Elderly Patients with Heart Failure Have Lower NAD+ Levels
A new study published in Experimental Gerontology found that among 170 blood donors, elderly patients with heart failure had the lowest NAD+ levels, which suggests a role for NAD+ precursors in supporting heart health [1].
NAD+: At the Heart of the Matter
A growing body of published preclinical and clinical evidence suggests that NAD+ supports cardiovascular health by regulating multiple cellular pathways that, when dysfunctional may contribute to cardiovascular disease.
While levels of NAD+ are known to decline with age, the risk of cardiovascular disease increases many-fold. As the population continues to get older, cardiovascular disease remains the leading cause of death in the U.S., accounting for nearly 3 million deaths annually.
One likely contributor to age-related cardiovascular dysfunction, and an important target for research into prevention and treatment of heart disease, is cardiovascular inflammation.
While inflammation is meant to protect the body against pathogens and deal with tissue injury, inflammation gone rogue can damage cells and tissues and lead to loss of essential function. Chronic inflammation of the cardiovascular system is known to cause atherosclerosis, a condition characterized by a dangerous build-up of plaque and stiffening of the blood vessels.
Stiff blood vessels increase blood pressure, which heightens the risk of heart failure. These inflammatory plaques can also detach and obstruct other vessels throughout the body, resulting in heart attacks, strokes, and heart failure.
A recent study conducted in human cell cultures found that raising NAD+ with the NAD+ precursor nicotinamide riboside (NR) could prevent inflammation in endothelial cells - the cells that line blood vessels [2]. NAD+ is known to regulate immune cells and decrease secretion of pro-inflammatory signaling molecules that contribute to inflammatory damage.
Regulating inflammation at the cellular level may translate to tangible health benefits. An earlier human trial published in Nature Communications in 2018 found that nicotinamide riboside (NR) reduced systolic blood pressure in pre-hypertensive patients relative to a placebo, perhaps by modulating this inflammation and supporting endothelial cells [3].
Could Raising NAD+ Ameliorate Heart Failure?
On top of its potential to improve elevated systolic blood pressure, raising NAD+ with NR has been suggested to have further applications in addressing heart failure.
A study recently published in the Journal of Clinical Investigations (JCI) found that NR supplementation could reduce markers of inflammation and immune cell dysfunction among a small group of Stage D heart failure patients [4].
That study found that twice daily supplementation with NR for 5-9 days could reduce pro-inflammatory cytokines like IL-6, which are known to be elevated in heart failure, among the participants. NR was also shown to improve the respiration rate of immune cells called peripheral blood mononuclear cells (PBMCs), reflecting an improvement in cell function that could explain the reduced inflammation [4].
While the JCI human trial was limited in that it only involved four patients [4], this latest study from Experimental Gerontology looked at NAD+ levels in 170 participants, and found that the levels of NAD+ among elderly heart failure patients were significantly reduced [1]. Nineteen heart failure patients between the ages of 75 and 101 were compared to a control group of 151 healthy participants between the ages of 19 and 68 [1].
NAD+ levels also tended to decrease with age among the male participants, but not the female participants [1], though previous studies have demonstrated that NAD+ is depleted with aging [5].
Based on the demonstrated loss of NAD+ among heart failure patients, the authors of the study concluded that “administration of NAD+ precursors to this type of patient should be tested for clinical benefit.” [1]
NR has already shown promising effects on cardiovascular health across numerous studies. However, specific, larger-scale trials will need to be conducted to assess whether NR can improve cardiovascular outcomes or heart function. Human trials are currently evaluating NR for its potential to improve function in peripheral artery disease, to boost the effects of exercise on hypertension, and to address high blood pressure in patients with chronic kidney disease.
With the unprecedented and growing global burden of heart disease, research into therapies of all types, such as raising NAD+ with NR, is more essential than ever.