“We’ve designed a series of experiments to examine how NAD3 supplementation affects cellular-molecular phenomena, and our recent study is one of the first few published on the topic,” said Michael Roberts, PhD, co-author on the study and professor at Auburn University’s School of Kinesiology. “Our current emphasis is examining cellular aging markers in humans, cells, and other models given that the ingredients in NAD3 have shown promise in past rodent and cell culture research in this area.”
This second human study, published in the journal Physiologia, was supported by JUVN3 Holdings, an ingredient incubator specializing in human longevity. Researchers on the project include associates from the Center for Applied Health Sciences and epigenetic company TruDiagnostic.
‘NAD3 goes beyond NAD+’
NAD3 is a patent-pending complex of Wasabia japonica extract, theacrine, and copper (I) niacin chelate developed by JUV3 that proposes to slow down biological aging. It is billed as the first nutraceutical to demonstrate an improvement in nicotinamide adenine dinucleotide (NAD+) status without utilizing a precursor.
Instead, preliminary pre-clinical and human studies suggest that it upregulates enzymes that boost the conversion of NAD+ precursors such as niacin, niacinamide, nicotinamide riboside (NR) and/or NMN to NAD+, while also suppressing the activity of proteins that deplete and consume NAD+. A coenzyme found in all living cells, NAD+powers metabolic processes across multiple systems.
“NAD3 goes beyond NAD+ by coordinating the activation or repression of important longevity genes,” according to Compound Solutions, which holds the exclusive distribution rights for NAD3. “Cellular data of NAD3 suggests it may improve NAD+ status by supporting its synthesis and limiting its degradation, in addition to activating the downstream signaling pathways of longevity.”
Dr. Roberts explained that the first NAD3 study in humans showed significant improvements in blood lipids, including decreases in total cholesterol (-11.1%), LDL (-15.2%), and LDL:HDL ratio (-18.9%). It also found that NAD3 maintained peripheral blood mononuclear cell (PBMC) NAD+: NADH levels better than those seen in a placebo group. (PBMC are mostly immune cells like lymphocytes and monocytes linked to increased inflammation with aging, also known as “inflammaging”.)
“While encouraging, it didn’t provide clear direction for next-level experiments, so we were motivated to perform a more thorough screening approach,” he said.
This second human study drew data from most of the 28 participants (due to sample yield limitations) from the team’s original 12-week investigation, hypothesizing that changes in DNA methylation and/or mRNA expression patterns may be linked to the positive effects previously observed regarding the effects of NAD3 supplementation on PBMC NAD+: NADH levels.
“Regarding methylation status, the control group had more hyper- and hypomethylated DNA sites compared to the [NAD3 group],” Dr. Roberts said. “Again, there is a good bit of literature showing that dysregulation in DNA methylation is associated with aging. “
Other direct assays suggested that NAD3 supplementation maintains SIRT activity – which plays an important role in controlling gene expression, DNA repair, metabolism, oxidative stress response, mitochondrial function, and biogenesis – through the potential maintenance of NAD+: NADH levels.
“PBMC SIRT activity decreased in CTL participants but not in NAD3 participants, and values at 12 weeks trended higher in NAD3 participants,” the study found. “Interestingly, the pre- to post- changes in SIRT activity values significantly correlated with changes in PBMC NAD+: NADH values obtained from a previous investigation in these participants.”
The researchers acknowledged the preliminary nature of the results due to limited sample size in middle-aged adults but said that the findings will be used to inform future research.
“In sum, the omics-based approach we’ve taken in our PBMC study is elaborate, and the analyses is helping guide our future experiments; some of which will be human and cell culture work,” Dr. Roberts said. “Moreover, this study is a great first step in uncovering the age-related cellular and molecular mechanisms potentially affected by NAD3 supplementation, and we’re going to continue to investigate these leads.”
He previewed that the team is currently dissecting data to elucidate methylation events that occurred across specific genes and any associated implications.
Source: Physiologia 2023, 3(2), 233-246
“The Effects of a Multi-Ingredient Supplement Containing Wasabia Japonica Extract, Theacrine, and Copper (I) Niacin Chelate on Peripheral Blood Mononuclear Cell DNA Methylation, Transcriptomics, and Sirtuin Activity”
Authors: Michael D. Roberts et al.