NAD, or nicotinamide adenine dinucleotide, is a molecule found in every living cell. It acts as a critical helper for energy production and DNA repair. Scientists have known for decades that NAD levels drop as we get older, a decline that has been linked to signs of aging and metabolic issues. This discovery has sparked a massive industry of NAD supplements, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), which promise to restore youthful levels. While these supplements reliably boost NAD in the blood, the evidence that they extend human life or reverse aging is still emerging and largely relies on animal studies. A previous Gromeus article on NAD supplements reached the same conclusion.
What is NAD and why do our bodies need it?
NAD is a coenzyme, which means it helps enzymes do their jobs. It exists in two forms, but the one most people talk about for health is NAD+. It plays two main roles that keep us alive. First, it turns the nutrients from our food into ATP, the cellular fuel that powers everything from muscle movement to brain thoughts. Without it, cells cannot produce energy.
Second, NAD acts as a sensor for stress. It activates a family of proteins called sirtuins. Sirtuins protect DNA, regulate inflammation, and are involved in aging processes. However, sirtuins can only work when NAD is present. When levels fall, these protective systems slow down, leaving cells more vulnerable to damage.
NAD levels decline with age
A 2019 study of blood samples found that plasma NAD levels decline steadily with age in healthy adults. By middle age, the amount of NAD in many tissues may have dropped significantly compared to youth.
Scientists believe this decline happens for two reasons. First, the body becomes less efficient at making new NAD. Second, chronic inflammation and DNA damage – both common in aging – force enzymes to consume more NAD to fix problems. This creates a shortage. This deficit has been linked to age-related conditions like fatigue, metabolic dysfunction, and weaker muscles.
Do NAD supplements work?
Because raw NAD is a large molecule, it is hard for cells to absorb it directly. Instead, most supplements provide “precursors,” smaller building blocks that the body converts into NAD. The two most studied precursors are nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN).
Nicotinamide Riboside (NR)
NR is a form of vitamin B3. A 2018 trial in adults aged 55 to 79 found that six weeks of NR safely raised blood NAD levels, with a trend toward lower blood pressure in participants whose blood pressure was already elevated. In 2024, a six-week trial in 40 people with COPD found that NR lowered a marker of airway inflammation by about 53% compared with placebo, without improving lung function. On muscle, a 2025 meta-analysis of trials in people over 60 concluded that current evidence does not support NMN or NR for preserving muscle mass and function.
Nicotinamide Mononucleotide (NMN)
NMN is another popular precursor. In a 2016 study, a year of NMN improved energy metabolism, insulin sensitivity and physical activity in aging mice. Human trials are newer and smaller. In 2021, ten weeks of NMN improved muscle insulin sensitivity in 25 prediabetic women. In 2022, a Japanese trial in men over 65 found that 250 mg of NMN a day for 12 weeks raised blood NAD and modestly improved walking speed and grip strength, with only 20 of 42 participants analyzed and no change in muscle mass, fat or insulin sensitivity.
Potential risks and side effects
Current research suggests that NAD supplements are generally safe for healthy adults in the short term. Common side effects are mild and include nausea, fatigue, headaches, or stomach discomfort.
However, long-term safety is not yet fully proven. One theoretical concern involves cancer. Because cancer cells grow fast, they also require high energy and high levels of NAD. Some researchers worry that boosting NAD might inadvertently help tumor cells grow, although no human data currently supports this fear. As always, caution is smart.
What you can do about it
If you are considering NAD supplements, understand that they are an investment in potential – not guaranteed – benefits. The science is promising but not finished.
- Prioritize lifestyle first: A 2025 trial found that a single exercise session boosts NAD production in immune cells, whether high-intensity intervals or moderate endurance. Fasting and a healthy diet also help.
- Triple-check your source: If you buy supplements, choose reputable brands with third-party testing, as quality varies wildly.
- Consult a doctor: Always speak to a healthcare professional before starting new supplements, especially if you have a history of cancer or take other medications.
- Track your own data: If you try them, monitor how you feel (energy, sleep) to see if the cost is worth it for you.
Sources and related information
Rejuvenation Research – The plasma NAD+ metabolome is dysregulated in “normal” aging – 2019
Blood analyses in healthy adults showed that NAD+ levels fall with age while related metabolites rise. Evidence type: observational study.
Nature Communications – Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults – 2018
A crossover trial in adults aged 55 to 79 found that six weeks of NR raised blood NAD+ and was well tolerated, with exploratory signs of lower blood pressure in those with elevated readings. Evidence type: randomized crossover trial.
Nature Aging – Effect of nicotinamide riboside on airway inflammation in COPD: a randomized, placebo controlled trial – 2024
In 40 people with COPD, six weeks of NR raised blood NAD+ and cut sputum IL-8 by about 53% versus placebo, with no effect on lung function or symptoms. Evidence type: randomized controlled trial.
Journal of Cachexia, Sarcopenia and Muscle – The effect of nicotinamide mononucleotide and riboside on skeletal muscle mass and function: a systematic review and meta-analysis – 2025
Pooling trials in adults aged 60 to 83, the authors conclude that current evidence does not support NMN and NR for preserving muscle mass and function. Evidence type: systematic review and meta-analysis.
Cell Metabolism – Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice – 2016
Twelve months of oral NMN in mice reduced age-related weight gain and improved energy metabolism, insulin sensitivity and physical activity. Evidence type: animal study.
Science – Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women – 2021
Washington University researchers report that ten weeks of NMN improved muscle insulin sensitivity in 25 overweight or obese prediabetic women, without changing other metabolic measures. Evidence type: randomized controlled trial.
npj Aging – Chronic nicotinamide mononucleotide supplementation elevates blood NAD levels and alters muscle function in healthy older men – 2022
In men over 65, 250 mg of NMN a day for 12 weeks raised blood NAD+ and nominally improved gait speed and left-hand grip strength; 22 of 42 participants were excluded after a supply error, and the authors call for larger studies. Evidence type: randomized controlled trial.
Brain, Behavior, and Immunity – Acute exercise boosts NAD+ metabolism of human peripheral blood mononuclear cells – 2025
Two trials in young adults showed that a single exercise session increases NAD+ synthesis in immune cells, with similar effects for high-intensity intervals and moderate continuous exercise. Evidence type: randomized crossover trial.
American Journal of Physiology – Safety of NAD – 2024
A systematic review concluded that supplementation with NADH and precursors was well tolerated in humans, with common side effects limited to mild issues like headaches or fatigue.
Molecular Metabolism – NMN efficacy – 2022
A randomized trial reported that NMN supplementation increases blood NAD concentrations and was safe in middle-aged adults, showing highest efficacy at doses around 600 mg daily.
