Life-long consumption of high level of fruits and vegetables reduces tumor incidence and extends median lifespan in mice

Authors: GUO, WEIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; ORTEGA, EDWIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LI, LIJUN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BRONSON, RODERICK - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BOEHM, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Frontiers in Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/16/2023
Publication Date: 12/6/2023
Citation: Guo, W., Ortega, E., Wu, D., Li, L., Bronson, R.T., Boehm, S., Meydani, S.N. 2023. Life-long consumption of high level of fruits and vegetables reduces tumor incidence and extends median lifespan in mice. Frontiers in Nutrition. https://doi.org/10.3389/fnut.2023.1286792.
DOI: https://doi.org/10.3389/fnut.2023.1286792

Interpretive Summary: Observational studies show that people who eat more fruits and vegetables (FV) have less incidence of certain cancers and lower mortality. An animal study was conducted to investigate the effects of life-long consumption of higher levels of FV on age-associate pathologies and median life span. Mice were fed a low-fat or a high-fat Western-style diet supplemented with and without a mixture of varieties of FV. Mice fed a western-style high-fat diet had significantly higher tumor incidence and mortality compared to those fed the low-fat diet. These beneficial effects of FV are at least in part due to reduced inflammation and reduced blood lipids including cholesterol levels.

Technical Abstract: Objective: Epidemiological studies suggest that consumption of fruits and vegetables (FV) is negatively associated with the incidence of certain cancers and mortality. However, a causal relationship has not been demonstrated. Thus, we investigated the effect of life-long consumption of high level of FV on median lifespan, key biological functions, and pathologies in mice fed low-fat (LF) or high-fat (HF) diets and the underlying mechanisms. Methods: Using a 2 x 2 factorial design, 5 week-old male C57BL/6J mice were randomly assigned to one of four groups (n=60/group): LF (LF-C, 10% kcal fat), HF (HF-C, 45% kcal fat) or each supplemented with 15% (w/w) of a unique FV mixture (LF+FV and HF+FV, respectively). Mice were euthanized when one group reached 50% mortality. Body weight and composition, tumor incidence, and death were monitored. Blood levels of lipids and pro-inflammatory cytokines were assessed. Results: After 21 months of feeding, HF-C group reached 50% mortality, at which time mice in all groups were terminated. HF-C had higher mortality (50.0%) compared to the LF-C group (18.3%, p=0.0008). Notably, HF-FV had lower mortality (23.3%) compared to HF-C group (p=0.008); there was no significant difference in mortality between HF-FV and LF-C groups. Tumors were found in all groups, and were predominantly present in the liver, followed by those of lung, intestine, and seminal vesicle. Tumor incidence in the HF-C group (73.3%) was higher than that in LF-C group (30.0%, p<0.0001). HF+FV group had 23.3% lower tumor incidence compared to the HF-C group (p=0.014). No significant difference in tumor incidence between the LF-C and LF+FV groups was observed. Long-term FV supplementation reduced systemic inflammation and blood lipids. Conclusion: We provide the first causal evidence that life-long intake of a diet, containing a high level and large variety of FV, decreases tumor incidence and extends median lifespan in mice fed a western-style high-fat diet. These effects of FV are at least in part due to reduced blood levels of pro-inflammatory cytokines and improved dyslipidemia.