Clinical trials

Hypertension continues to pose a significant global health challenge, with rates of optimal blood pressure control remaining low - particularly in China, where fewer than 5% of individuals with hypertension achieve guideline-recommended targets. Age-associated endothelial dysfunction and arterial stiffness are recognized as the key contributors to the development of hypertension and the unique role of nicotinamide adenine dinucleotide (NAD) depletion in the pathogenesis of vascular dysfunction has been recently discovered. Treatment with nicotinamide riboside (NR), an NAD precursor, has shown promise in preliminary clinical trials for improving blood pressure and vascular health in at-risk populations. In parallel, aerobic exercise is a well-established non-pharmacologic intervention known to improve cardiovascular outcomes. Emerging studies suggest that exercise may modulate NAD biosynthesis pathways, pointing toward a synergistic potential when combined with NAD-boosting strategies. However, clinical data evaluating the combined effects of NR supplementation and aerobic exercise remain scarce. Our randomized, placebo-controlled, four-arm, parallel-group design seeks to address this gap. The investigators will investigate the independent and combined effects of 10-week NR supplementation and brisk walking on blood pressure and vascular health in post-menopausal women with elevated/stage I hypertension. This population is specifically targeted due to their heightened risk for vascular dysfunction post-menopause and the observed responsiveness to NR-based interventions in prior studies. The investigators believe the findings from this trial will provide insight into the feasibility, safety, and efficacy of combining NAD-boosting supplementation with structured exercise in a uniquely vulnerable and previously understudied population. The potential to identify a low-risk, non-pharmaceutical therapeutic approach holds strong implications for public health, particularly in aging women with early-stage hypertension.

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.