What Is NAD+? A Plain-English Guide to the Evidence

What NAD+ is and what it does

A 2021 review in Nature Reviews Molecular Cell Biology describes NAD+ as a coenzyme for redox reactions, which makes it central to energy metabolism. A coenzyme is a helper molecule that enzymes need to do their work. In redox (oxidation and reduction) reactions, NAD+ accepts and passes on electrons as cells break down nutrients for energy.

NAD+ has a second role. It is also consumed by other enzymes, including:

• Sirtuins: NAD+-dependent enzymes that regulate metabolism, stress responses, and aging-related processes. The review notes that two of them, SIRT1 and SIRT2, account for about a third of basal NAD+ consumption.
• PARPs: enzymes that use NAD+ during DNA repair. PARP1 is the best-characterized member and a major consumer of NAD+.
• CD38 and related enzymes: surface enzymes that break down NAD+, whose expression rises with inflammation and aging according to the review.

Cells make NAD+ from several starting materials. The review lists making it from the amino acid tryptophan, from nicotinic acid (a form of niacin, vitamin B3) through the Preiss-Handler pathway, and recycling nicotinamide through the salvage pathway, which supplies most of a cell's NAD+.

Does NAD+ really decline with age?

The idea that NAD+ falls as we age is widespread. The same 2021 review states that aging is accompanied by a gradual decline in tissue and cellular NAD+ in several model organisms, including rodents and humans, with reported drops ranging from 10 to 65 percent depending on organ and age. It also says much remains to be learned about how NAD+ influences human health and aging, including how to restore NAD+ during aging effectively and whether doing so is safe.

Newer work is more cautious. A 2025 review in Nature Metabolism notes that an age-related NAD+ decline in humans has been consistently observed in only a limited number of studies, that data on NAD+ in human tissues remain sparse, and that rodent findings do not translate straightforwardly. And a 2026 Nature Metabolism study that measured whole-blood NAD+ across seven independent human cohorts found it stable across age and lifestyle interventions, although it did change after nicotinamide riboside supplementation. The authors concluded that their results challenge the usefulness of blood NAD+ as a biomarker of aging.

Putting the two together: NAD+ may fall with age in some tissues, but this is not settled in people, and blood levels may not tell you much. "Low NAD+ with age" is a hypothesis under active study, not a diagnosis you can confirm with a routine test.

NAD+ itself versus its precursors

Most human studies have not tested NAD+. They have tested precursors, molecules the body can convert into NAD+, mostly given by mouth:

• Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN): the two precursors most studied for raising NAD+ in people.
• Niacin (nicotinic acid) and nicotinamide: forms of vitamin B3 that feed NAD+ production through the pathways described above.
• NAD+ itself: a larger molecule that is given by injection or infusion in some wellness settings, with very little published outcome data.

Results for one compound do not automatically apply to another or to a different route of administration. For a head-to-head comparison, see NAD+ vs NMN.

What human trials do and do not show

A 2026 systematic review in Ageing Research Reviews screened studies from 2010 to October 2025 and included 113 eligible studies, 33 in humans (28 randomized) and 80 in rodents. In rodents, raising NAD+ was often linked to better metabolic, mitochondrial, inflammatory, and functional results, though findings varied by model and endpoint.

In humans, oral NR and NMN consistently raised NAD-related levels in plasma, whole blood, or immune cells and were generally well tolerated over weeks to months. But effects on functional, metabolic, and vascular outcomes were mixed, often null or limited to a single endpoint. The review found no eligible outcome trials testing intravenous or intramuscular NAD+ for anti-aging or wellness. It concluded that clinical effectiveness for anti-aging or wellness is inconclusive, and called for larger, longer randomized trials, especially of parenteral (non-oral) approaches.

The 2025 Nature Metabolism review reached a similar place, saying human clinical trials of precursors have shown limited efficacy. The honest summary is that raising NAD+ works as biochemistry, and whether that translates into a health benefit you can feel or measure is not yet shown. For what is known about safety, read our guide to NAD+ injection side effects.

Regulatory status

NAD+ injections offered by telehealth companies are typically compounded. Compounded medications are not FDA-approved. FDA states that it does not verify the safety, effectiveness, or quality of compounded drugs before they are marketed.

FDA also keeps a list of bulk substances nominated for use in compounding under section 503A. In the version updated May 14, 2026, nicotinamide adenine dinucleotide (NAD) appears in Category 1, bulk drug substances under evaluation. That is neither an approval nor a finding that NAD+ works.

How Gala's longevity program works

You complete an online health questionnaire, and a licensed provider reviews it asynchronously in a roughly 5 to 7 minute consult, with no video call required. Intake screens for two exclusions: a hematocrit of 52% or higher, and a known allergy to NAD. If NAD+ is appropriate, your provider confirms the dosing before anything ships. It is a subcutaneous injection you give yourself at home.

Learn more about NAD+ at Gala, browse the longevity program, or start your online longevity intake.

Sources

1. Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology. 2021.
2. Vinten KT, et al. NAD+ precursor supplementation in human ageing: clinical evidence and challenges. Nature Metabolism. 2025.
3. Trętowicz MM, et al. Human whole-blood NAD+ levels do not vary with age or lifestyle interventions. Nature Metabolism. 2026.
4. Gallagher C, Emmanuel OO. NAD+ supplementation for anti-aging and wellness: a PRISMA-guided systematic review. Ageing Research Reviews. 2026.
5. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A (updated May 14, 2026).
6. FDA. Compounding and the FDA: Questions and Answers.

This article is for general information and is not medical advice. Talk to a licensed provider about your own health.