In a Simplycure webinar led by Antoine Loth (SuperSmart), we took a close look at its biological role, the signs of functional deficiency and, above all, what the literature says about supplementation.
Why does it matter? Because NAD+ sits at the heart of ATP production, DNA repair and metabolic regulation. And because its levels fall with age, oxidative stress and certain chronic conditions.
So when, how, and in which patients should you consider supporting it? That’s what this article sets out to cover, concisely and practically.
The key functions of NAD+: what you may already be seeing in the clinic
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 profiles with silent inflammation.
Function Role of NAD+ Clinical implications Energy production (ATP) Electron transporter essential to glycolysis, beta-oxidation and the respiratory chain Chronic fatigue, reduced exercise tolerance, slow recovery DNA repair (PARP) ADP-ribose donor that activates the PARP enzymes which repair DNA breaks Vulnerability to oxidative stress, cellular ageing, accumulation of DNA damage Regulation of gene expression (sirtuins) Cofactor for sirtuins, involved in histone deacetylation and epigenetic regulation Low-grade inflammation, metabolic dysregulation, impaired autophagy Recycling and loss with age Recycled via nicotinamide, but degraded by PARPs, 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’s a problem)
With age, the body gradually loses its ability to maintain an optimal NAD+ level. Three main mechanisms explain this decline:
1. Reduced synthesis
Endogenous production of NAD+ from tryptophan or vitamin B3 becomes less efficient with age. The result: less raw material available to replenish cellular stores.
2. Overconsumption
The enzymes that use NAD+ (notably PARPs and sirtuins) become more active with oxidative stress, DNA damage or low-grade inflammation. CD38, an enzyme that degrades 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, such as muscle, brain and liver.
A chronic decline in 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 may 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’s pointless)
When it comes to NAD+ supplementation, the first thing to know is that… NAD+ itself doesn’t work. Why? Because it isn’t absorbed orally: it is broken down in the gut and never reaches the target cells.
Certain precursors, on the other hand, cross the digestive barrier, enter the cell, and are efficiently converted into NAD+.
The three main metabolic pathways of NAD+
Pathway Precursor Note "de novo" pathway Tryptophan Mainly active in the liver. Not very effective at raising NAD+ in practice Main pathway (salvage pathway) Nicotinamide (= B3) Well tolerated, inexpensive, but requires several conversion steps Fast, direct pathway NR (nicotinamide riboside), NMN (nicotinamide mononucleotide) Highly bioavailable, with demonstrated effects on NAD+ levels
In clinical practice:
- Nicotinamide is useful for prevention, but soon reaches its limits.
- The direct precursors NR and NMN are the most studied in supplementation: they allow a rapid increase in intracellular NAD+ levels, including in hard-to-reach tissues such as the brain.
- Studies show measurable effects from as little as 250 to 1000 mg per day, depending on the patient’s profile (age, weight, associated conditions).
What to avoid:
- Supplementing directly with NAD+
- Assuming diet alone is enough: dietary intake of NR and NMN is negligible (less than 1 mg/100 g)
When should you consider supporting NAD+? Practical clinical applications
Clinical indication Profiles to look out for Recommended precursor Observed benefits Cellular ageing & chronic fatigue Persistent fatigue, slow recovery, patients > 50 years NMN or NR (500 to 1000 mg/day) Mitochondrial support, reduced senescence Neurology & neuroprotection Cognitive trouble, Parkinson’s terrain, cerebral oxidative stress NR (1 g/day) ↑ cerebral NAD, ↓ inflammation, activation of protective genes Physical performance & recovery Fatigued athletes, active seniors, post-COVID recovery NMN (300 to 1200 mg/day) ↑ endurance, better muscle recovery Metabolic & cardiovascular health Mildly hypertensive, overweight subjects, metabolic syndrome NR (1 g/day) ↓ blood pressure, ↑ endothelial function Insulin sensitivity & prediabetes Overweight menopausal women, insulin resistance NMN (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 applied.
In summary: NAD+, a lever worth knowing and personalising
Declining NAD+ is a key mechanism to factor into many clinical presentations: persistent fatigue, insulin resistance, poor recovery, signs of cellular senescence…
The 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 and physical performance.
Would you like to bring these protocols into your practice, or structure your recommendations on a single interface? Do get in touch with us!
