Every Other Day Fasting May Reduce Cancer Risk

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

A new study by researchers at the University of California, Berkeley, 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 was only slightly less than 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.

The results of the study are scheduled to appear in the May 2005 issue of the American Journal of Physiology-Endocrinology and Metabolism, but are now available online.

"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 UC Berkeley's College of Natural Resources. Hellerstein is 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, then 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."

Cell proliferation contributes to carcinogenesis in a number of other ways, as well, collectively termed "cancer promotion."

Studies over the past 70 years have established that substantial calorie reduction - up to 50 percent in some studies - not only can reduce the rate of cell proliferation, it can extend the maximum life span of a variety of 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, who has a joint appointment at UC San Francisco. He noted 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.

The 5% reduction in calories used for mice translates into about 100 calories per day for humans. Many obese people overeat by about that amount and have little luck dieting to avoid those extra 100 calories. This brings into question the practicality of implementing this research in human diets.

Can some of the benefits of calorie restriction really be achieved by fasting every other day? To prove that this experiment would need to be run on mice and rats for years in order to find out whether this regimen increases their life expectancies and if so by how much.

Another question: Would one derive more benefit from even longer periods of fasting and eating? A week on and a week off perhaps? Or just 2 days fasting alternated with 2 days eating?

The researchers conducted several trials with a control group of mice that ate "ad lib," or freely. They compared the control group with mice that ate 5 percent fewer calories but were fed three times a week with mice that were given 33 percent fewer calories. Trial periods ranged from two weeks to three months.

As expected, the researchers found that mice on the 33 percent reduced calorie diet exhibited significantly decreased proliferation rates for skin, breast and T (lymphocyte) cells. The greatest effect was seen after one month on the regimen, when proliferation of skin cells registered only 61 percent of that for mice fed freely.

The surprising finding came with the results of the more modest 5 percent reduced calorie diet that was fed intermittently. Mice in this group had skin cell division rates that were 81 percent of those for mice fed freely.

Fasting every other day may decrease the chances of breast cancer the most. But I can not imagine many women being willing to fast every other day for weeks, months, and years on end.

In all cases, division rates for breast cells were reduced the most. Mice with the lowest calorie diet had breast cell proliferation results that were only 11 percent of those for the control group mice, and mice fed intermittently had results that were 37 percent of those for the control group.

The researchers said this may be partly related to the reduction in estrogen, which stimulates breast cell division. Tests revealed that the estrus cycle stopped for mice on the lowest calorie diet. The mice fed intermittently, on the other hand, continued to cycle regularly.

Results of the refeeding trials indicated that any weight lost during the calorie restriction period was regained once a normal feeding pattern was resumed.

Every other day fasting was tried on a small pilot study of humans.

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.

Would even shorter fasting periods provide any benefit? It would be interesting to see if any benefit could be derived by eating very day but having at least 12 hour stretches every day when no food is consumed. That might be more achievable. Don't eat before bedtime and then entirely skip breakfast and make lunch be the first meal of the day.

Even if intermittent fasting is eventually shown to deliver real human health benefits (and I expect it will) few people are going to be up for fasting every other day. Though perhaps more people could manage to do intermittent fasting than can manage to stay on a calorie restriction diet.

However, once safe appetite suppressant drugs are developed fasting could become a lot easier and may become popular as a method to slow aging and lower the risk of degenerative diseases. Appetite suppressants that could work for differing lengths of time would be handy. One could take an appetite suppressant for 12 hours or 24 hours depending on your fasting regime.

Another approach that may eventualy obviate the need for fasting is a class of drugs called calorie restriction mimetics. The idea behind calorie restriction mimetics (which are the subject of active research in a number of labs) is that they'll fool your metabolism into thinking you haven't eaten. Then your cells would throw themselves into the same state they go into when they are not getting as much calories. Appetite suppressants would remain useful for anyone who is overweight. But the benefit of fasting would be delivered by a separate calorie restriction mimetic drug.

Update: A previous study found that rodents genetically engineered to have less fat in fat cells lived longer without calorie restriction. This is not surprising because fat cells appear to excrete pro-inflammatory compounds. In fact. Rudolph Liebel of Columbia University says adipose fat cells excrete at least 25 hormones and other signalling compounds including adiponectin and resistin. The fatter you get the bigger the problem you'll have with accumulated damage from chronic inflammation. If we can develop treatments that prevent fat cells from converting excess calories into fat then we may be able to get many of the benefits of calorie restriction.

Also, see my previous post which reports that rodents which were made to skip meals had lower blood insulin and their brains were more resistant to damage from neurotoxins. Being skinny is good. Skipping meals is good too.