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Fasting every other day may slow cell proliferation - a positive sign for inhibiting cancer activity

| 31 March 2005

An apple a day keeps the doctor away, but could eating an apple every other day be even better?

A new study by Berkeley researchers raises such a possibility. It shows that healthy mice given only 5 percent fewer calories than mice allowed to eat freely experienced a significant reduction in cell proliferation in several tissues, considered an indicator for cancer risk. The key was that the mice eating 5 percent fewer calories were fed intermittently, or three days a week.

What is encouraging about the findings is that the reduction in cell proliferation from that intermittent-feeding regimen closely approximated that of a more severe 33-percent reduction in calories. Until now, scientists have been certain only of a link between a more substantial calorie reduction and a reduction in the rate of cell proliferation.

"Cell proliferation is really the key to the modern epidemic of cancer," said Marc Hellerstein, professor of human nutrition in the Department of Nutritional Sciences and Toxicology at the College of Natural Resources, and principal investigator of the study.

Cancer is essentially the uncontrolled division of cells, and its development typically requires the presence of multiple mutations. "Normally, a cell will try to fix any damage that has occurred to its DNA," said Hellerstein. "But if it divides before it has a chance to fix the damage, that damage becomes memorialized as a mutation in the offspring cells. Slowing down the rate of cell proliferation essentially buys time for the cells to repair genetic damage."

Studies over the past 70 years have established that substantial calorie reduction - up to 50 percent in some studies - can not only reduce the rate of cell proliferation but extend the maximum life span of a variety of non-human organisms, including rats, flies, worms, and yeast. The results can be dramatic, with 30- to 70-percent increases in life span reported in the studies.

"Significant caloric restriction is the one and only thing that has been scientifically proven to extend life span," said Hellerstein, noting that while exercise and good nutrition can prevent premature death by disease, they have not been shown to extend a maximum life span.

Cutting calories has also been shown to reduce the development of cancer, enhance insulin sensitivity, and lower the risk of heart disease.

Yet, as remarkable as those studies may be, their applicability to a human diet is clearly limited. The researchers refer to an old joke that goes along with their findings on caloric restriction: "It's not that you're living longer, it just feels that way."

People unwilling to embark on what amounts to a lifetime of food deprivation might well find the prospect of a more viable intermittent-feeding pattern appealing. "What we found is that it may not be necessary to severely restrict calories to reap some of those health benefits," said Elaine Hsieh, a Ph.D. student in molecular and biochemical nutrition and lead author of the study. "Cutting just a few calories overall, but feeding intermittently, may be a more feasible eating pattern for some people to maintain."

The researchers found that any weight lost during the calorie-restriction period was regained once a normal feeding pattern was resumed. "Overall, we found that the effects of the diet regimens were rapid and reversible, with cell-division rates and weight going back to normal after refeeding," said Hsieh. "Although it's too early to say whether similar results would be seen in humans, this study at least provides some hope that another option to severe calorie reduction exists."

It goes without saying that there is more to changes in eating patterns, such as fasting, than just the physical effects. Both scientific and anecdotal evidence indicates that eating also can impact one's mental state and emotions. For example, a recent pilot study of 16 non-obese adults by researchers at the Pennington Biomedical Research Center in Louisiana found that eating only every other day was feasible when the participants successfully followed an alternate-day fasting regimen for three weeks. However, the people also reported feeling hungry and irritable on their fasting days.

The authors of the pilot study said that adding a small meal, fulfilling no more than 20 percent of the day's caloric needs, might just take the edge off and make the feeding pattern more palatable.

The results of the Berkeley study are scheduled to appear in the May issue of the American Journal of Physiology-Endocrinology and Metabolism, but are now available online.