Can short-term dietary restriction and fasting have a long-term anticarcinogenic effect?

Long-term dietary restriction (DR) robustly inhibits various types of carcinogenesis in rodents. Because malignancies are a major cause of death in humans, reducing the incidence or, at least, delaying the time of onset of neoplasia may significantly increase longevity of a large proportion of the human population. Long-term DR may not however be practical in humans and, judging from religious practices, several days of fasting to several weeks of DR is what a large segment of the human population can adhere to. In contrast to long-term DR, a single episode of fasting or several fasting-refeeding cycles did not have any long-lasting beneficial and usually had even a deleterious effect on carcinogenesis in rodent models. On the other hand, DR of a relatively short (1-3 months) duration often significantly increased latency and reduced the incidence of cancer over the entire life span. These results suggest that the immediate anticarcinogenic action of DR is to slow down the expansion of initiated clones, but that several months of DR may be sufficient for the elimination of a significant portion of initiated precancerous clones through apoptosis. The development of optimized DR regimens for humans will be contingent on further advances in our understanding of the mechanisms of cancer suppression by DR.