MAAFIM 6th International Conference 2026

Background & Clinical Gap

Depression and cognitive decline are increasingly recognized as metabolic disorders of the brain, not just neurotransmitter imbalances. Yet most clinicians lack a practical framework to assess and target cerebral metabolism.

What This Session Delivers

You will leave with a clinically actionable model linking three convergent mechanisms:

• Brain insulin resistance (impaired glucose uptake, reduced synaptic plasticity)
• Mitochondrial dysfunction (low ATP, oxidative stress, poor mitophagy)
• Neuroinflammation (microglial activation driven by metabolic signals)

Key Clinical Insights

1. Standard glucose metabolism is only half the story. The brain can run on ketones and lactate. Measuring fuel flexibility (fasting β-hydroxybutyrate, postprandial lactate) predicts treatment response better than any single neurotransmitter marker.
2. β-hydroxybutyrate is not just fuel. At levels achievable with intermittent ketogenic protocols(0.5–1.5 mM), it reduces NLRP3 inflammasome activation, increases BDNF, and enhances mitochondrial biogenesis — effects independent of calorie restriction.
3. Subtyping matters. Patients with high inflammatory-metabolic load (elevated hs-CRP, low T3, flat cortisol curve, insulin resistance) respond poorly to SSRIs alone but often improve dramatically with metabolic interventions.

Interventions You Can Implement (with biomarker guidance)

1. Time-restricted feeding (14:10 or 16:8) Insulin sensitivity, circadian entrainment. Fasting insulin, HOMA-IR.
2. Cyclic ketogenic protocol (5:2 or monthly 3-day) Fuel flexibility, BDNF, NLRP3. β-hydroxybutyrate, hs-CRP.
3. Transcranial photobiomodulation (660/850 nm) Mitochondrial cytochrome c oxidase. Subjective cognition + optional EEG.
4. Methylene blue (low dose, 0.5–1 mg/kg) Mitochondrial electron transport. No routine lab; monitor serotonin syndrome risk.
5. Omega-3 EPA/DHA (≥2 g EPA) Neuroinflammation. Omega-3 index, hs-CRP.

Learning Objectives

1. Assess brain fuel flexibility using available labs (insulin, β-hydroxybutyrate, lactate, hs-CRP, T3/rT3).
2. Identify patients most likely to benefit from metabolic interventions vs. standard pharmacotherapy.
3. Implement a stepped metabolic protocol starting with lifestyle (time-restricted eating, cyclic ketogenic) and escalating to adjunctive nutraceutical/photobiomodulation strategies.