In a mouse model with a heart ailment called dilated cardiomyopathy, the levels of cardiac NAD+ decline with age, leading to heart failure. Restoring NAD+ levels enhances heart performance, including the volume of blood ejected from the heart with each beat, known as ejection fraction. NAD+ replenishment also thwarts heart disease characteristics, including tissue damage. Heart failure (HF) is a growing concern, particularly for individuals over 50 years. The prevalence of HF doubles with every passing decade. While surgeries and medications can alleviate symptoms, a standard curative intervention remains hard to find. However, recent research suggests that lifestyle interventions and anti-ageing agents, such as an NAD+ supplement, might prevent heart failure. In a new study published in Nature Cardiovascular Research, scientists from the Canadian Hospital for Sick Children unveiled surprising findings. They said NAD+ can potentially stop the onset of dilated cardiomyopathy (DCM), a major heart condition. What is NAD+ Supplement’s Role in Preventing Heart Disease? The study’s senior author, Dr. Paul Delgado-Olguín, noted an interesting revelation. He mentioned one of the early signs of heart failure may be the dysregulation of energy production. While energy deficiency is often associated with advanced heart failure, this research suggests it could be the root of heart failure and not just a consequence. Replenishing NAD+ for Maintaining Heart Function Dilated cardiomyopathy (DCM) is characterised by an enlarged left ventricle incapable of pumping sufficient blood. This ultimately leads to HF if left untreated. While the DCM’s inherited type accounts for approximately 30% of cases, the remaining 70% is still a mystery. To explore the role of energy metabolism in DCM, Canadian researchers devised a unique animal model. They genetically removed the gene ‘Kdm8’ from the hearts of mice. This gene is linked to heart failure in mice before birth and congenital heart conditions in humans. The resulting mouse model, referred to as the HF mouse, displayed hallmark features of DCM. It included enlarged ventricles that succumbed prematurely to heart failure. These mouse hearts also exhibited an age-associated fall in NAD+ levels, a pivotal mediator of energy metabolism. To see whether replenishing with NAD+ supplements could halt the progression of DCM, the research team administered daily injections of 50 mg/kg of NAD+ to the mice for two months. The NAD+ supplement treatment commenced before any signs of heart disease manifested. The outcomes were remarkable. The NAD plus supplement injections prevented heart dysfunction and ventricle enlargement, evidenced by measures like ejection fraction. This highlights the NAD+ supplement benefits to preserve heart function and mitigate the progression of DCM. Protection Against Cardiac Tissue Damage In heart disease, damaged cardiac cells are often replaced by collagen and not living cells. This results in tissue scarring, known as fibrosis. The study disclosed that HF mice experienced an age-linked surge in fibrosis, marked by an increase in collagen levels. However, when HF mice were injected with NAD+, the elevation in fibrosis was prevented. This shows the protective role of the NAD+ supplement in averting cardiac tissue damage, a factor that might contribute to improved heart function. NAD+ in Human Studies A preliminary human study demonstrated the potential of NAD+ as a therapeutic agent. The NAD+-boosting nicotinamide riboside was shown to reduce inflammation in patients of HF, although this study involved only five participants. Encouragingly, a larger study involving 40 participants is currently underway to determine whether bolstering NAD+ could effectively treat HF patients. Direct NAD+ Boosting vs. Precursors The research by Ahmed and his team suggests that directly boosting NAD+ may be more effective in preventing heart disease when administered proactively before heart failure indicators emerge. Dr. Delgado-Olguín emphasises that this research opens the door to the possibility of altering metabolic pathways, staving off heart failure before the heart sustains damage. While the findings are promising, it’s essential to recognise that this study’s model is skewed specifically towards the Kdm8 gene, which might not fully replicate DCM’s cellular pathology. Thus, more mouse models will have to be explored. Nevertheless, many of DCM’s characteristics, like fibrosis and reduced ejection fraction, are traits of heart ageing. This suggests that NAD+ may have the potential to mitigate heart ageing and other diseases, offering hope for a future where heart failure can be averted before it takes hold. The research conducted by the Hospital for Sick Children in Canada unveils an exciting potential in the form of NAD+ for preventing heart failure. By addressing energy dysregulation and preserving heart function in a DCM model, NAD+ emerges as a promising supplement for further exploration. As larger human trials are underway, the possibility of using NAD+ to combat heart failure becomes more compelling. While new research is needed to fully understand its impact, NAD+ offers a beacon of hope in the quest to mitigate heart ageing and other cardiovascular diseases linked to ageing.