NAD+

What it is

NAD+, short for nicotinamide adenine dinucleotide, is made of two nucleotide units joined together rather than a string of amino acids, so scientists classify it as a coenzyme, not a peptide. Every cell depends on it for the core chemistry that produces energy and for switching on a group of DNA repair proteins called sirtuins.

Because NAD+ levels decline naturally with age, part of the research interest in it concerns whether restoring those levels, either by giving NAD+ directly or by giving a related building-block molecule the body converts into NAD+, changes markers of cellular energy and aging.

How it is studied

Research on NAD+ spans a rat brain injury model given the coenzyme directly into the nose, a randomized, placebo-controlled human trial giving a related building-block molecule called nicotinamide riboside by mouth over two six week periods, and a study measuring the coenzyme's natural levels in human skin samples from donors of different ages.

What studies report

• A study in rats reported that delivering NAD+ into the nose immediately after a simulated brain injury protected neurons in three regions of the hippocampus and reduced activation of the brain's resident immune cells measured a week later, though it did not protect neurons in the cortex. [1]
• A randomized, double-blind, placebo-controlled crossover trial of a related molecule the body converts into NAD+, called nicotinamide riboside, reported that taking it by mouth for six weeks was well tolerated and raised NAD+ related markers in the blood of healthy middle-aged and older adults, testing this precursor molecule directly rather than NAD+ itself. [2]
• A study of pelvic skin samples from 49 human donors ranging from newborns to 77 years old reported that natural NAD+ levels fell significantly with age in both men and women, alongside rising markers of DNA and lipid damage. [3]

What is not known

The human trial cited here tested a precursor molecule rather than NAD+ given directly, so it does not show what happens when NAD+ itself is given to a person. The rat brain injury finding has not been shown to apply to people, and the skin tissue study looked at one tissue type in a cross-section of donors rather than tracking the same people over time. Whether restoring NAD+ levels in older adults changes long term health outcomes, rather than just blood markers, is not established in the citations reviewed for this entry.

Reported adverse findings

• The human trial reported that taking the NAD+ precursor nicotinamide riboside by mouth was well tolerated over the six week study periods, without describing serious adverse events. [2]

Regulatory status

NAD+ itself, given by injection or infusion, is not approved by the United States Food and Drug Administration as a drug. Nicotinamide riboside, the related precursor tested in the cited human trial, is available in some markets as a dietary supplement ingredient rather than as an approved medicine.