Do NAD+ Levels Decline with Age?

The pitch for NAD+ boosting as an anti-aging strategy goes as follows: all species, including humans, naturally experience a decline in NAD+ levels over time, and this decline is, in fact, one of the major reasons organisms age. By restoring youthful levels, the argument goes, these age-related disorders can be delayed or even reversed. Two leaders in the field, one from Harvard and the other MIT, have said, respectively, that NAD+ boosters may “hold the promise of increasing the body’s resilience, not just to one disease, but to many, thereby extending healthy human lifespan,” and that sirtuin activation by NAD+ repletion “may be the most actionable item to emerge from aging research.” Of course, they have both been involved in multimillion-dollar dietary supplement companies.

The first premise, that NAD+ levels decline with age, has been called into question. For example, this 2022 review “Age-Dependent Decline of NAD+—Universal Truth or Confounded Consensus?” concluded that, despite systemic claims to the contrary, the evidence supporting the premise is very limited. Indeed, the most comprehensive study to date found significant changes in NAD+ levels in less than half of the tested tissues in old versus young mice. The human data are similarly inconsistent.

NAD+ boosting supplement shills make claims like “By middle age, our NAD+ levels have plummeted to half that of our youth,” but the cited source only shows a drop (in brain levels) of about 13 percent between about the ages 20 to 60. A similar study estimated about an 18 percent drop from age 25 to 70, both broadly consistent with a 14 percent drop in spinal tap fluid samples taken from those over age 45 (average age 71), compared to those under age 45 (average age 34). It’s unclear if such modest differences would have any consequences, and a more recent study found no significant differences at all in brain nor muscle levels between a young group (average age 21) and an older group (average age 69).

A study of skin samples found a greater than 50 percent drop in young adults compared to the skin of newborns, and a further drop of about 60 percent from young adults to middle age. However, there did not seem to be a further decline from middle to old age. There was a small study that found the NAD+ levels in the liver samples of six older individuals (average age 66) was about 30 percent lower than that of six younger individuals (average age 39). NAD+ levels also may be lower in macrophage white blood cells in older individuals, but in the blood more generally half the studies showed a decline with age, and the other half didn’t. By far the largest study (enrolling 10 times more people than the other studies combined) found a slight drop in NAD+ in the aging bloodstreams of men but no drop in women.

The bottom line is that, given the conflicting findings from the remarkably few studies on the subject, it’s misleading to say NAD+ universally decreases with age. Regardless, the proof is in the pudding. What about the second premise that boosting levels late in life can improve health and longevity? We’ll address that question, next.