NAD+ (nicotinamide adenine dinucleotide) is a molecule found in every cell of your body that plays two essential roles: it helps convert food into energy, and it acts as a helper molecule for enzymes that maintain DNA, regulate aging, and keep cells functioning properly. Your body cannot produce energy without it. NAD+ levels drop significantly as you age, which has made it one of the most studied molecules in aging research over the past decade.
How NAD+ Powers Your Cells
NAD+ works primarily as an electron carrier, a molecule that shuttles electrons between chemical reactions inside your cells. When you eat food, your body breaks down carbohydrates, fats, and proteins into smaller molecules. NAD+ picks up electrons from these molecules and becomes NADH (its reduced form), then delivers those electrons to the mitochondria, your cell’s power generators.
Inside the mitochondria, NADH donates its electrons to a chain of protein complexes embedded in the inner membrane. As electrons pass along this chain, protons are pumped across the membrane, creating a gradient that drives the production of ATP, the energy currency your cells use for virtually everything. NAD+ is then regenerated and cycles back to pick up more electrons. This loop runs continuously. NAD+ levels are the limiting factor in this reaction, meaning when NAD+ drops, energy production becomes less efficient.
In the cell’s main compartment (the cytoplasm), NAD+ also keeps glycolysis running. Without oxygen or functioning mitochondria, cells convert pyruvate to lactate specifically to recycle NADH back into NAD+, so glycolysis can continue producing at least some energy. This is why NAD+ availability matters even in low-oxygen conditions like intense exercise.
NAD+ Beyond Energy: DNA Repair and Cell Maintenance
Energy production is only half the story. NAD+ also serves as a raw material that gets consumed by enzymes critical for cell maintenance. Two families of enzymes are especially important here: PARPs and sirtuins.
PARPs are your cell’s emergency DNA repair crew. When DNA gets damaged, whether from UV radiation, toxins, or normal metabolic stress, PARPs rush to the site and use NAD+ to attach chemical tags to proteins near the break. These tags act as a beacon, recruiting other repair machinery to fix the damage. The catch is that this process consumes NAD+ rather than recycling it. A burst of DNA damage can rapidly deplete NAD+ stores as PARPs go into overdrive.
Sirtuins, a family of seven enzymes, use NAD+ to remove chemical groups from proteins, which in turn regulates gene expression, boosts antioxidant defenses, supports DNA repair, and influences inflammation. Sirtuins are often called “longevity genes” because of their role in stress resistance and metabolic health. They compete with PARPs for the same pool of NAD+, which creates a tug-of-war inside the cell. A third enzyme called CD38 also consumes NAD+, and its activity increases with age. When one of these consumers ramps up, less NAD+ is available for the others.
NAD+ Declines Substantially With Age
NAD+ levels fall across virtually every tissue as you get older. Human skin samples show at least a 50% decline over the course of adult aging, with levels several-fold lower in adults compared to newborns. Brain imaging studies estimate a 10% to 25% decline between young adulthood and old age. Liver samples from people over 60 show roughly 30% lower NAD+ compared to those under 45. Even cerebrospinal fluid shows about a 14% drop after age 45.
The reasons are interconnected. As you age, accumulated DNA damage keeps PARPs chronically active, steadily draining NAD+. CD38 activity also rises with age. Meanwhile, the enzymes that produce NAD+ may become less efficient. Lower NAD+ means less sirtuin activity, which in turn reduces the cell’s ability to handle DNA damage and oxidative stress, creating a downward spiral where NAD+ depletion accelerates further damage.
How Your Body Makes NAD+
Your body produces NAD+ through several pathways. The de novo pathway builds it from scratch using tryptophan, an amino acid found in protein-rich foods. The salvage pathway, which handles most day-to-day NAD+ production, recycles nicotinamide (a form of vitamin B3) that gets released every time sirtuins or PARPs consume NAD+. A third route, the Preiss-Handler pathway, converts nicotinic acid (another form of B3) into NAD+ through a series of enzymatic steps.
Daily NAD+ needs can be met with dietary tryptophan or about 15 mg of niacin per day, which is the collective term for nicotinic acid and nicotinamide. Meat, fish, and dairy products are the richest sources of these precursors. Smaller amounts of newer precursors like NMN are found in broccoli (0.25 to 1.88 mg per 100 grams), avocado and tomato (0.26 to 1.60 mg per 100 grams), and cucumbers, cabbage, and immature soybeans. Raw beef and shrimp contain trace amounts. These food-based levels are far lower than what supplementation studies use, which is why diet alone is unlikely to dramatically raise NAD+ in older adults.
NAD+ Precursor Supplements: NR and NMN
Two supplemental precursors have dominated NAD+ research: nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). Both raise blood NAD+ levels in humans, but their metabolic routes are more similar than marketing often suggests.
NMN is one step closer to NAD+ in the biochemical pathway, which initially led to assumptions that it would be more efficient. However, research has shown that NMN is typically broken down outside the cell into NR before being absorbed. Once NR enters the cell, it gets converted back into NMN, then into NAD+. Some evidence points to a dedicated NMN transporter on certain cells, but this finding remains contested among researchers. Meanwhile, orally administered NR and NMN both appear to be substantially converted to nicotinamide by the liver, meaning the liver may treat them similarly regardless of which one you take.
In a randomized, double-blind trial of 80 middle-aged adults, NMN at doses of 300, 600, or 900 mg daily for 60 days significantly increased blood NAD+ levels compared to placebo. The 600 mg dose appeared to hit a sweet spot, with the 900 mg dose offering no meaningful additional benefit in NAD+ levels or physical performance. NR has shown superior pharmacokinetics compared to nicotinic acid and nicotinamide in human studies, meaning it enters the bloodstream more effectively.
Safety of NAD+ Supplements
Human trials to date have not reported significant side effects from either NR or NMN supplementation. Single doses of NMN up to 500 mg are well tolerated in healthy adults. Longer-term studies have tested NMN at 250 mg daily for 12 weeks, 1,250 mg daily for 4 weeks, and up to 1,000 mg twice daily for 14 days, all without notable adverse effects. NMN has been classified as nonmutagenic in safety testing.
That said, no upper intake limit has been formally established for either NR or NMN. Some researchers have suggested that supplementation should stay below the established upper limit for niacin (35 mg per day), though this is a conservative guideline based on a different compound, and most trials have used doses well above that threshold without problems.
What NAD+ Restoration Does in Disease Models
Most of the disease-related evidence for NAD+ comes from animal and cell studies rather than large human trials. In Alzheimer’s disease models, boosting NAD+ reduced the hallmark brain plaques and tangled proteins, improved memory, enhanced the brain’s ability to form new connections, and promoted the growth of new neurons. In Parkinson’s disease models, NAD+ supplementation restored mitochondrial function, reduced oxidative stress, and protected dopamine-producing neurons. Huntington’s disease models showed that NAD+ precursors helped clear toxic protein aggregates and improved motor function. In ALS models, strengthening the NAD+ salvage pathway protected motor neurons from damage caused by neighboring cells carrying disease-linked mutations.
NAD+ supplementation has also extended healthspan and lifespan in animal models of premature aging conditions like ataxia telangiectasia and Cockayne syndrome, diseases characterized by accelerated DNA damage. These results are promising, but translating findings from mice and flies to humans is a long process, and clinical trials in people with these conditions are still in relatively early stages.