Long-Term Supplementation with Fruits and Vegetables Prolongs Lifespan and Reduces Tumor Incidence in Mice Fed a Western-Style High-Fat Diet

Abstract Objectives Epidemiological studies suggest that consumption of fruits and vegetables (FV) was negatively associated with the incidence of certain cancers and positively associated with life expectancy. To date, a causal relationship has not been demonstrated. The objectives of the current study were to investigate the effects of long-term FV supplementation on health- and life-span in normal weight and obese mice. Methods Male C57BL/6J mice (5-wk) were randomly assigned to one of four groups (60/group): low fat control (LF-C, 10% kcal fat), high fat control (HF-C, 45% kcal fat), and each with 15% of a unique mixture of FV (patent pending) (w/w) (LF-FV and HF-FV). All mice were euthanized when a group reached 50% mortality. Survival analysis was performed using log-rank (Mantel-Cox) test; a two-sided Fisher's exact test was performed to compare difference in tumor incidence. Results After 21 months of feeding, HF-C group was the first to reach 50% mortality. Further, a Kaplan-Meier survival curve demonstrated that, at termination, HF-C group had higher mortality (50.0%) compared to LF-C group (18.3%, p = 0.0008). Notably, HF-FV group had significantly lower mortality (23.3%) compared to HF-C mice (p = 0.008), and there was no significant difference in mortality between HF-FV and LF-C. Mortality was lower in LF-FV (11.7%) compared to LF-C (18.3%), although this difference was not statistically significant. Furthermore, tumor incidence in HF-C group (73.3%) was significantly higher than that in LF-C group (30.0%, p < 0.0001). HF-FV group had 23.3% lower tumor incidence compared to HF-C group (p = 0.014). There was no significant difference in tumor incidence between LF-C (30.0%) and LF-FV groups (31.7%). Conclusions Our findings provide the first causal evidence that long-term intake of a diet supplemented with a wide variety of fruits and vegetables could extend lifespan and decrease tumor incidence in mice fed a Western-style high-fat diet. These results provide a foundation for further investigation into the benefits of fruit and vegetable supplementation on aging and age-related disease. Funding Sources This material is based upon work supported by the U.S. Department of Agriculture – Agricultural Research Service (ARS), under Agreement No. 58–8050-9–004.