NAD+ 500mg

NAD+ is a vital coenzyme present in all living cells, essential for various metabolic processes and cellular functions. It acts as a mediator in redox reactions, alternating between its oxidized (NAD+) and reduced (NADH) forms to facilitate electron transfer, crucial for energy production and sustaining life. Involved in over 500 enzymatic reactions, NAD+ is central to maintaining cellular homeostasis.

Mechanism of Action

NAD+ plays a pivotal role in energy metabolism by participating in redox reactions, where it alternates between NAD+ and NADH forms to transfer electrons. This electron transfer is essential for ATP production, the primary energy currency of the cell. Beyond energy metabolism, NAD+ supports DNA repair and gene regulation through enzymes like sirtuins and PARPs. Sirtuins utilize NAD+ to regulate cellular functions such as DNA repair, gene expression, and aging, while PARPs employ it to repair DNA damage and maintain genomic stability. These roles underscore NAD+'s importance in cellular integrity and combating aging.

NAD+ Research

Anti-Aging Research and NAD+

One of the fundamental aspects of aging is the decline in mitochondrial quality and activity. Mitochondria, the cell’s power plants, produce energy vital for functions ranging from neuron firing to muscle movement and digestion. Mitochondrial dysfunction is linked not only to normal aging but also to several age-related diseases. Studies show that mitochondrial aging contributes to cellular senescence, inflammation, and altered stem cell activity, reducing the body’s ability to heal and recover with age.

Nuo Sun from the National Institutes of Health emphasizes that mitochondria serve not only as energy producers but also as platforms for intracellular signaling, immune regulation, and stem cell modulation. Mitochondria are central to aging processes such as tissue decline, senescence, and inflammation. Protecting mitochondrial function is critical to slowing or reversing aging.

NAD+ and Mitochondrial Rejuvenation

Recent research highlights that age-related mitochondrial decline can be partially reversed through supplementation with NAD+ (nicotinamide adenine dinucleotide). This was popularized by David Sinclair of Harvard University, who showed in 2013 that injecting NAD+ precursors restored youthful mitochondrial function in mouse muscle.

Declining NAD+ leads to a pseudohypoxic state that disrupts communication between the nucleus and mitochondria. Supplementation restores mitochondrial function and reestablishes this essential signaling. NAD+ activates SIRT1, a gene encoding sirtuin 1, a protein involved in metabolism, stress response, longevity, and inflammation regulation. Maintaining SIRT1 expression helps counteract age-related cellular decline.

NAD+ in Muscle Aging

Skeletal muscle aging progresses in two stages: first, reduced mitochondrial gene expression lowers oxidative phosphorylation; second, gene regulation malfunctions in both mitochondria and nucleus. Early NAD+ supplementation can reverse stage one, improving mitochondrial function and preventing progression to irreversible dysfunction. This highlights the importance of early intervention.

Exercise similarly maintains mitochondrial health by preserving PGC-1α signaling, protecting mitochondrial DNA and promoting angiogenesis, thus maintaining muscle oxidative capacity over a lifetime.

NAD+ and Neurodegenerative Diseases

NAD+ levels influence central nervous system health and are linked to diseases like Alzheimer’s and Huntington’s. NAD+ enhances mitochondrial function, reducing damaging reactive oxygen species (ROS) that accelerate aging and inflammation.

Studies suggest NAD+ supplementation protects against Parkinson’s disease symptoms and neuronal death, potentially slowing or preventing disease onset. Research on the kynurenine pathway (KP) shows NAD+ supplementation may prevent neurotransmitter depletion caused by KP imbalances, implicated in neurodegenerative and psychiatric disorders.

NAD+ and Inflammation

NAD+ levels are regulated partly by NAMPT, an enzyme linked to inflammation and overexpressed in some cancers. High NAMPT levels contribute to obesity, type 2 diabetes, and fatty liver disease by promoting inflammation. NAD+ supplementation may modulate NAMPT activity, reducing inflammation.

Obesity-induced inflammation lowers NAD+, increasing free fatty acids and glucose production, causing insulin resistance. The pancreas compensates by producing more insulin, ultimately leading to diabetes.

NAD+ in Addiction Recovery

Drugs and alcohol deplete NAD+ levels, causing nutritional deficits and cognitive changes. Since the 1960s, NAD+ supplementation combined with amino acids has helped reduce cravings and improve stress and anxiety during addiction rehabilitation.

Future Directions

Animal studies support NAD+ supplementation in reversing mitochondrial aging effects. Clinical trials are underway for neurodegenerative diseases and type 2 diabetes, with NAD+ showing promise to slow disease progression or potentially reverse some conditions. NAD+ exhibits minimal side effects and good bioavailability in animals but is for research use only.

Research Applications

Studies have investigated the potential therapeutic effects of NAD+ in various conditions associated with mitochondrial dysfunction, including:

• Neurological Disorders: Research suggests that NAD+ may play a role in protecting against age-related cognitive decline and neurodegenerative diseases.
• Metabolic Diseases: NAD+ has been shown to improve insulin sensitivity and reduce obesity in animal models.
• Cardiovascular Conditions: Preliminary studies indicate that NAD+ may help improve endothelial function and reduce vascular calcification.
• Musculoskeletal Health: NAD+ treatment has been associated with increased exercise capacity and muscle strength in aging models.
• While these findings are promising, further research is needed to fully understand the therapeutic potential and safety profile of NAD+ in humans.

Safety and Usage

NAD+ is currently available for research purposes only and is not approved for human consumption. It is typically provided in a lyophilized (powder) form to ensure maximum stability. Researchers interested in studying NAD+ should adhere to appropriate safety protocols and ethical guidelines.

Referenced Citations

• NAD+ Science 101 - What Is NAD+ & Why It's Important, Elysium Health. Available: https://www.elysiumhealth.com/en-us/knowledge/science-101/everything-you-need-to-know-about-nicotinamide-adenine-dinucleotide-nad 
• Nicotinamide Riboside: Benefits, Side Effects and Dosage, Healthline. Available: https://www.healthline.com/nutrition/nicotinamide-riboside 
• Matthews RT, Yang L, Browne S, Baik M, Beal MF. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Natl Acad Sci USA. 1998;95(15):8892–8897. [PMC] 
• What You Need to Know About Resveratrol Supplements, WebMD. Available: https://www.webmd.com/heart-disease/resveratrol-supplements 
• Sun N, Youle RJ, Finkel T. The Mitochondrial Basis of Aging. Mol Cell. 2016;61(5):654-666. [PMC] 
• Stipp D. Beyond Resveratrol: The Anti-Aging NAD Fad, Scientific American Blog. Available: https://blogs.scientificamerican.com/guest-blog/beyond-resveratrol-the-anti-aging-nad-fad 
• Gomes AP, et al. Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging. Cell. 2013;155(7):1624-1638. [PMC] 
• Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014;24(8):464-471. [PubMed] 
• Mendelsohn AR, Larrick JW. Partial reversal of skeletal muscle aging by restoration of normal NAD+ levels. Rejuvenation Res. 2014;17(1):62-69. [PubMed] 
• Kang C, Chung E, Diffee G, Ji LL. Exercise training attenuates aging-associated mitochondrial dysfunction in rat skeletal muscle: role of PGC-1α. Exp Gerontol. 2013;48(11):1343-1350. [PubMed] 
• Ringholm S, et al. Effect of lifelong resveratrol supplementation and exercise training on skeletal muscle oxidative capacity in aging mice; impact of PGC-1α. Exp Gerontol. 2013;48(11):1311-1318. [PubMed] 
• Lloret A, Beal MF. PGC-1α, Sirtuins and PARPs in Huntington’s Disease and Other Neurodegenerative Conditions: NAD+ to Rule Them All. Neurochem Res. 2019. [PubMed] 
• Shan C, et al. Protective effects of β-nicotinamide adenine dinucleotide against motor deficits and dopaminergic neuronal damage in a mouse model of Parkinson’s disease. Prog Neuropsychopharmacol Biol Psychiatry. 2019;94:109670. [PubMed] 
• Maddison DC, Giorgini F. The kynurenine pathway and neurodegenerative disease. Semin Cell Dev Biol. 2015;40:134-141. [PubMed] 
• Garten A, Schuster S, Penke M, Gorski T, de Giorgis T, Kiess W. Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nat Rev Endocrinol. 2015;11(9):535-546. [PubMed] 
• Yamaguchi S, Yoshino J. Adipose Tissue NAD+ Biology in Obesity and Insulin Resistance: From Mechanism to Therapy. BioEssays. 2017;39(5). [PMC] 
• Humiston JE. Nicotinamide Adenine Dinucleotide. FDA Report. [Online]