Intermittent Fasting and Cancer Metabolism:   A Four Part Series

PART 3: Intermittent Fasting and Insulin Like Growth Factor (IGF-1)

 

Intermittent fasting (IF) reduces insulin-like growth factor 1 (IGF-1) levels through several specific mechanisms:

1. Protein Restriction: The reduction in IGF-1 is primarily attributed to the restriction of protein intake, particularly essential amino acids, during fasting periods8.

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1. Calorie Restriction: The decrease in overall calorie intake during fasting supports the reduction in IGF-1 levels8.
2. Insulin Reduction: Fasting leads to a significant decrease in circulating insulin levels, which in turn promotes the reduction of IGF-182.
3. Metabolic Switch: IF induces a metabolic switch that mimics water fasting, leading to a decrease in IGF-1 levels. For example, a 4-day fasting-mimicking diet (FMD) can reduce IGF-1 levels by approximately 45%3.
4. IGFBP-1 Increase: Fasting causes a substantial increase in IGF binding protein 1 (IGFBP-1), which can bind to IGF-1 and reduce its bioavailability. Studies have shown that prolonged fasting can lead to a 5-fold increase in IGFBP-13.
5. Signaling Pathway Modulation: IF down-regulates nutrient signaling pathways such as TOR-S6K and PKA, which are involved in IGF-1 regulation3.
6. Hepatic Gene Expression: Fasting specifically decreases IGF-1 mRNA in the liver, indicating a direct effect on IGF-1 gene expression4.

It's important to note that the effects of IF on IGF-1 levels can vary depending on the specific fasting protocol. For instance, while prolonged fasting and fasting-mimicking diets have shown significant reductions in IGF-1, some studies on time-restricted eating (TRE) have not observed changes in IGF-1 levels over shorter periods6.

These mechanisms collectively contribute to the reduction of IGF-1 levels during intermittent fasting, which may have implications for various health outcomes, including cancer prevention and treatment123.