And how to apply it to cancer treatment
The circadian theory of health presupposes that the human body has an internal 24-hour clock and needs an appropriate amount of time to rest and reset. During a fasting period, it relates to food intake and the availability and accessing of stored nutrients. Dr.Valter Longo and Dr. Satchidananda Panda are two experts in the field of longevity and the body's internal clock. They believe that bodily functions, in particular the ability to repair and rejuvenate cells and organs, rest heavily on the fasting and feeding cycle9.
In his research, Dr. Panda highlighted the importance of when you eat, not just what you eat. He performed an experiment in which two identical sets of mice were given the same high fat diet. One set ate as much as they wanted and the other set could only eat within an 8-10 hour window. The unrestricted mice developed obesity and were more prone to diabetes, while the mice that were restricted, were completely healthy8.
Fasting regimens, including calorie restriction which reduces the amount of calories a person normally desires, have proven successful in increasing lifespan and delaying the onset of different types of cancers and cardiovascular diseases.
When studied in rodents, monkeys, flies, yeast, worms, and fish, dietary restriction has proven to be very effective in extending average life span. In a recent study, calorie-restricted monkeys, which developed lower amounts of body weight and fat, saw higher survival rates than the non-calorie-restricted control group. The median survival rates for the calorie-restricted older male monkeys reached the 90th percentile for their species7. Similarly, rodents on a restricted diet saw an 60% increase in lifespan, along with the delay of chronic disease and effects of aging1.
Starvation or fasting have also found to be potent enough to resemble the effects of chemotherapeutical drugs widely used for different cancers. Fasting can delay the growth of tumors and even stimulate the performance of cancer-fighting drugs. Specifically, when looking at neuroblastoma cancer cells, fasting combined with chemotherapeutic drugs produced greater long-term cancer-free survival. The results of fasting can make the cancerous cells more sensitive to the treatment they are receiving5. Similarly, in a study conducted on breast cancer, the combination of calorie restriction and radiation suppressed the growth of the cancerous tumor. These results suggest that a combined therapy of radiation and restriction of calories is more effective than a therapeutic approach on its own2.
Additionally, short-term starvation can protect normal cells in mice, but does not have the same effect on cancer cells treated with chemotherapy drugs. Starvation results in a decrease of IGF-1 signaling which is a major insulin-like growth factor in our bodies and plays a crucial role in the progression of tumors. It is believed to be a risk factor for cancer, as higher levels of IGF-1 are connected to higher rates of tumor growth11. This discovery provides a new direction in cancer treatment, one that increases protection of non-cancer cells. It is important to note, however, that the restriction of calories is not feasible for cancer patients prone to weight loss from cancer itself or chemo treatment.
There is long-standing evidence that obesity and physical inactivity are risk factors of certain cancers. Combined with the positive impacts of fasting, nutritional intervention can be administered to reduce calorie intake. For example, in a longitudinal study performed on patients with colon cancer, the rate of glycemic loading and total carbohydrate intake were measured and analyzed against the recurrence and mortality of stage III colon cancer. The results showed that a typical western-style diet (large amounts of fat and processed grains, meats, and sugars) in stage III colon cancer patients revealed a 3-fold rise in cancer recurrence and deaths3. Additionally, a calorie-restricted diet was implemented for 6 weeks in a small subset of men with prostate cancer. The results showed that the baseline weight of the men significantly declined coupled with an increase in the protein IGFBP-3, which inhibits the growth and proliferation of prostate cancer cells. This highlights the power that weight loss can have on patients with prostate cancer, even with short-term intervention4.
Dr. Longo addressed the difficulty of enforcing a calorie restricted diet by developing the fasting-mimicking diet (FMD), which is a diet low in calories, sugar, and protein, but high in unsaturated fats.
Mice were fed this diet for four days, every two months and the results showed extended longevity, lowered body fat, decreased risk of cancer, and a revitalized immune system. While on FMD, the level of white blood cells, which are disease-fighting cells, increased in the older mice. The mice on the regular diet developed early-onset tumors compared to mice on the FMD6. In a human clinical trial of the FMD, prediabetes glucose levels were lowered to their normal amounts, and IGF-1 had a large drop, which could translate to a decrease in the risk of cancer. Lastly, the increase in the number of stem cells for people on the diet, recognizes a promising approach for multi-system rejuvenation.
Implementing nutritional interventions, such as calorie restriction into a patient’s “health plan” may take a role in future diagnoses. The idea of fasting is an elemental idea, formulated into a treatment that could be the next big avenue in cancer prevention and other chronic diseases.
1. Fontana, L., Partridge, L., & Longo, V. D. (2010). Dietary Restriction, Growth Factors and Aging: from yeast to humans. Science (New York, N.Y.), 328(5976), 321–326.
2. Anthony Saleh, Brittany Simone, Juan Palazzo, Jason E. Savage, Yuri Sano, Tu Dan, Lianjin Jin, Colin Champ, Shuping Zhao, Meng Lim, Frederica Sotgia, Kevin Camphausen, Richard Pestell, James Mitchell, Michael Lisanti & Nicole L. Simone (2013) Caloric restriction augments radiation efficacy in breast cancer, Cell Cycle, 12:12, 1955-1963.
3. Jeffrey A. Meyerhardt, Kaori Sato, Donna Niedzwiecki, Cynthia Ye, Leonard B. Saltz, Robert J. Mayer, Rex B. Mowat, Renaud Whittom, Alexander Hantel, Al Benson, Devin S. Wigler, Alan Venook, Charles S. Fuchs; Dietary Glycemic Load and Cancer Recurrence and Survival in Patients with Stage III Colon Cancer: Findings From CALGB 89803, JNCI: Journal of the National Cancer Institute, Volume 104, Issue 22, 21 November 2012, Pages 1702–1711
4. Wright, J. L., Plymate, S., D’Oria-Cameron, A., Bain, C., Haugk, K., Xiao, L., … McTiernan, A. (2013). A study of caloric restriction versus standard diet in overweight men with newly diagnosed prostate cancer: a randomized controlled trial. The Prostate, 73(12), 1345–1351.
5. Lee, C., Raffaghello, L., Brandhorst, S., Safdie, F. M., Bianchi, G., Martin-Montalvo, A., … Longo, V. D. (2012). Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy. Science Translational Medicine, 4(124), 124ra27.
6. Brandhorst, S., Choi, I. Y., Wei, M., Cheng, C. W., Sedrakyan, S., Navarrete, G., … Longo, V. D. (2015). A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance and healthspan. Cell Metabolism, 22(1), 86–99.
7. Mattison, J. M., Colman, R. J., Beasley, M. T., Allison, D. B., Kemnitz, J. W., Roth, G. S., . . . Anderson, R. M. (2017). Caloric restriction improves health and survival of rhesus monkeyss. Nature Communications, 8(14063).
8. Chiax, A., Lin, T., Chang, M., & Panda, S. (2018). Time-Restricted Feeding Prevents Obesity and Metabolic Syndrome in Mice Lacking a Circadian Clock. Cell Metabolism.
9. Longo, V. D., & Panda, S. (2016). Fasting, circadian rhythms, and time restricted feeding in healthy lifespan. Cell Metabolism, 23(6), 1048–1059.
10. Wei, M., Brandhorst, S., Shelehchi, M., Mirzaei, H., Cheng, C., Budniak, J., . . . Cohen, P. (2017). Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular diseases. Science Translational Medicine.
11. Raffaghello, L., Lee, C., Safdie, F. M., Wei, M., Madia, F., Bianchi, G., & Longo, V. D. (2008). Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy. Proceedings of the National Academy of Sciences of the United States of America, 105(24), 8215–8220.