Apigenin — The CD38 Inhibitor
Apigenin is a flavonoid found in parsley, chamomile, and celery that has gained significant attention in longevity science as a CD38 inhibitor. CD38 is an NAD+-consuming enzyme that increases dramatically with aging and is a major driver of the age-related NAD+ decline. By inhibiting CD38, apigenin preserves NAD+ levels and potentiates the effects of NMN and NR.
Mechanism of Action
CD38 is a cyclic ADP-ribose hydrolase that consumes NAD+ at a rate far exceeding PARP1 or sirtuins. With aging, CD38 expression in immune cells and tissues increases ~2-3×, creating a major NAD+ sink. Apigenin inhibits CD38 with an IC50 of ~10 μM, preserving NAD+ for sirtuin and PARP1 activity. Apigenin also activates SIRT1 directly and has anti-inflammatory effects via NF-κB inhibition.
Human Trial Evidence
No large human RCTs specifically for apigenin's longevity effects. Andrew Huberman and David Sinclair both include apigenin in their protocols. Chamomile tea (high in apigenin) has been associated with reduced all-cause mortality in elderly Mexican-American women (Annals of Epidemiology, 2015). Human pharmacokinetic studies confirm apigenin is absorbed and reaches relevant tissue concentrations.
Dosing Protocol
50–100 mg/day of apigenin. Best taken with NMN or NR (synergistic CD38 inhibition preserves NAD+). Chamomile extract standardised to apigenin content is the most common form. Andrew Huberman takes 50 mg/day. Best taken in the evening (mild sedating effect via GABA modulation).
Safety & Contraindications
Well-tolerated at typical supplement doses. Mild sedating effect (GABA-A receptor modulation) — may enhance sleep. Inhibits CYP1A2 and CYP2C9 — potential drug interactions. Mild estrogenic activity at high doses (phytoestrogen) — caution in hormone-sensitive conditions. No serious adverse events in human studies.