NAD+ Therapy New Zealand: A Clinical Reference

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme present in every living cell, central to energy metabolism, DNA repair, and cellular signalling. NAD+ therapy in New Zealand has emerged as a clinical intervention of increasing interest, driven by a growing body of research linking declining NAD+ levels to ageing, neurodegeneration, and metabolic dysfunction. This article provides a comprehensive examination of NAD+ biology, the rationale for intravenous and injectable delivery, the current evidence base, and what a clinical NAD+ infusion involves in practice.

What is NAD+?

Nicotinamide adenine dinucleotide exists in two primary forms: the oxidised form (NAD+) and the reduced form (NADH). Together, these constitute a redox couple fundamental to cellular metabolism. NAD+ functions as an electron carrier in catabolic reactions — accepting hydride ions during glycolysis, the citric acid cycle, and fatty acid oxidation — before transferring them to the mitochondrial electron transport chain for adenosine triphosphate (ATP) production.

Beyond its role as a metabolic shuttle, NAD+ serves as a consumed substrate for several families of enzymes with critical regulatory functions:

Sirtuins (SIRT1–SIRT7): A family of NAD+-dependent deacylases and ADP-ribosyltransferases that regulate gene expression, mitochondrial biogenesis, inflammation, circadian rhythm, and stress resistance. Sirtuins cleave NAD+ to produce nicotinamide and O-acetyl-ADP-ribose as part of their catalytic cycle, meaning their activity is directly constrained by NAD+ availability (Imai & Guarente, 2014).

Poly(ADP-ribose) polymerases (PARPs): Enzymes critical to DNA damage detection and repair. PARP1 in particular is a major consumer of cellular NAD+, and chronic DNA damage — as occurs with ageing and genotoxic stress — can substantially deplete NAD+ pools (Cantó et al., 2015).

CD38 and CD157: Ectoenzymes that hydrolyse NAD+ and play roles in immune cell signalling and calcium mobilisation. CD38 expression increases with age, and research has identified it as a primary driver of age-related NAD+ decline in multiple tissues (Camacho-Pereira et al., 2016).

NAD+ is synthesised through several biosynthetic pathways: the de novo pathway from tryptophan (the kynurenine pathway), the Preiss-Handler pathway from nicotinic acid, and the salvage pathway from nicotinamide. The salvage pathway, catalysed by the rate-limiting enzyme nicotinamide phosphoribosyltransferase (NAMPT), is the dominant route for maintaining intracellular NAD+ in most mammalian tissues. Intracellular NAD+ concentrations decline significantly with age. Studies in murine models have demonstrated reductions of 30–50% in key tissues including liver, skeletal muscle, and brain by mid-to-late life (Yoshino et al., 2011). This decline is attributed to a combination of decreased NAMPT expression, increased CD38-mediated degradation, and heightened PARP activity secondary to accumulated DNA damage. The functional consequences of this decline — impaired mitochondrial function, dysregulated gene expression, diminished DNA repair capacity, and increased inflammation — overlap substantially with the hallmarks of ageing.

How it works

The therapeutic rationale for NAD+ replenishment centres on restoring the coenzyme to concentrations sufficient to support optimal sirtuin activity, PARP-mediated DNA repair, and mitochondrial electron transport. The mechanisms through which elevated NAD+ may confer benefit operate at several interconnected levels.

MITOCHONDRIAL FUNCTION AND ENERGY METABOLISM

NAD+ is indispensable to oxidative phosphorylation. As the primary electron acceptor in mitochondrial complex I (NADH:ubiquinone oxidoreductase), the NAD+/NADH ratio directly influences the rate of ATP generation. Declining NAD+ levels are associated with reduced mitochondrial membrane potential, impaired oxygen consumption, and a shift toward glycolytic metabolism — a profile characteristic of both ageing and metabolic disease. Preclinical studies have demonstrated that NAD+ repletion restores mitochondrial function in aged tissues, increases oxygen consumption rates, and enhances exercise capacity in murine models (Gomes et al., 2013).

SIRTUIN ACTIVATION AND EPIGENETIC REGULATION

SIRT1 and SIRT3 are particularly NAD+-sensitive. SIRT1 deacetylates key transcriptional regulators including PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), promoting mitochondrial biogenesis and fatty acid oxidation. SIRT3 resides in the mitochondrial matrix and regulates enzymes of the tricarboxylic acid cycle and electron transport chain. By providing substrate for these enzymes, NAD+ supplementation may support metabolic flexibility, reduce oxidative stress, and modulate inflammatory pathways mediated by NF-κB (Zhang et al., 2016).

DNA REPAIR AND GENOMIC STABILITY

PARP1 activation in response to DNA strand breaks consumes substantial quantities of NAD+. In conditions of chronic genotoxic stress, this consumption can outpace biosynthesis, creating a deficit that impairs both repair capacity and sirtuin-dependent protective mechanisms. Supplementation strategies that restore NAD+ pools have been shown to enhance DNA repair kinetics in preclinical models, with particular relevance to tissues with high replicative rates and environmental exposure (Li et al., 2017).

NEURONAL FUNCTION

NAD+ plays a role in axonal integrity and neuronal survival. The enzyme SARM1 (sterile alpha and TIR motif-containing 1) degrades NAD+ during Wallerian degeneration following axonal injury. Maintaining elevated NAD+ levels has been shown to delay axonal degeneration in animal models, prompting investigation into NAD+ supplementation for neurodegenerative conditions (Essuman et al., 2017).

The evidence

The research landscape for NAD+ supplementation spans robust preclinical data in animal models and a growing but still early-stage body of human clinical evidence. It is important to distinguish between these evidence tiers when evaluating therapeutic claims.

PRECLINICAL EVIDENCE

Animal studies have produced consistently encouraging results. Supplementation with NAD+ precursors (nicotinamide riboside and nicotinamide mononucleotide) in aged mice has been associated with improved mitochondrial function, enhanced insulin sensitivity, reduced inflammation, extended healthspan, and in some models, increased lifespan (Mills et al., 2016; Zhang et al., 2016). Direct intraperitoneal administration of NAD+ has demonstrated neuroprotective effects in models of ischaemia and neurodegeneration (Wang et al., 2016).

HUMAN CLINICAL EVIDENCE

Human trials remain comparatively limited in scope and duration, though the pace of investigation has accelerated markedly since 2020.

A randomised controlled trial of nicotinamide riboside (NR) supplementation in healthy older adults demonstrated that oral NR effectively elevated NAD+ metabolites in blood, though functional clinical endpoints showed modest or mixed results (Martens et al., 2018). A subsequent trial found that chronic NR supplementation reduced circulating inflammatory cytokines in older adults, suggesting potential anti-inflammatory effects (Elhassan et al., 2019).

Nicotinamide mononucleotide (NMN) has been evaluated in several human trials. A Japanese randomised controlled trial in prediabetic women demonstrated that oral NMN improved skeletal muscle insulin sensitivity and glucose uptake (Yoshino et al., 2021). A study in amateur runners found that NMN supplementation enhanced aerobic capacity, though the effect was modest and requires replication (Liao et al., 2021).

Direct intravenous NAD+ administration has a smaller but emerging evidence base. A pilot pharmacokinetic study demonstrated that IV NAD+ rapidly and substantially elevates plasma NAD+ levels, achieving concentrations that oral precursors do not replicate in blood (Grant et al., 2019). Clinical case series have reported subjective improvements in energy, cognitive clarity, and general wellbeing following IV NAD+ infusions, though controlled trial data for this specific route of administration remain limited [citation needed].

NEW ZEALAND CONTEXT

NAD+ is not a registered pharmaceutical in New Zealand and is not listed in the Medsafe database as a prescription medicine. Its use in clinical settings falls under the regulatory framework for compounded or imported preparations administered by registered health professionals. There are currently no New Zealand–specific clinical guidelines addressing NAD+ supplementation. The Ministry of Health New Zealand and BPAC NZ have not published formal position statements on NAD+ therapy, though general guidance on intravenous supplementation practices applies (health.govt.nz; bpac.org.nz).

IV and injectable delivery versus oral supplementation

A critical distinction in NAD+ therapy relates to the route of administration and its pharmacokinetic implications.

ORAL NAD+ PRECURSORS

NAD+ itself is poorly bioavailable when taken orally. The molecule is hydrolysed in the gastrointestinal tract and undergoes extensive first-pass hepatic metabolism. For this reason, oral supplementation strategies have focused on NAD+ precursors — primarily nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) — which can be absorbed intact and converted to NAD+ intracellularly via the salvage pathway. While oral precursors do elevate whole-blood and tissue NAD+ levels, the magnitude of increase is constrained by absorption variability, hepatic extraction, and the rate-limiting enzymatic steps in conversion (Trammell et al., 2016).

INTRAVENOUS NAD+

Intravenous infusion bypasses gastrointestinal degradation and hepatic first-pass metabolism entirely, delivering NAD+ directly into the systemic circulation. Pharmacokinetic data indicate that IV administration produces substantially higher plasma NAD+ concentrations compared with equimolar oral doses of precursors (Grant et al., 2019). Whether these supraphysiological plasma levels translate to proportionally greater intracellular repletion across all tissues remains an active area of investigation, as NAD+ transport across cell membranes involves specific transporters and may be tissue-dependent.

The clinical rationale for IV delivery is that achieving higher systemic concentrations may overcome rate-limiting steps in cellular uptake and facilitate more rapid restoration of depleted NAD+ pools — particularly in individuals with substantial baseline deficits due to age, metabolic stress, or chronic inflammation.

INTRAMUSCULAR AND SUBCUTANEOUS INJECTION

Injectable NAD+ formulations offer an alternative parenteral route with a slower absorption profile than IV infusion. These may be appropriate for maintenance protocols following an initial IV loading period, or for individuals who prefer shorter appointment durations. Comparative pharmacokinetic data between injectable and IV routes in humans remain limited.

Who may benefit

NAD+ infusion therapy may be appropriate for several clinical profiles, though it is not a substitute for the diagnosis or management of specific medical conditions.

Individuals experiencing age-related changes in energy, cognitive function, or recovery capacity may benefit from NAD+ repletion, given the well-documented decline in NAD+ levels with ageing. Those with high metabolic demands — including endurance athletes, individuals in physically demanding occupations, or those recovering from periods of significant physiological stress — may find NAD+ supplementation supports recovery and cellular repair.

Individuals with suboptimal metabolic markers, including early insulin resistance or features consistent with metabolic syndrome, represent a population of interest based on the Yoshino et al. (2021) human trial data, though NAD+ infusion should complement rather than replace standard metabolic management.

Those seeking to support longevity-oriented health strategies may incorporate NAD+ therapy as one component of a broader programme that includes exercise, nutrition, sleep optimisation, and appropriate medical screening.

NAD+ infusion has also been explored in the context of alcohol withdrawal and substance recovery programmes, with some clinical facilities reporting favourable outcomes, though robust controlled trial evidence for this application remains sparse. It is not possible to determine suitability for NAD+ therapy without an individualised clinical assessment. Pre-existing medical conditions, concurrent medications, and overall health status must be evaluated by a qualified health professional prior to any infusion.

What to expect

A clinical NAD+ infusion at Drips is delivered by a registered nurse with intravenous therapy experience. Every appointment is preceded by a doctor’s consultation and assessment to determine suitability, review health history, and identify any contraindications.

BEFORE THE INFUSION

Clients are advised to be well-hydrated and to have eaten within the preceding hours. A brief health screening is conducted, including review of medical history, current medications, and any previous adverse reactions to intravenous therapies. As a fully mobile service, Drips conducts infusions at the client's preferred location — whether at home, in the workplace, or at a suitable private setting.

DURING THE INFUSION

NAD+ is administered via a peripheral intravenous cannula, typically in the forearm. The infusion rate is carefully controlled, as NAD+ infused too rapidly is associated with transient side effects including chest tightness, abdominal cramping, nausea, and a sensation of warmth or flushing. These effects are rate-dependent and resolve with slowing or pausing the infusion. Clinical protocols therefore employ a gradual titration, adjusting the drip rate to the client's tolerance. A standard NAD+ infusion typically takes between two and four hours, depending on the dose administered and individual tolerance. During this time, the nurse remains present to monitor the infusion rate, observe for any adverse effects, and adjust the administration as needed.

AFTER THE INFUSION

Clients commonly report a sense of increased mental clarity and energy in the hours and days following an NAD+ infusion, though individual responses vary. Some individuals experience mild fatigue in the immediate post-infusion period. There is no required downtime, and most clients resume normal activities the same day. Protocols vary, but initial courses may involve multiple infusions over a concentrated period, with subsequent maintenance sessions at longer intervals. The specific protocol is determined on an individual basis following clinical assessment.

Considerations and safety

NAD+ infusion is generally well tolerated when administered by trained clinical staff at appropriate rates. The most commonly reported adverse effects — nausea, flushing, chest tightness, and abdominal discomfort — are infusion-rate dependent and manageable through rate adjustment. Serious adverse events are rare in published literature.

There are limited data on NAD+ supplementation in pregnancy and lactation, and infusion is generally not recommended in these populations. Individuals with active malignancy should discuss NAD+ therapy with their oncologist, as theoretical concerns exist regarding the role of NAD+ in rapidly proliferating cells, though this remains an area of active investigation (Navas & Carnero, 2021). Potential interactions with concurrent medications have not been comprehensively characterised. Individuals taking anticoagulants, antihypertensives, or medications metabolised via NAD+-dependent pathways should disclose all medications during the clinical assessment.

All Drips services are nurse-administered and overseen by our medical director. A doctor’s consultation precedes every appointment to evaluate suitability and ensure that NAD+ infusion is appropriate given the individual's health profile and goals.

REFERENCES

Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014;24(8):464-471. PMID: 24786309.

Cantó C, Menzies KJ, Auwerx J. NAD+ metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus. Cell Metab. 2015;22(1):31-53. PMID: 26118927.

Camacho-Pereira J, Tarragó MG, Chini CCS, et al. CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell Metab. 2016;23(6):1127-1139. PMID: 27304511.

Yoshino J, Mills KF, Yoon MJ, Imai S. Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011;14(4):528-536. PMID: 21982712.

Gomes AP, Price NL, Ling AJY, et al. Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell. 2013;155(7):1624-1638. PMID: 24360282.

Zhang H, Ryu D, Wu Y, et al. NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science. 2016;352(6292):1436-1443. PMID: 27127236.

Li J, Bonkowski MS, Moniot S, et al. A conserved NAD+ binding pocket that regulates protein-protein interactions during aging. Science. 2017;355(6331):1312-1317. PMID: 28336669.

Essuman K, Summers DW, Sasaki Y, et al. The SARM1 Toll/interleukin-1 receptor domain possesses intrinsic NAD+ cleavage activity that promotes pathological axonal degeneration. Neuron. 2017;93(6):1334-1343. PMID: 28334607.

Mills KF, Yoshida S, Stein LR, et al. Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Metab. 2016;24(6):795-806. PMID: 28068222.

Wang P, Xu TY, Guan YF, et al. Nicotinamide phosphoribosyltransferase protects against ischemic stroke through SIRT1-dependent adenosine monophosphate-activated kinase pathway. Ann Neurol. 2011;69(2):360-374. PMID: 21246601.

Martens CR, Denman BA, Mazzo MR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286. PMID: 29599478.

Elhassan YS, Kluckova K, Fletcher RS, et al. Nicotinamide riboside augments the aged human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures. Cell Rep. 2019;28(7):1717-1728. PMID: 31412242.

Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. PMID: 33888596.

Liao B, Zhao Y, Wang D, et al. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. J Int Soc Sports Nutr. 2021;18(1):54. PMID: 34238308.

Grant R, Berg J,"; et al. A pilot study investigating changes in the human plasma and urine NAD+ metabolome during a 6 hour intravenous infusion of NAD+. Front Aging Neurosci. 2019;11:257. PMID: 31572174.

Trammell SAJ, Schmidt MS, Weidemann BJ, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016;7:12948. PMID: 27721479.

Navas LE, Carnero A. NAD+ metabolism, stemness, the immune response, and cancer. Signal Transduct Target Ther. 2021;6(1):2. PMID: 33384409.

This article is intended for educational purposes only and does not constitute medical advice. Individual health needs vary. All Drips services are delivered by registered health professionals and are preceded by a clinical assessment to determine suitability.