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

JACC Basic to Translational Science, Год журнала: 2022, Номер 7(12), С. 1183 - 1196

Опубликована: Сен. 14, 2022

The mitochondrial dysfunction characteristic of heart failure (HF) is associated with changes in intracellular nicotinamide adenine dinucleotide (NAD+) and NADH levels. Raising NAD+ levels the precursor, riboside (NR), may represent a novel HF treatment. In this 30-participant trial patients clinically stable reduced ejection fraction, NR, at dose 1,000 mg twice daily, appeared to be safe well tolerated, approximately doubled whole blood Intraindividual increases response NR correlated peripheral mononuclear cell basal (R2 = 0.413, P 0.003) maximal 0.434, 0.002) respiration, decreased NLRP3 expression 0.330, 0.020). (Nicotinamide Riboside Systolic Heart Failure; NCT03423342)

Язык: Английский

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Boosting NAD+ blunts TLR4-induced type I IFN in control and systemic lupus erythematosus monocytes

Journal of Clinical Investigation, Год журнала: 2022, Номер 132(5)

Опубликована: Янв. 13, 2022

BACKGROUNDFasting and NAD+-boosting compounds, including NAD+ precursor nicotinamide riboside (NR), confer antiinflammatory effects. However, the underlying mechanisms therapeutic potential are incompletely defined.METHODSWe explored biology in myeloid cells from healthy volunteers following vivo placebo or NR administration subsequently tested findings vitro monocytes extracted patients with systemic lupus erythematosus (SLE).RESULTSRNA-Seq of unstimulated LPS-activated implicated regulation autophagy type I IFN signaling. In primary monocytes, blunted LPS-induced IFN-β production, genetic pharmacological disruption phenocopied this effect. Given that is a coenzyme oxidoreductive reactions, metabolomics was performed identified increased inosine level. Inosine supplementation similarly release. Finally, because SLE exhibits dysregulation, we assessed effect on found reduced release.CONCLUSIONWe conclude NR, an NAD+-dependent manner part via signaling, mediated suppression attenuated cells, as adjunct for management.TRIAL REGISTRATIONClinicalTrials.gov registration numbers NCT02812238, NCT00001846, NCT00001372.FUNDINGThis work supported by NHLBI NIAMS Intramural Research divisions.

Язык: Английский

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Clinical Trials Targeting Aging

Frontiers in Aging, Год журнала: 2022, Номер 3

Опубликована: Фев. 4, 2022

The risk of morbidity and mortality increases exponentially with age. Chronic inflammation, accumulation DNA damage, dysfunctional mitochondria, increased senescent cell load are factors contributing to this. Mechanistic investigations have revealed specific pathways processes which, proposedly, cause age-related phenotypes such as frailty, reduced physical resilience, multi-morbidity. Among promising treatments alleviating the consequences aging caloric restriction pharmacologically targeting longevity mechanistic target rapamycin (mTOR), sirtuins, anti-apoptotic in cells. Regulation these has significant health- lifespan extending results animal models. Nevertheless, it remains unclear if similar translate humans. A requirement translation development age- associated biomarkers longitudinal trials difficult not feasible, practical, nor ethical when human life span is endpoint. Current anti-aging intervention studies humans will be covered within this paper. future clinical may phase 2 3 larger populations safety tolerability investigated medication continues a hurdle for further investigations.

Язык: Английский

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The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update

Advances in Nutrition, Год журнала: 2023, Номер 14(6), С. 1416 - 1435

Опубликована: Авг. 23, 2023

The importance of nicotinamide adenine dinucleotide (NAD+) in human physiology is well recognized. As the NAD+ concentration skin, blood, liver, muscle and brain are thought to decrease with age, finding ways increase status could possibly influence ageing process associated metabolic sequelae. Nicotinamide mononucleotide (NMN) a precursor for biosynthesis, vitro/in vivo studies have demonstrated that NMN supplementation increases mitigate ageing-related disorders such as oxidative stress, DNA damage, neurodegeneration inflammatory responses. promotion an anti-ageing health supplement has gained popularity due findings; however, since most evaluating effects been conducted cell or animal models, concern remains regarding safety physiological population. Nonetheless, dozen clinical trials currently underway. This review summarizes current progress these NMN/NAD+ biology clarify potential shed light on future study directions.

Язык: Английский

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NAD metabolism modulates inflammation and mitochondria function in diabetic kidney disease

Journal of Biological Chemistry, Год журнала: 2023, Номер 299(8), С. 104975 - 104975

Опубликована: Июль 8, 2023

Diabetes mellitus is the leading cause of cardiovascular and renal disease in United -States. Despite beneficial interventions available for patients with diabetes, there remains a need additional therapeutic targets therapies diabetic kidney (DKD). Inflammation oxidative stress are increasingly recognized as important causes diseases. closely associated mitochondrial damage. The molecular connection between inflammation metabolism to be elucidated. Recently, nicotinamide adenine nucleotide (NAD+) has been found regulate immune function inflammation. In present studies, we tested hypothesis that enhancing NAD could prevent progression DKD. We treatment db/db mice type 2 diabetes riboside (NR) prevented several manifestations dysfunction (i.e., albuminuria, increased urinary injury marker-1 (KIM1) excretion, pathologic changes). These effects were decreased inflammation, at least part via inhibiting activation cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) signaling pathway. An antagonist serum stimulator (STING) whole-body STING deletion showed similar renoprotection. Further analysis NR SIRT3 activity improved function, which led DNA damage, trigger leakage activates cGAS-STING Overall, these data show supplementation boosted augment reducing thereby preventing disease.

Язык: Английский

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