Vilnius University researchers find that whole-blood NAD levels remain stable with age in healthy men and increase slightly in women, but are lower in people with cardiovascular disease, particularly hypertension.
Blood levels of NAD (nicotinamide adenine dinucleotide), a molecule at the centre of growing interest in longevity and anti-ageing supplements, do not decline with age in healthy adults, but are significantly lower in people with cardiovascular disease, particularly hypertension. This is the main finding of a study involving 1,068 adults, conducted by researchers at Vilnius University in Lithuania and published in Nature Metabolism.
The findings challenge the widespread assumption that declining NAD levels in the blood are a natural and universal feature of human ageing. Instead, the research suggests that whole-blood NAD levels may be more closely associated with cardiovascular health than with chronological age.
Is NAD really the key to healthy ageing?
NAD is an essential molecule involved in cellular metabolism and energy production. Previous studies in animals have reported age-related declines in NAD levels in various tissues, including skeletal muscle, the brain and the skin. These findings have helped fuel growing interest in NAD-boosting supplements, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), which are marketed as potential tools for supporting healthy ageing.
However, whether NAD levels also decline in human blood as people grow older has remained controversial, with previous studies reporting inconsistent results.
To investigate this question, the Vilnius University research team analysed whole-blood NAD levels in 1,068 adults, including healthy individuals and people with chronic diseases. The researchers conducted 1,340 NAD measurements as part of a broader research programme, using dried blood spot samples collected under standardised conditions.
Cardiovascular disease is linked to lower NAD levels
The findings revealed a different picture of how NAD levels relate to ageing and health. Among healthy adults, whole-blood NAD levels did not decline with age, remaining stable in men and showing a modest but statistically significant increase in women. However, a different pattern emerged when the researchers looked at participants with chronic conditions: NAD levels were lower in people with cardiovascular disease, with the clearest differences observed among those with hypertension.
The findings suggest that health status, especially cardiovascular health, may be an important factor when interpreting whole-blood NAD measurements.
'For years, the prevailing narrative has been that NAD declines as we age and therefore needs to be restored. Our findings suggest that this is not what happens in the blood of healthy adults,' said Dr Dalius Ratautas, who led the research at Vilnius University.
'Instead, we found a clear association between lower NAD levels and cardiovascular disease. This raises a different and potentially important question: could NAD levels tell us something about cardiovascular health?' he added.
What do the findings mean for NAD supplements?
The results add an important dimension to the ongoing discussion about NAD supplementation and healthy ageing.
Although NAD-boosting supplements are increasingly promoted as a way to counteract age-related NAD depletion, the study found no evidence of a universal decline in whole-blood NAD among healthy adults.
The researchers emphasise, however, that their findings do not establish a cause-and-effect relationship between NAD levels and cardiovascular disease.
It remains unclear whether lower NAD levels contribute to cardiovascular disease, result from the disease itself, or reflect other underlying factors. The study also does not demonstrate that increasing NAD levels through supplementation can prevent or treat cardiovascular disease or hypertension.
What blood NAD reveals about tissue health
The findings also contribute to an ongoing scientific discussion about whether NAD measured in blood can reliably reflect NAD levels in other tissues.
In a commentary published alongside the study, researchers Stephen Gardell and Joseph Baur highlight the limitations of using blood NAD as a proxy for NAD levels in tissues such as muscle or the brain. Red blood cells, which account for most of the NAD measured in whole blood, have different metabolic characteristics from other cell types.
The Vilnius University researchers acknowledge that blood NAD measurements do not necessarily mirror NAD concentrations in individual tissues. However, they argue that a blood biomarker does not need to reproduce tissue-level measurements to provide clinically useful information.
Many established clinical biomarkers are measured in blood precisely because they offer accessible information about physiological processes and disease. Unlike direct tissue measurements, which may require invasive biopsies or specialised imaging, blood testing offers the potential for large-scale monitoring.
The next step will be to determine whether whole-blood NAD measurements can help predict cardiovascular risk and to investigate the biological mechanisms underlying the association between NAD levels and cardiovascular disease.
