Boosting NAD+ works better when you also block its breakdown
NAD+ supplements have attracted enormous attention as potential anti-aging interventions. But a new mouse study suggests that simply taking more of the compound misses half the problem, because aging bodies are also destroying it faster.
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.