In the body, nrXPRO’s nicotinamide riboside (NR) is rapidly converted to NAD+. NAD+ is an amazing molecule deeply involved in the health of all the cells in your body. NAD+ is critical for DNA repair, inflammation and cellular health. As you age you lose the ability to make sufficient NAD+. You also lose NAD+ through smoking, alcohol, prescription medications, stress and lack of sleep. You need to recover your NAD+ for health aging.
- Supercharge your energy and your overall health for healthy aging
- Power your brain cells for enhanced cognitive performance
- Support your heart cells for cardiovascular resilience
- Keep your muscles working properly and increase your endurance
- Enhances your gut health through increased short chain fatty acid production
- Manage your daily stressors
nrXPRO is at the cutting edge of aging science and cellular therapy, professionally formulated to address the negative effects of aging with a breakthrough synthesis called RiboGEN®, which is 99%+ pure Nicotinamide Riboside Chloride (NR). Nicotinamide Riboside Chloride is highly bioavailable and contains 33% more active nicotinamide riboside than the malate form which is the other available form. And unlike other NR products, nrXPRO features only high-quality top-manufacturer delayed release vegan capsules which are clinically proven to resist stomach acids for targeted absorption in the small intestine, providing maximum bioavailability – this means it’s made available where it’s needed most.
nrXPRO is the new standard of NAD+ cellular therapy, proudly synthesized, encapsulated, bottled and made available in the USA. Every batch of NR is third-party tested to ensure professional-grade quality and purity. Our packaging includes BPA free ultraviolet glass for superior preservation, as well as FSC mix box material and soy-based inks to help protect forests, reduce deforestation and promote sustainable packaging practices.
The science of healthy aging and cellular therapy is clear: Cell health = Your health.
Take one (1) capsule daily, without food in the morning, or as directed by your healthcare professional. Consult your healthcare professional before taking any dietary supplement, if you are pregnant, nursing, or taking any medication. Keep out of reach of children.
Store in a cool, dry place away from direct sunlight. Do not use if tamper-evident packaging is broken or missing.
The Science behind Nicotinamide Riboside
nrXPRO contains ultra-pure Nicotinamide Riboside Chloride (NR). NR is rapidly converted to NAD+ in the body, thereby increasing levels of NAD+ in all cells. Here we’re going to explore the science to learn how nrXPRO’s NR is converted into NAD+, and we’re going to learn why NAD+ is so important for cellular health and healthy aging.
NR is rapidly converted into NAD+
You don’t want to consume NAD+ directly because it is a large, unstable molecule that cannot pass through your cell membranes into your cells. (1) The best way to increase levels of NAD+ in your cells is to consume NR. There are two forms of NR available. The first and best form is NRCl (nicotinamide riboside chloride) This is the form we use. The other form is NRMalate (nicotinamide riboside malate). The chloride form (our form) is highly bioavailable and is easily and rapidly utilized by the body (see below). But also, a 300 mg dose of nrXPRO contains about 263 mg of useful nicotinamide riboside, while an equivalent dose of NRMalate contains only about 197 mg of useful nicotinamide riboside. That’s about 33% less of the active compound. Don’t buy products with NRMalate as you are getting 33% less of the active compound!
Now let’s look at how NR is transported across the cell membranes into cells. The transport mechanism uses equilibrated nucleoside transporters (ENTs). (2) NR is then converted into NAD+ in the cells through two different pathways: These pathways are called the Nrk1 and Urh1/Pnp1/Meu1 pathways. (3) The NrK1 pathway (Nicotinamide Riboside Kinase 1) is a critical metabolic route that converts NR into nicotinamide mononucleotide (NMN), which is subsequently converted to NAD+. NrK1 is an enzyme (a catalyst) for the conversion, which takes place in the cytoplasm of all cells (the cytoplasm is the gel-like part of the cell outside the nucleus). The second pathway is an independent parallel pathway, for conversion of NR to NAD+. In this pathway, other enzymes work to split NR releasing a sugar called ribose and then converting the remaining part into NAD+. It is the combination of these two different pathways that helps with the rapid conversion of NR to NAD+.
How NR is converted to NAD+ in the body
How NAD+ works
Now that we know how NAD+ is made from RN, let’s examine the biochemical mechanisms which are occurring in the body in order to understand how NAD+ works. This section is heavy biochemistry – if it is hard reading – here’s the cheat sheet – NAD+ is involved in many biochemical and physiological processes in the body. NAD+’s diverse roles in regulating critical physiological processes underscore its importance in health and disease, particularly in aging-associated conditions. (4, 5) Getting sufficient NAD+ levels in your body are paramount to your healthy aging.
NAD+ is a coenzyme. Coenzymes are organic molecules that bind to the active sites of enzymes to assist in their catalytic activity – meaning they help enzymes work better and faster. As a coenzyme, NAD+ helps maintain specific physiological processes, enabling the cell to adapt to environmental changes. It is essential for cellular oxidative metabolic reactions, facilitating energy generation through such physiological processes as glycolysis and mitochondrial respiration, which supports cell growth and survival. (6, 7, 8, 9) NAD+ drives metabolic pathways by transferring hydrogen in oxidation-reduction reactions, and functions as a critical cofactor for non-redox NAD+ dependent enzymes including sirtuins, CD38, and poly(ADP-ribose) polymerases (PARPs) 9. NAD+ is involved in DNA repair, cell proliferation, differentiation, redox regulation, oxidative stress response, and protein balance. (4, 6, 7, 9) Additionally, NAD+ acts as a signaling molecule, influencing processes such as calcium signaling, circadian rhythms, metabolism, inflammation, and immune cell function. (7, 8, 10, 11) NAD+ is critical for maintaining cellular and tissue homeostasis, influencing processes such as energy production, DNA repair, chromatin remodeling, cellular senescence, and immune cell function. (4) Its diverse roles in regulating critical physiological processes underscore its importance in health and disease, particularly in aging-associated conditions. (4, 5) The maintenance of NAD+ levels are paramount for healthy aging.
The Role of NAD+ in Cellular Metabolism and Aging
Now that we understand how NR is converted into NAD+ in the body, and how NAD+ is utilized in the body, now it’s finally time to learn why NAD+ is such a powerhouse for cellular health. As we go through each aspect of health for NAD+, remember that NR is converted into NAD+.
Mitochondrial Health: (12,13) Increased NAD+ levels from NR supplementation lead to enhanced mitochondrial biogenesis and reduced oxidative stress. (12,13,14) In older study participants, NR supplementation has been shown to lead to an elevation of the muscle NAD+ metabolome, as shown by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products, while muscle RNA sequencing revealed NAD+-mediated downregulation of energy metabolism and mitochondrial pathways in muscle tissue without altering mitochondrial bioenergetics. (15) These findings highlight the many effects of NAD+ on improving mitochondrial function.
Metabolic Health: The impact of NAD+ on metabolic health has been a key area of research. Preclinical studies have shown promising results on insulin sensitivity and mitochondrial biogenesis. (12) A human study has demonstrated that NAD+ improves metabolic function, protects against high-fat diet-induced obesity, and enhances oxidative metabolism by activating sirtuin enzymes. (15,17) Other studies however, have not demonstrated improvements illustrating the difficulties of doing clinical studies.
Aging and Longevity: NR has emerged as a major candidate for the promotion of longevity and healthy aging owing to its ability to increase NAD+ levels in humans. Clinical trials have demonstrated that NR supplementation can lead to significant increases in whole blood NAD+ levels, with one study reporting a dose-dependent increase of up to 142% after two weeks of consumption. (18) This finding is particularly relevant, given the consistent decline in NAD+ levels observed across multiple organisms, including humans, as they age. (19,20).
Age-related decrease in NAD+ levels, which occurs in various tissues, is now considered a hallmark of aging. (21) A large-scale study involving 1,518 participants revealed a declining trend in whole blood NAD+ content with aging, particularly before 50 years of age. (22) The decline in NAD+ levels has been linked to various age-associated diseases, including metabolic disorders, cancer, neurodegenerative diseases, and cognitive decline. (4,19,23) This decrease impairs tissue function and cellular processes, such as DNA repair, chromatin remodeling, and immune cell function. (4) Restoring NAD+ levels through has shown promise in ameliorating age-related disorders and potentially extending lifespan. (23,24).
NAD+ plays a crucial role in longevity and transcriptional regulation through NAD-dependent deacetylases such as the Sir2p family. (4,25,26) The relationship between NAD+ concentration and longevity is strong. Current evidence primarily highlights NR’s potential to counteract biochemical markers of aging, through enhancing the NAD+ levels. NR supplementation has shown promising results in e potentially mitigating age-related decline. Studies on the effects of NR on human longevity are still ongoing (27,28) with more to come in the future.
Neurodegenerative Management*: NAD+ levels are crucial for neuronal health and function. (29,30) In animal models of Alzheimer’s disease, NAD+ reduced senescence, attenuated DNA damage, and decreased neuroinflammation. (31) A clinical trial in patients with Parkinson’s disease found that short-term high-dose therapy led to increased cerebral NAD+ levels, altered cerebral metabolism, and mild clinical improvements in some patients. (32)
Liver Health: Studies have shown that NAD+ can protect against liver injury and metabolic disorders. NAD+ exerts protective effects against alcohol-induced liver injury by activating SirT1, reducing oxidative stress, and improving mitochondrial function through the SirT1/PGC-1α/mitochondrial biosynthesis pathway. (33) It can also prevent and reverse liver fibrosis by suppressing the activation of hepatic stellate cells through Sirt1-mediated deacetylation of the SMAD signaling pathway. (34) In alcohol-related liver diseases, NAD+ and its precursors (including NR) are significantly reduced, which correlates with disease severity. (35)
Gut Health: In a recent human clinical study NR was found to significantly improve gut health, through the production of NAD+.(36) This was determined by measuring the increases in short chain fatty acids (SCFAs) – these acids are markers for gut health. SCFAs enhance the integrity of epithelial tissue, mitigating mucosal inflammation and maintaining intestinal homeostasis. All of these conditions are related to the G.I. system and gut health.
Stem Cells: NAD+ has demonstrated significant potential in promoting stem cell health and tissue regeneration in various cell types. In hematopoietic stem cells (HSCs), NAD+ supports regeneration by reducing mitochondrial stress and enhancing mitochondrial clearance, which are crucial for blood recovery and immune function. (13) NAD+ has been shown to rejuvenate muscle stem cells (MuSCs) in aged mice by inducing the mitochondrial unfolded protein response and synthesis of prohibitin proteins, while also preventing MuSC senescence in a muscular dystrophy model and delaying senescence of neural and melanocyte stem cells. (37) In aged HSCs (stem cells), NAD+ works to restore youthful metabolic capacity by modifying mitochondrial function, resulting in a more youthful bone marrow composition and improved regenerative capacity. (38)
What does this all mean for you?
NR is converted in the cell to NAD+. NAD+ is a powerhouse with a multitude of improvements in cellular health and anti-aging. Through the biochemical mechanisms discussed above and a scientific understanding of its effects on body functions, science has shown that taking just one capsule a day of nrXPRO’s N can*:
- Supercharge your energy and your overall health for healthy aging
- Power your brain cells for enhanced cognitive performance
- Enhances your gut health through increased short chain fatty acid production
- Support your heart cells for cardiovascular resilience
- Keep your muscles working properly and increase your endurance
- Manage your daily stressors
How everything connects together
The Safety of NR
We pay close attention to the safety of all our products. NR is very safe to consume. Safety is scientifically determined by a suite of specific toxicity studies and then is confirmed in clinical studies. Toxicity studies have shown NR to be safe to at least 300 mg/kg/day. This means that for an average size women of 150 lb (68 kg), the safe dose is over 20 grams. This is almost 70 times the recommended daily dose of 300 mg – a huge safety factor. NR is even safer for larger people. In addition, human clinical trials have further confirmed the safety profile, with tested doses of 2,000 mg/day being well-tolerated. (39,40) Our scientists confirm the safety of NR based on these studies.
* FDA has not evaluated these product claims. This dietary supplement is not intended to diagnose, treat, cure, or prevent any disease.
References:
1. Makarov, M. V. & Migaud, M. E. Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives. Beilstein Journal of Organic Chemistry 15, 401–430 (2019).
2. Kropotov, A. et al. Purine nucleoside phosphorylase controls nicotinamide riboside metabolism in mammalian cells. Journal of Biological Chemistry 298, 102615 (2022).
3. Belenky, P. et al. Nicotinamide Riboside Promotes Sir2 Silencing and Extends Lifespan via Nrk and Urh1/Pnp1/Meu1 Pathways to NAD +. Cell 129, 473–484 (2007).
4. Covarrubias, A. J., Perrone, R., Verdin, E. & Grozio, A. NAD+ metabolism and its roles in cellular processes during ageing. Nature reviews. Molecular cell biology 22, 119–141 (2020).
5. Verdin, E. NAD+ in aging, metabolism, and neurodegeneration. Science 350, 1208–1213 (2015).
6. Griffiths, H. B. S., Williams, C., Allison, S. J. & King, S. J. Nicotinamide adenine dinucleotide (NAD+): essential redox metabolite, co-substrate and an anti-cancer and anti-ageing therapeutic target. Biochemical Society Transactions 48, 733–744 (2020).
7. Tannous, C. et al. Nicotinamide adenine dinucleotide: Biosynthesis, consumption and therapeutic role in cardiac diseases. Acta Physiologica 231, (2020).
8. Xie, N. et al. NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential. Signal Transduction and Targeted Therapy 5, (2020).
9. Zhu, Y., Liu, J., Park, J., Rai, P. & Zhai, R. G. Subcellular compartmentalization of NAD+ and its role in cancer: A sereNADe of metabolic melodies. Pharmacology & therapeutics 200, 27–41 (2019).
10. Katsyuba, E., Hofer, D., Romani, M. & Auwerx, J. NAD+ homeostasis in health and disease. Nature Metabolism 2, 9–31 (2020).
11. Imai, S.-I. & Guarente, L. NAD+ and sirtuins in aging and disease. Trends in Cell Biology 24, 464–471 (2014).
12. Chi, Y. & Sauve, A. A. Nicotinamide riboside, a trace nutrient in foods, is a Vitamin B3 with effects on energy metabolism and neuroprotection. Current Opinion in Clinical Nutrition and Metabolic Care 16, 657–661 (2013).
13. Vannini, N. et al. The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance. Cell Stem Cell 24, 405-418.e7 (2019).
14. Li, Q. et al. Improving Mitochondrial Function in Skeletal Muscle Contributes to the Amelioration of Insulin Resistance by Nicotinamide Riboside. International Journal of Molecular Sciences 24, 10015 (2023).
15. Elhassan, Y. et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Reports 28, 1717-1728.e6 (2019).
16. Nascimento, E. B. M. et al. Nicotinamide Riboside Enhances In Vitro Beta-adrenergic Brown Adipose Tissue Activity in Humans. The Journal of Clinical Endocrinology & Metabolism 106, 1437–1447 (2021).
17. Cantó, C. et al. The NAD+ Precursor Nicotinamide Riboside Enhances Oxidative Metabolism and Protects against High-Fat Diet-Induced Obesity. Cell Metabolism 15, 838–847 (2012).
18. Conze, D., Kruger, C. L. & Brenner, C. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Scientific Reports 9, (2019).
19. Aman, Y., Qiu, Y., Tao, J. & Fang, E. F. Therapeutic potential of boosting NAD+ in aging and age-related diseases. Translational Medicine of Aging 2, 30–37 (2018).
20. Strømland, Ø., Diab, J., Ferrario, E., Sverkeli, L. J. & Ziegler, M. The balance between NAD+ biosynthesis and consumption in ageing. Mechanisms of Ageing and Development 199, 111569 (2021).
21. Soma, M. & Lalam, S. K. The role of nicotinamide mononucleotide (NMN) in anti-aging, longevity, and its potential for treating chronic conditions. Molecular Biology Reports 49, 9737–9748 (2022).
22. Yang, F. et al. Association of Human Whole Blood NAD+ Contents With Aging. Frontiers in endocrinology 13, (2022).
23. Rahman, S. U., Qadeer, A. & Wu, Z. Role and Potential Mechanisms of Nicotinamide Mononucleotide in Aging. Aging and disease 15, 565 (2024).
24. Johnson, S. & Imai, S. NAD + biosynthesis, aging, and disease. F1000Research 7, 132 (2018).
25. Lin, S.-J. & Guarente, L. Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease. Current Opinion in Cell Biology 15, 241–246 (2003).
26. Rajman, L., Chwalek, K. & Sinclair, D. A. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metabolism 27, 529–547 (2018).
27. Orlandi, I., Vai, M. & Alberghina, L. Nicotinamide, Nicotinamide Riboside and Nicotinic Acid-Emerging Roles in Replicative and Chronological Aging in Yeast. Biomolecules 10, 604 (2020).
28. Sharma, A., Ewald, C. Y., Chabloz, S., Lapides, R. A. & Roider, E. Potential Synergistic Supplementation of NAD+ Promoting Compounds as a Strategy for Increasing Healthspan. Nutrients 15, 445 (2023).
29. Sharma, C., Donu, D. & Cen, Y. Emerging Role of Nicotinamide Riboside in Health and Diseases. Nutrients 14, 3889 (2022).
30. Mehmel, M., Jovanović, N. & Spitz, U. Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Nutrients 12, 1616 (2020).
31. Larrick, J. W. & Mendelsohn, A. R. Modulation of cGAS-STING Pathway by Nicotinamide Riboside in Alzheimer’s Disease. Rejuvenation Research 24, 397–402 (2021).
32. Brakedal, B. et al. The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson’s disease. Cell Metabolism 34, 396-407.e6 (2022).
33. Wang, S. et al. Nicotinamide riboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1α/mitochondrial biosynthesis pathway. Redox Biology 17, 89–98 (2018).
34. Jiang, R. et al. Nicotinamide riboside protects against liver fibrosis induced by CCl4 via regulating the acetylation of Smads signaling pathway. Life Sciences 225, 20–28 (2019).
35. Parker, R., Gunson, B., Brenner, C., Cain, O. & Schmidt, M. S. Nicotinamide Adenine Dinucleotide Metabolome Is Functionally Depressed in Patients Undergoing Liver Transplantation for Alcohol‐Related Liver Disease. Hepatology Communications 4, 1183–1192 (2020).
36. Christen S. et al. The differential impact of three different NAD+ boosters on circulatory NAD and microbial metabolism in humans. Nature Metabolism 8,62-73 (2026)
37. Zhang, H. et al. NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science 352, 1436–1443 (2016).
38. Sun, X. et al. Nicotinamide riboside attenuates age-associated metabolic and functional changes in hematopoietic stem cells. Nature Communications 12, (2021).
39. Conze, D., Kruger, C. & Crespo-Barreto, J. Safety assessment of nicotinamide riboside, a form of vitamin B3. Human & Experimental Toxicology 35, 1149–1160 (2016).
40. Dollerup, O. L. et al. A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. The American Journal of Clinical Nutrition 108, 343–353 (2018).