From the Guidelines
NAD+ supplementation is recommended for individuals looking to improve cellular health and potentially slow aging, but it should be approached with caution due to limited long-term human research and potential risks. NAD+ is a coenzyme vital for energy metabolism, DNA repair, and cellular signaling that naturally declines with age 1. Supplementation may improve mitochondrial function, enhance cellular energy production, support DNA repair mechanisms, and potentially slow certain aspects of aging. Some studies suggest benefits for cardiovascular health, cognitive function, and metabolic conditions. Common supplement forms include nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), typically taken at doses of 250-1000mg daily. Key benefits of NAD+ supplementation include:
- Improved mitochondrial function and energy production
- Enhanced DNA repair mechanisms
- Potential slowing of certain aspects of aging
- Benefits for cardiovascular health, cognitive function, and metabolic conditions However, risks and considerations include:
- Gastrointestinal side effects
- Potential interactions with medications
- Unknown long-term safety profiles
- Theoretical risk of promoting cancer cell growth in existing tumors
- High cost of quality supplements For those interested in trying NAD+ supplements, starting with lower doses of reputable products is advisable, preferably under healthcare supervision, especially for individuals with existing health conditions or those taking medications. The upper intake level (UL) for nicotinamide, a form of vitamin B3, is 12.5 mg/kg body weight/d or approximately 900 mg/d for adults, with no adverse effects observed at doses up to 25 mg/kg body weight/d in prolonged studies 1.
From the Research
Benefits of NAD+ Supplementation
- NAD+ supplementation has been shown to protect against metabolic disease, neurodegenerative disorders, and age-related physiological decline in mammals 2.
- Administration of NMN, a precursor to NAD+, has demonstrated amelioration of pathological conditions in some age-related disease mouse models, including diabetes, ischemia-reperfusion injury, heart failure, Alzheimer's disease, and retinal degeneration 3.
- Nicotinamide riboside (NR) supplementation has been found to improve muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in humans 4.
- NMN supplementation may have anti-aging effects by increasing NAD+ concentration and mitigating aging-related disorders such as oxidative stress, DNA damage, neurodegeneration, and inflammatory responses 5.
Risks and Limitations of NAD+ Supplementation
- Most short-term clinical trials conducted so far have not reported positive outcomes of NR supplementation 4.
- NR supplementation did not ameliorate adiposity or metabolic health in humans 4.
- The safety and physiological effects of NMN supplementation in the human population are still being studied, with a dozen human clinical trials currently underway 5.
- The in vivo metabolic pathways of NMN and NR are complex and involve gut microbiota-mediated deamidation and conversion to nicotinic acid, which is then used in the liver to synthesize NAD+ 6.
Mechanisms of NAD+ Supplementation
- NAD+ is synthesized from NMN, which is converted to NR and then taken up by cells to produce NAD+ 2.
- NRK1 is necessary and rate-limiting for the use of exogenous NR and NMN for NAD+ synthesis 2.
- NMN and NR facilitate NAD+ synthesis via enterohepatic circulation, involving gut microbiota-mediated deamidation and conversion to nicotinic acid 6.