Fasting has always been touted as one of the most innate and safest ways the body has to restore good health. In the case of disease prevention, fasting has become a popular topic, especially in the field of oncology. What if the best medicine was an integrative nutritional approach where fasting, combined with conventional treatments, maximized results? This question has been explored by several researchers, including Dr. Valter Longo of the University of Southern California. In a press release, he said: “It may be that by being always exposed to so much food, we no longer benefit from the natural protective systems that allow the body to kill cancer cells (…) But by following a diet reduced in calories like fasting, you can let the body use sophisticated mechanisms capable of identifying and destroying bad cells in a natural way”.

Autophagy and fasting

It is due to the Japanese specialist in cell biology Yoshinori Ohsumi that we owe the explanations of the cellular process called “autophagy”, for which he obtained the Nobel Prize for Medicine and Physiology in 2016. In a stressful situation, such as during a deficiency of nutrients, autophagy represents a natural regulatory mechanism. It consists of the partial degradation of the contents of the cell by the cell itself. It is a form of cleaning or recycling waste or non-essential items to meet the immediate needs of the cells. Autophagy is essential to maintain the proper functioning of the body, since it allows the transformation of damaged structures into molecules that can be used for metabolism. In the presence of cancer or infection, the cell can similarly eliminate its defective or potentially toxic constituents, or even destroy itself, in order to protect the organism as a whole.

Although reduced autophagy may allow tumor formation and short-term survival, cancer cells would generally exhibit lower autophagic capacity than healthy cells. Indeed, several studies highlight how the lack of autophagy leads to lower levels of tumor suppressor genes. Among the anticancer benefits of the autophagic process, we find better stability in gene expression, reduced cell proliferation capacity and a marked decrease in inflammation required for tumor development. Autophagy is also known to amplify cell death induced by radiotherapy and chemotherapy treatments. Significant advantages! Fasting could thus represent a potentially new way of devising more effective cancer treatment strategies.

Beneficial effects on the quality of life in chemotherapy

In a popular study, conducted in the United States, nearly 40 people fasted in combination with chemotherapy and reported that fasting was not only possible, but reduced a wide range of side effects, including nausea. Fasting would also improve the following symptoms:

  • General tolerance to the treatment,
  • Tiredness,
  • Headaches,
  • Vomiting,
  • Diarrhea and
  • Cramps when the latter is combined with chemotherapy compared to chemotherapy alone.

Among the deleterious effects of chemotherapy, the decrease in blood cells is the most common factor delaying cycles of chemotherapy, leaving the person more vulnerable to opportunistic infections. Fasting seems to offer an interesting solution on this point. It is believed to protect red and white blood cells from harmful effects during treatment, providing additional immune protection, including a higher neutrophil count, allowing treatment to be continued.

Other benefits of fasting for fighting cancer

The tumor cell has its own characteristics, which distinguish it from healthy or so-called normal cells. Among its peculiarities, it expresses a significant change in its energy metabolism, which gives it a sweet tooth. Indeed, in the absence of glucose, the tumor cell struggles to develop and maintain its viability. Fasting, in all its forms, triggers a reduction in glucose levels and improves insulin sensitivity. Better insulin sensitivity makes it harder for cancer cells to grow. As a reminder, this results in a decrease in the activity of the growth factor called IGF-1, a hormone associated with cell proliferation in the majority of cancers. During a fast, our cells find ways to save on activities that normally require a lot of energy, such as cell growth and proliferation. Fasting here represents a strategic proposition in order to limit tumor growth.

Because fasting promotes the most drastic change in the availability of nutrients, including glucose and the growth factors that depend on it, it has the potential to maximize the sensitivity of cancer cells to the toxic effects of chemotherapy, which thereby limits the phenomenon of resistance to treatment, which is, unfortunately, a common reality. During fasting, the fall in nutrients allows the establishment of a mode of cellular protection called Differential Stress Resistance (DSR). This maneuver allows healthy cells to protect themselves against the toxic effects of chemotherapy compared to cancer cells, unable to develop this strategy. Improved efficacy of a variety of chemotherapeutic agents has been seen in multiple malignant cell lines expressed in breast cancer, melanoma, neuroblastoma, pancreatic cancer and colorectal cancer. In addition, fasting has been shown to also potentiate the therapeutic performance of tyrosine kinase inhibitors, which represent the new era of immunotherapy treatment.

Fasting or severe calorie restriction (lowering calorie intake by 30-70%) also has powerful effects on the immune system. Dr. Longo’s team has demonstrated that among these, there is a favorable increase in the level of T lymphocytes, B lymphocytes and natural killer cells, whose role is to infiltrate the tumor to destroy it, and these are, by the way, the same cells in our immunity that help fight viral infections. Fasting and calorie restriction are inexpensive ways to make a wide range of cancer cells more vulnerable to attack by immune cells, while making cancer more susceptible to chemotherapy, says Dr. Longo.

Since fasting causes a decrease in circulating growth factors, it forces the cell to reduce its activities to the detriment of its proliferation. Thus, a set of oncogenes and strategies favorable to the disease are found to be negatively affected (RAS, MAPK, PI3K-AKT, Hif-1). These underlie several essential tumor characteristics, including:

  • The growth,
  • Cellular multiplication,
  • The escape of apoptosis and
  • Angiogenesis.

Calorie restriction is also able to modulate the tumor microenvironment, reducing inflammation and consequently the resulting fatigue. But still, fasting improves the functionality of a protein essential for healthy cell replication and destruction of malignant cells, p53. This protein is subject to mutations which inhibit its protective and anticancer power in the great majority of tumor cells; however, fasting would reverse this inhibition.

2 forms of fasting to prioritize

Among the different forms of fasting, the one that attracts the most followers is intermittent fasting. The latter results in a cessation of food intake over a period of 16 hours. It is therefore the form most accessible and easy to apply on a daily basis. To apply this condition, simply avoid eating at least 3 to 4 hours before bedtime and delay the first meal of the day the following day. For example, the most popular meal schedule comes down to having your last meal no later than 6 p.m. and having the first bite of the day at 10 a.m. the next morning. This approach appears to provide tangible benefits in cancers sensitive to hormones, such as breast, ovarian and prostate cancer.

However, to achieve maximum benefit, induce autophagy, and significantly reduce blood glucose, prolonged fasting remains the best option. According to studies (animal and human), the act of fasting over a period of 72 hours, starting the day before chemotherapy treatment, maintaining it the same day and continuing it until the day after treatment would bring about the most advantages. That being said, you should maintain your intake of water or even broth, if your discomfort is severe.

Is this an approach that’s right for you?

Unlike most cancer therapies, fasting causes only mild discomfort, such as transient weakness, dizziness, and short-term weight loss in humans. However, not all of the people dealing with this disease are candidates for the application of fasting. People who have already experienced severe weight loss, those suffering from advanced sarcopenia, cachexia or severe malnutrition induced by drug-induced anorexia or multiple lesions in the digestive tract should refrain from taking such a step.

Conclusion

Most tumors are generated and grow in a nutrient-rich environment. Yet current therapy does not include dietary changes that can create a hostile environment for cancer cells. As a non-pharmacological intervention to improve health and increase the quality of life, fasting and calorie restriction represent, abundant and convincing evidence, an encouraging springboard for developing future strategies in the treatment of this disease. Although fasting and calorie restriction are promising interventions for a wide variety of tumors, it is always wise to talk to your healthcare team to assess your general condition beforehand.

 

Visit the Fasting section of the Vitoli blog to learn even more about the subject!

 

 

References:

  • Bourbeau Véronique. Existe-t-il une relation entre le sucre et le cancer? Vitalité Québec, avril 2020
  • Catherine R. Marinac, BA, Sandahl H. Nelson, MS, Caitlin I. Breen et al. Prolonged Nightly Fasting and Breast Cancer Prognosis. JAMA Oncol. 2016 Aug 1; 2(8): 1049–1055.
  • Cheng CW, Adams GB, Perin L, et al. Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. Cell Stem Cell. 201
  • David Berrigan, Susan N. Perkins, Diana C. Haines, Stephen D. Hursting. Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice. Carcinogenesis, Volume 23, Issue 5, May 2002, Pages 817–822
  • Fasting-Like Diet May Naturally Fight Cancer and Boost Chemotherapy’s Effectiveness. Immuno-oncology News, 2016
  • Fernanda Antunes, Adolfo Garcia Erustes et al. Autophagy and intermittent fasting: the connection for cancer therapy? Clinics (Sao Paulo). 2018
  • Irene Caffa1, Vito D’Agostino et al. Fasting potentiates the anticancer activity of tyrosine kinase inhibitors by strengthening MAPK signaling inhibition. Oncotarget, Vol. 6, No. 14
  • Lee C, Raffaghello L, Brandhorst S, Safdie FM, et al. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Science Translational Medicine 2012
  • M. Kalamian, Keto for cancer, ketogenic metabolic therapy as a targeted nutritional strategy. Ed Chelsea Green, 2017, p.90
  • Raffaghello L, Lee C, Safdie FM, Wei M, et al. Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy. Proc Natl Acad Sci U S A. 2008
  • Raffaghello L, Safdie F, Bianchi G, Dorff T, Fontana L, Longo VD. Fasting and differential chemotherapy protection in patients. Cell Cycle 2010
  • Stefanie de Groot, Hanno Pijl, Jacobus J. M. van der Hoeven & Judith R. Kroep. Effects of short-term fasting on cancer treatment. Journal of Experimental & Clinical Cancer Research
  • Stefano Di Biase, Changhan Lee, Sebastian Brandhorst et al. Fasting mimicking diet reduces HO-1 to promote T cell-mediated tumor cytotoxicity. Cancer Cell. 2016
  • Stephan P. Bauersfeld , Christian S. Kessler et al. The effects of short-term fasting on quality of life and tolerance to chemotherapy in patients with breast and ovarian cancer: a randomized cross-over pilot study. Bauersfeld et al. BMC Cancer, 2018
  • Thissen JP, Ketelslegers JM, Underwood LE. Nutritional regulation of the insulin-like growth factors. Endocr Rev. 1994