NAD+ Therapy: Energy, DNA Repair, Sirtuins

NAD+ is in every cell of your body right now. It's involved in over 500 enzymatic reactions. Without it, your mitochondria can't produce energy, your DNA repair enzymes can't function, and your sirtuins (the proteins most longevity researchers obsess over) shut down.

And your levels are dropping every year.

What NAD+ does

Three core jobs:

Energy production. NAD+ is an electron carrier in glycolysis, the citric acid cycle, and oxidative phosphorylation. These are the pathways that turn food into ATP (usable energy). When NAD+ drops, these pathways slow down. You feel it as fatigue that sleep doesn't fix.

DNA repair. PARP enzymes repair single-strand DNA breaks. They consume NAD+ as fuel. When NAD+ is scarce, DNA damage accumulates. Unrepaired DNA damage is a hallmark of aging and a contributor to age-related disease.

Sirtuin activation. Sirtuins (SIRT1-7) are NAD+-dependent enzymes that regulate gene expression, inflammation, stress response, and mitochondrial biogenesis. SIRT1 alone deacetylates over 50 targets involved in metabolism, circadian rhythm, and cell survival. No NAD+, no sirtuin activity.

Why levels decline

Between ages 40 and 60, NAD+ levels can drop by about 50% (Massudi et al., PLoS ONE, 2012). Several factors drive this:

• CD38 enzyme activity increases with age. CD38 is the primary NAD+ consumer in aging tissue, and it accelerates during chronic inflammation.
• NAD+ biosynthetic pathways slow down.
• DNA damage accumulates, requiring more PARP activity, which depletes the NAD+ pool further.

It's a downward spiral. Less NAD+ means worse repair means more damage means even less NAD+.

What the research shows

Gomes et al. (Cell, 2013) gave NAD+ precursors to aged mice. Mitochondrial function in their muscles reverted to levels seen in young mice within one week. One week.

Zhang et al. (Science, 2016) showed NAD+ supplementation improved DNA repair capacity and extended lifespan in mice with DNA repair deficiencies. The PARP activity increase was measurable within days.

Neurological data is earlier stage but interesting. Mills et al. (Cell Metabolism, 2016) found NAD+ supplementation improved cognition and neuronal function in aging mice. The brain's extreme metabolic demand makes it especially sensitive to NAD+ availability.

Metabolic markers improved too: better insulin sensitivity, healthier lipid profiles, improved body composition in animal models. Human clinical trials are ongoing but the preclinical picture is consistent.

Vial or pen?

[[NAD+|14]] comes in a 500mg vial. Reconstitute with bacteriostatic water, draw your dose with an insulin syringe, inject subcutaneously. Gives you full flexibility on concentration and dosing increments.

[[NAD+ Pen|35]] is a pre-filled 500mg pen. No reconstitution, no math. Dial the dose, attach a needle, inject. Takes 30 seconds. Better for travel, better if you don't want to deal with vials.

Same compound, same amount. The choice is convenience vs. flexibility.

Storage

Both formats: refrigerate at 2-8°C. Don't freeze reconstituted vials. Pen goes in the fridge door. Standard peptide rules. After reconstituting a vial, use within 90 days.

Who this is for

If you're over 35-40 and noticing fatigue that isn't explained by sleep or training. If cognitive sharpness has dipped. If recovery between workouts takes longer than it used to. NAD+ addresses the metabolic root of these changes.

Check out [[NAD+|14]] (vial) or [[NAD+ Pen|35]] (pen). If you need help choosing a format or building it into a broader protocol, reach out to us.

This article is for educational purposes. Peptides are intended for research use. Consult a healthcare professional before starting any protocol.