Declining NAD and Matters of the Heart

Heart failure is a common and devastating chronic disease that happens when the heart cannot pump enough blood to support all the body’s organs. Unfortunately, while there are some medications available to treat heart failure, there is no cure, and half of all heart failure patients die within 5 years of receiving their diagnosis1. One main cause of heart failure is that the cells of the heart lack the energy they need to function properly2. Mitochondria, tiny power houses within our cells, take the energy from the food we eat and convert it into energy that the heart can use to beat. If these mitochondria are not working properly, then the heart will not generate the energy it needs, leading to heart failure. This understanding as caused researchers to look to molecules that improve mitochondrial function in hopes of discovering new ways to treat heart failure.

Previous research tells us that mitochondrial function can be improved by taking supplements of nicotinamide riboside (NR)3. Inside the body, NR is converted to nicotinamide adenine dinucleotide (NAD), a molecule known to improve mitochondrial health. To examine how NR and NAD+ contribute specifically to heart function, a team of researchers led by Dr. Mathias Mericksay and Dr. Charles Brenner examined levels of NAD in failing hearts of humans and mice and found that NAD levels decline during heart failure4. They also found that genes needed to convert NR to NAD are more active in failing hearts than in normal healthy hearts. These changes indicate that during heart failure, heart cells attempt to replenish NAD to improve energy production. The finding that heart failure prompts similar changes in NAD in both humans and mice is particularly important, because it suggests mice are an appropriate model for identifying heart failure treatments that can eventually help patients.

Since NAD can be efficiently created from NR and hearts that are failing have low level of NAD in them, the researcher team designed experiments to determine whether a diet supplemented with NR could increase NAD levels in mice with heart failure. They found that NR supplements did indeed restore NAD levels, and remarkably, this stabilization of NAD levels preserved cardiac function in mice that would normally develop heart failure. The researchers also found that NR treatment increased levels of several markers of heart function, which may be used to gauge the success of treatments in the future.

Results of this foundational research expand our understanding of NR’s role in supporting heart health potential and demonstrate that NR supplementation may help patients suffering from heart failure boost their limited energy supplies by restoring NAD levels. This important work paves the way for additional research aimed at determining the therapeutic potential of NR in heart failure patients as well as determine the safe and effective NR doses at which to test these effects in humans.

1. Heart Disease Facts & Statistics | [Internet]. 2017 [cited 2018 Jan 22]. Available from:
2. Neubauer S. The Failing Heart – An Engine Out of Fuel. N Engl J Med. 2007 Mar 15;356(11):1140-51.
3. Cantó C, Houtkooper RH, Pirinen E, Youn DY, Oosterveer MH, Cen Y, et al. The NAD+ Precursor Nicotinamide Riboside Enhances Oxidative Metabolism and Protects against High-Fat Diet-Induced Obesity. Cell Metab. 2012 Jun;15(6):838-47.
4. Diguet N, Trammell SAJ, Tannous C, Deloux R, Piquereau J, Mougenot N, et al. Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated Cardiomyopathy. Circulation. 2017 Dec 7

2018-02-19T08:29:16+00:00 February 15th, 2018|