 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, with 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, and 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 they 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 end chronic diseases based on the observation, then 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 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 act of beneficial defense mechanism. Now, obviously chronic under nutrition can impair our defenses, but data suggests 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 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 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 bloodstreams ability to kill off cancer cells by 24%. So fasting is said to improve anti-cancer 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 and palliative cancer treatment is to avoid weight loss and to counteract the wasting syndrome known as catechia, which is the ultimate cause of death in many cancer cases. Tumors are voracious, rapidly expanding, 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 catechia, and that seemed 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 catechia have met with little success. The best treatment for cancer catechia, 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. 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 multi-billion-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 nutrition interventions in malnourished patients with cancer, like giving them bottles of inshore, 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 that they're not eating enough already. But you don't know until you put it to the test, which we'll explore next.