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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 percent 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 seems 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 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? Okay, but that was 2,400 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 percent alive versus 95 percent dead after the same infection, but that was in mice (starved for 48 hours). Obviously, we can’t randomize people to a fatal infection, but what they showed is that the blood from starved mice was nearly eight 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 ability, a boost in antibody production, and natural killer cell activity increased by an average of 24 percent. 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 percent.
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? The reason fasting therapy has traditionally not even been considered as a treatment option in cancer is because so much about cancer care revolves around keeping people’s weight up to try to counteract the cancer-wasting syndrome.
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, needing lots of energy and protein, and so cancer metabolically reprograms the 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 the 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 parental nutrition––where people no longer had to eat—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 put it to the test, which we’ll explore, next.
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