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NAD+, sirtuins and mitochondrial function sustain cellular energy and the processes associated with longevity. This guide brings together the clinical evidence on the ingredients that may support cellular vitality with age — and how they fit into the Pleniage portfolio.
From the age of 40, plasma levels of NAD+ (nicotinamide adenine dinucleotide) decline progressively, reaching a loss of up to 50% by the age of 60. NAD+ is an essential cofactor for more than 500 cellular reactions, including mitochondrial ATP production and the activity of sirtuins, regulatory proteins associated with longevity.
This decline is not theoretical: it translates into less sustained energy, slower recovery after exertion, and greater vulnerability to oxidative stress and the accumulation of DNA damage. Without sufficient NAD+, sirtuins are silenced — and with them, an important layer of the cellular maintenance system is lost.
The Pleniage approach to caring for cellular vitality combines bioavailable NAD+ precursors (Nicotinamide Riboside or NR) with complementary cofactors, in clinically studied doses. It is not a cure-all: it is metabolic support backed by science.
The most studied strategy in humans for supporting NAD+ levels is supplementation with precursors. Three levers concentrate the available clinical evidence.
Nicotinamide Riboside (NR). It is a form of vitamin B3 that acts as a direct precursor of NAD+ via the NRK enzyme. Human clinical trials have documented that oral supplementation with NR raises plasma NAD+ levels safely and sustainably (studies of up to 12 weeks at doses of 300-1000 mg/day). NR has a better tolerability profile than other forms of B3 (niacin, nicotinamide).
Sirtuin activation. Sirtuins (SIRT1-7) are a family of enzymes that regulate longevity processes: DNA repair, mitochondrial biogenesis, inflammatory control. Their activity depends on available NAD+. Restoring NAD+ via NR is one of the most documented approaches to reactivating sirtuin signalling.
Mitochondrial function. NAD+ is a cofactor in the mitochondrial respiratory chain — the system that produces ATP. The decline of NAD+ with age correlates with a decrease in mitochondrial efficiency. Studies on NR document improvements in markers of mitochondrial function over periods of 8-12 weeks.
Three ingredients with robust clinical evidence to support cellular vitality. Discover each complete profile.
Both fat- and water-soluble mitochondrial cofactor: it protects the respiratory chain from oxidative damage and has been studied in contexts of fatigue and metabolic function.
Essential cofactor for DNA replication, neuronal myelination and cellular energy. Active methylcobalamin form with high bioavailability.
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NAD+ is a cofactor that sirtuins need in order to regulate key longevity processes: DNA repair, mitochondrial biogenesis, inflammatory control. With age, plasma NAD+ levels decline progressively (up to 50% by the age of 60), and sirtuins lose activity. Restoring NAD+ via precursors such as NR is one of the most studied approaches in longevity research.
All are forms of vitamin B3, but their metabolic route differs. NR (nicotinamide riboside) is converted into NAD+ via the NRK enzyme with a good tolerability profile. NMN is an intermediate metabolite. Niacin activates the GPR109A receptor and produces skin flushing at therapeutic doses. Nicotinamide is an indirect precursor but at high doses can inhibit sirtuins. NR is the form with the most human clinical trials for supporting cellular NAD+.
The normalisation of plasma NAD+ levels is relatively quick after supplementation with NR (weeks). Subjective functional improvements (energy, recovery, mental clarity) usually appear between 4 and 12 weeks. Effects on objective markers of longevity require longer periods of use and are the subject of active clinical research.
For NR, there are human clinical trials showing that oral supplementation safely increases NAD+ levels in the blood. Its effects on longevity markers (telomeres, ageing biomarkers) are the subject of active research, with promising but inconclusive results. Supplements are metabolic support, not cure-alls — sleep, exercise, intermittent fasting and diet remain the foundation.
The safety profile of NR at the doses studied (300–1000 mg/day) is good in trials of up to 12 weeks. Adverse effects are mild and transient. For prolonged use, the prudent approach is to alternate cycles with 4-week breaks and to consult a healthcare professional, especially if you are taking chronic medication. NOT recommended during pregnancy or breastfeeding.
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