NAD for the Treatment of Heart Failure

Heart failure with preserved ejection fraction (HFpEF) is a prevalent form of cardiac decompensation that is increasing with population aging and there still no evidence-based therapies for it. 

Although is the leading cause of hospitalization in the elderly with almost a third of discharged patients being admitted or dying within 3 months. The search for effective pharmacotherapies have failed due to the heterogeneous nature of the disease. 

One therapy that is being studied is the use of nicotinamide adenine dinucleotide (NAD+). Restoring NAD+ abundance can attenuate metabolic abnormalities in animal models of aging and obesity, which are also 2 major risk factors for HFpEF. 

Recently, a team of scientists examined whether supplementation of the NAD+ precursor nicotinamide (NAM) attenuated diastolic dysfunction, which is commonly seen in HEpEF, using animal models of aging, hypertension, and metabolic syndrome. The study appears in the journal Science Translational Medicine. 

Potential Therapeutic Agents

The researchers found that the cardioprotective effect of NAM on diastolic function was mediated apparently by  non-exclusive NAD+ effects on systemic energy metabolism and on cardiomyocyte local signaling. The beneficial effect of NAM was also evident in the absence of obesity and hypertension suggesting that it might also act directly on the heart. 

The oral supplementation of NAM in rats improved diastolic dysfunction induced by advanced aging, hypertension and cardiometabolic syndrome. NAM induced fatty acid oxidation and improved passive cardiomyocyte stiffness. 

In a long-term human cohort study, high dietary intake of naturally occurring NAD+ precursors was associated with lower blood pressure and reduced risk of cardiac mortality.

Their results suggest that NAD+ precursors such as nicotinamide are potential therapeutic agents to treat diastolic dysfunction in humans that need further studies. 

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Source:

Abdellatif M, et al. Nicotinamide for the treatment of heart failure with preserved ejection fraction. Sci Transl Med. 2021 Feb 10;13(580):eabd7064. doi: 10.1126/scitranslmed.abd7064. PMID: 33568522; PMCID: PMC7611499.

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