AGE/DOSE calc
user-icon

A New, Multifaceted Approach to Increasing Cellular NAD+ Levels

British researchers designed a nutraceutical to maximize nicotinamide adenine dinucleotide (NAD+) levels that significantly lowers biological age.

By Bennett M. Sherman

Key Points:

  • The nutraceutical contains the NAD+ precursor nicotinamide as well as other ingredients meant to activate NAD+ synthesis enzymes and impede NAD+-degrading enzymes.
  • Not only did the newly-designed nutraceutical significantly increase blood NAD+, it also reduced biological age — an age assessment based on how well tissues and organs function— by about 1.26 years.
  • Moreover, the nutraceutical reduced levels of inflammatory proteins and increased blood levels of enzymes called sirtuins that control metabolism and DNA repair.

Multiple studies have shown that taking an NAD+ precursor increases blood NAD+ levels. Yet, aside from raising NAD+, there has been a lack of human trial-based evidence that NAD+-targeting supplements work against aging, even though some rodent studies suggest that they do.

Now, published in NPJ Aging, Ford and colleagues from Northumbria University in England show that using an approach that targets multiple aspects of NAD+ biosynthesis and breakdown increases blood NAD+. Not only that but their nutraceutical lowered biological age by about 1.26 years, reduced proinflammatory proteins, and increased metabolism- and DNA repair-regulating enzymes called sirtuins in the blood. Their data provide some of the first evidence that increasing NAD+ with such a combination of compounds positively influences pathways associated with aging in humans.

For reference, the notable compounds included in the nutraceutical were the NAD+ precursor nicotinamide, alpha lipoic acid, zinc, vitamin C, green tea extract, rutin, parsley leaf extract, and black pepper fruit extract. The nicotinamide provided the substrate for NAD+ synthesis, and alpha lipoic acid and rutin were included to activate the rate-limiting enzyme for NAD+ synthesis—referred to as NAMPT. Zinc and vitamin C are antioxidants that were added to support immune function. What’s more, green tea extract was included to tamp down the degradation of NAD+, and parsley leaf extract was used to inhibit the degradation of NAD+ via an enzyme called CD38. Furthermore, black pepper root extract was put in for preventing the oral degradation of all of the nutrients in the mixture.

The compounds contained in the nutraceutical target multiple NAD+ biosynthesis- and breakdown-related enzymes.
(Henderson et al., 2024 | NPJ Aging) The compounds contained in the nutraceutical target multiple NAD+ biosynthesis- and breakdown-related enzymes. Moving clockwise, rutin is believed to promote activation of the rate-limiting NAD+ synthesis enzyme, NAMPT; alpha lipoic acid promotes activation of AMPK to drive NAMPT activation; nicotinamide (NAM) serves as the NAD+ synthesis substrate; parsley extract inhibits NAD+ breakdown by impeding activation of the enzyme, CD38; and EGCG from green tea extract suppresses activation of the enzyme NNMT that also breaks down NAD+.

A Nutraceutical Targeting Multiple NAD+-Related Enzymes Lowers Biological Age

The British researchers enrolled participants between the ages of 21 and 72 to test whether their product increases blood NAD+. As expected, it did, with some variability between those who took the supplement. Moreover, the researchers did not find that the age of the participants had any effect on the degree to which the supplement increased blood NAD+ levels.

The nutraceutical targeting multiple enzymes related to NAD+ biosynthesis and breakdown significantly increased blood NAD+.
(Henderson et al., 2024 | NPJ Aging) The nutraceutical targeting multiple enzymes related to NAD+ biosynthesis and breakdown significantly increased blood NAD+. The average NAD+ increase with the supplement (NT; gold lines) was about 26.5% compared to those who did not take the nutraceutical (Placebo; black lines) in whole blood. As the lines representing NAD+ level changes show, those who took the supplement exhibited wide variability in increased whole blood NAD+.

Perhaps a more interesting finding was that the nutraceutical reduced biological age by an average of about 1.26 years. The research team measured biological age using a technique called GlycanAge that measures the attachment of sugars to antibodies.

The supplement targeting multiple NAD+-related enzymes lowered biological age by about 1.26 years.
(Henderson et al., 2024 | NPJ Aging) The supplement targeting multiple NAD+-related enzymes lowered biological age by about 1.26 years. Those who took the supplement (NT) exhibited an average biological age 1.26 years lower than those who did not take the supplement (Placebo) who had an average increase of about 0.36 years.

To assess how their nutraceutical affects other pathways associated with aging, the researchers measured markers of inflammation in the blood, such as levels of the protein interleukin-2 (IL-2) as well as pro-longevity enzymes called sirtuins. Inflammation is a well-known hallmark of aging, and supplementation was associated with reduced concentrations of the proinflammatory IL-2 protein in the blood. Supplementing was also associated with increased levels of a sirtuin called SIRT1, which is believed to play roles in regulating metabolism as well as DNA repair. In that sense, taking the nutraceutical was associated with positive effects on pathways related to aging.

Comparing the Newly Designed Supplement to NAD+ Precursors Used on Their Own

The study evaluated the degree to which targeting multiple NAD+-related enzymes could increase blood NAD+ levels. While the researchers found that supplementing with the mix of compounds for 28 days significantly boosted NAD+, they did not include tests of how taking their nutraceutical compares to simply taking an NAD+ precursor alone to increase blood NAD+ levels. It is unclear why the researchers did not compare the nutraceutical’s NAD+-boosting capabilities with other NAD+ precursors; however, this may have been cost prohibitive.

Previous studies using nicotinamide riboside (NR), an NAD+ precursor, found that taking it in doses of 300 mg per day confers a modest increase in blood NAD+, along the lines of 40% to 59% increases. In the current study, the increased blood NAD+ from the multi-enzyme targeting nutraceutical gave a range of about a 100% increase to no increase, with an average increase of about 26.5%. In that regard, there seemed to be no significant enhancement in boosting NAD+ with the newly designed nutraceutical compared to NR supplementation on its own.

This study from Ford and colleagues did provide evidence that their nutraceutical significantly lowers biological age. Along those lines, a quick search of the scientific literature did not show any other studies suggesting that using an NAD+ precursor lowers biological age. Whether Ford and colleagues’ results suggesting lowered biological age came from the effects of an NAD+ precursor or the combination with added compounds remains unclear. However, the possibility remains that the combination worked additively to lower biological age better than using an NAD+ precursor on its own.

Results from this study also showed that the nutraceutical lowers levels of the proinflammatory protein IL-2 and increases sirtuin levels in blood. These are effects that many aging researchers believe would work against aging. In that sense, this study provides some of the first evidence that targeting multiple NAD+ synthesis-related pathways with a combination of compounds lowers biological age, reduces age-driving inflammation, and increases pro-longevity sirtuin enzymes.

Model and Dosage

Model: Humans between the ages of 21 and 72

Dosage: Oral dosage of 500 mg of nicotinamide, 600 mg of alpha lipoic acid, 10 mg of zinc, 20 mg of vitamin C, and 2,110 mg of a botanical blend containing green tea extract, rutin, parsley leaf extract, and black pepper fruit daily for 28 days

Source

Henderson JD, Quigley SNZ, Chachra SS, Conlon N, Ford D. The use of a systems approach to increase NAD+ in human participants. NPJ Aging. 2024 Feb 1;10(1):7. doi: 10.1038/s41514-023-00134-0. PMID: 38302501; PMCID: PMC10834541.

References

López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023 Jan 19;186(2):243-278. doi: 10.1016/j.cell.2022.11.001. Epub 2023 Jan 3. PMID: 36599349.

comment Comments
To The Top