Anti-aging cocktails that combine different compounds with nicotinamide adenine dinucleotide (NAD+) precursor Nicotinamide Mononucleotide (NMN) are becoming more common. Uncertainty surrounds the effects of these combinations in boosting NAD+, an essential molecule that decreases in abundance with age in different organs and tissues. Falling NAD+ levels with age have been linked to numerous age-related diseases, with differences in NAD+ levels between organs and tissue types. Along those lines, combining molecules to target individual organs could be paramount in treating specific age-related diseases.
Published in Pharmacology Research and Perspectives, Jiang and colleagues from Macau University of Science and Technology in China demonstrate that combining NMN with resveratrol increases NAD+ levels in heart and skeletal muscle of mice significantly more than NMN alone. Furthermore, NMN combined with ginsenosides almost doubles NAD+ levels in lung tissue compared to NMN on its own. These results point to using NMN combo therapies to boost NAD+ levels in particular organs to treat the age-related diseases that affect them.
To find how NMN and resveratrol – an antioxidant associated with increasing lifespan -synergistically influence NAD+ levels in different organ systems, the China-based researchers provided oral doses of the two substances to adult mice. The research group found that NMN and resveratrol work together to boost NAD+ levels in the heart and skeletal muscle, 1.59-fold and 1.72-fold, respectively, six hours after treatment. These findings suggest that an NMN plus resveratrol treatment regimen could be used for age-related diseases affecting either the heart or skeletal muscle, such as cardiovascular disease or frailty.
Another combination the research team looked at was NMN and the ginsenosides – a class of molecules derived from Korean red ginseng root. Jiang and colleagues found that NMN and the ginsenosides synergistically increase NAD+ levels almost two-fold in lung tissue. These results indicate that combining NMN with ginsenosides could be tailored to treat age-related diseases pertaining to the lungs like scar tissue buildup (lung tissue fibrosis).
Interestingly, NMN alone does not increase NAD+ levels significantly in the brain, but NMN with resveratrol, or NMN with ginsenosides results in reduced NAD+ levels in the brain compared to no treatment. Explaining why NMN with resveratrol or ginsenosides actually results in reduced NAD+ levels in the brain remains unclear.
“Our study elucidates an in sight into combination therapy for supplementing NAD+ in daily or NAD+ metabolic disorder levels, especially in cardiopulmonary failure diseases,” said Jiang and colleagues.
If increasing NAD+ levels is truly effective for treating age-related diseases, targeting cardiovascular diseases with NMN and resveratrol may be a good option. Moreover, musculoskeletal disorders like frailty may be alleviated with the same supplement combination. Additionally, increasing NAD+ levels with NMN and ginsenosides may be a promising way to counteract age-related lung disease, including lung fibrosis in cigarette smokers. Other research suggests that smoking induces lung tissue fibrosis, which boosting NAD+ levels alleviates, so targeting this disease with NMN and ginsenosides could provide a way to boost lung health in people who smoke. Further studies using mouse models for these disorders, along with clinical trials, will be required before making any conclusions.
Complications from the study come from the observation that NMN with resveratrol or with ginsenosides reduces NAD+ levels in the brain six hours after intake. Longer periods need to be studied to find how long this effect lasts. If NAD+ levels in the brain drop for extended periods with these supplement combinations, there may be a tradeoff between increasing NAD+ levels in the heart, skeletal muscle, or lung tissue and reducing them in the brain. Moreover, the adult mice used in the study were quite young (six to eight weeks old). Finding whether these supplement combinations work the same way to increase NAD+ in certain organs across age groups will require experimentation with aged mice.