Here's something that will change how you think about NAD+ supplements. You can take all the NMN and NR you want, but if CD38 is active, you're fighting a losing battle.
CD38 is an enzyme that increases with age and chronic inflammation. Its job? Destroying NAD+. By the time you're 50, CD38 activity has roughly doubled compared to your 20s. It's literally eating the NAD+ your body makes -- and the NAD+ precursors you're spending money on.
Apigenin inhibits CD38. Not partially. Significantly. A 2020 study in Cell Metabolism showed that CD38 inhibition raised NAD+ levels in aged mice by 50% -- without any NMN or NR supplementation at all. Just by stopping the drain, you fill the tank.
Think about that. You could be spending $60/month on NMN while CD38 destroys half of it before your cells can use it. Or you could add $5/month of apigenin and let your NMN actually work. The maths aren't complicated.
Apigenin binds to GABA-A receptors in the brain. Same receptors that benzodiazepines target. But without the addiction, the tolerance buildup, or the morning hangover. It's a mild anxiolytic and sedative -- enough to ease you into sleep, not enough to knock you unconscious.
Andrew Huberman put apigenin on the map when he mentioned taking 50mg before bed. Since then, it's become one of the most talked-about sleep supplements in the biohacking community. But the longevity angle -- the CD38 inhibition -- is far more interesting and far less discussed.
Here's why both matter. Poor sleep accelerates aging. Period. Short sleep increases inflammation, impairs autophagy, raises cortisol, and -- you guessed it -- elevates CD38 expression. It's a vicious cycle. Bad sleep raises CD38, which lowers NAD+, which impairs cellular repair, which makes sleep worse. Apigenin breaks that cycle at two points simultaneously.
The sleep studies typically use 50mg of apigenin before bed. The CD38 inhibition studies used higher concentrations, but oral apigenin at 50-100mg appears to have meaningful effects based on the available data.
You won't feel knocked out. This isn't melatonin. There's no chemical cosh. What most people report is falling asleep more easily, staying asleep longer, and waking up without that groggy, drugged feeling. It's subtle. But consistent.
One thing to flag: apigenin has mild anti-aromatase activity, meaning it could slightly reduce oestrogen conversion. For men, that's generally neutral or positive. For women, particularly those with low oestrogen, it's worth knowing about and discussing with a doctor.
The longevity supplement space is obsessed with NAD+ precursors. Billions of dollars in NMN and NR sales. But almost nobody talks about the drain. CD38 is the hole in the bucket. You can pour all the water you want -- if the hole is still there, the bucket stays empty.
Apigenin plugs the hole. And helps you sleep while it does it. For less than the price of a chamomile tea. Sometimes the most powerful tools are the ones nobody's marketing.
Science-backed health tips delivered every week.