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This article was originally published on January 7, 2022.

Calorie restriction and intermittent fasting are touted as a way to prolong good health well into later years. After all, for nearly a century, studies have found it limiting calories in some animals and insects, it prolongs their life and delays age-related diseases.

But calorie restriction (CR) isn’t always what it’s cracked up to be, reports a 2003 paper. Science of Aging Knowledge Environment. Rodents on a restricted diet are smaller and less muscular than those fed a regular diet; they are also more sensitive to the cold, more susceptible to bacterial infection, heal more slowly from wounds and are much less fertile, the paper reported. Unfortunately, there are no long-term human studies, but some diets regain the weight they lost if they cannot maintain the diet.

The main disadvantages of calorie-restricted diets are practical and health-related. The average person isn’t going to stick to an unnatural diet “even if it works for them,” says Matt Kaberlein, director of the Institute for Healthy Aging and Longevity Research at the University of Washington in Seattle. Based on the available data, CR would benefit people with most genetic backgrounds, he says, “but there are some where it is harmful. We want to be really careful before we recommend [a CR diet] to the general public. This is where I feel the diet gurus have gotten ahead of themselves.”

There is no one size fits all

A calorie-restricted diet with optimal nutrition is defined as eating one-third fewer calories than standard guidelines while still getting enough food. But there is more than one way to achieve this. In intermittent fasting (IF), people skip meals for one or two days a week or eat only one meal a day. Time-restricted feeding (TRF) relies on eating all meals within a given time period, such as 8 hours, and fasting for the remaining 16 hours. There’s no one-size-fits-all when it comes to diet, nutrition and health, says Kaberlein, whose research separating fact from fiction among anti-aging diets was published in Science last November.

For example, CR can make the body actually hold on to calories because we evolved to conserve energy during times of hunger, says UCLA Fielding School of Public Health professor Dana Ellis Hunnes, a registered dietitian. When people are faced with starvation or extreme calorie restriction, their bodies lower their metabolism, reducing the number of calories burned at rest.

CR is also associated with increased appetite, increased depressive symptoms and weight regain over time, according to Hunnes. “I think a lot of it has to do with the fact that when you restrict energy, your mind starts thinking about food,” she says. “If you don’t eat enough or restrict calories, you may be more likely to overeat the next time you eat. When you’re hungry, you have less impulse control. Deprivation of food has been shown to make animals, including humans, desire for more food. When laboratory rodents given a calorie-restricted diet were allowed to eat as much as they wanted, they ate even more food than their relatives on standard diets.

Read more: The science of forming healthy habits

The average person experiences strong psychological effects from restrictive diets as well, Kaberlein says. He remembers one of his alumni who stopped his diet for CR while the two attended a conference together. The student returned to the buffet dining table with a plate piled high with bacon, saying he couldn’t stop craving it while practicing CR. People on these diets can’t help but think about their diets and talk about them.

Is a calorie restricted diet healthy?

Calorie-restricted diets may work for some but not others, says Gary Churchill, who directs a lab that studies the genetics of health and disease at the Jackson Laboratory in Maine. “A person can lose weight and recover [to their prior weight], another person may not recover and another may not lose weight at all. That’s important to keep in mind.” Many of the touted studies are done on rodents, which are genetic clones that are clearly not the same as genetically diverse humans, he says.

Churchill’s lab experimented with two strategies with genetically identical mice. In one, he and his colleagues applied various forms of calorie restriction, sometimes reducing food a little, sometimes more. Other studies involved subjecting the mice to intermittent fasting, in which researchers deprived them of food for one or two days a week. For mice, one day without food is equivalent to four days of starvation for humans, Churchill says.

“Over the course of a week, fasted mice eat the same amount of food as non-fasted mice, but lose weight,” he says. During the first 12 hours, the body burns carbohydrates for energy; but then the body’s metabolism shifts and starts burning fat. Mice on a calorie-restricted diet lose fat, he says, but when subjected to severe CR, they lose muscle mass. The mice that do best are those that are not obese but eat enough to keep body fat.

But interpretations of animal studies applied to humans are overenthusiastic, Kaeberlein reminds us. It is difficult to draw firm conclusions about the long-term effects of calorie restriction or other popular diets because the long-term effects are simply not known. Kaeberlein says he also doesn’t know the long-term effects on those who try a calorie-restricted diet, then binge and regain the lost weight, compared to those who eat a poor diet continuously.

There’s no doubt that calorie restriction can help most overweight and obese people lose weight, he says, and that reducing weight to a healthy range reduces age-related risk factors for cancer, type 2 diabetes, heart and kidney disease, and dementia. The average diet in rich countries does not contain enough nutrients. So when people eat a Mediterranean, vegan or ketogenic diet compared to the average diet, they’re better, Kaeberlein adds. “Do they slow down aging? Increasing longevity? It depends on what you compare them to.”

And there’s another problem with the one-size-fits-all diet: Optimal nutrition for health changes as people age. On average, those who eat a low-protein diet before age 65 have a lower risk of cancer and death from all causes, Kaeberlein says. But after 65 years adopting a low-protein diet increases the risk of disease.

Correcting a few misconceptions about calorie-restricted diets

Before you try CR yourself, consider the truth behind these common myths surrounding calorie-restricted diets, according to Kaeberlein’s article in Science.

  • Although there are many reports of life expectancy and health extension by CR, there are also published examples in which CR fails to extend life expectancy. These include studies of wild mice and genetically inbred mice. Studies involving rhesus monkeys have also had mixed results on increased lifespan.

  • Another misconception is that CR extends life only by preventing cancer. Although CR has been shown to have potent anticancer effects in rodents, it also slows age-related decline in the brain, heart, immune system, muscles, kidneys, reproductive tissues, and other tissues.

  • The composition of one’s diet, total caloric intake and the intervals between meals could potentially affect longevity and health in later years – but the mechanisms underlying these effects are still poorly understood.

  • There is no strong evidence that antiaging diets studied in laboratory animals have significant long-term health benefits in non-obese people.

Diets are not fundamentally different from drugs, Kaberlein says. “If I started saying you have to take this medicine, people would back off. Diets are a really dirty drug. They affect many biological targets.

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