obesity, anorexia nervosa and aging.⁶⁰ Allowing additional time between meals allows MMC to do its job.^{61 62} IF may even enhance intestinal stem cell function, which can enhance intestinal regeneration.⁶³

Weight Loss

Weight loss is a common side effect of IF, likely due to a natural reduction of calories and a shift to fat burning as the body uses up its available glucose and shifts towards fat for energy instead.^{64 65 66 67} Some studies have found that although weight decreased, fat mass didn’t, indicating a loss of lean muscle mass. This can be overcome by including strength/resistance training a few times a week.^{68 69 70} In animals IF also appears to increase brown adipose tissue, possibly by turning white adipose tissue into brown adipose tissue.^{71 72} Brown adipose, or fat, tissue is more metabolically active than white adipose tissue and increases the metabolic rate.

How to Intermittently Fast?

IF can take many different forms. Alternate-day fasting, often used in animal research, involves water only or very low calorie (~25% of normal caloric intake) intake for 24 hours followed by free eating for 24 hours, in a repeating cycle. Periodic fasting is usually used to refer to a fast lasting anywhere from two days to two weeks that is undertaken 1-12 times a year, bookended with normal eating. A popular take on this is 5:2 IF which involves zero or low-calorie intake 2 nonconsecutive days of the week with regular eating the remaining 5 days. Time-restricted feeding, or a compressed eating window, limits the daily eating window, such as eating only between 10 am and 6 pm, thus extending the nightly fast. Generally, outside of the specified fasting time, eating is allowed freely, without regard to caloric intake, although, for good health, food quality should still be considered.

For many, switching from a regular ad lib diet (as much food as often as desired) to a diet that requires you to go long periods without eating can be quite challenging. A good place to start is to try time-restricted feeding or a compressed eating window one or more days a week. Begin by simply extending your overnight fast little by little. At first this might look like simply eating breakfast 30-60 minutes later than normal or avoiding an after-dinner snack. Gradually you can increase the time between dinner and breakfast. As you do this, your body will begin to regain “metabolic flexibility”, the ability to switch back and forth easily between burning glucose and burning fat for fuel.⁷³ As you feel more comfortable, you can delay your first meal of the day until you naturally feel hungry. This should be a natural delay, not a forced starvation. Although 16 to 18 hours might be ideal, even a 12-hour fast, say from 7:00 pm to 7:00 am, offers benefits, so allow your body to be your guide.

Who is Intermittent Fasting Not Appropriate For?

IF is not appropriate for everyone. It is not appropriate for those with thyroid problems or HPA axis dysregulation (a.k.a. adrenal fatigue or burnout), those under a high amount of stress, women who are pregnant or breast-feeding, children and teens, or anyone who has or has ever had any type of eating disorder.^{74 75 76} Women who are trying to maximize their fertility should also avoid IF, unless they are highly overweight and have blood sugar issues that are affecting their fertility.⁷⁷ People who take prescription medications that should be taken with food may need to check with their doctor to ensure the medication is taken at the appropriate times. It should also be noted that much more research on IF is needed to fully understand the benefits and possible risks. Introducing IF at different ages or to different genders has led to different outcomes, reminding us that each person is individual and needs to adjust their diet, which may or may not include IF, to meet their personal needs.⁷⁸

Tips for Success

• Eat a healthy diet based on real, whole foods when not fasting.
• Eat to satiety when not fasting. Calorie counting and restricted food intake are generally not necessary, or good, when intermittently fasting.
• Aim to finish dinner at least two hours before bedtime. Eating a late dinner is correlated with higher morning blood glucose levels and a greater risk of prostate and breast cancer.^{79 80}
• Drink plenty of non-caloric fluids while fasting. This includes water, tea, herbal teas and coffee. Some people like to add a fat such as heavy whipping cream, coconut oil, ghee or MCT oil to their morning coffee while fasting. Although this does supply calories, fat calories are highly satiating and shouldn’t interfere too much with the body’s burning of fat, insulin sensitivity or autophagy.⁸¹
• People who are already keto-adapted tend to have an easier time adjusting to IF fasting, likely because their body is already accustomed to burning fat for fuel.
• If you experience things like fatigue, brain fog, insomnia, or irritability, these may be signs IF may not be appropriate for you or that it needs to be scaled back.⁸²

References

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