Temporal and Dose-response Effects of Nicotinamide Riboside Supplementation on Metabolic Flexibility During Zone 2 Training in Adults: a Double-blinded, Randomized, Controlled, Crossover Trial

Zone 2 training, a low-intensity endurance exercise performed at approximately 66-80% of VO₂max or near the first ventilatory threshold, has gained popularity for improving aerobic capacity, fat metabolism, and mitochondrial efficiency. It preserves glycogen stores and delays fatigue, making it an essential training method for both athletes and recreational exercisers. Nicotinamide adenine dinucleotide (NAD) is a vital metabolite that regulates cellular energy metabolism and redox homeostasis. It participates in oxidative reactions within the tricarboxylic acid cycle and electron transport chain, sustaining ATP synthesis and mitochondrial efficiency. Exercise influences multiple pathways of NAD metabolism, altering the NAD⁺/NADH ratio and thereby affecting energy production and fatigue resistance. Studies have shown that both aerobic exercise and NAD precursor supplementation (e.g., nicotinamide riboside [NR]) can elevate body NAD levels and enhance mitochondrial function, though findings remain inconsistent due to variations in dosage and participants' characteristics. This study aims to investigate how acute NR supplementation interacts with Zone 2 cycling training in adults. Specifically, it examines the temporal and dose-dependent effects of NR supplementation on metabolic flexibility and exercise performance. The results may clarify the potential synergistic benefits of combining NAD supplementation with low-intensity endurance training to improve aerobic adaptability.