[Jackie07]

Exp Gerontol. 2013 Feb 20. pii: S0531-5565(13)00047-8. doi: 10.1016/j.exger.2013.02.016. [Epub ahead of print]
Short-term calorie and protein restriction provide partial protection from chemotoxicity but do not delay cancer progression.

Brandhorst S, Wei M, Hwang S, Morgan TE, Longo VD.
Source

Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA; Centre for Medical Biotechnology, Faculty of Biology, University Duisburg-Essen, Essen, Germany.

Abstract

Short-term starvation (STS) protects normal cells while simultaneously sensitizing malignant cells to high-dose chemotherapeutic drugs in mice and possibly patients. The fasting-dependent protection of normal cells and sensitization of malignant cells depends, in part, on reduced levels of insulin-like growth factor-1 (IGF-1) and glucose. Calorie restricted diets with defined macronutrient (carbohydrate, protein, fat) ratios were evaluated for the effects on stress sensitization markers and protection in mice treated with high-dose chemotherapy.

We show that short-term CR significantly reduced both glucose and IGF-1 levels, but when specific macronutrient deficiencies were tested, only the complete lack of proteins reduced IGF-1 levels. Short-term 50% CR combined with either severe protein-deficiency or ketogenic diets improved chemotoxicity resistance similarly to the standard 50% CR, but did not result in the high protection caused by STS.

Notably, a high protein diet reversed the beneficial effects of short-term CR. In a subcutaneous mouse model of glioma, feeding a low protein (4% calories from protein) diet for more than 20 days did not delay tumor progression once the tumor became palpable. Also, cycles of short-term (3 days) 50% CR did not augment the chemotherapy efficacy of cisplatin in a murine breast cancer model.

These results indicate that the protection from chemotoxicity and retardation of the progression of certain tumors achieved with fasting is not obtained with short-term calorie and/or macronutrient restriction.