Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study

Dolopikou, C. F.; Kourtzidis, Ioannis A.; Margaritelis, Nikos V.; Vrabas, Ioannis S.; Koidou, Irene; Kyparos, Antonios; Theodorou, Anastasios A.; Paschalis, Vassilis; Nikolaidis, Michalis G.

doi:10.1007/s00394-019-01919-4

Cited by 85 publications

(84 citation statements)

References 33 publications

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“…33 Recent human clinical reports suggested potential benefits of NR intervention on improving redox homeostasis and exercise performance while reducing systolic blood pressure and arterial stiffness. 33,34 Our study provides a rationale for exploring NR as a potential therapeutic approach for both accelerated and normal sensorineural hearing loss in humans. Hearing loss in CS resembles ARHL as both are sensorineural and progressive rather than congenital.…”

Section: Discussionmentioning

confidence: 97%

Short-term NAD+ supplementation prevents hearing loss in mouse models of Cockayne syndrome

et al. 2020

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Age-related hearing loss (ARHL) is one of the most common disorders affecting elderly individuals. There is an urgent need for effective preventive measures for ARHL because none are currently available. Cockayne syndrome (CS) is a premature aging disease that presents with progressive hearing loss at a young age, but is otherwise similar to ARHL. There are two human genetic complementation groups of CS, A and B. While the clinical phenotypes in patients are similar, the proteins have very diverse functions, and insight into their convergence is of great interest. Here, we use mouse models for CS (CSA −/− and CSB m/m ) that recapitulate the hearing loss in human CS patients. We previously showed that NAD + , a key metabolite with various essential functions, is reduced in CS and associated with multiple CS phenotypes. In this study, we report that NAD + levels are reduced in the cochlea of CSB m/m mice and that short-term treatment (10 days) with the NAD + precursor nicotinamide riboside (NR), prevents hearing loss, restores outer hair cell loss, and improves cochlear health in CSB m/m mice. Similar, but more modest effects were observed in CSA −/− mice. Remarkably, we observed a reduction in synaptic ribbon counts in the presynaptic zones of inner hair cells in both CSA −/− and CSB m/m mice, pointing to a converging mechanism for cochlear defects in CS. Ribbon synapses facilitate rapid and sustained synaptic transmission over long periods of time. Ribeye, a core protein of synaptic ribbons, possesses an NAD (H) binding pocket which regulates its activity. Intriguingly, NAD + supplementation rescues reduced synaptic ribbon formation in both CSA −/− and CSB m/m mutant cochleae. These findings provide valuable insight into the mechanism of CS-and ARHL-associated hearing loss, and suggest a possible intervention.npj Aging and Mechanisms of Disease (2020) 6:1 ; https://doi.

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Section: Discussionmentioning

confidence: 97%

Short-term NAD+ supplementation prevents hearing loss in mouse models of Cockayne syndrome

et al. 2020

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“…It has also been proposed that DHA is important in regulating neurogenesis, increasing neural synapses and membrane fluidity and protecting against neuronal damage [58]. In addition, ageing is associated with a deficiency in antioxidants in the body and an aberrant redox homeostasis compared to in younger adults [59]. Inflammation is also a characteristic of many neurodegenerative diseases like dementia.…”

Section: Discussionmentioning

confidence: 99%

“…Even though there is contradictory evidence regarding the effects of antioxidant intakes on exercise performance, it has been suggested that individuals with antioxidant deficiency or with high oxidative stress levels may benefit from the antioxidant treatments [73][74][75]. In support of this assertion, a recent study has shown that antioxidant supplementation decreased oxidative stress and improved physical performance in old but not in young adults [59]. Therefore, we may possibly conclude that the seniors enrolled in the present study might have been benefited from the specific antioxidant vitamins found in the formula used in a way that has partially contributed to the observed augmentation on functional capacity.…”

Section: Discussionmentioning

confidence: 99%

The Effects of a 6-Month High Dose Omega-3 and Omega-6 Polyunsaturated Fatty Acids and Antioxidant Vitamins Supplementation on Cognitive Function and Functional Capacity in Older Adults with Mild Cognitive Impairment

et al. 2020

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The aim of the present study was to examine the effects of a high-dose omega-3 and omega-6 fatty acids supplementation, in combination with antioxidant vitamins, on cognitive function and functional capacity of older adults with mild cognitive impairment (MCI), over a 6-month period in a randomized, double-blind, placebo-controlled trial. Forty-six older adults with MCI (age: 78.8 ± 7.3 years) were randomized 1:1 to receive either a 20 mL dose of a formula containing a mixture of omega-3 (810 mg Eicosapentaenoic acid and 4140 mg Docosahexaenoic acid) and omega-6 fatty acids (1800 mg gamma-Linolenic acid and 3150 mg Linoleic acid) (1:1 w/w), with 0.6 mg vitamin A, vitamin E (22 mg) plus pure γ-tocopherol (760 mg), or 20 mL placebo containing olive oil. Participants completed assessments of cognitive function, functional capacity, body composition and various aspects of quality of life at baseline and following three and six months of supplementation. Thirty-six participants completed the study (eighteen from each group). A significant interaction between supplementation and time was found on cognitive function (Addenbrooke’s Cognitive Examination -Revised (ACE-R), Mini-Mental State Examination (MMSE) and Stroop Color and Word Test (STROOP) color test; p < 0.001, p = 0.011 and p = 0.037, respectively), functional capacity (6-min walk test and sit-to-stand-60; p = 0.028 and p = 0.032, respectively), fatigue (p < 0.001), physical health (p = 0.007), and daily sleepiness (p = 0.007)—showing a favorable improvement for the participants receiving the supplement. The results indicate that this nutritional modality could be promising for reducing cognitive and functional decline in the elderly with MCI.

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“…NR has a different time course compared to NAM and NA and produces more NAD + than the other precursors in equivalent doses (Trammell et al, 2016). NR increases the ratio of NAD + /NADH more significantly compared NMN, NAM and NA and this can contribute to improving the oxidative capacity of mitochondria (Cantó et al, 2012) and to decrease the rate of oxidative damage against DNA and mitochondrial stress (Ramamoorthy et al, 2012;Srivastava, 2016;Dolopikou et al, 2019) (Table 2).…”

Section: Precursors Of Nad +mentioning

confidence: 99%

Antioxidant Alternatives in the Treatment of Amyotrophic Lateral Sclerosis: A Comprehensive Review

et al. 2020

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that produces a selective loss of the motor neurons of the spinal cord, brain stem and motor cortex. Oxidative stress (OS) associated with mitochondrial dysfunction and the deterioration of the electron transport chain has been shown to be a factor that contributes to neurodegeneration and plays a potential role in the pathogenesis of ALS. The regions of the central nervous system affected have high levels of reactive oxygen species (ROS) and reduced antioxidant defenses. Scientific studies propose treatment with antioxidants to combat the characteristic OS and the regeneration of nicotinamide adenine dinucleotide (NAD +) levels by the use of precursors. This review examines the possible roles of nicotinamide riboside and pterostilbene as therapeutic strategies in ALS.

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Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study

Cited by 85 publications

References 33 publications

Short-term NAD+ supplementation prevents hearing loss in mouse models of Cockayne syndrome

Short-term NAD+ supplementation prevents hearing loss in mouse models of Cockayne syndrome

The Effects of a 6-Month High Dose Omega-3 and Omega-6 Polyunsaturated Fatty Acids and Antioxidant Vitamins Supplementation on Cognitive Function and Functional Capacity in Older Adults with Mild Cognitive Impairment

Antioxidant Alternatives in the Treatment of Amyotrophic Lateral Sclerosis: A Comprehensive Review

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