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NAD+

○ Preclinical / Early Phase I
Nicotinamide Adenine Dinucleotide (Oxidized Form)
Also known as: NAD, NAD+ IV, Coenzyme I, beta-NAD+
Brand names: Tru Niagen (NR precursor), Elysium Basis (NR+PT precursor)
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Quick Summary

NAD+ is a coenzyme present in every cell, essential for mitochondrial ATP production via electron transport, DNA repair via PARP enzymes, and sirtuin deacetylase activation. Levels decline approximately 50% between age 20 and 60. Restored through IV therapy or oral precursors NMN and NR. A primary target in longevity and metabolic health research.

Metabolic & Mitochondrial Widely Studied
NAD+ (Nicotinamide Adenine Dinucleotide) is the oxidized form of the essential coenzyme NAD, present in every living cell. It is critical for mitochondrial energy production (as a hydrogen carrier in the electron transport chain), DNA repair (as PARP substrate), and cellular signaling via sirtuin deacetylases (SIRT1-7). NAD+ levels decline ~50% between age 20 and 60. Restoring NAD+ through IV therapy or oral precursors (NMN, NR) is a major anti-aging and metabolic health strategy.
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Storage Stability
Lyophilized
1-2 years (-20°C)
Reconstituted
N/A (oral)
Room temp
Stable (dry)

Mechanism of Action

Mitochondrial Energy Production

NAD+ accepts electrons from the citric acid cycle intermediates (NADH form), then donates them to Complex I of the electron transport chain. Without NAD+, mitochondria cannot efficiently produce ATP.

Sirtuin Activation

NAD+ is the obligate substrate for sirtuin deacetylases (SIRT1-7). Sirtuins regulate mitochondrial biogenesis (SIRT1 via PGC-1α), DNA repair (SIRT6), and metabolic homeostasis. Low NAD+ → low sirtuin activity → accelerated aging phenotypes.

PARP-Mediated DNA Repair

PARP enzymes consume NAD+ to add poly-ADP-ribose chains to DNA strand breaks, recruiting repair machinery. DNA damage (from oxidative stress, UV) depletes NAD+, a vicious cycle in aging cells.

CD38 Competition

CD38 (a major NAD+ consumer) increases with age and inflammation. CD38 competition is a key reason NAD+ declines with age beyond reduced biosynthesis.

Research Summary

Preclinical Longevity

NMN and NR supplementation in aged mice restores NAD+ levels, improves muscle function, reverses metabolic decline, and extends healthy lifespan in multiple studies.

IV NAD+ in Addiction Recovery

Off-label IV NAD+ (high-dose infusions 500-1,500 mg over 4-6 hours) is used in addiction clinics for withdrawal support, reporting improvements in energy, cognitive clarity, and craving reduction.

Human Phase I/II (NMN/NR)

Oral NMN (500 mg/day) and NR (300-1,000 mg/day) safely raise blood NAD+ levels in humans in multiple small RCTs. Functional outcomes in published trials are modest but consistent with NAD+ elevation.

Parkinson's & Neurodegeneration

Preclinical and small pilot data suggests NAD+ precursors may slow neurodegeneration through SIRT3/SIRT1 mitochondrial protection in dopaminergic neurons.

Research Protocols

IV Protocol

250-1,000 mg NAD+ in 500 mL saline infused over 2-4 hours. Faster infusion rate causes flushing, chest tightness, and GI discomfort. Must be given slowly. 3-5 days consecutively for "loading" series.

IM Protocol (Research Clinics)

100-500 mg IM daily for 10 days. Faster than IV but no rate control. Calculate draw volume carefully.

Oral Precursors

NMN 500 mg/day or NR 500 mg/day orally. Sublingual NMN may improve bioavailability. Take in the morning with food.

Storage & Handling

Lyophilized NAD+ powder: store at -20°C. Highly hygroscopic, keep sealed and dry. Reconstitute with sterile saline for IV. Use immediately after reconstitution. Do not store reconstituted solution. For IM use: reconstitute with sterile water or saline.


References

  • [1]Yoshino J, et al. "NAD+ and sirtuins in aging and disease." Trends Cell Biol, 2018.
  • [2]Rajman L, Chwalek K, Sinclair DA. "Therapeutic potential of NAD-boosting molecules." Cell Metab, 2018.
  • [3]Trammell SA, et al. "Nicotinamide riboside raises NAD+ in humans." Nat Commun, 2016.
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Source: peer-reviewed literature  ·  Domain: ascendpeptide.org
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