Melatonin for ALS
Also known as: N-acetyl-5-methoxytryptamine
Melatonin is a potent mitochondrial antioxidant that accumulates in neuronal mitochondria, targeting oxidative stress at its source in ALS.
Mechanism of Action
Melatonin concentrates in mitochondria where it scavenges ROS, enhances Complex I and IV activity, stabilizes mitochondrial membrane potential, and activates Nrf2-dependent antioxidant genes. It also has anti-inflammatory effects through NLRP3 inflammasome suppression.
General mechanism: Pineal hormone. Mitochondrial antioxidant, Nrf2 activator, NLRP3 inhibitor, circadian regulator, anti-amyloid, immunomodulator.
Current Evidence
Preclinical ALS models show motor neuron preservation and extended survival. Small clinical studies show safety at high doses (300mg). Biomarker effects documented.
Clinical Status: Preclinical. High-dose pilot studies for ALS safety.
Safety Profile
Extremely safe even at high doses. Drowsiness. No addiction potential. May affect reproductive hormones at very high doses.
Key Research Questions
- What melatonin dose is needed for mitochondrial neuroprotection in ALS?
- Does melatonin extend survival in ALS patients as add-on therapy?