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The NAD+ + SS-31 (Elamipretide) stack targets mitochondrial function from two complementary angles. NAD+ is an essential coenzyme that declines with age, fueling sirtuins, PARP DNA repair enzymes, and mitochondrial electron transport. SS-31 is a mitochondria-targeted peptide that concentrates 5000-fold within the inner mitochondrial membrane, stabilizing cardiolipin and optimizing electron transport chain efficiency while reducing reactive oxygen species. Together, NAD+ provides the fuel for mitochondrial enzymes while SS-31 repairs the machinery itself.
NAD+ is the master coenzyme that declines 50%+ by age 60. It fuels sirtuins (SIRT1-7) which regulate gene expression, DNA repair, and metabolism. It powers PARP enzymes for DNA damage repair. It is a critical cofactor in mitochondrial Complex I of the electron transport chain. Replenishing NAD+ restores these fundamental cellular processes.
SS-31 (Elamipretide) is a tetrapeptide that targets the inner mitochondrial membrane with extraordinary specificity. It stabilizes cardiolipin, a phospholipid essential for ETC complex assembly, and optimizes electron flow to reduce ROS production. While NAD+ provides the fuel, SS-31 repairs the engine. This combination addresses both the substrate and structural components of mitochondrial decline.
| Protocol | Compound 1 | Compound 2 | Timing | Duration |
|---|---|---|---|---|
| Standard | NAD+ 250mg IV 1x/week | SS-31 5mg SubQ daily | Weekly IV + daily SubQ | 8 weeks |
| Enhanced | NAD+ 500mg IV 2x/week | SS-31 10mg SubQ daily | 2x/week IV + daily SubQ | 8-12 weeks |
| SubQ Only | NAD+ 100mg SubQ daily | SS-31 5mg SubQ daily | Both AM SubQ | 8-12 weeks |
| Panel | Markers | Timing |
|---|---|---|
| Oxidative Stress | 8-OHdG, MDA, glutathione ratio | Baseline, Week 8 |
| Metabolic | Fasting glucose, lactate, pyruvate | Baseline, Week 6 |
| NAD+ | Intracellular NAD+ (specialized) | Baseline, Week 8 |
| Basic | CBC, CMP, LFTs | Baseline, Week 6 |
Oxidative stress markers (8-OHdG, MDA) should decrease with SS-31. Intracellular NAD+ testing confirms restoration. Lactate/pyruvate ratio reflects mitochondrial function.
SubQ has lower bioavailability but avoids clinic visits and IV side effects. SubQ 100-200mg daily can achieve similar steady-state levels as weekly IV, though it takes longer. Many prefer SubQ convenience.
SS-31 creates structural mitochondrial improvements lasting weeks to months. NAD+ levels decline within days of stopping. Most run periodic cycles (8-12 weeks on, 4 off).
NAD+ fuels mitochondrial enzymes and sirtuins but is limited if the machinery is damaged. SS-31 repairs the inner mitochondrial membrane by stabilizing cardiolipin and optimizing electron transport. NAD+ provides the fuel while SS-31 ensures the engine runs properly.
SubQ has lower bioavailability but avoids clinic visits and IV side effects. SubQ 100-200mg daily can achieve similar steady-state levels as weekly IV, though it takes longer. Many prefer SubQ convenience.
SS-31 creates structural mitochondrial improvements lasting weeks to months. NAD+ levels decline within days of stopping. Most run periodic cycles (8-12 weeks on, 4 off).
NAD+ fuels mitochondrial enzymes and sirtuins but is limited if the machinery is damaged. SS-31 repairs the inner mitochondrial membrane by stabilizing cardiolipin and optimizing electron transport. NAD+ provides the fuel while SS-31 ensures the engine runs properly.
SubQ has lower bioavailability but avoids clinic visits and IV side effects. SubQ 100-200mg daily can achieve similar steady-state levels as weekly IV, though it takes longer. Many prefer SubQ convenience.
SS-31 creates structural mitochondrial improvements lasting weeks to months. NAD+ levels decline within days of stopping. Most run periodic cycles (8-12 weeks on, 4 off).