Calorie restriction (CR) without malnutrition is the most potent and reproducible physiological intervention for increasing lifespan and protecting against cancer in mammals.
—RESEARCHERS VALTER D. LONGO AND LUIGI FONTANA1
CANCER REFERS TO A DISEASED STATE IN WHICH certain abnormal cells in the body start to grow and multiply in an out-of-control manner. While there are close to one hundred different kinds of cancers, they all replicate themselves in a similar fashion. Cells that grow and invade other healthy, normal cells are considered cancerous. When their progress continues unimpeded, the result is serious illness or death.
According to the National Cancer Institute (a branch of the National Institutes of Health), more than 1.6 million new cases of cancer were expected to be diagnosed during 2015 in the United States, with nearly 600,000 people dying from the disease. The most common types were projected to be cancers of the breast, lung and bronchus, prostate, colon and rectum, bladder, melanoma (skin), and half a dozen more.2 These are sobering statistics—even frightening. Cancer is so prevalent in developed economies that in the United States alone, about 45 percent of men and 37 percent of women are expected to develop cancer in their lifetime. The situation would be hopeless, if recent studies had not provided a genuine ray of hope.
After reviewing current research on the role of fasting and other nutritional interventions in cancer prevention, here is how a pair of researchers summarized their findings: “An important discovery of recent years has been that lifestyle and environmental factors affect cancer initiation, promotion and progression, suggesting that many malignancies are preventable. Epidemiological studies strongly suggest that excessive adiposity, decreased physical activity, and unhealthy diets are key players in the pathogenesis and prognosis of many common cancers. In addition, calorie restriction (CR), without malnutrition, has been shown to be broadly effective in cancer-prevention in laboratory strains of rodents. Adult-onset moderate CR also reduces cancer incidence by 50 percent in monkeys.”3
Perhaps one of the greatest discoveries of the modern era is the fact that we can literally prevent, or at least reduce the risks of, cancer and other terrible diseases. This occurs through two primary methods: change in lifestyle and reduced exposure to environmentally hazardous agents. Biomedical studies have repeatedly shown that eating a healthy diet rich in fruits and vegetables, engaging in physical activity, and maintaining a healthy weight can significantly reduce the risk of cancer, diabetes, and cardiovascular diseases.
The lifestyle changes of healthy diet, exercise, and healthy weight are interrelated. Still, getting adequate exercise and eating healthy are a problem for most people, even the well-intentioned and highly educated. In developed countries, people tend to consume excesses of energy-dense foods and get less physical activity. This is a deadly combination that fuels the risk of contracting cancer and other deadly diseases. The obesity epidemic is the topic of another chapter, but here I would observe that the seeming helplessness of Western culture to curb excessive eating is continuing to increase the incidence of such life-threatening diseases as cancer.
Fortunately there is one more option that studies have shown can significantly reduce the risk of cancer: reducing calorie intake. Although physical activity is a wise step toward improving health, CR doesn’t require exercise. Nor does it require a strict weight-loss program—at least as we traditionally think of such Spartan regimens. Healthy eating is still a must, though, and one way to eat healthier is to incorporate intermittent calorie reductions in your diet. The results from studies on the ability of CR to prevent cancer are so startling that they can only be termed “amazing.”
Scientists first documented that fasting may be beneficial in cancer reduction more than a century ago. In 1909 a Japanese scientist published the first scientific paper showing that calorie reduction in mice helped to inhibit the growth of tumors.4 Since then several other studies have confirmed this early twentieth century observation: calorie reduction inhibits tumor growth in all kinds of animals.
For example, in 1987 a scientist at the National Institutes of Health conducted a thorough review of all relevant studies on the relationship between caloric intake, body weight, and cancer incidence. He chose a total of eighty-two published experiments on fasting and different kinds of cancer. On average, experimental animals had their total energy intake restricted as follows: 29 percent fewer calories, 50 percent less total fat, and 11 percent less protein than animals fed a full, normal diet. At the end of the experiments, the incidence of cancer in animals placed on limited intake was 42 percent lower than in animals fed normally.5 In fact, when all those studies were combined and averaged, they showed the incidence of tumor occurrence increased with increasing caloric intake and body weight. Those studies showed calorie reductions as modest as 7 to 20 percent had significant cancer-reducing effects as well.6
For a while scientists wondered if the interesting results observed in rodents and other animals could be replicated in nonhuman primates such as monkeys and chimpanzees. Thus, in 1989, researchers embarked on a twenty-year-long project to study the effects of calorie reduction in prevention of age-related diseases, such as cancer and cardiovascular diseases, in rhesus monkeys. As noted earlier, their results were published in 2009 in the prestigious journal Science, and showed—among other things—that a 30 percent reduction in rhesus monkeys’ calorie intake reduced incidence of cancer by as much as 50 percent.7 These results from a reputable randomized, controlled, peer-reviewed study stunned the scientific community (albeit in a good way).
Indeed, results from this study, along with others like it, were so encouraging that scientists from the National Institutes of Health—in collaboration with other medical research groups nationwide—began to seriously consider the possible effects of CR on prevention of human cancer and other age-related diseases. So, the NIH’s National Institute on Aging instituted the first ever randomized clinical trial to test the effect of CR in humans (this CALERIE study was first noted in chapter 3). Usually CR studies involving humans are filled with certain inherent limitations. For example, you cannot just inject humans with cancer to test how they are faring with CR. In addition, ethical requirements mean that you can only restrict the calories of sick patients to certain levels; it may also prove difficult for a sick person to sustain CR for a long time.
With these limitations in mind, phase 1 of this study involved calorie reductions of 20 to 30 percent for six months. At the end of this period researchers checked for biomarkers of health, which predict whether a person can develop cancer, diabetes, or cardiovascular diseases. They found that patients placed on CR had reduced levels of oxyradicals (remember those free oxygen radicals?) and other internal health hazards. High levels of free radicals lead to cancer and other diseases.
Cancer patient studies
These studies could be seen as studies on the potential preventive role of fasting in cancer. But how about cancer patients? Is there any study of humans showing that fasting could be beneficial to them?
In 2009 a group of colleagues from the University of Southern California published a series of case studies conducted on ten cancer patients. The study tested the role of prolonged fasting on recovery of cancer patients undergoing chemotherapy, especially whether fasting had any role in reducing side effects associated with chemotherapy. Note that prolonged fasting means a period of forty-eight to one hundred twenty hours, which is different than short-term fasts of twenty-four hours or calorie restriction.
In this study the three male and seven female patients (ages ranging from forty-four to seventy-eight) voluntarily fasted between forty-eight and one hundred fifty hours before or shortly after chemotherapy. The types of cancer varied, such as breast, ovarian, uterine, and prostate. These scientists noticed a significant reduction in side effects reported, both in frequency and severity.8
Anyone who has been through chemotherapy knows that such symptoms as nausea, vomiting, abdominal cramps, mucosis, diarrhea, and weakness are common. Interestingly patients in this study reported fewer side effects than those who did not fast. They also noticed that fasting before or after their chemotherapy did not have any complications or side effects—showing that fasting could be safe even for cancer patients undergoing treatment. Although this is only a set of case studies and needs to be further confirmed through randomized, double-blind clinical trials, the implications of these findings are still worth noting.
What could be the reason for this observation in cancer patients? One plausible explanation is that prolonged fasting results in more profound physiological changes at the cellular level than calorie restriction or short-term fasting. During prolonged fasting, cells essentially switch completely to metabolism based on fats and ketone bodies. This results in reducing pro-growth factors and activation of signaling pathways, which increase cellular resistance to toxins in both human and animal models.
For example, a study done by researcher J. W. Lee and coworkers showed that prolonged fasting in mice protects them against chemotoxicity by reducing the amount of insulin-like growth factor-1 (IGF-1), a growth-factor hormone that has been linked to aging, and tumor risk and progression. Therefore, it seems that fasting protects normal cells by rearranging their energy allocation away from reproduction and growth processes (desperately needed by cancer cells) toward maintenance pathways (needed more by normal cells) whenever nutrients are scarce or lacking.9 Fortunately the switch to this “protected mode” occurs only in normal cells and not cancer cells, since cancer cells by nature tend to prevent the activation of stress resistance. Hence, during times of induced stress such as prolonged fasting, there is an opportunity to selectively protect normal cells and improve cancer treatment.
A major side effect suffered by cancer patients, especially those undergoing chemotherapy, is myelosuppression. This is a condition in which bone marrow activity is reduced. When this happens, then there are fewer white blood cells, red blood cells, and platelets. Of course, the result of such decrease is reduced immunity. The reason chemotherapy results in myelosuppression is because it damages the stems cells (regenerative cells) in bone marrow, which then impairs tissue repair and regeneration.
Can prolonged fasting help with this myelosuppression by helping to facilitate regenerative stem cells? Several researchers set out to investigate this question a few years ago, among mice and in human patients. The results of their study were published in 2014. The study showed that fasting increased the body’s immunity and regenerative process, with reduced side effects and death associated with chemotherapy. Prolonged fasting reduced circulating IGF-1 levels and protein kinase A (PKA) activity.10 (PKA refers to a key gene that when it shuts down signals those stem cells to start regenerating.) This study has wide implications for improving immunity and fighting diseases beyond cancer.
In another study involving yeast cells stimulated to express cancer symptoms in mice and engineered to express different kind of cancers, researchers showed that cycles of fasting followed by normal feeding were as effective as cancer drugs in the treatment of the cancer or delaying the worsening of the cancer in yeasts. In animal models used, when periodic prolonged fasting was used in conjunction with cancer drugs, those mice became cancer-free for a prolonged period of time.11 In the words of the authors, “These studies suggest that multiple cycles of fasting promote differential stress sensitization in a wide range of tumors and could potentially replace or augment the efficacy of certain chemotherapy drugs in the treatment of various cancers.”12
There are numerous studies in animal models demonstrating the preventive role of fasting against cancer. For example, in 2011 Olga P. Rogozina, coworkers from the University of Minnesota, and a researcher from the Mayo Clinic published the results of their study on the role of fasting in reducing the risk of cancer in mice. They examined the effect of intermittent and chronic (prolonged) calorie restriction on serum adiponectin and leptin levels in relation to mammary tumorigenesis (breast cancer). Several ten-week-old mice were divided into three groups:
• One group ate a normal diet.
• A second group was on a rotation of 50 percent calorie reduction for three weeks (achieved by diet modification—2x protein, fat, vitamins, and minerals), followed by another three weeks of normal feeding, for seventy-nine to eighty-two weeks.
• The third group was placed on repeating cycles of a 50 percent calorie reduction (achieved by reduction in total calorie and energy intake) for six weeks, followed by another six weeks of normal feeding, for seventy-nine to eighty-two weeks.
At the end of seventy-nine to eighty-two weeks, the mice were killed and their blood samples analyzed for mammary tumors. At the end of the study, for animals that were fed normal meals, the incidence of mammary cancer was 71 percent. The calorie-restricted animals showed an incidence of mammary tumors of 35.4 percent, and for those on intermittent fasting, only 9.1 percent.13 This study provides additional scientific support to the fact that fasting may have some beneficial effects in reducing cancer risks. About 62 percent less risk in a scientific study is hard to ignore, even if it is an animal model.
Calorie restriction is believed to inhibit cancer growth in part by regulating expression of IGF factors, as noted before. So, in 2013 a team of researchers from the University of California at Los Angeles set out to investigate the role of fasting and IGF-1 on prostate cancer. Their study was published in the International Journal of Molecular Sciences. Mice models were divided into four groups:
• The first group ate a normal diet.
• A second group was placed on a 40 percent calorie restriction.
• A third group was placed on ganitumab (this drug is a specifically monoclonal antibody that works against IGF-1 factor and is used to treat cancers).
• The fourth group followed a 40 percent calorie restriction in addition to receiving the ganitumab drug.
At the end of the study results showed that the mice on 40 percent calorie reduction had decreased tumor weight, reduced plasma insulin and IGF-1 levels, and increased apoptosis (programmed cell death). On the other hand, even though the cancer drug reduced tumor growth, it had no effect on final tumor weight. The group that had both the drug and calorie restriction showed the best improvement: decreased tumor progression and tumor weight, decreased levels of insulin and IGF-1, and increased apoptosis (programmed cell death).14 As expected, the control group that followed the traditional diet fared much worse than the groups that received either the drug or calorie-restricted diet.
While NIH and research laboratories continue to investigate the full effect of CR on humans, it is important to note that NIH does not waste its resources on unpromising medical options. There must be something going on for NIH and other agencies to fund these studies, which proceeded to phase 2 trials on humans. If CR can reduce cancer in primates by up to 50 percent, and if NIH thinks this simple lifestyle change has such a potential to prevent a disease as serious as cancer, then it makes sense to look into this at a personal level before it is too late.