The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson’s disease

Brakedal, Brage; Dölle, Christian; Riemer, Frank; Ma, Yilong; Nido, Gonzalo S.; Skeie, Geir; Craven, Alexander R.; Schwarzlmüller, Thomas; Brekke, Njål; Diab, Joseph; Sverkeli, Lars Jansen; Skjeie, Vivian; Varhaug, Kristin Nielsen; Tysnes, Ole‐Bjørn; Peng, Shichun; Haugarvoll, Kristoffer; Ziegler, Mathias; Grüner, Renate; Eidelberg, David; Tzoulis, Charalampos

doi:10.1016/j.cmet.2022.02.001

Cited by 168 publications

(151 citation statements)

References 78 publications

(93 reference statements)

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“…Thus, NR supplementation is a safe and effective treatment for PD. 295 Nutritional intervention also benefits the symptoms of AD. The evidence shows that dietary intervention during neurodegenerative treatments enables relief of the AD process.…”

Section: Dietary Intervention In Tissue Health and Diseasementioning

confidence: 99%

Dietary regulation in health and disease

Gao

et al. 2022

Sig Transduct Target Ther

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Nutriments have been deemed to impact all physiopathologic processes. Recent evidences in molecular medicine and clinical trials have demonstrated that adequate nutrition treatments are the golden criterion for extending healthspan and delaying ageing in various species such as yeast, drosophila, rodent, primate and human. It emerges to develop the precision-nutrition therapeutics to slow age-related biological processes and treat diverse diseases. However, the nutritive advantages frequently diversify among individuals as well as organs and tissues, which brings challenges in this field. In this review, we summarize the different forms of dietary interventions extensively prescribed for healthspan improvement and disease treatment in pre-clinical or clinical. We discuss the nutrient-mediated mechanisms including metabolic regulators, nutritive metabolism pathways, epigenetic mechanisms and circadian clocks. Comparably, we describe diet-responsive effectors by which dietary interventions influence the endocrinic, immunological, microbial and neural states responsible for improving health and preventing multiple diseases in humans. Furthermore, we expatiate diverse patterns of dietotheroapies, including different fasting, calorie-restricted diet, ketogenic diet, high-fibre diet, plants-based diet, protein restriction diet or diet with specific reduction in amino acids or microelements, potentially affecting the health and morbid states. Altogether, we emphasize the profound nutritional therapy, and highlight the crosstalk among explored mechanisms and critical factors to develop individualized therapeutic approaches and predictors.

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Section: Dietary Intervention In Tissue Health and Diseasementioning

confidence: 99%

Dietary regulation in health and disease

Gao

et al. 2022

Sig Transduct Target Ther

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“…Treatments for mitochondria dysfunction are understudied but evidence favors standard treatment to support the mitochondria to improving energy production [ 26 , 61 , 62 ]. Abnormalities in NADP metabolism associated with EPI points to targeting the nicotinamide adenine dinucleotide precursors, which has been shown to have therapeutic biological effects on dyslipidemia [ 61 ], aging [ 62 ], Parkinson’s disease [ 63 ] and mitochondrial function [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Central Nervous System Metabolism in Autism, Epilepsy and Developmental Delays: A Cerebrospinal Fluid Analysis

et al. 2022

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Neurodevelopmental disorders are associated with metabolic pathway imbalances; however, most metabolic measurements are made peripherally, leaving central metabolic disturbances under-investigated. Cerebrospinal fluid obtained intraoperatively from children with autism spectrum disorder (ASD, n = 34), developmental delays (DD, n = 20), and those without known DD/ASD (n = 34) was analyzed using large-scale targeted mass spectrometry. Eighteen also had epilepsy (EPI). Metabolites significantly related to ASD, DD and EPI were identified by linear models and entered into metabolite–metabolite network pathway analysis. Common disrupted pathways were analyzed for each group of interest. Central metabolites most involved in metabolic pathways were L-cysteine, adenine, and dodecanoic acid for ASD; nicotinamide adenine dinucleotide phosphate, L-aspartic acid, and glycine for EPI; and adenosine triphosphate, L-glutamine, ornithine, L-arginine, L-lysine, citrulline, and L-homoserine for DD. Amino acid and energy metabolism pathways were most disrupted in all disorders, but the source of the disruption was different for each disorder. Disruption in vitamin and one-carbon metabolism was associated with DD and EPI, lipid pathway disruption was associated with EPI and redox metabolism disruption was related to ASD. Two microbiome metabolites were also detected in the CSF: shikimic and cis-cis-muconic acid. Overall, this study provides increased insight into unique metabolic disruptions in distinct but overlapping neurodevelopmental disorders.

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“…Although further studies are needed to conclusively determine the impact of SARS-CoV-2-mediated NAD+ depletion in PACS pathogenesis, preclinical and clinical data has suggested that supplementation with NAD+ or its analogs may accelerate PACS recovery. 55 - 59 Moreover, there is one ongoing pilot study with NAD+ investigating its effect on reducing fatigue in PACS. 60 Despite the evidence supporting NAD+ supplementation as potential PACS therapy, considerably more information about the safety, efficacy and potential long-term sequel of IV NAD+ administration is required to claim a therapeutic effect in PACS patients.…”

Section: Rationale For Nad+ Intravenous Administration Therapy For Pa...mentioning

confidence: 99%

Rationale for Nicotinamide Adenine Dinucleotide (NAD+) Metabolome Disruption as a Pathogenic Mechanism of Post-Acute COVID-19 Syndrome

Block

Kuo

2022

Clin Med�Insights�Pathol

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Many acute COVID-19 convalescents experience a persistent sequelae of infection, called post-acute COVID-19 syndrome (PACS). With incidence ranging between 31% and 69%, PACS is becoming increasingly acknowledged as a new disease state in the context of SARS-CoV-2 infection. As SARS-CoV-2 infection can affect several organ systems to varying degrees and durations, the cellular and molecular abnormalities contributing to PACS pathogenesis remain unclear. Despite our limited understanding of how SARS-CoV-2 infection promotes this persistent disease state, mitochondrial dysfunction has been increasingly recognized as a contributing factor to acute SARS-CoV-2 infection and, more recently, to PACS pathogenesis. The biological mechanisms contributing to this phenomena have not been well established in previous literature; however, in this review, we summarize the evidence that NAD+ metabolome disruption and subsequent mitochondrial dysfunction following SARS-CoV-2 genome integration may contribute to PACS biological pathogenesis. We also briefly examine the coordinated and complex relationship between increased oxidative stress, inflammation, and mitochondrial dysfunction and speculate as to how SARS-CoV-2-mediated NAD+ depletion may be causing these abnormalities in PACS. As such, we present evidence supporting the therapeutic potential of intravenous administration of NAD+ as a novel treatment intervention for PACS symptom management.

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The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson’s disease

Cited by 168 publications

References 78 publications

Dietary regulation in health and disease

Dietary regulation in health and disease

Central Nervous System Metabolism in Autism, Epilepsy and Developmental Delays: A Cerebrospinal Fluid Analysis

Rationale for Nicotinamide Adenine Dinucleotide (NAD+) Metabolome Disruption as a Pathogenic Mechanism of Post-Acute COVID-19 Syndrome

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