NAD+ vs SS-31 (Elamipretide)

NAD+ is a coenzyme involved in cellular metabolism, mitochondrial function, DNA repair and stress-response signalling ¹. A 2026 systematic review of 113 studies (33 human, 80 rodent) found that in rodents (animal data) raising NAD+ was often associated with metabolic and functional changes, while in humans oral NR and NMN consistently raised NAD-related blood markers but had heterogeneous and often null effects on functional and metabolic outcomes ².

For NAD+ given directly by vein, the same review found no eligible outcome trials ². A pilot study in a small human cohort found that infused NAD+ was rapidly removed from plasma, with no rise in plasma NAD+ or its metabolites for the first 2 hours ³. A 2026 narrative review describes the human evidence for intravenous NAD+ as sparse, mainly small uncontrolled studies and case reports, and lists nausea, cramping, flushing and chest discomfort among reported effects ¹.

Elamipretide (SS-31) is a tetrapeptide that, in laboratory studies, associates with cardiolipin and binds lipid bilayers in the inner mitochondrial membrane ^10,11. Its FDA label describes it as a mitochondrial cardiolipin binder ⁶.

In humans, the FDA granted accelerated approval in September 2025 for Barth syndrome, based on improved knee extensor muscle strength as an intermediate endpoint ⁷. The label notes that in the 12-patient randomised crossover trial, elamipretide was not superior to placebo on its primary endpoints (6-minute walk and fatigue), and strength gains were seen only in the open-label extension ⁶. In the phase 3 MMPOWER-3 trial in 218 adults with primary mitochondrial myopathy, it did not meet its primary endpoints ⁸. A single-infusion trial in 36 patients with heart failure with reduced ejection fraction reported changes in left ventricular volumes at the highest dose ⁹.