We have a lot of choices to make about our diet. Add to that – doing the right thing when it comes to treating a chronic illness, 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 conclude our two-part series on fasting and cancer. And, we start with a story about how the benefits of short-term fasting translate in the clinical setting.
The first randomized prospective clinical evaluation of the effects of fasting on chemotherapy––the “incidence of chemotherapy-induced nausea and vomiting in cancer patients”––was published in 2014, but the patients were dogs. Cancer-bearing dogs presenting at a veterinary hospital were randomized to be fasted for 24 hours before chemotherapy, and those that were were significantly less likely to suffer from vomiting—only 1 in 10 compared to 2 out of 3 in the nonfasted group, which is great.
But what can that tell us about human medicine? Evidently, not much. It is nearly impossible to rely on most animal data to predict whether or not an intervention will have a favorable clinical benefit–risk ratio in human subjects.
For example, mice have a metabolic rate approximately seven times higher than humans; so, a single day of fasting can cut lean body mass by about 15 percent. That would take over a month of fasting in people. So, that dramatic study on mice showing 100 percent alive versus 100 percent dead on high dose chemo depending on whether they were fasted for 60 hours? What can that really tell us? And when it comes to cancer, rodents can bear massive tumor loads, whereas people generally waste away and die when tumor masses have reached just a thousandth of our body weight. You can’t even necessarily extrapolate from one rat to another, even within the same strain bought from different dealers.
The only way to see what happens in humans, the only way to guarantee findings are relevant, is to study people. The theory is that combining fasting cycles with chemotherapy could extend the survival of advanced-stage cancer patients by both retarding tumor progression and reducing side effects––or even providing an alternative to chemotherapy altogether in early-stage cancer patients. But that’s all contingent on being confirmed in human clinical trials.
First, there was a case series. Several patients diagnosed with a wide variety of cancers elected to undertake fasting prior to chemotherapy and share their experiences. Those who underwent chemo both with or without fasting reported a reduction in fatigue, weakness, and gastrointestinal side effects while fasting; in fact, felt better across the board, with zero vomiting in the fasting group. The weight lost during the few days of fasting was rapidly recovered in most of the patients, and did not lead to any detectable harm; so, overall was looking feasible, safe, with the potential to ameliorate side effects.
But only randomized clinical studies could tell for sure, and so here we go. Breast and ovarian cancer patients fasting started 36 hours before and ending 24 hours after chemotherapy, and it did appear to improve quality of life and fatigue, but another study found no such beneficial effects. There did appear to perhaps be less bone marrow toxicity, given the higher counts of red blood cells and platelet-making cells. But no benefit when it came to killing off white blood cells—the immune system cells—so that was a disappointment. Perhaps they didn’t last long enough? They only fasted 24 hours before and after.
To find out the optimal duration, 20 cancer patients were split up into three groups, fasting for 24, 48, or a total of 72 hours. All those in the 24-hour group suffered nausea after chemo, but less than half in the 72-hour group, and most were vomiting in the 24-hour group, but none in the longest fasting group. Longer fasting groups also tended to suffer less nerve damage and less serious bone marrow suppression. Even after 24 hours of fasting, two cycles of chemo can knock people’s white blood cells down to suboptimal levels. But with 72 hours, chemo knocked their immune system down but not out.
Okay, so short-term fasting may reduce chemotherapy-induced toxicity. But what I want to know is if it makes it work better. A systematic review of 22 studies found that overall, fasting was found to not only reduce chemotherapy side effects (like organ damage, immune suppression, and chemotherapy-induced death), but also to suppress tumor progression, including tumor growth and metastasis, resulting in improved survival. But…nearly all of the studies were on lab animals. The studies on humans are limited to evaluating safety and side effects. The tumor-suppression effects of fasting, for example, its influence on tumor growth, metastasis, and prognosis, have not been evaluated, until now. To be continued…
In our final story, we ask – how might we replicate the protective effects of fasting with food?
Short-term food withdrawal during chemotherapy may begin to solve the long-standing problem with most cancer treatments: how to kill the tumor without killing the patient. Short-term fasting––for example, for 48 hours before chemo and 24 hours afterwards––may reduce side effects, reduce chemotherapy-induced toxicity. However, the potential tumor-suppressing effects of fasting, for example, its influence on tumor growth, metastasis, and prognosis, have not been evaluated, until now. No, actually, sadly they mean “have not been evaluated-until-now,” meaning have not been evaluated yet, period. So, in answering the question, “To fast, or not to fast before chemotherapy?,” “It should be emphasized that the evidence provided by human studies is still very limited.”
Some argue that reducing the side effects alone could improve efficacy, since patients could withstand higher doses. For example, the heart and kidney damage associated with the widely prescribed anti-cancer drugs limit their full therapeutic potential. It’s not clear, though that maximizing the tolerated chemo dose would achieve longer survival or better quality of life. For now, I think we should just be satisfied with the fewer side effects for fewer side effects sake.
Some cancer docs urge caution, concerned about malnutrition. That concern is echoed in official guidelines on nutrition in cancer patients. Because of the risks of malnutrition and yeah, maybe a day or two might not hurt. But because patients might be tempted to prolong fasting episodes, without ﬁrm evidence of a beneﬁt, they feel fasting during chemotherapy cannot be recommended.
Fasting proponents agree that patients with severe weight loss, muscle wasting, or malnutrition are probably not good candidates for even short-term fasting. But out of the hundreds of patients that have been tracked, there is no evidence of severe adverse events in terms of malnutrition or weight loss with short-term fasting or fasting-mimicking diets. And those patients who did experience a weight loss during fasting typically recovered their weight before the subsequent cycle of chemo without detectable harm.
But look, even if there is a risk, we’re talking about cancer here. Accepting trade-offs is kind of the name of the game. People are willing to put up with the risk of severe and even life-threatening side effects all the time, and even if it just helped alleviate some of the side effects, it might be worth a try.
Of course, meanwhile Big Pharma is busy trying to come up with drugs aimed at reproducing the beneficial effects of fasting. Although fasting-mimicking drugs may be preferred by patients who would rather pop a pill than go without eating, it will be years before they’ll ever be on the market, and it’s hard to imagine drugs will be developed that are both as effective and as safe as fasting. So, is there anything we can tweak in our diet to get similar benefits without having to fast?
The way fasting works is by reducing the levels of a cancer-promoting growth hormone known as insulin-like growth factor 1. It’s the reduced levels of IGF-1 that mediate the differential protection of normal and cancer cells in response to fasting and improves chemo’s ability to kill cancer but spare normal cells. How do we know this? Because restoration of IGF-1 was sufficient to reverse the protective effect of fasting.
So, reducing IGF-1 signaling may provide dual benefits by protecting normal tissues while reducing tumor progression, and may even help prevent the cancer in the first place. Fasting isn’t the only way to drop IGF-1 levels. Yes, a few days of fasting can cut levels in half, but that’s largely because you’re cutting your protein intake. Protein is a key determinant of circulating IGF-1 levels in humans––suggesting that reduced protein intake may become an important component of anticancer and antiaging dietary interventions, particularly a reduction in animal protein.
If you compare those eating strictly plant-based diets getting about the recommended daily intake of protein, .8 grams per kg of body weight, and compare them to people just as slender but eating more typical American protein intake, going on a calorie-restricted diet may lower IGF-1 a little, but eating a plant-based diet can lower it more. So, not only may a diet centered around whole plant foods down-regulate IGF-1 activity, potentially slowing the aging process, but it may be a way of turning anti-aging genes against cancer.
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