Intermittent Fasting and Health – What’s the Scientific Evidence?

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Although we have recently seen tremendous progress in the development of medical treatments for metabolic disorders and obesity, I still believe that nutritional and lifestyle measures are key to long-term success. As such, intermittent fasting is an exciting approach that, if used sensibly, is likely to reduce body weight and improve metabolic health. Animal studies have even suggested that it may promote healthy aging and increase longevity.

Our human ancestors had different food habits than we do. They did not routinely eat two to three regularly spaced, large meals every day. Indeed, food was often scarce, and there may have been long periods between meals. Furthermore, through the ages, fasting has been practiced in many communities for cultural and religious purposes.

As a result, the human body has developed many adaptive mechanisms that allow survival when food is not available. Hence, intermittent fasting is usually well tolerated and appears to be harmless for healthy, normal-weight, and obese adults. Nevertheless, it is crucial to eat a balanced diet and conform to healthy eating rules during intermittent fasting.

Intermittent fasting allows drinking unsweetened beverages such as water, coffee, and tea during the fasting period.

This article aims to answer several essential questions about intermittent fasting and the current scientific evidence supporting its benefits.

What Is Intermittent Fasting?

Intermittent fasting involves alternating cycles of fasting and eating. This may be done in many different ways.

Examples of methods used include alternate-day fasting, modified alternate-day fasting, the 5:2 diet, and the 16:8 diet.

Alternate-day fasting implies fasting every other day (1).

Modified alternate-day fasting allows for some caloric intake on the “fasting day”, though severely restricted (~75% caloric restriction).

The 5:2 diet (also termed the “Fast” diet) prescribes two days of severe caloric restriction per week and a regular diet five days a week (2). The diet allows for the consumption of about 400–600 kcal on the “fasting” days.

Overeating on the “feed day” due to increased hunger following the “fast day” often becomes a concern with intermittent fasting. However, studies have concluded that even after fasting every other day, participants report no compensatory eating and high satiety (3).

Time-Restricted Eating 

Time-restricted eating focuses on the timing of eating. It implies that eating is restricted to specific hours of the day (4).

Three variants of time-restricted eating are most common: 16:8, 18:6, and 20:4.

The 16:8 method has become quite popular. It consists of a 16-hour fast and then an 8-hour nutritional window where food is consumed. This can, for instance, be achieved by skipping breakfast and not eating after dinner.

Human studies have suggested that time-restricted feeding promotes weight loss (5,6). Some of these studies also showed beneficial effects on fasting blood sugar (fasting glucose) as well as LDL and HDL cholesterol.

Some experts have been skeptical about time-restricted eating because it often involves skipping breakfast (7). However, whether skipping breakfast is bad or not is still a matter of debate (8).

Are the Effects of Intermittent Fasting due to Calorie Restriction?

Calorie restriction means reducing the average daily caloric intake below what is habitual. 

There are many similarities between calorie restriction and intermittent fasting. During intermittent fasting, a person does not eat or severely limits food intake during certain periods. This often leads to fewer calories consumed. However, it is believed that the benefits of intermittent fasting are not due to calorie restriction alone (1).

The Metabolic Effects of Intermittent Fasting

Glucose, fatty acids, and ketone bodies are the primary fuel for most cells and organs in the body.

After meals, glucose is used for energy, and fat is stored as triglycerides. During periods of fasting, triglycerides are broken down to make fatty acids available.

During intermittent fasting, the body’s cells will periodically not have access to glucose. Instead, they will use free fatty acids and ketone bodies as their primary fuel.

This is called intermittent metabolic switching or glucose-ketone (G-to-K) switchover (10).

The body can store excess glucose in the form of glycogen. Glycogen consists of long chains of glucose molecules and is primarily found in the liver and skeletal muscle (11).

When the body’s glycogen stores become depleted, as happens during fasting, the body starts to break down fat. The breakdown of fats increases the availability of fatty acids, which most cells can use for energy.

The onset of the metabolic switch occurs when liver glycogen stores are depleted, which is typically 12 hours after the fasting is initiated.

Indeed, the switching from the use of glucose to fatty acids and ketone bodies may explain many of the health benefits of intermittent fasting.

The Role of Ketone Bodies

Ketone bodies are produced by the liver and used as an energy source by many cells and organs. Research indicates that the heart, kidneys, and brain prefer ketone bodies rather than glucose as their fuel resource.

When glucose is unavailable, as during fasting, the liver increases the production of ketone bodies.

Ketone levels may build up in the blood during fasting, resulting in a condition known as ketosis. Ketosis may also be caused by restricting carbohydrate consumption.

Excess ketones are excreted in urine and exhaled from the lungs.

Ketone bodies are not only used as a fuel resource. They are also potent signaling molecules that can have numerous beneficial effects on cells and organs (1).

Ketone bodies regulate the activity of many chemical substances that influence health and aging (12).

Intermittent Fasting, Physical Training, and Fitness

Both physical training and fasting have beneficial effects on health.

Aerobic exercise training and fasting increase the breakdown of fat (13). Thus, body composition is improved and lean body mass is reduced.

It has been shown that mice on intermittent fasting have better running endurance than mice that have unlimited access to food (1).

A human study showed that young men who fasted daily for 16 hours lost fat during resistance training.  At the same time, muscle mass was maintained (14).

However, a recent summary of the current scientific evidence indicates that our understanding of the effects of fasting on physical performance is not complete. Although some studies are clearly positive, others have reported decreased performances, while others showed no effect. In fact, endurance athletes are often advised to avoid high-intensity training while fasting (13).

Intermittent Fasting For Weight Loss

Obesity and being overweight are strong predisposing factors for developing diabetes, heart disease, and many cancer types.

The first clinical study of fasting for the treatment of obesity was performed in 1915. The study showed that short periods of four to six days of fasting reduced body weight (14).

Many studies in rodent models of obesity have shown beneficial effects of intermittent fasting (15). Studies also show that intermittent fasting results in weight loss in humans (16, 17, 18, 19, 20). Weight loss is usually rapid in the beginning, mostly due to the loss of sodium and water (21). A randomized human study showed that the 5:2 diet-induced weight loss (22).

In summary, there is abundant scientific evidence showing that intermittent fasting promotes weight loss in obese individuals. However, the longer-term benefits or harms of intermittent fasting amongst overweight or obese people are unknown (23).

Intermittent Fasting and Diabetes

Patients with diabetes mellitus, both types 1 and 2, comprise about 10% of the population in the United States (24).

Insulin resistance is a key feature of type-2 diabetes. Many studies have shown that intermittent fasting improves insulin sensitivity, thereby reducing insulin resistance (25).

It has been proposed that patients with diabetes may benefit from intermittent fasting. However, studies on the safety and benefits of intermittent fasting with diabetes are very limited.

One study showed intermittent fasting to be easily tolerated in patients with type 2 diabetes (26 .A recent overview of the available scientific knowledge found that intermittent fasting may be beneficial in patients with diabetes (24). Weight loss and reduced insulin requirements are among the benefits achieved.

Results from a recently published study have suggested that three months of intermittent fasting may be able to reverse type 2 diabetes (27).

However, patients with diabetes should use intermittent fasting carefully. Blood sugar has to be monitored and medication adjustments may have to be performed.

The Effects on Heart Disease and Stroke

Coronary artery disease and stroke are common illnesses and frequent causes of early death worldwide.

Measures that improve blood pressure, blood lipids and reduce the risk of diabetes may reduce the risk of these disorders.

Alternate-day fasting in rodent models of obesity has been shown to reduce blood levels of cholesterol and triglycerides (28).

Human studies have shown that fasting lowers total cholesterol, triglycerides, and LDL cholesterol (29,30). Furthermore, the size of LDL particles was increased.

High blood pressure (hypertension) is a common medical disorder that increases the risk of heart disease, stroke, and kidney disorders. It is one of the most important causes of premature death worldwide (31). Animal and human studies suggest that intermittent fasting lowers blood pressure (32, 33).

Animal studies also suggest that intermittent fasting may help to reduce the risk of stroke (34).

Intermittent Fasting and Cancer

Almost 90 years ago, German physician Otto Warburg first posed the question of why cells consume nutrients differently.

Warburg observed that cancer cells seemed to depend on glucose for energy. However, healthy cells can easily cope with glucose deprivation.

The phenomenon was coined “the Warburg effect” and earned Warburg the Nobel Prize in 1931 (35).

Hence, in theory, cancer cells may suffer when glucose is not available, whereas healthy cells will do fine.

Numerous animal studies have shown that caloric restriction and intermittent fasting reduce spontaneous cancers in rodents (1).

Furthermore, intermittent fasting may increase the sensitivity of some cancers to chemotherapy and reduce the side effects of cancer drugs (36). Animal studies suggest that fasting could replace or augment the efficacy of certain cancer drugs (37).

In contrast to most cancer therapies, intermittent fasting only has mild side effects. These may include headaches, dizziness, nausea, weakness, and short-term weight loss (38).

The effects of intermittent fasting on the risk of developing cancer and prognosis after a diagnosis of cancer are unknown because there is a lack of human studies (39). Hence, it is crucial to underscore that clinical research in this area till in its infancy. 

Clinical trials of intermittent fasting in patients with cancer are currently in progress.

Effects on Cognitive Function and the Central Nervous System

Studies in animals show that intermittent fasting enhances cognitive function, including memory (40).

In a study involving overweight adults with mild cognitive impairment, caloric restriction led to improvements in verbal memory and other cognitive measures (41).

There is strong evidence from animal studies that fasting can delay the onset of Alzheimer’s disease and Parkinson’s disease (42).

Excessive accumulation of a protein called amyloid-β (Aβ) in the brain is found in patients with Alzheimer’s disease (43). The removal of Aβ has been considered to be crucial in the development of the disease.

One study showed that intermittent fasting seems to protect against Alzheimer’s disease in mice. This may be due to the prevention of Aβ deposition in the brain (44).

In addition, chronic intermittent fasting improves cognitive functions and brain structures in mice (45).

Studies on the effects of intermittent fasting on cognitive function in humans are scarce.

Intermittent Fasting and Inflammation

Inflammation can be both acute and chronic. Acute inflammation is the initial response of the body to harmful stimuli. It is an essential part of bodily defenses and helps to fight off infections. Prolonged or chronic inflammation, on the other hand, is often associated with tissue damage.

When inflammation is appropriate, it protects  from disease. When inflammation is inappropriate or gets out of hand, it can cause disease (46).

Inflammation plays a crucial role in many chronic diseases such as heart disease, type 2 diabetes, and many cancers (47).

It is also well-documented that our dietary choices may affect inflammatory responses in the body (48). In a study published recently, Mount Sinai researchers found that fasting reduces inflammation and improves chronic inflammatory diseases (49).

The Effects on Life Expectancy and Aging

Calorie restriction increases both the average lifespan and the maximal lifespan of laboratory animals (50).

One study showed that rats’ average lifespan increased by 80 percent during intermittent fasting (51).

Another study compared mice that were fed one meal per day to mice that were fed freely. The total calorie content was the same for both groups. The mice that were fed one meal per day lived approximately 11 to 14 percent longer. This suggests that time-restricted feeding may contribute to longevity, even in the absence of calorie restriction (52).

During fasting, cells seem to become more able to remove and repair damaged molecules (53).

It has not been scientifically proven that intermittent fasting increases life expectancy in humans.

Intermittent Fasting and Women

It has been suggested that intermittent fasting may affect men and women differently.

Some experts have pointed out that women may be more sensitive to caloric restriction than men. Furthermore, the effects of intermittent fasting on glucose metabolism may vary between men and women.

There have also been anecdotal stories of women who have experienced changes to their menstrual cycles after intermittent fasting (50).

However, there is no scientific data that suggests that intermittent fasting has fewer benefits in women than men. Hence, intermittent fasting appears to be a safe medical intervention that can improve women’s health (51).

Nonetheless, intense fasting is not recommended for pregnant or breastfeeding women.

The Bottom Line

Unfortunately, much of the hype surrounding intermittent fasting arises from animal studies.

To date, there have been no well-controlled scientific studies to determine the effects of long-term intermittent fasting on humans.

Animal studies suggest that intermittent fasting may have several health benefits.

In humans, intermittent fasting helps to promote weight loss, improves insulin resistance and lipid abnormalities, and positively affects hypertension and inflammation.

Although short-term studies are promising, we do not know whether long-term intermittent fasting is effective for weight loss.

Clinical trials of intermittent fasting in patients with cancer are currently in progress.

Animal studies suggest that intermittent fasting may increase life expectancy and promote healthy aging. However, it has not been scientifically proven that intermittent fasting increases life expectancy in humans.

Randomized studies are desperately needed to further assess the possible benefits of intermittent fasting.

The article was initially published January 12, 2020

It was revised, updated and republished on February 6, 2023.