The Difference Between NAD+ Precursors and NAD+ Boosters

Nicotinamide adenine dinucleotide, or NAD+, is a compound that is fundamental to our lives. Without NAD+, hundreds of life-giving reactions would not be able to take place. As a coenzyme, NAD+ helps other enzymes to function properly and carry out these reactions. Essentially, NAD+ is a vital molecule that every cell in our body needs—without it, we’d die instantly, and with declining levels, age-related conditions can develop. 

However, as it turns out, most people experience a drop in NAD+ activity as they age. Research has found that NAD+ levels can drop by as much as 50% between the ages of 40 and 60, with an additional decline upon reaching older age. Concurrent with this drop in NAD+ comes increases in signs of accelerated aging. Therefore, finding ways to support healthy NAD+ levels is critical to living a long and healthy life. 

If NAD+ is so crucial to our health, you may wonder why we can’t just supplement with NAD+ itself. Put simply, NAD+ in capsule form cannot easily cross over membrane barriers to enter cells—it would first have to be converted into another compound before it could be taken up by the cell and utilized. Fortunately, researchers have found that some compounds act as NAD+ precursors, NAD+ boosters, or both. 

NAD+ Precursors: NMN, NR, and More 

NAD+ precursors include the building blocks we need to synthesize NAD+ in the body. As the “N” in NAD+ is nicotinamide—a derivative of vitamin B3, niacin—you can imagine that other niacin-containing compounds are related to NAD+. 

The most well-known NAD+ precursors are nicotinamide mononucleotide (NMN), nicotinamide or niacinamide (NAM), nicotinamide riboside (NR) and niacin itself. While they work in different ways, they all participate in the NAD+ biosynthesis pathway. Known as the “NAD salvage pathway,” this internal recycling program produces NAD+ from unused forms of nicotinamide, including NMN and NR.  

Research across several species—including yeast, worms, flies and rodents—has shown that supplementing with NAD+ precursors like NMN and NR promotes various aspects of healthspan and lifespan. In humans, NMN and NR have been found to support aspects of cardiovascular, cellular and metabolic health. 

For example, clinical studies have reported that NMN improves blood sugar sensing in postmenopausal women, supports muscle function in older men, and increases aerobic capacity in athletes. Research with NR shows that this NAD+ precursor supports healthy metabolism and muscle function in older adults. 

NAD+ Boosters: From Apigenin to Trans-Resveratrol

While all NAD+ precursors are also NAD+ boosters, compounds that are NAD+ boosters are not always NAD+ precursors. 

In addition to NMN, NR, NAM and niacin, there are other molecules that enhance NAD+ synthesis in the body. These compounds typically act on specific enzymes that either support NAD+ synthesis or inhibit its degradation. 

There are three main classes of NAD+ boosters, including CD38 inhibitors, PARP inhibitors and sirtuin activators. 

CD38 Inhibitors

CD38 is an enzyme that activates immune cells to produce inflammatory compounds called cytokines. This process is a significant source of NAD+ consumption—so inhibiting CD38 can preserve NAD+ levels as we age.

Popular CD38 inhibitors include: 

• Quercetin: A flavonoid compound found in several fruits and vegetables, quercetin has been found to inhibit CD38 activity and support healthier inflammatory responses.  
• Apigenin: The active ingredient in chamomile, apigenin is thought to increase antioxidant activity and inhibit CD38 to support healthy aging.
• Luteolin: A flavonoid similar to quercetin, luteolin also inhibits CD38 activity to prevent NAD+ degradation.

PARP Inhibitors 

PARP1 is an enzyme that requires NAD+ to function and helps with DNA repair. PARP1 works as a multifunctional enzyme, repairing single-strand and double-strand breaks in DNA. While PARPs are necessary, the DNA damage that accumulates with age or disease uses more and more NAD+ to repair the damage.

PARP inhibitors can help to prevent this process from going into overdrive, although these compounds are typically marketed as pharmaceutical drugs.  

Sirtuin Activators

Sirtuins are a family of proteins nicknamed “longevity genes.” Involved in mitochondrial repair, reducing cellular senescence and slowing down the aging process, sirtuins are essential for health and longevity. 

Although sirtuins are dependent on NAD+ to function, compounds that activate sirtuins can also be recognized as NAD+ boosters, including: 

• Trans-resveratrol: Found in grapes and red wine, this bioavailable form of resveratrol activates sirtuins—especially SIRT1—to support cognitive and cardiovascular health.
• Fisetin: An antioxidant compound found in fruits such as strawberries and apples that  activates sirtuins and acts as a senolytic that clears senescent cells. 
• Pterostilbene: A potent sirtuin activator that promotes longevity by reducing oxidative stress and supporting brain health. 
• Quercetin: A flavonoid compound found in several fruits and vegetables, quercetin has been found to modulate sirtuin activity and support healthier inflammatory responses. 
• Curcumin: The active compound in turmeric, curcumin upregulates SIRT1 and supports several aspects of health, including cognitive, immune and cardiovascular health. 
• Berberine: Known to support healthy blood sugar levels, berberine also promotes healthy mitochondrial function by promoting SIRT3 activity. 

NAD+ Boosters and NAD+ Precursors: Which Are Best? 

NAD+ boosters and NAD+ precursors support different, albeit overlapping, actions in the body. Therefore, most can be used concurrently to best support healthy aging and longevity. Although you certainly don’t need to take all of these compounds, some work particularly well together.

Two compounds that support each other well are NMN and trans-resveratrol, which work together to boost NAD+ levels. There isn’t one best NAD+ precursor, as both NMN and NR have produced clinically meaningful results. 

Similarly, some NAD+ boosters overlap in functions—for example, quercetin activates sirtuins and inhibits CD38 activity. Although we still have plenty to learn about these compounds, picking one from each list could be a beneficial way to maintain or increase NAD+ levels—and with it, healthy aging and longevity. 

References: 

Elhassan YS, Kluckova K, Fletcher RS, et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Rep. 2019;28(7):1717-1728.e6. doi:10.1016/j.celrep.2019.07.043

Igarashi M, Nakagawa-Nagahama Y, Miura M, et al. Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men. NPJ Aging. 2022;8(1):5. Published 2022 May 1. doi:10.1038/s41514-022-00084-z

Iside C, Scafuro M, Nebbioso A, Altucci L. SIRT1 Activation by Natural Phytochemicals: An Overview. Front Pharmacol. 2020;11:1225. Published 2020 Aug 7. doi:10.3389/fphar.2020.01225

Radenkovic D, Reason, Verdin E. Clinical evidence for targeting nad therapeutically. Pharmaceuticals. 2020;13(9):247. doi:10.3390/ph13090247 

Ray Chaudhuri A, Nussenzweig A. The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat Rev Mol Cell Biol. 2017;18(10):610-621. doi:10.1038/nrm.2017.53

Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. doi:10.1126/science.abe9985