Dihydromyricetin — The Flavonoid for Liver Health and Metabolic Resilience
Dihydromyricetin (DHM) is a natural flavonoid extracted from the Japanese raisin tree, traditionally used for its hepatoprotective properties and ability to mitigate alcohol intoxication. In the context of longevity, DHM is gaining attention for its potential to activate AMPK and SIRT1 pathways, improving metabolic health, reducing inflammation, and protecting against age-related liver and cognitive decline.
Mechanism of Action
Dihydromyricetin (DHM) exerts its effects primarily through the modulation of metabolic and inflammatory pathways. It activates the AMPK/SIRT1/PGC-1α signaling axis, which enhances mitochondrial biogenesis, improves respiratory capacity, and regulates lipid metabolism. DHM also mitigates oxidative stress by scavenging reactive oxygen species (ROS) and inhibiting the TLR4/NF-κB pathway, thereby reducing cellular inflammation. Additionally, it has been shown to interact with GABA-A receptors, which underlies its neuroprotective effects and ability to counteract acute alcohol intoxication.
Human Trial Evidence
Human evidence for DHM is limited but emerging, primarily focusing on metabolic health and liver function. A double-blind, placebo-controlled clinical trial in 60 adults with non-alcoholic fatty liver disease (NAFLD) demonstrated that DHM supplementation (600 mg/day) improved glucose and lipid metabolism, and reduced markers of liver injury. Phase I dose-escalation studies are currently underway to further evaluate its safety and pharmacokinetics in healthy volunteers.
Dosing Protocol
300–600 mg/day is the most commonly studied and supplemented range in humans, typically taken in divided doses or before/after alcohol consumption. Clinical trials for NAFLD have used doses of 300 mg twice daily (600 mg/day total). It is available over-the-counter as a dietary supplement. Due to its short half-life and poor bioavailability, sustained-release or liposomal formulations are sometimes used.
Safety & Contraindications
DHM is generally well-tolerated in human studies at standard doses (up to 600 mg/day), with no severe adverse events reported. Mild side effects may include gastrointestinal discomfort or headaches. Due to its interaction with GABA-A receptors and alcohol metabolism, caution is advised when combining it with central nervous system depressants. Long-term safety data and its effects in pregnant or breastfeeding women remain unestablished.