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Is a frequent disease that is characterized by the existence of many symptoms together at the same time. The main symptom is the generalized pain of the musculoskeletal system, i.e. muscles, ligaments and joints, but it is accompanied by significant fatigue, sleep disturbances, loss of concentration and memory, anxiety and sadness. The most recent research has found that in fibromyalgia there is an alteration in the neurotransmitters, that is, the substances that allow the communication between the neurotransmitters and the nerve cells.

Also recent studies determine that oxidative stress, inflammation and mitochondrial dysfunction together with deficiencies of CoQ10 demonstrate an important role in the origin of fibromyalgia. These studies provide new insights into FM and suggest new therapeutic interventions for disease.

Neurotransmitters such as Serotonin, Noradrenaline, Adrenaline, Dopamine and many others, when they are produced in adequate amounts and at the precise times, achieve a correct functioning of all the circuits of the nervous system. When there is an alteration in their production, the circuits that depend on them are functioning badly, causing the symptoms of the disease. This is precisely what happens to the pathways of pain, where a malfunction of the responsible neurotransmitters leads to a situation in which the perception of some stimulus is greater than usual, and produces the generalized pain so characteristic of fibromyalgia. The specific causes that produce fibromyalgia are not known. Many possible causes have been studied such as viral infections, hormonal diseases, muscular or toxic environmental diseases, among others, but at the present time we still do not know them.

Energy and Metabolism

Our body needs energy to maintain our vital functions, the cells of our tissues produce that energy through Cellular Metabolism. Mitochondria are the cellular organelles responsible for supplying energy to cells (ATP) for proper cellular function. Metabolism requires hundreds of chemical reactions. When one of the intermediaries in such reactions does not work, an energy crisis occurs. Incomplete metabolism products can accumulate in the body in the form of Free Radicals and other compounds. Such products may interrupt other major chemical reactions, worsening the crisis. In addition, the same products can act as free radicals, causing damage to mitochondria over time. Producing Mitochondrial Diseases.

Mitochondrial Diseases

Are the result of failure in the functioning of the mitochondria, in turn, constituent parts of the organism cells whose function is to generate the necessary energy to maintain life, development and correct organs and systems functioning.

Fibromyalgia is associated with mitochondrial dysfunction and oxidative stress. Recent studies have shown that oxidative stress may play a role in fibromyalgia physiology, and that coenzyme Q10 deficiency, demonstrated in mononuclear blood cells of patients with Fibromyalgia alters the function of the mitochondria. (Cordero 2011,Cordero 2010).


Mitochondria are cellular organelles responsible for supplying most of the energy required for cellular activity (cellular respiration). They act, therefore like energy centers of the cell and synthesize ATP to Muscles Skeletal expenses of the metabolic fuels ( glucose acids Fatty ).

Organs with greater Mitochondrial metabolism dependence

  • Brain, heart, liver
  • Skeletal muscles
  • Nervous system
  • Kidney, eyes, ear

These organs require more energy supply and in turn are the most sensitive in processes in the mitochondrial dysfunction.

Mitochondria is the main producer of free radicals of the cell

In states of mitochondrial disease or mitochondrial dysfunction, free radicals generated by mitochondria are very reactive in their formation due to their altered Number of valence electrons This situation produces an increase of Oxidative Stress.

Oxidative Stress

Oxidative Stress is defined as the imbalance between the production of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) and the antioxidant defense mechanisms We have basal levels of oxidative stress, mechanisms such as the bacterial activity of phagocytes or in signal transduction or the redox state of cells are necessary for life. The problem arises in the continuous imbalance causing the origin of degenerative diseases and muscular damage.

Mitochondrial Diseases Symptoms

Motor control loss, Muscle weakness and pain, Gastrointestinal disorders. Difficulties Heart disease, Depression, Diabetes Swallowing problems, visual, cognitive, auditory.

In patients with chronic musculoskeletal pain, chronic fatigue and / or fatigue, Q10coenzyme deficiency is common. In combination with the basic nutrients, they may improve symptomatology.

Fibromyalgia and Chronic Fatigue there is evidence to administer Q10 NADH as an adjunct to conventional medical treatment.
Has recently published a macro survey conducted in France, in order to know the quality of life of people affected by this pathology, involved more than 2,100 Patients at the question:

Do you usually suffer one of these symptoms?

The result is very significant, most respondents frequently had all the symptoms described. Concentrating painful points on muscles, tendons and bones.

Frequent painful spots in Fibromyalgia.

Fibromyalgia (FM) is a chronic pain syndrome of unknown etiology and a broad spectrum of symptoms such as allodynia, debilitating fatigue, joint stiffness, and migraine. Recent studies have shown some evidence that oxidative stress is associated with clinical symptoms in FM. Recent results from our group have shown reduced levels of CoQ10, reduced mitochondrial membrane potential, increased mitochondrial superoxide levels, and increased levels of lipid peroxidation in Mononuclear blood cells of patients with FM, mitochondrial dysfunction was also associated with increased expression of autophagic genes and the elimination of dysfunctional mitochondria by mitofagia [Cordero et al., 2010]. In another study, patients with FM were clinically assessed using the Visual Analogue Pain Scale (EVA), and the Fibromyalgia Impact Questionnaire (FIQ). Patients with FM with CoQ10 deficiency showed a significant reduction in symptoms after the CoQ10 treatment [Cordero et al., 2011, 2012. Determination of CoQ10 deficiency and subsequent FM supplementation may lead to significant clinical improvement.

Chronic fatigue syndrome

Chronic fatigue syndrome (CFS) is a medical condition characterized by persistent and intense physical and mental fatigue for more than 6 months that is not relieved by rest. It is accompanied by severe exercise intolerance, non-restorative sleep, and concentration and memory impairment. 

 It is a ‘complex’ medical condition, more common in women, genetically related to different triggering factors, such as infectious agents, injuries, the postpartum period, chemical agents, and physical or psychological stress, which cause alterations in intracellular proteins and higher immunological activity.

 It is diagnosed using the Fukuda Criteria. According to these criteria, CFS diagnosis is based on the occurrence of 2 major criteria and the coexistence of at least 4 associated criteria, mainly related to muscular and neuropsychological symptoms.  

 According to several scientific studies, it is estimated that between 0.2 % and 6.41 % of the world population are affected by CFS (4), which results in more than 1,500,000 people only in Europe (5).

Fukuda Diagnostic Criteria 

Major Criteria (both must be present)

  1. Persistent or recurrent chronic fatigue during 6 months, which is of new or definite onset, not the result of ongoing exertion, not substantially alleviated by rest, and results in substantial reduction in previous levels of the patient’s daily activities.
  2. The exclusion of any potential medical condition that may explain the presence of chronic fatigue.

Minor criteria: 
There must be a concurrent occurrence of four or more of the following signs and symptoms, all of which must have persisted during six or more consecutive months and must not have predated the fatigue:

  1. Substantial impairment in short-term memory or concentration
  2. Oesophagodynia or sore throat
  3. Painful cervical or axillary adenopathy
  4. Myalgia
  5. Multi-joint pain without swelling
  6. Headaches of a new type or with patterns different from the usual
  7. Unrefreshing sleep



Coexistence between CFS and other disorders aggravates prognosis, functional ability and, therefore, patient’s quality of life.  


There are some frequent associated pathologies, as for example: 


  •   Fibromyalgia
  •   Dry Eye Syndrome
  •   Myofascial Pain Syndrome
  •   Psychiatric Disorders 
  •   Sexual and Family Dysfunction 
  •   Hypersensitivities
  •   Tendinopathies 
  •   Autoimmune Diseases
  •   Vascular risk
  •   Decreases in Neurovegetative Functions


CFS Treatment 

 Due to the complex symptomatology of CFS and the current lack of specific pharmacological treatment, the best therapy is the one that ensures a multidisciplinary management and provides individual treatment. 

 This multidisciplinary team should be formed by specialists in internal medicine, rheumatology, primary care, clinical psychologists, psychiatrists, nursing graduates, physiotherapists, and social workers, among others. 

The multidisciplinary team’s performance will result in an improvement of the patient’s quality of life, since it will allow continuity and interaction between different education and health promotion programs. Patients with CFS will notice an improvement in their quality of life thanks to health care, socio-sanitary and social interventions.  

 Also worth mentioning are the different interconsultations and potential referrals between different clinics and units (such as those related to pain, cephalalgia, sleep, arrhythmia, and obesity or other comorbid diseases).

 Coenzyme Q10 (CoQ10) and NADP are antioxidant supplements. The benefits obtained with their administration have been thoroughly evaluated in different conditions (Braun et al. 1991, Porter et al. 1995, Malm et al. 1997, Cooke et al. 2008). Several studies have shown that there is a mitochondrial dysfunction that reduces ATP production in most CFS and/or ME patients, as a primary or secondary effect caused by symptoms of this syndrome (Twisk and Maes 2009; Booth et al. 2012; Marrero et al. 2013; Myhill et al. 2013; Castro- Marrero et al. 2016).

 Recently, the working group lead by Castro-Marrero (Castro-Marrero et al. 2017) ‘conducted a proof‐of‐concept, 8 week RCT in 80 Spanish CFS/ME patients who met the 1994 CDC/Fukuda definition and were allocated to receive CoQ10 plus NADH or matching placebo’. Their findings suggested that ‘the combination of CoQ10 plus NADH was safe and potentially effective in reducing the max HR (P = 0.022) during the exercise challenge test. There was also a trend towards a reduction in self‐reported measures of fatigue (FIS 40) in the active group compared with placebo (P = 0.030)’ (5).

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1,Article: Coenzyme Q10 Therapy. Juan Garrido Maraver · Mario D. Cordero · Manuel Oropesa-Ávila · Alejandro Fernández Vega · Mario de la Mata · Ana Delgado Pavón · Manuel de Miguel · Carmen Pérez Calero · Marina Villanueva Paz · David Cotán · José A. Sánchez-Alcázar. Full-text · Article · Jul 2014 · Molecular syndromology

2,Article: Oxidative stress, mitochondrial dysfunction and, inflammation common events in skin of patients with Fibromyalgia,Benito Sánchez-Domínguez · Pedro Bullón · Lourdes Román-Malo · Fabiola Marín-Aguilar · Elísabet Elísabet Alcocer-Gómez · Angel M. Carrión · José Antonio Sánchez-Alcazar · Mario D. Cordero,Full-text · Article · Feb 2015 · Mitochondrion

3,Article: Effect of coenzyme Q(10) evaluated by 1990 and 2010 ACR Diagnostic Criteria for Fibromyalgia and SCL-90-R: Four case reports and literature review- Elísabet Alcocer-Gómez · Francisco Javier Cano-García · Mario D Cordero Full-text · Article · Nov 2013 · Nutrition

4,Article: Does Oral Coenzyme Q 10 Plus NADH Supplementation Improve Fatigue and Biochemical Parameters in Chronic Fatigue Syndrome?. Jesús Castro-Marrero · Mario D. Cordero · María José Segundo · Naia Sáez-Francàs · Natalia Calvo · Lourdes Román-Malo · Luisa Aliste · Paula Riera Rios · Tomas Fernández de Sevilla · José Alegre-Martín. Full-text · Article · Nov 2014 · Antioxidants and Redox Signaling

5,Article: Mutation in Cytochrome b gene of mitochondrial DNA in a family with Fibromyalgia is associated with NLRP3-Inflammasome activation. Mario D Cordero · Elísabet Alcocer-Gómez · Fabiola Marín-Aguilar · Tatyana Rybkina · David Cotán · Antonio Pérez-Pulido · José Miguel Alvarez-Suarez · Maurizio Battino · José Antonio Sánchez-Alcazar · Angel M Carrión · Ognjen Culic · José M Navarro-Pando · Pedro Bullón,Full-text · Article · Oct 2015 · Journal of Medical Genetics

6,Article: The inflammasome in fibromyalgia and CRPS: A microglial hypothesis?. Mario D Cordero. Full-text · Article · Sep 2015 · Nature Reviews Rheumatology

7,Article: AMPK Phosphorylation Modulates Pain by Activation of NLRP3 Inflammasome. Pedro Bullon · Elisabet Alcocer-Gómez · Angel M Carrión · Juan Garrido-Maraver · Fabiola Marín-Aguilar · Lourdes Román-Malo · Jesus Ruiz-Cabello · Ognjen Culic · Bernhard Ryffel · Lionel Apetoh · François Ghiringhelli · Maurizio Battino · José Antonio Sánchez-Alcazar · Mario D. Cordero. Full-text · Article · Jun 2015 · Antioxidants & Redox Signaling

8,Article: Aging-Related Changes in Inflammatory and LKB1/AMPK Gene Expression in Fibromyalgia Patients. Elisabet Alcocer-Gómez · José Antonio Sánchez-Alcazar · Maurizio Battino · Pedro Bullón · Mario D. Cordero. Full-text · Article · Feb 2014 · CNS Neuroscience & Therapeutics

9,Article: Coenzyme Q10 Regulates Serotonin Levels and Depressive Symptoms in Fibromyalgia Patients: Results of a Small Clinical Trial.,Elísabet Alcocer-Gómez · Jose Antonio Sánchez-Alcázar · Mario D Cordero. Full-text · Article · Feb 2014 · Journal of clinical psychopharmacology

10,Article: Clinical applications of coenzyme Q10. Juan Garrido-Maraver · Mario D Cordero · Manuel Oropesa-Avila · Alejandro Fernandez Vega · Mario De La Mata · Ana Delgado Pavon · Elisabet Alcocer-Gomez · Carmen Perez Calero · Marina Villanueva Paz · Macarena Alanis · Isabel De Lavera · David Cotan · Jose A Sanchez-Alcazar. Full-text · Article · Jan 2014 · Frontiers in Bioscience

11,Article: NLRP3 Inflammasome Is Activated in Fibromyalgia: The Effect of Coenzyme Q 10,Mario D Cordero · Elisabet Alcocer-Gómez · Ognjen Culic · Angel M Carrión · Manuel de Miguel · Eduardo Díaz-Parrado · Eva M Perez-Villegas · Pedro Bullon · Maurizio Battino · José Antonio Sánchez-Alcazar,Full-text · Article · Jul 2013 · Antioxidants & Redox Signaling

12,Article: Could Mitochondrial Dysfunction Be a Differentiating Marker Between Chronic Fatigue Syndrome and Fibromyalgia?,Jesus Castro-Marrero · Mario D Cordero · Naia Saez-Francas · Conxita Jimenez-Gutiérrez · Francisco J Aguilar-Montilla · Luisa Aliste · José Alegre-Martin. Full-text · Article · Apr 2013 · Antioxidants & Redox Signaling

13,Article: Can Coenzyme Q 10 Improve Clinical and Molecular Parameters in Fibromyalgia?,Mario D Cordero · Elisabet Alcocer-Gómez · Manuel de Miguel · Ognjen Culic · Angel M Carrión · José Miguel Alvarez-Suarez · Pedro Bullon · Maurizio Battino · Ana Fernández-Rodríguez · José Antonio Sánchez-Alcazar. Full-text · Article · Mar 2013 · Antioxidants & Redox Signaling

14,Article: Oral coenzyme Q10 supplementation improves clinical symptoms and recovers pathological alterations in BMCs in a fibromyalgia patient. Mario D Cordero · David Cotán · Yaiza Del-Pozo-Martín · Angel M Carrión · Manuel de Miguel · Pedro Bullón · José Antonio Sánchez-Alcazar. Full-text · Article · Aug 2012 · Nutrition

15,Article: Oxidative Stress Correlates with Headache Symptoms in Fibromyalgia: Coenzyme Q10 Effect on Clinical Improvement. Mario D Cordero · Francisco Javier Cano-García · Elísabet Alcocer-Gómez · Manuel De Miguel · José Antonio Sánchez-Alcázar,Full-text · Article · Apr 2012 · PLoS ONE

16,Article: Coenzyme Q(10) in salivary cells correlate with blood cells in Fibromyalgia: Improvement in clinical and biochemical parameter after oral treatment. Mario D Cordero · Rocio Santos-García · David Bermejo-Jover · Benito Sánchez-Domínguez · María Reyes Jaramillo-Santos · Pedro Bullón. Full-text · Article · Feb 2012 · Clinical biochemistry

17,Article: The Role of Oxidative Stress and Mitochondrial Dysfunction in the Pathogenesis of Fibromyalgia,Mario D. Cordero · Manuel de Miguel · Jose? Antonio Sa?nchez Alca?zar,Full-text · Chapter · Jan 2012

18,Article: Clinical Symptoms in Fibromyalgia Are Better Associated to Lipid Peroxidation Levels in Blood Mononuclear Cells Rather than in Plasma. Mario D Cordero · Elísabet Alcocer-Gómez · Francisco J Cano-García · Manuel De Miguel · Angel M Carrión · Plácido Navas · José A Sánchez Alcázar. Full-text · Article · Oct 2011 · PLoS ONE

19,Article: Amitriptyline induces coenzyme Q deficiency and oxidative damage in mouse lung and liver. María Rosa Bautista-Ferrufino · Mario D Cordero · José Antonio Sánchez-Alcázar · Matilde Illanes · Ana Fernández-Rodríguez · Plácido Navas · Manuel de Miguel Article · Jul 2011 · Toxicology Letters

20,Article:Mitochondrial Dysfunction and Chronic Disease: Treatment With Natural Supplements. Garth L. Nicolson, PhD. Integr Med (Encinitas). 2014 Aug; 13(4)

21,Article.-PSICOBIOQUIMICA (ESTRÉS, ANSIEDAD Y DEPRESIÓN) EN FIBROMIALGIA.  Pedro T. Sánchez , Julia M. Sánchez , Miguel de Lamo , Gema Peiró .

22,Article..-EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) European Food Safety Authority (EFSA), Parma, Italy ,EFSA Journal 2009; 7(9):1216 Scientific Opinion on the substantiation of health claims related to magnesium and electrolyte balance (ID 238), energy-yielding metabolism (ID 240, 247, 248), neurotransmission and muscle contraction including heart muscle (ID 241, 242), cell division (ID 365), maintenance of bone (ID 239), maintenance of teeth (ID 239), blood coagulation (ID 357) and protein synthesis (ID 364) pursuant to Article 13(1) of Regulation (EC) No 1924/20061

23,Article..-Is magnesium citrate treatment effective on pain, clinical parameters and funcional status in patients with fibromyalgia? Selda Bagis • Mehmet Karabiber • I ̇smet As • Lu ̈lu ̈fer Tamer • Canan Erdogan • Ayc ̧e Atalay

24,Article..-Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome e A randomized, controlled, double-blind trial Jesus Castro-Marrero a, *, 1, Naia Saez-Franca s b, d, 1, María Jose Segundo c, Natalia Calvo d, Monica Faro a, Luisa Aliste a, Toma s Fernandez de Sevilla a, Jose Alegre 

25,Article..-Lower plasma Coenzyme Q10 in depression:a marker for treatment resistance and chronic fatigue in depression and a risk factor to cardiovascular disorder in that illness Michael Maes , Ivanka Mihaylova , Marta Kubera , Marc Uytterhoeven , Nicolas Vrydags , Eugene Bosmans .

26,Article.. Effect of Coenzyme Q10 on Myopathic Symptoms in Patients Treated With Statins. Giuseppe Caso, MD, MSc, PhDa,*, Patricia Kelly, DOb, Margaret A. McNurlan, PhDa, and William E. Lawson, MD

27,Article..-Kynurenine pathway pathologies: do nicotinamide and Other pathway co-Factors have Therapeutic Role in Reduction of symptom severity, Including chronic Fatigue syndrome (cFs) and Fibromyalgia (FM) Adele Blank eld

28,Article..-Tryptophan Biochemistry: Structural, Nutritional, Metabolic, and Medical Aspects in Humans Lionella Palego, Laura Betti, Alessandra Rossi, and Gino Giannaccini .

Chronic Fatigue Syndrom (CFS)

30.Article. Bates, DW, Schmitt, W, Buchwald, D, et al. Prevalence of fatigue and chronic fatigue syndrome in a primary care practice. Arch Intern Med 1993; 153:2759.

31.-Article. Prins, JB, van der, Meer JW, Bleijenberg, G. Chronic fatigue syndrome. Lancet 2006; 367:346.

32- Article. Centro Cochrane Iberoamericano y Agència de Qualitat i Avaluació Sanitàries de Catalunya. Evaluación y abordaje de la fibromialgia y el síndrome de fatiga crónica. Barcelona: Agència de Qualitat i Avaluació Sanitàries de Catalunya. Departament de Salut. Generalitat de Catalunya; 2017 

33.-Article. Castro‐Marrero J., Sáez‐Francàs N., Santillo D., and Alegre J. (2017) Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: all roads lead to Rome. British Journal of Pharmacology, 174: 345–369. doi: 10.1111/bph.13702.

34.-Article. Chronic Fatigue Syndrome: A Critical Review Jens D. Rollnik. DOI Fortschr Neurol Psychiatr 2017; 85: 79–85 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0720-4299Altern Ther Health Med. 2014 Winter;20 Suppl 1:18-25.

35.-Article. Mitochondrial dysfunction and chronic disease: treatment with natural supplements. Nicolson GL.Altern Ther Health Med.2014 Winter;20 Suppl 1:18-25. PMID: 24473982

36,Article.- Santaella ML, Font I, Disdier OM. 2004. Comparison of oral nicotinamide adenine dinucleotide (NADH) versus conventional therapy for chronic fatigue syndrome. P R Health Sci J 23: 89–93.

37,Article.- Glycophospholipid Formulation with NADH and CoQ10 Significantly Reduces Intractable Fatigue in Western Blot-Positive ‘Chronic Lyme Disease’ Patients: Preliminary Report,Functional Foods in Health and Disease 2012, 2(3):35-47 

38,Article.- Garth L. Nicolson, Robert Settineri, Rita Ellithorpe Functional Foods in Health and Disease 2012, 2(3):35-47 PMID: 24473982