Cortisol, Carbs, and the Case for Cellular Resilience

Exploring the intersection of hormones, mitochondria, and mood

In psychiatric and wellness spaces, cortisol is often framed as a threat—something to be “quieted” with frequent carbohydrate intake. But this oversimplifies a complex system. Cortisol is not inherently harmful; it is a dynamic hormone essential for adaptation, energy mobilization, and emotional regulation. The real issue is not cortisol itself, but how the body responds to it.

Glucocorticoid Resistance: A Root-Cause Psychiatric Concern

Glucocorticoid resistance—where tissues fail to respond appropriately to cortisol—is increasingly recognized in major depressive disorder (MDD), particularly in treatment-resistant cases. This resistance impairs feedback regulation of the HPA axis and perpetuates inflammation, emotional instability, and metabolic dysfunction.

Perrin et al. (2019) conducted a meta-analysis showing that patients with MDD and elevated cortisol levels also exhibited increased pro-inflammatory cytokines, suggesting impaired glucocorticoid signaling and immune dysregulation. This resistance may underlie the chronic low-grade inflammation seen in depression and other stress-related disorders.

“Glucocorticoid resistance may be a requisite for increased cytokine production in depression” (Perrin et al., 2019).

The Carb-Cortisol Myth: A Misguided Fix

Claims that high-carbohydrate meals “quiet” cortisol are based on transient postprandial effects. While insulin and glucose can acutely suppress cortisol, frequent carb feeding may promote insulin resistance, glycemic volatility, and poor sleep—all of which impair HPA axis function over time.

Instead of suppressing cortisol, the goal should be to restore cortisol sensitivity. This requires reducing inflammation, stabilizing blood sugar, and supporting mitochondrial function—all achievable through a whole-food, low-carbohydrate diet.

Ketogenic Diets and Depression: A Metabolic Psychiatry Lens

A 2025 meta-analysis by Janssen-Aguilar et al. reviewed 50 studies and found that ketogenic diets were associated with small to moderate reductions in depressive symptoms, especially in trials that verified ketosis and used very low-carbohydrate protocols. Improvements were strongest in non-obese participants and when compared to high-carbohydrate control diets.

Mechanisms include:

  • Enhanced mitochondrial function

  • Reduced neuroinflammation

  • Stabilized glutamate/GABA balance

  • Improved insulin and cortisol dynamics

These findings support the use of ketogenic therapy as a metabolic intervention in root-cause psychiatry, particularly for patients with inflammatory or HPA axis-related mood disorders.

Exercise and Cortisol: A Functional Relationship

Concerns that exercise “raises cortisol” miss the adaptive nature of this response. Physical activity temporarily elevates cortisol—but this is a training signal, not a pathology. Regular movement improves HPA axis regulation, enhances cortisol clearance, and builds emotional resilience.

Arvidson et al. (2020) demonstrated that aerobic exercise modulates HPA axis reactivity and autonomic responses to stress, supporting its role in stress adaptation and mood regulation. Both aerobic and resistance training contribute to improved hormonal balance and reduced anxiety.

“Exercise training improves HPA axis reactivity and autonomic recovery following acute stress” (Arvidson et al., 2020).

Building Resilience: A Systems-Based Approach

To support mental health and hormonal balance, we must move beyond symptom suppression and toward systems repair. That means:

  • Prioritizing nutrient-dense, low-carbohydrate meals

  • Incorporating movement that matches nervous system tone

  • Protecting sleep architecture and circadian rhythm

  • Addressing inflammation and mitochondrial health

This approach aligns with the principles of metabolic psychiatry and root-cause care—where resilience is built from the cellular level up.

References

Arvidson, E., Sjörs Dahlman, A., Börjesson, M., Gullstrand, L., & Jonsdottir, I. H. (2020). The effects of exercise training on hypothalamic-pituitary-adrenal axis reactivity and autonomic response to acute stress—a randomized controlled study. Trials, 21(888). https://doi.org/10.1186/s13063-020-04803-3

Janssen-Aguilar, R., Vije, T., Peera, M., et al. (2025). Ketogenic diets and depression and anxiety: A systematic review and meta-analysis. JAMA Psychiatry. https://doi.org/10.1001/jamapsychiatry.2025.3261

Perrin, A. J., Horowitz, M. A., Roelofs, J., Zunszain, P. A., & Pariante, C. M. (2019). Glucocorticoid resistance: Is it a requisite for increased cytokine production in depression? A systematic review and meta-analysis. Frontiers in Psychiatry, 10, 423. https://doi.org/10.3389/fpsyt.2019.00423


Jennifer theriault