NMN supplementation promotes heart health, prevents heart failure

Studies have shown that heart failure is associated with mitochondrial dysfunction. Mitochondrial dysfunction has been recognized as critical to the pathogenesis of heart disease. Restoring or improving mitochondrial function has a very important role in the treatment of heart failure.

In 2017, a joint study by Dr. Rongli Zhang of Case Western Reserve

University School of Medicine and Tongji Hospital Affiliated to Tongji University showed that short-term intraperitoneal injection of NMN successfully protected mice from heart failure caused by pressure overload. This is because NMN protects the ultrastructure of mitochondria, reduces reactive oxygen species levels, and prevents cardiac cell death.

The level of NAD+ is closely related to mitochondrial function, and increasing the level of NAD+ helps to repair mitochondrial function.

The study conducted experiments on mice with heart-specific defects and

found that short-term administration of nicotinamide mononucleotide (NMN) successfully protected mutant mice from stress-induced heart failure. NMN maintained mitochondrial ultrastructure, reduced ROS and prevented cell death in the heart. These results demonstrate that hyperacetylation of mitochondrial proteins is critical in the pathogenesis of heart disease and that NMN administration may be a promising therapeutic approach.

Mice with specific heart defects and normal mice were used in this experiment. The mice in the experimental group were injected with NMN at a daily dose (500 mg/kg/day), and the control group was injected with the same amount of placebo. Testing the mice found hyperacetylation of mitochondrial proteins in the hearts of the deficient mice, which are associated with mitochondrial dysfunction and heart failure.

NMN supplementation corrects mitochondrial acetylation and saves the heart NMN administration increased mouse cardiac tissue NAD+ levels and normalized mitochondrial protein acetylation levels in the heart. NMN

treatment did not affect the expression of the hypertrophic genes ANF, β- MHC, but attenuated the induction of the inflammatory genes IL1β, CCL2 and IL6 in the hearts of deficient mice, suggesting that NMN supplementation maintains the normal hypertrophic response to pressure overload and reduces cardiac damage .

NMN supplementation improves mitochondrial fatty acid oxidation The study tested whether short-term administration of NMN affects

mitochondrial respiration. When palmitate was used as a long-chain fatty acid substrate, NMN treatment significantly increased basal and maximal OCR, indicating that NMN improved fatty acid oxidation (FAO). Collectively, these mitochondrial respiration-based studies suggest that NMN treatment improves oxidation of long-chain fatty acids, even in a short-term. This effect of NMN can be achieved by deacetylation of key fatty acid oxidase, long-chain fatty acids are the main fuel of the heart, so NMN can significantly improve cardiac energy and cardiac function.

NMN administration preserves mitochondrial ultrastructure and reduces cell death in pressure overloaded hearts Upon stress overload, heart-deficient mice developed acute heart failure with severely disrupted mitochondrial homeostasis, manifested by marked changes in mitochondrial ultrastructure. In contrast, this change was not observed in normal mice. NMN administration almost completely restored mitochondrial ultrastructure to levels comparable to normal mice. showed that NMN successfully maintained mitochondrial homeostasis in deficient mouse hearts during pressure overload, thereby improving cardiac function.

NMN administration preserves mitochondrial ultrastructure and reduces cell death in pressure overloaded hearts

Upon stress overload, heart-deficient mice developed acute heart failure with severely disrupted mitochondrial homeostasis, manifested by marked changes in mitochondrial ultrastructure. In contrast, this change was not observed in normal mice. NMN administration almost completely restored mitochondrial ultrastructure to levels comparable to normal mice (Panel B). showed that NMN successfully maintained mitochondrial homeostasis in

deficient mouse hearts during pressure overload, thereby improving cardiac function.

Mitochondrial damage is often associated with ROS oxidative stress and cell death. Experiments found a marked increase in ROS in the myocardium of heart-deficient mice, and NMN treatment reduced this ROS burst.

In cardiac deficient mice treated with NMN, aortic arch constriction (TAC)- induced cardiac cell death was reduced to <5%. These data suggest that short-term administration of NMN preserves cardiac mitochondrial function, reduces TAC-induced mitochondrial damage, reduces myocardial ROS and prevents cell death. The combined effects of these multiple levels mediated by NMN contribute to the maintenance of normal function of cardiac mitochondria, cardiomyocytes and ultimately the heart.