written by Pharm. D. Candidate Trisha KhongThe Use of NAD+ IV Therapy for Energy Rejuvenation, Cognitive Clarity, and Maintenance of Cellular HealthNicotinamide adenine dinucleotide (NAD) is a carrier molecule/coenzyme that carrieselectrons and protons to be utilized by the mitochondria to produce energy, ATP. This coenzymeplays a role in cellular energy metabolism, energy production, DNA repair, and immune cellfunction, and is also believed to be beneficial in maintaining cardiometabolic health. It isexpected that NAD+ levels gradually decline with increasing age, which may lead to age-relatedcomplications: neurodegeneration, cancer, metabolic disorders, cardiovascular disease, andfrailty. Thus, NAD+ supplementation, available on the market as IV therapy or oral precursors(such as nicotinamide, nicotinic acid, nicotinamide mononucleotide (NMN)), has gainedpopularity as a therapeutic approach to improve tissue and organ function, prevent cognitivedecline, improve metabolic health, reduce inflammation, and restore energy. It is important tonote, however, that NAD+ therapy is not FDA-approved, and this pharmacological approachrequires additional and larger studies to be conducted to produce reliable data and determine itstherapeutic efficacy.Taking a look at the cellular mitochondria level, NAD+ is essential in the production ofenergy in the form of ATP through the Kreb’s cycle. This enzymatic reaction requires the use ofNAD+. First, glycolysis breaks down a molecule of glucose to produce 2 molecules of pyruvate.As this occurs, NAD+ takes 2 electrons and one proton from the hydrogen molecules present inglucose to yield NADH and frees the remaining proton. Pyruvate then enters the Kreb’s cycle,where NADH is also produced. The NADH releases electrons and protons in the mitochondrialspace; the electrons enter the electron transport chain embedded in the mitochondrial membranethereby allowing the protons to be pushed into the intermembrane space, resulting in a highproton concentration. The hydrogen ions (protons) then diffuse down their concentration gradientand back into the mitochondria via ATP synthase resulting in the production of ATP. Hence,NAD+ is an important coenzyme that drives ATP production needed for important bodilyfunctions, such as muscle contraction, nerve impulse transmission, and protein synthesis.In addition to its role in energy production, NAD+ aids in metabolism and regulatesmultiple metabolic pathways. Studies have shown that exercise, caloric restriction,time-restricted feeding, and a ketogenic diet increases NAD+ levels, which lead to the activationof sirtuins, which are NAD(+)-dependent protein deacetylases that are involved in cell survival,proliferation, DNA repair, and cell metabolism. A high-fat content diet, postpartum weight loss,and disruption of the circadian rhythm interferes with metabolic status and leads to lower NAD+levels, and in turn, reduces sirtuin activity. In contrast, increased NAD+ levels has been shown toreduce reductive stress, drive metabolic reactions, and promote deacylase activity, which regulatemitochondrial function and protects the individual from metabolic disease due to a high-fat diet.Low levels of NAD+ are seen in the obese population, which in turn, accelerates aging and putsthese individuals at risk for insulin resistance, high blood glucose levels, high blood pressure,and dyslipidemia. Hence, there is growing evidence that targeting NAD+ metabolism andboosting NAD+ levels via IV or oral, are possible therapeutic approaches to help treat andprotect against metabolic disease and aging in these patients.Moreover, there is evidence that NAD+ has neuroprotective properties. As the agingprocess takes place, there is decreased expression of NAMPT enzyme, which is one of the majorcauses of NAD+ decline. Low levels of NAD+ not only is a result of old age, but is also depletedin those with Alzheimers and Parkinsons disease, although the cause of NAD+ loss in the braindue to neurodegenerative diseases remains unknown. Axonal degeneration is one of the firstsigns of neuronal disorders and is characterized by rapid NAD+ depletion. There is evidence thatNAD+ is a crucial player in the maintenance of a healthy nervous system and can impact thefunction of multiple brain cell types. It is hypothesized that restoring NAD+ levels with NAD+supplements may prevent axon degeneration, improve neuronal cell health, memory, andcognitive function. Currently, there are several clinical trials taking place to determine the use ofNAD+ precursors in treating neurological disorders and to promote healthy aging.Specialized IV therapy services may offer NAD+ IV therapy, however, it is currently notcovered by Medicare, Medicaid, and insurance companies. NAD+ therapy is not approved by theFDA for the treatment of any condition. NAD+ may be administered intravenously,intramuscularly, or orally. An intravenous administration typically runs 1-4 hours for a period of4 consecutive days upon initial treatment, followed by maintenance doses every 4-8 weeks. Itmay cost between $6,000 to $17,000. The IV infusion contains amino acids and other nutritionalsupplements to help provide energy and increase NAD+ levels in the body, which results inincreased energy, improved mood, and restored cognitive function. Off-label conditions that callfor the use of NAD+ treatment include chronic fatigue syndrome, Alzheimer’s and Parkinson’sdisease, high cholesterol, high blood pressure, symptoms of aging, and alcohol and illicit drugaddiction.ReferencesAmjad, Sara, et al. “Role of Nad+ in Regulating Cellular and Metabolic Signaling Pathways.”Molecular Metabolism, July 2021,www.ncbi.nlm.nih.gov/pmc/articles/PMC7973386/.Covarrubias, Anthony J, et al. “Nad+ Metabolism and Its Roles in Cellular Processes duringAgeing.” Nature Reviews. Molecular Cell Biology, 22 Dec. 2020,www.ncbi.nlm.nih.gov/pmc/articles/PMC7963035/#BX1.McGhee, Moira K. “Nad Therapy.” Help.Org, 26 Aug. 2020, www.help.org/nad-therapy/.“NAD IV Therapy - RESTORE HYPER WELLNESS®.” Restore Hyper Wellness.,www.restore.com/services/nad-iv-drip-therapy. Accessed 17 May 2023.Radenkovic, Dina, et al. “Clinical Evidence for Targeting NAD Therapeutically.”Pharmaceuticals (Basel, Switzerland), 15 Sept. 2020,www.ncbi.nlm.nih.gov/pmc/articles/PMC7558103/.