Is fasting good for health? / David Stipe

Occasional periods of fasting may improve health, but medical information on the subject is thin

In AB White's beloved children's book, The Magic Farm, an elderly sheep advises Templeton, the gluttonous rat, that he will live longer if he eats less. "Who wants to live forever?" Templeton asks scornfully. "I get infinite satisfaction from the pleasure of devouring."

It is easy to sympathize with Templeton, but there is some truth in the lamb's claims. Studies have shown that reducing the accepted caloric intake, usually by 30% to 40%, extends life span by a third or more in many animals, including nematodes, fruit flies and rodents. However, we still do not know if such calorie restriction also extends the lives of primates and humans. Although there are studies that show monkeys eating less live longer, a recent 25-year study concluded that caloric restriction does not extend lifespan in rhesus monkeys. But even if calorie restriction does not extend life, many data support the idea that limiting food intake reduces the risk of common diseases in old age and extends the healthy period during life.

If only we could gain these benefits without being hungry all the time. Well, there may be such a possibility. In recent years, researchers have focused on a strategy known as intermittent fasting as a promising alternative to continuous calorie restriction.

Intermittent fasting, ranging from periodic fasting periods of several days to skipping a meal or two on certain days of the week, may provide the same health benefits as continuous caloric restriction. The thought of intermittent fasting is more palatable to most people because, as Templeton will be happy to hear, there is no need to abstain from the pleasures of gluttony. Studies show that rodents that binge one day and fast the next often consume fewer calories than they normally would, and live as long as rats whose caloric intake is restricted daily. In a 2003 study on mice, led by Mark Mattson, head of the Neuroscience Laboratory at the American Institute on Aging, it was found that mice that fasted regularly were healthier in several measures than mice that were subject to calorie restriction. For example, they had lower levels of insulin and blood glucose, indicators of increased insulin sensitivity and a reduced risk of diabetes.

The first fasts

For years the various religions have championed the idea that fasting is good for the soul, but its physical benefits were not known until the beginning of the 20th century, when doctors began to recommend fasting as a treatment for various problems, such as diabetes, obesity and epilepsy.

Studies on calorie restriction began to gain acceptance in the 30s when nutritionist Clive McKay of Cornell University discovered that rats raised on a strict diet from a young age lived longer and suffered less cancer and other diseases in their old age, compared to animals that ate as they pleased. Studies of calorie restriction and intermittent fasting crossed paths in 1945, when scientists at the University of Chicago reported that intermittent feeding (one day on and one day off) extended the lifespan of rats just as much as the constant diet in McKay's earlier studies. What's more, intermittent fasting appears to "inhibit the development of diseases that cause death," the Chicago researchers wrote.

In the decades that followed, research on anti-aging diets took a secondary place compared to more influential medical developments, such as the development of various types of antibiotics and heart bypass surgery. But more recently, Matson and other researchers are promoting the idea that intermittent fasting may reduce the risk of neurodegenerative diseases in late life. Mattson and his colleagues showed that intermittent fasting protects neurons from various stress injuries, at least in rodents. One of his first studies showed that intermittent feeding made the rats' brains resistant to toxins that cause cell damage similar to what the cells face when they age. In follow-up studies in rodents, his research group found that intermittent fasting protects against stroke damage, reduces motor deficits in a mouse model of Parkinson's, and slows cognitive decline in mice genetically engineered to shed symptoms of Alzheimer's disease. Mattson, a decidedly slim man, has long skipped his breakfast and lunch, except on weekends. "It makes my mind more fertile," he says. The 55-year-old researcher, who has a PhD in biology but no medical degree, has written or co-authored more than 700 articles.

Mattson believes that intermittent fasting acts like a mild stress that each time stimulates the cellular defense mechanisms against molecular damage. For example, intermittent fasting increases the level of "chaperone proteins", which prevent poor organization of other molecules in the cell. Also, fasted mice have higher levels of the protein BDNF, a survival factor that prevents the death of nerve cells under stress conditions. Low levels of BDNF are associated with a variety of conditions from depression to Alzheimer's, although it is not yet clear whether these findings reflect cause and effect or just correlation. Fasting also increases the process of autophagy, which acts in cells as a garbage disposal system that gets rid of damaged molecules, including molecules associated with Alzheimer's, Parkinson's and other diseases of the nervous system.

One of the main effects of intermittent fasting is increasing the body's sensitivity to insulin, the hormone that regulates blood sugar. Reduced insulin sensitivity often accompanies obesity and is associated with diabetes and heart failure. Long-lived animals and people often have particularly low levels of insulin, probably because their cells are more sensitive to the hormone and therefore need less of it. A recent study conducted at the Salk Institute for Biological Research in La Hoya, California, showed that mice that ate fatty foods eight hours a day and fasted for the rest of the day did not suffer from obesity and their insulin levels did not rise to dangerous levels.

The idea that intermittent fasting might provide the same health benefits as continuous caloric restriction, and allow for a bit of bingeing while losing weight, has convinced a growing number of people to try the method, says Steve Mount, a professor of genetics at the University of Maryland who for seven years has led an intermittent fasting discussion group at the Yahoo. But intermittent fasting "isn't a cure-all, it's always hard to lose weight," says Mount, who has been fasting three days a week since 2004. "But the theory [that it activates the same biological signaling pathways in the cell as caloric restriction] sounds reasonable."

on uneven ground

Despite the growing enthusiasm for intermittent fasting, researchers have done very few well-designed clinical trials, and the long-term effects in humans have yet to be elucidated. However, a 1956 Spanish study sheds some light on the issue, says James B. Johnson, a Louisiana physician who co-authored a 2006 paper analyzing the results of that study. In the Spanish study, 60 elderly men and women fasted every other day for 3 years. The participants visited a total of 123 days in clinics, and six of them died. In contrast, 60 elderly people who did not fast accumulated 219 hospital days, and 13 of them died.

In 2007, Johnson, Mattson, and colleagues published the results of a clinical study that examined nine overweight asthmatics who underwent near-absolute fasting every other day for two months. The study showed a rapid and significant relief in the symptoms of the disease and various signs of inflammation.

However, in the medical literature dealing with intermittent fasting there are also some red flags that detract from these promising results. A 2011 Brazilian study in rats found that in the long term, intermittent fasting raises blood glucose levels and the level of oxidizing compounds in tissues, which can damage cells. Moreover, a 2010 study, one of whose authors was Matson, found that intermittently fasted rats in an unknown way developed rigid heart tissue, which impaired the organ's ability to pump blood.

There are also weight loss experts who question fasting, and mention the hunger pangs and the possible dangers of compensatory eating. Indeed, the most recent study on calorie restriction in primates, the one in which life expectancy did not increase, highlights the need for caution when radically changing people's dietary habits.

However, from an evolutionary perspective, three meals a day is a strange modern invention. Fluctuations in the food supply of our ancestors were obviously accompanied by frequent fasting, and there is no need to say about malnutrition and starvation. However, Mattson believes that such evolutionary pressures selected genes that strengthened the areas of the brain involved in learning and memory, to increase the chance of finding food and surviving. If he is right, intermittent fasting may be both a smart and a wise way to manage life.

Sources: Calorie Restriction Delays Disease and Death in Rhesus Monkeys, by Ricky J. Coleman et al., Science, Vol. 325, July 10, 2009 (above); Effect of caloric restriction on the health and survival rate of rhesus monkeys participating in the NIA study, by Julie A. Mattison and colleagues, Nature, Vol. 489, 13 September 2012 (below).

About the author

David Stipe is a Boston-based science reporter focused on the study of aging. He is the author of the book "The Pill of Youth: Scientists on the Brink of an Anti-Aging Revolution" (Current Publishing, 2010).