Just when it seems like the picture of diet and prostate cancer is finally coming into focus, PCF-funded scientist Nicole Simone, M.D., a radiation oncologist at Thomas Jefferson University, has added a new dimension. It may not be just a question of the good foods you do eat, and the bad foods you don’t eat: It also appears to matter, very strongly, how much you eat at all.
Simone’s research in prostate cancer and also in breast cancer suggests that restricting calories has many anti-cancer effects in the body – including, in mice, decreasing the likelihood of metastasis. It lowers inflammation, changes the gut microbiome, may decrease the side effects of systemic therapy and generally seems to slow down cancer. In effect, caloric restriction gives cancer a “brown-out,” limiting its energy. “We’re just beginning to understand the promise and the power of caloric restriction,” says medical oncologist and molecular biologist Jonathan Simons, M.D. “If there were a drug that could do all these things, we’d prescribe it in a heartbeat.”
Wait… aren’t people with cancer supposed to keep their calories up? If you’re thinking that limiting calories when someone’s fighting cancer seems like the opposite of the common wisdom – well, you’re right! “This is not what we were all taught in medical school,” says Simone. And she’s not entirely sure why this approach produces as many good effects as it does – but here’s a clue: One way to look for various forms of cancer is with a PET scan, which involves injecting a radioactive dye. “That dye is actually a radio-labeled glucose,” which is eagerly taken up by tumor cells because “cancer loves to eat. Cancer is metabolically active, and sugar is one of its favorite foods!”
Simone’s laboratory has been investigating caloric restriction for several years. “Initially, we were looking for a way to increase the effectiveness of radiation and chemotherapy in tumors that have a poor response to standard therapies.” In mouse models of hormone-sensitive breast cancer, Simone found that simply restricting the mice’s daily caloric intake made a big difference: it not only altered cell metabolism and made cancer cells more vulnerable to radiation and chemotherapy. It also “decreased metastasis and increased overall survival.”
If this worked in breast cancer, would it work in prostate cancer? Yes! “In several models of hormone-sensitive prostate cancer, we found the same,” she says. “We were able to decrease tumor growth, decrease metastasis, and increase survival.” Then Simone’s lab tested caloric restriction in mice with castrate-resistant prostate cancer (CRPC), cancer that is no longer controlled by androgen deprivation therapy (ADT). Again, caloric restriction affected how tumors responded to radiation. “We saw some really interesting systemic, molecular changes,” Simone says. “We wanted to take it a step further, and use that preliminary data as a launching pad to see what would happen in patients with prostate cancer if we put them on a caloric restriction diet.”
Eating 25 percent less: In a pilot study, 20 patients – men diagnosed with localized prostate cancer who were scheduled to have prostatectomy – underwent caloric restriction for 21 days. Simone individually tailored each man’s daily calorie total, based on what he had reported eating for several days ahead of time. “We figured out their average caloric intake and then decreased that by 25 percent.” Simone’s team also gave the men some dietary guidelines, encouraging (but not requiring) an anti-inflammatory diet with less refined sugar and processed food, more fruits, vegetables and complex carbohydrates. “The men were able to stick to the diets really nicely,” she says. “We went over their diet logs and calculated their dietary inflammatory index. They did increase their anti-inflammatory foods! They also lost an average of 12 pounds each.”
Could just three weeks of restricted-calorie, pretty much anti-inflammatory diet make a difference? Yes, in several ways:
A decrease in systemic inflammation. Men had changes in inflammatory markers in the blood, including a lower sedimentation rate (a blood test that measures inflammation).
Changes in the gut microbiome. Rectal swabs, taken before the men started the diet and three weeks later, were sent to PCF-funded investigator Karen Sfanos, Ph.D., at Johns Hopkins, who performed in-depth analysis. In the swabs taken at three weeks, Sfanos found a significant change in the gut microbes known to produce more butyrate! Butyrate is an important fatty acid that helps control inflammation and is made by beneficial bacteria. The fact that these microbes that make butyrate increased suggests that the population of bacteria in the gut changed for the better, simply with caloric restriction and an anti-inflammatory diet.
Less inflammation in the gut wall, as measured by lipopolysaccharides (LPS) in the blood. “When there is inflammation in the gut, it creates spaces between the epithelial cells in the gut wall.” Inflammatory cells can “leak” out of the gut into the blood, and increase inflammation elsewhere.
Less inflammation in the tumor. “We saw a decrease in inflammatory markers such as NF-κB (an inflammatory pathway) in the tumor itself, and in MIR21.” MIR21 is a microRNA gene (which makes RNA instead of proteins) that is believed to drive cancer development, growth, metastasis, and resistance to treatments. Simone is discussing this aspect with another scientist she met at PCF’s Scientific Retreat, Shawn Lupold, Ph.D., of Johns Hopkins, who is a pioneer in the study of MIR21.
Ultimately, Simone believes, caloric restriction can play an important role for men with all stages of prostate cancer – but to make it even more effective will also require precision nutrition, based on precision oncology. In this case, that means figuring out whether someone’s cancer prefers a diet that is sweet or savory. “Prostate cancer can metabolize through the glucose pathway, or through lipid pathways,” says Simone. Understanding which pathway really appeals to a particular cancer – some prefer sugar, some really go for fat – “can tell us how your cancer is driving its own energy.”
Thus, “if the tumor’s feeding on lipids, we change the dial on fat content in the diet.” And if the tumor prefers sugar, then a diet aimed at keeping sweets and simple carbohydrates to a minimum will foil the cancer’s gustatory pleasure.
One of the biggest challenges with chemotherapy, ADT, or even radiation therapy, is resistance to treatment: the cancer evolves to minimize the damage of attempts to kill it. “Diet can almost be a more powerful tool,” says Simone. “Cancers get smarter; a drug will work well for a while, then all of a sudden, cancer will figure out a way around it. The power of restricting food is that it provides less energy for the cancer to use up.”
Note: Caloric restriction is done under careful supervision by medical professionals. It is strongly recommended that you talk with your doctor before making changes to your diet.
