Novel Oral LNAD+ Increases Intracellular NAD and Metabolic Flux Without Elevating Circulating NAD: Evidence from a Randomized Controlled Trial

ABSTRACT Declines in nicotinamide adenine dinucleotide (NAD+) are linked to mitochondrial dysfunction, genomic instability, and metabolic stress that accompany aging and associated processes. While precursor-based approaches elevate systemic NAD, their clinical translation can be constrained by biosynthetic bottlenecks and first-pass metabolism. RENEWAL-NAD+ ( ClinicalTrials.gov NCT07336836 ; retrospectively registered 01/04/2026) was a double-blind, randomized, placebo-controlled Phase 0/1b trial in healthy adults aged 45–75 years (60 randomized; primary analysis n=50) evaluating 5 days of oral LathMized™ NAD+ (LNAD+), a proprietary physiochemically modulated formulation designed to alter the supramolecular organization and solution behavior of NAD+ while preserving its native molecular structure. The primary endpoints were change in intracellular NAD (icNAD), measured in whole blood, and circulating NAD (cirNAD), measured in separated plasma, relative to baseline. At Day 6, icNAD increased by 53% versus placebo (p=5.48e −14 ; Hedges’ g=3.66), while cirNAD was unchanged (p=0.60), demonstrating compartment-selective intracellular NAD+ delivery. Plasma NAD catabolites increased substantially (1-methyl-nicotinamide, MeNAM p=5.39e −13 ; N1-methyl-2-pyridone-5-carboxamide, 2PY p=2.95e −16 ), consistent with engagement of downstream NAD metabolic flux. Exploratory analyses identified non-overlapping correlates for the two compartments (cirNAD tracking inflammatory and metabolic markers, icNAD tracking red blood cell indices and NAM). Treatment was very well tolerated: symptom incidence was comparable between groups (p=0.68), only one mild adverse event (nausea, Grade 1) occurred in the LNAD+ arm, and no secondary clinical laboratory, vital sign, wellbeing, or wearable-derived endpoint survived multiplicity correction. These data demonstrate rapid intracellular NAD augmentation after oral LNAD+ dosing with pharmacodynamic evidence of downstream metabolism, compartment-specific physiological signatures, and a favorable short-term safety profile.