Monday, April 30, 2018

Fasting Can Make You Healthier

By Jesica Levingston Mac leod, PhD

Believe it or not, breakthrough new research has shown that fasting could be good for you. The article was indeed featured in the Nature journal and the impact of this study relies on the conclusion that fasting promotes haematopoietic stem cell (HSC) function. Stem cells are good for you because they can differentiate into specialized cells and can divide to produce more stem cells.

I personally challenged myself by fasting during Ramadan. Ramadan is one of the pillars of the Muslim religion. It consists of fasting during a month from sunrise to sunset in order to reflect the essence of piety and to be aware of the plight of the underprivileged. Other cultures include fasting in their practices. In the Jewish religion, the fasting day is named Yom Kippur, the Day of Atonement. It is described as a Jewish festival without food, but full of praying, introspection and self-judgment.

During my fasting period, my friends noticed an off character onset of passive-aggressiveness in me, and indeed I was pretty cranky… and super hungry. One of my favorite comedians, Luis CK, once said that we incorrectly overuse the “I am starving” phrase, while people in Africa are really dying for starvation… so I won’t say I was starving, but certainly, I was in a glucose deprived state of mind, which was affecting my behavior.

The most challenging part for me was being dehydrated, as you should also fast liquids during Ramadan, fasting liquids seemed counterproductive in my experience.

Fasting is often indicated in general medical practice particularly prior to surgery or other procedures that require general anesthetics, because of the risk of pulmonary aspiration of gastric contents after induction of anesthesia (i.e., vomiting and inhaling the vomit, causing life-threatening aspiration pneumonia). One should also fast if undergoing a cholesterol or glucose test, as these measurements require a 12 hour fasting period so that a baseline can be established. These acute/short fasting periods are generally safe.

What more, a study in mice published in 2008 showed that short-term fasting (less than 48 hours) is effective in protecting normal cells but not cancer cells against high dose chemotherapy. The following year another study published in Science proved that caloric restriction delays disease onset and mortality in rhesus monkeys. In a human study, including 10 cancer patients under chemotherapy, Sadfie and collaborators did not report significant side effects caused by fasting alone other than hunger and lightheadedness. In this study, all patients voluntarily fasted for a total of 48 to 140 hours prior to and/or 5 to 56 hours following chemotherapy administered by their treating oncologists. In those patients whose cancer progression could be assessed, fasting did not prevent the chemotherapy-induced reduction of tumor volume or tumor markers. Fasting was well-tolerated and was associated with a self-reported reduction in multiple chemotherapy-induced side effects, suggesting that fasting in combination with chemotherapy is feasible, safe, and has the potential to ameliorate side effects caused by chemotherapies.

In the significant article that I mentioned before, Chen and collaborators showed that prolonged fasting (PF), exceeding 48 hours, activates a metabolic switch to lipid- and ketone-based catabolism and decreases circulating insulin-like growth factor-1 (IGF-1), which has been shown to reduce chemotoxicity (1) How? They couldn’t find an answer yet. However, they clearly demonstrated that the decrease of circulating IGF-1 in the blood was accompanied by a reduction in protein kinase A (PKA) pathway activity in a variety of cell types. PKA has several functions in the cell, I.e. regulation of glycogen, sugar, and lipid metabolism and it regulates other proteins with a valuable role in stem cell stress resistance, self-renewal and pluripotency maintenance.

Interestingly, when Chen and collaborators exposed mice to cycles of prolonged fasting followed by challenges with cyclophosphamide (a drug used in chemotherapy), they noticed the reduction in the mortality and apoptosis (programmed cell death) of long- and short-term HSCs as well as multipotent progenitors in the bone marrow. In addition, multi-lineage differentiation was improved in these animals compared with fed mice, in vitro and in transplantation experiments. These positive effects of prolonged fasting were independent of the chemotherapy treatment, as they were also present in aged animals, which naturally exhibit a reduction in HSC function and multi-lineage potential. The effects of prolonged fasting could be reproduced in mice lacking the growth hormone receptor, which also have low levels of IGF-1. Transplantation experiments showed that low levels of IFG-1 in animals led to a reduction in IGF-1-mediated PKA signaling, both in haematopoietic cells and in associated stromal cells. Strikingly, the researchers could restore haematopoietic function by reducing the levels of either IGF-R1 or the PKA catalytic subunit. Conversely, the benefits were abolished if exogenous IGF-1 was added.

The scientific community is excited about these findings, and we hope understanding the positive effects of fasting can have implications in improving the quality of life of cancer patients… and all the humanity in general. On the other hand, I must cite one of the best Americans: “He that lives upon hope will die fasting”, Benjamin Franklin.

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