Boosting NAD+ works better when you also block its breakdown
NAD+ supplements have attracted enormous attention as potential anti-aging interventions.
NAD+ — nicotinamide adenine dinucleotide — is present in every cell and plays a central role in energy metabolism, DNA repair, and the regulation of proteins linked to aging called sirtuins. As organisms age, NAD+ levels in tissues fall measurably. That decline is not incidental: lower NAD+ concentrations are associated with muscle loss, weakened immune function, and metabolic deterioration.
The obvious response — topping up NAD+ through precursor supplements like NMN (nicotinamide mononucleotide) or NR (nicotinamide riboside) — has shown measurable effects in earlier research. But a second contributor to falling NAD+ levels has received less attention: the molecule is actively broken down by enzymes. One of these, CD38, increases in activity with age, consuming NAD+ at an accelerating rate.
Turning up the tap and closing the drain
Researchers combined NMN supplementation with apigenin, a natural compound found in parsley, chamomile, and several other plants, which inhibits CD38. The hypothesis was straightforward: if you simultaneously increase supply and slow breakdown, NAD+ levels should rise higher and stay elevated longer than with either intervention alone.
In aged mice, the combination treatment restored muscle mass and muscle function, and improved bone structure — two parameters that decline sharply with aging. The effects were larger than those observed with NMN or apigenin individually, supporting the idea of a synergistic interaction. The animals also showed improved endurance in physical performance tests.
What this means — and what it doesn’t
The results are promising, but the standard caveat applies: mice are not humans. Dosage, timing, and biological translation remain uncertain. Apigenin is already commercially available as a supplement, but concentrations used in the study exceed what is typically obtained through diet.
What the research does establish conceptually is that a strategy focused only on increasing intake is incomplete without accounting for the rate of loss. Within NAD+ research, this represents a meaningful shift in framing: not simply optimising production, but extending the working life of the molecule in the cell. Whether that combination produces comparable results in human tissue — and at what doses — is a question that clinical trials have yet to answer.