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In recent years, interest in intermittent fasting—that is, not eating at all for a certain number of days per week—has been increasing. Intermittent fasting (IF) has been practiced worldwide based mostly on traditional, cultural, or religious grounds, but recent experimental data suggest it’s not only safe but also effective for achieving weight loss. What’s more, evidence is accumulating that it can produce a myriad of other health benefits. In this article, I summarize the data supporting the use of IF and include my recommendations for who might want to try it and how they should do it.

For Weight Loss

One concern about reducing calorie intake on a daily basis (that is, dieting) to lose weight is that it lowers the basal metabolic rate (in one study as much as 504 cal/day!), making weight loss harder to achieve. Some studies have suggested this effect continues for a full four years after beginning a diet, and may continue longer or even indefinitely, explaining one of the reasons why it’s so easy to regain any weight that’s lost, as opposed to maintaining the weight you’ve always been.

In one study of IF, however, basal metabolic rate was actually found to increase after both 36 and 60 hours of fasting, likely due to an increase of norepinephrine (which was likely caused by lower blood sugar induced by the fast). Fat metabolism also increased (meaning fat was preferentially burned for energy over glycogen, or carbohydrate), likely caused by the increase in norepinephrine levels (rather than a decrease in insulin levels, which wasn’t seen). Muscle breakdown wasn’t seen until the end of the third day of fasting. Other studies have shown that prolonged fasting—that is, beyond three days or more—can reduce the basal metabolic rate by 20%.

After a 36-hour fast, when you start eating again you continue to burn fat in excess of glycogen (carbohydrate) for energy. Long-term use of IF may, in fact, shift the substrate the body uses for energy preferentially to fat, though it’s not clear how often you need to fast to bring about this shift. One concern about every-other-day fasting, however, is that it might represent too great a metabolic challenge: in the long-term it seems to decrease glucose tolerance, which might lead to or predispose to the development of diabetes. More work needs to be done to sort out the ideal frequency with which you should fast to lose weight.

Interestingly, IF doesn’t appear to make you hungrier on days you eat. In fact, studies show people actually eat 20% less on eating days. This may be because eating less itself seems to reduce the amount of food that makes you feel full.

Studies suggest you’ll lose muscle if you only eat 0.9 g of protein/kg of body weight on non-fasting days when you’re intermittently fasting. It seems you need to eat 1.2 g of protein/kg of body weight on non-fasting days to preserve fat-free mass. That is to say, IF can cause muscle loss if you don’t eat enough protein and exercise.

In comparing the weight-loss effects of IF to continuous calorie restriction (a standard diet) multiple studies (admittedly all small) testing multiple different IF regimens demonstrated comparable reductions in body weight (with perhaps a slight advantage seen in IF). A longer-term, larger study called the HELENA trial will conclude in May of 2017. It will compare IF, continuous calorie restriction, and control groups for a year and look not only at effects on weight loss, BP, quality of life, and self-image, but also 82 pre-defined genes that encode proteins involved in energy metabolism, inflammation, immune function, aging, and neurological function. I’ll report back on the results later this year once they’re published, which should help guide us more definitively in how to make IF work for weight loss.

Time restricted feeding (TRF), in which all food is consumed in a narrower window than what’s traditional (8 hours instead of 10 or 12) may mimic the positive effects of a longer fast. In one study, TRF was found to increase fat loss without compromising muscle mass in men who lifted weights (though it reduced anabolic hormones like testosterone and IGF-1) compared to men who lifted weights but ate on a normal schedule (the same total number of calories were consumed by both groups). The notion that the timing and interval of eating affects weight loss finds evidence in another study of women who ate their largest meal in the morning rather than in the evening and had greater weight loss than women who ate their largest meal in the evening (same number of total calories consumed per day in both groups). This was thought to be due to decreased insulin sensitivity at the end of the day, leading to higher levels of insulin around the evening meal. Higher levels of insulin may contribute to weight gain because insulin works to promote fat storage, decrease fat burning, and increase glycogen (carbohydrate) burning.

My recommendations for using IF for weight loss:

1. You should always make sure that whatever strategy you use to lose weight is a strategy you use to maintain weight loss, that you can maintain indefinitely. Otherwise, you’ll almost certainly regain any lost weight once you change your eating lifestyle after achieving your weight-loss goals. That is, if you’re going to use IF, make sure you can continue some form of IF (albeit perhaps fewer days per week or fasting on individual days for a shorter duration) indefinitely.
2. Don’t fast longer than 3 days in a row (to preserve muscle mass and prevent a reduction in basal metabolic rate).
3. I suggest fasting for 36 hours  at a time (e.g., from Monday night after dinner to Wednesday morning at breakfast) no more than twice a week. Alternatively, you could eat your first meal of the day around noon and your last meal no later than 8 pm every day. You will, of course, get hungry on days you fast, but you won’t feel hungry all day long. Your hunger will come and go, typically around the times you would normally eat. If you distract yourself by becoming engaged in the tasks of your day when you feel that hunger, it will tend to fade within 10-30 minutes. Make sure to drink adequate amounts of water during fasting so you don’t become dehydrated.
4. Make sure to exercise and take in adequate levels of protein on non-fasting days to maintain your muscle mass.
5. Combine IF with a low-carb diet on days you eat. I’d also include a cheat day as I described in a previous article.
6. If you have diabetes, make sure to embark on IF only under the close supervision of your doctor.
7. If you have or have had an eating disorder, IF is not for you.

Other benefits of IF might include:

1. Cardiovascular: Levels of adiponectin, which has anti plaque-forming and insulin-sensitizing properties, are increased through IF. Leptin, a pro plaque-forming adipokine, is reduced. No studies have yet looked at cardiovascular outcomes, however, with IF (e.g., risk reduction in heart attacks).
2. Neurological: Calorie restriction increases the transcription of genes coding proteins involved in neuroplasticity and neuron survival. In rats and mice on an alternate-day fasting regimen, proteins that function to prevent protein damage in neurons are elevated. Calorie restriction in general up-regulates autophagy (which enhances removal of damaged proteins in cells). Energy restriction of 30% below what subjects typically consumed improved glucose metabolism, suppressed oxidative damage and inflammation, and protected against cancer, heart disease, diabetes, and muscle wasting in a study of non-human primates. It also preserves volumes of brain structures involved in emotional control. In animal models of reduced calorie intake, outcomes from stroke and traumatic brain injury are improved. Animals with experimentally induced strokes recover function better on restricted diets. Alternate day fasting protects rats from cognitive impairment in Alzheimer models. Calorie restriction protects dopaminergic neurons in rodent Parkinson’s disease models. Fasting improves memory in human subjects who reduce their caloric intake by 30%. It’s important to note that while many studies strongly suggest there very well could be multiple benefits to our brains from IF, no definitive study has been done in humans that proves IF has a significant impact on the risk of getting a neurologic disease or effect on reducing the impact of a neurologic disease.
3. Extended lifespan: We don’t actually know if the extension of lifespan reported in animal studies of calorie restriction are due to the effects of calorie restriction itself or to the effects of intermittent fasting as in all of them the subjects ended up intermittently fasting as well as eating a lower calorie diet. It’s certainly exciting to imagine that we could extend our lifespan simply by fasting a certain number of days a week, but currently we have no definitive proof that IF provides this benefit. More work in this area is needed.
4. Cancer risk reduction: A retrospective study of 7000 women with a history of anorexia nervosa showed a 50% reduction in the incidence of breast cancer, suggesting that severe calorie restriction may protect against breast cancer. This doesn’t mean that if you’re worried about cancer or have cancer that you should restrict your calories as severely as patients with anorexia do. While there is evidence that IF both immediately before and after receiving chemotherapy can reduce the side effects of chemotherapy and possibly enhance its effectiveness, IF alone without chemotherapy hasn’t been shown to improve survival if you have cancer. On the other hand, calorie restriction has been shown to decrease cellular proliferation and angiogenesis (the creation of new blood vessels that feed cancer cells). Calorie restriction is also associated with a significant anti-inflammatory response in humans, which may inhibit cancer progression and malignant conversion. Calorie restriction in combination with radiation therapy aids in tumor regression and may delay metastasis. Also, in mice, calorie restriction caused a 55% decrease in the incidence of breast cancer. Its effect on cancer rates in humans, however, remains unknown.
5. Diabetes control: The dramatic improvement rates of resolution of diabetes (83%) in patients undergoing gastric bypass are likely due not to the surgery itself but to the dramatic restriction in calories that results. IF may mimic this result.

In conclusion, current evidence suggests—though doesn’t yet prove—that IF may have a multitude of health benefits in humans. The HELENA trial will more definitively answer many of the questions that remain and hopefully provide even clearer proof that long-term use of IF is safe. If you’re interested in losing weight, in maintaining weight loss, or gaining some of the other possible benefits of IF, IF may indeed be something you want to try. It may take a strong determination, but it’s something most people can do.

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