NAD+

Human trials · 2 studies linked

Studied in: Adults overweight obese, European finnish, Mean age 40

Overall HbA1c within normal range throughout. Subgroup divergence (lean vs heavy) warrants attention in future trials.

• Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study (2023)
• Nicotinamide Effects Oxidative Burst Activity of Neutrophils in Patients with Poorly Controlled Type 2 Diabetes Mellitus (2004)

Human trials · 1 study linked

Studied in: Adults overweight obese, European finnish, Mean age 40, 5 month intervention

Adverse metabolic signal. Remained within normal range. May reflect niacin-like gluconeogenesis effect or weight gain confound (+2.6 kg). Contested by animal models showing glucose improvement.

• Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study (2023)

Human trials · 1 study linked

Studied in: Adults overweight obese, European finnish, Mean age 40

• Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study (2023)

Human trials · 5 studies linked

Studied in: Adults overweight obese, European finnish, Mean age 40, 5 month intervention

Insulin resistance worsened over 5 months. Matsuda index decreased 5.7→4.4 (p<0.001). Weight gain confound cannot be fully excluded (no placebo arm for primary cohort).

• Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study (2023)
• Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin. (2023)
• 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-dependen (2023)
• A Multicentre, Randomised, Double Blind, Parallel Design, Placebo Controlled Study to Evaluate the Efficacy and Safety of Uthever (NMN Supplement), an Orally Administered Supplementation in Middle Age (2022)
• Quantum Dot Nanomedicine Formulations Dramatically Improve Pharmacological Properties and Alter Uptake Pathways of Metformin and Nicotinamide Mononucleotide in Aging Mice. (2021)

Human trials · 5 studies linked

Studied in: Adults overweight obese, European finnish, Healthy, Overweight

Evidence_type corrected from rct_single to rct_multiple. NR monotherapy null for LDL; NRPT formulation LDL increase is pterostilbene-specific.

• Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study (2023)
• 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. (2019)
• Nicotinamide mononucleotide enhances the developmental potential of mouse early embryos exposed to perfluorooctanoic acid. (2025)
• Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study. (2023)
• Nicotinamide suppresses hyperphosphatemia in hemodialysis patients (2004)

Human trials · 4 studies linked

Studied in: Adults overweight obese, European finnish, Healthy, Overweight

Evidence_type corrected from rct_single to rct_multiple.

• Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study (2023)
• 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. (2019)
• Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study. (2023)
• Nicotinamide suppresses hyperphosphatemia in hemodialysis patients (2004)

1 study linked

Studied in: Healthy, Overweight, Age 40 60

• 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. (2019)

1 study linked

Studied in: Healthy, Overweight, Age 40 60

• 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. (2019)

Human trials · 1 study linked

Studied in: Adults overweight obese, European finnish

Faecalibacterium increase was negatively associated with hs-CRP change (indirect anti-inflammatory signal)

• Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study (2023)

Human trials · 1 study linked

10 corpus studies mention IL-6 but no full-text enrichment performed. Preclinical data suggests decrease via SIRT1-NF-κB deacetylation. Human confirmation needed.

• Effect of nicotinamide riboside on airway inflammation in COPD: a randomized, placebo-controlled trial. (2024)

Human trials · 2 studies linked

13 corpus studies mention TNF-α but no full-text enrichment performed. Same preclinical mechanism as IL-6. Priority extraction target for future passes.

• Effects of nicotinamide riboside supplementation during late gestation and lactation on sow performance, milk metabolome, and gut microbiome. (2026)
• Anti-inflammatory effects of nicotinamide mononucleotide (NMN) in human skeletal muscle after BFR-exercise. (2026)

Human trials · 12 studies linked

Studied in: Adults overweight obese, European finnish, Healthy, Overweight

Hepatosafety reassuring at NR 1g/day x 5 months; heavier cotwins had higher baseline ALT (33 vs 20 U/L) reflecting obesity-associated hepatic steatosis but no worsening

• Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study (2023)
• 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. (2019)
• NAD⁺ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence. (2026)
• Oral MIB-626 (β Nicotinamide Mononucleotide) Safely Raises Blood Nicotinamide Adenine Dinucleotide Levels in Hospitalized Patients With COVID-19 and Acute Kidney Injury: A Randomized Controlled Trial. (2021)
• Feasibility of telehealth exercise and nicotinamide riboside supplementation in survivors of childhood cancer at risk for diabetes: A pilot randomized controlled trial. (2025)
• Towards personalized nicotinamide mononucleotide (NMN) supplementation: Nicotinamide adenine dinucleotide (NAD) concentration. (2024)
• +6 more studies

Human trials · 8 studies linked

Studied in: Healthy, Overweight, Age 40 60

Safety confirmed at supratherapeutic doses. No hepatotoxicity. COI: ChromaDex-sponsored. Grade corrected from A to B: single source RCT only.

• 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. (2019)
• Nicotinamide mononucleotide enhances the developmental potential of mouse early embryos exposed to perfluorooctanoic acid. (2025)
• Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study. (2023)
• Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. (2021)
• Effects of Nicotinamide Riboside on Endocrine Pancreatic Function and Incretin Hormones in Nondiabetic Men With Obesity. (2019)
• Quantum Dot Nanomedicine Formulations Dramatically Improve Pharmacological Properties and Alter Uptake Pathways of Metformin and Nicotinamide Mononucleotide in Aging Mice. (2021)
• +2 more studies

Human trials · 2 studies linked

Studied in: Healthy, Overweight, Age 40 60

Grade corrected from A to B: single source RCT only.

• 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. (2019)
• Nicotinamide riboside and pterostilbene reduces markers of hepatic inflammation in NAFLD: A double-blind, placebo-controlled clinical trial. (2023)

1 study linked

Studied in: Healthy, Overweight, Age 40 60

• 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. (2019)

Human trials · 5 studies linked

Studied in: Adults overweight obese, European finnish, Healthy, Overweight

Evidence_type corrected from rct_single to rct_multiple. Grade A confirmed: two independent RCTs.

• Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study (2023)
• 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. (2019)
• Oral MIB-626 (β Nicotinamide Mononucleotide) Safely Raises Blood Nicotinamide Adenine Dinucleotide Levels in Hospitalized Patients With COVID-19 and Acute Kidney Injury: A Randomized Controlled Trial. (2021)
• Nicotinamide riboside with pterostilbene (NRPT) increases NAD (2020)
• Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. (2020)

Human trials · 2 studies linked

Studied in: Healthy, Overweight, Age 40 60

Grade corrected from A to B: single source RCT only.

• 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. (2019)
• Randomized crossover clinical trial of coenzyme Q10 and nicotinamide riboside in chronic kidney disease (2023)

Human trials · 2 studies linked

Studied in: Healthy, Overweight, Age 40 60

Grade corrected from A to B: single source RCT only.

• 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. (2019)
• Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men. (2020)

Human trials · 2 studies linked

Studied in: Adults overweight obese, European finnish

Authors attributed to repeated blood draws rather than true adverse hematologic effect

• Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study (2023)
• Association between blood nicotinamide adenine dinucleotide levels and blood laboratory parameters at baseline and after nicotinamide mononucleotide supplementation in middle-aged healthy individuals: (2025)

Human trials · 1 study linked

Studied in: Healthy, Overweight, Age 40 60

Grade corrected from A to B: single source RCT only.

• 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. (2019)

Human trials · 1 study linked

Studied in: Healthy, Overweight, Age 40 60

Grade corrected from A to B: single source RCT only.

• 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. (2019)

Human trials · 1 study linked

Studied in: Healthy, Overweight, Age 40 60

Grade corrected from A to B: single source RCT only.

• 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. (2019)

Human trials · 1 study linked

Studied in: Healthy, Overweight, Age 40 60

Grade corrected from A to B: single source RCT only.

• 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. (2019)

Human trials · 1 study linked

5 corpus studies. Lipid peroxidation marker relevant to membrane integrity assessment.

• Nicotinamide riboside attenuates myocardial ischemia-reperfusion injury via regulating SIRT3/SOD2 signaling pathway. (2024)

Human trials · 1 study linked

3 corpus studies — priority extraction target for oxidative stress assessment.

• Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study. (2020)

Human trials · 3 studies linked

12 corpus studies — highest oxidative stress coverage. SIRT3→SOD2 and NRF2→GCLC mechanisms predict GSH increase. Critical extraction gap.

• Effects of nicotinamide riboside supplementation during late gestation and lactation on sow performance, milk metabolome, and gut microbiome. (2026)
• A Combination of Nicotinamide and D-Ribose (RiaGev) Is Safe and Effective to Increase NAD+ Metabolome in Healthy Middle-Aged Adults: A Randomized, Triple-Blind, Placebo-Controlled, Cross-Over Pilot Cl (2022)
• Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study. (2020)

Human trials · 3 studies linked

Studied in: Adults overweight obese, European finnish, Lean subgroup, Healthy

Direction discordance resolved as duration-dependent: null at 8 weeks, increased in lean subgroup at 5 months. Aggregate direction = contested. Mechanistically plausible via NNMT-mediated methyl donor depletion. Duplicate cardiac-cluster entry removed; this is the canonical entry.

• Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study (2023)
• 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. (2019)
• NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease (2023)

Human trials · 1 study linked

7 corpus studies — priority extraction target. NAADP (NAD+ metabolite) is a calcium signaling second messenger; calcium homeostasis effects are mechanistically plausible.

• Nicotinamide suppresses hyperphosphatemia in hemodialysis patients (2004)

Human trials · 1 study linked

10 corpus studies — highest electrolyte coverage. SIRT1-FGF23 axis in renal phosphate handling provides mechanistic basis. Priority extraction target.

• A Combination of Nicotinamide and D-Ribose (RiaGev) Is Safe and Effective to Increase NAD+ Metabolome in Healthy Middle-Aged Adults: A Randomized, Triple-Blind, Placebo-Controlled, Cross-Over Pilot Cl (2022)

Human trials · 4 studies linked

• Nicotinamide riboside combined with exercise to treat hypertension in middle-aged and older adults: a pilot randomized clinical trial (2025)
• Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial. (2023)
• Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans. (2020)
• Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. (2020)

Human trials · 2 studies linked

• Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study. (2023)
• Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study (2023)

Large effect · 6 studies linked

Studied in: General adults, Older adults, Athletes, Japanese adults

Robust and consistent across NR and NMN precursors, doses 250–1000 mg/day, and multiple populations. Effect persists across COI and non-COI studies. Upgraded to Grade A on this pass: ≥6 RCTs now in source pool. COI flag retained due to ChromaDex and NMN-manufacturer affiliation in majority of studies.

• Nicotinamide Riboside Is a Major NAD+ Precursor Vitamin in Cow Milk (2016)
• Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study. (2020)
• Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study (2023)
• Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD (2019)
• Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial. (2023)
• 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. (2024)

2 studies linked

Studied in: Healthy, Overweight, Age 40 60, Western european

Conze 2019 establishes clear dose-response in whole blood NAD+ with NR (NIAGEN); effect sustained at 8 weeks. Lapatto 2023 provides independent replication. COI present in both studies.

• Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study (2023)
• 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. (2019)

Moderate effect · 1 study linked

Studied in: Postmenopausal women, Prediabetic, Aged 55 75

• Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. (2021)

Moderate effect · 1 study linked

Studied in: Older adults, Aged 70

NR 1000 mg/day significantly augments the muscle NAD+ metabolome in aged humans, including NAAD (nicotinic acid adenine dinucleotide), which is established here as a validated systemic biomarker of NAD+ repletion. COI: ChromaDex-linked. Critical caveat: muscle NAD+ repletion did NOT translate to improved mitochondri...

• Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD (2019)

Moderate effect · 1 study linked

Studied in: Older adults, Aged 65 80

PSQI-measured sleep quality improved with NMN vs placebo in community-dwelling older adults. Exploratory finding with mechanistic plausibility via SIRT1–CLOCK–BMAL1 circadian axis (NAD+ is a rate-limiting substrate for SIRT1 deacetylase activity). Single manufacturer-funded RCT; Grade B pending independent replication.

• 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. (2024)

Small effect · 1 study linked

Studied in: Older adults, Aged 65 80, Community dwelling

β-NMN 250 mg/day preserved 4-meter walk test speed over 12 weeks in older adults while placebo group declined significantly. Novel functional endpoint for NMN. Mechanistic plausibility: NAD+-driven muscle energetics and neuromuscular efficiency. Requires independent replication — all authors affiliated with Meiji (N...

• 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. (2024)

1 study linked

Studied in: Middle aged, Japanese, Mild arterial stiffness

NMN 250 mg/day x 12 weeks did not significantly improve brachial-ankle pulse wave velocity vs placebo. Primary endpoint not met. NAD+ bioavailability was confirmed (blood NAD+ increased). Interpretation: either 250 mg/day is insufficient for vascular structural change, duration is too short, or the NAD+→endothelial ...

• Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial. (2023)