Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) potentially reverse blood vessel dysfunction. NR has better bioavailability than NMN, which requires conversion to NR through enzymes like CD73 to enter cells. NMN’s anti-inflammatory properties depend on the CD73 pathway, which is not the case for NR. NMN and NR counteract endothelial dysfunction caused by angiotensin II in mouse aortic rings. The role of CD73 in NAD+ metabolism and vascular disorders warrants more detailed study. Recent research spearheaded by Mateuszuka and the team has cast a spotlight on the promising effects of NAD+ precursors. The focus was explicitly on nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) in the fight against blood vessel dysfunction. The study unveils that these compounds enhance the intracellular NAD+ content within endothelial cells and significantly inhibit inflammation in these cells. This discovery pivots NAD+ supplement benefits to the forefront as potential vasoprotective agents. It has also opened new avenues in the preservation and maintenance of healthy endothelial function. Their dual action showcases a major leap in the present understanding of vascular protection. The findings have underscored the promise these NAD+ precursors hold in reversing detrimental changes within blood vessels that can lead to disease. Exploring the Bioavailability: NR vs. NMN in Vascular Protection To understand the crux of vascular protection, the study brought to light the differential bioavailability of NAD+ precursors. Nicotinamide riboside (NR) stands out with its superior bioavailability, being easily detectable in everyday dietary sources such as cow milk and yeast-containing products. Once ingested, NR is efficiently metabolised between the cells to nicotinamide mononucleotide (NMN), readying it for its vasoprotective role. On the other side of the spectrum is NMN, whose initial bioavailability is hindered by its molecular size. This makes NMN too large to diffuse through the cellular membranes of endothelial cells passively. The study underscores that NMN must undergo a critical transformation outside the cell: it is converted to NR by the action of the enzyme CD73 located on the cell surface or to nicotinamide (NA) via CD38. This conversion is a prerequisite for NMN to bolster the NAD+ synthesis inside endothelial cells, indispensable for its protective effects against vascular ailments. The research further illuminates the intricate metabolic pathways that govern the efficacy of these precursors. It showcases the paramountcy of enzymes like CD73 in the extracellular space, which orchestrates the conversion of NMN to NR. As a result, it enables NMN to circumvent its native bioavailability issues. The implications of this are profound, as the enzymatic activity of CD73 directly influences the vasoprotective outcomes of NMN administration. The NAD+ Meaning in Inflammation and the Endothelium As per recent research, NR and NMN are potent modulators of endothelial health. Both precursors are highlighted for their capacity to modulate intracellular NAD+ levels. These levels are crucial for cellular processes, including regulating inflammatory responses. The research indicates that to boost NAD levels, the administration of NR and NMN is needed. This administration can then inhibit key inflammatory pathways within endothelial cells. It’s also found that NMN exerts its anti-inflammatory action following conversion to NR via the surface enzyme CD73. This process responds to endothelial inflammation, as the study documents an upregulation of CD73 in inflamed endothelial cells. Furthermore, NMN supplement’s anti-inflammatory effects are comparable to NR’s, implying a shared end goal for both precursors. How NR and NMN Offer New Hope in Combating Vascular Dysfunction NR and NMN, as NAD+ precursors, help sustain endothelial function. The study’s experiments with cultured endothelial cells and aortic rings from mice provide compelling evidence of these precursors’ ability to prevent and reverse endothelial dysfunction. This dysfunction, often precipitated by factors like the vasoconstrictor angiotensin II, a known contributor to hypertension and atherosclerosis. The research demonstrates that NR and NMN can effectively counteract the endothelial impairment caused by such vasoconstrictors. Future Implications for NMN and NR Central to the study’s findings is the role of NMN and NR in mitigating endothelial inflammation, a common precursor to atherosclerosis and hypertension. The anti-inflammatory properties of these precursors contribute to their therapeutic potential. Their ability to maintain and enhance endothelial function signifies a major stride in vascular medicine, offering a preventative approach to vascular health. Further, the study’s observation is that the vasoprotective effects of NMN are lost in the absence of CD73. At the same time, NR remains effective and provides a critical differentiation between the two precursors. NMN and NR could mean a new era in vascular therapy, but side effects of NAD+ supplements are still under the microscope. Beyond the Lab: The Potential for NAD+ Precursors in Clinical Settings The groundbreaking study unveils the remarkable potential of NAD+ supplements as frontrunners in promoting vascular health. The research decisively illustrates that NMN, alongside NR (nicotinamide riboside), can reverse endothelial dysfunction. By augmenting the body’s NAD+ levels and using the enzyme CD73 to convert NMN to NR, NMN emerges as a powerhouse in combating inflammation and maintaining the robustness of blood vessels.