Intermittent Calorie Restriction Delays Prostate Tumor Detection and Increases Survival Time in TRAMP Mice

Abstract

Prostate cancer is the most frequently diagnosed cancer in men. Whereas chronic calorie restriction (CCR) delays prostate tumorigenesis in some rodent models, the impact of intermittent caloric restriction (ICR) has not been determined. Here, transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were used to compare how ICR and CCR affected prostate cancer development. TRAMP mice were assigned to ad libitum (AL), ICR (2 wk 50% AL consumption followed by 2 wk pair feeding to AL consumption), and CCR (25% AL consumption) groups at 7 wk of age and followed until disease burden necessitated euthanasia or mice reached terminal endpoints (48 or 50 wk of age). Body weights fluctuated in response to calorie intake (P < 0.0001). ICR mice were older at tumor detection than AL (P = 0.0066) and CCR (P = 0.0416) mice. There was no difference for age of tumor detection between AL and CCR mice (P = 0.3960). Similar results were found for survival. Serum leptin, adiponectin, insulin, and IGF-I were all significantly different among the groups. These results indicate that the way in which calories are restricted impacts both time to tumor detection and survival in TRAMP mice, with ICR providing greater protective effect compared to CCR.

Pelleting Diets Impairs TRAMP Prostate Carcinogenesis

“…Food intake was not significantly different between groups (Table 3). Average food intake was similar to other studies of TRAMP mice consuming pelleted diets [20] [21], but 50% less than powdered diets fed by Zuniga et al [3]. Body weights were not significantly different between groups.…”

Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients

“…Contrary to this dogma, many studies suggest that a 20-40% reduction in calorie intake protects the host against toxins and retards the growth of tumors (Moreschi, 1909;Tannenbaum, 1945;Hursting et al, 1994Hursting et al, , 2001Hursting et al, , 2003Fontana et al, 2001Fontana et al, , 2006Harper et al, 2006;Bonorden et al, 2009;Colman et al, 2009;Longo and Fontana, 2010). However, this has never been translated into clinical applications because the effects are limited, as reduced calorie intake unavoidably causes weight loss, and because it was not clear that DR could not also protect cancer cells from chemotherapy.…”

“…Among the problems associated with the translation of DR into clinical applications is that chronic DR delays but does not stop the progression of the disease (Mukherjee et al, 2004;Bonorden et al, 2009;Shelton et al, 2010), and that this delay will occur for only a subset of malignancies (Kalaany and Sabatini, 2009). Although weight loss and cachexia in the early stages of cancer progression are not as common as thought (Tisdale, 2002;Fearon et al, 2003;Fox et al, 2009), the B15% loss of body mass index caused by a moderate (20%) calorie restriction (Racette et al, 2006) would prevent its use in the great majority of cancer treatment scenarios.…”

Dietary Interventions to Extend Life Span and Health Span Based on Calorie Restriction

“…In mice, IF administered as 30%-50% CR over periods of 2-3 weeks followed by ad libitum feeding for an equal amount of time has been shown to be protective against tumor formation in models for both prostate cancer and breast cancer (125,126). In humans, IF has been shown to be both attainable and beneficial to health (127,128).…”