"Long before it's in the papers"
January 27, 2015


Fasting found to help beat cancer in mice

Feb. 8, 2012
Courtesy of the University of Southern California
and World Science staff

Chem­o­ther­a­py drugs work bet­ter against can­cer when com­bined with cy­cles of short, se­vere fast­ing, a study has found.

Re­search­ers sug­gest the fast­ing might help be­cause nor­mal cells tend to put off try­ing to di­vide when nu­tri­ents are lack­ing—but can­cer cells keep try­ing, and this pro­cess ul­ti­mately kills them.

Fast­ing, even on its own, ef­fec­tively treated a ma­jor­ity of can­cers tested in mice, in­clud­ing trans­planted can­cer tu­mors made of hu­man cells, re­search­ers said. Their stu­dy, pub­lished in the jour­nal Sci­ence Trans­la­t­ional Med­i­cine, found that five out of eight can­cer types in mice re­sponded to fast­ing alone: just as with chem­o­ther­a­py, fast­ing slowed the growth and spread of tu­mors. And with­out ex­cep­tion, “the com­bina­t­ion of fast­ing cy­cles plus chem­o­ther­a­py was ei­ther more or much more ef­fec­tive than chemo alone,” said study sen­ior au­thor Val­ter Longo of the Uni­vers­ity of South­ern Cal­i­for­nia.

Mul­ti­ple cy­cles of fast­ing com­bined with chem­o­ther­a­py cured 20 per­cent of mice with a highly ag­gres­sive type of chil­dren’s can­cer that had spread through­out the body, and 40 per­cent of mice with a more lim­it­ed spread of the same can­cer, the au­thors added. No mice sur­vived in ei­ther case if treated only with chem­o­ther­a­py.

“We don’t know wheth­er in hu­mans it’s ef­fec­tive,” said Longo, adding that it would take a clin­i­cal tri­al of sev­er­al years to find out. Re­sults from the first phase of a clin­i­cal tri­al with breast, uri­nary tract and ovar­i­an can­cer pa­tients, con­ducted at the uni­vers­ity, have been sub­mit­ted for pre­s­enta­t­ion at the next an­nu­al meet­ing of the Amer­i­can So­ci­e­ty of Can­cer On­col­o­gists. But the first phase tests only the safe­ty of a ther­a­py, in this case wheth­er pa­tients can tol­er­ate two-day fasts be­fore and af­ter chem­o­ther­a­py.

Fast­ing is­n’t safe for eve­ry­one, Longo warned. The clin­i­cal tri­al did­n’t en­roll pa­tients who al­ready had lost more than 10 per­cent of their nor­mal weight or who had oth­er risk fac­tors, such as di­a­be­tes. Fast­ing al­so can cause a drop in blood pres­sure and headaches, which could make driv­ing and oth­er ac­ti­vi­ties dan­ger­ous for some.

In a case re­port study with self-re­ported da­ta pub­lished in the jour­nal Ag­ing in 2010, 10 can­cer pa­tients who tried fast­ing cy­cles per­ceived few­er side ef­fects from chem­o­ther­a­py.

In mice, the new study found that fast­ing cy­cles with­out chem­o­ther­a­py could slow the growth of breast can­cer as well as the can­cers mel­a­no­ma, gli­o­ma and hu­man neu­rob­las­toma. In sev­er­al cases, the fast­ing cy­cles were as ef­fec­tive as chem­o­ther­a­py, the re­search­ers said. Fast­ing al­so ex­tend­ed sur­viv­al in mice bear­ing a hu­man ovar­i­an can­cer. In the case of mel­a­no­ma, a deadly skin can­cer, the can­cer cells be­came re­sist­ant to fast­ing alone af­ter a sin­gle round, but the sin­gle cy­cle of fast­ing was as ef­fec­tive as chem­o­ther­a­ in re­duc­ing the spread of can­cer to oth­er or­gans.

For all can­cers tested, fast­ing com­bined with chem­o­ther­a­py im­proved sur­viv­al, slowed tu­mor growth and/or lim­it­ed the spread of tu­mors, the in­ves­ti­ga­tors re­ported.

As with any po­ten­tial can­cer treat­ment, fast­ing has its lim­its, Longo stressed. The growth of large tu­mor mass­es was re­duced by mul­ti­ple fast­ing and chem­o­ther­a­py cy­cles, but can­cer-free sur­viv­al was­n’t achieved, the re­search­ers said. Longo spec­u­lat­ed that cells in­side a large tu­mor may be pro­tected some­how or that the va­ri­e­ty of muta­t­ions in a large tu­mor may make it more adapt­a­ble.

But he not­ed that in most pa­tients, on­col­o­gists have at least one chance to at­tack the can­cer be­fore it grows too large.

Longo and col­la­bo­ra­tors at the U.S. Na­t­ional In­sti­tute on Ag­ing stud­ied one type of breast can­cer in de­tail to try to un­der­stand fast­ing’s ef­fects. While nor­mal cells de­prived of nu­tri­ents en­ter a dor­mant state si­m­i­lar to hi­berna­t­ion, the re­search­ers saw that the can­cer cells tried to make new pro­teins and took oth­er steps to keep grow­ing and di­vid­ing. The re­sult, Longo said, was a “cas­cade of events” that led to the crea­t­ion of dam­ag­ing mo­le­cules called free rad­i­cals. These broke down the can­cer cells’ DNA and de­stroyed them.

“The cell is, in fact, com­mit­ting cel­lu­lar su­i­cide. What we’re see­ing is that the can­cer cell tries to com­pen­sate for the lack of all these things mis­sing in the blood af­ter fast­ing. It may be try­ing to re­place them, but it can’t,” Longo said.

The new study book­ends re­search pub­lished in the jour­nal Pro­ceed­ings of the Na­t­ional Acad­e­my of Sci­ences in 2008. In that work, Lon­go’s team showed that fast­ing pro­tected nor­mal cells against chem­o­ther­a­py, but did­n’t ad­dress the ef­fect on can­cer cells. The study al­so fo­cused only on a sin­gle can­cer and chem­o­ther­a­py drug. The new work ex­tends those re­sults by show­ing that fast­ing not only fails to pro­tect can­cer cells, but makes them more vul­ner­a­ble, Longo said. He called the ef­fect “d­if­fer­en­t stress sen­sit­iz­a­tion” to re­flect the change in vul­ner­a­bil­ity be­tween nor­mal and can­cerous cells.

Lon­go’s in­ter­est in fast­ing and can­cer grew from years of stud­ies on the ben­e­fi­cial ef­fects of fast­ing in yeast and oth­er or­gan­isms. He found 15 years ago that starved yeast cells en­ter a stress-re­sist­ant mode as they wait for bet­ter times. By con­trast, he said, the muta­t­ions in can­cer cells come at a cost, such as a loss in adapt­abil­ity to di­verse en­vi­ron­ments.

“A way to beat can­cer cells may not be to try to find drugs that kill them spe­cif­ic­ally but to con­fuse them by gen­er­at­ing ex­treme en­vi­ron­ments, such as fast­ing, that only nor­mal cells can quickly re­spond to,” Longo said.

* * *

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Chemotherapy drugs work better against cancer when combined with cycles of short, severe fasting, a study has found. Researchers propose the fasting might help because normal cells tend to put off trying to divide when nutrients are lacking—but cancer cells keep trying, and this process ultimately destroys them. Fasting, even on its own, effectively treated a majority of cancers tested in mice, including transplanted cancer tumors made of human cells, researchers said. Their study, published in the journal Science Translational Medicine, found that five out of eight cancer types in mice responded to fasting alone: just as with chemotherapy, fasting slowed the growth and spread of tumors. And without exception, “the combination of fasting cycles plus chemotherapy was either more or much more effective than chemo alone,” said study senior author Valter Longo of the University of Southern California. Multiple cycles of fasting combined with chemotherapy cured 20 percent of mice with a highly aggressive type of children’s cancer that had spread throughout the body, and 40 percent of mice with a more limited spread of the same cancer, the authors added. No mice survived in either case if treated only with chemotherapy. “We don’t know whether in humans it’s effective,” said Longo, adding that it would take a clinical trial of several years to find out. Results from the first phase of a clinical trial with breast, urinary tract and ovarian cancer patients, conducted at the university, have been submitted for presentation at the next annual meeting of the American Society of Cancer Oncologists. But the first phase tests only the safety of a therapy, in this case whether patients can tolerate short-term fasts of two days, before and after chemotherapy. Fasting isn’t safe for everyone, Longo warned. The clinical trial didn’t enroll patients who already had lost more than 10 percent of their normal weight or who had other risk factors, such as diabetes. Fasting also can cause a drop in blood pressure and headaches, which could make driving and other activities dangerous for some. In a case report study with self-reported data published in the journal Aging in 2010, 10 cancer patients who tried fasting cycles perceived fewer side effects from chemotherapy. In mice, the new study found that fasting cycles without chemotherapy could slow the growth of breast cancer as well as the cancers melanoma, glioma and human neuroblastoma. In several cases, the fasting cycles were as effective as chemotherapy, the researchers said. Fasting also extended survival in mice bearing a human ovarian cancer. In the case of melanoma, a deadly skin cancer, the cancer cells became resistant to fasting alone after a single round, but the single cycle of fasting was as effective as chemotherapy in reducing the spread of cancer to other organs. For all cancers tested, fasting combined with chemotherapy improved survival, slowed tumor growth and/or limited the spread of tumors, the investigators reported. As with any potential cancer treatment, fasting has its limits, Longo stressed. The growth of large tumor masses was reduced by multiple fasting and chemotherapy cycles, but cancer-free survival wasn’t achieved, the researchers said. Longo speculated that cells inside a large tumor may be protected somehow or that the variety of mutations in a large tumor may make it more adaptable. But he noted that in most patients, oncologists have at least one chance to attack the cancer before it grows too large. Longo and collaborators at the U.S. National Institute on Aging studied one type of breast cancer in detail to try to understand fasting’s effects. While normal cells deprived of nutrients enter a dormant state similar to hibernation, the researchers saw that the cancer cells tried to make new proteins and took other steps to keep growing and dividing. The result, Longo said, was a “cascade of events” that led to the creation of damaging molecules called free radicals. These broke down the cancer cells’ DNA and destroyed them. “The cell is, in fact, committing cellular suicide. What we’re seeing is that the cancer cell tries to compensate for the lack of all these things missing in the blood after fasting. It may be trying to replace them, but it can’t,” Longo said. The new study bookends research published in Proceedings of the National Academy of Sciences in 2008. In that study, Longo’s team showed that fasting protected normal cells against chemotherapy, but didn’t address the effect on cancer cells. The study also focused only on a single cancer and chemotherapy drug. The new study on a range of cancers and common chemotherapy drugs extends the 2008 results by showing that fasting not only fails to protect cancer cells, but makes them more vulnerable, Longo said. He called the effect “differential stress sensitization” to reflect the change in vulnerability between normal and cancerous cells. Longo’s interest in fasting and cancer grew from years of studies on the beneficial effects of fasting in yeast and other organisms. He found 15 years ago that starved yeast cells enter a stress-resistant mode as they wait for better times. By contrast, he said, the mutations in cancer cells come at a cost, such as a loss in adaptability to diverse environments. “A way to beat cancer cells may not be to try to find drugs that kill them specifically but to confuse them by generating extreme environments, such as fasting, that only normal cells can quickly respond to,” Longo said.