Insulin-Lowering Diets in Metastatic Cancer

Hyperinsulinemia is an independent risk factor for cancer mortality. Insulin-lowering dietary strategies such as calorie restriction (CR), low-carbohydrate or ketogenic diets (KD), and intermittent fasting (IF) are aimed at reducing systemic stores of nutrients utilized by cancer cells, attenuating insulin-related growth signaling, and improving obesity-related metabolic parameters. In this narrative review, we searched the published literature for studies that tested various insulin-lowering diets in metastatic cancer in preclinical and clinical settings. A total of 23 studies were identified. Of these, 14 were preclinical studies of dietary strategies that demonstrated improvements in insulin levels, inhibition of metastasis, and/or reduction in metastatic disease burden in animal models. The remaining nine clinical studies tested carbohydrate restriction, KD, or IF strategies which appear to be safe and feasible in patients with metastatic cancer. These approaches have also been shown to improve serum insulin and other metabolic parameters. Though promising, the anti-cancer efficacy of these interventions, such as impact on tumor response, disease-specific-, and overall survival, have not yet been conclusively demonstrated. Studies that are adequately powered to evaluate whether insulin-lowering diets improve cancer outcomes are warranted.