NAD+ IV

Full ingredient list

Exact amounts delivered in each size. Formulas are compounded per patient and can be adjusted by your provider.

Supporting studies

• 1

  NAD+ is the molecule that physically carries electrons into the mitochondrial electron transport chain, making it indispensable for ATP energy production.

  This authoritative review in Cell Metabolism details how NADH generated by metabolism is oxidized at Complex I of the mitochondrial electron transport chain, relaying electrons through the downstream complexes to build the proton gradient that F0F1-ATP synthase uses to phosphorylate ADP into ATP. The authors describe NAD+ as a vital cofactor that can rewire metabolism, activate sirtuins, and maintain mitochondrial fitness — including through the mitochondrial unfolded protein response. NAD+ levels rise in response to energy stresses such as fasting, caloric restriction, and exercise, positioning NAD+ as the cell's central energy sensor.

  Mechanistic review Carles Cantó et al. NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus. Cell Metabolism. 2015. PMID 26118927 ↗

• 2

  The sirtuin longevity enzymes and the PARP DNA-repair enzymes cannot work without NAD+ — restoring NAD+ levels has been shown to slow and even reverse aging-associated changes.

  This Nature Reviews Molecular Cell Biology review establishes NAD+ as both a redox coenzyme central to energy metabolism and an essential cofactor for non-redox enzymes including the sirtuins, CD38, and the poly(ADP-ribose) polymerases (PARPs). Through these enzymes NAD+ governs DNA repair, chromatin remodeling, cellular senescence, metabolic pathways, and immune function. The authors note that NAD+ declines progressively with age across multiple organisms and that this decline is causally linked to cognitive decline, metabolic disease, sarcopenia, and frailty — and that many of these aging-associated conditions can be slowed and even reversed by restoring NAD+ levels, making NAD+ metabolism a therapeutic target for extending healthspan.

  Systematic review (mechanistic) Anthony J. Covarrubias et al. NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology. 2021. PMID 33353981 ↗

• 3

  NAD+ levels measurably fall with age in human tissue, and that fall tracks directly with accumulated DNA damage and overworked repair enzymes.

  Researchers analyzed pelvic skin tissue from 49 human subjects spanning ages 0 to 77 years. DNA damage rose significantly with age in both males (p = 0.029) and females (p = 0.003), PARP activity rose sharply with age in males (p < 0.0001), and PARP activity was inversely correlated with tissue NAD+ (p = 0.0003). NAD+ concentrations declined significantly with age in both sexes. The authors concluded this provides quantitative human evidence that PARP hyperactivation driven by lifelong oxidative DNA damage consumes NAD+, and that the resulting NAD+ depletion may be a major driver of aging by limiting energy production, DNA repair, and genomic signaling.

  Observational human tissue study Hassina Massudi et al. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012. PMID 22848760 ↗

• 4

  Non-invasive brain imaging shows that NAD+ and the NAD+/NADH energy ratio decline steadily with age in the living human brain.

  Using a 7-Tesla magnetic resonance scanner, researchers developed the first in vivo assay capable of simultaneously measuring intracellular NAD+ and NADH concentrations and the NAD+/NADH ratio in intact human brain tissue, applied to 17 healthy volunteers aged 21-68. Brain NAD+ concentration correlated negatively with age (r = -0.75), NADH correlated positively with age (r = 0.68), and the NAD+/NADH redox ratio declined strongly with age (r = -0.76). The authors concluded these results provide direct evidence of declining mitochondrial function accompanying normal human aging.

  Observational human imaging study (in vivo 31p mrs) Xiao-Hong Zhu et al. In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proceedings of the National Academy of Sciences of the United States of America. 2015. PMID 25730862 ↗

• 5

  Human research has directly tracked what happens to NAD+ during an intravenous infusion, confirming that infused NAD+ is taken up and metabolized by the body rather than simply passing through.

  This pilot study infused 750 mg of NAD+ in normal saline intravenously over 6 hours (about 3 micromoles/minute) in healthy men aged 30-55, with saline controls, and tracked plasma and urine NAD+ and its metabolites through 8 hours. The researchers found that at this infusion rate NAD+ was rapidly and completely cleared from the plasma for at least the first two hours — evidence of avid tissue uptake and metabolism — before plasma NAD+ and metabolites began to rise. The metabolite pattern was consistent with NAD+ glycohydrolase and NAD+ pyrophosphatase activity, and by 6 hours NAD+ and methylnicotinamide appeared in the urine. This is the first human study to document the fate of directly infused intravenous NAD+.

  Clinical trial (human intravenous pharmacokinetic pilot study) Ross Grant et al. A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD+. Frontiers in Aging Neuroscience. 2019. PMID 31572171 ↗

• 6

  Supplying an NAD+ precursor raises whole-blood NAD+ dose-dependently in humans — by 142% at the highest dose — and those elevated levels hold.

  In an 8-week randomized, double-blind, placebo-controlled trial in healthy overweight adults, oral nicotinamide riboside (NR) at 100 mg, 300 mg, and 1000 mg per day raised whole-blood NAD+ by 22 ± 9%, 51 ± 7%, and 142 ± 14% respectively by day 14, and those elevations were maintained for the remainder of the study. The route studied was oral. There were no reports of flushing and no significant differences in adverse events between the NR and placebo groups or between dose groups, and NR did not elevate LDL cholesterol or dysregulate 1-carbon metabolism.

  Randomized controlled trial Dietrich Conze et al. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Scientific Reports. 2019. PMID 31278280 ↗

• 7

  Raising NAD+ reaches aging human muscle tissue itself and lowers circulating inflammatory signals.

  Twelve aged men received 1 g/day of oral nicotinamide riboside for 21 days in a placebo-controlled, randomized, double-blind, crossover trial with muscle biopsies. Targeted metabolomics confirmed that NR elevated the skeletal muscle NAD+ metabolome, shown by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products — establishing that a boosted NAD+ supply is genuinely delivered to aged human muscle, not just to the bloodstream. Muscle RNA sequencing showed NR-driven changes in energy metabolism and mitochondrial gene programs, and NR also depressed levels of circulating inflammatory cytokines. The route studied was oral.

  Randomized controlled trial (double-blind, placebo-controlled, crossover) Yasir S. Elhassan et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Reports. 2019. PMID 31412242 ↗

• 8

  Niacin (B3) raised blood NAD+ up to eight-fold and increased muscle strength in a human clinical trial.

  In this clinical trial published in Cell Metabolism, adults with adult-onset mitochondrial myopathy and matched healthy controls took escalating niacin doses of 750-1000 mg/day (10 months for patients, 4 months for controls). Blood NAD+ rose up to 8-fold, muscle NAD+ in patients normalized to control levels, and muscle strength and mitochondrial biogenesis increased in all subjects. Muscle metabolite profiles shifted toward the healthy control pattern and liver fat decreased. This is direct human evidence that niacin is the working precursor that refills the NAD+ pool driving cellular energy production. Route was oral.

  Clinical trial (human interventional, with mechanistic analyses) Pirinen E, et al. Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy. Cell Metabolism. 2020. PMID 32386566 ↗

• 9

  Boosting NAD+ improved muscle insulin sensitivity in a rigorous trial published in Science — measured by the gold-standard clamp technique.

  In a 10-week randomized, placebo-controlled, double-blind trial, postmenopausal women with prediabetes who were overweight or obese received the NAD+ precursor nicotinamide mononucleotide (NMN) or placebo. Insulin-stimulated glucose disposal, measured by hyperinsulinemic-euglycemic clamp — the gold standard for insulin sensitivity — increased after NMN supplementation but did not change with placebo. Skeletal muscle insulin signaling (AKT and mTOR phosphorylation) also increased, and NMN upregulated platelet-derived growth factor receptor beta and other genes tied to muscle remodeling. The route studied was oral (NCT03151239).

  Randomized controlled trial Mihoko Yoshino et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021. PMID 33888596 ↗

• 10

  An NAD+ precursor improved aerobic capacity in trained runners, apparently by helping skeletal muscle use oxygen more efficiently.

  Forty-eight recreationally trained amateur runners were randomized to placebo or nicotinamide mononucleotide at 300, 600, or 1200 mg/day for six weeks alongside structured aerobic training, with cardiopulmonary exercise testing before and after. Oxygen uptake (VO2), percentage of VO2max, power at the first ventilatory threshold, and power at the second ventilatory threshold all increased to a greater degree in the medium- and high-dose groups than in controls. Because cardiac output measures were unchanged, the authors concluded the improvement in aerobic capacity is likely the result of enhanced oxygen utilization by skeletal muscle. The route studied was oral.

  Randomized controlled trial (double-blind) Bagen Liao et al. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. Journal of the International Society of Sports Nutrition. 2021. PMID 34238308 ↗

• 11

  Raising NAD+ increased NAD+ levels inside the living human brain and shifted brain metabolism, with signs of clinical benefit in Parkinson's disease.

  In the double-blind, randomized NADPARK phase I trial, 30 newly diagnosed, treatment-naive Parkinson's patients received 1,000 mg/day of the NAD+ precursor nicotinamide riboside or placebo for 30 days. Treatment was well tolerated and produced a significant increase in cerebral NAD levels measured by 31-phosphorus magnetic resonance spectroscopy, along with increased NAD-related metabolites in cerebrospinal fluid. Participants whose brain NAD rose showed altered cerebral metabolism on 18F-FDG PET associated with mild clinical improvement, plus transcriptional upregulation of mitochondrial, lysosomal, and proteasomal pathways in blood and muscle and reduced inflammatory cytokines in serum and CSF. The authors nominated NAD+ repletion as a potential neuroprotective therapy warranting larger trials. The route studied was oral.

  Randomized controlled trial (phase i, double-blind) Brage Brakedal et al. The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease. Cell Metabolism. 2022. PMID 35235774 ↗

• 12

  In older adults, raising blood NAD+ was accompanied by faster walking speed and better sleep quality.

  Sixty older adults were randomized in a double-blind, placebo-controlled, parallel-group trial to 250 mg/day of nicotinamide mononucleotide or placebo for 12 weeks. After 12 weeks the NMN group had significantly higher blood NAD+ and NAD metabolite levels and a significantly shorter 4-meter walking time than placebo, and the improvement in walking time correlated with the rise in blood NAD+ and its metabolites. The NMN group also showed improved sleep quality versus placebo, with lower scores for daytime dysfunction and lower global Pittsburgh Sleep Quality Index scores. No adverse effects related to the test substance were observed. The route studied was oral.

  Randomized controlled trial (double-blind, placebo-controlled) Masashi Morifuji et al. Ingestion of β-nicotinamide mononucleotide increased blood NAD levels, maintained walking speed, and improved sleep quality in older adults in a double-blind randomized, placebo-controlled study. GeroScience. 2024. PMID 38789831 ↗

• 13

  NADH-based mitochondrial support reduced fatigue and improved quality of life in people with chronic fatigue syndrome.

  In a 12-week prospective, randomized, double-blind, placebo-controlled trial of 207 patients with myalgic encephalomyelitis/chronic fatigue syndrome, participants received 200 mg coenzyme Q10 plus 20 mg NADH daily or matching placebo. The active group showed a significant reduction in cognitive fatigue perception and in overall Fatigue Impact Scale (FIS-40) score, along with improved health-related quality of life on the SF-36. Sleep duration improved significantly at 4 weeks and habitual sleep efficiency at 8 weeks. The authors concluded that CoQ10 plus NADH is a potentially safe therapeutic option for cognitive fatigue and quality of life in ME/CFS. The route studied was oral, and NADH was given in combination with CoQ10.

  Randomized controlled trial (double-blind, placebo-controlled) Jesús Castro-Marrero et al. Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2021. PMID 34444817 ↗

References

• 1Carles Cantó et al. NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus. Cell Metabolism. 2015. PMID 26118927 ↗
• 2Anthony J. Covarrubias et al. NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology. 2021. PMID 33353981 ↗
• 3Hassina Massudi et al. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012. PMID 22848760 ↗
• 4Xiao-Hong Zhu et al. In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proceedings of the National Academy of Sciences of the United States of America. 2015. PMID 25730862 ↗
• 5Ross Grant et al. A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD+. Frontiers in Aging Neuroscience. 2019. PMID 31572171 ↗
• 6Dietrich Conze et al. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Scientific Reports. 2019. PMID 31278280 ↗
• 7Yasir S. Elhassan et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Reports. 2019. PMID 31412242 ↗
• 8Pirinen E, et al. Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy. Cell Metabolism. 2020. PMID 32386566 ↗
• 9Mihoko Yoshino et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021. PMID 33888596 ↗
• 10Bagen Liao et al. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. Journal of the International Society of Sports Nutrition. 2021. PMID 34238308 ↗
• 11Brage Brakedal et al. The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease. Cell Metabolism. 2022. PMID 35235774 ↗
• 12Masashi Morifuji et al. Ingestion of β-nicotinamide mononucleotide increased blood NAD levels, maintained walking speed, and improved sleep quality in older adults in a double-blind randomized, placebo-controlled study. GeroScience. 2024. PMID 38789831 ↗
• 13Jesús Castro-Marrero et al. Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2021. PMID 34444817 ↗