Abstract
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Objectives Many aggressive cancers share a glycolytic phenotype associated with increased 18F-2-fluoro, 2-deoxyglucose (FDG) positron emission tomography (PET) uptake. Carbohydrate restricted (CR) diets, by inhibiting insulin secretion, enlist plausible but unproven mechanisms to limit cancer growth. Our goal was to examine CR feasibility in patients with advanced FDG-avid cancers and to compare exit vs. baseline PET scan changes as surrogate measures for tumor response.
Methods Eligible patients, either faculty or self-referred, had failed or refused > two standard chemotherapy courses and demonstrated FDG-positive scans. Exclusions included end-organ disease, hypoglycemic medications, difficult compliance, or BMI < 20. A supervised carbohydrate restricted diet was monitored weekly for macronutrient intake, body weight, serum electrolytes, betahydroxybutyrate concentrations [BHB], [insulin], [IGF1,2]. An exit four-week PET scan was obtained.
Results Ten subjects with diverse cancers completed > 26 days of RECHARGE without associated adverse effects. Mean caloric intake decreased (35 + 6) % vs. predicted requirements, mean weight loss (3.8 + 1.4) % was not judged a health risk. One patient had indolent but advanced disease. Among nine with pre-trial progressive disease (PD), stabilization (SD or PR) on PET was uncorrelated with reduced calorie intake (p=0.65); but correlated with three-fold higher dietary ketosis (n=5) vs. those with continued progression (n=4), (p=0.02) and ketosis correlated with insulin inhibition (r=0.62, p<0.001).
Conclusions Preliminary study suggests disease stabilization correlated with metabolic ketosis and insulin inhibition, not caloric restriction. Results in small sample size support further VLC study for adjunctive role with metabolic or cytotoxic therapies.
Research Support State University New York Research Foundation The Robert and Veronica Atkins Foundatio