Fasting: What the Science Says

The concept of fasting in religious and medical practice has been established for thousands of years, dating back to ancient Chinese, Greek, and Roman civilizations. Even research on human evolution indicates that early humans in hunter-gatherer societies spent extended periods of time with access to very little or no food. While it wasn’t until the 1950s and 1960s that fasting gained significant popularity, the first scientific study was conducted years earlier in 1914 and examined the effects of fasting in the treatment of type 1 and type 2 diabetes. (1) Recently, we have seen a renewed interest in fasting, with a growing body of literature providing a better understanding of its benefits, clinical implications, and safety.

What is fasting?

Fasting involves abstaining from or restricting intake of calorie-containing food and drink for a period of time. (15) The purpose of fasting is to shift the body into a metabolic state known as “ketogenesis”. When the body’s glycogen stores are depleted, it will utilize fatty acids and fatty acid-derived ketones as its primary source of energy, helping to preserve muscle mass and function. The point at which our bodies switch from utilizing glucose to fatty acids as fuel is sometimes referred to as the “metabolic switch”, which typically occurs approximately 12 to 36 hours after cessation of food intake. (1) Ketogenesis has been shown to affect a number of metabolic pathways and cellular processes, including lipolysis, resistance to stress, and autophagy. (12)

To learn more about the metabolic effects and mechanisms of action for fasting, visit the Fullscript blog.

Dr. Holly Lucille discusses the evidence-based research surrounding fasting.

Types of fasting regimens

Outlined below are some of the most common types of fasting and fasting mimicking programs. 

The Fasting Mimicking Diet

A meal program developed by Dr. Valter Longo, the Fasting Mimicking Diet is intended to mimic the effects of fasting in order to improve a number of physiological markers, including inflammation, fasting glucose, and blood lipids. The program involves restricting caloric intake to approximately 900 calories per day for five days out of the month, followed by a return to an individual’s regular diet for the remainder of the month. 

The Master Cleanse

Also known as the “Lemonade Diet”, the Master Cleanse is essentially a modified juice cleanse. It involves 10 days of caloric restriction, in which individuals consume only a liquid diet comprised of lemon juice, cayenne pepper, maple syrup, and water. 

Water fasts 

Water fasts involve the complete abstinence from all foods and beverages, except for pure water, for a period of time. (5)

Intermittent fasting 

Perhaps the most well-known and studied fasting method, intermittent fasting (IF) is actually an umbrella term that encompasses a number of different fasting regimens, which involve consuming few or no calories for a predetermined period of time. (1)(19) The various types of IF regimens include:

Alternate day fasting involves alternating between fasting days, during which no energy-containing foods or beverages are consumed, and eating days, during which individuals may consume food and beverages as desired. (1)(15

Periodic fasting (or cyclic fasting) – involves fasting for one or two days per week and consuming food as desired for the remaining days. (1) One example of periodic fasting is the eat-stop-eat diet, which involves fasting for 24 hours one or two days per week and consuming food as desired for the remaining days. (16

Time-restricted feeding (or time-restricted eating) – involves a regular daily fasting period when food and beverages are consumed as desired within a specific window, (15) typically between 8 to 12 hours. (1

Modified fasting – involves limiting food consumption to 20-25% of daily energy requirements on fasting days, rather than a complete restriction of energy intake. Examples of modified fasting regimens include alternate day modified fasting and the 5:2 diet, in which energy intake is restricted for two non-consecutive days per week and food is consumed as desired the remainder of the week. (1)(15)  

Religious fasting – Many religious or spiritual fasts can be characterized as intermittent fasting. For example, Ramadan involves fasting from dawn until dusk, resulting in approximately 12 hours of fasting. (15)

Intermittent fasting vs. calorie restriction 

Calorie restriction involves maintaining meal frequency while consistently reducing calorie intake by 20–40%. (12) While caloric restriction has demonstrated effectiveness in weight loss and cardiometabolic health, this type of diet is difficult to sustain, resulting in poor long-term adherence. 

Research has shown that IF may induce similar benefits, while improving patient adherence, placing IF as an exciting alternative to traditional calorie restriction. Compared to calorie restriction, IF has been shown to result in similar levels of weight loss and comparable improvements in several cardiometabolic risk factors, including inflammatory markers, visceral fat mass, insulin resistance, and lipid profiles. (1) A systematic review was conducted to compare the effectiveness of intermittent energy restriction with daily energy restriction in overweight and obese adults. The review concluded that weight loss resulting from intermittent energy restriction was comparable to that of daily energy restriction, supporting the theory that intermittent fasting may be an effective alternative strategy for weight loss in overweight and obese individuals. (4)

DOWNLOAD A PATIENT GUIDE TO INTERMITTENT FASTING

Fasting involves abstaining from or restricting intake of calorie-containing food and drink for a period of time.

The clinical applications of fasting

Historically, much of the research on fasting and its apparent health benefits were supported only by animal, in vitro, or observational data. However, results from human trials are now supporting some of the benefits and potential clinical applications of fasting, including its use in a number of inflammatory and cardiometabolic conditions, such as rheumatoid arthritis, asthma, cardiovascular disease, hypertension, type 2 diabetes, and weight loss. (12) A number of mechanisms have been suggested to explain this relationship, including the effects of fasting on the gastrointestinal microbiota, circadian biology, and lifestyle behaviors. (15

Weight loss and cardiometabolic risk factors

Numerous studies support the use of fasting as a strategy for improving body weight and cardiometabolic risk factors. An 8-week study examining the effects of alternate day fasting in obese adults noted favorable reductions in body weight and in a number of cardiometabolic risk factors, including systolic blood pressure, total cholesterol, LDL cholesterol, and triacylglycerol concentrations. Another study found that intermittent energy restriction (e.g., alternate day fasting, the 5:2 diet), when compared with standard care, was as effective as standard care for short-term weight loss in overweight and obese individuals. (7

Research also suggests that individuals of normal weight may experience similar benefits from IF. A 12-week study examined the effects of alternate day fasting in 32 non-obese subjects, randomized into a fasting group or a control group. Results demonstrated reductions in weight, fat mass, leptin, and CRP. Plasma adiponectin and LDL particle size increased, while no changes were observed in LDL cholesterol, HDL cholesterol, homocysteine levels, or resisten levels. (21

Furthermore, interventions combining alternate day fasting and exercise may produce greater benefit than either therapy on its own. In one study, 64 obese subjects were randomized into a fasting group, an exercise group, a combination group (fasting and exercise), or a control group (no intervention). When compared to the individual interventions, the combination group demonstrated greater improvements in body weight and composition, plasma lipid levels, and risk of heart disease. The combination group also demonstrated superior retention of lean body mass. (3

Type 2 diabetes

Studies have noted improvements in glucose metabolism and type 2 diabetes as a result of IF. During the two-week trial, individuals with type 2 diabetes consumed all daily calories over a 4- to 8-hour period daily. Results showed improvements in body weight, fasting glucose, and postprandial hyperglycemia following the two-week period. However, fasting glucose levels reversed to baseline values after individuals returned to a regular eating patterns. (2) In a 12-week randomised, open, crossover, single-centre study, 54 patients with type 2 diabetes taking oral hypoglycemic medication consumed two meals per day (breakfast and lunch) or six meals per day, both regimens meeting daily nutritional needs. Individuals consuming two meals per day demonstrated reductions in body weight, fasting plasma glucose and glucagon, hepatic fat content, and C-peptide, suggesting that type 2 diabetic patients may benefit from eating two larger meals per day at breakfast and lunch, compared to six smaller meals. (10

Fasting has been shown to improve risk factors associated with certain metabolic conditions, such as obesity, type 2 diabetes, and metabolic syndrome.

Metabolic syndrome 

A major risk factor for atherosclerotic heart disease, myocardial infarction, and heart failure, metabolic syndrome is a group of health conditions, including obesity, hypertension, and insulin resistance, that occur concomitantly. (1) Many factors related to metabolic syndrome appear to be improved by adherence to an IF regimen, including body composition, blood pressure, and glucose metabolism. (12) One study specifically examined the effects of a short- to mid-term fast (7-18 days) on impaired insulin resistance in 25 patients with metabolic syndrome. After fasting, significant reductions were noted in body mass index, fasting insulin, fasting glucose, and insulin resistance. The study also noted that improvements in insulin resistance were greater in patients with type 2 diabetes (38%) compared to those without type 2 diabetes (23%). While these findings indicate safety and effectiveness, all parameters, except improvements in body weight, completely or partially rebounded by 80 days post-fasting. (18

Another study examined the effects of time-restricted feeding on body weight and risk factors for metabolic disease in 23 obese adults compared to a control group. The 12-week intervention involved restricting feeding hours from 10 am to 6 pm, allowing for only water consumption during fasting hours. Results indicated reductions in energy intake, weight, and systolic blood pressure. However, compared to the control, no changes were observed in blood lipid levels, diastolic blood pressure, fasting glucose and insulin, fat mass, HOMA-IR, or homocysteine. (6

Inflammation

In addition to cardiometabolic conditions, fasting may be beneficial in the treatment of certain inflammatory conditions, such as asthma and rheumatoid arthritis (RA). An 8-week study examined the effects of an alternate day calorie restricting diet, in which asthmatic participants with a BMI greater than 30 consumed 20% of a normal caloric intake on alternating days. Within two weeks, results demonstrated improvements in weight, symptoms of asthma, peak expiratory flow (PEF), and quality of life questionnaires. Improvements were also noted in serum cholesterol and triglycerides, as well as markers of oxidative stress and inflammation. (9

In a seven-day study, the effects of fasting for seven days in 13 patients with rheumatoid arthritis were examined. Results demonstrated improvements in weight, joint inflammation, and erythrocyte sedimentation rate (ESR) in the fasting group, while the control group did not demonstrate any changes in these measures. (20

Research on fasting and rheumatoid arthritis suggests that fasting, followed by adherence to a vegetarian diet may produce long-term sustainable benefits. (14) In one study, 16 patients with rheumatoid arthritis were instructed to follow a fasting diet for 7-10 days, followed by a lactovegetarian diet for nine weeks. Compared to the control group, the fasting patients reduced their consumption of analgesics and demonstrated improvements in pain, stiffness, and serum concentration of orosomucoid. (17) Similarly, a randomised, single-blind controlled study examined the longer term effects of fasting when followed by a one-year vegetarian diet. Twenty-seven RA patients followed a 7-10 day subtotal fast. They were then instructed to adhere to an individually adjusted gluten-free vegan diet for 3.5 months, followed by a lactovegetarian diet for the remainder of the year. After four weeks, individuals in the treatment group demonstrated improvements in ESR, C-reactive protein, white blood cell count, grip strength, and joint pain, swelling, and stiffness. In comparison, the control group only demonstrated improved pain scores. These benefits were still noted after one year, indicating that this dietary regimen may be useful in the long-term treatment of rheumatoid arthritis. (11

Fasting may provide beneficial effects on physical performance during exercise.

Athletic performance

Some studies have shown that fasting may provide beneficial effects on physical performance during exercise. One study examined the effects of time-restricted feeding in 34 healthy, resistance-trained men compared to a group following a normal diet. The subjects in the fasting group consumed all of their daily energy requirements in three meals over an 8-hour period between 1 pm and 8 pm. The fasting group experienced reductions in fat mass with maintenance of muscle mass and strength. Results of the study also suggest that intermittent fasting, when used in conjunction with resistance training, could affect other health-related biomarkers, including increased adiponectin and decreased insulin-like growth factor 1, testosterone, leptin, and respiratory ratio. (13) Another randomized controlled trial examined the effects of IF on physical performance in men. Over one month, subjects followed a regimen involving 20 hours of fasting, four days per week. Compared to the control group, these subjects demonstrated greater improvements in upper and lower body endurance during resistance training. (1)

Longevity

Energy restriction may improve several factors related to aging, including oxidative damage, inflammation, and elevated levels of IGF-1, IGFBP1, glucose, and insulin. (12) Studies suggest that time-restricted feeding, in which individuals adhere to a longer fasting period on a daily basis, may provide an anti-aging effect. A four-day randomized crossover study with 11 overweight adults examined the effects of time-restricted feeding on gene expression, circulating hormones, and diurnal patterns in cardiometabolic risk factors. Subjects consumed food between 8 am and 2 pm or between 8 am and 8 pm. Subjects who limited their food intake from 8 am to 2 pm demonstrated improvements in 24-hour glucose levels, lipid metabolism, and circadian clock gene expression. Researchers also noted changes in the expression of certain genes, suggesting increased autophagy and anti-aging effects. (8)

The bottom line

Research has demonstrated promising results for the therapeutic use of fasting in a number of inflammatory and cardiometabolic conditions, such as rheumatoid arthritis, asthma, cardiovascular disease, hypertension, type 2 diabetes, and weight loss. Fasting may also promote longevity and improve athletic performance. Numerous ongoing clinical trials will only expand our knowledge of fasting and its long-term therapeutic applications.

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