Does low energy availability lower basal cortisol and reduce metabolic resilience?

Low energy availability (LEA) significantly alters the hypothalamic-pituitary-adrenal (HPA) axis, but the resulting physiological state is more complex than a simple "downshift." While energy deficits do suppress certain hypothalamic signals, the clinical outcome regarding cortisol output often contradicts the notion of hypocortisolism.

HPA Axis Response and Cortisol Output

The assertion that chronic LEA leads to lower basal cortisol is generally unsupported by clinical evidence in the context of energy deficiency and Relative Energy Deficiency in Sport (RED-S).

• Hypercortisolemia: Multiple studies of athletes with chronic LEA or functional hypothalamic amenorrhea demonstrate significantly elevated morning serum and salivary cortisol levels. This hypercortisolemia acts as a chronic stress response to the metabolic deficit.
• Adrenal Activation: Rather than a downshift in output, the HPA axis remains heightened to mobilize energy stores, often at the expense of the reproductive axis (suppressing LH and estrogen).
• Contrast with Burnout: While hypocortisolism is observed in late-stage overtraining syndrome or chronic fatigue, primary LEA is characterized by an active, elevated cortisol drive.

Mechanistic Signaling Changes

LEA does impact hypothalamic signaling, specifically within the paraventricular nucleus (PVN), through metabolic sensing pathways.

• Metabolic Sensors: Low levels of leptin and insulin, characteristic of LEA, inhibit hypothalamic neurons, leading to reduced expression of corticotropin-releasing hormone (CRH) mRNA.
• Survival Prioritization: This signaling shift represents an allostatic adaptation where the body prioritizes survival and energy mobilization over non-essential processes like reproduction and bone formation.

Implications for Metabolic Resilience

Metabolic resilience—the ability to maintain homeostasis under stress—is compromised by any significant deviation in cortisol levels.

• Iron and Albumin Regulation: Mechanistically, low cortisol (if present) disrupts metabolic resilience by increasing albumin synthesis and interfering with iron sequestration, potentially increasing oxidative stress.
• Catabolic State: Conversely, the high cortisol levels actually seen in LEA reduce resilience by promoting muscle proteolysis and inhibiting bone formation, leading to a diminished capacity to recover from physiological stressors.

Bottom line

While LEA suppresses hypothalamic CRH signaling, it typically results in elevated, not lower, basal cortisol levels as a stress response. This hypercortisolemia, rather than a "downshift" in output, is what primarily reduces metabolic resilience and impairs long-term health.