Dietary restriction before surgery may help prevent some complications

January 25, 2012

A period of semi-starvation before surgery may one day be just what the doctor orders — if an experiment in rats is borne out by studies in people.

Removing protein from their diet for about a week dramatically protected rats from damage to kidneys and livers when blood flow was temporarily cut off from those organs, according to a study published Wednesday. That insult is similar to what occurs during a stroke and heart attack, or what can happen to organs during long and complicated operations.

Restricting protein — but not sugar or fat — appears to kick in an ancient evolutionary response with many consequences, one of them a quelling of inflammation.

“What’s surprising is that you can do it for a really short period of time and still get a benefit,” said James R. Mitchell, a researcher at the Harvard School of Public Health who led the experiment, reported in Science Translational Medicine.

The study is the latest evidence that when it comes to food and health, less is often more — at least up to a point.

“I think it’s very exciting. I think it will be very interesting to see how quickly and effectively it can be applied to patients,” said Valter D. Longo, a molecular geneticist at the University of Southern California who is doing other, unrelated research on the effects of dietary restriction.

Reducing food intake can double the life span of yeast cells and primitive worms, and increase the longevity of mice by one-third. In people, dietary restriction has many beneficial effects, including reduced cholesterol and blood pressure. A 2008 study by Longo and his collaborators showed that short-term starvation protected mice against the damage of high-dose chemotherapy.

People are instructed not to eat the day of surgery, but that’s simply so their stomachs are empty and the risk of vomiting is reduced. The notion that food restriction lasting days might be helpful goes against nearly ­everything that surgeons are taught.

The new research does not overthrow the belief that people who are well nourished are the best candidates for surgery. Its authors note dryly: “Our studies were performed in young, healthy rodents; it will be necessary to determine whether this approach will work when needed most, such as in elderly or obese individuals.”

In the key experiment, Mitchell, Wei Peng and other members of the Harvard team allowed eight rats to eat as much as they wanted of a protein-free chow for six days. Another group of animals ate a normal diet. The artery and vein serving each kidney were then clamped, cutting off blood flow and oxygen for 35 minutes.

Within a week, 60 percent of the animals on the normal diet suffered kidney failure and died. All of the protein-restricted animals survived.

The no-protein diet appears to protect against “reperfusion ­injury” — damage to cell membranes, DNA and enzymes caused by compounds created when oxygen-rich blood returns to the blood-starved tissue. An influx of white blood cells can make matters worse by triggering further inflammation.

Protein is the general term for molecules made from compounds called amino acids that are attached one to another in long chains. The body can make some amino acids, but there are eight it can’t produce. (There are two it can’t make in sufficient quantity under certain circumstances.) These “essential amino acids,” as they are known, must be obtained from food.

Mitchell and his colleagues did other experiments that showed that removing a single essential amino acid — the well-known tryptophan, popularly associated with turkey dinners, is one example — from the diet also had a protective effect.

The evolutionary advantage of this effect isn’t known, but it probably involves “metabolic ­triage” in times of starvation. When there aren’t enough starting materials to make all the proteins the body wants, certain production lines may be shut down earlier than others. The inflammatory and immune response may be among the first to go on furlough.

The Harvard researchers also experimented with a drug, halo­fuginone, that mimics deprivation of proline, an amino acid essential during times of illness or stress. Three days of the medicine activated the “starvation response” and protected the rats.

Halofuginone is produced in industrial quantities and used in veterinary medicine to fight intestinal parasites in poultry and cattle. It is being used experimentally for some human illnesses. It is a synthetic version of a compound found in a Chinese herb, chang shan.

Mitchell said there are no plans at the moment to study halofuginone in people as a possible surgery pre-treatment.

“I think diet is simpler and might even be more efficacious,” he said. “People are very well adapted to periods of nutrient deprivation. Trying that is a more rational choice than testing a compound.”

He and collaborators at Brigham and Women’s Hospital in Boston are now making plans for a study in which some patients would have a three-day “juice-only fast” before surgery.

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