| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Obesity and Metabolic Health (Animal Models) In rodent models, NR supplementation enhanced oxidative metabolism, activated SIRT1 and SIRT3, increased energy expenditure, reduced cholesterol, and protected against high-fat diet-induced obesity and metabolic abnormalities (Cantó et al., 2012). Reviews confirm NAD+-boosting molecules improve metabolic regulation in animal models (Rajman et al., 2018). No human obesity trials have been conducted. | Improves (the measure goes down) | Moderate effect | 3 studies | |||
Studies that measured obesity and metabolic health (animal models) | ||||||
Supplement
NAD+ is a molecule found in every cell, where it helps turn food into energy and supports DNA repair and cell signaling. People mostly look at it, usually through precursors like nicotinamide riboside, to slow the effects of aging, and small human trials found blood and muscle NAD+ levels reliably went up, though the evidence is limited. Those studies were small, and whether higher levels translate into healthier aging remains unclear, since most other findings come from animal or lab work.
Sources: PMID 27721479; PMID 31412242
- Updated
- How we grade
- 19 studies cited
- Best evidence
- Grade C
- Conditions studied
- 4
- Outcomes
- 10
- Graded outcomes
- 0019
Evidence by condition
- Strong
- Moderate
- Limited
- Very limited
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Cellular NAD+ Levels Multiple small human trials demonstrate that NAD+ precursors (NR, NMN) reliably raise blood and tissue NAD+ levels. In a pharmacokinetic study of 12 healthy subjects, single-dose oral NR produced up to 2.7-fold increases in blood NAD+ (Trammell et al., 2016). Similar NAD+ elevations were confirmed in aged skeletal muscle (Elhassan et al., 2019) and in the brains of Parkinson's patients (Brakedal et al., 2022). Note: direct oral NAD+ has poor bioavailability; most evidence uses precursors NR or NMN. | Improves (the measure goes up) | Moderate effect | 7 studies | 84 people | ||
Studies that measured cellular nad+ levels
| ||||||
| Systemic Inflammation Reduced inflammatory markers were observed across multiple human and animal studies. In aged men, NR reduced circulating inflammatory cytokines (Elhassan et al., 2019). In Parkinson's patients, NR lowered inflammatory markers in serum and CSF (Brakedal et al., 2022). NAD+ metabolism modulates immune response, T cell function, and inflammaging pathways (Navarro et al., 2022). Evidence is consistent but from small, heterogeneous studies. | Improves (the measure goes down) | Small effect | 5 studies | 72 people | ||
Studies that measured systemic inflammation
| ||||||
| Skeletal Muscle NAD+ Metabolome and Anti-inflammatory Markers A double-blind, placebo-controlled crossover RCT in 12 aged men showed that 1g daily NR for 21 days augmented the skeletal muscle NAD+ metabolome and induced transcriptomic anti-inflammatory signatures, with reduced circulating inflammatory cytokines (Elhassan et al., 2019). In prediabetic women, NMN also upregulated muscle remodeling genes (Yoshino et al., 2021). Evidence limited to two small trials. | Changes; see studies | Small effect | 2 studies | 37 people | ||
Studies that measured skeletal muscle nad+ metabolome and anti-inflammatory markers | ||||||
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Cardiac Remodeling and Heart Function Preclinical evidence and reviews indicate NAD+ homeostasis is disrupted in failing hearts and that NAD+ supplementation may prevent adverse cardiac remodeling by improving mitochondrial redox state (Mericskay, 2016; Pei et al., 2022). The Nampt/NAD axis has been shown to suppress atrial fibrillation by modulating calcium handling in cellular models (Shan et al., 2020). No human cardiac trials have been completed. | Improves (the measure goes up) | Small effect | 5 studies | |||
Studies that measured cardiac remodeling and heart function
| ||||||
Alzheimer’s Disease
- Neuroinflammation in Alzheimer's Disease Models: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Neuroinflammation in Alzheimer's Disease Models In transgenic Alzheimer's mouse models, 5-month NR supplementation reduced microglial activation, suppressed NLRP3 inflammasome, decreased DNA damage and cellular senescence, and improved cognitive function and synaptic plasticity via the cGAS-STING pathway (Hou et al., 2021). Additional preclinical and review evidence supports NAD+ precursors for neurodegeneration, but no human trials have tested cognitive endpoints in Alzheimer's patients. | Improves (the measure goes down) | Moderate effect | 4 studies | |||
Studies that measured neuroinflammation in alzheimer's disease models
| ||||||
General
- Age-Related Oocyte Quality and Female Fertility: improves
- Anti-Tumor Immune Response: improves
- Muscle Insulin Sensitivity: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Age-Related Oocyte Quality and Female Fertility Two independent rodent studies demonstrated that NMN supplementation restored oocyte quality during reproductive aging. Bertoldo et al. (2020) showed NAD+ repletion rescued fertility in aged mice, improving ovulation rates and embryo development. Miao et al. (2020) confirmed NMN reversed age-related oocyte decline by restoring mitochondrial function and reducing ROS. No human studies have been conducted. | Improves (the measure goes up) | Moderate effect | 3 studies | |||
Studies that measured age-related oocyte quality and female fertility | ||||||
| Anti-Tumor Immune Response In preclinical cancer models, NAD+ supplementation enhanced T cell tumor-killing capacity by rescuing defective NAMPT transcription in tumor-infiltrating T cells, improving glycolysis and ATP production in CAR-T and anti-PD1 models (Wang et al., 2021). Cancer cells also show heightened NAD+ dependency, suggesting dual therapeutic potential (Griffiths et al., 2020). All evidence is preclinical. | Improves (the measure goes up) | Small effect | 3 studies | |||
Studies that measured anti-tumor immune response
| ||||||
| Muscle Insulin Sensitivity A double-blind, placebo-controlled RCT of 25 postmenopausal prediabetic women found that 10 weeks of NMN supplementation (250 mg/day) increased skeletal muscle insulin signaling (AKT, mTOR phosphorylation) and glucose disposal (Yoshino et al., 2021, Science). Impaired NAD+ metabolism in diabetic tissues provides mechanistic support (Okabe et al., 2020), but this is a single small trial. | Improves (the measure goes up) | Small effect | 2 studies | 25 people | ||
Studies that measured muscle insulin sensitivity | ||||||
| Parkinson's Disease Biomarkers The NADPARK phase I RCT in 30 newly diagnosed, treatment-naive Parkinson's patients found that NR supplementation was well-tolerated, significantly increased brain NAD+ levels, altered cerebral metabolism, upregulated mitochondrial and cellular repair genes, and reduced inflammatory markers in serum and cerebrospinal fluid (Brakedal et al., 2022). However, clinical motor outcomes were not a primary endpoint and larger trials are needed. | Improves (the measure goes up) | Small effect | 2 studies | 30 people | ||
Body Composition
- Obesity and Metabolic Health (Animal Models): improves
Key findings
- Cellular NAD+ LevelsImproves (the measure goes up)
- Cardiac Remodeling and Heart FunctionImproves (the measure goes up)
- Systemic InflammationImproves (the measure goes down)
Safety notes in the studies
- Preclinical evidence and reviews indicate NAD+ homeostasis is disrupted in failing hearts and that NAD+ supplementation may prevent adverse cardiac remodeling by improving mitochondrial redox state (Mericskay, 2016; Pei et al., 2022).
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- Grade C
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Studies cited
19 studies from PubMed
- The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease.
- Nicotinamide adenine dinucleotide metabolism in the immune response, autoimmunity and inflammageing.
- Nicotinamide Adenine Dinucleotide in the Development and Treatment of Cardiac Remodeling and Aging.
- NAD(+) supplementation reduces neuroinflammation and cell senescence in a transgenic mouse model of Alzheimer's disease via cGAS-STING.
- NAD(+) supplement potentiates tumor-killing function by rescuing defective TUB-mediated NAMPT transcription in tumor-infiltrated T cells.
- NAD(+) Repletion Rescues Female Fertility during Reproductive Aging.
- Nicotinamide Mononucleotide Supplementation Reverses the Declining Quality of Maternally Aged Oocytes.
- Nicotinamide adenine dinucleotide (NAD+): essential redox metabolite, co-substrate and an anti-cancer and anti-ageing therapeutic target.
- Therapeutic potential of nicotinamide adenine dinucleotide (NAD).
- Nicotinamide Phosphoribosyltransferase (Nampt)/Nicotinamide Adenine Dinucleotide (NAD) Axis Suppresses Atrial Fibrillation by Modulating the Calcium Handling Pathway.
- Impaired nicotinamide adenine dinucleotide (NAD(+)) metabolism in diabetes and diabetic tissues: Implications for nicotinamide-related compound treatment.
- Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD(+) Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures.
- Nicotinamide adenine dinucleotide emerges as a therapeutic target in aging and ischemic conditions.
- Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence.
- Nicotinamide riboside is uniquely and orally bioavailable in mice and humans.
- Nicotinamide adenine dinucleotide homeostasis and signalling in heart disease: Pathophysiological implications and therapeutic potential.
- NAD⁺ in aging, metabolism, and neurodegeneration.
- NAD+ and sirtuins in aging and disease.
- The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity.