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Nicotinamide adenine dinucleotide (NAD+) plays an essential role in multiple physiological processes, including energy metabolism, DNA repair, and immune activation. Cellular NAD+ production declines with age, however, and its depletion has been implicated in the onset and progression of a wide range of age-related conditions. Findings from a new study suggest that NAD+ is beneficial in treating heart failure with preserved ejection fraction.

The heart’s ejection fraction is a measure of how much blood the left ventricle pumps with each contraction. Heart failure with preserved ejection fraction, a condition in which the heart muscle contracts normally but the ventricles don’t properly relax, is a leading cause of hospitalization in older adults. Few therapies for the condition exist, but caloric restriction has been shown to improve disease status in people with heart failure with preserved ejection fraction. Increasing cellular levels of NAD+ mimics the effects of caloric restriction.

The study involved both rodents and humans. In the rodent portion of the study, the authors gave nicotinamide, a precursor to NAD+, to mice and rats that had cardiovascular dysfunction related to aging, salt-sensitivity, or obesity. The animals' heart function improved in each of the three scenarios via enhanced diastolic function, improved heart bioenergetics, and reduced comorbidities, including blood pressure and body fat.

The human study drew on nutritional and death rate data from a prospective, population-based survey of atherosclerosis among 40- to 79-year-old men and women. The data indicated that higher dietary intake of NAD+ precursors reduced the risk of all causes of premature death, especially those related to cardiovascular diseases. People who consumed more NAD+ precursors were also less likely to have high blood pressure. These findings held true even after taking into account other factors, including age, sex, smoking, diabetes, alcohol intake, body mass index, and total cholesterol.

These findings demonstrate that NAD+ precursors show promise as a means of treating heart failure with preserved ejection fraction. The FMF team has developed a collection of articles related to NAD+ and its precursors, nicotinamide mononucleotide and nicotinamide riboside.

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