What is NAD+?

Nicotinamide adenine dinucleotide, abbreviated NAD+, is a dinucleotide coenzyme built from an adenine nucleotide linked to a nicotinamide nucleotide through a pyrophosphate bridge. It is the oxidised form of the pair; the reduced form is NADH. Synonyms in the literature include diphosphopyridine nucleotide (DPN) and coenzyme I. As a dinucleotide it belongs to the pyridine nucleotide class, and it is conventionally described as a coenzyme rather than a vitamin, since it is assembled in cells from precursors rather than absorbed intact as a nutrient. The evidence block used for this page does not supply a sequence, molecular formula or molecular weight, so none is stated here.

The work indexed below centres on NAD+ as a substrate and product of the sirtuin and CD38/NADase families of enzymes, and on the salvage pathway enzymes that regenerate it from precursors such as nicotinamide, nicotinamide riboside and nicotinamide mononucleotide.

Research Studies

Oral NAD+ and whole-blood NAD+ change in healthy adults

A registered clinical trial is assessing the absorption, safety and efficacy of an oral nicotinamide adenine dinucleotide supplement in healthy adults [1]. The primary question is the change in NAD+ levels in whole blood from baseline to day 56, comparing the supplement against placebo. Participants complete questionnaires, provide blood samples, consume supplement or placebo for 55 days, and undergo evaluation of endothelial function [1]. This is a registered protocol; the evidence block does not report results.

Nicotinamide and retinal nerve layer thinning in primary open-angle glaucoma

The NADIR trial is testing whether high-dose nicotinamide, a vitamin B3 form, protects retinal nerve cells in adults with primary open-angle glaucoma who are already receiving standard eye drops or laser treatment [2]. The primary question is whether adding nicotinamide slows the rate of thinning of the inner retinal nerve cell layer, measured by a non-invasive eye scan, compared with standard therapy alone over 12 months. Participants are randomised to nicotinamide tablets by mouth, starting at 1.5 grams per day, or to the comparison arm [2].

Nicotinamide riboside and six-minute walk distance in peripheral artery disease

NICE-PAD II randomises 250 participants with peripheral artery disease aged 50 and older to nicotinamide riboside or placebo for six months [3]. The hypothesis under test is that the NR arm will show greater improvement or less decline in six-minute walk distance at six-month follow-up. Secondary outcomes include Walking Impairment Questionnaire distance score, PROMIS Mobility score, and calf muscle perfusion measured by magnetic resonance arterial spin labelling [3].

Delayed-release nicotinamide and post-COVID syndrome

An observational study is examining CICR-NAM, a nicotinamide tablet formulated to release its active substance selectively in the lower intestine, in patients with post-COVID syndrome and documented tryptophan deficiency [4]. The rationale given is that tryptophan metabolism, energy metabolism and the gut microbiome may be altered in post-COVID syndrome, and that in an earlier nutritional study patients with COVID-19 recovered physical performance more quickly when taking nicotinamide, with responders developing post-COVID syndrome less frequently [4]. The formulation is described as well tolerated in several studies [4].

MIB-626 (NMN) dose escalation in adults with Down syndrome

A trial is determining the safety and tolerability of increasing daily doses of MIB-626, a microcrystalline form of beta-nicotinamide mononucleotide, given for 28 consecutive days to adults with Down syndrome [6]. The study also explores pharmacokinetics and pharmacodynamics. Twenty-four adults with Down syndrome will be enrolled, with monitoring for adverse events and safety measurements including blood counts, chemistries, coagulation profile and electrocardiogram [6].

Topical nicotinamide riboside and facial skin ageing

A trial is evaluating topical niacinamide riboside, also called nicotinamide riboside, on signs of facial skin ageing [7]. The stated rationale is that skin NAD+ levels were reported to correlate negatively with age in both males and females, and that aged skin was also correlated with increased DNA damage, leading to the proposal that supporting skin NAD+ with precursors such as NR may address DNA damage associated with undesirable signs of skin ageing [7]. The evidence block notes that oral NR use as a dietary supplement has produced effective, efficient and reproducible results, without giving figures.

Nicotinamide riboside and brain vessel health, memory and physical function in Parkinson's disease

A trial is testing whether nicotinamide riboside, a form of vitamin B3 also known as NR, can improve blood vessel health in the brain, memory and physical function in eligible participants [8]. NR is described as investigational for this specific use because it is not yet established for it. The main questions are whether NR improves non-invasive measures of brain blood vessel health, memory testing results and physical function, with participants randomised to NR or placebo [8].

Nicotinamide and urinary tract diagnostics in catheter users

A separate trial enrols patients seeking care at a rehabilitation hospital clinic who believe they have a urinary tract infection [5]. Participants are pre-screened after consent using a standard-of-care symptom measure, the USQNB, and those at high or moderate likelihood of UTI are assigned to the presumed UTI arm and asked to attend for a urine sample and standard diagnostic testing; those not so assigned do not present to the clinic. Testing includes a repeated questionnaire about the UTI [5]. This study concerns diagnostic pathways rather than NAD+ supplementation, and is included here only because it appears in the same evidence set.

Mitochondrial homeostasis in myocardial fibrosis

Work on Guizhi Wuling Decoction, a combined prescription of the classical formulas Wuling San and Guizhi Fuling Wan, reports that the preparation alleviates myocardial fibrosis by restoring mitochondrial homeostasis, using network pharmacology, molecular docking and multi-omics integration [9]. The decoction has been clinically applied for cardiovascular diseases, and prior studies reported cardioprotective and anti-fibrotic effects [9]. This is a reference-only item: it supports context on mitochondrial and NAD+-adjacent biology and is not itself a study of an NAD+ compound.

Sources

• [1] A Clinical Trial to Assess the Absorption, Safety, and Efficacy of an Oral Nicotinamide Adenine Dinucleotide (NAD+) Supplement in Healthy Adults — https://clinicaltrials.gov/study/NCT07692633
• [2] Nicotinamide for Retinal Protection in Primary Open-Angle Glaucoma (NADIR Trial) — https://clinicaltrials.gov/study/NCT07808333
• [3] The NICE-PAD II Trial — https://clinicaltrials.gov/study/NCT07782671
• [4] Observational Study With CICR-NAM as a Food for Special Medicinal Purposes in Post-COVID Syndrome (PCS) — https://clinicaltrials.gov/study/NCT07798570
• [5] Rapid UTI Diagnostics in Lower Urinary Tract Dysfunction Among Catheter Users — https://clinicaltrials.gov/study/NCT07784829
• [6] NAD Augmentation to Prevent or Reverse Alzheimer's Disease in People With Down Syndrome — https://clinicaltrials.gov/study/NCT07278492
• [7] Efficacy of Topical Niacinamide Riboside on the Signs of Facial Skin Aging — https://clinicaltrials.gov/study/NCT07774000
• [8] NAD Supplementation in Parkinson's Disease — https://clinicaltrials.gov/study/NCT07703137
• [9] Guizhi Wuling Decoction alleviates myocardial fibrosis by restoring mitochondrial homeostasis: Evidence from network pharmacology, molecular docking, and multi-omics integration. — https://pubmed.ncbi.nlm.nih.gov/42462419/

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