Safety and metabolic effects of the fasting mimicking diet in cancer patients

Background: Preclinical studies have shown that a plant-based, low-calorie, low-protein, low-carbohydrate diet, also known as fasting mimicking diet (FMD), modifies systemic metabolism and displays significant antitumor effects. Nonetheless, no clinical data are available yet. In this study, we explored the safety and metabolic modifications of the FMD in cancer pts. Methods: We prospectively evaluated cancer pts who followed a 5-days FMD (700 Kcal on day 1 and 300 kCal on days 2-5) every 21-28 days. Inclusion criteria were: pts with any cancer type (except for small cell lung cancer), stage and concomitant antitumor therapy. Main exclusion criteria were: BMI < 20 kg/m2, recent unintentional weight loss >5%, insulin-dependent diabetes and severe comorbidities,. Before and at the end of the FMD, we collected blood and urine samples to measure changes in metabolites and growth factors. We show data of FMD safety and metabolic effects at the end of the first cycle. Results: We recruited 29 pts from November 2016 to April 2017. 20 had metastatic disease, and 27 received concomitant anticancer treatment. Breast (12), lung (3), prostate (3) and pancreatic (3) cancer were the most represented tumors. All pts completed at least one cycle of FMD. Based on the analysis of diet diaries, compliance to the diet was good, with only minor deviations (±10%) in the quantitative intake of permitted aliments. 79% of pts reported G1-G2 AEs, in particular fatigue (72%) and headache (10%), more likely to be related to the diet. One patient experienced G2 symptomatic hypoglycemia that required sucrose intake. No G3-G4 toxicities were observed. Relative weight loss during the first cycle was 4.65% (range 2.5-6.5%). The FMD reduced median glycemia by 15.6%, IGF-1 blood levels by 27% and insulin levels by 32%, while median triglyceride, total cholesterol and uric acid levels increased by 31.5%, 11% and 80%, respectively; finally, we observed an increase of average urine ketone body levels from 0.38 mg/dl (range 0-10) to 62 mg/dl (range 20-100). Conclusions: Our interim analysis suggests that the proposed FMD scheme is safe and significantly modifies systemic metabolism in a heterogeneous population of cancer pts.