High blood glucose levels, a side effect of common cancer drug use, may render healthy cells vulnerable to chemotherapy damage. However, short-term fasting may counter blood sugar increases and protect cells, finds a recent study published in PLoS Biology.

Researchers gave mice either doxorubicin or a combination of dexamethasone and rapamycin, common drugs used to alleviate chemotherapy side effects, but known to increase blood glucose levels. Mice that received the combination drug suffered worse side effects, including damage to heart cells, than mice that received only doxorubicin. “This combination could be very dangerous; it made the mice much more sensitive to chemotherapy and it could also make patients more sensitive to chemotherapy,” said lead researcher Valter Longo, PhD, professor at University of Southern California (USC) Leonard Davis School of Gerontology and director of the USC Longevity Institute in Los Angeles.

Based on their previous studies in yeast, Dr Longo and colleagues suspected that high glucose levels might make cells more sensitive to toxins. To combat high glucose levels the researchers fasted mice for short periods or fed mice a low-calorie diet designed to be similar to fasting. The fasting mice had less damage to heart cells than mice that were fed a normal diet.

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The researchers hypothesized that the PKA/EGR1 genetic signaling pathway may play a role in the protective effect of fasting. Their previous studies found that the yeast PKA Msn2/4 pathway, a pathway similar to the mammalian PKA/EGR1 pathway, was activated by glucose, which caused the cells to be less resistant to stress.

“These findings in mice, together with previous studies indicating that high glucose levels in combination with chemotherapy in patients is associated with an increased risk of developing complicated infections and with a significant increase in overall mortality, should discourage physicians from recommending combination of drugs that promote hyperglycemia and chemotherapy, particularly to reduce relatively minor side effects,” said Dr Longo.


1. Biase SD, Shim HS, Kim KH, et al. Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy [published online March 30, 2017]. PLoS Biology. doi:10.1371/journal.pbio.2001951