What is NAD+?

What is NAD+?

NAD+ (nicotinamide adenine dinucleotide) is a central redox coenzyme in cellular energy metabolism. It is supplied for research purposes in a pre-filled 1000 mg multi-dose pen.

It is studied in longevity and metabolism research for its role in mitochondrial function and the NAD+/NADH ratio. Research results vary with dose and protocol.

Mechanism of action

NAD+ is the coenzyme that accepts electrons in glycolysis, the Krebs cycle and fatty-acid oxidation, and is regenerated to NAD+ in the respiratory chain. Beyond that redox role it is the substrate for three families of enzymes that consume it: the sirtuins (regulators of mitochondrial function and gene expression), the PARPs (DNA repair) and CD38/CD157 (calcium signalling).

Cellular NAD+ concentrations fall with age in several tissues, partly through increased CD38 activity, and in animal models that decline is associated with mitochondrial dysfunction and loss of repair capacity. That is the basis of longevity research with NAD+ and with its precursors, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN).

Most human trials have been done with oral precursors. Direct subcutaneous or intravenous administration of NAD+, which is what a pen corresponds to, has far less literature: the published protocols come from clinics rather than controlled trials.

What the published research says

1. 1.
   Covarrubias et al., Nat Rev Mol Cell Biol, 2021PMID 33353981

   Review of NAD+ metabolism and its decline with age: synthesis, consumption by sirtuins, PARPs and CD38, and its relationship with the hallmarks of ageing.

2. 2.
   Martens et al., Nat Commun, 2018PMID 29599478

   Crossover trial in 24 middle-aged and older adults: 1 g/day of nicotinamide riboside for 6 weeks raised blood NAD+ by around 60% and was well tolerated.

3. 3.
   Yoshino et al., Science, 2021PMID 33888596

   Randomised placebo-controlled trial in postmenopausal women with prediabetes: 250 mg/day of NMN for 10 weeks improved skeletal-muscle insulin sensitivity.

4. 4.
   Yoshino et al., Cell Metab, 2018PMID 29249689

   Review of the biology of the NAD+ intermediates (NMN and NR) and of the results in animal models of ageing and metabolic disease.

What side effects does NAD+ have?

• Flushing is the most reported effect when large doses are given too quickly: injecting slowly noticeably reduces it.
• Mild, transient injection-site reactions.

How is NAD+ dosed?

There are two alternative regimens. Intermittent: 10–50 mg two or three times a week for the first 4 weeks, then 20–80 mg two or three times a week. Daily: 10–20 mg a day 5 days a week, then 20–30 mg a day. Pick one and stick to it, injecting slowly to limit flushing. The dial is marked at 20, 30, 40 and 50 mg and goes up to 200 mg a day; doses below or between the printed marks, 10 mg included, can also be set.

Storing the pen

Keep the pen between 2 and 8 °C, protected from light and never frozen. Unopened it has a 24-month shelf life; from the first puncture, 12 months. If no fridge is available it keeps for up to 30 days at room temperature, below 30 °C. Let it reach room temperature before giving a dose. The dial sets each dose directly in milligrams: there is no reconstitution, no bacteriostatic water and no volume calculation.

How do you get NAD+?

Body Pharm's NAD+ 1000 pen is a sealed, HPLC-verified device with a published certificate of analysis (CoA) and discreet delivery in Spain. It is sold exclusively for research purposes.

How much does NAD+ cost per month?

≈ 129 € per 1000 mg pen, which at a daily research dose of 20–30 mg covers about a month.

How it compares

Against MOTS-c, the other mitochondrial peptide in the catalogue, NAD+ acts as a substrate and cofactor rather than a signal: MOTS-c activates AMPK and mimics the metabolic signal of exercise, NAD+ replenishes the pool those pathways consume. In longevity research they are usually studied on the same sirtuin-mitochondria axis.

The most characteristic effect of subcutaneous administration is flushing when large doses are injected quickly; the clinic literature attributes it to the speed of administration rather than the total dose.

• How to dose NAD+
• What is MOTS-c?
• Peptides for longevity