The relationship between fasting and Insulin-like Growth Factor 1 (IGF-1) often causes confusion. IGF-1 is a powerful hormone that drives growth and cell proliferation. When fasting begins, the pituitary gland increases Growth Hormone (GH) secretion, which is the primary signal for IGF-1 production. Although GH rises, a metabolic switch overrides this signal, resulting in a net decrease in circulating IGF-1. This biological mechanism is a core survival strategy, explaining why fasting is used to modulate this growth-promoting pathway.
Understanding IGF-1 and the Growth Hormone Axis
IGF-1 is a peptide hormone similar to insulin, playing a major role in the body’s anabolic processes. The central regulatory system is the Growth Hormone (GH)/IGF-1 axis. The pituitary gland releases GH, which travels to the liver, the main source of circulating IGF-1. In response to GH, the liver produces IGF-1, which promotes cell division, tissue repair, and bone growth throughout the body. Because IGF-1 is secreted continuously, its blood level is often used as a stable marker for the overall activity of the GH system.
The Counterintuitive Mechanism: Why Fasting Lowers IGF-1
Despite the increase in Growth Hormone during a fast, the liver becomes unresponsive to the signal, resulting in “hepatic GH resistance.” This resistance is the core reason IGF-1 levels drop during nutrient deprivation. The primary signals inhibiting the liver’s response are the low levels of insulin and glucose characteristic of fasting.
The liver downregulates the number of GH receptors on its surface, preventing GH from effectively binding and initiating IGF-1 production. The internal signaling pathway, specifically involving STAT5, is severely blunted in the fasted liver, further impairing the GH signal. This metabolic adaptation shifts the body from an anabolic state to a resource-conserving, catabolic one. By suppressing IGF-1, the body pauses growth functions to prioritize survival and cellular repair processes, such as autophagy.
Health Implications of Modulating IGF-1 Levels
Fasting’s ability to temporarily lower IGF-1 is a primary reason it is studied for longevity and disease prevention. Chronically elevated IGF-1 signaling is associated with accelerated cellular aging and an increased risk for certain cancers, as this potent growth factor encourages cell division. Conversely, temporarily lowering IGF-1 promotes a protective cellular state. This reduction activates cellular cleanup mechanisms, such as autophagy, which helps repair damaged DNA and remove senescent cells. Studies suggest that reduced GH/IGF-1 activity is linked to extended lifespan and a lower incidence of age-related diseases.
Variables That Influence the Fasting Response
The degree to which fasting lowers IGF-1 depends on several variables. Fasting duration is a major factor, as hepatic GH resistance takes time to fully activate. While a shorter overnight fast may not alter IGF-1, extended periods of 48 to 72 hours lead to substantial decreases. Nutritional status, particularly the restriction of protein and amino acids, is also a powerful determinant of the IGF-1 response. Finally, age naturally influences the baseline level, as circulating IGF-1 concentrations progressively decline as part of the aging process.