BREAst Cancer Personalised NuTrition (BREACPNT): dietary intervention in breast cancer survivors treated with endocrine therapy - a protocol for a randomised clinical trial.

INTRODUCTION: Breast cancer survivors treated with adjuvant endocrine therapy commonly experience weight gain, which has been associated with low adherence to therapy and worse breast cancer prognosis. We aim to assess whether a personalised postprandial glucose targeting diet will be beneficial for weight management as compared with the recommended Mediterranean diet in this patient population METHODS AND ANALYSIS: The BREAst Cancer Personalised NuTrition study is a phase-2 randomised trial in hormone receptor positive patients with breast cancer, treated with adjuvant endocrine therapy. The study objective is to assess whether dietary intervention intended to improve postprandial glycaemic response to meals results in better weight and glycaemic control in this population as compared with the standard recommended Mediterranean diet. Consenting participants will be assigned in a single blinded fashion to either of two dietary arms (Mediterranean diet or an algorithm-based personalised diet). They will be asked to provide a stool sample for microbiome analysis and will undergo continuous glucose monitoring for 2 weeks, at the initiation and termination of the intervention period. Microbiome composition data will be used to tailor personal dietary recommendations. After randomisation and provision of dietary recommendations, participants will be asked to continuously log their diet and lifestyle activities on a designated smartphone application during the 6-month intervention period, during which they will be monthly monitored by a certified dietitian. Participants' clinical records will be followed twice yearly for 5 years for treatment adherence, disease-free survival and recurrence. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee in the Sheba medical centre (file 5725-18-SMC, Ramat Gan, Israel) and the Weizmann Institutional Review Board (file 693-2, Rehovot, Israel). The findings of this study will be published in a peer reviewed publication. TRIAL REGISTRATION NUMBER: NCT04079270.

L-Lactate Promotes Adult Hippocampal Neurogenesis.

Neurogenesis, the formation of new neurons in the adult brain, is important for memory formation and extinction. One of the most studied external interventions that affect the rate of adult neurogenesis is physical exercise. Physical exercise promotes adult neurogenesis via several factors including brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). Here, we identified L-lactate, a physical exercise-induced metabolite, as a factor that promotes adult hippocampal neurogenesis. While prolonged exposure to L-lactate promoted neurogenesis, no beneficial effect was exerted on cognitive learning and memory. Systemic pharmacological blocking of monocarboxylate transporter 2 (MCT2), which transports L-lactate to the brain, prevented lactate-induced neurogenesis, while 3,5-dihydroxybenzoic acid (3,5-DHBA), an agonist for the lactate-receptor hydroxycarboxylic acid receptor 1 (HCAR1), did not affect adult neurogenesis. These data suggest that L-lactate partially mediates the effect of physical exercise on adult neurogenesis, but not cognition, in a MCT2-dependent manner.