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Diagram of heart and circulatory systsem with red blood cells

Many studies consider the impact of NAD levels on heart health, blood vessels, and the failing heart.

Here are the studies:

Aug 26, 2023

Heart - Vascular - Endothelium

Toxicology in Vitro

Nicotinamide mononucleotide inhibits oxidative stress-induced damage in a SIRT1/NQO-1-dependent manner

Nakajo, Takahisa


We used human umbilical vein endothelial cells (HUVECs) to demonstrate that NMN inhibits oxidative stress-induced damage by activating the sirtuin 1 (SIRT1)/NAD(P)H: quinone oxidoreductase 1 (NQO-1) axis. We found that NMN inhibited H2O2-induced cytotoxicity and senescence-associated protein expression, such as p16 and p21. Furthermore, NMN prevented H2O2-induced actin cytoskeletal disorganization via inhibiting reactive oxygen species (ROS) production. NMN increased NQO-1 mRNA and protein expression that in turn was abrogated by SIRT1 inhibition, suggesting that NMN-inducible NQO-1 was associated with SIRT1 activity. SIRT1 and NQO-1 inhibition attenuated the inhibitory effect of NMN on H2O2-inducible cytotoxicity, senescence-related protein upregulation, and actin cytoskeletal disorganization. Our findings provide new insights into the mechanism by which NMN exerts protective effects against vascular oxidative stress.

Aug 18, 2023

Heart - Vascular

European Journal of Clinical Investigation

Effects of NAD+ precursors on blood pressure, C-reactive protein concentration and carotid intima-media thickness: A meta-analysis of randomized controlled trials

Lei, Langhuan


Meta-analyses of [29 random controlled trials with 8,664 participants]...indicated a significant reduction in systolic...and diastolic blood pressure...with the NAD+ precursors supplementation compared with the control group. In addition, a greater effect of supplementation with NAD+ precursors in reducing blood pressure (BP) were observed with the highest dose (≥2 g) and duration of the intervention (>12 weeks)...These findings suggest that NAD+ precursor supplementation might have a beneficial effect on cardiovascular risk factors such as blood pressure, C-reactive protein concentration and carotid intima-media thickness.

Feb 16, 2023

Heart - Vascular - Endothelium

Scientific Reports

Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial

Katayoshi, Takeshi


A 12-week randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted. A total of 36 healthy middle-aged participants received one capsule of either 125 mg NMN or placebo twice a day. Among the NAD+ metabolites, the levels of nicotinamide in the serum were significantly higher in the NMN intake group than in the placebo group. Pulse wave velocity values indicating arterial stiffness tended to decrease in the NMN intake group. However, no significant difference was found between the two groups. Long-term NMN supplementation at 250 mg/day was well tolerated and did not cause adverse events. NMN safely and effectively elevated NAD+ metabolism in healthy middle-aged adults. Additionally, NMN supplementation showed potential in alleviating arterial stiffness.

Feb 6, 2023

Metabolism - Heart / Vascular - NMN - Obesity

Journal of Clinical Endocrinology & Metabolism

Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study

Pencina, Karol Mateusz


NMN administration in overweight or obese, middle-aged and older adults safely increased circulating NAD levels, and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure.

Feb 4, 2023

Heart / Vascular - Aging


NAD+ Homeostasis and NAD+-Consuming Enzymes: Implications for Vascular Health

Campagna, Roberto


Although future studies are required to better clarify the potential of targeting NAD+ homeostasis, the strategies based on administering NAD+ precursors or inhibiting NAD+-dependent enzymes seem to be an attractive approach for reducing chronic low-grade inflammation, enhancing mitochondrial biogenesis, and improving oxidative metabolism in vascular cells.

Dec 31, 2022

Kidney - Heart / Vascular

Journal of Molecular and Cellular Cardiology

Nicotinamide riboside improves MI-induced acute kidney injury through increasing nicotinamide phosphorybosil transferase and NAD renal levels

Habeichi, Nada


NR supplementation holds a promising therapeutic potential for myocardial infarction-induced acute kidney injury

Oct 11, 2022

Circadian Rhythm - Aging - Heart

American Journal of Physiology - Cell Physiology

Circadian cardiac NAD+ metabolism, from transcriptional regulation to healthy aging

Carpenter, Bryce J.


...Recent studies have expanded on the role of circadian rhythms and the core clock factors that maintain them in the regulation of NAD+ levels in the heart. This has revealed that NAD+ pools and their use are tightly linked to cardiac function, but also heart failure. The convergence of these fields, namely, clock regulation, heart disease, and NAD+ metabolism present a complex network ripe with potential scientific and clinical discoveries, given the growing number of animal models, recently developed technology, and opportunity for safe and accessible precursor supplementation...

Oct 1, 2022

Heart / Vascular - Mitochondrial Disorder

Molecular Metabolism

Nicotinamide riboside alleviates exercise intolerance in ANT1-deficient mice

Schaefer, Patrick


Increasing NAD+ levels with nicotinamide riboside can alleviate the exercise intolerance associated to ANT1-deficiency, indicating the therapeutic potential of NAD+-stimulating compounds in mitochondrial myopathies.

Sep 14, 2022

Heart / Vascular - Aging

Journal of Cardiovascular Aging

Metabolic targets in cardiac aging and rejuvenation

Liu, Chang


NAD+ repletion can delay several hallmarks of aging and suppress the deterioration of age-related diseases[95]. This suggests a significant potential for the treatment of cardiac diseases in the elderly population with supplementation of NAD+ precursors. Indeed, the dietary intake of NAM could reduce cardiac hypertrophy and diastolic dysfunction in aged mice

Sep 14, 2022

Heart / Vascular

JACC: Basic to Translational Science

Safety and Tolerability of Nicotinamide Riboside in Heart Failure With Reduced Ejection Fraction

O'Brien, Kevin


The mitochondrial dysfunction characteristic of heart failure (HF) is associated with changes in intracellular nicotinamide adenine dinucleotide (NAD+) and NADH levels. Raising NAD+ levels with the NAD+ precursor, nicotinamide riboside (NR), may represent a novel HF treatment. In this 30-participant trial of patients with clinically stable HF with reduced ejection fraction, NR, at a dose of 1,000 mg twice daily, appeared to be safe and well tolerated, and approximately doubled whole blood NAD+ levels...

May 9, 2022

Heart - Vascular - Circadian Rhythm - Aging

Frontiers in Molecular Medicine

Nicotinamide Riboside Improves Cardiac Function and Prolongs Survival After Disruption of the Cardiomyocyte Clock

Dierickx, Pieterjan


Here, we show that supplementation with the NAD+ precursor NR as a dietary supplement improves heart function and extends the lifespan of female mice lacking cardiac REV-ERBs. Thus, boosting NAD+ levels can improve cardiac function in a setting of heart failure caused by disruption of circadian clock factors, providing new insights into the links between the circadian clock, energy metabolism, and cardiac function.

Dec 3, 2021

Heart / Vascular


Therapeutic Potential of Emerging NAD+-Increasing Strategies for Cardiovascular Diseases

Rotllan, Noemi


Compelling evidence suggests that NAD+ homeostasis is required for normal cardiovascular function. Numerous studies suggest that declining NAD+ concomitant with mitochondrial dysfunction is a common trait in myocardial and cardiovascular diseases...Except for NA, which causes some adverse clinical outcomes, vitamin B3 intermediates have been demonstrated to be safe and to have promising beneficial effects in combating cardiovascular diseases in vivo...

Nov 29, 2021

Reproduction - Pregnancy - Stem Cells - Heart / Vascular

Cell Death & Disease

Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells

Meng, Ya


This study not only demonstrates nicotinamide as a useful factor for cardiomyocyte production in regenerative medicine, but also implicates that nicotinamide could have a profound impact on embryogenesis if it is prescribed during pregnancy.

Aug 27, 2021

Heart / Vascular

Frontiers in Cardiovascular Medicine

Enhancing NAD+ Metabolome in Cardiovascular Diseases: Promises and Considerations

Jahan, Fahmida


Clinical trials with various NAD+ precursors such as Trp, NA, or NR showed that increasing NAD+ levels is associated with reduced risk of developing CVD, lowers blood pressure and improves hypocholesteremia, enhances cardiac mitochondrial function and decreases aortic stiffness

Apr 22, 2021

Heart / Vascular

Circulation Research

NAD+ Repletion Reverses Heart Failure With Preserved Ejection Fraction

Tong, Dan


...We tested whether oral NR could correct the NAD+ deficiency and improve mitochondrial function in Heart failure with preserved ejection fraction (HFpEF). Remarkably, after full development of HFpEF (5 weeks of HFD+L-NAME), 8 weeks of NR supplementation ameliorated NAD+ deficiency and reversed hyperacetylation of VLCAD in animals maintained on HFpEF treatment...We have discovered that oral NR effectively corrected cardiac NAD+ deficiency, reversed the hyperacetylation status of key FAO enzymes, and improved mitochondrial function in our murine HFpEF model. This correlated with remarkable attenuation of left ventricular hypertrophy and diastolic dysfunction and dramatic improvement of HFpEF functional manifestations, suggesting that NR could potentially emerge as a promising therapeutic agent for HFpEF. It is worth emphasizing that restoration of all these parameters occurred in the continued presence of the HFpEF-triggering comorbidities of mechanical and metabolic stress.

Apr 1, 2021

Heart / Vascular

Clinica Chimica Acta

NAD+ and cardiovascular diseases

Lin, Qiuzhen


...NAD+ protects against metabolic syndrome, heart failure, ischemia-reperfusion (IR) injury, arrhythmia and hypertension. Accordingly, the subsequent loss of NAD+ in aging or during stress results in altered metabolic status and potentially increased disease susceptibility. Therefore, it is essential to maintain NAD+ or reduce loss in the heart. This review focuses on the involvement of NAD+ in the pathogenesis of cardiovascular disease and explores the effects of NAD+ boosting strategies in cardiovascular health.

Dec 15, 2020

Heart / Vascular - Obesity

Life Sciences

Nicotinamide riboside reduces cardiometabolic risk factors and modulates cardiac oxidative stress in obese Wistar rats under caloric restriction

Macedo de Castro, Josimar


This is the first study to report effects of nicotinamide riboside on cardiac oxidative stress in an obesity model. Nicotinamide riboside, a natural dietary compound, presented antiobesity effects and cardiometabolic benefits, in addition to positively modulating oxidative stress in the heart, in a state-dependent manner.

Oct 12, 2020

Heart / Vascular - Inflammation

Journal of Clinical Investigation

Boosting NAD level suppresses inflammatory activation of PBMCs in heart failure

Zhou, Bo


While mitochondria play an important role in innate immunity, the relationship between mitochondrial dysfunction and inflammation in heart failure is poorly understood. In this study we aimed to investigate the mechanistic link between mitochondrial dysfunction and inflammatory activation in peripheral blood mononuclear cells (PBMCs), and the potential antiinflammatory effect of boosting the NAD level. ...Oral nicotinamide riboside (NR) administration enhanced PBMC respiration and reduced proinflammatory cytokine gene expression in 4 subjects with heart failure. These findings suggest that systemic inflammation in patients with heart failure is causally linked to mitochondrial function of the PBMCs. Increasing NAD levels may have the potential to improve mitochondrial respiration and attenuate proinflammatory activation of PBMCs in heart failure.

Aug 1, 2020

Heart / Vascular

Biochemical Pharmacology

Reversal of endothelial dysfunction by nicotinamide mononucleotide via extracellular conversion to nicotinamide riboside

Mateuszuk, Lukasz


NMN and NR modulate intracellular NAD content in endothelium, inhibit endothelial inflammation and improve NO-dependent function by CD73-dependent and independent pathways, respectively. Extracellular conversion of NMN to NR by CD73 localized in the luminal surface of endothelial cells represent important vasoprotective mechanisms to maintain intracellular NAD.

Mar 21, 2020

Heart / Vascular

Journal of Molecular and Cellular Cardiology

Modulation of the Cardiac Sodium Channel Nav1.5 Peak and Late Currents by NAD+ Precursors

Matasic, Daniel S.


These findings provide substantial evidence for a direct role of NAD+ in regulating the electrical activity of the heart through modulation of NaV1.5.

NAD Research - Heart

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