Nicotinamide Test

Your cells run on a molecule called NAD+, and nicotinamide is the raw material they use to make it. NAD+ drives hundreds of reactions inside every cell, from extracting energy out of food to repairing damaged DNA to activating the longevity-linked enzymes called sirtuins. When nicotinamide levels drop, NAD+ production slows, and those protective processes suffer.

What makes this biomarker particularly relevant for anyone focused on aging well is that NAD+ levels decline steadily with age. Measuring nicotinamide gives you a window into whether the supply side of this equation is keeping up with demand, and whether interventions like supplementation or exercise are actually working inside your body.

What Nicotinamide Does in Your Body

Nicotinamide (the amide form of vitamin B3, also called niacinamide) is recycled back into NAD+ through what biochemists call the salvage pathway. This recycling route is the dominant way your cells maintain their NAD+ supply, because every time NAD+ is consumed by sirtuins, PARP enzymes (which repair DNA breaks), or the immune enzyme CD38, nicotinamide is released as a byproduct. The enzyme NAMPT then converts it back into NAD+, completing the loop.

This recycling system means nicotinamide sits at a metabolic crossroads. It reflects both how much NAD+ your cells are producing and how fast they are consuming it. A low level can signal either inadequate dietary intake of vitamin B3 or excessive NAD+ consumption from chronic inflammation, DNA damage, or immune activation.

The NAD+ Decline with Aging

One of the most consistent findings in aging biology is that NAD+ levels fall as you get older, across multiple tissues and organs. This decline is driven by two simultaneous problems: the rate-limiting salvage enzyme NAMPT becomes less active with age, and the NAD+-consuming enzyme CD38 becomes more active due to chronic low-grade immune activation. The result is that your cells produce less NAD+ from the same amount of nicotinamide while burning through it faster.

Whole blood NAD+ levels show measurable sex differences. Men tend to have higher NAD+ levels than women before age 50 (median 34.5 vs. 31.3 micromol/L in one community study), though this gap narrows after 50. Women, on the other hand, show higher plasma NAD+/NADH ratios (a measure of the balance between the oxidized and reduced forms), with a median of 1.33 compared to 1.09 in men. NAD+ content declines with aging in men, particularly during middle age, but this pattern is less consistent in women.

Cardiovascular Risk: A Complicated Picture

The relationship between nicotinamide metabolism and heart disease is not straightforward. Higher dietary niacin intake appears protective: in a study of nearly 27,000 U.S. adults followed for a median of 9.17 years, those in the highest intake quartile had roughly 26% lower all-cause mortality (HR 0.74) and 27% lower cardiovascular mortality (HR 0.73) compared to the lowest quartile. A separate analysis of people with fatty liver disease found a similar inverse relationship between dietary niacin intake and mortality.

But the story reverses when you look at certain nicotinamide breakdown products. The terminal metabolites 2PY and 4PY (waste products created when your body finishes processing nicotinamide) are associated with increased cardiovascular risk. In a study spanning three cohorts totaling over 4,300 cardiac patients followed for 3 years, higher 2PY levels were linked to about 64% to 100% greater risk of major cardiovascular events, and higher 4PY levels showed similarly elevated risk.

This apparent contradiction likely reflects the difference between having adequate nicotinamide coming in (protective) versus having excessive breakdown and clearance of NAD+ metabolites (potentially harmful). It also means that interpreting your nicotinamide level in isolation, without understanding your metabolite profile, gives you an incomplete picture.

Metabolic Disease Associations

Higher whole blood NAD+ levels have been paradoxically associated with more metabolic disease in at least one large cross-sectional study. Among 1,394 participants from a Chinese community cohort (mean age 43.2 years), those in the highest NAD+ quartile were about 3 times as likely to have metabolic disease compared to the lowest quartile (OR 3.01). Risk began climbing at NAD+ levels above 31.0 micromol/L.

This finding is counterintuitive given the general narrative that higher NAD+ is better, and it reinforces the idea that context matters enormously. A high level could reflect a compensatory response to metabolic stress rather than genuine health. Cross-sectional data cannot establish whether high NAD+ is a cause, a consequence, or simply a bystander. What it does tell you is that a single reading without clinical context can be misleading.

Kidney Function and Nicotinamide Metabolism

Your kidneys play a central role in clearing nicotinamide and its metabolites. In chronic kidney disease, NAD+ biosynthesis is impaired because key synthesis enzymes are downregulated, and nicotinamide metabolites accumulate as filtration declines. Serum nicotinamide levels are independently associated with estimated kidney filtration rate (eGFR). If your kidney function is reduced, your nicotinamide level may be artificially elevated, not because you have more of it but because your body is not clearing it efficiently.

In kidney transplant recipients, lower urinary excretion of the nicotinamide metabolite N-methylnicotinamide was associated with higher all-cause mortality over a median follow-up of 5.4 years (HR 0.57 per standard deviation increase in excretion). This suggests that the ability to actively metabolize and excrete nicotinamide products may be a marker of overall metabolic health in this population.

Reference Ranges

There are no universally standardized clinical reference ranges for serum or plasma nicotinamide. This biomarker is measured primarily in research settings, and the published analytical ranges reflect method validation rather than population-based health thresholds. Your kidney function significantly influences your level, so any interpretation must account for eGFR.

These ranges are drawn from published analytical and pharmacokinetic studies. Your lab may use different assays and cutpoints. Compare your results within the same lab over time for the most meaningful trend. Blood levels of nicotinamide alone are not considered reliable for diagnosing niacin deficiency; urinary metabolite testing (N1-methylnicotinamide and 2-pyridone) is the standard method, with combined urinary excretion below 1.59 mg/day indicating deficiency. The urinary approach achieves about 91% sensitivity and 72% specificity for detecting pellagra.

Tracking Your Trend

A single nicotinamide reading is far less useful than tracking your level over time, and this biomarker is a particularly strong case for serial measurement. Blood NAD+ and NADP+ concentrations appear tightly regulated under steady-state conditions, with excess nicotinamide excreted in urine rather than accumulating in blood. This means that meaningful shifts in your level probably reflect real changes in your metabolic status rather than random noise, but it also means that transient disruptions (intense exercise, acute illness, cold exposure) can temporarily skew a reading.

If you are supplementing with nicotinamide, NR, or NMN, a baseline measurement before starting is essential. Follow up at 4 to 8 weeks to confirm that supplementation is actually raising your levels, since interindividual variability is high (one NMN study reported coefficients of variation ranging from 29% to 113%). After confirming a response, retest every 6 to 12 months to verify that your levels are holding. If you are not supplementing but are tracking NAD+ biology as part of a longevity strategy, an annual check is a reasonable cadence, with retesting sooner if you make significant changes to diet or exercise.

When Results Can Be Misleading

The most common source of a misleading nicotinamide reading is impaired kidney function. Because the kidneys clear nicotinamide and its metabolites, even mildly reduced eGFR can push your level higher without reflecting a genuine increase in NAD+ metabolism. Always interpret nicotinamide alongside a recent eGFR.

Acute illness can dramatically alter results. In hospitalized COVID-19 patients, the nicotinamide metabolite 1-methylnicotinamide increased more than 10-fold compared to healthy controls, reflecting massively increased NAD+ turnover during systemic inflammation. Any acute infection, surgery, or significant physical stressor (including cold exposure) can temporarily reshape your nicotinamide metabolite profile. Wait at least two to three weeks after recovering from an acute illness before testing.

Intense exercise within 24 to 72 hours before a blood draw may lower serum nicotinamide, because working muscles ramp up NAD+ production by pulling nicotinamide out of circulation. Fasting status also matters: being in a fed state is associated with higher water-soluble vitamin levels, though the specific magnitude for nicotinamide is not well quantified. For the most consistent results, test fasted and avoid vigorous exercise the day before.

Nicotinamide metabolite excretion follows a daily rhythm, peaking in the afternoon, though blood NAD+ and NADP+ concentrations themselves remain relatively stable throughout the day. The enzyme that recycles nicotinamide (Nampt/visfatin) has its own circadian pattern, peaking in early afternoon. Morning blood draws will give the most standardized snapshot.