Nicotinamide adenine dinucleotide (NAD+) or NADH (reduced nicotinamide adenine dinucleotide) is an essential metabolic cofactor that is central to energy metabolism. NAD+ concentrations in cells decline with aging and is linked to numerous aging-associated diseases, including loss of muscle tissue and frailty, metabolic disease such as high blood sugar, and cognitive decline.1 Many of these diseases may be slowed down by replenishing NAD+ levels and therefore, targeting NAD+ levels has emerged as a potential therapeutic approach to moderate ageing-related disease, and extend the human healthspan and lifespan.
Potential health benefits of boosting NAD+ levels vary by body tissue and include:1-3
- Brain – Improved brain function and protection from degeneration of the nervous system, especially of neurons in the brain
- Vasculature (blood vessels) – Increased formation of new blood vessels and improved blood flow
- Liver – Improved liver function and reduced fatty liver disease
- Muscle – Reduced atrophy, enhanced mitochondrial function (energy production), increased insulin sensitivity and increased physical activity
- Pancreas – Increased insulin secretion and reduced inflammation
- Fat tissue – Reduced dyslipidemia (defined as elevated total or low-density lipoprotein cholesterol levels, or low levels of high-density lipoprotein cholesterol) and prevention of insulin resistance
- Inflammageing (age-related increase in the levels of pro-inflammatory markers in blood and tissues) – Reduced inflammation and improved immune cell function
Several clinical studies have shown promising results but others have shown little or no benefit, suggesting that benefits may be highest in those with low tissue NAD+ concentration at baseline. In a recent, 10-week, randomized, placebo-controlled, double-blind study (highest quality study), increasing NAD+ levels improved skeletal muscle insulin signaling and sensitivity in postmenopausal prediabetic women who were overweight or obese.4 An addition benefit was that genes related to muscle remodeling and regeneration were also up-regulated. These findings demonstrate the safety and effectiveness of NAD+ supplementation, although additional research is needed.
Strategies that boost NAD+ levels include lifestyle changes, such as increasing exercise, reducing number of calories consumed, eating a healthy diet and following a consistent daily pattern of healthy sleeping habits and mealtimes. Another approach is the use of inhibitors or activators to boost NAD+ production and the use of dietary supplements.1
- Covarrubias, A.J., Perrone, R., Grozio, A. & Verdin, E. NAD(+) metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol 22, 119-141 (2021).
- Hepler, C. & Bass, J. Supplements to treat prediabetes. Science 372, 1147-1148 (2021).
- Katsyuba, E., Romani, M., Hofer, D. & Auwerx, J. NAD(+) homeostasis in health and disease. Nat Metab 2, 9-31 (2020).
- Yoshino, M., et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science 372, 1224-1229 (2021).