Restricting calorie intake stresses and kills cancer cells, for a variety of reasons both direct (cancer cells have high metabolic requirements) and indirect (calorie restriction improves immune function). Calorie restriction, a flat reduction in calorie intake, and intermittent application of fasting or fasting mimicking diets have been shown to improve outcomes in animal studies and human trials. Which of these options are better, however? Researchers here provide evidence to suggest that calorie restriction is better than a fasting mimicking diet when it comes to slowing cancer.
Calorie restriction (CR) is without a doubt the most robust non-pharmacological intervention against induced and spontaneous cancers. Numerous studies have shown the ability of daily CR to delay neoplasia in multiple tissues and inhibit the growth of chemically induced and spontaneous tumors, including breast cancer. Despite the far-reaching improvements in health and reduction in cancer incidence associated with daily CR, its long-term implementation is not a feasible approach for most humans.
Implementation of protocols that involve intermittent fasting (IF) as clinically viable alternatives to daily CR has been shown to promote similar improvements in metabolic markers and provide protection against cancer growth. However, it is unclear whether optimization of diet composition in these less stringent feeding regimens would provide equal or better protection against tumor growth as daily CR. In this work, we begin to address this knowledge gap by directly assessing the effects of cycles of fasting-mimicking diet (FMD) vs. daily CR.
Using a breast cancer model in mice, we compare the potency of daily CR to that of periodic caloric cycling on FMD or an isocaloric standard laboratory chow against primary tumor growth and metastatic burden. Here, we report that daily CR provides greater protection against tumor growth and metastasis to the lung, which may be in part due to the unique immune signature observed with daily CR. Earlier work has suggested that upregulation of immune-fighting T-cells, specifically CD8+ and CD4+, leads to slower tumor growth and is a good indicator of survival outcome. Conversely, depletion of CD8+ partially eliminates CR-mediated delay in tumor growth. Here, our findings show that daily CR led to an increase in CD8+ and CD4+ cells in peripheral tissues. This is a key observation because T cell exhaustion is one of the major drivers of tumor progression and is indicative of poor prognosis in breast cancer patients.