Overall, the findings discussed in this article suggest that NAD+ boosting is a promising therapeutic strategy for cardiovascular diseases. However, the choice of NAD+ precursor, their appropriate dosing and long-term effects in humans need to be critically evaluated and investigated. Long-term effect of these precursors could be tested in animal models at various doses to determine impact on molecular parameters such as DNA methylation, homocysteine metabolism and SARM1 activation. Exercise performance or physical activity should also be evaluated. In non-medicated, metabolically healthy obese individuals, NAD+ boosting for 12 weeks did not improve glucose tolerance even though in pre-clinical models of Type 2 diabetes, NAD+ precursor supplementation has been shown to be effective. This may suggest that a therapeutic benefit may only be achieved in conditions with metabolic dysfunction and a preventative benefit may require even longer or repeated treatment periods. Thus, such aspects need to be carefully considered for designing clinical trials.