NICOTINAMIDE ADENINE DINUCLEOTIDE (NAD)

Mechanism of Action
NAD⁺ (nicotinamide adenine dinucleotide) is a universal coenzyme present in all cells and is essential for more than 500 enzymatic reactions in metabolism. It functions as an electron carrier in redox reactions, interconverting between its oxidized form (NAD⁺) and reduced form (NADH), and plays a critical role in mitochondrial energy production. In addition, NAD⁺ is a required cofactor for key enzymes involved in cellular longevity regulation, such as sirtuins (e.g., SIRT1) and poly(ADP-ribose) polymerases (PARPs), which are involved in DNA repair. Adequate NAD⁺ levels support mitochondrial function, genomic repair, and circadian homeostasis; conversely, age-related declines in NAD⁺ have been linked to aging and to metabolic and neurodegenerative diseases. Current research focuses on strategies to increase NAD⁺ levels (such as supplementation with precursors like nicotinamide riboside or NMN) to counteract these age-associated declines.
 
Clinical Uses
Although NAD⁺ itself is not a traditional “drug,” indirect supplementation (via precursors or infusions) is being explored for several therapeutic purposes. Increasing NAD⁺ levels has been proposed as a way to slow aging and extend health span in older adults. Early studies suggest potential benefits in protecting against neurodegenerative diseases (such as Alzheimer’s and Parkinson’s disease) and in improving cognitive function in aging populations. Its role in improving cardiac function in heart failure and preventing metabolic decline in conditions such as diabetes is also under investigation.
In private clinical settings, intravenous NAD⁺ therapies have been used to aid addiction recovery (by reducing withdrawal symptoms), combat chronic fatigue, and enhance mental clarity, although these indications are largely anecdotal. Additionally, boosting NAD⁺ levels may exert anti-inflammatory effects and support tissue repair, leading to ongoing research in inflammatory diseases and musculoskeletal injuries.
 
Side Effects and Risks
Supplementation with NAD⁺ (or its precursors) is generally well tolerated at moderate doses, but some reactions can occur. One of the most common acute effects—especially with IV NAD⁺ infusion—is cutaneous flushing (warmth and redness), due to prostaglandin-mediated vasodilation. Other reported effects include mild nausea, gastrointestinal discomfort, headache, and transient dizziness during or after rapid infusions.
High-dose oral supplementation with NAD⁺ precursors (such as niacinamide, NR, or NMN) may elevate liver enzymes and, if excessive doses are used, potentially cause hepatotoxicity, as excess vitamin B3 places stress on the liver. Animal studies have raised concerns that very high doses of NAD⁺/NR might promote tumor development, although this has not been confirmed in humans. Overall, long-term safety data are limited, and the effects of chronically elevated NAD⁺ levels in older adults are not fully understood. Caution is advised in individuals with a history of active cancer (due to possible interactions with cell growth pathways), and use during pregnancy or childhood should be avoided because of insufficient safety data.