NMN administration in overweight or obese, middle-aged and older adults safely increased circulating NAD levels, and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure.

Although future studies are required to better clarify the potential of targeting NAD+ homeostasis, the strategies based on administering NAD+ precursors or inhibiting NAD+-dependent enzymes seem to be an attractive approach for reducing chronic low-grade inflammation, enhancing mitochondrial biogenesis, and improving oxidative metabolism in vascular cells.

NR supplementation holds a promising therapeutic potential for myocardial infarction-induced acute kidney injury

...Recent studies have expanded on the role of circadian rhythms and the core clock factors that maintain them in the regulation of NAD+ levels in the heart. This has revealed that NAD+ pools and their use are tightly linked to cardiac function, but also heart failure. The convergence of these fields, namely, clock regulation, heart disease, and NAD+ metabolism present a complex network ripe with potential scientific and clinical discoveries, given the growing number of animal models, recently developed technology, and opportunity for safe and accessible precursor supplementation...

Increasing NAD+ levels with nicotinamide riboside can alleviate the exercise intolerance associated to ANT1-deficiency, indicating the therapeutic potential of NAD+-stimulating compounds in mitochondrial myopathies.

NAD+ repletion can delay several hallmarks of aging and suppress the deterioration of age-related diseases[95]. This suggests a significant potential for the treatment of cardiac diseases in the elderly population with supplementation of NAD+ precursors. Indeed, the dietary intake of NAM could reduce cardiac hypertrophy and diastolic dysfunction in aged mice

The mitochondrial dysfunction characteristic of heart failure (HF) is associated with changes in intracellular nicotinamide adenine dinucleotide (NAD+) and NADH levels. Raising NAD+ levels with the NAD+ precursor, nicotinamide riboside (NR), may represent a novel HF treatment. In this 30-participant trial of patients with clinically stable HF with reduced ejection fraction, NR, at a dose of 1,000 mg twice daily, appeared to be safe and well tolerated, and approximately doubled whole blood NAD+ levels...

Here, we show that supplementation with the NAD+ precursor NR as a dietary supplement improves heart function and extends the lifespan of female mice lacking cardiac REV-ERBs. Thus, boosting NAD+ levels can improve cardiac function in a setting of heart failure caused by disruption of circadian clock factors, providing new insights into the links between the circadian clock, energy metabolism, and cardiac function.

Compelling evidence suggests that NAD+ homeostasis is required for normal cardiovascular function. Numerous studies suggest that declining NAD+ concomitant with mitochondrial dysfunction is a common trait in myocardial and cardiovascular diseases...Except for NA, which causes some adverse clinical outcomes, vitamin B3 intermediates have been demonstrated to be safe and to have promising beneficial effects in combating cardiovascular diseases in vivo...

This study not only demonstrates nicotinamide as a useful factor for cardiomyocyte production in regenerative medicine, but also implicates that nicotinamide could have a profound impact on embryogenesis if it is prescribed during pregnancy.

Clinical trials with various NAD+ precursors such as Trp, NA, or NR showed that increasing NAD+ levels is associated with reduced risk of developing CVD, lowers blood pressure and improves hypocholesteremia, enhances cardiac mitochondrial function and decreases aortic stiffness

...We tested whether oral NR could correct the NAD+ deficiency and improve mitochondrial function in Heart failure with preserved ejection fraction (HFpEF). Remarkably, after full development of HFpEF (5 weeks of HFD+L-NAME), 8 weeks of NR supplementation ameliorated NAD+ deficiency and reversed hyperacetylation of VLCAD in animals maintained on HFpEF treatment...We have discovered that oral NR effectively corrected cardiac NAD+ deficiency, reversed the hyperacetylation status of key FAO enzymes, and improved mitochondrial function in our murine HFpEF model. This correlated with remarkable attenuation of left ventricular hypertrophy and diastolic dysfunction and dramatic improvement of HFpEF functional manifestations, suggesting that NR could potentially emerge as a promising therapeutic agent for HFpEF. It is worth emphasizing that restoration of all these parameters occurred in the continued presence of the HFpEF-triggering comorbidities of mechanical and metabolic stress.

...NAD+ protects against metabolic syndrome, heart failure, ischemia-reperfusion (IR) injury, arrhythmia and hypertension. Accordingly, the subsequent loss of NAD+ in aging or during stress results in altered metabolic status and potentially increased disease susceptibility. Therefore, it is essential to maintain NAD+ or reduce loss in the heart. This review focuses on the involvement of NAD+ in the pathogenesis of cardiovascular disease and explores the effects of NAD+ boosting strategies in cardiovascular health.

This is the first study to report effects of nicotinamide riboside on cardiac oxidative stress in an obesity model. Nicotinamide riboside, a natural dietary compound, presented antiobesity effects and cardiometabolic benefits, in addition to positively modulating oxidative stress in the heart, in a state-dependent manner.

While mitochondria play an important role in innate immunity, the relationship between mitochondrial dysfunction and inflammation in heart failure is poorly understood. In this study we aimed to investigate the mechanistic link between mitochondrial dysfunction and inflammatory activation in peripheral blood mononuclear cells (PBMCs), and the potential antiinflammatory effect of boosting the NAD level. ...Oral nicotinamide riboside (NR) administration enhanced PBMC respiration and reduced proinflammatory cytokine gene expression in 4 subjects with heart failure. These findings suggest that systemic inflammation in patients with heart failure is causally linked to mitochondrial function of the PBMCs. Increasing NAD levels may have the potential to improve mitochondrial respiration and attenuate proinflammatory activation of PBMCs in heart failure.

NMN and NR modulate intracellular NAD content in endothelium, inhibit endothelial inflammation and improve NO-dependent function by CD73-dependent and independent pathways, respectively. Extracellular conversion of NMN to NR by CD73 localized in the luminal surface of endothelial cells represent important vasoprotective mechanisms to maintain intracellular NAD.

These findings provide substantial evidence for a direct role of NAD+ in regulating the electrical activity of the heart through modulation of NaV1.5.

Hypertension is a leading cause of cerebral small vessel disease (CSVD). Currently, treatments for CSVD are limited. Nicotinamide riboside (NR) can protect against vascular injury and cognitive impairment in neurodegenerative diseases. In this study, the protective effects of NR against angiotensin - (Ang -)–induced CSVD were evaluated...Our results indicated that NR administration alleviated Ang -–induced CSVD by protecting BBB integrity, vascular remodeling, neuroinflammation, and white matter injury (WMI)–associated cognitive impairment.

One week of NR supplementation was well tolerated in all participants but had no effect on postprandial oxidative stress and microvascular function.

Endothelial-to-mesenchymal transition (EndMT) plays an important role in the progression of cardiac fibrosis but its mechanism and treatment need to be further understood. Herein, we have found that...NAD + precursor nicotinamide riboside (NR) could attenuate TGF-β1-induced EndMT and improve the levels of mtUPR. Significantly, prohibitin proteins (PHB and PHB2) was also regulated by nicotinamide riboside...In conclusion, our results indicate that nicotinamide riboside improved the expression of prohibitin proteins to ameliorate EndMT via promotion of mtUPR. Nicotinamide riboside is a potential therapeutic target for cardiac fibrosis.