The chemical NAD+ has been shown to have critical roles in health and lifespan in laboratory animals such as rats, flies, and roundworms.
NAD+-boosting molecules include metabolic precursors that stimulate NAD+ production and chemicals that impact particular enzymes to promote or inhibit NAD+ breakdown. The main distinctions between these NAD+ boosters are their impact on various tissues. One may enhance NAD+ levels in the liver while another may increase NAD+ levels in the skeletal muscle.
Given the tissue-specific effects of different NAD+ boosters, it is expected that utilizing them will result in a variety of physiological advantages. In order to get into further depth regarding these distinctions, the next section will provide a quick comparison of the various NAD+-boosting compounds available.
NAD+ precursors are the building elements needed by cells to manufacture the vital bioenergetic NAD+ molecule. This includes NAM, NA, NR, NAM and NMN. The molecules use the salvage route, which is the most common mechanism for cells to recycle NAD+ chemical components and synthesize NAD+. A number of research have demonstrated that supplementing with NAD+ precursors NMN or NR can benefit rats and possibly humans. Unlike NAM, NMN and NR do not cause flushing or nausea, nor do they block DNA repair and metabolism-promoting proteins such PARPs and sirtuins.
Clinical trials have demonstrated that ingesting this NAD+ precursor enhances insulin sensitivity in elderly women, muscular performance in older men, and oxygen utilization capacity in marathon runners. An NR investigation in humans found that it, too, may improve muscular performance by boosting metabolism and lowering the number of inflammatory chemicals in the muscles of elderly people, according to the results of the research.
Active Enzymes in the Synthesis of NAD+
An additional method of causing an increase in NAD+ levels is to directly activate the NAD+ biosynthesis enzymes. Among the proteins that slow down the rate of NAM to NAD+ conversion is NAMPT, which functions as a rate-limiting enzyme. In light of the fact that NAMPT levels fall with age, determining methods to stimulate its production and activation has emerged as a hot subject in the anti-aging community. At this point, just a few NAMPT activators have been discovered. One of them is known as P7C3, and it has been proven to have neuroprotective properties. Another is known as SBI-797812, and it has been shown to increase NAD+ levels in many mouse organs.
NAD+ Degradation Inhibitors
Another way to boost NAD+ levels in cells is to stop NAD+ breakdown. The enzyme CD38, which activates T cells to create inflammatory chemicals (cytokines), presumably consumes the most NAD+. Researchers utilize CD38 inhibitors like apigenin and 78c to stop it from using NAD+. Similarly, luteolinidin suppresses CD38 to avoid cardiac failure following ischemia.
The three groups of NAD+ boosters, which comprise precursors, molecules that stimulate NAD+ production, and chemicals that block NAD+ degradation, all have the potential to play a substantial role in enhancing health and increasing longevity.
Clinical Trials using NAD+ Boosters
Along the familiar ground, the NAD+ precursor that has been investigated the most in clinical trials is niacin, which improves blood cholesterol levels when ingested in dosages of more than a gram. Additionally, nicotinamide and niacin are being studied as potential therapies for acne, renal illness, Alzheimer’s disease, schizophrenia, diabetes, lung cancer, obesity, and liver disease. If niacin and nicotinamide are found to be beneficial in treating these conditions, more studies can be conducted to see whether NMN and NR increase these advantages. Which one is better? Check this research article.