Getting Started with Intermittent Fasting

Answers by Dr. Krista Varady, Associate Professor of Nutrition at the University of Illinois, Chicago and author of “The Every-Other-Day Diet.” Varady has published results from over 10 clinical trials of intermittent fasting interventions.

Intermittent fasting (IF) often involves a daily cycle of fasting and feeding. IF is an umbrella term that refers to at least three different approaches to restricting calories intermittently. These include alternate day fasting, which involves eating fewer than 500 calories every other day, the 5:2 approach to fasting, which involves two fast days of fewer than 500 calories per week, and time-restricted feeding, which involves eating within a narrow 8-10-hour window each day.

A popular time-restricted feeding approach is the 16:8. This involves fasting during a 16-hour window and eating during an 8-hour window, either every day or several days per week. During your 8-hour eating window, for example from 10 a.m. to 6 p.m., you don’t have to count calories or necessarily change the way you eat. You simply confine any calories you consume to this window.

“It’s important to remember that with intermittent fasting, you do typically get to eat at least a little bit every day,” Dr. Krista Varady says. “There’s also no limitation on types of food or number of calories you eat during your feeding windows or ‘feast’ days.”

Based on current research in humans, there is limited consensus around optimal meal timing for people who practice intermittent fasting. We generally become more insulin resistant as the day progresses, or less able to clear blood glucose and get it to where it needs to go in our bodies. For this reason, it’s probably best to consume most of your calories earlier in the day and to start your fasting window several hours before you go to sleep.

“Your body can’t deal with nutrients (glucose) as efficiently later in the day, so you might as well give your body a break from glucose then,” Dr. Krista Varady says. “Early in the day, your body is primed and ready to deal with an influx of nutrients.”

If you are practicing an alternate day fasting regimen in which you eat under 500 calories on your fast days, you can either eat these calories in a single meal or divide them into three small meals throughout the day. Allowing for flexible meal timing on these fast days may help you maintain your fasting practice long term.

Scientific research studies have not yet fully evaluated the efficacy of different types of post-fast meals on metabolic health in humans.

A handful of existing studies suggest that some people may experience an acute blood sugar spike, associated with insulin resistance, following a post-fast meal high in carbohydrates. However, this acute postprandial insulin resistance may be more likely to occur in individuals not accustomed to prolonged periods of fasting (16-24 hours). If you are new to fasting, you may want to break your overnight or longer fasts with meals low in glycemic index and high in fiber and plant fats (olives, nuts, seeds, avocado, coconut, etc.) After practicing intermittent fasting for several months, your body will likely experience different metabolic reactions to an influx of nutrients post-fast. IF generally leads to improved insulin sensitivity and lower blood glucose levels over time.

Fasting has metabolic health benefits independent of what you are eating during your feeding periods. However, fasting will not turn a junk food diet into a good one.

In a study of people practicing IF and eating either a regular (25% fat) or high-fat diet (45% fat), Dr. Krista Varady found no significant differences in metabolic health between these two treatment groups over time. Each group displayed similar decreases in weight and coronary heart disease risk factors including LDL cholesterol and triglyceride levels.

Varady is currently exploring whether there are any links between fasting, low-carb diets and improved metabolic health. Many people who practice IF pair their fasting schedule with a ketogenic or very low-carb diet. However, there is little scientific research from human trials to determine any benefits or issues of pairing these interventions. The problem with ketogenic dieting is that it often leads people to eat an overabundance of unhealthy animal fats as opposed to healthier plant fats.

“I’d recommend eating your typical American Heart Association diet, or a balanced diet of protein, carbs and fats,” Dr. Krista Varady says.

Absolutely. In fact, combining fasting with endurance exercise can produce superior changes in body weight, body composition and lipid indicators of heart disease risk, compared to either exercise or fasting alone.

Contrary to popular belief, it is safe to exercise on alternate fast days or during fasts not exceeding 24 hours. In fact, in studies of IF, research participants often report boosts of energy on days when they fast or eat fewer than 500 calories.

“In the first 10 days of an alternate day fasting practice, you may notice decreases in energy or concentration levels,” Dr. Krista Varady says. “But after these first 10 days, most people find it easy to still exercise on their fast days.”

In one of the first studies to combine fasting and exercise interventions, Varady ran a 12-week study of intermittent fasting combined with endurance exercise (brisk walking / cycling). Obese research participants on an alternate day fasting schedule came into the lab three days per week to exercise on stationary bikes and treadmills. When given the option of training during either “feast” or fast days, participants chose to exercise on fast days just as often as on feast days.

If your primary goal is weight loss, however, you may also want to wait until after exercise to eat during an alternate fast day, according to Varady’s study. Participants who consumed their one allotted fast day meal before exercise tended to get a burst of hunger an hour or so after exercising, leading them to often cheat and eat extra calories that day.

Intermittent fasting has potential benefits independent of weight loss, including increased insulin sensitivityfat oxidation and reduced inflammation. You can still practice IF even if you don’t want to lose weight, although you will need to make a concerted effort to eat enough on your “feast” days or during your daily feeding window to maintain your current weight and energy use.

“People who don’t want to lose weight can add a few more calories to their fast days,” Dr. Krista Varady says. In a study of research participants of healthy weight, she found that these people lost half a pound per week, on average, while practicing alternate day fasting, while obese individuals lost 2-3 pounds per week. “Healthy individuals need to make sure they get enough calories and carefully monitor their weight to make sure they don’t fall into the underweight category. But they can still expect to see metabolic benefits with very little weight loss.”

It’s important to be flexible. Intermittent fasting is ideally a lifestyle, not a fad diet. In Dr. Krista Varady’s studies of alternate day fasting, she tells people not to worry if they miss two or three fast days in a month. Sometimes your fast days might land on a holiday or during another family event, and it may be more stressful to stringently stick to your fast than to enjoy a piece of cake.

However, some people find that “cheating” derails their whole fasting schedule. If you are the type of person who needs a lot of structure to succeed at a healthy behavior, Varady suggests not skipping your fast days for family events or other occasions. However, for most people the occasional cheat day won’t significantly impede weight loss progress or metabolic health.

It can take anywhere from 12 to 24 hours to get into a state of partial ketosis. During a fast, once your serum glucose level drops by 20% your liver will start producing ketones to supplement the energy your brain needs.

Achieving full ketosis can up to 10 days on a ketogenic diet. Upon entering ketosis, some people notice a fruity smell on their breath, a decrease in appetite or lethargy, while other people don’t experience these symptoms at all. Remaining in full ketosis over time requires consuming fewer than 30 grams of carbohydrates per day.

The metabolic benefits of intermittent fasting, however, don’t depend on achieving a state of full ketosis while fasting. In studies of healthy obese individuals, Dr. Krista Varady has observed insulin resistance levels decrease by up to 40% when these individuals stick to an IF regimen for just a few weeks.

There are ketone ester supplements available for mass consumption today that can raise your blood ketone levels and help you achieve ketosis. For athletes, these supplements may help the body produce ketones that can be advantageous as an energy source during strenuous workouts. However, unless you are already on a ketogenic diet these supplements give your body mixed signals in terms of whether it should be burning primarily fats or sugars for fuel. These supplements may not be effective or necessarily safe for metabolic health long term, says Dr. Krista Varady.

Studies of intermittent fasting have generally not shown any significant impacts on ghrelin, the gut hunger hormone. It’s normal to feel hungry while fasted, even after practicing intermittent fasting for several months. You may find that over time, however, you are better able to deal with feelings of hunger and better able to distinguish between actual hunger and externally triggered food cravings, for example. Drinking plenty of calorie-free fluids or eating up to 500 calories on a fast day can help manage your feelings of hunger while in a fasted state.

In studies of alternate day fasting, Dr. Krista Varady has tracked dietary restraint, hunger, fullness hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), and adipokines or cell signaling proteins secreted by adipose tissue including leptin. In clinical studies, IF has been found to decrease leptin, a hormone that helps control energy expenditure, and increase experiences of satiety after meals.

First-time intermittent fasters often find the first 10 days of a time-restricted feeding or alternate day fasting regimen to be the toughest. According to Dr. Krista Varady, it typically takes people an average of five fast days to become accustomed psychologically and in terms of experiencing normal energy levels during fast days. However, after the first 10 days most individuals can adhere to their fast days or fasting windows and exercise as easily while fasted as fed.

One of the benefits of time restricted feeding (based on a 16:8 fasting schedule, for example) is that many people experience natural caloric restriction and weight loss without counting calories. In a study of time-restricted feeding (fasting for 16 hours per day), Dr. Krista Varady found that most research participants naturally reduced their daily caloric intake by 300 calories on average and lost 3% of their body weight after a three-month period, even while being instructed to eat normally.

Research on intermittent fasting for people with type 2 diabetes or at risk for type 2 diabetes is still preliminary, with much of the research in this area still being conducted in animal models. However, there are promising pilot study findings coming out of Dr. Krista Varady’s lab related to improved glucose regulation over time. Recent studies have found that IF may have a greater positive impact on insulin resistance than traditional calorie restriction diets. While more research is needed, diabetics and pre-diabetics may stand to benefit the most from IF.

All diabetic and pre-diabetic individuals should work with their primary care physician before and while practicing fasting in any form, as this intervention may alter their medication needs and other symptoms.

Intermittent fasting is a form of hormetic or “good” stress, which the body often responds to with improvements in metabolic and cellular performance. Theoretically, fasting prompts “self-eating” within the body, helping the body clean up damaged cells and cellular components including proteins that can cause issues when they accumulate later in life. If you are overweight, fasting and losing weight can help you shrink your body in such a way that many damaged and senescent cells are eliminated naturally.

Human research studies on fasting, however, have focused on its potential benefits for people at risk of developing obesity and cardiovascular disease, major health problems in the United States. These studies have revealed that IF can have substantial positive impacts on weight loss, metabolic and heart health.

Dr. Krista Varady has found in human clinical studies that IF is an effective weight maintenance strategy, where people are more likely to stick to fasting regimens as opposed to diets long term, helping them lose weight and maintain weight loss as opposed to yo-yo dieting.

Time-restricted feeding (12+ hours per day) and alternate-day (500 calories every other day) fasting interventions lasting six to eight weeks in human trials have been associated with lowered cholesterol and triglyceride levels in adults.

In intermittent fasting trials incorporating several hundred subjects, Dr. Krista Varady has consistently observed 20-30% decreases in triglyceride levels over the course of three months of regular fasting. She has also observed modest declines in LDL cholesterol levels, primarily among people with elevated levels starting out, increases in total LDL particle size, and modest increases in HDL or “good” cholesterol levels. HDL levels can also increase with exercise and niacin supplementation.

Intermittent fasting can promote weight loss and may improve metabolic health over time, via effects on nutrient signaling, circadian biology and the gut microbiome. These effects can take time. Weight loss studies of IF typically involve interventions that last three to six months. For most people in these studies, it takes two to three months to lose 10 pounds, Dr. Krista Varady says. For diabetic or pre-diabetic individuals seeking to change their A1C or blood glucose levels, it usually takes at least three months to see these levels meaningfully change.

In a 2016 study of time-restricted feeding (all calories consumed in an 8-hour window each day) in conjunction with resistance training in healthy males, research participants who followed the fasting program for eight weeks experienced a decrease in fat mass with no significant change in muscle mass. Fasting individuals also experienced a decrease in IGF-1 and an increase in adiponectin, a hormone that can be an insulin sensitizer in the liver and muscle and help improve glucose and fat metabolism.

It’s important to find a diet or metabolic lifestyle intervention that you can incorporate into your lifestyle long term, given the negative impacts of “yo-yo dieting” for most people. Many people would benefit from continuing intermittent fasting long term if possible, Varady says.

There are promising animal studies showing that dietary restriction, including caloric restriction and intermittent fasting, may at least in some cases extend healthy lifespan and delay diseases aging for various species from yeast to mice to monkeys. The molecular mechanisms of these impacts involve the elimination or improved function of senescent cells, or damaged cells that have been marked by the body and prevented from dividing. Intermittent fasting may prime senescent cells for cellular recycling, which in the end can improve the function of aging tissues.

However, it is very difficult to study aging and senescence cell biomarkers in humans, especially because most people can’t or won’t participate in long-term intervention studies. Data from such studies in humans are rare, and the fields of caloric restriction and IF are no exception.

While IF can theoretically improve tissue function, particularly as it relates to metabolic function and circadian rhythms, more research is needed on the impacts of long-term fasting on healthspan and lifespan.

Research on the benefits of intermittent fasting in humans, in the form of clinical intervention studies, is still early in development. Animal studies have demonstrated various fasting health benefits, from enhanced collagen production and wound healing to neuroplasticity, improved brain function and alleviation of neurodegenerative disease symptoms. Most studies of IF in humans so far have focused on weight loss and metabolic health benefits.

Safety Considerations for Intermittent Fasting

Answers informed by Dr. Krista Varady.

Most people can benefit from practicing moderate fasting (shorter than 24 hours). However, there are safety concerns for pregnant women, children, individuals with type 1 diabetes and individuals who are malnourished or not getting proper nutrition. These individuals are advised not to practice intermittent fasting and should talk to their doctor before contemplating doing so in the future.

There are also concerns for young children, although not eating after dinner and fasting overnight for 8-12 hours is probably not a concern for young adolescents. Preliminary data suggest that alternate day fasting (with 500 calories or less on fast days) may be safe and effective for obese young adolescents. However, Dr. Krista Varady recommends against IF for children under 12 years of age.

Water fasts up to 24 to 36 hours in duration are generally safe and well tolerated based on clinical studies, Dr. Krista Varady says. However, from a weight loss and maintenance perspective, 24-hour water fasting on a regular basis can be difficult to stick to and adopt as a long-term health practice. People with eating disorders should not to practice IF without oversight from a physician. However, alternate day fasting has been found to decrease feelings of depression and binge eating behavior in obese subjects, while improving body image perceptions.

It’s best for your metabolic health to stick to a fasting regimen you can easily maintain over time, with the caveat that you should stop fasting and see a physician if you experience light-headedness or significant discomfort, or if you are at risk of becoming underweight. Intermittent fasting is not the only way to improve your metabolic health; it’s important to find the meal composition and timing plan that works best for you long term.

There is limited research on the impacts or safety of long term periodic fasting for 3-5 days at a time.

You should consult with your physician or oncologist before practicing intermittent fasting during any type of cancer treatment, especially if you are experiencing muscle wasting, poor nutrition or other side effects from treatment. However, there is evidence from in vitro studies, animal studies and early clinical studies in humans conducted by Dr. Valter Longo of the USC Longevity Institute and colleagues that periodic fasting or low-protein fasting-mimicking diets may sensitize cancer cells to the impacts of chemotherapy while protecting healthy immune cells and other cells against side effects. The IGF-1R (Insulin-like growth factor 1 receptor) pathway appears to play a key role in the impact of dietary restriction on tumor progression and treatment sensitivity.

Research findings on the benefits of IF for cancer patients undergoing chemotherapy, based on the differential stress resistance of cancerous versus non-cancerous cells, are promising but preliminary. Long-term fasting on the order of several days may have other side effects and should never be undertaken without consultation with a physician, oncologist or other healthcare expert.

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There is no indication that intermittent fasting compromises bone health. In a study of post-menopausal women conducted in Dr. Krista Varady’s lab, six months of alternate day fasting had no impact on bone density according to DEXA scans.

A small-scale study published in 2017 raised concerns about breakfast skipping (front-end fasting) creating an acute state of muscle glucose intolerance upon refeeding. There is some evidence, based on natural daily cycles of insulin sensitivity, that it is better to skip dinner or start a prolonged overnight fast early in the evening as opposed to skipping breakfast or fasting until late afternoon. However, acute fasting studies that look at the impacts of 24 to 48-hour fasts on individuals who may not be accustomed to fasting periods of this duration are not necessarily indicative of what would happen for individuals who practice fasting on a regular basis, Dr. Krista Varady says. After a month of alternate day fasting, research participants in intermittent fasting studies overwhelmingly experience reductions in glucose levels and insulin resistance, based on cellular adaptations to the stress of fasting.

As in all forms of dietary restriction that lead to weight loss, intermittent fasting may cause both fat and lean mass loss over time. However, there is some evidence that losing weight through IF may lead to less muscle loss as compared to fat loss than traditional dieting or caloric restriction. While traditional dieting without exercise typically leads to body mass loss that is 75% fat, 25% muscle, IF may lead to either an equivalent or smaller percentage of muscle loss, or as little as 10%. However, you will always lose some percentage of muscle when you lose weight. Regular exercise, especially weight-bearing or resistance training, can alleviate muscle loss during IF regimens that lead to weight loss.

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