NMN May Improve Cardiovascular Health in 3 Surprising Ways

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Cardiovascular disease is a leading cause of death in the United States.

Heart disease is the leading cause of death amongst both men and women in the United States, with 1 in 4 deaths per year being attributed to the various forms of the disease. Increasing age is a top risk factor for cardiovascular disease; however, growing older doesn’t have to result in declining heart health. 

The compound NMN, or nicotinamide mononucleotide, is a promising supplement for protecting the heart against this age-related dysfunction. 

Research has indicated that NMN is cardioprotective in several ways: through improving blood vessel integrity, reducing atherosclerosis and oxidative damage, and preventing or ameliorating common causes of cardiovascular diseases.  

What Is NMN? An Overview

NMN is important for health and longevity, as it is a precursor to NAD+ (nicotinamide adenine dinucleotide), an essential coenzyme needed by all cells in the body.

Although essential, levels of NAD+ tend to decline with age, contributing to premature aging — both internally and externally — and chronic disease development. NAD+ also regulates a family of proteins called sirtuins, which play a crucial role in longevity. 

NMN has been linked to increased lifespan in animals, improved cognition and metabolism, DNA repair, obesity reduction, and improved cardiovascular health, which we will discuss in more detail. 

Can NMN Improve Cardiovascular Health? 

Due to its ability to quickly and efficiently enter cells and convert into NAD+, NMN is involved in many cellular and biochemical processes, including those of the heart and vascular systems. 

1. Improves Blood Vessel Health

Damage to the vascular endothelium, a thin layer of cells that line the inside of blood vessels, is a leading cause of cardiovascular disease and mortality. 

Endothelial damage precedes atherosclerosis, the buildup of plaque in the arteries that restricts blood flow and can ultimately lead to heart attacks or strokes. 

With age, both the number and quality of vascular endothelial cells decline. Researchers believe that the subsequent age-related decline in NAD+ levels and sirtuin activity are, in part, responsible for this dysfunction in blood vessel integrity. 

In a March 2018 study published in Cell, older mice who received supplemental NMN experienced improved blood flow and capillary density, similar to levels of young mice. This process was mediated by an increase in the activity of sirtuins (specifically, SIRT1) in their endothelial cells. 

Similar results were found in a June 2016 paper published in Aging Cell, which looked at older mice with impaired endothelium‐dependent dilation, a measure of endothelial function. After NMN supplementation, the endothelial function of the mice was significantly improved by reducing arterial stiffness and activation of SIRT1. 

Lastly, an August 2019 study published in GeroScience found that NMN-supplemented older mice had improved vascular function, including reductions in atherosclerotic buildup and epigenetic rejuvenation of their aortic microRNA profiles. Alterations in microRNA profiles are thought to play a large role in vascular aging and dysfunction. 

Together, these animal studies indicate that supplemental NMN may be a therapeutic method for reducing the commonly seen age-related vascular dysfunction, thereby reducing the risk of cardiovascular diseases. 

NMN has been found to reduce atherosclerosis and improve blood vessel health in animal studies. 

2. Reduces Oxidative Damage

The blood vessels’ endothelium is often a target of oxidative damage, including a buildup of free radicals and reactive oxygen species (ROS). These harmful molecules also contribute to atherosclerosis because oxidized cholesterol particles are responsible for arterial plaque. 

In addition, high levels of ROS reduce the availability of nitric oxide, which dilates blood vessels and regulates blood pressure.  

Oxidative damage tends to increase with age, as the accumulation of these inflammatory molecules can compound over the years. In the vascular system, oxidative damage can ultimately lead to the senescence of endothelial cells. However, there are ways to mitigate this cellular stress.

In the previously mentioned study published in Aging Cell, NMN supplementation also led to a significant reduction in the oxidative compound superoxide in older mice, as well as an increase in nitric oxide production. 

As discussed in a January 2019 review published in Antioxidants & Redox Signaling, SIRT1 acts as a sensor for ROS, which can offer cardioprotection by inducing oxidative cell death. Upregulating SIRT1 through supplemental NMN and its subsequent conversion into NAD+ may activate this oxidative sensor. 

3. Exhibits Cardioprotective Activity  

NMN may be able to protect the heart against various forms of cardiovascular disease. 

Cardiovascular disease encompasses many disorders, including coronary artery disease, myocardial infarctions (heart attacks), stroke, heart failure, and arrhythmias. 

The heart requires a steady supply of energy via ATP to maintain its primary function of circulating blood. Mitochondria produces over 95% of the heart’s ATP; a breakdown in mitochondrial function is linked to heart failure. Mitochondrial dysfunction is common with age and occurs more rapidly when oxidative stress is present. 

In a November 2017 study published in the Journal of Molecular and Cellular Cardiology, mice that were genetically susceptible to cardiac stress received short-term administration of NMN, which protected the mice against heart failure, preserved mitochondrial structure, and reduced the prevalence of ROS in the heart.  

Another name for coronary artery disease is ischemic heart disease; ischemia is when blood flow and oxygen to the heart are reduced. A complication after ischemia is called reperfusion injury, or ischemia followed by reperfusion (I/R). I/R is the tissue damage that occurs when blood supply returns to the tissue after a period of ischemia and is a life-threatening event that often causes heart failure. 

A June 2014 study published in PLoS One aimed to determine if NMN could protect the heart against the damage associated with ischemia and I/R. In mice, NMN preserved heart function and reduced damage from I/R injury when injected before an ischemic event, as well as before and during the reperfusion injury. 

This effect was mediated by sirtuins. In contrast, mice whose genes were modified not to contain SIRT1 did not experience the same cardiac benefits. 

The results from these studies indicate that NMN may exhibit cardioprotective effects during times of low oxygen and blood flow to the heart and with cases of high oxidative stress or mitochondrial dysfunction, all of which are risk factors for various cardiovascular diseases. 

Key Takeaway

  • Cardiovascular disease is a leading health concern, especially with older adults, as vascular function declines with age. 
  • Supplemental NMN has been shown in animal studies to improve blood vessel health and integrity, reduce oxidative damage in the heart and blood vessels, and protect the heart against damaging events. 
  • However, more research is needed to determine if these cardioprotective benefits apply to humans and the aging population. 

Show references

Braidy N, Berg J, Clement J, et al. Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes. Antioxid Redox Signal. 2019;30(2):251-294. doi:10.1089/ars.2017.7269

Das A, Huang GX, Bonkowski MS, et al. Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging. Cell. 2018;173(1):74-89.e20. doi:10.1016/j.cell.2018.02.008

de Picciotto NE, Gano LB, Johnson LC, et al. Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell. 2016;15(3):522-530. doi:10.1111/acel.12461

Heart Disease Facts. Centers for Disease Control and Prevention. Updated June 2020.  www.cdc.gov/heartdisease/facts.htm.

Kiss T, Giles CB, Tarantini S, et al. Nicotinamide mononucleotide (NMN) supplementation promotes anti-aging miRNA expression profile in the aorta of aged mice, predicting epigenetic rejuvenation and anti-atherogenic effects. GeroScience. 2019;41(4):419-439. doi:10.1007/s11357-019-00095-x

Poddar SK, Sifat AE, Haque S, Nahid NA, Chowdhury S, Mehedi I. Nicotinamide Mononucleotide: Exploration of Diverse Therapeutic Applications of a Potential Molecule. Biomolecules. 2019;9(1):34. Published 2019 Jan 21. doi:10.3390/biom9010034

Senoner T, Dichtl W. Oxidative Stress in Cardiovascular Diseases: Still a Therapeutic Target?. Nutrients. 2019;11(9):2090. Published 2019 Sep 4. doi:10.3390/nu11092090

Yamamoto T, Byun J, Zhai P, Ikeda Y, Oka S, Sadoshima J. Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and reperfusion. PLoS One. 2014;9(6):e98972. Published 2014 Jun 6. doi:10.1371/journal.pone.0098972

Zhang R, Shen Y, Zhou L, et al. Short-term administration of Nicotinamide Mononucleotide preserves cardiac mitochondrial homeostasis and prevents heart failure. J Mol Cell Cardiol. 2017;112:64-73. doi:10.1016/j.yjmcc.2017.09.001

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