ubiquinone and Fatigue-Syndrome--Chronic

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is characterised by unexplained fatigue for at least 6 months accompanied by a diverse but consistent set of symptoms. Diet modification and nutritional supplements could be used to improve patient outcomes, such fatigue and quality of life. We reviewed and discussed the evidence for nutritional interventions that may assist in alleviating symptoms of CFS/ME.. Medline, Cinahl and Scopus were systematically searched from 1994 to May 2016. All studies on nutrition intervention were included where CFS/ME patients modified their diet or supplemented their habitual diet on patient-centred outcomes (fatigue, quality of life, physical activity and/or psychological wellbeing).. Seventeen studies were included that meet the inclusion criteria. Of these, 14 different interventions were investigated on study outcomes. Many studies did not show therapeutic benefit on CFS/ME. Improvements in fatigue were observed for nicotinamide adenine dinucleotide hydride (NADH), probiotics, high cocoa polyphenol rich chocolate, and a combination of NADH and coenzyme Q10.. This review identified insufficient evidence for the use of nutritional supplements and elimination or modified diets to relieve CFS/ME symptoms. Studies were limited by the number of studies investigating the interventions, small sample sizes, study duration, variety of instruments used, and studies not reporting dietary intake method. Further research is warranted in homogeneous CFS/ME populations.

Topics: Diet; Dietary Supplements; Exercise; Fatigue Syndrome, Chronic; Humans; NAD; Patient Outcome Assessment; Polyphenols; Probiotics; Quality of Life; Randomized Controlled Trials as Topic; Ubiquinone

Despite considerable worldwide efforts, no single etiology has been identified to explain the development of chronic fatigue syndrome (CFS). It is likely that multiple factors promote its development, sometimes with the same factors both causing and being caused by the syndrome. A detailed review of the literature suggests a number of marginal nutritional deficiencies may have etiologic relevance. These include deficiencies of various B vitamins, vitamin C, magnesium, sodium, zinc, L-tryptophan, L-carnitine, coenzyme Q10, and essential fatty acids. Any of these nutrients could be marginally deficient in CFS patients, a finding that appears to be primarily due to the illness process rather than to inadequate diets. It is likely that marginal deficiencies not only contribute to the clinical manifestations of the syndrome, but also are detrimental to the healing processes. Therefore, when feasible, objective testing should identify them and their resolution should be assured by repeat testing following initiation of treatment. Moreover, because of the rarity of serious adverse reactions, the difficulty in ruling out marginal deficiencies, and because some of the therapeutic benefits of nutritional supplements appear to be due to pharmacologic effects, it seems rational to consider supplementing CFS patients with the nutrients discussed above, along with a general high-potency vitamin/mineral supplement, at least for a trial period.

Topics: Antioxidants; Coenzymes; Fatigue Syndrome, Chronic; Fatty Acids, Essential; Humans; Metals; Tryptophan; Ubiquinone; Vitamins

Topics: Adult; Dietary Supplements; Double-Blind Method; Fatigue Syndrome, Chronic; Female; Humans; Male; Middle Aged; Mitochondria; NAD; Perception; Prospective Studies; Quality of Life; Ubiquinone

Though affecting many thousands of patients, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) should be considered an orphan disease, since the cause remains elusive and no treatment is available that can provide complete cure. There is reasonable insight into the pathogenesis of signs and symptoms, and treatments specifically directed to immunological, inflammatory and metabolic processes offer relief to an increasing number of patients. Particular attention is given to the importance of co-morbidity requiring appropriate therapy. Promising results are obtained by treatment with Metformin, or possibly Momordica charantia extract, which will correct insulin resistance, with Meldonium improving the transportation of glucose into the mitochondria, with sodium dichloroacetate activating pyruvate dehydrogenase, and with nutraceutical support reducing oxidative and inflammatory impairment.

Topics: Adult; Animals; Antiviral Agents; Autoimmune Diseases; Comorbidity; Dichloroacetic Acid; Dietary Supplements; Drug Evaluation, Preclinical; Drug Therapy, Combination; Endocrine System Diseases; Fatigue Syndrome, Chronic; Female; Humans; Infections; Insulin Resistance; Male; Mental Disorders; Methylhydrazines; Middle Aged; Mitochondria; Neuroimaging; Pyruvate Dehydrogenase Complex; Severity of Illness Index; Thiamine; Thioctic Acid; Tomography, Emission-Computed, Single-Photon; Ubiquinone

Chronic Fatigue Syndrome (CFS) is a complex condition, characterized by severe disabling fatigue with no known cause, no established diagnostic tests, and no universally effective treatment. Several studies have proposed symptomatic treatment with coenzyme Q10 (CoQ10) and nicotinamide adenine dinucleotide (NADH) supplementation. The primary endpoint was to assess the effect of CoQ10 plus NADH supplementation on age-predicted maximum heart rate (max HR) during a cycle ergometer test. Secondary measures included fatigue, pain and sleep.. A proof-of-concept, 8-week, randomized, controlled, double-blind trial was conducted in 80 CFS patients assigned to receive either CoQ10 plus NADH supplementation or matching placebo twice daily. Maximum HR was evaluated at baseline and at end of the run-in period using an exercise test. Fatigue, pain and sleep were evaluated at baseline, and then reassessed at 4- and 8-weeks through self-reported questionnaires.. The CoQ10 plus NADH group showed a significant reduction in max HR during a cycle ergometer test at week 8 versus baseline (P = 0.022). Perception of fatigue also showed a decrease through all follow-up visits in active group versus placebo (P = 0.03). However, pain and sleep did not improve in the active group. Coenzyme Q10 plus NADH was generally safe and well tolerated.. Our results suggest that CoQ10 plus NADH supplementation for 8 weeks is safe and potentially effective in reducing max HR during a cycle ergometer test and also on fatigue in CFS. Further additional larger controlled trials are needed to confirm these findings. Clinical trial registrationThis trial was registered at clinicaltrials.gov as NCT02063126.

Topics: Adolescent; Adult; Aged; Dietary Supplements; Double-Blind Method; Endpoint Determination; Exercise Test; Fatigue Syndrome, Chronic; Female; Follow-Up Studies; Heart Rate; Humans; Male; Middle Aged; NAD; Pain; Sample Size; Sleep; Surveys and Questionnaires; Treatment Outcome; Ubiquinone; Young Adult

The aim of this study was to evaluate the benefit of oral ubiquinol-10 supplementation in CFS patients using an open-label study and a randomized, double-blinded, placebo-controlled (RCT) study. Twenty patients with CFS were randomly enrolled in an 8-week open-label oral ubiquinol-10 (150 mg ubiquinol-10/day) study. The patients and the attending physicians were not blinded to the supplementation. Forty-three patients with CFS were randomly assigned to receive either ubiquinol-10 (150 mg/day) or placebo every day for 12 weeks. The patients and the attending physicians were blinded to the supplementation, and a total of 31 patients (N = 17 in the ubiquinol group and 14 in the placebo group) completed the study. The beneficial effects of ubiquinol-10 were observed in the open-label study we conducted prior to the RCT. The RCT results suggest that supplementation with ubiquinol-10 for 12 weeks is effective for improving several CFS symptoms. © 2016 BioFactors, 42(4):431-440, 2016.

Topics: Administration, Oral; Adult; Antioxidants; Autonomic Nervous System; Biomarkers; Dietary Supplements; Double-Blind Method; Fatigue; Fatigue Syndrome, Chronic; Female; Humans; Male; Treatment Outcome; Ubiquinone

Chronic fatigue syndrome (CFS) is a chronic and extremely debilitating illness characterized by prolonged fatigue and multiple symptoms with unknown cause, diagnostic test, or universally effective treatment. Inflammation, oxidative stress, mitochondrial dysfunction, and CoQ10 deficiency have been well documented in CFS. We conducted an 8-week, randomized, double-blind placebo-controlled trial to evaluate the benefits of oral CoQ10 (200 mg/day) plus NADH (20 mg/day) supplementation on fatigue and biochemical parameters in 73 Spanish CFS patients. This study was registered in ClinicalTrials.gov (NCT02063126). A significant improvement of fatigue showing a reduction in fatigue impact scale total score (p<0.05) was reported in treated group versus placebo. In addition, a recovery of the biochemical parameters was also reported. NAD+/NADH (p<0.001), CoQ10 (p<0.05), ATP (p<0.05), and citrate synthase (p<0.05) were significantly higher, and lipoperoxides (p<0.05) were significantly lower in blood mononuclear cells of the treated group. These observations lead to the hypothesis that the oral CoQ10 plus NADH supplementation could confer potential therapeutic benefits on fatigue and biochemical parameters in CFS. Larger sample trials are warranted to confirm these findings.

Topics: Administration, Oral; Dietary Supplements; Fatigue Syndrome, Chronic; Humans; NAD; Ubiquinone

The approach towards myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remains in a permanent state of crisis with fierce competition between the psychosocial school, which attributes ME/CFS to the perception of effort, and the medical approach (Maes and Twisk, BMC Med, 2010, 8, 35). The aim of this paper is to review how to construct a nomothetic model of ME/CFS using Partial Least Squares (PLS) path analysis and ensembling causome (bacterial translocation as assessed with IgM/IgA responses to LPS), protectome (lowered coenzyme Q10), adverse outcome pathways (AOP) including increased lysozyme, CD38+ T cell activation, cell-mediated immune activation (CMI), and IgM responses to oxidative specific epitopes and NO-adducts (IgM OSENO).Using PLS, we trained, tested and validated this knowledge- and data-driven causal ME/CFS model, which showed adequate convergence, construct and replicability validity.This bottom- up explicit data model of ME/CFS objectivates the descriptive narratives of the ME/CFS phenome, using causome-protectome-AOP data, whereby the abstract concept ME/CFS is translated into pathways, thereby securing the reification of the ME/CFS phenome. We found that 31.6% of the variance in the physiosomatic symptom dimension of ME/CFS was explained by the cumulative effects of CMI and CD38+ activation, IgM OSENO, IgA LPS, lysozyme (all positive) and coenzyme Q10 (inversely). Cluster analysis performed on the PLS-generated latent vector scores of all feature sets exposed three distinct immune groups of ME/CFS, namely one with increased lysozyme, one with increased CMI + CD38 activation + depressive symptoms, and another with increased bacterial translocation + autoimmune responses to OSENO.

Topics: ADP-ribosyl Cyclase 1; Fatigue Syndrome, Chronic; Humans; Immunoglobulin A; Immunoglobulin M; Lipopolysaccharides; Membrane Glycoproteins; Muramidase; Oxidative Stress; Ubiquinone

Loss of function in mitochondria, the key organelle responsible for cellular energy production, can result in the excess fatigue and other symptoms that are common complaints in almost every chronic disease. At the molecular level, a reduction in mitochondrial function occurs as a result of the following changes: (1) a loss of maintenance of the electrical and chemical transmembrane potential of the inner mitochondrial membrane, (2) alterations in the function of the electron transport chain, or (3) a reduction in the transport of critical metabolites into mitochondria. In turn, these changes result in a reduced efficiency of oxidative phosphorylation and a reduction in production of adenosine-5'-triphosphate (ATP). Several components of this system require routine replacement, and this need can be facilitated with natural supplements. Clinical trials have shown the utility of using oral replacement supplements, such as L-carnitine, alpha-lipoic acid (α-lipoic acid [1,2-dithiolane-3-pentanoic acid]), coenzyme Q10 (CoQ10 [ubiquinone]), reduced nicotinamide adenine dinucleotide (NADH), membrane phospholipids, and other supplements. Combinations of these supplements can reduce significantly the fatigue and other symptoms associated with chronic disease and can naturally restore mitochondrial function, even in long-term patients with intractable fatigue.

Topics: Carnitine; Dietary Supplements; Fatigue Syndrome, Chronic; Humans; Mitochondrial Diseases; NAD; Thioctic Acid; Ubiquinone

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/cfs) is classified by the World Health Organization as a disorder of the central nervous system. ME/cfs is an neuro-immune disorder accompanied by chronic low-grade inflammation, increased levels of oxidative and nitrosative stress (O&NS), O&NS-mediated damage to fatty acids, DNA and proteins, autoimmune reactions directed against neoantigens and brain disorders. Mitochondrial dysfunctions have been found in ME/cfs, e.g. lowered ATP production, impaired oxidative phosphorylation and mitochondrial damage. This paper reviews the pathways that may explain mitochondrial dysfunctions in ME/cfs. Increased levels of pro-inflammatory cytokines, such as interleukin-1 and tumor necrosis factor-α, and elastase, and increased O&NS may inhibit mitochondrial respiration, decrease the activities of the electron transport chain and mitochondrial membrane potential, increase mitochondrial membrane permeability, interfere with ATP production and cause mitochondrial shutdown. The activated O&NS pathways may additionally lead to damage of mitochondrial DNA and membranes thus decreasing membrane fluidity. Lowered levels of antioxidants, zinc and coenzyme Q10, and ω3 polyunsaturated fatty acids in ME/cfs may further aggravate the activated immuno-inflammatory and O&NS pathways. Therefore, it may be concluded that immuno-inflammatory and O&NS pathways may play a role in the mitochondrial dysfunctions and consequently the bioenergetic abnormalities seen in patients with ME/cfs. Defects in ATP production and the electron transport complex, in turn, are associated with an elevated production of superoxide and hydrogen peroxide in mitochondria creating adaptive and synergistic damage. It is argued that mitochondrial dysfunctions, e.g. lowered ATP production, may play a role in the onset of ME/cfs symptoms, e.g. fatigue and post exertional malaise, and may explain in part the central metabolic abnormalities observed in ME/cfs, e.g. glucose hypometabolism and cerebral hypoperfusion.

Topics: Adenosine Triphosphate; Antioxidants; Biomarkers; Brain; Cytokines; Energy Metabolism; Fatigue Syndrome, Chronic; Glucose; Humans; Inflammation; Magnesium; Mitochondria; Mitochondria, Muscle; Mitochondrial Diseases; Neuroimaging; Neuroimmunomodulation; NF-kappa B; Oxidation-Reduction; Oxidative Phosphorylation; Oxidative Stress; Phenotype; Reactive Nitrogen Species; Reactive Oxygen Species; Ubiquinone; Vitamins

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are complex and serious illnesses that affect approximately 2.5% and 5% of the general population worldwide, respectively. The etiology is unknown; however, recent studies suggest that mitochondrial dysfunction has been involved in the pathophysiology of both conditions. We have investigated the possible association between mitochondrial biogenesis and oxidative stress in patients with CFS and FM. We studied 23 CFS patients, 20 FM patients, and 15 healthy controls. Peripheral blood mononuclear cell showed decreased levels of Coenzyme Q10 from CFS patients (p<0.001 compared with controls) and from FM subjects (p<0.001 compared with controls) and ATP levels for CFS patients (p<0.001 compared with controls) and for FM subjects (p<0.001 compared with controls). On the contrary, CFS/FM patients had significantly increased levels of lipid peroxidation, respectively (p<0.001 for both CFS and FM patients with regard to controls) that were indicative of oxidative stress-induced damage. Mitochondrial citrate synthase activity was significantly lower in FM patients (p<0.001) and, however, in CFS, it resulted in similar levels than controls. Mitochondrial DNA content (mtDNA/gDNA ratio) was normal in CFS and reduced in FM patients versus healthy controls, respectively (p<0.001). Expression levels of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha and transcription factor A, mitochondrial by immunoblotting were significantly lower in FM patients (p<0.001) and were normal in CFS subjects compared with healthy controls. These data lead to the hypothesis that mitochondrial dysfunction-dependent events could be a marker of differentiation between CFS and FM, indicating the mitochondria as a new potential therapeutic target for these conditions.

Topics: Adenosine Triphosphate; Adult; Biomarkers; Case-Control Studies; Fatigue Syndrome, Chronic; Female; Fibromyalgia; Humans; Leukocytes, Mononuclear; Lipid Peroxidation; Male; Middle Aged; Mitochondria; Oxidation-Reduction; Oxidative Stress; Risk Factors; Ubiquinone

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a medical illness characterized by disorders in inflammatory and oxidative and nitrosative (IO&NS) pathways.. This paper examines the role of Coenzyme Q10 (CoQ10), a mitochondrial nutrient which acts as an essential cofactor for the production of ATP in mitochondria and which displays significant antioxidant activities. Plasma CoQ10 has been assayed in 58 patients with ME/CFS and in 22 normal controls; the relationships between CoQ10 and the severity of ME/CFS as measured by means of the FibroFatigue (FF) scale were measured.. Plasma CoQ10 was significantly (p=0.00001) lower in ME/CFS patients than in normal controls. Up to 44.8% of patients with ME/CFS had values beneath the lowest plasma CoQ10 value detected in the normal controls, i.e. 490 microg/L. In ME/CFS, there were significant and inverse relationships between CoQ10 and the total score on the FF scale, fatigue and autonomic symptoms. Patients with very low CoQ10 (<390 microg/L) suffered significantly more from concentration and memory disturbances.. The results show that lowered levels of CoQ10 play a role in the pathophysiology of ME/CFS and that symptoms, such as fatigue, and autonomic and neurocognitive symptoms may be caused by CoQ10 depletion. Our results suggest that patients with ME/CFS would benefit from CoQ10 supplementation in order to normalize the low CoQ10 syndrome and the IO&NS disorders. The findings that lower CoQ10 is an independent predictor of chronic heart failure (CHF) and mortality due to CHF may explain previous reports that the mean age of ME/CFS patients dying from CHF is 25 years younger than the age of those dying from CHF in the general population. Since statins significantly decrease plasma CoQ10, ME/CFS should be regarded as a relative contraindication for treatment with statins without CoQ10 supplementation.

Topics: Adult; Autonomic Nervous System; Cognition Disorders; Coronary Artery Disease; Fatigue Syndrome, Chronic; Female; Heart Failure; Humans; Male; Middle Aged; Oxidative Stress; Risk Factors; Ubiquinone; Vasculitis

Unexplained chronic fatigue is a frequent complaint in primary care. A prospective observational study design was used to evaluate whether certain commonly used therapies for unexplained chronic fatigue may be effective.. Subjects with unexplained chronic fatigue of unknown etiology for at least 6 months were recruited from the Wisconsin Chronic Fatigue Syndrome Association, primary care clinics, and community chronic fatigue syndrome presentations. The primary outcome measure was change in a 5-question fatigue score from 6 months to 2 years. Self-reported interventions tested included prescribed medications, non-prescribed supplements and herbs, lifestyle changes, alternative therapies, and psychological support. Linear regression analysis was used to test the association of each therapy with the outcome measure after adjusting for statistically significant prognostic factors.. 155 subjects provided information on fatigue and treatments at baseline and follow-up. Of these subjects, 87% were female and 79% were middle-aged. The median duration of fatigue was 6.7 years. The percentage of users who found a treatment helpful was greatest for coenzyme Q10 (69% of 13 subjects), dehydroepiandrosterone (DHEA) (65% of 17 subjects), and ginseng (56% of 18 subjects). Treatments at 6 months that predicted subsequent fatigue improvement were vitamins (p = .08), vigorous exercise (p = .09), and yoga (p = .002). Magnesium (p = .002) and support groups (p = .06) were strongly associated with fatigue worsening from 6 months to 2 years. Yoga appeared to be most effective for subjects who did not have unclear thinking associated with the fatigue.. Certain alternative therapies for unexplained chronic fatigue, especially yoga, deserve testing in randomized controlled trials.

Topics: Adolescent; Adult; Aged; Antioxidants; Coenzymes; Complementary Therapies; Dehydroepiandrosterone; Fatigue Syndrome, Chronic; Female; Health Status; Humans; Male; Middle Aged; Panax; Personality Inventory; Plant Extracts; Prospective Studies; Psychiatric Status Rating Scales; Self-Help Groups; Social Support; Surveys and Questionnaires; Treatment Outcome; Ubiquinone; Vitamins