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Cellular Energy / Mitochondrial Repair StackEvidence Grade: B (Both Compounds)

NAD+ + SS-31 Stack Protocol Guide

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.

Protocol Overview

Compounds
NAD+ + SS-31 (Elamipretide)
Category
Cellular Energy / Mitochondrial Repair
Mechanism
NAD+: sirtuin activation, PARP DNA repair, electron transport cofactor. SS-31: cardiolipin stabilization, ETC optimization, ROS reduction
Half-Life
NAD+ (IV): ~30-45 min | SS-31: ~4 hrs
Route
NAD+: IV infusion or SubQ | SS-31: SubQ
Frequency
NAD+: 1-3x/week | SS-31: 1x daily
Cycle Length
8-12 weeks

Synergy & Mechanism

NAD+ Mechanism

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 Synergy

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.

Combined Dosing Protocol

ProtocolCompound 1Compound 2TimingDuration
StandardNAD+ 250mg IV 1x/weekSS-31 5mg SubQ dailyWeekly IV + daily SubQ8 weeks
EnhancedNAD+ 500mg IV 2x/weekSS-31 10mg SubQ daily2x/week IV + daily SubQ8-12 weeks
SubQ OnlyNAD+ 100mg SubQ dailySS-31 5mg SubQ dailyBoth AM SubQ8-12 weeks

Reconstitution & Preparation

NAD+ Preparation

  • NAD+ for IV: pre-mixed infusion bags (250mg, 500mg)
  • NAD+ SubQ: vials for injection (100-200mg/mL)
  • IV infusion: 2-4 hour drip at clinic
  • SubQ: inject slowly, expect stinging

SS-31 Preparation

  • SS-31 vial: 5mg or 10mg lyophilized
  • 5mg vial + 1mL BAC water = 5mg/mL
  • 5mg dose = 100 units (full vial)
  • Refrigerate, use within 14 days

Stacking Schedule (AM/PM Timing)

AM Protocol

  • Morning: SS-31 5mg SubQ, abdomen
  • NAD+ IV days: Schedule clinic infusion
  • NAD+ SubQ: 100mg SubQ, different site
  • Can inject SS-31 and NAD+ SubQ sequentially

PM Protocol

  • No PM dosing typically required
  • NAD+ IV days: afternoon energy surge normal
  • Stay hydrated
  • Quality sleep supports mitochondrial repair

Expected Timeline

Week 1-2
NAD+ replenishes cellular stores. SS-31 concentrates in mitochondria. Early improvements in energy and clarity. NAD+ IV may cause temporary chest tightness.
Week 3-4
Sirtuin activation improving cellular repair. SS-31 optimizing ETC. Noticeable improvement in exercise recovery and stamina.
Week 5-8
Full mitochondrial restoration. Significant improvements in physical and cognitive energy. Skin quality improving.
Week 9-12
Sustained rejuvenation. Oxidative stress markers improving. Subjects report feeling years younger.

Side Effects & Monitoring

Common Side Effects

  • NAD+ IV: nausea, chest/abdominal pressure during infusion
  • NAD+ SubQ: injection site stinging (common, transient)
  • SS-31: injection site irritation (mild)
  • Flushing or warmth (NAD+)
  • Headache (first few treatments)

Precautions

  • NAD+ IV should be administered by professional
  • Slow infusion rate reduces side effects
  • SS-31 still in clinical trials for some indications
  • Monitor liver and kidney function
  • Start with lower NAD+ doses

Blood Work Recommendations

PanelMarkersTiming
Oxidative Stress8-OHdG, MDA, glutathione ratioBaseline, Week 8
MetabolicFasting glucose, lactate, pyruvateBaseline, Week 6
NAD+Intracellular NAD+ (specialized)Baseline, Week 8
BasicCBC, CMP, LFTsBaseline, Week 6

Oxidative stress markers (8-OHdG, MDA) should decrease with SS-31. Intracellular NAD+ testing confirms restoration. Lactate/pyruvate ratio reflects mitochondrial function.

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