The Science Behind NatureNewborn® Triple-action NAD+ Supplement: Boost NAD+ and Activate Sirtuins

NatureNewborn® addresses the metabolic effects of aging at the cellular level by combining Nicotinamide Riboside Hydrogen Malate (NRHM), an NAD+ precursor, with two proprietary SIRTs activators. The formulation is designed to boost levels of NAD+, a key metabolite that universally declines with age, and synergistically activate the mitochondrial sirtuins, SIRTs, to support mitochondrial function and health.

Targeting Metabolic Aging with NAD+

Nicotinamide Adenine Dinucleotide (NAD+) is a crucial key metabolite whose levels are tightly regulated by the cell to tune and balance its metabolic reactions[1]. Effective regulation of these numerous metabolic reactions is vital for cell health, as it maintains homeostasis between energy production and usage. Notably, NAD+ levels decline as we age.

Direct NAD+ supplementation is not practical, as the molecule is too large to enter cells. Other NAD+ precursors must first undergo metabolic conversion into NR to successfully cross the cell membrane (refer to the graph below)[2]. This necessary additional conversion step may reduce their overall efficiency and effectiveness in boosting mitochondrial NAD+ levels.

NatureNewborn® delivers an immediate NAD+ precursor called NRHM (Nicotinamide Riboside Hydrogen Malate), a combination of NR and malate. This specific form is engineered for enhanced stability, improved tolerance, and potentially greater bioavailability than standard NR. NR stands out as one of the most efficient NAD+ precursors because it requires the fewest reaction steps and the least amount of energy for cellular conversion to NAD+ inside the cells.

Human Clinical Trials with NR ——Safety, Oral Bioavailability, and NAD+ Restoration

Among the available NAD+ precursors, Nicotinamide Riboside (NR) is notable for having the most extensive support from human clinical trials. These studies consistently demonstrate that dietary supplementation with NR is uniquely and orally bioavailable in the human body[3].

Specifically, a randomized, double-blind, placebo-controlled trial involving a six-week regimen of 1000 mg/day of NR supplementation reported no significant adverse events, confirming a favorable safety profile. Furthermore, independent research corroborated this finding, establishing that the 1000 mg/day dose of NR for six weeks is well-tolerated by healthy middle-aged and older adults, while simultaneously demonstrating its effectiveness in increasing blood cellular NAD+ concentrations [4].

Beyond blood, oral NR supplementation has shown positive effects on tissue levels. One study, for instance, demonstrated that oral NR supplementation successfully elevated the muscle NAD+ metabolome in aged participants [5]. This evidence suggests that orally supplemented NR is safe and well absorbed by body cells and actively works at the cellular level in tissues like muscle. Moreover, there is ongoing research exploring NR's positive effects on other critical systems, including the brain and cardiovascular health[6].

Grounded in scientific evidence, NatureNewborn is uniquely designed to address age-related metabolic shifts. By effectively increasing the crucial NAD+ levels that decline naturally with age, our product supports the restoration of metabolic balance and optimal cellular function.

The SIRTs Activation Pathway: Mitochondrial Protection Using Naturally Occurring Compounds

Sirtuins (SIRTs) are a family of seven proteins that function as NAD-dependent enzymes, playing a critical role in essential processes such as DNA repair, metabolism, and cellular stress responses[7]. Due to their regulatory nature, they are involved in a wide range of physiological functions, including cardiovascular protection, influencing longevity, and maintaining genome stability. Crucially, the activity of sirtuins is significantly impacted by NAD+ levels; however, they can also be modulated by other specific activators.

NatureNewborn takes a comprehensive approach by blending the naturally occurring compounds Calcium Alpha-Ketoglutarate (Ca-AKG) and Resveratrol, which are specifically designed to activate SIRTs via the FoXO and AMPK pathways. Published clinical studies have extensively validated the benefits of these two compounds for human health and longevity.

While most NAD+ supplements on the market focus solely on increasing NAD+ levels, they often fail to address the challenge of maintaining that elevated level longer in the cells. Recognizing this gap, NatureNewborn incorporates Ca-AKG, a metabolite known to increase the NAD+/NADH ratio. This action may help the NAD+ level to be stored and sustained longer at the cellular level. AKG is widely studied as a potent regulator for lifespan and healthspan[8], and has been shown to offer benefits such as protection against age-related bone loss, support for muscle maintenance, promotion of collagen production, and reduction of oxidative stress[9]. Since bone loss and muscle weakness are often underestimated yet profoundly affect the ability to live a vibrant, high-quality life, initiating proactive care is essential, especially if you are over 35.

Similarly, Resveratrol, a compound found in a wide variety of fruits, vegetables, and nuts, has been intensely studied. It possesses countless beneficial effects (e.g., antioxidant, anti-inflammatory, cardio- and neuroprotective, anticancer, and antidiabetic), achieved by targeting diverse cellular processes and enzymes[10].

Both NAD+ levels and the activity of mitochondrial sirtuins decline as we age. NatureNewborn combines the NAD+ precursor (NRHM) with Ca-AKG and Resveratrol to synergistically activate SIRTs, help maintain overall mitochondrial health, and promote optimal mitochondrial energy production and utilization.

SHOP 🛒  NAD+ Supplement 

Reference:

1. Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021 Feb;22(2):119-141. doi: 10.1038/s41580-020-00313-x. Epub 2020 Dec 22. PMID: 33353981; PMCID: PMC7963035.
2. Nikiforov, Andrey et al. Pathways and Subcellular Compartmentation of NAD Biosynthesis in Human Cells, Journal of Biological Chemistry, Volume 286, Issue 24, 21767 - 21778
3. Trammell, S. A. et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat. Commun. 7, 12948 (2016).
4. Martens CR, Denman BA, Mazzo MR, Armstrong ML, Reisdorph N, McQueen MB, Chonchol M, Seals DR. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018 Mar 29;9(1):1286. doi: 10.1038/s41467-018-03421-7. PMID: 29599478; PMCID: PMC5876407.
5. Elhassan, Yasir S., et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-Inflammatory Signatures. Cell Reports, vol. 28, no. 7, 13 Aug. 2019, pp. 1717-1728.e6
6. Braidy, Nady, and Yue Liu. Can Nicotinamide Riboside Protect against Cognitive Impairment? Current Opinion in Clinical Nutrition & Metabolic Care, vol. Publish Ahead of Print, 10 Sept. 2020,
7. Houtkooper, R., Pirinen, E. & Auwerx, J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol 13, 225–238 (2012).
8. Xu M, Zhang Q, Liu X, Lu L, Li Z. Impact of Alpha-Ketoglutarate on Skeletal Muscle Health and Exercise Performance: A Narrative Review. Nutrients. 2024 Nov 20;16(22):3968. doi: 10.3390/nu16223968. PMID: 39599754; PMCID: PMC11597751.
9. Saghi Hakimi Naeini, Laleh Mavaddatiyan, Zahra Rashid Kalkhoran, Soroush Taherkhani, Mahmood Talkhabi, Alpha-ketoglutarate as a potent regulator for lifespan and healthspan: Evidences and perspectives, Experimental Gerontology, Volume 175, 2023, 112154, ISSN 0531-5565
10. Anca Ungurianu, Anca Zanfirescu, Denisa Margină, Sirtuins, resveratrol and the intertwining cellular pathways connecting them, Ageing Research Reviews, Volume 88, 2023, 101936, ISSN 1568-1637