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  • We have a lot of choices to make about our diet.

  • Add to that, doing the right thing

  • when it comes to preventing

  • and treating a chronic disease,

  • fighting a virus, or losing weight,

  • and suddenly our nutrition choices

  • can seem almost overwhelming.

  • Well, I'm here to help.

  • Welcome to the Nutrition Facts Podcast.

  • I'm your host, Dr. Michael Greger.

  • Today we begin a two-part series on the effects of fasting on cancer.

  • Do we feed cancer?

  • Do we starve it?

  • What do randomized trials tell us?

  • Here's our first story.

  • In 1974, an influential paper was published decrying

  • physician-induced malnutrition as the skeleton in the hospital closet ---

  • the fact that many patients in hospitals were malnourished,

  • which the editorial board of the journal of the AMA

  • described as shocking.

  • "Even a single case is one too many,"

  • yet still to this day the issue persists.

  • If anything, people with serious illness would seem to need

  • even more nutrition, not less, yet underfeeding

  • persists, involving as many as 50% of hospitalized patients.

  • The ethical principle of justice requires that every patient

  • be fed enough, given that hospital malnutrition

  • has been associated with increased

  • risk of disease and death, but is it cause and effect?

  • Does eating less make you sicker,

  • or does being sicker just make you eat less?

  • You don't know until you put it to the test.

  • But would it be ethical to randomize patients to remain starved?

  • I mean wouldn't nutritional support obviously help?

  • It turns out, no.

  • Not one, but 22 randomized controlled

  • trials involving thousands of malnourished patients

  • found that, sure, you can plump them up;

  • however, there seemed to be little effect on clinical outcomes.

  • In fact, sometimes it can actually make things worse.

  • Maybe your body is losing your appetite on purpose.

  • Ever since Hippocrates, fasting has been offered as a treatment

  • for acute and chronic diseases, based on the observation

  • that when people get sick, they frequently lose their appetite,

  • so maybe that's part of our body's wisdom and we shouldn't force it?

  • OK, but that was 2400 years ago.

  • What have we learned since?

  • Along with fever, decreased food consumption is indeed

  • one of the most common signs of infection, often regarded

  • as an undesirable manifestation of sickness,

  • but it's actually an active, beneficial defense mechanism.

  • Now obviously, chronic under-nutrition can impair

  • our defenses, but data suggest that in the short-term,

  • immune function can be enhanced by lowering food intake.

  • Some of the data are crazy, like 95% alive versus 95% dead

  • after the same infection,

  • but that was in mice starved for 48 hours.

  • Obviously, you can't randomize people to a fatal infection,

  • but what they showed is that the blood from starved mice was

  • nearly 8 times better at killing off the invading bacteria

  • in a petri dish.

  • It dramatically boosted

  • the capacity of their white blood cells to kill off the pathogens.

  • Why can't we just test people like that?

  • Indeed, we can.

  • Researchers fasted people for two weeks

  • on an 80 calorie a day diet,

  • and their white blood cells showed the same kind of boost

  • in bacteria-killing activity, a boost in antibody production,

  • and natural killer cell activity increased by an average of 24%.

  • Now that's especially interesting because our natural killer cells

  • don't just help clear infections, but also kill cancer cells.

  • In fact, that's how they measured natural killer cell activity by pitting

  • them against K562 cells --- those are tumor cells, human leukemia cells.

  • So two weeks of fasting boosted their bloodstream's ability

  • to kill off cancer cells by 24%.

  • So fasting is said to improve anticancer immunosurveillance,

  • or more poetically

  • "stimulate the appetite of the immune system for cancer.

  • "

  • So why isn't fasting used more to treat cancer?

  • Until recently,

  • fasting therapy was not considered to be a treatment option

  • in cancer, related to the fact that a common therapeutic goal

  • in palliative cancer treatment is to avoid weight loss

  • and to counteract the wasting syndrome known as cachexia,

  • which is the ultimate cause of death in many cancer cases.

  • Tumors are voracious, rapidly expanding,

  • and needing lots of energy and protein,

  • and so metabolically reprograms our body

  • to start breaking down to feed it.

  • It does this by triggering inflammation throughout the body.

  • It's not just that people lose their appetite.

  • The fundamental difference between weight loss

  • observed in cancer cachexia and that seen in simple starvation

  • is the lack of reversibility with feeding alone.

  • For example, here's the weight of a cancer patient that started to drop.

  • No wonder: they were only taking in a few hundred calories a day.

  • So in addition to giving them about 100 grams of protein a day,

  • they stuck a tube into a vein and infused up to 4,000 calories a day.

  • But it didn't matter.

  • They continued to lose weight.

  • Therapeutic nutritional interventions to correct or reverse

  • cachexia have met with little success.

  • The best treatment for cancer cachexia therefore

  • is to treat the cause and cure the cancer.

  • In fact, maybe forcing extra nutrition on cancer patients

  • could be playing right into the tumor's hands.

  • Like in pregnancy when the fetus gets first dibs on nutrients

  • even at the mother's expense,

  • the tumor may be first in the feeding line.

  • Maybe our loss of appetite when we get cancer

  • is even a protective response.

  • But in the 1960s, TPN was born --- total parenteral nutrition ---

  • where people no longer had to eat;

  • and you could infuse all the nutrition people needed straight

  • into their veins, and the modern era of nutrition support was born.

  • It became widely accepted and implemented,

  • growing into a multibillion-dollar industry.

  • So should it be routinely given to malnourished cancer patients?

  • The answer is not as obvious as one might think.

  • When it was put to the test in dozens of randomized trials,

  • the results were both disappointing and surprising.

  • Parenteral nutrition didn't just fail to provide any benefit

  • to these patients; it caused harm.

  • Not only did it appear to provide zero survival benefit,

  • there was an increase in complications and infections,

  • and a decrease in tumor response to chemotherapy,

  • presumed to be due to all those extra nutrients

  • stimulating tumor growth.

  • Similarly, oral nutritional

  • interventions in malnourished patients with cancer,

  • like giving them bottles of Ensure, found no survival advantage.

  • Despite the lack of demonstrated benefit, the knee jerk reaction

  • of many oncologists to the idea of cancer patients fasting

  • is the concern they're not eating enough already.

  • But you don't know until you until you put it to the test,

  • which we'll explore next.

  • For the past 50 years, chemotherapy has been a major medical treatment

  • for a wide range of cancers.

  • Its main strategy has been largely based on targeting cancer cells,

  • by means of DNA damage caused in part by the

  • production of free radicals.

  • Although these drugs were first believed to be

  • quite selective for tumor cells,

  • we now know that normal cells also experience severe

  • chemotherapy-dependent damage, leading to dose-limiting side effects

  • including bone marrow and immune system suppression,

  • fatigue, vomiting, diarrhea, and in some cases even death.

  • And if you do survive, the DNA damage to normal cells

  • can even lead to new cancers down the road.

  • There are cell-protecting drugs that have been tried

  • to reduce the side effects,

  • so you can pump in higher chemo doses,

  • but these drugs have not been shown to increase survival,

  • in part because they may also be protecting the cancer cells.

  • What about instead using fasting

  • for cellular protection during cancer treatment?

  • Fasting may have an unrecognized role

  • in cancer prevention and treatment.

  • Short-term fasting before and immediately after chemotherapy

  • may minimize side effects, while at the same time

  • may actually make cancer cells more sensitive to treatment.

  • That's exciting.

  • During nutrient deprivation, healthy cells switch from growth

  • to maintenance and repair, but tumor cells are unable

  • to slow down their unbridled growth due to growth-promoting mutations

  • that led them to become cancer cells in the first place.

  • This inability to adapt to starvation may represent an important

  • Achilles' heel for many types of cancer cells.

  • As a consequence of these differential responses

  • of healthy versus cancer cells to short-term fasting,

  • chemotherapy causes more DNA damage and cell suicide

  • in tumor cells, while potentially leaving healthy cells unharmed.

  • Thus, short-term fasting may protect