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These studies suggest that nicotinamide adenine dinucleotide (NAD+) and its precursors, such as nicotinamide riboside and nicotinamide mononucleotide, may support neuronal health, improve muscle and heart function, and offer therapeutic potential for age-related and neurodegenerative diseases.
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Nicotinamide adenine dinucleotide (NAD+) is a vital coenzyme found in all living cells, playing a crucial role in various cellular processes, including energy metabolism, DNA repair, and cell signaling . NAD+ can be synthesized de novo from tryptophan or through salvage pathways using precursors such as nicotinic acid (NA), nicotinamide (NAM), and nicotinamide riboside (NR), collectively known as niacin or vitamin B3.
NAD+ is essential for oxidative phosphorylation and ATP production, serving as a cofactor for enzymes involved in redox reactions . It also acts as a substrate for sirtuins and poly(ADP-ribose) polymerases (PARPs), which are involved in gene expression, DNA repair, and cell death regulation . The depletion of NAD+ can lead to impaired cellular functions and has been linked to various age-related diseases and metabolic disorders .
NAD+ precursors have shown promise in protecting against neurodegenerative diseases. Nicotinamide, a form of vitamin B3, has been associated with neuronal development and survival and may offer therapeutic benefits in conditions like Alzheimer's disease (AD) by inhibiting PARP-1, reducing neuroinflammation, and improving mitochondrial function . Nicotinamide riboside (NR) supplementation has also been found to elevate NAD+ levels in aged human muscle, showing anti-inflammatory effects and potential benefits for neurodegenerative conditions.
NAD+ levels decline with age, contributing to metabolic dysfunction. Supplementation with NAD+ precursors like nicotinamide mononucleotide (NMN) has been shown to improve insulin sensitivity and muscle remodeling in prediabetic women, indicating potential therapeutic action in metabolic diseases. NR supplementation has also been reported to ameliorate metabolic dysfunction in rodents and increase the NAD+ metabolome in aged humans.
The heart, being one of the most metabolically demanding organs, relies heavily on NAD+ for energy metabolism and mitochondrial function. In models of heart failure, NAD+ levels are often depressed due to mitochondrial dysfunction and inflammation. Regulating NAD+ homeostasis through precursor supplementation has shown therapeutic efficiency in improving myocardial bioenergetics and function.
The refinement of personalized therapy using NAD+ precursors and improved detection methodologies will enhance our understanding of their therapeutic roles in human diseases. Future research should focus on the specific effects of different NAD+ precursors in various tissues and their potential in treating age-related and degenerative diseases.
Nicotinamide adenine dinucleotide (NAD+) and its precursors play a critical role in maintaining cellular health and have significant therapeutic potential in treating neurodegenerative, metabolic, and cardiovascular diseases. As research progresses, personalized NAD+ precursor therapies may offer new avenues for enhancing health span and combating age-related disorders.
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