This 2016 review summarizes various pathways by which IGF and insulin suppression may slow or inhibit tumor growth.
Multiple pathways related to insulin and IGF may play roles in tumor suppression. Both insulin and IGF-1 are growth-stimulating and anabolic hormones, and insulin and IGF receptor activation upregulates pathways central to carcinogenesis (see Figure 2). Many of these effects are tied to the PI3K-AKT-mTORC1 pathway, the upregulation of which is linked to tumor growth and progression. High glucose levels may independently promote tumor growth due to the dependence of tumor cells on high glucose uptake, though some rat studies have suggested elevated IGF-1 levels reverse the growth-inhibiting effects of lowered glucose levels. These effects are most pronounced within insulin-sensitive tumors, which include breast and colon cancers.
While carbohydrate restriction (including through a ketogenic diet) has been shown to lower both insulin and glucose levels, both rodent and human studies have shown that fasting has a greater effect on IGF-1 suppression — and in humans, specifically when fasting includes protein restriction. Rodent studies have consistently shown that various forms of caloric restriction inhibit tumor growth and/or prevent tumor development or metastasis, and a handful of preclinical studies show direct benefits from carbohydrate-restricted (but not calorie-restricted) diets. Human evidence, however, remains preliminary and is primarily limited to small pilot studies and case reports.
Notably, the effects seen in rodents may not extrapolate directly to humans. Insulin and glucose kinetics in rodents and humans differ significantly, and rodents are able to tolerate a degree of fasting-related weight loss (up to 50% of baseline body weight) that would be harmful to humans. Future research will need to better understand the dose-response relationship between various forms of dietary restriction and insulin and/or IGF-1 suppression in humans to develop dietary restriction regimens that suppress cancer growth without harmful side effects. The authors note the use of specific glucose- and/or insulin-suppressing drugs, independently or alongside dietary restriction, may help to safely moderate hormonal responses.
Overall, the authors find compelling mechanistic evidence that insulin and IGF-1 suppression may have anti-cancer effects. They also find substantial evidence that diets that reduce insulin and IGF-1 levels reduce tumor progression in rats; human evidence, however, is preliminary and must be gathered cautiously given the known harms of weight loss and cachexia in humans.