NAD

Authors:

Mario Mehmel, Nina Jovanović

Findings:

This review summarizes research on Nicotinamide Riboside (NR), an NAD+ precursor. It highlights accumulating evidence from animal and human studies suggesting potential health benefits via NAD+ elevation for cardiovascular, neurodegenerative, and metabolic disorders, as well as potential therapeutic use against infections like SARS-CoV-2. The review discusses NR's bioavailability, safety profile (generally regarded as safe, well-tolerated in trials), and advantages over other NAD+ precursors, while also addressing challenges like variable bioavailability and the need for further research to support therapeutic translation.

Participants:

The text reviews studies involving animal models (mice, rats) and human participants (healthy volunteers, obese men, aged subjects, overweight adults). It also mentions clinical trials investigating NR for various conditions, implying patient populations.

Dosage:

The text mentions several dosages from different studies: '400 mg/kg/day' (mice, high-fat diet study); '2000 mg/day' (1000 mg twice daily) (human study on obese men; human pharmacokinetic study); 'up to 1 g' daily (human safety/bioavailability study in overweight adults); NOAEL of '300 mg/kg/day' and LOAEL of '1000 mg/kg/day' (rat toxicology study). It also contrasts therapeutic doses with baseline requirements met by '< 20 mg of niacin daily'.

Study Quality Assessment:

The text describes itself as a review summarizing available data, primarily from open-access peer-reviewed journals found via PubMed and ResearchGate, prioritizing recent publications. It mentions specific study types reviewed, including 'animal and human studies', 'clinical trials' (some specified as 'randomized placebo-controlled', 'open-label, non-randomized'). Safety assessments mentioned include 'GRAS status' for NR chloride, a '90-day toxicology rat study', and safety findings from clinical trials. Methodological aspects noted include measuring NAD+ levels and biomarkers like NAAD. Limitations discussed include NR's instability in blood, variable oral bioavailability among individuals, results from animal models not always replicating in humans (e.g., insulin sensitivity), and the need for more research (e.g., long-term effects, metabolism details). A conflict of interest is declared by the review authors (employees of a company selling NR derivatives, one author holds related intellectual property).

All Effects:

Authors:

Eun Seong Hwang, Seon Beom Song

Findings:

Nicotinamide (NAM) at high doses is suggested to be effective against neurological dysfunctions, depression, other psychological disorders, and inflammatory diseases. The study likely focuses on its mechanisms and safety assessment.

Dosage:

Doses far above those recommended for vitamins are mentioned.

All Effects:

Findings:

Daily consumption of 100, 300, and 1000 mg Nicotinamide Riboside (NR) for 8 weeks dose-dependently increased whole blood NAD+ (by 22%, 51%, and 142% respectively at 2 weeks) and other NAD+ metabolites, with increases maintained throughout the study. There were no reports of flushing, no significant differences in adverse events between NR and placebo groups (or between NR doses), and NR did not elevate LDL cholesterol or plasma homocysteine levels.

Participants:

140 healthy male and female participants, 40–60 years of age, with a body mass index between 25–30 kg/m2. Described as 'Healthy Overweight Adults'.

Dosage:

100 mg/day, 300 mg/day, or 1000 mg/day of NIAGEN (NR chloride) taken once daily (after breakfast) for 8 weeks (56 days).

Study Quality Assessment:

Randomized, double-blind, placebo-controlled parallel study (N=140, n=35/group) over 8 weeks. Conducted following Good Clinical Practice (GCP) guidelines, reviewed by NHPD (Health Canada) and an IRB. Registered on clinicaltrials.org (NCT0271593). Used LC-MS-MS for metabolite quantification. Statistical analyses performed (ANCOVA, Mann-Whitney U, t-test, Wilcoxon). Limitations mentioned: conducted in predominantly white, middle-aged adults consuming a diet limited in niacin equivalents. Funding source mentioned: ChromaDex funded the study.

All Effects:

Authors:

Carles Cantó

Findings:

This review summarizes that Nicotinamide adenine dinucleotide (NAD+) metabolism is crucial for regulating diverse physiological processes, including energy metabolism, redox homeostasis, DNA repair, gene expression, immunity, and circadian rhythms, primarily through its roles as a redox cofactor and a substrate for enzymes like sirtuins and PARPs. Disequilibrium in NAD+ homeostasis contributes to various pathologies, including metabolic diseases, cancer, aging, and neurodegenerative disorders, often linked to NAD+ decline. Boosting NAD+ levels via precursors (e.g., NMN, NR), inhibiting NAD+-consuming enzymes (e.g., CD38, PARPs), or lifestyle interventions (caloric restriction, exercise) shows therapeutic potential for these conditions, though further research, particularly long-term human studies, is needed.

Participants:

The text reviews studies involving various models and subjects, including mammalian cells (e.g., U2OS, HEK293T, NIH/3T3, HeLa, human SMCs), yeast, bacteria, worms, flies, rodents (mice, rats), nonhuman primates, and humans (human tissues, cells, patients with various diseases like cancer, metabolic diseases, neurodegenerative disorders, AKI, HF, aged participants, athletes, obese/nonobese subjects).

Dosage:

The text mentions 'acute pharmacological dose of NAM', 'high doses of NAM', and 'pharmacological dosing of NA' but does not specify exact dosages or administration frequencies used in the reviewed studies.

Study Quality Assessment:

This text is a review article. It mentions various methodologies used in the cited studies, including: enzymatic cycling assays, capillary electrophoresis (CE), high-performance liquid chromatography coupled with mass spectrometry (HPLC-LC/MS/MS), autofluorescence, fluorescence lifetime imaging microscopy (FLIM), genetically encoded fluorescent sensors (Frex, LigA-cpVenus, SoNar, Peredox, RexYFP, iNap1-4, Apollo-NADP+), 31P-magnetic resonance spectroscopy (31P-MRS), and isotope-tracer methods. It discusses preclinical models (e.g., genetic knockouts, overexpression, high-fat diet models, disease models) and mentions clinical trials assessing NAD+ boosters (NR, NAM, Niacin). The text notes controversies (e.g., NMN transport mechanism, NAMPT levels in aging) and areas requiring further research.

All Effects:

Findings:

This review summarizes NAD+ metabolism, highlighting its crucial roles in cellular processes like energy production, DNA repair, redox homeostasis, gene expression, circadian rhythm, immunity, and signaling via NAD+-dependent enzymes (sirtuins, PARPs, CD38, SARM1). It discusses how NAD+ levels decline with age and in various pathophysiological conditions (metabolic diseases, cancer, neurodegeneration, infection, cardiac/renal failure). Strategies to boost NAD+ (precursors like NMN/NR, enzyme inhibitors, lifestyle changes) show therapeutic potential in preclinical models and early human trials, although long-term safety requires further investigation.

Participants:

Review covers studies using various models: mammalian cells (including specific lines like U2OS, HEK293T, HeLa), yeast, bacteria, worms, flies, mice (including specific disease/genetic models like 3xTgAD/Polβ+/-, APPswePS1DE9, SOD1G93A, WldS), rats, primates, and human tissues/cells/participants (including healthy, aged, athletes, obese, and patients with various diseases like cancer, metabolic disorders, neurodegenerative diseases, infections, cardiac/renal failure).

Study Quality Assessment:

Review article summarizing findings from numerous studies. Mentions various detection methods (enzymatic assays, CE, HPLC-MS, autofluorescence, FLIM, genetically encoded sensors, 31P-MRS, isotope tracers) with some limitations noted (e.g., for enzymatic assays, autofluorescence). Discusses preclinical studies (cell culture, animal models like mice, rats, worms, flies, primates) and human clinical trials (e.g., NAD+ boosters NR, NAM, Niacin; EH301 for ALS; NMN for cancer - see Table 1, though table content not fully provided in snippet). Acknowledges controversies in the field (e.g., NAMPT levels in aging, NMN transport, circulating NAMPT in NAFLD). Funding sources acknowledged.

All Effects: