Feasibility and metabolic outcomes of a well-formulated ketogenic diet as an adjuvant therapeutic intervention for women with stage IV metastatic breast cancer: The Keto-CARE trial

Purpose:

Ketogenic diets may positively influence cancer through pleiotropic mechanisms, but only a few small and short-term studies have addressed feasibility and efficacy in cancer patients. The primary goals of this study were to evaluate the feasibility and the sustained metabolic effects of a personalized well-formulated ketogenic diet (WFKD) designed to achieve consistent blood beta-hydroxybutyrate (βHB) >0.5 mM in women diagnosed with stage IV metastatic breast cancer (MBC) undergoing chemotherapy.

Methods: 

Women (n = 20) were enrolled in a six-month two-phase, single-arm WFKD intervention (NCT03535701). Phase I was a highly-supervised, ad libitum, personalized WFKD, where women were provided with ketogenic-appropriate food daily for three-months. Phase II transitioned women to a self-administered WFKD with ongoing coaching for an additional three-months. Fasting capillary βHB and glucose were collected daily; weight, body composition, plasma insulin, and insulin resistance were collected at baseline, three- and six-months. 

Results:

Capillary βHB indicated women achieved nutritional ketosis (Phase I mean: 0.8 mM (n = 15); Phase II mean: 0.7 mM (n = 9)). Body weight decreased 10% after three-months, primarily from body fat. Fasting plasma glucose, plasma insulin, and insulin resistance also decreased significantly after three-months (p < 0.01), an effect that persisted at six-months.

Conclusions:

Women diagnosed with MBC undergoing chemotherapy can safely achieve and maintain nutritional ketosis, while improving body composition and insulin resistance, out to six-months.

Methods
Analyses and graphs were performed using GraphPad Prism (ver. 9.1.0, GraphPad Software, San Diego, California USA). Two-tail α significance was set at p < 0.05. All the variables of interest were screened for normality and homogeneity of variance using the Shapiro-Wilk test and Mauchly’s sphericity test, respectively. Violations of sphericity were treated with the Greenhouse-Geisser adjustment. For Phase I endpoints, we analyzed the main effects of time using paired samples t-tests (BL vs. 3 MO). When including Phase II endpoints, we used a 1 (condition) x 3 (time) repeated-measures mixed-effects analysis of variance (RM ANOVA) with Bonferroni post-hoc corrections to analyze the differences between BL and 3 MO; BL and 6 MO; and 3 MO and 6 MO. We additionally compared weekly fasting glucose/βHB mean concentrations and variability between phases using an unpaired t-test (Phase I vs. Phase II).