You have probably already heard of NAD+ in connection with ageing or longevity. But what is really behind this technical name (nicotinamide adenine dinucleotide) in clinical practice?
During a Simplycure webinar led by Antoine Loth (SuperSmart), we broke down its biological role, the signs of a functional deficiency, and, above all, what the literature says about supplementing it.
Why does this matter? Because NAD+ is central to ATP production, DNA repair and metabolic regulation. And its levels fall with age, oxidative stress or certain chronic conditions.
So when, how, and in whom should you consider supporting it? That is what this article sets out to cover, in a concise and actionable way!
The key functions of NAD+: what you may already be observing in practice
As you probably already know, NAD+ is far more than a simple energy cofactor.
This coenzyme is involved in ATP production, DNA repair and the regulation of gene expression... and a deficit quickly translates into a loss of cellular efficiency.
In clinical practice, this often shows up as unexplained fatigue, abnormally slow recovery, premature cellular ageing or a silent inflammation profile1.
Here is a summary table, based on the webinar led by Antoine Loth, to help visualise the functional impact of NAD+:
FunctionRole of NAD+Clinical implicationsEnergy production (ATP)Electron carrier essential for glycolysis, beta-oxidation and the respiratory chainChronic fatigue, reduced exercise tolerance, slow recoveryDNA repair (PARP)ADP-ribose donor that activates the PARP enzymes which repair DNA breaksVulnerability to oxidative stress, cellular ageing, accumulation of DNA damageRegulation of gene expression (sirtuins)Cofactor for sirtuins, involved in histone deacetylation and epigenetic regulationLow-grade inflammation, metabolic dysregulation, reduced autophagyRecycling and age-related lossRecycled via nicotinamide, but broken down by PARP, sirtuins and CD38 (activity increases with age)Functional NAD+ deficit in high-demand tissues (brain, muscle, liver, etc.)
Why NAD+ levels fall with age (and why that is a problem)
With age, the body progressively loses its ability to maintain an optimal NAD+ level2.
Three main mechanisms explain this decline:
1. Reduced synthesis
Endogenous NAD+ production from tryptophan or vitamin B3 becomes less efficient with age.
Result: less raw material available to replenish cellular stores.
2. Overconsumption
The enzymes that use NAD+ (particularly PARP and sirtuins) become more active with oxidative stress, DNA damage or low-grade inflammation.
CD38, an enzyme that breaks down NAD+, also becomes more active over the years.
3. Imbalance between recycling and breakdown
Even though the body recycles some of its NAD+, this balance becomes insufficient over time, especially in tissues with high demand (muscle, brain, liver...).
What is the clinical implication of falling NAD+? Chronically low NAD+ can limit cellular regeneration capacity, weaken the metabolic response, and accelerate markers of ageing (silent inflammation, senescence, insulin resistance...). In patients over 50, exposed to chronic stress or living with degenerative conditions, this decline can be one of the keys to a clinical picture of persistent fatigue, slow recovery, or metabolic fragility.
How to support NAD+ levels: what works (and what is pointless)
When it comes to NAD+ supplementation, the first thing to know is that... NAD+ itself does not work.
Why? Because it is not absorbed orally: it is broken down in the gut and never reaches its target cells.
Certain precursors, however, cross the digestive barrier, enter the cell, and are efficiently converted into NAD+.
The three main metabolic pathways for NAD+
PathwayPrecursorNoteThe “de novo” pathwayTryptophanMainly active in the liver. Not very effective at raising NAD+ in practiceMain pathway (salvage pathway)Nicotinamide (= B3)Well tolerated and inexpensive, but requires several conversion stepsFast, direct pathwayNR (nicotinamide riboside), NMN (nicotinamide mononucleotide)Highly bioavailable, with demonstrated effects on NAD+ levels
In clinical practice:
Nicotinamide is useful for prevention, but it quickly reaches its limits.
The direct precursors NR and NMN are the most studied for supplementation: they can rapidly raise intracellular NAD+ levels, including in hard-to-reach tissues (e.g. the brain).
The studies cited during the webinar show measurable effects from as little as 250 to 1000 mg/day, depending on the patient’s profile (age, weight, associated conditions).
What to avoid:
Supplementing directly with NAD+
Assuming that diet alone is enough: dietary intake of NR and NMN is negligible (less than 1 mg/100 g).
When to consider supporting NAD+: concrete clinical applications
So specifically, which patient profiles should you think of when it comes to supporting NAD+?
Here are the main indications to keep in mind, along with the typical clinical signs and the best-documented protocols.
Clinical indicationProfiles to look out forRecommended precursorObserved benefitsCellular ageing & chronic fatiguePersistent fatigue, slow recovery, patients > 50 yearsNMN or NR (500 to 1000 mg/day)Mitochondrial support, reduced senescenceNeurology & neuroprotectionCognitive disorders, Parkinson’s terrain, cerebral oxidative stressNR (1 g/day)↑ Cerebral NAD, ↓ inflammation, activation of protective genesPhysical performance & recoveryFatigued athletes, active seniors, post-COVID recoveryNMN (300 to 1200 mg/day)↑ Endurance, better muscle recoveryMetabolic & cardiovascular healthMildly hypertensive individuals, overweight, metabolic syndromeNR (1 g/day)↓ Blood pressure, ↑ endothelial functionInsulin sensitivity & prediabetesOverweight menopausal women, insulin resistanceNMN (250 mg/day)↑ Insulin sensitivity, effects comparable to a 10 kg weight loss
These different indications help you target NAD+ precursor supplementation more precisely according to the patient’s profile.
Whether the aim is to support cellular vitality, prevent the effects of ageing or strengthen metabolic function, this lever fits naturally into a personalised, preventive approach, provided the right indications are mastered3.
In summary: NAD+, a lever worth knowing and personalising
A decline in NAD+ is a key mechanism to factor into many clinical pictures: persistent fatigue, insulin resistance, poor recovery, signs of cellular senescence...
Available studies show that targeted supplementation with precursors such as NR or NMN can offer a relevant, well-tolerated lever, backed by a growing body of literature, including in still-exploratory areas such as neuroprotection or physical performance.
Would you like to bring these protocols into your practice, or organise your recommendations on a single interface? Do not hesitate to get in touch with us!
