Protocol·Longevity·Intermediate·Reviewed June 9, 2026
NAD+ Optimization Protocol.
A precursor-driven stack designed to raise and sustain cellular NAD+ levels, which decline with age and underpin mitochondrial energy production and DNA repair. It pairs an NAD+ precursor with sirtuin-activating polyphenols and methyl-donor support to back the increased methylation demand of NAD+ turnover.
The nad+ optimization protocol in brief.
A quick summary. The full stack, with dose and timing for each supplement, is below.
The NAD+ Optimization Protocol is an intermediate stack of 5 supplements aimed at longevity: Nicotinamide Riboside, Trimethylglycine, Pterostilbene, Resveratrol, and Coenzyme Q10 Ubiquinol. 2 are core and the rest are optional add-ons, at roughly $70-130/mo. Each supplement below lists its dose, timing, role, and the evidence behind it.
What is in the nad+ optimization protocol.
Dose, timing, role, and evidence tier for each supplement. Core items carry the protocol; optional ones are situational. Open any name for the full profile.
| Supplement | Dose | Timing | Role | Evidence |
|---|---|---|---|---|
| Nicotinamide Riboside | 300-500 mg | Morning with food | Core | Moderate |
| Trimethylglycine | 500-1000 mg | Morning with food | Core | Emerging |
| Pterostilbene | 100-150 mg | Morning with food | Optional | Emerging |
| Resveratrol | 150-500 mg | Morning with food | Optional | Emerging |
| Coenzyme Q10 Ubiquinol | 100-200 mg | Morning with food | Optional | Moderate |
An NAD+ precursor that is efficiently converted to NAD+ via the salvage pathway; human trials show oral nicotinamide riboside reliably and dose-dependently raises whole-blood NAD+ levels, making it the anchor of the stack.
NAD+ precursor metabolism consumes methyl groups when excess nicotinamide is methylated and cleared; betaine (TMG) is a methyl donor that supports the methionine cycle, helping offset the methylation demand created by higher NAD+ turnover.
A methylated, more bioavailable analog of resveratrol that activates sirtuins (notably SIRT1), the NAD+-dependent deacetylases through which elevated NAD+ is thought to exert many of its benefits; commonly paired with NAD+ precursors in human trials.
A polyphenol that activates SIRT1, an NAD+-consuming enzyme, complementing the NAD+ precursor by promoting downstream sirtuin signaling linked to mitochondrial biogenesis and metabolic health.
An electron carrier in the mitochondrial respiratory chain whose function is intertwined with the NAD+/NADH redox couple; supplementation supports mitochondrial energy output, the cellular system that NAD+ optimization is ultimately meant to protect with age.
How the pieces combine.
The mechanistic rationale for stacking these together rather than taking them in isolation.
- Nicotinamide Riboside supplies the NAD+ precursor while Resveratrol and Pterostilbene activate the NAD+-dependent sirtuins, so raising substrate and downstream enzyme activity together is more rational than either alone.
- Trimethylglycine replenishes methyl groups consumed when surplus nicotinamide is methylated and excreted, buffering the methylation cost of sustained higher NAD+ turnover.
- Coenzyme Q10 Ubiquinol supports the mitochondrial electron transport chain that depends on the NAD+/NADH redox balance the precursor is meant to restore.
Cost and commitment.
A rough monthly cost and how involved the protocol is to run.
The evidence behind it.
Overview citations for this protocol. Each supplement's own profile carries its full source list.
- Rajman L, Chwalek K, Sinclair DA. Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell Metabolism. 2018.
- Covarrubias AJ, et al. NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology. 2021.
Common questions.
Quick answers drawn from the stack above.
What is in the NAD+ Optimization Protocol?
The NAD+ Optimization Protocol combines 5 supplements for longevity: Nicotinamide Riboside, Trimethylglycine, Pterostilbene, Resveratrol, and Coenzyme Q10 Ubiquinol. 2 are core; the rest are optional.
How much does the NAD+ Optimization Protocol cost?
NutriStack estimates the NAD+ Optimization Protocol at about $70-130/mo, depending on the forms and brands you choose and whether you run the optional add-ons.
Is the NAD+ Optimization Protocol backed by evidence?
Each supplement in the protocol carries its own evidence tier (0 rated strong here) and links to PubMed-cited sources. NutriStack does not rank or score brands and takes no manufacturer payments; this is an informational reference, not medical advice.
Build it in the app
Run the nad+ optimization protocol in NutriStack.
Add the stack to NutriStack to track timing, screen it for interactions, and see a Stack Score that updates as you tune it.