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  • "Fasting for Cancer: What About Cachexia?"

  • 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.

"Fasting for Cancer: What About Cachexia?"

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Fasting for Cancer: What About Cachexia?(Fasting for Cancer: What About Cachexia?)

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    林宜悉 に公開 2022 年 10 月 18 日
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