Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial

Castro-Marrero, Jesús; Segundo, María José; Lacasa, Marcos; Martínez-Martínez, Alba; Sentañes, Ramon Sanmartin; Alegre, José

doi:10.3390/nu13082658

Cited by 28 publications

(29 citation statements)

References 59 publications

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“…The PRISMA flowchart for the literature search is shown in Figure 1 . After removing duplicate articles and excluding non-relevant articles by an examination of titles and abstracts, we ultimately included 13 RCTs in the final analysis ( Berman et al, 2004 ; Lee et al, 2011 ; Cordero et al, 2013 ; Lesser et al, 2013 ; Castro-Marrero et al, 2015 ; Fukuda et al, 2015 ; Peel et al, 2015 ; Sanoobar et al, 2016 ; Di Pierro et al, 2017 ; Morikawa et al, 2019 ; Mizuno et al, 2020 ; Mousavi et al, 2020 ; Castro-Marrero et al, 2021 ). The articles excluded in the final stage and the reasons for exclusion are listed in Supplementary Table S3 ( Singh et al, 2003 ; Langsjoen et al, 2005 ; Kumar et al, 2007 ; Mizuno et al, 2008 ; Gökbel et al, 2010 ; Cordero et al, 2012a ; Cordero et al, 2012b ; Fedacko et al, 2013 ; Gharahdaghi et al, 2013 ; Miyamae et al, 2013 ; Castro-Marrero et al, 2016 ; Fukuda et al, 2016 ; Iwase et al, 2016 ; Menon et al, 2017 ; Langsjoen et al, 2019 ; Moccia et al, 2019 ; Negro et al, 2019 ; Gomez-Centeno et al, 2020 ; Schweiger et al, 2020 ; Suzuki et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…The study duration ranged from four ( Mousavi et al, 2020 ) to 24 weeks ( Lesser et al, 2013 ). Subject diagnoses included chronic fatigue syndrome ( Castro-Marrero et al, 2015 ; Castro-Marrero et al, 2021 ), fibromyalgia ( Cordero et al, 2013 ; Di Pierro et al, 2017 ), end-stage heart failure ( Berman et al, 2004 ), obesity ( Lee et al, 2011 ), breast cancer (with patients undergoing chemotherapy) ( Lesser et al, 2013 ), end-stage renal disease ( Fukuda et al, 2015 ), poliomyelitis ( Peel et al, 2015 ), and multiple sclerosis ( Sanoobar et al, 2016 ), and we also evaluated healthy subjects ( Morikawa et al, 2019 ) and healthy individuals with fatigue ( Mizuno et al, 2020 ; Mousavi et al, 2020 ). The details of the retrieved trials are summarized in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

“…A statistically significant inverse relationship has also been found between CoQ10 levels and fatigue severity ( Maes et al, 2009a ). Thus, CoQ10 supplementation has been successfully applied for reducing fatigue in patients with various conditions, including chronic fatigue syndrome ( Castro-Marrero et al, 2015 ; Castro-Marrero et al, 2016 ; Fukuda et al, 2016 ; Castro-Marrero et al, 2021 ) and fibromyalgia ( Cordero et al, 2013 ; Miyamae et al, 2013 ; Di Pierro et al, 2017 ), as well as in healthy subjects ( Morikawa et al, 2019 ; Mizuno et al, 2020 ). However, inconsistencies in clinical outcomes have been identified across different trials.…”

Section: Introductionmentioning

confidence: 99%

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Effectiveness of Coenzyme Q10 Supplementation for Reducing Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

et al. 2022

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Coenzyme Q10 (CoQ10) is a popular nutritional supplement, an antioxidant and an essential component of the mitochondrial electron transport chain. Several clinical studies have suggested that fatigue can be reduced by antioxidant supplementation. However, the data on this topic has been sparse to date. Hence, we conducted this meta-analysis with the aim of investigating the effectiveness of fatigue reduction via CoQ10 supplementation. More specifically, we searched electronic databases for randomized controlled trials (RCTs) published from the database inception to January 2022. A random effects model was implemented to conduct the meta-analysis among 13 RCTs (with a total of 1,126 participants). As compared with the placebo groups evaluated in each RCT, the CoQ10 group showed a statistically significant reduction in fatigue scores (Hedges’ g = −0.398, 95% confidence interval = −0.641 to −0.155, p = 0.001). The directions of the treatment effects were consistent between the healthy and diseased participants. Compared with the placebo group, the effect of reducing fatigue was statistically significant in the subgroup using the CoQ10-only formulation but not in the subgroup using CoQ10 compounds. The results of our meta-regression demonstrate that increases in the daily dose (coefficient = −0.0017 per mg, p < 0.001) and treatment duration (coefficient = −0.0042 per day, p = 0.007) of CoQ10 supplementation were correlated with greater fatigue reduction. There was only one adverse (gastrointestinal) event in the 602 participants who underwent the CoQ10 intervention. Based on the results of this meta-analysis, we conclude that CoQ10 is an effective and safe supplement for reducing fatigue symptoms.Systematic Review Registration:https://inplasy.com/inplasy-2022-1-0113/, identifier INPLASY202210113

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effectiveness of Coenzyme Q10 Supplementation for Reducing Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

et al. 2022

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“…Fatigue, which is characterised by feelings of tiredness and a lack of energy, is well-known to negatively influence cognitive function [ 60 ]. Co-supplementation with NADH (20 mg) and co-enzyme Q10 (200 mg) daily over 12 weeks in a randomized, placebo-controlled, double-blind trial resulted in reduced cognitive fatigue perception and improved scores for FIS-40 (a fatigue impact scale with a cognitive domain) and SF-36 (a health-related quality of life scale) [ 61 ]. The individual effect of NADH was not investigated.…”

Section: Other Contextsmentioning

confidence: 99%

Supplementation with NAD+ and Its Precursors to Prevent Cognitive Decline across Disease Contexts

Campbell

2022

Nutrients

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The preservation of cognitive ability by increasing nicotinamide adenine dinucleotide (NAD+) levels through supplementation with NAD+ precursors has been identified as a promising treatment strategy for a number of conditions; principally, age-related cognitive decline (including Alzheimer’s disease and vascular dementia), but also diabetes, stroke, and traumatic brain injury. Candidate factors have included NAD+ itself, its reduced form NADH, nicotinamide (NAM), nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and niacin (or nicotinic acid). This review summarises the research findings for each source of cognitive impairment for which NAD+ precursor supplementation has been investigated as a therapy. The findings are mostly positive but have been made primarily in animal models, with some reports of null or adverse effects. Given the increasing popularity and availability of these factors as nutritional supplements, further properly controlled clinical research is needed to provide definitive answers regarding this strategy’s likely impact on human cognitive health when used to address different sources of impairment.

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“…Previous studies by our group ( 5 , 6 ) have demonstrated a beneficial effect of CoQ10 supplementation on clinical symptoms and mitochondrial function in ME/CFS; however, no randomized-controlled trials (RCTs) have been conducted using CoQ10 combined with selenium in ME/CFS patients. Most adults in Spain have circulating selenium levels below the optimum range ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Does Coenzyme Q10 Plus Selenium Supplementation Ameliorate Clinical Outcomes by Modulating Oxidative Stress and Inflammation in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?

Castro-Marrero

Domingo

Cordobilla

et al. 2022

Antioxidants & Redox Signaling

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a neuroinflammatory, multifaceted chronic disorder of unknown cause. Accumulating data indicate a link between a redox imbalance, mitochondrial dysfunction, and inflammation status in ME/CFS. Coenzyme Q10 (CoQ10) and selenium as effective antioxidant and anti-inflammatory agents have shown potential clinical implications in chronic diseases; however, their therapeutic benefits in ME/CFS remain elusive. This open-label exploratory study aimed to evaluate the effectiveness of combined CoQ10 plus selenium supplementation on clinical features and circulating biomarkers in ME/CFS. Twenty-seven ME/CFS patients received an oral combination of 400 mg of CoQ10 and 200 μg of selenium daily for 8 weeks. The primary endpoint was patient-reported changes in outcome measures from baseline to 8 weeks' postintervention. Secondary endpoint included changes in circulating biomarkers from baseline to each participant. After an 8-week intervention, a significant improvement was found for overall fatigue severity ( p = 0.021) and global quality of life ( p = 0.002), while there was no significant effect on the sleep disturbances ( p = 0.480) among participants. After 8 week's intervention, there was significantly increased total antioxidant capacity, and there were reduced lipoperoxide levels from the participants ( p < 0.0001 for both). Circulating cytokine levels decreased significantly ( p < 0.01 for all), but with no significant changes in the C-reactive protein, FGF21, and NT-proBNP biomarkers after supplementation. Based on these findings, we hypothesized that long-term supplementation of combined CoQ10 and selenium may indicate a potentially beneficial synergistic effect in ME/CFS. Antioxid. Redox Signal. 36, 729–739.

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Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial

Cited by 28 publications

References 59 publications

Effectiveness of Coenzyme Q10 Supplementation for Reducing Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Effectiveness of Coenzyme Q10 Supplementation for Reducing Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Supplementation with NAD+ and Its Precursors to Prevent Cognitive Decline across Disease Contexts

Does Coenzyme Q10 Plus Selenium Supplementation Ameliorate Clinical Outcomes by Modulating Oxidative Stress and Inflammation in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?

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