Fast before surgery. That's a common recommendation doctors give patients to ensure a safe procedure. Now a new study in mice suggests that the advice may have benefits beyond the operation itself: Extensive presurgical fasting appears to protect organs from postsurgical damage. Although preliminary, the finding builds on evidence that short-term starvation helps the body guard against stress and may be a useful medical tool.
Researchers have known for decades that drastically cutting calories can help animals live longer, although exactly why is uncertain. One popular idea is that when calories are curbed, the body has to adapt to the nutrient deficiency—and in doing so, it becomes more resistant to stress generally. The type of long-term calorie restriction tested in animals is too extreme to apply widely to people, but some scientists have wondered what effect very short-term restrictions, of just a few days, might have.
James Mitchell, who studies stress resistance at the Harvard School of Public Health in Boston, was especially interested in ischemic reperfusion injury, a problem that often occurs with heart attacks and strokes, and sometimes even from heart and vascular surgery. When someone has a heart attack due to a blocked artery, the heart is deprived of oxygen (an effect called ischemia) and cells die. Counterintuitively, when blood flow is restored (called reperfusion) that can also do damage by triggering inflammation. This kind of double whammy can be induced experimentally in other organs, too.
Mitchell focused on the kidney and liver in part because it's relatively easy to measure their function. Two years ago, he and his colleagues reported in Aging Cell that cutting the calories ingested by mice by 30% for up to 4 weeks protected the rodents' kidneys when their blood supply was cut off and then restored. Others have found that short-term calorie restriction does the same for the heart in mice.
But was it just a component of the restricted diet that mattered, such as slashing sugar, or did all calories need to be trimmed? Some studies had suggested that cutting sugars and fats wasn't all that important, so Mitchell turned to protein. Over a series of experiments, he divvied dozens of mice into two main groups: some offered as much food as they wanted to eat, and some that consumed the same number of calories as the first group but via a protein-free diet. The animals were fed this way for 6 to 14 days. Then the researchers briefly clamped off blood flow to the kidneys before allowing blood to flow back into them and then tested kidney function. In a separate study, the researchers did the same to the animals' livers after feeding them a diet lacking tryptophan, a constituent of proteins.
Mice that were on protein-free diets had about 50% better organ function, based on common markers in the blood, than those eating as much as they liked, Mitchell's group reports today in Science Translational Medicine. This organ protection was superior to what the researchers have seen with calorie restriction, suggesting that just cutting protein is even better—or that doing both at once might be best of all.
Mitchell can't say for sure, but he suspects that protein deprivation, like calorie restriction generally, activates some internal programs in cells that in turn improve the body's ability to handle stress. "These animals might be better conditioned to deal with an energy depletion" that comes from cutting off oxygen to an organ "because that's the stress they're under" when they're not eating protein, he says. The mice on special diets also had less inflammation, suggesting that protein restriction somehow dampens the body's inflammatory response.
That remains a hypothesis, for now. "What we don't understand yet is what is the exact mechanism of this, what's actually happening in the body," says Mark Talan, a cardiovascular researcher at the National Institute on Aging in Baltimore, Maryland. (The institute funded Mitchell's work, but Talan was not involved in it.)
One of Mitchell's next steps is to explore whether the dietary regimen improves surgical outcomes in humans. He's in discussions now with vascular surgeons at Brigham and Women's Hospital to see whether some sort of short-term fasting or protein-free diet before cardiovascular surgery is even doable in people. "You might think that the best way to be resistant to an upcoming surgery is to be well-rested and well-fed, but in fact that might not be the case," Mitchell says. Still, he cautions that no one about to have surgery should experiment with radical diets on their own until the approach has gotten more scrutiny.