Intermittent fasting

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Intermittent fasting is an eating pattern that includes hours or days of no or minimal food consumption without deprivation of essential nutrients. Commonly studied regimens include alternate day fasting, 5:2 intermittent fasting (fasting two days each week), and daily time-restricted feeding (such as eating only during a six-hour window).

Intermittent fasting
Intermittent fasting

Hundreds of animal studies and scores of human clinical trials have shown that intermittent fasting can lead to improvements in health conditions such as obesity, diabetes, cardiovascular disease, cancers and neurological disorders.

Effect on weight

Although intermittent fasting often results in reduced calorie consumption, weight loss is not the main driver of the health benefits observed in preclinical and clinical studies, according to the authors. Rather, the key mechanism is metabolic switching, in which fasting triggers the body to switch its source of energy from glucose stored in the liver to ketones, which are stored in fat.

Research

There are a variety of fasting diets, sometimes called "intermittent fasting." You may have read about:

  • Time-restricted feeding—Meals are consumed within a limited number of hours (such as 6-8 hours) each day, with nothing consumed during the other hours.
  • Alternate-day fasting—Eating is unrestricted every other day, and no or minimal calories can be consumed on the days in between.
  • 5:2 eating pattern—Eating is unrestricted for 5 straight days each week, followed by 2 days of restricted caloric intake.
  • Periodic fasting—Caloric intake is restricted for multiple consecutive days, such as 5 days in a row once a month, and unrestricted on all other days.

Calorie restriction versus fasting

More animal research has been done on calorie restriction than on fasting. In some experiments, calorie restriction is also a form of fasting because the lab animals consume all their daily allotted food within hours and go many more hours without any food.

Intermittent fasting
Illustration on intermittent fasting

In these studies, when rodents and other animals were given 10 percent to 40 percent fewer calories than usual but provided with all necessary nutrients, many showed extension of lifespan and reduced rates of several diseases, especially

What's the Evidence from Human Studies of Calorie Restriction?

Some study results suggest that calorie restriction may have health benefits for humans, but more research is needed before we understand its long-term effects. There are no data in humans on the relationship between calorie restriction and longevity.

Some people have voluntarily practiced extreme degrees of calorie restriction over many years in the belief that it will extend lifespan or preserve health. Studies on these individuals have found markedly low levels of risk factors for cardiovascular disease and diabetes. The studies have also found many other physiologic effects whose long-term benefits and risks are uncertain, as well as reductions in sexual interest and the ability to maintain body temperature in cold environments. These people generally consume a variety of nutritional supplements, which limits knowing which effects are due to calorie restriction versus other factors.

CALERIE trail

To conduct a more rigorous study of calorie restriction in humans, NIA supported a pioneering clinical trial called Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE).In CALERIE, 218 young and middle-aged, normal-weight or moderately overweight adults were randomly divided into two groups. People in the experimental group were told to follow a calorie-restriction diet for 2 years, while those in the control group followed their usual diet.

The study was designed to have participants in the experimental group eat 25 percent fewer calories per day than they had regularly consumed before the study. Although they did not meet this target, they reduced their daily caloric intake by 12 percent and maintained, on average, a 10 percent loss in body weight over 2 years. A follow-up study 2 years after the intervention ended found that participants had sustained much of this weight loss.

It's important to note that calorie-restriction regimens are not starvation diets. The weight loss achieved with calorie restriction in the CALERIE trial resulted in body weights within the normal or overweight range. Compared to participants in the control group, those in the calorie-restriction group had reduced risk factors (lower blood pressure and lower cholesterol) for age-related diseases such as diabetes, heart disease, and stroke. They also showed decreases in some inflammatory factors and thyroid hormones. There is some evidence that lower levels of these measures are associated with longer lifespan and diminished risk for age-related diseases. Moreover, in the calorie-restricted individuals, no adverse effects (and some favorable ones) were found on quality of life, mood, sexual function, and sleep.

Why the Science Is Uncertain

Despite a lot of research on calorie restriction and fasting, there are no firm conclusions about the benefits for human health. Here's a summary of the reasons why:

  • Most of the relevant studies have been conducted in laboratory and animal models, from yeast cells to primates. These findings do not necessarily apply to humans.
  • Most clinical trials with humans have been short (a few weeks or months), conducted in overweight subjects, and focused on weight loss rather than aging processes. The longest trial so far (CALERIE) lasted 2 years, which isn't long enough to learn about the long-term health effects of calorie restriction.
  • These clinical trials have typically recruited adults age 60 or younger, so the results don't necessarily apply to children or people older than age 60.
  • A tremendous number of organic and chemical processes keep the human body functioning. Researchers must sort out how these processes are affected under different dietary conditions.
  • Humans are quite different from each other in terms of gender, size, age, genetics, environment, lifestyle, and other factors. An eating pattern that's found to help one person might not have the same effect on another.
  • With animal studies, the researcher provides the food so knows how much has been eaten and when. This kind of reliable evidence is harder to obtain in human studies. Although new techniques can objectively measure overall caloric intake, it is still challenging to get accurate reports of diet information from individuals going about their lives.

What's Next in Research?

Most calorie-restriction and fasting-diet studies have been in younger people, but researchers are beginning to study older adults. A clinical trial conducted by NIA is testing the 5:2 diet in obese people, age 55 to 70, with insulin resistance. (This is a condition in which cells do not respond normally to the hormone insulin. This can lead to serious diseases such as diabetes.) People in the experimental group can eat at will for 5 days, and then for 2 consecutive days are restricted to 500 to 600 calories per day. The experiment is designed to find out how 8 weeks of the 5:2 diet, compared to a regular diet, affects insulin resistance and the brain chemicals that play a role in Alzheimer's disease.

In the coming years, researchers will continue to explore many unresolved questions. What are the long-term benefits and risks of the various eating patterns? Which diets are feasible as a long-term practice? What specific biological effects on aging and disease are triggered by a particular eating pattern? If a specific way of eating is recommended, at what age is it best to start, and is it safe to continue as you get older?

Sources and references

References

1. De Cabo R and Mattson MP. Effects of intermittent fasting on health, aging, and disease. New England Journal of Medicine. 2019;381(26):2541-2551.doi:10.1056/NEJMra1905136

 

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