Understanding NAD+: The Essential Molecule for Life

What is NAD+ and why is it Crucial?

You may have heard about NAD+ therapy or NAD+-boosting dietary supplements. They have become quite the trend in anti-aging treatments. What is the theory behind their use?

To begin, here is a quick rundown on NAD+, which is the acronym for Nicotinamide Adenine Dinucleotide. NAD+ is a coenzyme that naturally exists throughout our bodies, in our mitochondria. The mitochondria, if you remember your high school science classes, are the powerhouses of the cell, and NAD+ plays a critical role as an energy shuttle in the mitochondria, specifically as a key factor in the electron transport chain, which is the major way in which we generate energy to fuel our bodies needs (muscle contraction, nerve function) throughout life. Further, NAD+ acts to help other critical enzymes in metabolism work correctly, and as a nutrient sensor. In short, NAD+ is a key player in cellular metabolism.

Key Roles in Energy Production and Cellular Health

NAD+ levels have been found to decrease with aging. And more so with disease states such as neurodegeneration, diabetes, and cancer. Therefore, it seems logical that boosting NAD+ levels could produce an anti-aging effect and potentially combat some forms of metabolic disease. Infusion IVs, intravenous injections of NAD+, or dietary supplementation with nicotinamide riboside or nicotinamide mononucleotide have all been attempted in an effort to boost NAD+ levels and improve health outcomes. Do they work?

The Benefits of Optimal NAD+ Levels for Health

NAD+ is great for mice

Mouse studies of NAD+ therapy have shown incredibly substantial results. Boosting NAD+ levels in mice has been found to provide a host of health benefits, including improved mitochondrial metabolism, improved muscle function, improved glucose and insulin metabolism, and cognitive health. If you have a pet mouse, I’d get them NAD+ supplements ASAP.

Human trials on NAD+ are less promising.

When it comes to NAD+, the distance between mouse and man is vast. While losses in NAD+ in aging and diseased humans have been well-documented, the available clinical trials on using NAD+ boosting supplements have shown less exciting results than those seen in mice.

A recent paper on the benefits of NAD+ for humans that was widely circulated on social media is a good example. While the paper does a great job accurately describing the theoretical benefits of NAD+, the (lack of) hard data supporting its use in humans is glossed over. In an appendix, accessible through a link in the main paper, the author provides data from specific clinical trials on humans. Of these 10, only three found statistically significant benefits following NAD+ supplementation.

Of the three positive findings, two studies found a reduction in proinflammatory cytokines, while one found “small but significant” improvements in body composition. Reductions in inflammatory cytokines and improvements in body composition are good findings, but when 7/10 cited works have null findings, the benefit of NAD+ supplementation on humans is less than clear. Also worth mentioning is that 1/10 studies found blood cholesterol (LDL) was a little worse following NAD+ supplementation. So, all told, more research on humans is needed before any clear recommendations on NAD+ supplementation can be confidently made.  

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