While the majority of Americans are overweight, a small number of people are experimenting with extremely low-calorie diets in the hope that by remaining extremely thin they will stave off disease and live longer. Advocates of extreme caloric restriction (CR) contend that sharply reducing caloric intake creates biochemical changes that slow the aging process, which theoretically should increase life expectancy.

Although most people would find it impossible to adhere to semi-starvation diets, there is sound scientific evidence that subsistence diets increase the life spans of fruit flies, worms, spiders, guppies, mice, and hamsters by between 10 and 40 percent. In theory, semi-starvation prolongs life by reducing metabolism—how quickly glucose is used for energy—in an evolutionary adaptation to conserve calories during periods of famine. Dieters are familiar with this process—they know from experience that as they eat less, their metabolic rates drop and it becomes increasingly more difficult to lose weight. CR adherents experience comparable drops in metabolic rate—one study found that their body temperature dropped by a full degree. Proponents of CR assert that while metabolism is vital for life it also is destructive, producing unstable molecules known as "free radicals" that can damage cells through a process called oxidation.

Animal studies have found that CR inhibits the growth of cancerous tumors, possibly because at lower body temperatures the body may be better able to repair damaged DNA. (Deoxyribonucleic acid molecules carry the genetic information necessary for the organization and functioning of most living cells and control inheritance of traits and characteristics.) Animals on calorie-restricted diets have reduced levels of blood sugar and insulin and greater insulin sensitivity, which reduce their risk for diabetes and cardiovascular disease. There is even evidence that CR boosts brain function. Mice with the tendency to develop such neurological conditions as Alzheimer's or Parkinson's diseases developed these conditions later and more slowly when they were placed on CR diets, and rodents on CR diets displayed better memory and learning than those on normal diets. There is also evidence that CR influences patterns of gene expression. As animals age, certain genes tend to "turnoff" and become inactive while others are activated. CR has been found to prevent 70 percent of change in gene expression in mice.

During 2004 the National Institutes of Health began a seven-year study to explore the effect of CR on human metabolism. The studies will explore the benefits and risks associated with CR. CR adherents report immediate health benefits including increased mental acuity, reduced need for sleep, sharply reduced cholesterol and fasting blood sugar levels, weight loss, and reduced blood pressure. The regimen is clearly not easy, and even its staunchest advocates, and members of the Caloric Restriction Society, concede that many people who practice CR experience constant hunger, obsessions with food, mood disorders such as irritability and depression, and lowered libido. CR can also cause people to feel cold, and even with adequate vitamin and mineral supplementation, can cause some people to suffer from osteoporosis (decreased bone mass) and hair loss.