NAD+ vs SS-31

NAD+ is a coenzyme central to cellular energy metabolism, serving as an electron carrier in glycolysis, the citric acid cycle, and oxidative phosphorylation. It is also a required substrate for sirtuins (SIRT1–7) and PARP enzymes, which regulate DNA repair, gene expression, and mitochondrial biogenesis. NAD+ levels decline measurably with age; IV or subcutaneous delivery aims to restore intracellular pools more directly than oral precursors such as NMN or NR.

NAD+ (nicotinamide adenine dinucleotide) is a coenzyme found in every cell, central to energy production, DNA repair, and sirtuin activation. While not a peptide in the traditional sense, it is widely administered by functional medicine and longevity providers via intravenous infusion or subcutaneous injection. Research interest centres on its role in mitochondrial health, cellular resilience, and neurological function as NAD+ levels decline with age. NAD+ IV therapy: intravenous NAD+ infusion is the administration route that has attracted the most clinical interest, particularly in longevity and functional medicine contexts. IV NAD+ therapy delivers the compound directly into the bloodstream, bypassing digestive absorption — a route considered relevant given that oral NAD+ precursors (NMN, NR) have variable bioavailability. NAD+ IV therapy cost typically ranges from $200–$1,000 per session depending on the clinic, infusion volume, and geographic market; treatment frequency in clinical settings commonly ranges from weekly to monthly maintenance infusions following an initial loading protocol. NAD+ IV therapy clinics operate across major US markets including Houston, Los Angeles, New York, and Las Vegas. For those researching where to find NAD+ IV therapy providers, PeptideBase maintains a directory of verified clinics and telehealth platforms offering NAD+ protocols.

Targets cardiolipin in inner mitochondrial membrane; stabilizes cristae structure; enhances electron transport chain efficiency; reduces mitochondrial ROS

SS-31 (elamipretide; Szeto-Schiller peptide 31; MTP-131; bendavia) is a synthetic cardiolipin-targeting tetrapeptide that selectively concentrates in the inner mitochondrial membrane through electrostatic interaction with cardiolipin, where it stabilizes cristae ultrastructure, preserves electron transport chain assembly, and reduces mitochondrial reactive oxygen species production to protect against ischemic and metabolic mitochondrial injury. By binding cardiolipin at the inner mitochondrial membrane, SS-31 maintains the protein-lipid interactions required for efficient electron transport chain supercomplex formation, preserving cytochrome c association with complexes I–IV, reducing electron leak, and sustaining the proton gradient required for ATP synthase activity — thereby protecting energy production in cardiomyocytes, neurons, and renal tubular cells under ischemic or oxidative stress. A randomized, placebo-controlled trial published in Circulation Heart Failure demonstrated that elamipretide improved cardiac function in patients with heart failure with reduced ejection fraction, and a Phase 2a trial published in Circulation Cardiovascular Interventions provided additional human evidence of mitochondrial protection in the context of renal artery stenosis revascularization. Elamipretide has not received FDA approval; it has received rare pediatric disease designation for Barth syndrome and has been studied in multiple Phase 2 trials including heart failure, primary mitochondrial myopathy, and geographic atrophy, with ongoing Phase 3 development programs as of 2025.