NAD+ (nicotinamide adenine dinucleotide) is a molecule found in every cell of your body that plays a central role in energy production, DNA repair, and cellular aging. Your NAD+ levels represent how much of this molecule is available to power these processes. In healthy adults, blood concentrations of NAD+ typically measure around 18 micromolar, but levels decline significantly with age, dropping by at least 50% over the course of adult life.
What NAD+ Does in Your Body
NAD+ works as a molecular shuttle, picking up electrons during the breakdown of food (carbohydrates, fats, and amino acids) and delivering them to your mitochondria, where they’re used to generate ATP, your cells’ primary energy currency. Without adequate NAD+, this entire energy pipeline slows down.
Beyond energy production, NAD+ fuels two other critical systems. The first involves a family of proteins called sirtuins, which regulate gene expression, circadian rhythm, and inflammation. Sirtuins can only function when NAD+ is available to activate them. SIRT1 and SIRT6, for example, help control your body’s internal clock and influence how genes related to aging are turned on and off. The second system involves DNA repair enzymes called PARPs, which detect and fix breaks in your DNA. PARP1, the most active of these, consumes NAD+ every time it repairs a damaged strand. When DNA damage accumulates (from UV exposure, oxidative stress, or normal metabolic activity), PARP enzymes use up more NAD+, leaving less available for other functions.
How NAD+ Levels Change With Age
NAD+ levels decline steadily as you get older, and the drop is measurable across multiple tissues. Human liver samples from people over 60 show roughly a 30% decline compared to those under 45. Brain imaging studies have found reductions of 10% to 25% between young adulthood and old age. Cerebrospinal fluid levels drop by about 14% after age 45. In skin tissue, the decline appears even steeper, with concentrations falling by at least half over the course of adult aging and measuring several times lower in adults than in newborns.
A major driver of this decline is an enzyme called CD38, which breaks down NAD+ and is the single largest NAD+-consuming enzyme in mammalian tissues. Here’s the key connection: inflammation increases CD38 activity. As you age, your body accumulates more senescent (worn-out) cells that release inflammatory signals. These signals trigger surrounding cells to produce more CD38, which chews through NAD+ faster. Mice genetically engineered to lack CD38 maintain significantly higher NAD+ levels in the brain and liver, confirming how central this enzyme is to the decline.
The NAD+ to NADH Ratio
Total NAD+ levels matter, but so does the balance between NAD+ and its reduced form, NADH. When NAD+ accepts electrons during metabolism, it converts to NADH. Both forms are essential, but the ratio between them needs to stay within a functional range for cells to operate normally. An imbalanced ratio can disrupt metabolic pathways and has been linked to neurodegenerative disorders, accelerated aging, and abnormal cell growth.
Complicating things further, this ratio varies between different compartments within each cell. The ratio in your mitochondria is different from the ratio in your nucleus, and both respond to different metabolic signals. This makes measuring a single “NAD+ level” only part of the picture.
What Low NAD+ Looks Like
The most dramatic example of NAD+ deficiency is pellagra, caused by severe vitamin B3 (niacin) deficiency. B3 is a building block for NAD+, and without it, people develop a characteristic triad of symptoms: photosensitive skin rashes, diarrhea, and cognitive decline progressing to dementia. Left untreated, pellagra is fatal. While pellagra is rare in developed countries today, it illustrates what happens when NAD+ synthesis is severely impaired.
Several rare genetic conditions also cause NAD+ deficiency from birth. Mutations in genes involved in NAD+ production or stability can lead to congenital heart and kidney defects, visual loss, progressive muscle weakness, or severe neurological problems in infants and children. These conditions are uncommon but reinforce how essential NAD+ is for normal development and organ function.
For most adults, the relevant concern isn’t outright deficiency but the gradual, age-related decline described above. Lower NAD+ levels have been observed in people with heart failure (averaging around 13 micromolar versus 18 in healthy controls) and in those with certain neurological conditions (around 14 micromolar). Whether the low NAD+ is a cause or consequence of these diseases is still being studied.
How NAD+ Is Measured
There’s no routine clinical test for NAD+ the way there is for cholesterol or blood sugar. The gold-standard measurement technique is liquid chromatography paired with mass spectrometry (LC-MS), which can detect NAD+ and its related metabolites with high sensitivity and specificity. Older methods like UV-based assays or colorimetric tests lack the precision needed for human biological samples.
Interpreting results is also tricky because NAD+ concentrations vary enormously depending on where you measure. Inside cells, concentrations range from 10 to 1,000 micromolar. In whole blood, healthy adults average around 18 micromolar. In blood plasma alone (the liquid portion without cells), levels can be as low as 2 to 70 nanomolar, roughly a thousand times less, because the vast majority of NAD+ resides inside cells. Any test result needs to specify exactly what was measured and how.
Exercise and Its Effect on NAD+ Production
Exercise is one of the most reliable ways to boost your body’s own NAD+ production. It works by increasing an enzyme called NAMPT, which is the rate-limiting step in the main NAD+ recycling pathway. A meta-analysis of human studies found that exercise training increased NAMPT levels by an average of 1.46-fold. Aerobic exercise had a 75% probability of raising NAMPT expression, while resistance training had a 66% probability. Overall, a person who exercises regularly has about a 72% chance of having higher NAMPT levels than a sedentary person.
This enzyme is also tied to your circadian rhythm. NAMPT activity oscillates throughout the day, regulated by your internal clock, which means NAD+ levels naturally rise and fall in a 24-hour cycle. Disrupted sleep patterns or irregular schedules may interfere with this rhythm.
NAD+ Precursor Supplements
Two supplements marketed to raise NAD+ levels have gained significant attention: nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). Both are precursors, meaning your body converts them into NAD+ after ingestion. Clinical trials have shown that both compounds do raise blood NAD+ and related metabolite concentrations. In one study, 250 mg of NMN daily was found to be safe, well-tolerated, and effective at boosting NAD+ metabolism in healthy older men. NR has been tested at doses ranging from 100 to 2,000 mg per day over periods up to 12 weeks, with most trials confirming it raises circulating NAD+ levels.
The catch is that raising blood NAD+ levels doesn’t automatically translate into measurable health improvements. A 2025 systematic review of all available preclinical and clinical evidence concluded that while NAD+ supplementation shows clear biological activity, its clinical effectiveness for anti-aging or wellness outcomes remains inconclusive. Effects on functional, metabolic, and vascular endpoints were mixed, with many trials finding no significant benefit on the outcomes that actually matter to people, like physical performance, cardiovascular health, or cognitive function. The supplements reliably hit the biochemical target (higher NAD+ in blood) but haven’t yet proven they change health outcomes in a meaningful, consistent way.