What is really known about the effects of nicotinamide riboside supplementation in humans

Science Advances, Год журнала: 2023, Номер 9(29)

Опубликована: Июль 21, 2023

Nicotinamide riboside is a precursor to the important cofactor nicotinamide adenine dinucleotide and has elicited metabolic benefits in multiple preclinical studies. In 2016, first clinical trial of was conducted test safety efficacy human supplementation. Many trials have since been aiming delineate health severe diseases humans. This review endeavors summarize critically assess 25 currently published research articles on supplementation identify any poorly founded claims assist field elucidating actual future potential for riboside. Collectively, oral displayed few clinically relevant effects, there an unfortunate tendency literature exaggerate importance robustness reported effects. Even so, may play role reduction inflammatory states shown some treatment diverse diseases.

Язык: Английский

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Exploring the Heart–Mind Connection: Unraveling the Shared Pathways between Depression and Cardiovascular Diseases

Biomedicines, Год журнала: 2023, Номер 11(7), С. 1903 - 1903

Опубликована: Июль 5, 2023

Civilization diseases are defined as non-communicable that affect a large part of the population. Examples such depression and cardiovascular disease. Importantly, World Health Organization warns against an increase in both these. This narrative review aims to summarize available information on measurable risk factors for CVD based existing literature. The paper reviews epidemiology main coexistence authors emphasize there is evidence link between Here, we highlight common disease, including obesity, diabetes, physical inactivity, well importance prevention treatment preventing other mental disorders. Conversely, effective can also help prevent improve health outcomes. It seems advisable introduce screening tests patients treated cardiac reasons. mood disorders, it worth controlling factors, example, by checking blood pressure pulse during routine visits. paying attention condition with CVD. study underlines interdisciplinary co-operation.

Язык: Английский

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Brain energy metabolism: A roadmap for future research

Journal of Neurochemistry, Год журнала: 2024, Номер 168(5), С. 910 - 954

Опубликована: Янв. 6, 2024

Although we have learned much about how the brain fuels its functions over last decades, there remains still to discover in an organ that is so complex. This article lays out major gaps our knowledge of interrelationships between metabolism and function, including biochemical, cellular, subcellular aspects functional imaging adult brain, as well during development, aging, disease. The focus on unknowns substrates associated transporters, roles insulin lipid droplets, emerging role microglia, mysteries cofactor signaling molecule NAD

Язык: Английский

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Dapagliflozin reduces systemic inflammation in patients with type 2 diabetes without known heart failure

Cardiovascular Diabetology, Год журнала: 2024, Номер 23(1)

Опубликована: Июнь 7, 2024

Abstract Objective Sodium glucose cotransporter 2 (SGLT2) inhibitors significantly improve cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that dapagliflozin improves cardiac via beneficial effects on systemic and inflammation fibrosis. Research design methods This randomized placebo-controlled clinical trial enrolled 62 adult patients (mean age 62, 17% female) with type diabetes (T2D) without known heart failure. Subjects were to 12 months of daily 10 mg or placebo. For all patients, blood/plasma samples magnetic resonance imaging (CMRI) obtained at time randomization end months. Systemic was assessed by plasma IL-1B, TNFα, IL-6 ketone levels PBMC mitochondrial respiration, an emerging marker sterile inflammation. Global myocardial strain feature tracking; fibrosis T1 mapping calculate extracellular volume fraction (ECV); tissue T2 mapping. Results Between baseline 12-month point, IL-1B reduced (− 1.8 pg/mL, P = 0.003) while ketones increased (0.26 mM, 0.0001) dapagliflozin. maximal oxygen consumption rate (OCR) decreased over period placebo group but did not change receiving 158.9 pmole/min/10 6 cells, 0.0497 vs. − 5.2 0.41), a finding consistent anti-inflammatory effect SGLT2i. strain, ECV relaxation both study groups. Clinical Trial.gov Registration NCT03782259.

Язык: Английский

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Energy metabolism in health and diseases

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 18, 2025

Язык: Английский

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Roles of Sirtuins in Cardiovascular Diseases: Mechanisms and Therapeutics

Circulation Research, Год журнала: 2025, Номер 136(5), С. 524 - 550

Опубликована: Фев. 27, 2025

Cardiovascular diseases (CVDs) are experiencing a rapid surge and widely recognized as the leading cause of mortality in current aging society. Given multifactorial etiology CVDs, understanding intricate molecular cellular mechanisms is imperative. Over past 2 decades, many scientists have focused on Sirtuins, family nicotinamide adenine dinucleotide–dependent deacylases. Sirtuins highly conserved across species, from yeasts to primates, play crucial role linking diseases. participate nearly all key physiological pathological processes, ranging embryogenic development stress response aging. Abnormal expression activity exist aging-related diseases, while their activation has shown efficacy mitigating these (eg, CVDs). In terms research, this field maintained fast, sustained growth recent years, fundamental studies clinical trials. review, we present comprehensive, up-to-date discussion biological functions roles regulating cardiovascular biology CVDs. Furthermore, highlight latest advancements utilizing Sirtuin-activating compounds dinucleotide boosters potential pharmacological targets for preventing treating The unresolved issues field—from chemicobiological regulation Sirtuin-targeted CVD investigations—are also discussed. This timely review could be critical updated knowledge Sirtuin CVDs facilitating accessibility Sirtuin-targeting interventions.

Язык: Английский

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Full Spectrum Flow Cytometry as a Powerful Technology for Cancer Immunotherapy Research

Frontiers in Molecular Biosciences, Год журнала: 2021, Номер 7

Опубликована: Янв. 29, 2021

The Nobel Prize-deserving concept of blocking inhibitory pathways in T cells, to unleash their anti-tumoral capacity, became one the pillars cancer treatment last decade and has resulted durable clinical responses for multiple types. Currently, two most important goals immunotherapy are understand mechanisms resulting failure checkpoint blockade identify predictive immunological biomarkers that correlate response, disease progression or adverse effects. identification validation routine use is not only critical monitor progression, but also personalize develop new therapies. To achieve these goals, powerful research tools needed. Flow cytometry stands as successful single-cell analytical used characterize immune cell phenotypes solid tumors, hematological malignancies, minimal residual metastatic progression. This technology been fundamental diagnosis, translational trials. Most recently, need evaluate simultaneously more features each pushed field implement adaptations beyond conventional flow cytometry, including Full Spectrum Cytometry (FSFC). FSFC captures full emission spectrum fluorescent molecules using arrays highly sensitive light detectors, date enabled characterization 40 parameters a single sample. We will summarize contributions this advancement studies discuss best practices obtain reliable, robust reproducible results.

Язык: Английский

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NAD ⁺ Metabolism in Cardiac Health, Aging, and Disease

Circulation, Год журнала: 2021, Номер 144(22), С. 1795 - 1817

Опубликована: Ноя. 29, 2021

Nicotinamide adenine dinucleotide (NAD + ) is a central metabolite involved in energy and redox homeostasis as well DNA repair protein deacetylation reactions. Pharmacological or genetic inhibition of NAD -degrading enzymes, external supplementation precursors, transgenic overexpression -generating enzymes have wide positive effects on metabolic health age-associated diseases. pools tend to decline with normal aging, obesity, hypertension, which are all major risk factors for cardiovascular disease, replenishment extends healthspan, avoids syndrome, reduces blood pressure preclinical models. In addition, experimental elevation improves atherosclerosis, ischemic, diabetic, arrhythmogenic, hypertrophic, dilated cardiomyopathies, different modalities heart failure. Here, we critically discuss cardiomyocyte-specific circuitries metabolism, comparatively evaluate distinct precursors their efficacy, raise outstanding questions the optimal design clinical trials supraphysiological elevations assessed prevention treatment cardiac We surmise that patients hitherto intractable diseases such failure preserved ejection fraction may profit from administration precursors. The development -centered treatments will rely technological conceptual progress fine regulation metabolism.

Язык: Английский

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Mitochondrial Dysfunction and Therapeutic Perspectives in Cardiovascular Diseases

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(24), С. 16053 - 16053

Опубликована: Дек. 16, 2022

High mortality rates due to cardiovascular diseases (CVDs) have attracted worldwide attention. It has been reported that mitochondrial dysfunction is one of the most important mechanisms affecting pathogenesis CVDs. Mitochondrial DNA (mtDNA) mutations may result in impaired oxidative phosphorylation (OXPHOS), abnormal respiratory chains, and ATP production. In dysfunctional mitochondria, electron transport chain (ETC) uncoupled energy supply reduced, while reactive oxygen species (ROS) production increased. Here, we discussed analyzed relationship between mtDNA mutations, mitophagy, decreased OXPHOS, elevated ROS, CVDs from perspective dysfunction. Furthermore, explored current potential therapeutic strategies for by eliminating (e.g., editing replacement), enhancing improving OXPHOS capacity supplement with NAD+, nicotinamide riboside (NR), mononucleotide (NMN), nano-drug delivery), reducing ROS Coenzyme Q10 other antioxidants), dissected their respective advantages limitations. fact, some are still a long way achieving safe effective clinical treatment. Although establishing remains challenging, starting holds bright prospects.

Язык: Английский

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Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects

Frontiers in Nutrition, Год журнала: 2022, Номер 9

Опубликована: Апрель 11, 2022

Nicotinamide mononucleotide (NNM) is an orally bioavailable NAD+ precursor that has demonstrated beneficial effects against aging and aging-associated diseases in animal models. NMN ultimately converted to NAD+, a redox cofactor mediates many metabolic enzymes. also serves as the substrate for poly(ADP-ribose) polymerase (PARP) sirtuins, regulates various biological processes, such metabolism, DNA repair, gene expression, stress responses. Previous mouse models showed administration can increase organs ameliorate aging-related diseases, obesity, diabetes, heart failure, stroke, kidney Alzheimer's disease through NAD+-mediated pathways. However, evidence of its effect on humans still scarce. In this study, we conducted placebo-controlled, randomized, double blind, parallel-group trial investigate safety administered efficacy levels thirty healthy subjects. Healthy volunteers received 250 mg/day (n = 15) or placebo 12 weeks, physiological laboratory tests were performed during period. addition, related metabolites whole blood examined. Oral supplementation weeks caused no abnormalities tests, obvious adverse observed. significantly increased after administration. We observed significant rise nicotinic acid (NAMN) levels, but not NMN. found amount was strongly correlated with pulse rate before These results suggest oral safe practical strategy boost humans. Clinical Trial Registration: JRCT [https://jrct.niph.go.jp/], identifier: [jRCTs041200034].

Язык: Английский

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