Nicotinamide Adenine Dinucleotide (NAD+) is an oxidized form of NADH (Nicotinamide Adenine Dinucleotide Hydroxide). NAD+ is a component of the Electron Transport Chain (ETC), apparently carrying electrons from biological reactions. It appears to act as a medium for shuttling energy within and outside the cell. It also appears to act as a mediator for various biological processes in the body, such as post-translational modification of the proteins and activation/deactivation of some enzymes. It may be a critical component in maintaining cell-to-cell communication in the body. The neurons present in blood vessels, intestines, and bladder, release NAD+ which appears to act as an extracellular signaling molecule, regulating bio-functions in the body. It appears to function as a cofactor in numerous bodily processes such as immune defense, DNA repair, circadian cycles, and energy conversion. However, like other naturally occurring mediators in the body, its level generally declines as age advances. Therefore, replenishing the levels of NAD+ in the body may help off-set various age-related progressive and degenerative processes. NAD+ is a naturally occurring compound, and may be used synergistically with other supplements to obtain potentially multiplied benefits.
SYNONYMS: Nicotinamide Adenine Dinucleotide, Beta-NAD, NAD, Endopride
MOLECULAR WEIGHT: 663.43 g/mol
MOLECULAR FORMULA: C21H27N7O14P2
PUBCHEM:CID 925
RECONSTITUTION: Required
NAD+ is of pivotal significance in numerous biological processes and greatly interests researchers. Studies have been developed to explore its natural role in the body and which properties it best exhibits. Listed below are areas of research in which NAD+ has been suggested to play a role:
NAD+ AND ANTI-AGING
Mitochondria are considered the powerhouse of the body. They serve as a platform for primary metabolic functions such as intracellular signaling and regulation of innate immunity. These processes are directly affected by mitochondrial senescence and ultimately alter cellular metabolism, inflammation, and even stem cell activity.[1] These altogether reduce the pace of healing following an injury. This illustrates the extent to which mitochondria are involved in age-related tissue and organ function decline. Potentially manipulating mitochondrial activity can slow, cease or even reverse the process of aging. A deficiency of NAD+ in the cell appears to induce a pseudo-hypoxic state which interrupts signaling within the nucleus. Studies have suggested that NAD+ supplementation may help in reversing at least some of the age-related decline in the function of mitochondria.[2] The scientists concluded that “raising NAD+ levels in old mice restores mitochondrial function to that of a young mouse in a SIRT1-dependent manner.” The mechanism underlying this property appears to involve the activation of the SIRT 1 function, whereby a gene encodes an enzyme called Sirtuin-1 (NAD+ dependent Deacetylase Sirtuin-1). Sirtuin-1 then may regulate the mediators involved in metabolism, inflammation, the longevity of cells, and the processes linked to stress.[3]
NAD+ AND MUSCLE FUNCTION
The decline in muscle function related to age is associated with mitochondrial senescence. It occurs in two steps. The first, reversible, step involves declined expression of mitochondrial genes. These genes are responsible for oxidative phosphorylation (the process by which mitochondria produce energy). The second, irreversible, step consists of a decline in genes responsible for oxidative phosphorylation in the nucleus. Mice experiments have observed an apparent step 1 reversal with the administration of NAD+ before the cell progresses to step 2.[4]
The mechanism behind this intervention in mitochondrial aging may involve stabilizing the activity of Peroxisome Proliferator-activated Receptor Gamma Co-activator 1-alpha (PGC-1-alpha). Studies have suggested that the effect mentioned above produced in the mitochondria may be similar to exercise on the mitochondria of skeletal muscles.[5]
NAD+ AND NEURODEGENERATIVE DISEASES
NAD+ is a cofactor that may play a significant neuroprotective role.[6] It appears to do so by improving mitochondrial function and reducing the production of Reactive Oxidative Stress (ROS). ROS is responsible for inflammatory changes associated with injury and degenerative changes associated with aging. This association provides its basis for treating certain neurodegenerative diseases such as Alzheimer’s, Huntington’s, and Parkinson’s disease. Research conducted on mice suggested the potential for NAD+ to protect against progressive motor deficits and the death of dopamine-producing cells in the substantia nigra.[7] According to the researchers “These results add credence to the beneficial role of NAD against parkinsonian neurodegeneration in mouse models of PD, provide evidence for the potential of NAD for the prevention of PD, and suggest that NAD prevents pathological changes in PD via decreasing mitochondrial dysfunctions.” The research findings implied that although NAD+ doesn’t appear to alleviate the symptoms, it may slow the progression if not entirely prevent the development of Parkinson’s disease.
NAD+ AND INFLAMMATION
NAMPT is an enzyme that is associated with inflammation. It appears overexpressed in certain types of cancers. An increase in the levels of NAMPT appears to correlate to NAD+ levels, and vice versa.[8] The NAMPT-associated inflammation appears to occur in cancers, obesity, type 2 diabetes, and nonalcoholic fatty liver disease. NAMPT may be a potent activator of inflammation whose levels may decrease dramatically following the administration of NAD+.
NAD+ AND ADDICTION
Drug and alcohol addiction has been suggested to be associated with a decline in the levels of NAD+. Addiction typically leads to significant nutritional deficiencies and cognitive deterioration. Supplementation with NAD+ may help overcome these changes and can be helpful in various addiction disorders. NAD+ supplementation has the potential to provide a wide range of benefits when used alone and may also be used in conjunction with other therapies to obtain multiplied effects.
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