From the Guidelines
NAD+ (nicotinamide adenine dinucleotide) is a critical coenzyme found in all living cells that plays essential roles in energy metabolism and cellular function, serving as an electron carrier in metabolic reactions and supporting various cellular processes. The function of NAD+ is multifaceted, involving the transfer of hydride ions (H–) within dehydrogenase–reductase systems, which is crucial for energy production and maintaining cellular health 1. NAD+ is also vital for DNA repair mechanisms, gene expression regulation through sirtuins, and supporting mitochondrial function, which helps regulate circadian rhythms and participates in calcium signaling pathways 2.
Key Functions of NAD+
- Energy metabolism: NAD+ serves as an electron carrier in processes like glycolysis, the citric acid cycle, and oxidative phosphorylation, converting nutrients into ATP, the cell's primary energy currency.
- DNA repair: NAD+ is crucial for DNA repair mechanisms, particularly through its role in poly (ADP-ribose) polymerases (PARP) that carry out DNA base excision repair processes.
- Gene expression regulation: NAD+ influences gene expression through sirtuins, proteins that play a significant role in aging processes and cellular health.
- Mitochondrial function: NAD+ supports mitochondrial function, which is essential for energy production, particularly in highly glycolytic cells like neurons and muscle tissue.
Importance of NAD+ Balance
The balance between NAD+ (oxidized) and NADH (reduced) is crucial for proper cellular metabolism and redox state maintenance. As individuals age, NAD+ levels naturally decline, which may contribute to various aspects of aging and age-related diseases. Maintaining adequate NAD+ levels is essential for preventing cellular energy crises, mitochondrial dysfunction, and the release of mitochondrial apoptosis-inducing factors, all of which can lead to cell death and contribute to the pathogenesis of conditions like sarcopenia 1.
Dietary Sources and Recommendations
Niacin, the precursor to NAD+, can be obtained from the diet through various whole and processed foods, with the highest contents found in fortified packaged foods, meat, poultry, and certain fish like tuna and salmon. Niacin can also be synthesized from the amino acid tryptophan in the liver. The recommended daily intake of niacin varies by age and condition, with specific guidelines provided for infants, children, and adults, including those on parenteral nutrition 2, 3.
Clinical Implications
Understanding the function and importance of NAD+ has significant clinical implications, particularly in the prevention and management of age-related diseases and conditions associated with NAD+ depletion, such as sarcopenia and neurodegenerative disorders. Maintaining adequate NAD+ levels through dietary intake, supplementation, or other means may help mitigate the decline in NAD+ associated with aging and contribute to improved health outcomes and quality of life 1, 2.
From the Research
Function of Nicotinamide Adenine Dinucleotide (NAD+)
- NAD+ is a central metabolic cofactor in eukaryotic cells that plays a critical role in regulating cellular metabolism and energy homeostasis 4
- NAD+ in its reduced form (i.e. NADH) serves as the primary electron donor in mitochondrial respiratory chain, which involves adenosine triphosphate production by oxidative phosphorylation 4
- The NAD+/NADH ratio regulates the activity of various metabolic pathway enzymes such as those involved in glycolysis, Kreb's cycle, and fatty acid oxidation 4
Role of NAD+ in Cellular Processes
- NAD+ is essential for cellular oxidative (catabolic) metabolic reactions, enabling energy generation through glycolysis and mitochondrial respiration to support cell growth and survival 5
- NAD+ is a co-substrate for many key enzymes that regulate diverse cell functions, including gene expression, proteostasis, and DNA repair 5
- NAD+ levels decline with age and are associated with neurodegeneration, cancer, and other age-related diseases 6, 7
NAD+ Metabolism and Homeostasis
- The cellular NAD+ pool is maintained by three biosynthesis pathways, which are largely conserved from bacteria to human 8
- NAD+ metabolism is an emerging therapeutic target for several human disorders, including diabetes, cancer, and neuron degeneration 8
- Factors regulating NAD+ homeostasis have remained incompletely understood due to the dynamic nature and complexity of NAD+ metabolism 8
Therapeutic Potential of NAD+
- Increasing NAD+ levels using NAD+ precursors has shown efficacy in various diseases, including aging, cancer, and neurodegenerative disorders 6, 7
- Targeting NAD+ metabolism has emerged as a potential therapeutic approach to ameliorate ageing-related disease, and extend the human healthspan and lifespan 7