written by Pharm. D. Candidate Trisha Khong
The Use of NAD+ IV Therapy for Energy Rejuvenation, Cognitive Clarity, and Maintenance of Cellular Health
Nicotinamide adenine dinucleotide (NAD) is a carrier molecule/coenzyme that carries
electrons and protons to be utilized by the mitochondria to produce energy, ATP. This coenzyme
plays a role in cellular energy metabolism, energy production, DNA repair, and immune cell
function, and is also believed to be beneficial in maintaining cardiometabolic health. It is
expected that NAD+ levels gradually decline with increasing age, which may lead to age-related
complications: neurodegeneration, cancer, metabolic disorders, cardiovascular disease, and
frailty. Thus, NAD+ supplementation, available on the market as IV therapy or oral precursors
(such as nicotinamide, nicotinic acid, nicotinamide mononucleotide (NMN)), has gained
popularity as a therapeutic approach to improve tissue and organ function, prevent cognitive
decline, improve metabolic health, reduce inflammation, and restore energy. It is important to
note, however, that NAD+ therapy is not FDA-approved, and this pharmacological approach
requires additional and larger studies to be conducted to produce reliable data and determine its
therapeutic efficacy.
Taking a look at the cellular mitochondria level, NAD+ is essential in the production of
energy in the form of ATP through the Kreb’s cycle. This enzymatic reaction requires the use of
NAD+. 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 in
glucose 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 mitochondrial
space; the electrons enter the electron transport chain embedded in the mitochondrial membrane
thereby allowing the protons to be pushed into the intermembrane space, resulting in a high
proton concentration. The hydrogen ions (protons) then diffuse down their concentration gradient
and 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 bodily
functions, such as muscle contraction, nerve impulse transmission, and protein synthesis.
In addition to its role in energy production, NAD+ aids in metabolism and regulates
multiple metabolic pathways. Studies have shown that exercise, caloric restriction,
time-restricted feeding, and a ketogenic diet increases NAD+ levels, which lead to the activation
of 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 to
reduce reductive stress, drive metabolic reactions, and promote deacylase activity, which regulate
mitochondrial 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 puts
these individuals at risk for insulin resistance, high blood glucose levels, high blood pressure,
and dyslipidemia. Hence, there is growing evidence that targeting NAD+ metabolism and
boosting NAD+ levels via IV or oral, are possible therapeutic approaches to help treat and
protect against metabolic disease and aging in these patients.
Moreover, there is evidence that NAD+ has neuroprotective properties. As the aging
process takes place, there is decreased expression of NAMPT enzyme, which is one of the major
causes of NAD+ decline. Low levels of NAD+ not only is a result of old age, but is also depleted
in those with Alzheimers and Parkinsons disease, although the cause of NAD+ loss in the brain
due to neurodegenerative diseases remains unknown. Axonal degeneration is one of the first
signs of neuronal disorders and is characterized by rapid NAD+ depletion. There is evidence that
NAD+ is a crucial player in the maintenance of a healthy nervous system and can impact the
function of multiple brain cell types. It is hypothesized that restoring NAD+ levels with NAD+
supplements may prevent axon degeneration, improve neuronal cell health, memory, and
cognitive function. Currently, there are several clinical trials taking place to determine the use of
NAD+ precursors in treating neurological disorders and to promote healthy aging.
Specialized IV therapy services may offer NAD+ IV therapy, however, it is currently not
covered by Medicare, Medicaid, and insurance companies. NAD+ therapy is not approved by the
FDA 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 of
4 consecutive days upon initial treatment, followed by maintenance doses every 4-8 weeks. It
may cost between $6,000 to $17,000. The IV infusion contains amino acids and other nutritional
supplements to help provide energy and increase NAD+ levels in the body, which results in
increased energy, improved mood, and restored cognitive function. Off-label conditions that call
for the use of NAD+ treatment include chronic fatigue syndrome, Alzheimer’s and Parkinson’s
disease, high cholesterol, high blood pressure, symptoms of aging, and alcohol and illicit drug
addiction.
References
Amjad, 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 during
Ageing.” 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,
Thank you Dr. Zhong for this cutting-edge contribution. Patients finding a better way towards preventative care and maintaining their health through non-traditional pathaways.