Nicotinamide adenine dinucleotide (NAD+) exists in every cell and plays a role in hundreds of enzymes. It is involved in a variety of important cellular processes, including energy production, metabolism, and DNA repair. This ubiquitous cofactor may also support a healthy cardiovascular system based on emerging studies connecting healthy levels of NAD+, sirtuins, and heart health.

NAD+, Sirtuins, and Heart Health

An important family of NAD+-consuming enzymes is sirtuins (SIRTs), also known as silent information regulators, of which there are seven. They play various roles in energy metabolism, cell survival, inflammation, circadian rhythm, and DNA transcription and repair. Increasing the activity of SIRTs may increase longevity and support healthy aging and cardiovascular function, especially with SIRT1 and SIRT3.

In animal studies, increased SIRT1 function has been associated with a decrease in atherosclerosis, endothelial inflammation, obesity, serum lipid levels, and hypertension, and a decrease in SIRT1 activity has the opposite effect. Human cell studies found an inverse correlation between age and SIRT1 protein expression. Furthermore, there is a correlation between lower levels of SIRT1 and atherosclerosis plaques, and there is reduced function in vascular smooth muscle cells. SIRT3 is associated with inhibited mitochondrial function and pulmonary arterial hypertension. According to one study on human ventricular tissue, the age-associated changes in SIRT1 and SIRT3 connected with cardiovascular inflammation and mitochondrial dysfunction may be more likely in women than men.

These animal and mechanistic studies have some substantiation in clinical practice. In a study on patients who were admitted for cardiac catheterization, SIRT1 levels in the monocytes were higher in those considered to be healthy subjects compared to those with stable coronary artery disease and those with acute coronary syndromes.

Increasing SIRT1 activity by boosting NAD+ may support normal cardiac function. One mouse study found that short-term administration of nicotinamide mononucleotide (NMN), an NAD+ precursor, increased NAD+ levels in the heart and protected the heart from ischemia/reperfusion injury through activating SIRT1.

NAD+ and Redox Balance

NAD+ also plays a role in redox balance in the cell. As part of the oxidation process of energy metabolism, NAD+ accepts a hydride group to become NADH, which then becomes re-oxidized during oxidative phosphorylation. The ratio of NAD+ to NADH can impact the redox balance. When this imbalance leads to excess oxidative stress, it may contribute to mitochondrial dysfunction in the heart, increasing the risk of heart failure and endothelial dysfunction in vascular aging. Improving the ratio has been shown in a mouse study to benefit heart failure.

The emerging research into the connection between NAD+, sirtuins, and heart health is highlighted, indicating promising areas of support for normal cardiovascular function. One such way may be to support NAD+ levels with substrates, including NAD+ precursors, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), which is a stable direct precursor to NAD+.

By Kendra Whitmore, MS, CNS