Scope and interpretation

This appendix explains NAD+ metabolism and summarizes selected primary studies relevant to discussions of NAD+ precursors in dogs and cats. It is an educational reference, not a pet dosing protocol or a systematic review of every publication. The intervention, species, design, and measured outcome are part of each finding. Human and laboratory results should not be presented as demonstrated clinical effects in companion animals.

1. NAD+ system architecture

NAD+ and NADH form a redox pair used in metabolic reactions. NAD+ also supplies enzymes involved in cellular signaling and maintenance. A coenzyme’s essential role in normal biology is distinct from evidence that additional oral precursor improves an outcome. Foundational NR research identified a conserved route into NAD+ synthesis; NAMPT work investigated a separate nicotinamide salvage step. [1] [2]

1.1 Precursor identity and pathway entry

Nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), nicotinamide (NAM), and nicotinic acid (NA) are related but distinct compounds. NR can be phosphorylated through NRK-dependent metabolism toward NMN and NAD+. NAM enters salvage through NAMPT. Nicotinic acid uses the Preiss–Handler route. Findings for one input cannot establish equivalent exposure, tolerability, or effects from another input. [1] [2] [3]

1.2 NRK-dependent metabolism

Ratajczak and colleagues used experimental gain- and loss-of-function approaches to examine NRK1. Their results supported NRK1-dependent use of supplied NR and NMN in the studied systems, including extracellular conversion of NMN to NR. The study informs a pathway model; it does not establish the fraction of an oral dose delivered to any particular canine or feline tissue. [3]

1.3 NAD+ consumers and cellular compartments

Sirtuins and PARPs use NAD+ as a substrate, while the NAD+/NADH pair participates in redox reactions. Measuring total NAD-related metabolites does not separately resolve each enzyme’s activity. Likewise, blood, muscle, and mitochondrial pools should not be treated as interchangeable measurements. An assay result needs its tissue, time point, and method attached. [3] [4]

1.4 Mitochondrial transport

Kory and colleagues identified MCART1/SLC25A51 as a mitochondrial NAD transporter using human-cell experiments. This supports a mechanism of intracellular compartmentalization. It is not a study of orally administered NR in dogs or cats. The publication is Science Advances, 2020, DOI 10.1126/sciadv.abe5310, PMID 33087354. [4]

2. Pharmacokinetics and measurement

Absorption of a precursor, changes in circulating NAD-related metabolites, tissue exposure, and a functional response are separate endpoints. Trammell and colleagues investigated oral NR and NAD-related responses in humans and mice. Their findings cannot supply feline or canine pharmacokinetic parameters, an optimal dosing interval, or a conversion factor from a human serving to a pet serving. [5]

2.1 What human muscle data can establish

Elhassan and colleagues studied NR in a placebo-controlled, randomized, double-blind crossover trial involving older men. Muscle NAD-related metabolites changed, but measured mitochondrial bioenergetics did not improve. The design was not open-label. The distinction between metabolite response and functional physiology matters when translating the result. [6]

2.2 Why this appendix gives no pet dose table

A rat toxicology threshold, a human trial regimen, and a commercial pet serving answer different questions. Converting by body weight or body surface area does not establish a validated canine or feline dose. The cited evidence does not support a general NR dose, long-term safety guarantee, or a claimed therapeutic range for all dogs and cats. Individual use requires review of the formulation and the animal’s veterinary care plan.

3. Safety evidence: the NR-E rat experiment

Marinescu and colleagues tested NR-E in Sprague-Dawley rats for 90 days and included a 28-day recovery arm. A body-weight effect in high-dose males contributed to different no-observed-adverse-effect levels by sex. This is formulation-specific rat toxicology, not a 90-day canine safety study. An absence of certain findings in that experiment does not establish absence of risk in pets. [7]

4. Direct canine research exists, with distinct interventions

It is incorrect to say that no NAD-precursor research has been published in dogs. The studies below address a disease model, short-term toxicology, and a combination intervention. Their existence also does not establish that NR alone improves longevity, cognition, or energy in healthy dogs.

4.1 NAM in a muscular dystrophy model

Cardoso and colleagues investigated dogs with golden retriever muscular dystrophy. The administered precursor was nicotinamide (NAM). The authors reported reduced muscle NAD+ in the disease model and modest effects on aspects of muscle disease after NAM treatment. This is not an NR experiment or a normal-aging study. [8]

4.2 Short-term NMN exposure in beagles

You and colleagues studied NMN in mice and beagle dogs. The dogs received NMN for 14 days, with mild increases in creatinine and uric acid reported. This is short-term NMN toxicology, not evidence of long-term NR safety or clinical efficacy. [9]

4.3 A precursor-and-senolytic combination in senior dogs

Simon and colleagues tested LY-D6/2 in senior dogs. The full-dose group showed the largest improvement in owner-assessed cognition at three months; measured activity and in-house cognitive testing did not show significant between-group improvement. Effects cannot be assigned to an isolated ingredient, and the findings do not transfer to Hollywood Elixir or NR alone. [10]

5. Feline evidence and its limits

Li and colleagues conducted an observational metabolomics comparison involving cats with hypertrophic cardiomyopathy and controls. NAD-related precursors were among the altered metabolites, but the study did not administer NR, NMN, or NAD+. An association with disease is not a supplementation trial, a demonstration of normal aging, or evidence of an effective feline dose. [11]

5.1 Clinical questions still open in this reference set

The selected primary studies do not establish the long-term safety, optimal dose, or clinical benefit of NR supplementation in cats. They also do not provide a diagnostic checklist for feline NAD deficiency. Future claims need direct evidence for the intended population and formulation. A lack of a relevant study in this reference set should not be rewritten as a claim that all possible veterinary research is absent.

6. Human NMN trials: separate from NR and pet evidence

Igarashi and colleagues reported increased blood NAD-related measures after NMN in older men, with exploratory functional findings requiring larger-study validation. Yi and colleagues studied NMN in healthy middle-aged adults and reported NAD and walking-test changes during the trial. These are human NMN studies, not canine or feline NR evidence. [12] [13]

6.1 Bibliographic details for the human NMN trials

Igarashi: npj Aging, 2022, volume 8, article 5; PMID 35927255; DOI 10.1038/s41514-022-00084-z. Yi: GeroScience, 2023, volume 45, pages 29–43; PMID 36482258; DOI 10.1007/s11357-022-00705-1. The references below link to the corresponding article records. [12] [13]

7. Reading a claim against its source

Check that the cited title, authors, identifier, and link describe the same publication. Then check the actual intervention, species, population, comparator, duration, and endpoint. A paper on NAM is not NR evidence; a combination does not isolate one component; a biomarker does not establish a clinical benefit. Quality-control testing establishes only the properties and samples measured, not clinical efficacy.

8. Practical evidence boundaries

The selected studies do not establish a predictable improvement timeline or lifespan extension from NR in pet dogs or cats. New fatigue, mobility changes, appetite loss, or behavioral changes are reasons for veterinary assessment rather than a diagnosis of low NAD+. Review any supplement within the complete diet, medication list, and medical history.

Related guides

For owner-facing explanations, see NAD+ for dogs, NAD+ for cats, NR for dogs, and NR for cats.

References

  1. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans. Bieganowski P, Brenner C Cell (2004).

    Foundational pathway evidence; not a canine or feline supplement trial.

  2. The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. Revollo JR, Grimm AA, Imai S The Journal of biological chemistry (2004).

    Cellular mechanism; not a pet dose or clinical efficacy result.

  3. NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells. Ratajczak J, Joffraud M, Trammell SA, et al. Nature communications (2016).

    Experimental pathway work; not canine or feline absorption, dosing, or clinical efficacy.

  4. MCART1/SLC25A51 is required for mitochondrial NAD transport. Kory N, Uit de Bos J, van der Rijt S, et al. Science advances (2020).

    Intracellular transport mechanism; no oral precursor trial in dogs or cats.

  5. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Trammell SA, Schmidt MS, Weidemann BJ, et al. Nature communications (2016).

    Human and mouse NAD-related biomarkers; not clinical benefit or a dose for pets.

  6. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Elhassan YS, Kluckova K, Fletcher RS, et al. Cell reports (2019).

    Older men; muscle NAD-related metabolites changed without improved mitochondrial bioenergetics. Not pet outcome evidence.

  7. Safety Assessment of High-Purity, Synthetic Nicotinamide Riboside (NR-E) in a 90-Day Repeated Dose Oral Toxicity Study, With a 28-Day Recovery Arm. Marinescu AG, Chen J, Holmes HE, et al. International journal of toxicology (2020).

    Sprague-Dawley rats, not dogs or cats. Rat toxicology cannot establish long-term pet safety or a pet serving.

  8. Replenishing NAD+ content reduces aspects of striated muscle disease in a dog model of Duchenne muscular dystrophy. Cardoso D, Barthélémy I, Blot S, et al. Skeletal muscle (2023).

    Dogs with inherited muscular dystrophy received NAM, not NR. Not healthy senior-dog or feline evidence.

  9. Subacute Toxicity Study of Nicotinamide Mononucleotide via Oral Administration. You Y, Gao Y, Wang H, et al. Frontiers in pharmacology (2020).

    Beagle exposure lasted 14 days and mild creatinine/uric-acid increases were reported. Not NR or long-term efficacy evidence.

  10. A randomized, controlled clinical trial demonstrates improved owner-assessed cognitive function in senior dogs receiving a senolytic and NAD+ precursor combination. Simon KE, Russell K, Mondino A, et al. Scientific reports (2024).

    Combination-specific owner-assessed cognition result; does not isolate NR or establish efficacy of another formula.

  11. Metabolic abnormalities and reprogramming in cats with naturally occurring hypertrophic cardiomyopathy. Li Q, Homilius M, Achilles E, et al. ESC heart failure (2025).

    Cats with hypertrophic cardiomyopathy compared with controls; associations do not establish a supplementation benefit or dose.

  12. Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men. Igarashi M, Nakagawa-Nagahama Y, Miura M, et al. npj aging (2022).

    Older men; biomarker and exploratory functional findings. Not NR or pet evidence.

  13. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. Yi L, Maier AB, Tao R, et al. GeroScience (2023).

    Healthy middle-aged adults; short-term human NMN results. Not NR or pet evidence.