Naringenin — The Citrus Flavanone

Naringenin is a flavonoid that activates sirtuin 1 (SIRT1) and modulates the AMPK/mTOR signaling pathway, promoting autophagy and mitochondrial function. It also regulates the Nrf2/HO-1 pathway to enhance antioxidant defenses and inhibits NF-κB to reduce inflammation. In preclinical models, naringenin has been shown to extend lifespan in C. elegans and slow signs of brain aging in mice by upregulating downstream antioxidant and anti-senescence markers.

Human trials have primarily focused on safety, pharmacokinetics, and cardiovascular or metabolic endpoints rather than longevity per se. A single-ascending-dose trial confirmed safety up to 900 mg/day. Other trials using naringenin or its glycoside naringin (often in complex citrus extracts) have reported improvements in endothelial function, reductions in LDL cholesterol in hypercholesterolemic patients, and potential benefits for weight management. No published human longevity trials exist.

150–900 mg/day has been shown to be safe and well-tolerated in healthy adults in single-ascending-dose trials. Some clinical studies use 600 mg/day as an adjuvant for weight management or cardiovascular protection. Bioavailability is generally low, so it is often consumed as an extract or with other citrus flavonoids.

Generally considered safe and well-tolerated at doses up to 900 mg/day. However, naringenin can interact with cytochrome P450 enzymes (such as CYP3A4) and may alter the pharmacokinetics of various drugs, similar to the grapefruit juice effect. Caution is advised for individuals taking medications metabolized by these pathways.

Key Papers