NAD+ Peptide

NAD⁺, or Nicotinamide Adenine Dinucleotide, is an endogenous nucleotide widely recognised for its role in regulating fundamental biological processes such as metabolism, cellular energy production, and DNA repair. It is also proposed to function as a secondary messenger in calcium-dependent signalling pathways and may contribute to immune system regulation.(1)(2)

NAD⁺ is naturally synthesised within the body, primarily through the de novo pathway, which involves the conversion of the amino acid tryptophan via a series of enzymatic reactions. In addition to this pathway, researchers identify several key precursors involved in NAD⁺ synthesis, including tryptophan, nicotinamide, nicotinic acid, nicotinamide riboside, and nicotinamide mononucleotide.(3)

Once produced, NAD⁺ is suggested to participate in hundreds of enzymatic reactions and cellular processes that support metabolic function.(12) It primarily acts as a coenzyme in redox reactions, where it is converted into its reduced form, NADH. This conversion is central to energy metabolism and is involved in multiple biochemical pathways that sustain cellular activity.

Overview

Researchers have suggested that Nicotinamide Adenine Dinucleotide (NAD⁺) functions as a coenzyme, primarily interacting with three major classes of enzymes, including:

  • Deacetylase enzymes in the sirtuin class (SIRTs)

  • Poly ADP ribose polymerase (PARPs) enzymes, and

  • Cyclic ADP ribose synthetase (cADPRS)

  • Research suggests that each class of enzymes interacts with NAD+ in the following possible respects:

  • SIRTs may stimulate mitochondrial homeostasis, stem cell regeneration, loss of stem cells, and nerve degeneration.

  • PARPs, composed of 17 different enzymes, may act alongside NAD+ enzymes and synthesize poly ADP ribose polymers, which may lead to genome stability.

  • cADPRS include CD38 and CD157, which are considered to be key immunological cells. cADPRS appears to hydrolyze NAD+ and thereby may stimulate stem cell regeneration and DNA repair, which may be important for maintaining cell cycles.

Researchers suggest that these enzyme classes are NAD⁺-dependent, meaning their activity may rely on the availability of Nicotinamide Adenine Dinucleotide. As a result, it has been proposed that these enzymes may compete with one another for NAD⁺ within the cell, particularly when availability is limited.

For example, increased activity of sirtuins (SIRTs) may potentially reduce the availability of NAD⁺ for other enzymes such as poly(ADP-ribose) polymerases (PARPs), which are involved in DNA repair processes. This competition may, in theory, influence the balance of cellular functions and could contribute to suboptimal system performance if not properly regulated. Consequently, maintaining an appropriate balance between NAD⁺ availability and its utilisation by various enzymatic pathways is considered important for supporting optimal cellular activity and metabolic function.(5)

Chemical Makeup

  • Molecular Formula: C21H27N7O14P2

  • Molecular Weight: 663.43 g/mol

  • Other Known Titles: nicotinamide adenine dinucleotide

Research and Clinical Studies
NAD+ Peptide and Productive Aging

Researchers have identified two key intermediates in NAD⁺ metabolism: nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). These compounds have been studied for their potential role in supporting “productive ageing,” due to their involvement in NAD⁺ synthesis and cellular energy regulation.

In one study,(7) normal ageing mice were administered NMN over a 12-month period. Following the intervention, researchers suggested that NMN exposure may have enhanced NAD⁺ synthesis in these models. This was associated with a range of observed physiological effects, including reduced weight gain, increased energy metabolism, elevated physical activity levels, and improvements in lipid profiles. These findings indicate that NAD⁺ intermediates such as NMN may influence metabolic and age-related processes, although further research is required to fully understand their mechanisms and long-term effects.

NAD+ Peptide and Neurodegenerative Activity

Scientists have suggested that mitochondrial dysfunction may impair the electron transport chain and ATP production, potentially contributing to the development of neurodegenerative conditions. In one study,(8) aged mice were administered nicotinamide mononucleotide (NMN), an NAD⁺ intermediate, over a period ranging from 3 to 12 months to assess its potential impact on mitochondrial function.

The study focused on evaluating mitochondrial respiratory activity by examining oxygen consumption rates in nerve and brain cells following administration of a fluorescently labelled NMN compound. The findings suggested that mitochondrial function in aged mice appeared to improve, with restored respiratory activity observed. Researchers proposed that NMN may be readily utilised by cells to support NAD⁺ production, thereby contributing to enhanced mitochondrial performance and energy metabolism.

NAD+ Peptide and DNA Repair After Ischemic Stress

The primary objective of this study(11) was to evaluate the potential neuroprotective effects of Nicotinamide Adenine Dinucleotide (NAD⁺) under conditions of ischemic stress. In this experiment, ischemic stress was induced in neuronal cultures by depriving them of oxygen and glucose for approximately two hours. NAD⁺ was then introduced into the culture medium either before or after the stress event. After 72 hours, researchers reported that DNA base excision repair (BER) activity, overall cell viability, and oxidative DNA damage repair were significantly improved, regardless of whether NAD⁺ was administered prior to or following the ischemic insult.

NAD⁺ is considered essential for maintaining DNA integrity, particularly through its role as a cofactor for enzymes such as poly(ADP-ribose) polymerase (PARP). In response to DNA damage, PARP is believed to bind to affected DNA regions and utilise NAD⁺ to add ADP-ribose units in a process known as PARylation. This process may help recruit and activate additional DNA repair proteins, facilitating the repair of damaged DNA strands.(15) The formation of poly(ADP-ribose) (PAR) chains may also act as a signal for cellular repair systems to identify and address DNA damage, including single-strand breaks.

However, this repair process can consume significant amounts of NAD⁺, potentially depleting intracellular levels and affecting other NAD⁺-dependent functions such as energy metabolism and cellular signalling. Research has suggested that extensive DNA damage may trigger rapid PAR synthesis, leading to substantial NAD⁺ utilisation. This depletion may influence pathways such as the NAD⁺/SIRT1 axis, with potential downstream effects on mitochondrial function, reactive oxygen species (ROS) production, and overall cell survival.(16)

In this context, replenishment of NAD⁺ may help restore cellular balance, supporting DNA repair mechanisms and enhancing cell viability under conditions of metabolic or oxidative stress.

NAD+ Peptide and the Liver, Kidney

Upon administration of NAD⁺ in experimental murine models, resulting in restoration of Nicotinamide Adenine Dinucleotide levels toward normal ranges, researchers suggested that the peptide may exhibit beneficial effects in preventing obesity and alcoholic hepatitis, while also potentially improving glucose regulation and overall liver function.

In studies involving aged mice, supplementation with NAD⁺ in kidney cells appeared to enhance the activity of sirtuins (SIRTs), which was associated with a protective effect against glucose-induced kidney cell hypertrophy. Additionally, when nicotinamide mononucleotide (NMN), an NAD⁺ intermediate, was administered, it was suggested to provide a protective effect against cisplatin-induced kidney injury. These findings indicate a potential role for NAD⁺ and its intermediates in supporting metabolic function and cellular resilience under stress conditions.(12)

NAD+ Peptide and Skeletal Function

Following daily administration of nicotinamide mononucleotide (NMN) to aged murine models over a 7-day period, researchers suggested that the intervention may have led to increased ATP production, reduced inflammatory markers, and improved mitochondrial function.(13) These effects were proposed to be linked to the role of NAD⁺ in cellular respiration and energy metabolism.

NAD⁺ is considered a key cofactor in redox reactions, facilitating the conversion of nutrients into usable cellular energy. During glycolysis—the initial stage of glucose metabolism—NAD⁺ is thought to accept electrons and hydrogen ions, forming NADH. This conversion enables NADH to transport high-energy electrons to subsequent stages of energy production. As glucose is further metabolised in the citric acid (Krebs) cycle, NAD⁺ continues to participate in reactions that generate additional NADH molecules.

The NADH produced during glycolysis and the citric acid cycle is believed to deliver electrons to the electron transport chain within the mitochondria. Here, the transfer of electrons contributes to the formation of an electrochemical gradient across the mitochondrial membrane, driving proton movement and ultimately facilitating ATP generation through oxidative phosphorylation. During this process, NADH is converted back into NAD⁺, allowing it to be reused in ongoing metabolic cycles.

This continuous regeneration of NAD⁺ is considered essential for sustaining ATP production and maintaining cellular energy balance. The observed effects of NMN supplementation in aged models may therefore reflect enhanced efficiency of these metabolic pathways, contributing to improved mitochondrial performance and overall cellular function.(13)

NAD+ Peptide and Cardiac Functions

Researchers have suggested that a deficiency in Nicotinamide Adenine Dinucleotide (NAD⁺) may lead to reduced activity of sirtuins (SIRTs), which could in turn contribute to decreased energy production and vascular effects such as aortic constriction. In experimental models, when mice were administered nicotinamide mononucleotide (NMN) approximately 30 minutes prior to induced ischemia, the compound was reported to exhibit cardioprotective effects, potentially reducing the extent of ischemic injury.(14)

NAD+ peptide is available for research and laboratory purposes only. Please speak to our friendly research team to find out more and for sourcing options.

References:

  1. Schultz, Michael B, and David A Sinclair. "Why NAD(+) Declines during Aging: It's Destroyed." Cell metabolism vol. 23,6 (2016): 965-966.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088772/

  2. Braidy N, Liu Y. NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis. Exp Gerontol. 2020 Apr;132:110831. doi: 10.1016/j.exger.2020.110831.  https://pubmed.ncbi.nlm.nih.gov/31917996/

  3. Johnson, Sean, and Shin-Ichiro Imai. "NAD + biosynthesis, aging, and disease." F1000Research vol. 7 132. 1 Feb 2018.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795269/

  4. Bieganowski P, Brenner C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans. Cell. 2004 May 14;117(4):495-502.  https://pubmed.ncbi.nlm.nih.gov/15137942/

  5. Fang, E. F., Lautrup, S., Hou, Y., Demarest, T. G., Croteau, D. L., Mattson, M. P., & Bohr, V. A. (2017). NAD+ in Aging: Molecular Mechanisms and Translational Implications. Trends in molecular medicine, 23(10), 899–916.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494058/

  6. Harden, A; Young, WJ (24 October 1906). "The alcoholic ferment of yeast-juice Part II.--The coferment of yeast-juice". Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character. 78 (526): 369–375.  https://royalsocietypublishing.org/doi/10.1098/rspb.1906.0070

  7. Mills KF, Yoshida S, Stein LR, Grozio A, Kubota S, Sasaki Y, Redpath P, Migaud ME, Apte RS, Uchida K, Yoshino J, Imai SI. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab. 2016 Dec 13;24(6):795-806.  https://pubmed.ncbi.nlm.nih.gov/28068222/

  8. Long AN, Owens K, Schlappal AE, Kristian T, Fishman PS, Schuh RA. Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer's disease-relevant murine model. BMC Neurol. 2015 Mar 1;15:19.  https://pubmed.ncbi.nlm.nih.gov/25884176/

  9. Safety & Efficacy of Nicotinamide Riboside Supplementation for Improving Physiological Function in Middle-Aged and Older Adults.  https://clinicaltrials.gov/ct2/show/NCT02921659

  10. Braidy N, Liu Y. NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis. Exp Gerontol. 2020 Apr;132:110831.  https://pubmed.ncbi.nlm.nih.gov/31917996/

  11. Wang S, Xing Z, Vosler PS, Yin H, Li W, Zhang F, Signore AP, Stetler RA, Gao Y, Chen J. Cellular NAD replenishment confers marked neuroprotection against ischemic cell death: role of enhanced DNA repair. Stroke. 2008 Sep;39(9):2587-95.   https://pubmed.ncbi.nlm.nih.gov/18617666/

  12. Rajman, Luis et al. "Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence." Cell metabolism vol. 27,3 (2018): 529-547.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342515/

  13. Heer C, et al, Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity. Journal of Biological Chemistry. Volume 295, Issue 52, Dec 2020.  https://www.jbc.org/article/S0021-9258(17)50676-6/fulltext

  14. Mehmel, Mario et al. "Nicotinamide Riboside-The Current State of Research and Therapeutic Uses." Nutrients vol. 12,6 1616. 31 May. 2020, doi:10.3390/nu12061616  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352172/

  15. Leung A, Todorova T, Ando Y, Chang P. Poly(ADP-ribose) regulates post-transcriptional gene regulation in the cytoplasm. RNA Biol. 2012 May;9(5):542-8. doi: 10.4161/rna.19899. Epub 2012 May 1. PMID: 22531498; PMCID: PMC3495734.

  16. Croteau DL, Fang EF, Nilsen H, Bohr VA. NAD+ in DNA repair and mitochondrial maintenance. Cell Cycle. 2017 Mar 19;16(6):491-492. doi: 10.1080/15384101.2017.1285631. Epub 2017 Feb 1. PMID: 28145802; PMCID: PMC5384578.

Dr. Marinov

Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.

NAD+ Peptide