In the process of doing research on fasting, one thing has become very clear; there is much more clinical scientific research being done on this subject now than ever before. And as you might expect, there are many theories for and against. Actually the “against” numbers are quickly disappearing. We found this to be fascinating. The text below is a compilation of excerpts taken from a paper published in the Cell Metabolism Journal, Volume 19, Issue 2, February 4, 2014 written by Valter D. Longo and Mark P. Mattson.

This is a highly technical document and I would not want to paraphrase any of it. If you find the information intriguing or interesting and want to read the full text please visit this web page. But I would like to highlight one point in reference to cancer treatment and fasting. As you will read below, it has been shown in clinical tests with mice, that combining fasting and chemotherapy helps protect the healthy cells while the cancer cells are being targeted. We all know the devastation chemotherapy causes to the body’s healthy cells in the process of targeting cancer cells. This could be a breakthrough in cancer treatment! If fasting can have this kind of impact on our cells, I can only imagine the healing power regular fasting can have on our long-term health.

Fasting: Clinical Applications

Fasting has been practiced for millennia, but, only recently, studies have shed light on its role in adaptive cellular responses that reduce oxidative damage and inflammation, optimize energy metabolism, and bolster cellular protection.

In humans, fasting is achieved by ingesting no or minimal amounts of food and caloric beverages for periods that can typically range from 12 hours to 3 weeks. Many religious groups incorporate periods of fasting into their rituals.

Fasting is distinct from caloric restriction (CR), in which the daily caloric intake is reduced chronically by 20%–40%, but meal frequency is maintained. We now know that fasting results in ketogenesis which promotes potent changes in metabolic pathways and cellular processes such as stress resistance, lipolysis, and autophagy; and can have medical applications that, in some cases, are as effective as those of approved drugs such as the dampening of seizures and seizure-associated brain damage, and the amelioration of rheumatoid arthritis. (Bruce-Keller et al., 1999Hartman et al., 2012 and Müller et al., 2001).

Fasting and the Brain

In mammals, severe CR/food deprivation results in a decrease in the size of most organs except the brain. From an evolutionary perspective, this implies that maintenance of a high level of cognitive function under conditions of food scarcity is of preeminent importance. Indeed, a highly conserved behavioral trait of all mammals is to be active when hungry and sedentary when satiated. In rodents, alternating days of normal feeding and fasting Intermittent Fasting (IF) can enhance brain function, as indicated by improvements in performance on behavioural tests of sensory and motor function.

Particularly interesting with regard to adaptive responses of the brain to limited food availability during human evolution is brain-derived neurotrophic factor (BDNF). The genes encoding BDNF and its receptor, TrkB, appeared in genomes relatively recently, as they are present in vertebrates, but absent from worms, flies, and lower species (Chao, 2000). The prominent roles of BDNF in the regulation of energy intake and expenditure in mammals is highlighted by the fact that the receptors for both BDNF and insulin are coupled to the highly conserved PI3-kinase-Akt and MAP kinase signalling pathways. Studies of rats and mice have shown that running wheel exercise and IF increase BDNF expression in several regions of the brain, and that BDNF in part mediates exercise- and IF-induced enhancement of synaptic plasticity, neurogenesis, and neuronal resistance to injury and disease.

Adaptive Responses to Fasting in Mammals

In most mammals, the liver serves as the main reservoir of glucose, which is stored in the form of glycogen. In humans, depending upon their level of physical activity, 12 to 24 hr of fasting typically results in a 20% or greater decrease in serum glucose and depletion of the hepatic glycogen, accompanied by a switch to a metabolic mode in which nonhepatic glucose, fat-derived ketone bodies, and free fatty acids are used as energy sources. Whereas most tissues can utilize fatty acids for energy, during prolonged periods of fasting, the brain relies on the ketone bodies β-hydroxybutyrate and acetoacetate, in addition to glucose, for energy consumption. Ketone bodies are produced in hepatocytes from the acetyl-CoA generated from β-oxidation of fatty acids released into the bloodstream by adipocytes, and also by the conversion of ketogenic amino acids. After hepatic glycogen depletion, ketone bodies, fat-derived glycerol, and amino acids account for the gluconeogenesis-dependent generation of approximately 80 g/day of glucose, which is mostly utilized by the brain. Depending on body weight and composition, the ketone bodies, free fatty acids, and gluconeogenesis allow the majority of human beings to survive 30 or more days in the absence of any food and allow certain species, such as king penguins, to survive for over 5 months without food (Eichhorn et al., 2011).

Fasting and Cancer

Fasting can have positive effects in cancer prevention and treatment. In mice, alternate day fasting caused a major reduction in the incidence of lymphomas (Descamps et al., 2005), and fasting for 1 day per week delayed spontaneous tumorigenesis in p53-deficient mice (Berrigan et al., 2002). However, the major decrease in glucose, insulin, and IGF-1 caused by fasting, which is accompanied by cell death and/or atrophy in a wide range of tissues and organs including the liver and kidneys, is followed by a period of abnormally high cellular proliferation in these tissues, driven in part by the replenishment of growth factors during refeeding. When combined with carcinogens during refeeding, this increased proliferative activity can actually increase carcinogenesis and/or precancerous lesions in tissues including liver and colon (Tessitore et al., 1996). Although these studies underline the need for an in-depth understanding of its mechanisms of action, fasting, when applied correctly even in the presence of carcinogens, is expected to have cancer-preventive effects, as indicated by the studies above and by the findings that multiple cycles of periodic fasting (PF) can be as effective as toxic chemotherapy in the treatment of some cancers in mice (Lee et al., 2012).

In the treatment of cancer, fasting has been shown to have more consistent and positive effects. PF for 2–3 days was shown to protect mice from a variety of chemotherapy drugs, an effect called differential stress resistance (DSR) to reflect the inability of cancer cells to become protected because oncogenes negatively regulate stress resistance, and prevent cancer cells from becoming protected (Raffaghello et al., 2008).

A number of ongoing trials should soon begin to determine the efficacy of fasting in enhancing cancer treatment in the clinic.

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The text for the above article is an excerpt from Cell Metabolism Journal, archive, Volume 19, Issue 2, February 4, 2014  Visit for the full text.