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Fibromyalgia
Fibromyalgia, according to the American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia in the newly proposed criteria for the classification of fibromyalgia are 1) widespread pain in combination with 2) tenderness at 11 or more of the 18 specific tender point sites(a) as a result in responding to pressure.
The Symptoms
Symptoms of Fibromyalgia may be depending on the patient gender, according to the joint study led by the Klinikum Saarbrücken, if you are female, you are at a 90% increased risk of fibromyalgia development(4) and you may experience more serve symptoms of fibromyalgia in a longer duration of chronic widespread pain and time if compared to your male counterparts(1), but no differences in somatic and psychological symptoms(1)(2).
The College of Medicine at Peoria, University of Illinois study insisted, "women experienced significantly more common fatigue, morning fatigue, hurt all over, the total number of symptoms, and irritable bowel syndrome. Women had significantly more tender points. Pain severity, global severity, and physical functioning were not significantly different between the sexes, nor were psychologic factors, eg, anxiety, stress, and depression" and " Gender differences have also been observed in other related syndromes, eg, chronic fatigue syndrome, irritable bowel syndrome, and headaches(3).
In further evaluation, Dr. Yunus MB said, "the mechanisms of gender differences in these illnesses are not fully understood, they are likely to involve an interaction between biology, psychology, and sociocultural factors"(4).
Other symptoms may include widespread musculoskeletal pain, multiple “tender points”, fatigue, sleep disturbance, stiffness, and other symptoms such as headache, dizziness, trouble with concentration, irritable bowel syndrome, urinary urgency, and depression(6).
According to the American College of Rheumatology Disordered sleep is a prominent symptom in fibromyalgia, others include symptoms such as waking unrefreshed, fatigue, tiredness, and insomnia in the 2010 diagnostic criteria for fibromyalgia(7).
Causes and Risk factors
A. Causes
1. Oxidative stress
There is some evidence demonstrating that oxidative stress is associated with clinical symptoms in chronic pain syndrome of fibromyalgia(8), particularly in lipid peroxidation (LPO) in blood mononuclear cells (BMCs) and plasma(9).
According to the Universidad de Sevilla, mitochondrial dysfunction is found to be associated with the increased risk of fibromyalgia, probably due to CoQ10 deficiency in blood mononuclear cells(10).
In a total of 60 female studies conducted by the King George's Medical University study, oxidative stress is a major cause of FMS. Moreover, the increased oxidative stress parameters are more strongly associated with the severity of FMS.(11).
2. Chronic stress and psychological symptoms
The relationship between stress, depression, and functionality seems to be part of a complex mechanism, which might affect the quality of life of patients with FM(12). According to the study led by the Universidade Federal de São Paulo, Stress index (96%), trait anxiety (over 50), and clinically relevant depression (greater than 20) are found in the female patient with FMS(13).
1. Oxidative stress
There is some evidence demonstrating that oxidative stress is associated with clinical symptoms in chronic pain syndrome of fibromyalgia(8), particularly in lipid peroxidation (LPO) in blood mononuclear cells (BMCs) and plasma(9).
According to the Universidad de Sevilla, mitochondrial dysfunction is found to be associated with the increased risk of fibromyalgia, probably due to CoQ10 deficiency in blood mononuclear cells(10).
In a total of 60 female studies conducted by the King George's Medical University study, oxidative stress is a major cause of FMS. Moreover, the increased oxidative stress parameters are more strongly associated with the severity of FMS.(11).
2. Chronic stress and psychological symptoms
The relationship between stress, depression, and functionality seems to be part of a complex mechanism, which might affect the quality of life of patients with FM(12). According to the study led by the Universidade Federal de São Paulo, Stress index (96%), trait anxiety (over 50), and clinically relevant depression (greater than 20) are found in the female patient with FMS(13).
In spouses of sexually active reproductive women with fibromyalgia, Dr. Yener M and colleagues said, "FM can cause deterioration of emotional status and lead to sexual dysfunction" and "Also, psychological status could be affected in spouses of women with FM at reproductive age, and the severity of depression of their spouses was significantly correlated to that of women with FM"(14).
3. Alpha1-Antitrypsin (AAT)
There is a possible relationship between AAT deficiency (AAT-D) and fibromyalgia (FM) due to
inflammation(15). According to the Hospital Valle del Nalón, AAT replacement therapy has shown to induce a rapid, progressive, and constant control of FM symptoms, in 2 Spanish sisters with alpha1-antitrypsin (AAT) deficiency and fibromyalgia (FM)(16).
4. Inflammatory rheumatic disorders
There is evidence to suggest that fibromyalgia occurs much more frequently than expected in
individuals with inflammatory rheumatic disorders(17). According to the cross-sectional study carried out in a hospital-based rheumatology unit. Standard clinical and laboratory data, FM patients with inflammatory and patients with noninflammatory rheumatic disorders, experience to fibromyalgic features dominate and become the main cause of morbidity(18).
Dr. Jiao J and colleagues in the joint study led by the China Academy of Chinese Medical Sciences, said, "FM patients with rheumatic diseases were found to have worse SF-36-assessed pain and physical health and less improvement in these measures following treatment from FTP than patients without rheumatic diseases. FM patients with the rheumatic disease may require additional intervention to address underlying rheumatic disease-related limitations."(19).
5. Sleep disturbance
There is a reciprocal relationship that exists between pain and sleep, and that intervention targeted primarily at insomnia may improve pain(20). According to the joint study led by the Penn State College of Medicine, rates of CFS, FM, or CFS + FM were high: 13% in SDB and 48% in insomnia. CFS occurred frequently in SDB and insomnia, but FM occurred frequently only in insomnia(21).
There is a report that low sleep quality has induced sexual dysfunction in female patients with fibromyalgia(22).
6. Etc.
B. Risk factors
1. Gender
If you are a woman, you are at higher risk than men to develop Fibromyalgia. According to the Katedra Propedeutyki Pediatrii i Klinika Immunologii Wieku Rozwojowego Akademii Medycznej we Wrocławiu, fibromyalgia may occur at any age, even in childhood, is much more common in women than in men(23).
Dr. Reiffenberger DH and Amundson LH said, "Fibromyalgia syndrome includes symptoms of widespread, chronic musculoskeletal aching and stiffness and soft tissue tender points. It is frequently accompanied by fatigue and sleep disturbance. Fibromyalgia is more common in women than in men, and it occurs at a mean age of 49 years"(24).
2. Family history
It appears that there are factors in this personality trait that are hereditary and that may contribute to the development of FM(25), including psychological distress(26), familial history of depression(27),... According to Dr. Hudson JI and colleagues, said, "the familial prevalence of major affective disorder were significantly higher in the fibromyalgia patients than the rheumatoid arthritis patients":(28).
3. Environment factors
Environmental susceptibility may be the possible cause of Fibromyalgia(29) such as chronic stress(30)
4. Chronic illness
There is a belief that certain illnesses are associated with the increased risk of Fibromyalgia(35) such as diseases of infection(33)(34), and Chronic fatigue syndrome (CFS)(32), affecting the quality of work and social life, according to Dr. Asbring P.(31).
5. Etc.
The Complications
1. Negative impact on relationships
Fibromyalgia can result in a substantial negative impact on important relationships with family and close friends(36), according to a survey of 6,126 adults, lots diagnosed with fibromyalgia, including mildly to moderately damaged relationship(s) with their spouse(s)/partner(s) or contributed to a break-up with a spouse or partner.(35).
Dr. Yener M and colleagues at the joint study led by the Suleyman Demirel University, said, "FM can cause deterioration of emotional status and lead to sexual dysfunction. Also, psychological status could be affected in spouses of women with FM at reproductive age, and the severity of depression of their spouses was significantly correlated to that of women with FM"(36). furthermore, fibromyalgia is also found to induce sexual dysfunction and quality of life of the spouse as well, according to the Harran University Medical School study(37)1. Negative impact on relationships
Fibromyalgia can result in a substantial negative impact on important relationships with family and close friends(36), according to a survey of 6,126 adults, lots diagnosed with fibromyalgia, including mildly to moderately damaged relationship(s) with their spouse(s)/partner(s) or contributed to a break-up with a spouse or partner.(35).
2. Psychological problem
According to the study by Monash University and Monash Medical Centre in comparison between FM patients and healthy individuals found significant differences in control (Perceived Control of Internal States Scale and Mastery S.cale), patients with fibromyalgia also are associated with both high and low levels of stress, mood, pain, and fatigue(38).
According to the study by Monash University and Monash Medical Centre in comparison between FM patients and healthy individuals found significant differences in control (Perceived Control of Internal States Scale and Mastery S.cale), patients with fibromyalgia also are associated with both high and low levels of stress, mood, pain, and fatigue(38).
Dr. Malin K Dr. Littlejohn GO said, "Stress in females with fibromyalgia associates with both key symptoms and a range of relevant psychological variables. Stress appears to have a major role in modulating several key 'up-stream' processes in fibromyalgia"(39). Spouses of reproductive age women also experience an enormous amount of psychological problems, including anxiety and depression(40).
3. Pain Disability
Fibromyalgia syndrome (FMS) has been found to exhibit pain disability but differences in genders
(41). Women with fibromyalgia reported higher intensity of pain, tender point count, and depression than men(41). According to the manual therapy, the protocol was effective to improve pain intensity, and reduce pressure pain sensitivity, with a significant impact on FMS symptoms, sleep quality, and depressive symptoms, particularly in women(42).
In fact, the joint study led by the McGill University Health Centre suggested, that the risk of disability for patients with fibromyalgia is substantially high in the Western World(one out of three)(43).
4. Impaired functionality, and impact on the quality of life
Women with Fibromyalgia also showed a positive correlation between impaired functionality(46), and impact on the quality of life in comparison to women without(44). According to the Pamukkale University Medical School, in the survey of 51 patients with FMS and 41 control subjects, patients with fibromyalgia reported higher impaired functional status(46) and diminished quality of life than control(45).
5. Fall risk and Postural control deficits
There were significant relationships between fall risk in patients with Fibromyalgia. Worse postural performance and fall risk found in fibromyalgia patients may be the result of the sleep quality in the last 24 h and level of fatigue(47). According to the Oregon Health & Science University, objective sensory deficits in dynamic posturography(48) and impaired balance(49) are also found consistently associated with middle-aged FM patients inducing fall rates.
The reduced fall risk and postural control deficits probably can be achieved through combining balance training with exercise and cognitive training(50).
Diseases(Comorbidity) & mortality associated with Fibromyalgia
1. Infections
There is a association between FM and HIV and hepatitis C virus infections in patients with Fibromyalgia(51).
Dr. Adak B and colleagues at the University of Yüzüncü Yil insisted that there is a correlated relationship of chronic hepatitis B carriage and the risk of FM probably due to altered liver function, viral infection, concerns associated with chronic disease(52). Other infectious diseases including hepatitis C, Lyme disease, coxsackie B, HIV, and parvovirus infection, may also cause or trigger fibromyalgia(53).
2. Tumors
Patients with chronic generalized pain may have an increased risk of developing cancer, including patients with Fibromyalgia(51). According to the University of Pamo patients with FM is found higher correlated to operated breast cancer patients than the report in normal populations in the literature(54). Others cancers may also be associated to FM include lymphatic and hematological cancers(55).
3. Cardiovascular disease
Patients with are at increased risk of early onset of cardiovascular disease(51). According to the joint study led by the China Medical University Hospital, fibromyalgia patients have an independent risk for CHD development(56)(57) and Fibromyalgia patients with concomitant comorbidities have markedly increased CHD risk relative to those with primary fibromyalgia(56).
4. Mortality
Risk of of accidental death and death from cancer is higher in patients with Fibromyalgia(51). In the study of a total of 8,186 fibromyalgia patients seen between 1974 and 2009 , mortality does not appear to be increased in patients diagnosed with fibromyalgia, but the risk of death from suicide and accidents was increased(58).
Dr. Dreyer L and colleagues at the Copenhagen University, Copenhagen University Hospital said, "The causes of a markedly increased rate of suicide among female patients with FM are at present unknown but may be related to increased rates of lifetime depression, anxiety, and psychiatric disorders. Risk factors for suicide should be sought at the time of the diagnosis of FM and at followup"(59).
5. Other related morbidities may include
5. 1. Psychological morbidity
Substantial lifetime psychiatric disorder in individuals with fibromyalgia(60).
5.2. Medical and unexplained disorders
Such as migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder are frequently associated to patients with Fibromyalgia(61)(62).
The Diagnosis
The American College of Rheumatology (ACR), evidence-based interdisciplinary German guidelines on the diagnosis and management of FMS by Klinikum Saarbrücken Internal Medicine 1 Winterberg 1 D-66119 Saarbrücken, recommended a step wise diagnostic work-up of patients with chronic widespread pain (CWP), including Fibromyalgia
1. Complete medical history including medication, complete medical examination, as wide spread pain with no medical condition may constitute the disease development.
2. Basic laboratory tests to screen for inflammatory or endocrinology diseases to rule out other condition with similar symptoms.
3. Referring to specialists only in case of suspected somatic diseases. As psychological problems are found to associate to patients with Fibromyalgia(38)(39).
Dr. Tavel ME said, " Depending upon the type of physician/specialist consulted, those individuals may receive disease labels that range from an implied psychological origin such as somatoform or psychosomatic disease, or to a presumed physical disease such as fibromyalgia"(64)
4. Referring to mental health specialists in case of mental disorder(63). Psycological treatment of patients with continual and widespread musculoskeletal pain, including multimodal therapy, hypnosis, cognitive-behavioral therapy for insomnia, behavioral therapies, mind-body-based techniques, and biofeedback component showed to reduce symptoms of FM(65).
[Here we quote the text and copy from the study of The American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia and Measurement of Symptom Severity by FREDERICK WOLFE,1 DANIEL J. CLAUW,2 MARY-ANN FITZCHARLES,3 DON L. GOLDENBERG,4
ROBERT S. KATZ,5 PHILIP MEASE,6 ANTHONY S. RUSSELL,7 I. JON RUSSELL,8 JOHN B. WINFIELD,9 AND MUHAMMAD B. YUNUS10
Objective. To develop simple, practical criteria for clinical diagnosis of fibromyalgia that are suitable for use in primary and specialty care and that do not require a tender point examination, and to provide a severity scale for characteristic fibromyalgia symptoms.
Methods. We performed a multicenter study of 829 previously diagnosed fibromyalgia patients and controls using physician physical and interview examinations, including a widespread pain index (WPI), a measure of the number of painful body regions. Random forest and recursive partitioning analyses were used to guide the development of a case definition of fibromyalgia, to develop criteria, and to construct a symptom severity (SS) scale.
Results. Approximately 25% of fibromyalgia patients did not satisfy the American College of Rheumatology (ACR) 1990 classification criteria at the time of the study. The most important diagnostic variables were WPI and categorical scales for cognitive symptoms, unrefreshed sleep, fatigue, and number of somatic symptoms. The categorical scales were summed to create an SS scale. We combined the SS scale and the WPI to recommend a new case definition of fibromyalgia: (WPI >7 AND SS >5) OR (WPI 3–6 AND SS >9).
Conclusion. This simple clinical case definition of fibromyalgia correctly classifies88.1% of cases classified by the ACR classification criteria, and does not require a physical or tender point examination. The SS scale enables assessment of fibromyalgia symptom severity in persons with current or previous fibromyalgia, and in those to whom the criteria have not been applied. It will be especially useful in the longitudinal evaluation of patients with marked symptom variability.
Please note:
This criteria set has been approved by the American College of Rheumatology (ACR) Board of Directors as Provisional.This signifies that the criteria set has been quantitatively validated using patient data, but it has not undergone validationbased on an external data set. All ACR-approved criteria sets are expected to undergo intermittent updates.As disclosed in the manuscript, these criteria were developed with support from the study sponsor, Lilly Research Laboratories.The study sponsor placed no restrictions, offered no input or guidance on the conduct of the study, did not participatein the design of the study, see the results of the study, or review the manuscript or submitted abstracts prior to thesubmission of the paper. The recipient of the grant was Arthritis Research Center Foundation, Inc. The authors receivedno compensation. The ACR found the criteria to be methodologically rigorous and clinically meaningful.ACR is an independent professional, medical and scientific society which does not guarantee, warrant or endorse anycommercial product or service. The ACR received no compensation for its approval of these criteria](66).
The Misdiagnosis
The American College of Rheumatology (ACR), evidence-based interdisciplinary German guidelines on the diagnosis and management of FMS by Klinikum Saarbrücken Internal Medicine 1 Winterberg 1 D-66119 Saarbrücken, recommended a step wise diagnostic work-up of patients with chronic widespread pain (CWP), including Fibromyalgia
1. Complete medical history including medication, complete medical examination, as wide spread pain with no medical condition may constitute the disease development.
2. Basic laboratory tests to screen for inflammatory or endocrinology diseases to rule out other condition with similar symptoms.
3. Referring to specialists only in case of suspected somatic diseases. As psychological problems are found to associate to patients with Fibromyalgia(38)(39).
Dr. Tavel ME said, " Depending upon the type of physician/specialist consulted, those individuals may receive disease labels that range from an implied psychological origin such as somatoform or psychosomatic disease, or to a presumed physical disease such as fibromyalgia"(64)
4. Referring to mental health specialists in case of mental disorder(63). Psycological treatment of patients with continual and widespread musculoskeletal pain, including multimodal therapy, hypnosis, cognitive-behavioral therapy for insomnia, behavioral therapies, mind-body-based techniques, and biofeedback component showed to reduce symptoms of FM(65).
[Here we quote the text and copy from the study of The American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia and Measurement of Symptom Severity by FREDERICK WOLFE,1 DANIEL J. CLAUW,2 MARY-ANN FITZCHARLES,3 DON L. GOLDENBERG,4
ROBERT S. KATZ,5 PHILIP MEASE,6 ANTHONY S. RUSSELL,7 I. JON RUSSELL,8 JOHN B. WINFIELD,9 AND MUHAMMAD B. YUNUS10
Objective. To develop simple, practical criteria for clinical diagnosis of fibromyalgia that are suitable for use in primary and specialty care and that do not require a tender point examination, and to provide a severity scale for characteristic fibromyalgia symptoms.
Methods. We performed a multicenter study of 829 previously diagnosed fibromyalgia patients and controls using physician physical and interview examinations, including a widespread pain index (WPI), a measure of the number of painful body regions. Random forest and recursive partitioning analyses were used to guide the development of a case definition of fibromyalgia, to develop criteria, and to construct a symptom severity (SS) scale.
Results. Approximately 25% of fibromyalgia patients did not satisfy the American College of Rheumatology (ACR) 1990 classification criteria at the time of the study. The most important diagnostic variables were WPI and categorical scales for cognitive symptoms, unrefreshed sleep, fatigue, and number of somatic symptoms. The categorical scales were summed to create an SS scale. We combined the SS scale and the WPI to recommend a new case definition of fibromyalgia: (WPI >7 AND SS >5) OR (WPI 3–6 AND SS >9).
Conclusion. This simple clinical case definition of fibromyalgia correctly classifies88.1% of cases classified by the ACR classification criteria, and does not require a physical or tender point examination. The SS scale enables assessment of fibromyalgia symptom severity in persons with current or previous fibromyalgia, and in those to whom the criteria have not been applied. It will be especially useful in the longitudinal evaluation of patients with marked symptom variability.
Please note:
This criteria set has been approved by the American College of Rheumatology (ACR) Board of Directors as Provisional.This signifies that the criteria set has been quantitatively validated using patient data, but it has not undergone validationbased on an external data set. All ACR-approved criteria sets are expected to undergo intermittent updates.As disclosed in the manuscript, these criteria were developed with support from the study sponsor, Lilly Research Laboratories.The study sponsor placed no restrictions, offered no input or guidance on the conduct of the study, did not participatein the design of the study, see the results of the study, or review the manuscript or submitted abstracts prior to thesubmission of the paper. The recipient of the grant was Arthritis Research Center Foundation, Inc. The authors receivedno compensation. The ACR found the criteria to be methodologically rigorous and clinically meaningful.ACR is an independent professional, medical and scientific society which does not guarantee, warrant or endorse anycommercial product or service. The ACR received no compensation for its approval of these criteria](66).
The Misdiagnosis
Inflammatory arthritis is an auto immune diseases induced tender and swollen joints causing pain, stiffness and joint damage my be misdiagnosed as Fibromyalgia fue to FM have a marked impact on tender joint count scores, resulting in a disproportionately high tender joint count to swollen joint count ratio similar to those of inflammatory arthritis(67). Dr. Pöyhiä R and colleagues at the McGill University Health Center,, said,"Patients with FM report a high rate of varied pain and adverse experiences throughout life" and "Patients with FM reported significantly more irritable bowel syndrome, migraine headaches, severe menstrual pain, physical and psychological trauma affecting well being, family history of FM, and family pain environment than subjects with IA or controls"(68).
2. Spondyloarthropathies (SpA) and connective tissue disease (CTD)
Spondyloarthropathies (SpA) and connective tissue disease (CTD) are joint disease similar to those of FM. According to the Sapienza University of Rome, although is FM is a wellknown clinical entity, differentiation of SpA, CTD and inflammatory arthritis can still be diagnosed as FM(69). But incorrect diagnosis can be avoid if rheumatologists recognise and distinguish primary and secondary FM(70).
Serotonin syndrome is a over production of hormone serotonin due to serotonergic medications, causing wide spread pain may be misdiagnosed as fibromyalgia, accordin to a 42-year-old woman referred for physical therapy with a diagnosis of fibromyalgia(71). But careful evaluation by the physical therapist indicated that signs and symptoms may alter intitial diagnosed Dr. Alnwick GM said.
it is not surprising that chronic pain disorders are often misdiagnosed as hysterical or psychological in origin" and "can significantly increase the likelihood of treatment failure"(72).
4. Others
Dr. Shapiro AP and Dr. Teasell RW in the study of Misdiagnosis of chronic pain said "it is not surprising that chronic pain disorders are often misdiagnosed as hysterical or psychological in origin" and "can significantly increase the likelihood of treatment failure"(72).
Delay diagnosis
According to the King's College London," Patients wait a significant period of time before presenting to a physician, adding to the prolonged time to diagnosis. Patients typically present with a multitude of symptoms, all resulting in a delay in diagnosis and eventual management"(73).
In a questionnaire survey of 1622 physicians in six European countries, Mexico and South Korea including Specialties of primary care physicians (PCPs; n=809) and equal numbers of rheumatologists, neurologists, psychiatrists and pain specialists, 53% of physicians reported difficulty with diagnosing FM, 54% reported their training in FM was inadequate, and 32% considered themselves not knowledgeable about FM(74). The high percentage of difficult diagnosis and inadequate training may contributed the delay diagnosis and contributing to widespread unnecessary pain and significant impact on quality of life and function to patients with FM(75).
In a questionnaire survey of 1622 physicians in six European countries, Mexico and South Korea including Specialties of primary care physicians (PCPs; n=809) and equal numbers of rheumatologists, neurologists, psychiatrists and pain specialists, 53% of physicians reported difficulty with diagnosing FM, 54% reported their training in FM was inadequate, and 32% considered themselves not knowledgeable about FM(74). The high percentage of difficult diagnosis and inadequate training may contributed the delay diagnosis and contributing to widespread unnecessary pain and significant impact on quality of life and function to patients with FM(75).
Dr. Clark P and colleagues at the Clinical Epidemiology Unit HIM-Federico Gómez Faculty of Medicine UNAM in the physician survey of fibromyalgia across Latin America and Europe,
said, "Patient and physician perspective concerning FM impact and disruption were often misaligned within the same region. Our observations may be representative of cultural differences in stoicism, expression, beliefs, and attitudes to pain perception and management. Better understanding of these complexities could help targeted educational/training programs incorporating cultural differences, to improve chronic care"(76)
said, "Patient and physician perspective concerning FM impact and disruption were often misaligned within the same region. Our observations may be representative of cultural differences in stoicism, expression, beliefs, and attitudes to pain perception and management. Better understanding of these complexities could help targeted educational/training programs incorporating cultural differences, to improve chronic care"(76)
Prevention and Management
The Do and do not’s list
What to avoid may be the first question of people age of 50 and over who concern that they may be in stage of developing the disease. Other people may want to know what they can do to protect themselves against the early onset.
1. Reduce intake of saturated and trans fat and increase intake of omega 3 fatty acids
Intake of omega-3 fatty acids may be used to treat and in the manage symptoms of fibromyalgia syndrome, according to Dr. Ozgocmen S and colleagues(81) due to its antioxidant effect in ameliorated oxidative stress and nitric oxide in the pathophysiology of FM(82). Although Limited studies have shown that certain dietary fatty acids (ie, oleic acid and alpha-linolenic acid) reduce biomarkers of inflammation(77).
Dr. Li Z and the research team at the Jilin University showed that ω3-polyunsaturated fatty acids (ω3-PUFAs) not only have beneficial effects on cardiovascular function but also promoted the docosahexaenoic acid (DHA) in reduced inflammation(78)(79).
The results of over 13 double-blind, placebo-controlled studies involving a total of more than 500 people suggest that omega-3 fatty acids may improve symptoms of rheumatoid arthritis. One of the ways it appears to work is by decreasing the production of inflammatory chemicals(80).
The results of over 13 double-blind, placebo-controlled studies involving a total of more than 500 people suggest that omega-3 fatty acids may improve symptoms of rheumatoid arthritis. One of the ways it appears to work is by decreasing the production of inflammatory chemicals(80).
Maintaining high levels of omega-3 fatty acids showed to neutralizing the saturated and trans fat involved high blood cholesterol in elevation of fibromyalgia pain caused by exhibited the function of pro inflammatory cytokines(83)(84)(85).
2. Increasing the ratio of (n-3) : (n-6) PUFA
2. Increasing the ratio of (n-3) : (n-6) PUFA
It is believed that omega-3 (n-3) polyunsaturated fatty acids (PUFA) suppress and n-6 PUFA have caused many kinds of disease, epidemiologically such as prostate cancer(90), colorectal cancers(91), breast cancer(92).
The industrial elocution induced Western style diet in over consumption of ω6 polyunsaturated fatty acids (PUFA) over many decades has been found to distort the ratio of ω3:ω6 fatty acids, one of the leading cause of chronic inflammatory diseases, including Fibromyalgia(78).
Increased ratio of (n-6) : (n-3) PUFA are found to promote chronic inflammatory diseases such as nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, obesity, inflammatory bowel disease (IBD), rheumatoid arthritis, and Alzheimer’s disease (AD)(86).
According to Dr. Yang LG and colleagues led by the Southeast University, an imbalance in the n-6/n-3 polyunsaturated fatty acid (PUFA) ratio, ameliorated lipid profiles, anti-inflammatory and anti-oxidative stress effects(87) in induction the widespread pain in patients with FM(88). Pro inflammatory cytokines of interleukin (IL)-1β is found to inversely associate higher cerebrospinal fluid (CSF) in induced dysfunctional pain (FM) in patients with FM(89).The industrial elocution induced Western style diet in over consumption of ω6 polyunsaturated fatty acids (PUFA) over many decades has been found to distort the ratio of ω3:ω6 fatty acids, one of the leading cause of chronic inflammatory diseases, including Fibromyalgia(78).
Increased ratio of (n-6) : (n-3) PUFA are found to promote chronic inflammatory diseases such as nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, obesity, inflammatory bowel disease (IBD), rheumatoid arthritis, and Alzheimer’s disease (AD)(86).
3. Increase intake of fruit and vegetable
Consumption of fruit and vegetable is associated in reduced the over expression of inflammation and oxidative stress, inducing chronic inflammatory diseases risk of stroke, coronary heart disease, etc,...(93). A cross-sectional study of ≈1200 Puerto Rican adults aged 45-75 y, we assessed FV intake with a food-frequency questionnaire, suggested, but not quantity, appears to be important in reducing inflammation(94).
According to the University of Kuopio, uncooked vegan diet called living food (LF) with risk sources of beta and alfa carotenes, lycopen and lutein, vitamin C and vitamin E (adjusted to cholesterol) showed to decrease joint stiffness and pain as well as an improvement of their self-experienced health.in fibromyalgic subjects(95), particular with regular intake of anti proinflammatory cytokine cruciferous vegetable(96).
Consumption of fruit and vegetable is associated in reduced the over expression of inflammation and oxidative stress, inducing chronic inflammatory diseases risk of stroke, coronary heart disease, etc,...(93). A cross-sectional study of ≈1200 Puerto Rican adults aged 45-75 y, we assessed FV intake with a food-frequency questionnaire, suggested, but not quantity, appears to be important in reducing inflammation(94).
According to the University of Kuopio, uncooked vegan diet called living food (LF) with risk sources of beta and alfa carotenes, lycopen and lutein, vitamin C and vitamin E (adjusted to cholesterol) showed to decrease joint stiffness and pain as well as an improvement of their self-experienced health.in fibromyalgic subjects(95), particular with regular intake of anti proinflammatory cytokine cruciferous vegetable(96).
3. Avoid high glycemic index diets
High glycemic index diets with low fiber content are rich in trans fat has showed to induce over activation of the immune system, leading to excessive production of pro-inflammatory cytokines of in promoting inflammatory diseases(97). According to the joint study led by the Isfahan University of Medical Science, a high glycemic index (LGI) diet has a negative effect on insulin concentration, fasting blood sugar (FBS), inflammatory markers, and serum adiponectin concentration, causing the development of inflammatory disorders(98).
4. Reduced intake of pro inflammatory foods, such as sugar, dairy products, red meat and processed, meat, alcohol, artificial ingredients, refined products, etc,....
According to the study by University of Hertfordshire Over consumption of fat content, especially from saturated fat, and cholesterol and reduced the intake of whole-grain foods, fruits, and vegetables, accompanied with the high amount of sugar, dairy products, red meat and processed, meat, alcohol, artificial ingredients, refined products, etc. in Western diet is found to be the leading causes of metabolic syndrome(99) of which induced risk of chronic inflammatory diseases(100).
5. Increase in take of anti inflammatory foods, such as fresh vegetables and fruits, seeds and sprouts whole grain, fish, turkey, chicken, legumes, etc(97).
6. Stop smoking
In comparison to non smokers, smokers with fibromyalgia may have greater pain intensity and function impairment(101)(102). Dr. Goesling J and colleagues at the joint study led by the University of Michigan, said, "Although FM+ smokers report the most negative clinical symptomatology (i.e., high pain, greater interference)smoking does not appear to have a unique association with pain or functioning in FM+ patients, rather the effect is additiv"(102)
7. Moderate exercise
Moderate exercise enhances immune function in fighting against inflammation and and reduced inflammatory (interleukin-6 [IL-6], C-reactive protein [CRP]) markers of that attenuate to risk of
Fibromyalgia(103). A single sessions of moderate cycling can improve the inflammatory status and decrease in the stress response in FM patients, according to the University of Extremadura(104), paticular in regular aquatic exercise in FM syndrome(105).
The diet
Dietary consumption plays an important part in reduce or increase risk of chronic inflammatory diseases. A typical American diet with high amount of red meat, fat and trans fat, processed, meat, artificial ingredients, refined products are associated to promote the expression of pro inflammatory cytokines, leading to all kinds of diseases including chronic inflammatory, cardiovascular diseases and diabetes.
1. Organic Soy
Soybean is genus Glycine, the family Fabaceae, one of the legumes that contains twice as much protein per acre as any other major vegetable or grain crop, native to Southeast Asia. The food other than organic is One of the first to apply the GMO technique used for enhancing the production of the crop with injection of ingredients in protection against insects, mold,.....Dietary rich in organic soy has been found to associate to decreased risk of chronic inflammatory diseases through attenuation of inflammatory marker by enhancing the immune modulatory effect related to risk of Fibromyalgia(106).
In a randomized, double-blind, placebo-controlled, early phase trial. conducted by the Mayo Clinic, Shakes containning soy and shakes containing casein used conjunction in a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms(107).
Dr. Nasca MM and the the research team at the Beth Israel Deaconess Medical Center suggested, Soy nuts were associated with a trend toward reduction in C-reactive protein in normotensive women, improved over all inflammatory process(108), particular in menopausal women(109).
2. Green tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
According to the survey of a complementary and alternative medical therapies by patients referred to a fibromyalgia treatment program at a tertiary care center., green tea has been used in 24% of patients(110).
Green tea polyphenols (GTP) has an effectiveness against chronic inflammation through attenuating the deterioration of bone microarchitecture, according to the Texas Tech University Health Sciences Center, in animal study(111).
Also in rat study, alcoholic extracts of green tea (AE) exhibited its analgesic and anti-inflammatory properties, through inhibited carrageenan-induced cell migration(112).
Decaffeinated dreen tea also expressed the immunomodulatory effects through enhanceing the immune system against inflammatory disease in rainbow trout(113).
Furthermore, in a study of forty-three of fifty-eight (74.1%) female patients with fibromyalgia completed an eight-week treatment period testing the combination of carisoprodol, paracetamol (acetaminophen) and caffeine versus placebo, found that the combination of carisoprodol and paracetamol (acetaminophen) and caffeine (from green tea) are effective in the treatment of fibromyalgia(113a).
3. Olive oil
Olive is belongs to the the family Oleaceae, native to the coastal areas of the eastern Mediterranean Basin and south end of the Caspian Sea. Its fruit, is a source of olive oil.
Consumption of extra virgin olive oil (EVOO) has been found to decrease joint edema, cell migration, cartilage degradation and bone erosion throguh attenuate the levels of proinflammatory cytokines and prostaglandin E2(114). according joint study by the University of Seville.In adult male Balb/C mice study, olive oil decreased the second phase of formalin-induced pain through its antinociceptive and anti-inflammatory activity(115).
The Chemistry and health of olive oil phenolics study also found, the positive effects of olive oil phenolics on certain physiological parameters, such as plasma lipoproteins, oxidative damage, inflammatory markers, platelet and cellular function, etc,.....(116).
Omega 3 fatty acids found abundantly in olive, according to university if Toronto exhibited anti neuropathic pain activities(117) and suggested that the oil fatty acids may be used for management of symptoms in patients with fibromyalgia(118).
In the evaluation of the oxidant/antioxidant status, lipid peroxidation and nitric oxide (NO) in untreated fibromyalgia (FM) patients and controls(119).
Similar to olive, nuts and seeds with rich in Omega 3 fatty acids is necessary to reduce risk of expressionless of markers of inflammation to attenuate the inflammatory response of the immune system, according to the study by the Tufts University(120).
High saturated fat diets with low omega 3 fatty acid intake increased omega-6:EPA+DHA ratio diets causing some measures of inflammation(121).
4. Circuit fruits
Circuit fruit contain high amount of Quercetin which can reduce the risk of chronic inflammatory diseases as a result of anti inflammatory(122) and antioxidant effects(123). Vitamin C, also known as L-ascorbate is a water soluble vitamin with a chemical structure formula of C6H6O6 found abundantly in circuit fruit, enhanced the activation of immune cells such as T and NK cells in attenuation of the inflammation caused by viral infection when used conjunction with red ginseng(124).
Dr. Yan H and colleagues in the study of Ascorbic acid (AA) in mitigating oxidative stress and inhibiting inflammation suggested, ascorbic acid significantly reduced clinical signs, inflammatory cytokines, myeloperoxidase (MPO) and malonaldehyde (MDA) activities in animal model(125).
Furthermore, the application of vitamin C and Quercetin, in exposure to fine particulate matter (PM2.5), exhibited the repressive roles in respiratory oxidative damage caused by PM2.5, through attenuated the depleted the cell viability of 16HBE cells, the elevated reactive oxygen species (ROS) generation, and the inhibited mitochondrial genes expressions(126).
The Phytochemicals
Different mediators of central inflammation in dysfunctional and inflammatory pain have been found to associate with patient with Fibromyalgia(127). Certain phytochemicals have found effectively for treatment of inflammatory symptoms of patient with FM, including the following
1. Polyphenols(-)-epigallocatechin-3-gallate (EGCG)(Green tea)
Epigallocatechin gallate (EGCG), including catechins, is phytochemicals of Flavan-3-ols, in the group of Flavonoids (polyphenols) found abundantly catechin in green tea.The majoe phytochemical has showed to process anti viral and bacterial effects through immune expression such as chronic or acute inflammation(128). Dr. Xiao J and the research team at the Shenzhen Institute of Advanced Technology suggested, pure extract of (-) epigallocatechin gallate (EGCG) inhibited inflammatory effects through its antioxidant activities against oxidative stress and down regulated pro-inflammatory markers(129).
According to the Universitat de Girona (UdG), Polyphenols(-)-epigallocatechin-3-gallate (EGCG) also showed to reduce pain in attenuate the alterations by diminishing apoptotic gene overexpression in skeletal muscles(130).
In the consideration of the safety amount for healthy individuals to take green tea, Dr. Chow HH and colleagues said, "green tea polyphenol products in amounts equivalent to the EGCG content in 8-16 cups of green tea once a day or in divided doses twice a day for 4 weeks. There is a >60% increase in the systemic availability of free EGCG after chronic green tea polyphenol administration at a high daily bolus dose (800 mg EGCG or Polyphenon E once daily)(131).
2. Curcumin
Curcumin, a phytochemical found in turmeric used in the Indian cooking recipe has found to process the antioxidants and anti inflammatory effects, epidemiologically.
The phytochemical also showed to inhibited muscle pain, muscle damage, inflammation and delayed onset muscle soreness, the SportsMed Canterbury study suggested.(132), through attenuate the inflammatory responses and production of reactive oxygen species (ROS) that sustain both inflammation and oxidative stress(133).
Dr. Ghosh S and colleagues at the Bose Institute suggested, " Oxidative stress and inflammation play a pivotal role in various diseases like diabetes, cancer, arthritis, Alzheimer's disease and cardiovascular diseases. Curcumin, therefore, could be a therapeutic option for the treatment of these diseases, provided limitations in its oral bioavailability can be overcome."(134), particular in various proinflammatory chronic diseases(135).In fact Dr. Anand P and the research team at the University of Texas M.D. Anderson Cancer Center, curcumin beside inhibited pain in many therapeutic levels but also linked to suppression of inflammation; angiogenesis, tumorigenesis and diseases of the cardiovascular, pulmonary, and neurological systems(136).
3. Resveratrol
Resveratrol (RES), a well-known antioxidant and anti-inflammatorycompound, is abundant in red wine and exerts numerous pharmacological effects, including hepatoprotection and cadioprotection(137).
The antioxidant exhibited anti-inflammatory effects through ameliorated the expression of proinflammatory (e.g., miR-155) in infections, injuries, atherosclerosis, diabetes mellitus, obesity, cancer, osteoarthritis, age-related macular degeneration, demyelination, and neurodegenerative diseases(138).
In the evaluation of the medical effect of resveratrol, the University of Wuxi, Jiangsu, insisted" Resveratrol prevented the accumulation of chronic oxidative stress and suppression of Tregs production in HFD mice, modulated changes of cytokines in the plasma and spleen, and decreased expressions of inflammatory mediators compared with those of the DIO group"(139).
Furthermore, the antioxidant also expressed anti age-associated chronic diseases through exhibited dysregulation of multiple cell signaling pathways in induction of inflammation(140).According to the University of Arizona study, resveratrol facilitated acute and chronic pain through activation of AMPK, the enzyme played a key role as a master regulator of cellular energy homeostasis(141).
In a Mouse Fibromyalgia-Like Model, resveratrol significantly reduced mechanical allodynia and thermal hyperalgesia in attenuated oxidative stress and reactive species, underlying mechanism of pathogenesis of the disease. through antinociceptive and antidepressant actions(142)
4. Boswellic acid
Gum-resin extracts of Boswellia serrata have been traditionally used in folk medicine for centuries to treat various chronic inflammatory diseases. recent study showed that the acid are also responsible for inhibition of pro-inflammatory enzymes(143). Dr Bishnoi M and the research team at the University Institute of Pharmaceutical Sciences, the phytochemical also may help to reduce the therapeutic doses of conventional NSAIDs and also reduce side effects when used conjunction with nimesulide(144).
In Lipopolysaccharide-Induced Cognitive Impairment in Mice, combination therapy of 3-acetyl-11-keto-β-boswellic acid (AKBA), a 5-lipoxygenase (5-LOX) inhibitor and celecoxib, and a selective cyclooxygenase-2 (COX-2) inhibitor expressed anti-inflammatory activity against amyloid beta peptide (Aβ) induced cognitive dysfunction(145).
Furthermore, oral administration of Boswellic acid inhibited airway hyperresponsiveness, inflammatory cell infiltration, Th2 cytokine and OVA-specific IgE production in a mouse model of asthma by ameliorated the over expression of anti body Th2 cytokines(146). In a Mouse Fibromyalgia-Like Model, resveratrol significantly reduced mechanical allodynia and thermal hyperalgesia in attenuated oxidative stress and reactive species, underlying mechanism of pathogenesis of the disease. through antinociceptive and antidepressant actions(142)
4. Boswellic acid
Gum-resin extracts of Boswellia serrata have been traditionally used in folk medicine for centuries to treat various chronic inflammatory diseases. recent study showed that the acid are also responsible for inhibition of pro-inflammatory enzymes(143). Dr Bishnoi M and the research team at the University Institute of Pharmaceutical Sciences, the phytochemical also may help to reduce the therapeutic doses of conventional NSAIDs and also reduce side effects when used conjunction with nimesulide(144).
In Lipopolysaccharide-Induced Cognitive Impairment in Mice, combination therapy of 3-acetyl-11-keto-β-boswellic acid (AKBA), a 5-lipoxygenase (5-LOX) inhibitor and celecoxib, and a selective cyclooxygenase-2 (COX-2) inhibitor expressed anti-inflammatory activity against amyloid beta peptide (Aβ) induced cognitive dysfunction(145).
5. Cucurbitacins
Cucurbitacins found in the common pumpkins and gourds has found to process anti-inflammatory and analgesic activity in redued pain through inhibition of the neurogenic (first phase) and inflammatory phase (second phase) of formalin-induced pain(147). The phytochemical also inhibited pain caused by chronic rheumatic disease through anti pro inflammayory cytokine activity(148).
In neuro injure response, cucurbitacins displayed anti nitric oxide, prostaglandins and inflammatory cytokines, activation of complement proteins inducing neuro damage through activation of the neuroprotection of Nrf2/ARE pathway(149).
The Antioxidants
Free radicals are atoms, molecules, or ions with unpaired electrons through chemical bonds with other atoms or molecules during a chemical reaction. They may have positive, negative or zero charge.
Free Radicals play an important role in the function of the Immune System. The immune system produces free radicals to kill foreign microbes(152)(153), but the production of free radical sometime can be excessive, leading to formation of a large number of free radicals(154)(155). The domino effects have shown to induce many chronic illness, such as cancers(155).
Furthermore, free radicals also displays over expression of oxidative stress, inducing varies form of chronic illness including metabolic syndrome(156).
The Free Radical scavengers
1. Vitamin A
vitamin A plays an essential roles in enhancing a broad range of immune processes, including white blood cells activation and proliferation(157)of T-helper-cell differentiation, the production of specific antibody in regulation of the immune response(158). According to the Suleyman Demirel University, Concentrations of vitamins A were significantly lower in patients with fibromyalgia than in controls, leading to over displayment of reactive oxygen species (ROS) in the etiology and pathogenesis of fibromyalgia(159).
Furthermore, in the evaluation of a total of 43 patients with FM and 44 healthy women, FM group
showed a mean consumption of nutrients lower than CT group, including vitamin A(160).
Deficiency of concentration may play an important role in exacerbate the over expression of Fibromyalgia but excess amount of vitamin A may also worsen the the symptoms of soft tissue rheumatism(161) Dr. Romano TJ. suggested.
2. Vitamin C
Vitamin C, also known as L-ascorbate, a water soluble vitamin with a chemical structure formula of C6H6O6 is best known for it's antioxidant property in strengthening the immune system.Due to recent promotion of western diet in some developed country, deficiencies of micronutrients are emerging as the limiting factors in ensuring children's optimal health, according Bayer Consumer Care Ltd(162). Deficiency of vitamin C and zinc in fact, interfere with normal children's growth and development(162). Researchers found that vitamin C raised the concentration in the blood of total immunoglobulin(163) in promotion of the ability of antibodies and phagocytic cells to clear pathogens(164).
Dr. Altindag O and Dr. Celik H. said, " patients with fibromyalgia are exposed to oxidative stress and this increased oxidative stress may play a role in the etiopathogenesis of the disease. Supplementation of antioxidant vitamins such as vitamins C and E to the therapy may be indicated"(165).
vitamin A plays an essential roles in enhancing a broad range of immune processes, including white blood cells activation and proliferation(157)of T-helper-cell differentiation, the production of specific antibody in regulation of the immune response(158). According to the Suleyman Demirel University, Concentrations of vitamins A were significantly lower in patients with fibromyalgia than in controls, leading to over displayment of reactive oxygen species (ROS) in the etiology and pathogenesis of fibromyalgia(159).
Furthermore, in the evaluation of a total of 43 patients with FM and 44 healthy women, FM group
showed a mean consumption of nutrients lower than CT group, including vitamin A(160).
Deficiency of concentration may play an important role in exacerbate the over expression of Fibromyalgia but excess amount of vitamin A may also worsen the the symptoms of soft tissue rheumatism(161) Dr. Romano TJ. suggested.
2. Vitamin C
Vitamin C, also known as L-ascorbate, a water soluble vitamin with a chemical structure formula of C6H6O6 is best known for it's antioxidant property in strengthening the immune system.Due to recent promotion of western diet in some developed country, deficiencies of micronutrients are emerging as the limiting factors in ensuring children's optimal health, according Bayer Consumer Care Ltd(162). Deficiency of vitamin C and zinc in fact, interfere with normal children's growth and development(162). Researchers found that vitamin C raised the concentration in the blood of total immunoglobulin(163) in promotion of the ability of antibodies and phagocytic cells to clear pathogens(164).
Dr. Altindag O and Dr. Celik H. said, " patients with fibromyalgia are exposed to oxidative stress and this increased oxidative stress may play a role in the etiopathogenesis of the disease. Supplementation of antioxidant vitamins such as vitamins C and E to the therapy may be indicated"(165).
According to the University of Kuopio, vegan diet rich in antioxidants, lactobacilli and fibre, have shown to benefit patient with rheumatoid disorder(166).
3. Vitamin D
Deficiency of vitamin D is found to associate to nonspecific musculoskeletal pain. According to Maccabi Healthcare Services, improvement of levels of 25OHD reduced Polymyalgia pain induced by the use of statins(167). According to the Spine Unit, Center of Excellence for Orthopaedic Pain Management, oral administration of vitamin D reduced remarkably in pain of patient with FM in visual analog scale scores(168).
Dr. Matthana MH said, "Vitamin D deficiency has to be considered in the management of fibromyalgia syndrome" as "Among the 100 fibromyalgia women, there were 61 women with 25(OH) D deficiency; with vitamin D supplementation, only 42 women showed a significant improvement when their blood level of 25(OH) D became>or=30 ng/mL, this improvement became more significant when their blood level of 25(OH) D exceeded 50 ng/ mL"(169).
In support to the above diagnosis, evaluation of Saudi Arabia women, also showed a significant negative correlation between vitamin D level and widespread pain index(170).
4. Vitamin E
According to Dr. Moriguchi S and Dr. Muraga M., vitamin E plays an essential role in enhanced immunity especially in cellular immunity with aging(171). Deficiency of vitamin E is found to induces the decreased differentiation of immature T cells associated to the increased infectious diseases and the incidence of tumors(171). According to the Suleyman Demirel University, intake of vitamins C and E (VCE) supplementation with exercise (EX) enhanced antioxidant vitamin and lipid peroxidation (LP) levels in blood of patients with fibromyalgia (FM)in protection of against FM-induced by oxidative stress(172).
Dr. Altindag O and Dr. Celik H. said, " patients with fibromyalgia are exposed to oxidative stress and this increased oxidative stress may play a role in the etiopathogenesis of the disease. Supplementation of antioxidant vitamins such as vitamins C and E to the therapy may be indicated"(173).
In support to the above analysis, Dr. Bagis S and colleagues at the Mersin University Medical School insisted, change of oxidant/antioxidant balances induced increase of free radical levels may be responsible for the development of fibromyalgia(174).4. Vitamin E
According to Dr. Moriguchi S and Dr. Muraga M., vitamin E plays an essential role in enhanced immunity especially in cellular immunity with aging(171). Deficiency of vitamin E is found to induces the decreased differentiation of immature T cells associated to the increased infectious diseases and the incidence of tumors(171). According to the Suleyman Demirel University, intake of vitamins C and E (VCE) supplementation with exercise (EX) enhanced antioxidant vitamin and lipid peroxidation (LP) levels in blood of patients with fibromyalgia (FM)in protection of against FM-induced by oxidative stress(172).
Dr. Altindag O and Dr. Celik H. said, " patients with fibromyalgia are exposed to oxidative stress and this increased oxidative stress may play a role in the etiopathogenesis of the disease. Supplementation of antioxidant vitamins such as vitamins C and E to the therapy may be indicated"(173).
In fact, dietary consumption including vitamin E significantly reduced the levels of inflammation by analyzing the pro and anti-inflammatory cytokines in the blood serum(175).
The Anti inflammatory Antioxidants
Anti inflammatory Antioxidants play an critical role in induction of oxidative stress in the pathogenesis of a number of disorders inflammation, Fibromyalgia , rheumatoid arthritis, asthma, psoriasis and contact dermatitis(176),
1. Glucosamine and chondroitin
Glucosamine used for treatment of osteoporosis and prevent the degenerative collagen, has been found to consist anti-inflammatory properties through reduction of the expression of proinflammatory cytokines such as C-reactive protein (hsCRP), interleukin (IL)-1β, IL-6(177). The supplement also exhibited a significant reduction in pain intensity at movement and resting state, according to a Russian study(178).
Dr. Fishman SM suggested, administration of Glucosamine and chondroitin may be used for management of pain in patients of Fibromyalgia(179). In a total of 71.4% women, and 65.0% with annual incomes of less than 25,000 dollars.researchers at the University of New Mexico Health Sciences Center indicated a higher percentage use of alternative medicine including oral supplement glucosamine and chondroitin for treatment with with osteoarthritis, rheumatoid arthritis, or fibromyalgia(180). Furthermore, the study also showed that use of alternative medicine was significantly associated with female, under 55 years of age, and having some college education(180).
Dr. Parcell S said, " ...sulfur compounds such as SAMe, dimethylsulfoxide (DMSO), taurine, glucosamine or chondroitin sulfate, and reduced glutathione may also have clinical applications in the treatment of a number of conditions such as depression, fibromyalgia,....."(181).
Anti inflammatory Antioxidants play an critical role in induction of oxidative stress in the pathogenesis of a number of disorders inflammation, Fibromyalgia , rheumatoid arthritis, asthma, psoriasis and contact dermatitis(176),
1. Glucosamine and chondroitin
Glucosamine used for treatment of osteoporosis and prevent the degenerative collagen, has been found to consist anti-inflammatory properties through reduction of the expression of proinflammatory cytokines such as C-reactive protein (hsCRP), interleukin (IL)-1β, IL-6(177). The supplement also exhibited a significant reduction in pain intensity at movement and resting state, according to a Russian study(178).
Dr. Fishman SM suggested, administration of Glucosamine and chondroitin may be used for management of pain in patients of Fibromyalgia(179). In a total of 71.4% women, and 65.0% with annual incomes of less than 25,000 dollars.researchers at the University of New Mexico Health Sciences Center indicated a higher percentage use of alternative medicine including oral supplement glucosamine and chondroitin for treatment with with osteoarthritis, rheumatoid arthritis, or fibromyalgia(180). Furthermore, the study also showed that use of alternative medicine was significantly associated with female, under 55 years of age, and having some college education(180).
Dr. Parcell S said, " ...sulfur compounds such as SAMe, dimethylsulfoxide (DMSO), taurine, glucosamine or chondroitin sulfate, and reduced glutathione may also have clinical applications in the treatment of a number of conditions such as depression, fibromyalgia,....."(181).
2. DLPA (dl- phenylalanine)
DLPA, a mixture of D-Phenylalanine and L-Phenylalanine, is a nutritional supplement amino acid. Taltirelin, a thyrotropin-releasing hormone analog, showed effectively to relieve inflammatory persistent pain through iots antiallodynic action(182).
Dr. Bai Y and colleagues at the China Medical University, 4-Chloro-DL-phenylalanine, a derivative of DLPA inhibited metalloproteinase (TIMP)-1 and TIMP-2 in in response to many cytokines and hormones , including inflammatory cytokines in reduced pulmonary vascular remodeling and lunginflammatio(183).
Dr. Ehrenpreis S. in the study of D-phenylalanine and other enkephalinase inhibitors, said, "
D-phenylalanine, is also anti-inflammatory. D-phenylalanine has proven to be beneficial in many human patients with chronic, intractable pain" and "... may alleviate other conditions associated with decreased endorphin levels such as opiate withdrawal symptoms"(184).
3. Methylsulfonylmethane
Methylsulfonylmethane, also known DMSO2 is an organosulfur compound with the formula (CH3)2SO2 showed to exhibit anti inflammatory effects in attenuated production of mitochondrial reactive oxygen species (ROS)(185).
Methylsulfonylmethane, also known DMSO2 is an organosulfur compound with the formula (CH3)2SO2 showed to exhibit anti inflammatory effects in attenuated production of mitochondrial reactive oxygen species (ROS)(185).
In a randomized, double-blind, placebo-controlled trial of Fifty men and women, 40-76 years of age MSM (3g twice a day) improved symptoms of pain and physical function during the short intervention without major adverse events, after 12 weeks(186)(187).
According to the joint study led by the Kangwon National University, Methylsulfonylmethane (MSM) inhibited expression of NLRP3(plays a crucial role in innate immunity and inflammation) in attenuated production of mitochondrial reactive oxygen species (ROS) and pro inflammatory cytokines such as IL-1α, IL-1β, IL-6(188).
In support of the use of sulfur organic compound of Methylsulfonylmethane as clinical applications in the treatment of a number of conditions such as depression, fibromyalgia, arthritis, interstitial cystitis, athletic injuries, congestive heart failure, diabetes, cancer, and AIDS, Dr. Parcell S said, " Methylsulfonylmethane (MSM), a volatile component in the sulfur cycle, is another source of sulfur found in the human diet. Increases in serum sulfate may explain some of the therapeutic effects of MSM, DMSO, and glucosamine sulfate. ......MSM may be effective for the treatment of allergy, pain syndromes, athletic injuries, and bladder disorders"(181).
4. Coenzyme Q10
CoQ10 treatment restored mitochondrial dysfunction and the mtDNA copy number, decreased oxidative stress, and increased mitochondrial biogenesis. The results suggest that CoQ10 could be an alternative therapeutic approach for FM(189). According to the University of SevillaSevilla, CoQ10 inhibited depressive symptoms in fibromyalgia through regulation of serotonin levels(190).
Oral supplementation showed an improvement in clinical symptoms and restored salivary cells (SCs) and mononuclear blood cells (BMCs) levels, in a study of 10 patients with intaking of supplemented daily with 300 mg of CoQ(10) during 3 months(191).
Dr. Alcocer-Gómez E and colleagues at the University of Seville said, " After treatment, all patients showed an important improvement in clinical symptoms in all evaluation methods. According to our results, and evaluated by three methods, patients with FM are candidates for treatment with CoQ10"(192).
The Treatment
In conventional medicine perspective
FM usually involves females, particular to women entering stage of menopause. But it is often diagnosed both in young as well as elderly individuals. Diagnosis of pediatric FMS is a lengthy and frustrated condition affecting children and adolescents physical and emotional development, as the disease mimicked a spectrum of inflammatory joint disorders such as juvenile idiopathic arthritis (JIA), juvenile ankylosing spondylitis, etc, according to the study by Soroka Medical Center, Beer-Sheva(193)
A. Non medication
1. Psychological control
According to the study by Monash University and Monash Medical Centre, psychological control may play an important role in manage the emotional aspects and mood, stress, fatigue, and pain in patient with FM(194).
In conventional medicine perspective
FM usually involves females, particular to women entering stage of menopause. But it is often diagnosed both in young as well as elderly individuals. Diagnosis of pediatric FMS is a lengthy and frustrated condition affecting children and adolescents physical and emotional development, as the disease mimicked a spectrum of inflammatory joint disorders such as juvenile idiopathic arthritis (JIA), juvenile ankylosing spondylitis, etc, according to the study by Soroka Medical Center, Beer-Sheva(193)
A. Non medication
1. Psychological control
According to the study by Monash University and Monash Medical Centre, psychological control may play an important role in manage the emotional aspects and mood, stress, fatigue, and pain in patient with FM(194).
The Systematic review of psychological treatment in patients with FM, with a literature search of studies published between 1990 and 2012 using Medline and PsycINFO in the Ovid and ProQuest platforms and hand searching, indicated a description of the interventions developed by using psychological control and treatment in order to improve FM symptoms(195).
In FM pain control in comparison to other therapies, Dr. Thieme K and Dr. Gracely RH. said, "Relaxation as a single treatment has not been proven useful. Hypnotherapy and writing intervention have demonstrated mild treatment effects, whereas psychological treatment is effective in FM pain"(196).
2. Cognitive-behavioral and operant-behavioral therapy
Operant behavioural (OBT) and cognitive behavioural (CBT) therapies may also applied for
treatment of fibromyalgia syndrome (FMS). According to the University of Heidelberg, Central Institute of Mental Health, Operant behavioural (OBT) and cognitive behavioural (CBT) therapies reduced physical functioning, pain, affective distress, and cognitive and behavioural variables after 6 and 12 months treatment in patient with. Fibromyalgia(198).
Dr. Bernardy K and research team at the Ruhr University Bochum, said, " Cognitive behavioural therapies provided a small incremental benefit over control interventions in reducing pain, negative mood and disability at the end of treatment and at long-term follow-up"(199).
In a total of 125 patients fulfilled the American College of Rheumatology FMS criteria randomly assigned to CBT (n = 42), OBT (n = 43), or attention placebo (AP; n = 40), cognitive-behavioral therapy (CBT) and operant-behavioral therapy (OBT treatment expressed a clinically significant improvements in physical impairment. attenuated higher levels of affective distress, lower coping, less solicitous spouse behavior, and lower pain behaviors in FM patients(200).
3. Exercise
Exercise is an effective treatment strategy for treatment of various chronic musculoskeletal pain disorders, including chronic neck pain, osteoarthritis, headache, fibromyalgia and chronic low back pain. But the therapy may be individually tailored with emphasis on prevention of symptom flares, (201).
The review of data base of literature from inception to October 2013 showed that aquatic training is beneficial for improving wellness, symptoms, and fitness in adults with fibromyalgia, except in muscle strength (very low quality evidence favoring land)(202).
On resistance exercise training, moderate- and moderate- exercise may improve multidimensional function, pain, tenderness, and muscle strength in women with fibromyalgia, the University of Saskatchewan study insisted(203).
Swimming, like walking, is an effective method for reducing pain and improving both functional capacity and quality of life in patients with FM(204).
Nordic walking twice a week for 15 weeks improved functional capacity and a decreased level of activity limitations except pain severity(205).
The result of moderated exercise in reduced symptoms of fibromyalgia probably is a result in decreasing their sensitivity to pain, via improving the functional capacity of the pain modulatory system in central nervous system(206).
4. Physical therapy
Epidemiological studies suggested, physiotherapy may reduce overloading of the muscle system, improve postural fatigue and positioning, and condition weak muscles and reduce localized as well as generalized pain in short term(207). When use conjunction with Mind and body therapy, physiotherapy may improve the effectiveness of improving physical functioning, pain and low mood for adults with fibromyalgia(208).
4. Physical therapy
Epidemiological studies suggested, physiotherapy may reduce overloading of the muscle system, improve postural fatigue and positioning, and condition weak muscles and reduce localized as well as generalized pain in short term(207). When use conjunction with Mind and body therapy, physiotherapy may improve the effectiveness of improving physical functioning, pain and low mood for adults with fibromyalgia(208).
In discussion of the treatment of physiotherapy, Dr. Winkelmann A and research team at the Klinikum der Universität München, insisted, "physical therapy with Low-to-moderate intensity aerobic exercise and strength training are strongly recommended"(209).
In deed, "the multimodal programme, (including those of above) incorporating deep water running (DWR) is a safe and effective intervention for fibromyalgia syndrome that is acceptable to patients" Dr. Cuesta-Vargas AI Dr. Adams N. said(210).
A.2. Medications
The aim of medicine is to relieve the symptoms of the disease
In a narrative review by the Indiana University School of Medicine, from meta-analyses and systematic reviews published since 2005. For a few medications, findings from multiple recent trials are synthesized if a systematic review had not yet been published. Classes of medications are first reviewed, include(211).
1. Simple analgesics(acetaminophen or nonsteroidal anti-inflammatory drugs)
The objective of analgesics is to reduce pain for patient with Fibromyalgia through their effects on the peripheral and central nervous system.
According to the National Cheng Kung University, R-Duloxetine and N-Methyl Duloxetine, the Novel Analgesics effectively alleviates intractable pain associated with diabetic peripheral neuropathy and fibromyalgia(212).
In a randomised, double-blind studies of eight weeks' duration or longer, comparing milnacipran with placebo or another active treatment in fibromyalgia in adults suggested, "Evidence available indicates that milnacipran 100 mg or 200 mg is effective for a minority in the treatment of pain due to fibromyalgia, providing moderate levels of pain relief (at least 30%) to about 40% of participants, compared with about 30% with placebo"(213).
Most common adverse effects, according to share care include allergic(hoarseness, swelling, difficulty breathing, hives, itching, and rash) gastrointestinal(stomach upset,constipation, diarrhea) symptoms and dizziness, or headache(214)
2. Tricyclic antidepressants (if neuropathic, back or fibromyalgia pain) or tramadol;
Fibromyalgia pain due to psychological syndrome may be treated with ricyclic antidepressants, a synthetic version of antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and norepinephrine reuptake inhibitors (NRIs) through by blocking the serotonin transporter (SERT) and the norepinephrine transporter (NET)(215). The medication through clinical expression have shown effectively for major treatment and management of fibromyalgia and other chronic pain syndromes(216).
Fibromyalgia pain due to psychological syndrome may be treated with ricyclic antidepressants, a synthetic version of antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and norepinephrine reuptake inhibitors (NRIs) through by blocking the serotonin transporter (SERT) and the norepinephrine transporter (NET)(215). The medication through clinical expression have shown effectively for major treatment and management of fibromyalgia and other chronic pain syndromes(216).
. Dr. Lawson K said, "Tricyclic antidepressants are the most effective drugs in use so far, especially when administered in combination with other therapies (e.g., selective serotonin re-uptake inhibitors), which suggests modulation of the neurotransmitters serotonin and noradrenaline"(215).
Duloxetine, in 2 randomized, placebo-controlled, double-blind, parallel-group, 12-week trials of duloxetine in the treatment of fibromyalgia, has been shown to be an effective and safe treatment for attenuation of symptoms associated with fibromyalgia, particularly for women(217).
Duloxetine, in 2 randomized, placebo-controlled, double-blind, parallel-group, 12-week trials of duloxetine in the treatment of fibromyalgia, has been shown to be an effective and safe treatment for attenuation of symptoms associated with fibromyalgia, particularly for women(217).
Most Common side effects, according to the Mayo Clinic, may include Dry mouth. Blurred vision. Constipation. Urinary retention. Drowsiness. Increased appetite leading to weight gain. .....(218)
3. Gabapentin, duloxetine or pregabalin if neuropathic pain
Neuropathic pain is a improper healing of injure tissue causing nerve fiber damage in sending uncorrected information to other pain centers, medication used for treatment of neuropathic pain of patient with fibromyalgia may include Gabapentin, duloxetine or pregabalin.
3. Gabapentin, duloxetine or pregabalin if neuropathic pain
Neuropathic pain is a improper healing of injure tissue causing nerve fiber damage in sending uncorrected information to other pain centers, medication used for treatment of neuropathic pain of patient with fibromyalgia may include Gabapentin, duloxetine or pregabalin.
According to the Aristotle University of Thessaloniki, in the review of data base of research literature suggested, pregabalin (PB) at a dose of 450 mg per day is most likely effective in treating FBM, although AE are not negligible(219). Other study suggested gabapentin at doses of 1200 mg or more was effective for some people with some painful neuropathic pain conditions(220), including fibromyalgia.
The most common side effects of above medicine used for treatment of neuropathic pain include bot not limit to Dizziness, drowsiness, dry mouth, edema (accumulation of fluid), blurred vision, double vision (diplopia), weight gain, fatigue (tiredness), tremor and difficulty concentrating,... according to medicine net(221).
4. Other oral administration medicines
4.1. Cyclobenzaprine
Cyclobenzaprine is muscle relaxant used to relieve chronic fibromyalgia pain, by blocking nerve impulses sending pain sesation to your brain. According to the Laval University, the medication is highly effective in reduced chronic pain a short term in patients with fibromyalgia(222), probably through induced sleep physiology and symptoms of fibromyalgia(223).
According to drug.com the side effects are mot limit to, headache, dizziness; drowsiness, tired feeling; trouble concentrating; blurred vision, dry mouth or throat, altered sense of taste; or. nausea, upset stomach, constipation(224).
4.2. Pregabalin(see above)
4.3. Duloxetine See above
4.4 Milnacipran
Milnacipran is a serotonin–norepinephrine reuptake inhibitor used in the clinical treatment of fibromyalgia, ysed for treatment of Fibromyalgia depending to expression of key sumptoms Accoridng to the Klinikum Saarbrücken(225).
According to LX list the side effects of the medicine are not limit to, nausea, vomiting, upset stomach, bloating, dry mouth, constipation, loss of appetite, dizziness, drowsiness, tired feeling, increased sweating, headache, hot flashes (flushing),....(227).
5. Topical analgesics(capsaicin, lidocaine, salicylates) if localized neuropathic or arthritic pain
Topical analgesics, such as formulated creams, gels, and patches are applied locally to the skin and influence for treatment of Fibromyalgia's pain(228)
In a double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia involved 102 patients, indicate that LAC may be of benefit in patients with FMS, as it induced statistically significant in ameliorated depression and musculo-skeletal pain(241).
4. S-adenosylmethionine
S-adenosylmethionine, found in almost every tissue and fluid in the body, plays an essential role involved many processes of the body, including the immune system, cell membranes, etc.....
S-adenosylmethionine may be used for treatment of symptoms of pain in patient with fibromyalgia.
Dr. Fetrow CW Dr. Avila JR insited, despite of several reviews and at least two meta-analyses agreed with efficacy as available evidence surrounding SAMe in the therapy of depression as SAMe was superior to placebo in treating depressive disorders in comparison to standard tricyclic antidepressant,as the risk profile of the supplement has not been assessed(243).
According to the Ahi Evran University, massage therapy significant improved pain intensity, pain pressure threshold in comparison of manual lymph drainage therapy(244).
In a system review conduced by Dr. Li YH and colleagues at the Liaocheng People's Hospital, 5 weeks and plus massage therapy showed an beneficial immediate effects on improving pain, anxiety, and depression in patients with FM, but large-scale randomized controlled trials with long follow-up are necessary to confirm the current findings(245).
A single session of muscle-biased therapy, using Cumulative Index to Nursing and Allied Health Literature (CINAHL) and MEDLINE from the inception of each database until July 2012, MBT was found effectively in reduced pressure pain thresholds in comparison to no-treatment and sham/inert groups and induced same effects comparable with those of other active treatments, according to the reports from 24 randomized controlled trials (23 articles) were included, representing 36 MBT treatment arms and 29 comparative groups(246).
Dr. Merchant RE and colleagues at the Medical College of Virginia Richmond also support the use of chlorella to relieve the symptoms of fibromyalgia in some patients, but suggested a larger, more comprehensive double-blind, placebo-controlled clinical trial in these patients is necessary(250).
7. Biofeedback
According to the University of Maryland Medical Center, Biofeedback plays an important role to improve health of patients with Fibromyalgia through controlling certain bodily process involved heart rate, blood pressure, muscle tension, and skin temperature. The therapy has gained some traction in complementary and alternative medicine for treatment among individuals with fibromyalgia syndrome (FMS)(248).
According to a randomized controlled trial involving two groups of FMS patients, biofeedback treatment modality reduced pain in patients with FMS, induced improvements in FIQ, SMWT and the number of tender points(251).Dr, Hassett AL and colleagues at the Robert Wood Johnson Medical School (UMDNJ-RWJMS in support of the use of biofeedback for treatment of patients with FM, suggested that the effectiveness of the therapy probably is the result of mediated by autonomic changes in stress, HPA axis activity, and brain function(252).
Unfortunately, a literature search conducted by the University of Marburg, revealed that only electromyographic(EMG) biofeedback and not Electroencephalograph (EEG) feedback significantly reduced pain intensity in comparison to control groups. BFB did not reduce sleep problems, depression, fatigue, or health-related quality of life in comparison to a control group(253).
8. Relaxation
Relaxation therapy, used in many cultures for reduced stress, eliminated body and mind tension for the body to heal itself against the development and for treatment of some diseases, such as Yoga, Tai Chi and meditation, etc,... According to the University Psychiatric Outpatient Clinic, relaxation therapy can be effective in treating fibromyalgia patients, especially if applied early.(255).
In deed, Psychological interventions therapies may be effective in improving physical functioning, pain and low mood for adults with fibromyalgia but relaxation therapies remains unclear as the quality of the evidence was very low or low(256).
8. Magnet therapies
Magnet therapies are the Use of magnetic fields for treatment of medical conditions in alternative medicine. According to the University of Virginia Health System, magnetic fields treatment of fibromyalgia showed improvements in functional status, pain intensity level, tender point count, and tender point intensity after 6 months(257).
Unfortunately, the average methodological quality of the identified studies was fairly low, according to the computerized search of databases from 1990 (year of publication of the ACR criteria for fibromyalgia) to July 2007 (258). A large sample size and multi center studies are necessary to validate it effect.
1. Ginkgo biloba
Ginkgo biloba is oldest living tree species, genus Ginkgo, belongings to the family Ginkgoaceae, native to China, from temperate zone to subtropical zone and some parts of north America. It Has been used in traditional herbal medicine in treating impotence, memory loss,respiratory diseases, circulatory disorders and deafness as well as preventing drunkenness, and bedwetting.
According to the Klinik für Rheumatologie, Topically applied capsaicin (CAS 404-86-4) may be used for treatment of chronic pain through induced the release of neurotransmitter in production of substance P and blockade of transport and de-novo synthesis of substance in patients with neuropathic pain or musculoskeletal disorders, with or without inflammatory components(265).
2. Cupping therapy
Cupping therapy is an ancient form of alternative medicine in which a local skin suction is used to induce blood flow through median for treatment of diseases due to blood blockage. According to the Beijing University of Chinese Medicine, cupping therapy in a follow-up period of 12 weeks improved both qualitatively (patient expectation and satisfaction) and quantitatively (pain intensity, quality of life, depression assessment) in patient with Fibromyalgia when used combination with accupuncture(271) with the effective rate of 15.9% (10/63) in the group B and 16.1% (9/56) respectively in patient with or without intake of TCM medicine(272).
5. Topical analgesics(capsaicin, lidocaine, salicylates) if localized neuropathic or arthritic pain
Topical analgesics, such as formulated creams, gels, and patches are applied locally to the skin and influence for treatment of Fibromyalgia's pain(228)
Most common side effects are skin irritation
6. Opioids
Opioids is an opiumlike compound binded to one or more of the three opioid receptors of the body for pain relief, including hydrocodone (e.g., Vicodin), oxycodone (e.g., OxyContin, Percocet). According to Dr. Ngian GS and research team at the Monash Medical Centre, suggested the medicine have a significant adverse effect profile, their inefficacy may be due to their inability to target the pathophysiologic processes involved in this central sensitization syndrome in patients with FM(229).
6. Opioids
Opioids is an opiumlike compound binded to one or more of the three opioid receptors of the body for pain relief, including hydrocodone (e.g., Vicodin), oxycodone (e.g., OxyContin, Percocet). According to Dr. Ngian GS and research team at the Monash Medical Centre, suggested the medicine have a significant adverse effect profile, their inefficacy may be due to their inability to target the pathophysiologic processes involved in this central sensitization syndrome in patients with FM(229).
The common side effects of Opioids are not limit to sedation,dizziness, nausea, vomiting, constipation, physical dependence, tolerance, and respiratory depression,./... according to the Millennium Pain Center, Bloomington(230).
In a randomised controlled multicentre trial, blinded to participants and to data analysts of a total of 164 participants aged over 17 years and diagnosed with fibromyalgia, patients with acupuncture treatment in primary care with fibromyalgia showed almelioration of pain with effect persisted at 1 year, and its side effects were mild and infrequent(235).
In a study of 60 premenopausal women diagnosed with fibromyalgia according to the ACR criteria and 20 healthy women, also suggested that low magnesium levels in the erythrocyte might be an etiologic factor on fibromyalgia symptoms, as the combined amitriptyline + magnesium citrate treatment significantly improved over all parameters except numbness(238).
B. Alternative treatments
Several types of alternative medicine have some potential for future clinical research. However, due to methodological inconsistencies across studies and the small body of evidence, no firm conclusions can be made at this time. we present here some of alternatives which have played an important role in human history for treatment of Fibromyalgia, according to the DePaul University(231) and Dicle University(232), in review of information regarding the efficacy of complementary and alternative medicine (CAM).
1. Acupuncture
Altering gaining Acceptance of the Western medication, acupuncture one of the most oldest form of traditional Chinese medicine technique has been used to treat vary form of diseases in including
chronic pain such as Fibromyalgia with or without homeopathic involvement. the recent study suggested that individually tailored acupuncture significantly lessens pain intensity in people with the chronic condition fibromyalgia(233).
Several types of alternative medicine have some potential for future clinical research. However, due to methodological inconsistencies across studies and the small body of evidence, no firm conclusions can be made at this time. we present here some of alternatives which have played an important role in human history for treatment of Fibromyalgia, according to the DePaul University(231) and Dicle University(232), in review of information regarding the efficacy of complementary and alternative medicine (CAM).
1. Acupuncture
Altering gaining Acceptance of the Western medication, acupuncture one of the most oldest form of traditional Chinese medicine technique has been used to treat vary form of diseases in including
chronic pain such as Fibromyalgia with or without homeopathic involvement. the recent study suggested that individually tailored acupuncture significantly lessens pain intensity in people with the chronic condition fibromyalgia(233).
In a randomised controlled multicentre trial, blinded to participants and to data analysts of a total of 164 participants aged over 17 years and diagnosed with fibromyalgia, patients with acupuncture treatment in primary care with fibromyalgia showed almelioration of pain with effect persisted at 1 year, and its side effects were mild and infrequent(235).
In support of using acupuncture for treatment of Fibromyalgia, Dr. Taw LB Dr. Henry E. said, "combination of trigger point injections and acupuncture provides improved clinical outcomes" in comparison of treatment with only acupuncture(236)But, according to the RMIT University, acupuncture improved pain and stiffness in people with fibromyalgia with only low to moderate-level evidence in comparison to no treatment and other standard therapy(234)
2. Magnesium therapy
Magnesium therapy or Transdermal magnesium therapy is one of easy, convenient, and affordable form of alternative medicine used of topical or oral administration magnesium for treatment of Fibromyalgia. According to the Centre Hospitalier de Toulon, slight lower levels of magnesium is found in patients with Fibromyalgia(237).
2. Magnesium therapy
Magnesium therapy or Transdermal magnesium therapy is one of easy, convenient, and affordable form of alternative medicine used of topical or oral administration magnesium for treatment of Fibromyalgia. According to the Centre Hospitalier de Toulon, slight lower levels of magnesium is found in patients with Fibromyalgia(237).
But in the study of the relationship between serum antioxidant vitamins, magnesium levels, and clinical parameters in patients with primary fibromyalgia syndrome, Dr. Sakarya ST and researchers at the Ondokuz Mayis University said, " ....other complex mechanism may play an important role in the pathophysiology of FM" other than plasma antioxidant vitamins and Mg levels(239).
3. L-carnitine
Involved in lipid metabolism, L-carnitine may be used for treatment as an althernative medicne for treatment of Fibromyalgia's symptoms. According to the, Acetyl-L-carnitine, a synthic form of L-carnitine attenuated depressive symptoms, pain, and improved the quality of life of FMS patients in comparison with the efficacy of duloxetine(240).
Involved in lipid metabolism, L-carnitine may be used for treatment as an althernative medicne for treatment of Fibromyalgia's symptoms. According to the, Acetyl-L-carnitine, a synthic form of L-carnitine attenuated depressive symptoms, pain, and improved the quality of life of FMS patients in comparison with the efficacy of duloxetine(240).
In a double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia involved 102 patients, indicate that LAC may be of benefit in patients with FMS, as it induced statistically significant in ameliorated depression and musculo-skeletal pain(241).
4. S-adenosylmethionine
S-adenosylmethionine, found in almost every tissue and fluid in the body, plays an essential role involved many processes of the body, including the immune system, cell membranes, etc.....
S-adenosylmethionine may be used for treatment of symptoms of pain in patient with fibromyalgia.
Dr. De Silva V and colleagues at theUniversity of Aberdeen, said, "...., S-adenosylmethionine each showed at least one statistically significant improved outcome compared with placebo" in the study of the management of fibromyalgia(242).
5. Massage therapy
Massage therapy is a technique manipulated to stimulate the function of soft tissues, including muscle, connective tissue, tendons and ligaments. As a stand-alone treatment, it reduces pain and improves function and some musculoskeletal conditions, particular in a short term benefit(247).
Massage therapy is a technique manipulated to stimulate the function of soft tissues, including muscle, connective tissue, tendons and ligaments. As a stand-alone treatment, it reduces pain and improves function and some musculoskeletal conditions, particular in a short term benefit(247).
According to the Ahi Evran University, massage therapy significant improved pain intensity, pain pressure threshold in comparison of manual lymph drainage therapy(244).
In a system review conduced by Dr. Li YH and colleagues at the Liaocheng People's Hospital, 5 weeks and plus massage therapy showed an beneficial immediate effects on improving pain, anxiety, and depression in patients with FM, but large-scale randomized controlled trials with long follow-up are necessary to confirm the current findings(245).
A single session of muscle-biased therapy, using Cumulative Index to Nursing and Allied Health Literature (CINAHL) and MEDLINE from the inception of each database until July 2012, MBT was found effectively in reduced pressure pain thresholds in comparison to no-treatment and sham/inert groups and induced same effects comparable with those of other active treatments, according to the reports from 24 randomized controlled trials (23 articles) were included, representing 36 MBT treatment arms and 29 comparative groups(246).
6. Chlorella
A common single-celled green alga of both terrestrial and aquatic habitats has been explored for commercial profits due to its health effects. According to webMD, the benefit of chlorella products can vary significantly depending geographic cultivation, time to harvest and process.
The supplement has been used in complementary and alternative medicine for treatment among individuals with fibromyalgia syndrome (FMS)( 248).
A common single-celled green alga of both terrestrial and aquatic habitats has been explored for commercial profits due to its health effects. According to webMD, the benefit of chlorella products can vary significantly depending geographic cultivation, time to harvest and process.
The supplement has been used in complementary and alternative medicine for treatment among individuals with fibromyalgia syndrome (FMS)( 248).
According to the study of 55 subjects with fibromyalgia, 33 with hypertension, and 9 with ulcerative colitis, conducted by Virginia Commonwealth University's Medical College of Virginia, dietray supplement of chlorella not only reduced high blood pressure, lowered serum cholesterol levels, accelerated wound healing, and enhanced immune functions, but also relieved symptoms, improved quality of life, and normalized body functions in patients with fibromyalgia(249).
7. Biofeedback
According to the University of Maryland Medical Center, Biofeedback plays an important role to improve health of patients with Fibromyalgia through controlling certain bodily process involved heart rate, blood pressure, muscle tension, and skin temperature. The therapy has gained some traction in complementary and alternative medicine for treatment among individuals with fibromyalgia syndrome (FMS)(248).
According to a randomized controlled trial involving two groups of FMS patients, biofeedback treatment modality reduced pain in patients with FMS, induced improvements in FIQ, SMWT and the number of tender points(251).Dr, Hassett AL and colleagues at the Robert Wood Johnson Medical School (UMDNJ-RWJMS in support of the use of biofeedback for treatment of patients with FM, suggested that the effectiveness of the therapy probably is the result of mediated by autonomic changes in stress, HPA axis activity, and brain function(252).
8. Relaxation
Relaxation therapy, used in many cultures for reduced stress, eliminated body and mind tension for the body to heal itself against the development and for treatment of some diseases, such as Yoga, Tai Chi and meditation, etc,... According to the University Psychiatric Outpatient Clinic, relaxation therapy can be effective in treating fibromyalgia patients, especially if applied early.(255).
Dr. Coppieters I. and colleagues at the Vrije Universiteit Brussel, said," Single relaxation session as well as cognitive stress may have negative acute effects on pain modulation in patients with FM, while cognitive stress and relaxation did not worsen bottom-up sensitization in chronic WAD patients and healthy persons"(254).
8. Magnet therapies
Magnet therapies are the Use of magnetic fields for treatment of medical conditions in alternative medicine. According to the University of Virginia Health System, magnetic fields treatment of fibromyalgia showed improvements in functional status, pain intensity level, tender point count, and tender point intensity after 6 months(257).
Unfortunately, the average methodological quality of the identified studies was fairly low, according to the computerized search of databases from 1990 (year of publication of the ACR criteria for fibromyalgia) to July 2007 (258). A large sample size and multi center studies are necessary to validate it effect.
C. In Herbal medicine perspective
In the survey of people of a total of 11,424 adults completed the survey in 2000-2001, according to the St. Joseph's Healthcare Hamilton,, over 23% of Canadian preferred the use of natural health products for treatment of Fibromyalgia(259) particular in female population in comparison to the male counterpart.
In the survey of people of a total of 11,424 adults completed the survey in 2000-2001, according to the St. Joseph's Healthcare Hamilton,, over 23% of Canadian preferred the use of natural health products for treatment of Fibromyalgia(259) particular in female population in comparison to the male counterpart.
1. Ginkgo biloba
Ginkgo biloba is oldest living tree species, genus Ginkgo, belongings to the family Ginkgoaceae, native to China, from temperate zone to subtropical zone and some parts of north America. It Has been used in traditional herbal medicine in treating impotence, memory loss,respiratory diseases, circulatory disorders and deafness as well as preventing drunkenness, and bedwetting.
Dr. Lister RE said, "oral doses of 200 mg coenzyme Q10 and 200 mg Ginkgo biloba extract daily for 84 days, (showed) a progressive improvement in the quality-of-life scores was observed over the study period and at the end, the scores showed a significant difference from those at the start"(260) without interfering to the intake of warfarin(261).
2. Capsicum frutescens (Cayenne)
Cayenne is also known as Cayenne Pepper, a red, hot chili pepper, belonging to Capsicum annuum, the family Solanaceae, native to sub-tropical and tropical regions. It has been used in traditional medicine to increases metabolism, enhance circulatory system and stomach and the intestinal tract, adjust blood pressure, lower LDL cholesterol and triglycerides, treat frostbite, muscles, arthritis, rheumatism, low back pain, strains, sprains, bruises and neuralgia, etc.The effective of Cayenne in reduced pain in patients with fibromyalgia, probably due to its anti inflammatory activity(264).
2. Capsicum frutescens (Cayenne)
Cayenne is also known as Cayenne Pepper, a red, hot chili pepper, belonging to Capsicum annuum, the family Solanaceae, native to sub-tropical and tropical regions. It has been used in traditional medicine to increases metabolism, enhance circulatory system and stomach and the intestinal tract, adjust blood pressure, lower LDL cholesterol and triglycerides, treat frostbite, muscles, arthritis, rheumatism, low back pain, strains, sprains, bruises and neuralgia, etc.The effective of Cayenne in reduced pain in patients with fibromyalgia, probably due to its anti inflammatory activity(264).
According to the Klinik für Rheumatologie, Topically applied capsaicin (CAS 404-86-4) may be used for treatment of chronic pain through induced the release of neurotransmitter in production of substance P and blockade of transport and de-novo synthesis of substance in patients with neuropathic pain or musculoskeletal disorders, with or without inflammatory components(265).
3. Other herbal medicine: Harpagophytum procumbens (Devil’s claw), Salix alba (White willow bark), and
Harpagophytum procumbens (Devil’s claw), Salix alba (White willow bark), according to the Systematic review of randomized controlled trials (RCTs) reduced chronic pain inpatient with lower back pain(262).
Harpagophytum procumbens (Devil’s claw), Salix alba (White willow bark), according to the Systematic review of randomized controlled trials (RCTs) reduced chronic pain inpatient with lower back pain(262).
The University of Michigan study in the review of databases up to September 2014: MEDLINE, EMBASE, CENTRAL, CINAHL, Clinical Trials.gov, suggested that Harpagophytum procumbens (Devil’s claw), Salix alba (White willow bark) also reduced more pain than placbo(263).
D. In traditional Chinese medicine perspective
1. Acupuncture
Acupuncture in the absence of other treatment improved pain and stiffness in people with fibromyalgia according to the School of Health Sciences, RMIT University(266). Dr. Martin DP and research team at the Mayo Clinic College of Medicine said, "acupuncture significantly improved symptoms of fibromyalgia. Symptomatic improvement was not restricted to pain relief and was most significant for fatigue and anxiety"(267), through stimulation of certain acupoint of a median, according to TCM differentiation(268).
1. Acupuncture
Acupuncture in the absence of other treatment improved pain and stiffness in people with fibromyalgia according to the School of Health Sciences, RMIT University(266). Dr. Martin DP and research team at the Mayo Clinic College of Medicine said, "acupuncture significantly improved symptoms of fibromyalgia. Symptomatic improvement was not restricted to pain relief and was most significant for fatigue and anxiety"(267), through stimulation of certain acupoint of a median, according to TCM differentiation(268).
In the review of Twenty-five RCTs with 1516 participants, traditional Chinese Medicine (TCM), ccupuncture treatment in patients with Fibromyalgia reduced the number of tender points and and pain scores compared with conventional medications(269).
Due its efficacy, acupuncture is recommended to be used for treatment in relief pain in primary care of patients with fibromyalgia in short term of 1 yea(270).
Cupping therapy is an ancient form of alternative medicine in which a local skin suction is used to induce blood flow through median for treatment of diseases due to blood blockage. According to the Beijing University of Chinese Medicine, cupping therapy in a follow-up period of 12 weeks improved both qualitatively (patient expectation and satisfaction) and quantitatively (pain intensity, quality of life, depression assessment) in patient with Fibromyalgia when used combination with accupuncture(271) with the effective rate of 15.9% (10/63) in the group B and 16.1% (9/56) respectively in patient with or without intake of TCM medicine(272).
Furthermore, a combination of acupuncture and cupping therapy was better than conventional medications for reducing pain and for improving depression scores with related to FM(274).
3. Qigong
The manifestation of movement of qi in the body is considered as one of the oldest Chinese ancient technique used as a mindful exercise, or complementary exercise for treatment of symptoms in fibromyalgia. According to Dr. Sawynok J and Dr. Lynch M, regular qigong practice (daily, 6-8 weeks) produces improvements in core domains for fibromyalgia (pain, sleep, impact, and physical and mental function)(275).
In a randomized controlled trial, qigong showed a significant impact of pain, impact, sleep, physical function and mental function in patient with FM(276).
Dr. Sawynok J and Dr. Lynch M, Marcon D. said, "A highly motivated subgroup of N = 5, who practiced the most, had the best outcomes in terms of end symptomology, and qualitative comments indicated health benefits in other domains as well" and " This extension trial indicates that diligent CFQ practice over time produces significant health gains in fibromyalgia in a subset of individuals"(277).
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(28) Fibromyalgia and major affective disorder: a controlled phenomenology and family history study by Hudson JI, Hudson MS, Pliner LF, Goldenberg DL, Pope HG Jr.(PubMed)
(29) Sleep disorders and fibromyalgia. by Roizenblatt S1, Neto NS, Tufik S.(PubMed)
(30) Vulnerability to traumatic stress in fibromyalgia patients: 19 month follow-up after the great East Japan disaster by Usui C, Hatta K, Aratani S, Yagishita N, Nishioka K, Okamura S, Itoh K, Yamano Y, Nakamura H, Asukai N, Nakajima T, Nishioka K.(PubMed)
(31) Chronic illness -- a disruption in life: identity-transformation among women with chronic fatigue syndrome andfibromyalgia by Asbring P1.(PubMed)
(32) Is chronic fatigue syndrome the same illness as fibromyalgia: evaluating the 'single syndrome' hypothesis by Abbi B1, Natelson BH.(PubMed)
(33) Prevalence and characteristics of fibromyalgia among HIV-positive patients in southern Israel. by Dotan I1, Riesenberg K2, Toledano R2, Schlaeffer F2, Smolyakov A2, Saidel-Odes L2, Wechsberg O1, Ablin JN3, Novack V1, Buskila D1.(PubMed)
(34) Rheumatic manifestations of hepatitis C virus chronic infection: Indications for a correct diagnosis by Palazzi C1, D'Amico E1, D'Angelo S1, Gilio M1, Olivieri I1.(PubMed)
(35) Chronic widespread pain and fibromyalgia: could there be some relationships with infections and vaccinations? by Cassisi G1, Sarzi-Puttini P, Cazzola M.(PubMed)
(36) The evaluation of anxiety and depression status in spouses of sexually active reproductive women withfibromyalgia by Yener M1, Askin A1, Soyupek F1, Akpinar A2, Demirdas A2, Sonmez S3, Soyupek S3.(PubMed)
(37) Quality of life, depression, and sexual dysfunction in spouses of female patients with fibromyalgia by Tutoglu A1, Boyaci A, Koca I, Celen E, Korkmaz N.(PubMed)
(38) Psychological control is a key modulator of fibromyalgia symptoms and comorbidities. by Malin K1, Littlejohn GO.(PubMed)
(39) Stress perception and depressive symptoms: functionality and impact on the quality of life of women withfibromyalgia.[Article in English, Portuguese] by Homann D1, Stefanello JM, Góes SM, Breda CA, Paiva Edos S, Leite N.(PubMed)
(40) The evaluation of anxiety and depression status in spouses of sexually active reproductive women withfibromyalgia by Yener M1, Askin A1, Soyupek F1, Akpinar A2, Demirdas A2, Sonmez S3, Soyupek S3.(PubMed)
(41) Gender differences in pain severity, disability, depression, and widespread pressure pain sensitivity in patients with fibromyalgia syndrome without comorbid conditions by Castro-Sánchez AM1, Matarán-Peñarrocha GA, López-Rodríguez MM, Lara-Palomo IC, Arendt-Nielsen L, Fernández-de-las-Peñas C.(PubMed)
(42) Short-term effects of a manual therapy protocol on pain, physical function, quality of sleep, depressive symptoms, and pressure sensitivity in women and men with fibromyalgia syndrome: a randomized controlled trial by Castro-Sánchez AM1, Aguilar-Ferrándiz ME, Matarán-Peñarr, the ocha GA, Sánchez-Joya Mdel M, Arroyo-Morales M, Fernández-de-las-Peñas C.(PubMed).
(43) Disability in Fibromyalgia Associates with Symptom Severity and Occupation Characteristics by Fitzcharles MA1, Ste-Marie PA1, Rampakakis E1, Sampalis JS1, Shir Y1.(PubMed)
(44) Stress perception and depressive symptoms: functionality and impact on the quality of life of women withfibromyalgia.[Article in English, Portuguese] by Homann D1, Stefanello JM, Góes SM, Breda CA, Paiva Edos S, Leite N.(PubMed)
(45) Relationship between the body image and level of pain, functional status, severity of depression, and quality of life in patients with fibromyalgia syndrome by Akkaya N1, Akkaya S, Atalay NS, Balci CS, Sahin F.(PubMed)
(46) Measuring health status in Israeli patients with fibromyalgia syndrome and widespread pain and healthy individuals: utility of the short form 36-item health survey (SF-36) by Neumann L1, Berzak A, Buskila D.(PubMed)
(47) Assessment of the relationship between postural stability and sleep quality in patients with fibromyalgia by Akkaya N1, Akkaya S, Atalay NS, Acar M, Catalbas N, Sahin F.(PubMed)
(48) Postural control deficits in people with fibromyalgia: a pilot study by Jones KD1, King LA, Mist SD, Bennett RM, Horak FB.(PubMed)
(49) Fibromyalgia is associated with impaired balance and falls by Jones KD1, Horak FB, Winters-Stone K, Irvine JM, Bennett RM.(PubMed)
(50) Postural control deficits in people with fibromyalgia: a pilot study by Jones KD1, King LA, Mist SD, Bennett RM, Horak FB.(PubMed)
(51) [Is there an association between fibromyalgia and an increase in comorbidity: neoplastic and cardiovascular diseases, infections and mortality?] [Article in Spanish] by Chamizo-Carmona E1.(PubMed)
(52) Fibromyalgia frequency in hepatitis B carriers by Adak B1, Tekeoğlu I, Ediz L, Budancamanak M, Yazgan T, Karahocagil K, Demirel A.(PubMed)
(53) Rheumatic mimics and selected triggers of fibromyalgia by Daoud KF1, Barkhuizen A.(PubMed)
(54) Frequency of fibromyalgia syndrome in breast cancer patients by Akkaya N1, Atalay NS, Selcuk ST, Alkan H, Catalbas N, Sahin F.(PubMed)
(55) Increased cancer risk in patients referred to hospital with suspected fibromyalgia by Dreyer L1, Mellemkjaer L, Kendall S, Jensen B, Danneskiold-Samsøe B, Bliddal H.(PubMed)
(56) Increased Risk of Coronary Heart Disease in Patients with Primary Fibromyalgia and Those with Concomitant Comorbidity-A Taiwanese Population-Based Cohort Study by Su CH1, Chen JH2, Lan JL2, Wang YC3, Tseng CH4, Hsu CY5, Huang L6.(PubMed)
(57) Fibromyalgia is associated with coronary heart disease: a population-based cohort study by Tsai PS1, Fan YC, Huang CJ.(PubMed)
(58) Mortality in fibromyalgia: a study of 8,186 patients over thirty-five years by Wolfe F1, Hassett AL, Walitt B, Michaud K.(PubMed)
(59) Mortality in a cohort of Danish patients with fibromyalgia: increased frequency of suicide by Dreyer L1, Kendall S, Danneskiold-Samsøe B, Bartels EM, Bliddal H.(PubMed)
(60) Comorbidity of fibromyalgia and psychiatric disorders by Arnold LM1, Hudson JI, Keck PE, Auchenbach MB, Javaras KN, Hess EV.(PubMed)
(61) Comorbidity of fibromyalgia with medical and psychiatric disorders by Hudson JI1, Goldenberg DL, Pope HG Jr, Keck PE Jr, Schlesinger L.(PubMed)
(62) Fibromyalgia and other unexplained clinical conditions by Aaron LA1, Buchwald D.(PubMed)
(63) Classification and clinical diagnosis of fibromyalgia syndrome: recommendations of recent evidence-based interdisciplinary guidelines by Fitzcharles MA1, Shir Y2, Ablin JN3, Buskila D4, Amital H5, Henningsen P6, Häuser W7.(PubMed)
(64) Somatic symptom disorders without known physical causes: one disease with many names? by Tavel ME1.(PubMed)
(65) Systematic review of psychological treatment in fibromyalgia by Lami MJ1, Martínez MP, Sánchez AI.(PubMed)
(66) The American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia and Measurement of Symptom Severity by the Arthritis Care & Research
(67) Joint counts in inflammatory arthritis by Scott IC1, Scott DL.(PubMed)
(68) Previous pain experience in women with fibromyalgia and inflammatory arthritis and nonpainful controls by Pöyhiä R1, Da Costa D, Fitzcharles MA.(PubMed)
(69) Misdiagnosis in fibromyalgia: a multicentre study by Di Franco M1, Iannuccelli C, Bazzichi L, Atzeni F, Consensi A, Salaffi F, Pietropaolo M, Alessandri C, Basili S, Olivieri M, Bombardieri S, Valesini G, Sarzi-Puttini P.(PubMed)
(70) Chronic widespread pain in the spectrum of rheumatological diseases by Atzeni F1, Cazzola M, Benucci M, Di Franco M, Salaffi F, Sarzi-Puttini P.(PubMed)
(71) Misdiagnosis of serotonin syndrome as fibromyalgia and the role of physical therapists by Alnwick GM1.(PubMed)
(72) Misdiagnosis of chronic pain as hysterical by Shapiro AP1, Teasell RW2.(PubMed)
(73) A patient survey of the impact of fibromyalgia and the journey to diagnosis by Choy E1, Perrot S, Leon T, Kaplan J, Petersel D, Ginovker A, Kramer E.(PubMed)
(74) Survey of physician experiences and perceptions about the diagnosis and treatment of fibromyalgia by Perrot S1, Choy E, Petersel D, Ginovker A, Kramer E.(PubMed)
(75) A patient survey of the impact of fibromyalgia and the journey to diagnosis by Choy E1, Perrot S, Leon T, Kaplan J, Petersel D, Ginovker A, Kramer E.(PubMed)
(76) A patient and physician survey of fibromyalgia across Latin America and Europe by Clark P1, Paiva ES, Ginovker A, Salomón PA.(PubMed)
(77) The effect of weight loss and dietary fatty acids on inflammation by Devaraj S1, Kasim-Karakas S, Jialal I.(PubMed)
(78) Effects of the Dietary ω3:ω6 Fatty Acid Ratio on Body Fat and Inflammation in Zebrafish (Danio rerio). by Powell ML1, Pegues MA2, Szalai AJ2, Ghanta VK3, D'Abramo LR4, Watts SA3.(PubMed)
(79) ω3-polyunsaturated fatty acids suppress lipoprotein-associated phospholipase A2 expression in macrophages and animal models vt Li Z1, Ren W1, Han X1, Liu X1, Wang G1, Zhang M1, Pang D1, Ouyang H1, Tang X1.(PubMed)
(80) Overview of Omega-3 Fatty Acid Therapies by J. Chris Bradberry, PharmD and Daniel E. Hilleman, PharmD(PubMed)
(78) Effects of the Dietary ω3:ω6 Fatty Acid Ratio on Body Fat and Inflammation in Zebrafish (Danio rerio). by Powell ML1, Pegues MA2, Szalai AJ2, Ghanta VK3, D'Abramo LR4, Watts SA3.(PubMed)
(79) ω3-polyunsaturated fatty acids suppress lipoprotein-associated phospholipase A2 expression in macrophages and animal models vt Li Z1, Ren W1, Han X1, Liu X1, Wang G1, Zhang M1, Pang D1, Ouyang H1, Tang X1.(PubMed)
(80) Overview of Omega-3 Fatty Acid Therapies by J. Chris Bradberry, PharmD and Daniel E. Hilleman, PharmD(PubMed)
(81) Effect of omega-3 fatty acids in the management of fibromyalgia syndrome by Ozgocmen S, Catal SA, Ardicoglu O, Kamanli A.(PubMed)
(82) Current concepts in the pathophysiology of fibromyalgia: the potential role of oxidative stress and nitric oxide by Ozgocmen S1, Ozyurt H, Sogut S, Akyol O.(PubMed)
(83) Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function by Valdearcos M1, Robblee MM2, Benjamin DI3, Nomura DK3, Xu AW4, Koliwad SK5.(PubMed)
(84) Influence of dietary saturated fat content on adiposity, macrophage behavior, inflammation, and metabolism: composition matters by Enos RT1, Davis JM, Velázquez KT, McClellan JL, Day SD, Carnevale KA, Murphy EA.(PubMed)
(85) Effect of industrially produced trans fat on markers of systemic inflammation: evidence from a randomized trial in women by Bendsen NT1, Stender S, Szecsi PB, Pedersen SB, Basu S, Hellgren LI, Newman JW, Larsen TM, Haugaard SB, Astrup A.(PubMed)
(86) Health implications of high dietary omega-6 polyunsaturated Fatty acids by Patterson E1, Wall R, Fitzgerald GF, Ross RP, Stanton C.(PubMed)
(87) Low n-6/n-3 PUFA Ratio Improves Lipid Metabolism, Inflammation, Oxidative Stress and Endothelial Function in Rats Using Plant Oils as n-3 Fatty Acid Source by Yang LG1, Song ZX1,2, Yin H1,3, Wang YY1, Shu GF4, Lu HX4, Wang SK1, Sun GJ5.(PubMed)
(88) The inflammatory hypothesis of mood spectrum broadened to fibromyalgia and chronic fatigue syndrome by Dell'Osso L1, Bazzichi L2, Baroni S1, Falaschi V1, Conversano C1, Carmassi C1, Marazziti D1.(PubMed)
(89) Evidence of different mediators of central inflammation in dysfunctional and inflammatory pain--interleukin-8 infibromyalgia and interleukin-1 β in rheumatoid arthritis by Kosek E1, Altawil R2, Kadetoff D3, Finn A4, Westman M2, Le Maître E2, Andersson M5, Jensen-Urstad M6, Lampa J2.(PubMed)
(90) A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer by Williams CD1, Whitley BM, Hoyo C, Grant DJ, Iraggi JD, Newman KA, Gerber L, Taylor LA, McKeever MG, Freedland SJ.(PubMed)
(91) [Dietary fatty acids and colorectal and prostate cancers: epidemiological studies].[Article in French]by Astorg P1.(PubMed)
(92) Dietary (n-3)/(n-6) fatty acid ratio: possible relationship to premenopausal but not postmenopausal breast cancer risk in U.S. women by Goodstine SL1, Zheng T, Holford TR, Ward BA, Carter D, Owens PH, Mayne S.(PubMed)
(93) Fruit and vegetable consumption and its relation to markers of inflammation and oxidative stress in adolescents by Holt EM1, Steffen LM, Moran A, Basu S, Steinberger J, Ross JA, Hong CP, Sinaiko AR.(PubMed)
(94) Greater variety in fruit and vegetable intake is associated with lower inflammation in Puerto Rican adults. by Bhupathiraju SN1, Tucker KL.(PubMed)
(93) Fruit and vegetable consumption and its relation to markers of inflammation and oxidative stress in adolescents by Holt EM1, Steffen LM, Moran A, Basu S, Steinberger J, Ross JA, Hong CP, Sinaiko AR.(PubMed)
(94) Greater variety in fruit and vegetable intake is associated with lower inflammation in Puerto Rican adults. by Bhupathiraju SN1, Tucker KL.(PubMed)
(95) Antioxidants in vegan diet and rheumatic disorders by Hänninen1, Kaartinen K, Rauma AL, Nenonen M, Törrönen R, Häkkinen AS, Adlercreutz H, Laakso J.(PubMed)
(96) Cruciferous vegetable intake is inversely correlated with circulating levels of proinflammatory markers in women by Jiang Y, Wu SH, Shu XO, Xiang YB, Ji BT, Milne GL, Cai Q, Zhang X, Gao YT, Zheng W, Yang G.(PubMed)
(97) [Role of diet on chronic inflammation prevention and control - current evidences].[Article in Portuguese] by Geraldo JM1, Alfenas Rde C.(PubMed)
(98) The Impact of a Low Glycemic Index Diet on Inflammatory Markers and Serum Adiponectin Concentration in Adolescent Overweight and Obese Girls: A Randomized Clinical Trial by Rouhani MH1, Kelishadi R2, Hashemipour M3, Esmaillzadeh A1, Surkan PJ4, Keshavarz A5, Azadbakht L1.(PubMed)
(99) [Dietary factors and metabolic syndrome].[Article in Portuguese] by Steemburgo T1, Dall'Alba V, Gross JL, Azevedo MJ.(PubMed)
(100) A gut microbiota-targeted dietary intervention for amelioration of chronic inflammation underlying metabolicsyndrome by Xiao S1, Fei N, Pang X, Shen J, Wang L, Zhang B, Zhang M, Zhang X, Zhang C, Li M, Sun L, Xue Z, Wang J, Feng J, Yan F, Zhao N, Liu J, Long W, Zhao L.(PubMed)
(100) A gut microbiota-targeted dietary intervention for amelioration of chronic inflammation underlying metabolicsyndrome by Xiao S1, Fei N, Pang X, Shen J, Wang L, Zhang B, Zhang M, Zhang X, Zhang C, Li M, Sun L, Xue Z, Wang J, Feng J, Yan F, Zhao N, Liu J, Long W, Zhao L.(PubMed)
(101) The Perception of Female Smokers with Fibromyalgia on the Effects of Smoking on Fibromyalgia Symptoms by Weingarten TN1, Vincent A2, Luedtke CA3, Beebe TJ4, Welch TL1, Chong EY5, Schroeder DR4, Warner DO1.(PubMed)
(102) Associations Between Pain, Current Tobacco Smoking, Depression, and Fibromyalgia Status Among Treatment-Seeking Chronic Pain Patients by Goesling J1, Brummett CM1, Meraj TS2, Moser SE1, Hassett AL1, Ditre JW3.(PubMed)
(103) A Systematic Review of the Acute Effects of Exercise on Immune and Inflammatory Indices in Untrained Adults by Brown WM1, Davison GW1, McClean CM1, Murphy MH1.(PubMed)
(104) Fibromyalgia: anti-inflammatory and stress responses after acute moderate exercise by Bote ME1, Garcia JJ, Hinchado MD, Ortega E.(PubMed)
(105) An exploratory study of the effect of regular aquatic exercise on the function of neutrophils from women withfibromyalgia: role of IL-8 and noradrenaline by Bote ME1, García JJ1, Hinchado MD1, Ortega E2.(PubMed)
(106) Immunomodulatory Effects of Soybeans and Processed Soy Food Compounds by Tezuka H1, Imai S.(PubMed)
(107) Dietary soy supplement on fibromyalgia symptoms: a randomized, double-blind, placebo-controlled, early phase trial by Wahner-Roedler DL1, Thompson JM, Luedtke CA, King SM, Cha SS, Elkin PL, Bruce BK, Townsend CO, Bergeson JR, Eickhoff AL, Loehrer LL, Sood A, Bauer BA.(PubMed)
(108) Effect of soy nuts on adhesion molecules and markers of inflammation in hypertensive and normotensive postmenopausal women by Nasca MM1, Zhou JR, Welty FK.(PubMed)
(107) Dietary soy supplement on fibromyalgia symptoms: a randomized, double-blind, placebo-controlled, early phase trial by Wahner-Roedler DL1, Thompson JM, Luedtke CA, King SM, Cha SS, Elkin PL, Bruce BK, Townsend CO, Bergeson JR, Eickhoff AL, Loehrer LL, Sood A, Bauer BA.(PubMed)
(108) Effect of soy nuts on adhesion molecules and markers of inflammation in hypertensive and normotensive postmenopausal women by Nasca MM1, Zhou JR, Welty FK.(PubMed)
(109) Effect of soy isoflavones on circulating C-reactive protein in postmenopausal women: meta-analysis of randomized controlled trials by Dong JY1, Wang P, He K, Qin LQ.(PubMed)
(110) Use of complementary and alternative medical therapies by patients referred to a fibromyalgia treatment program at a tertiary care center by Wahner-Roedler DL1, Elkin PL, Vincent A, Thompson JM, Oh TH, Loehrer LL, Mandrekar JN, Bauer BA.(PubMed)
(111) Green tea polyphenols attenuate deterioration of bone microarchitecture in female rats with systemic chronicinflammation. by Shen CL1, Yeh JK, Samathanam C, Cao JJ, Stoecker BJ, Dagda RY, Chyu MC, Dunn DM, Wang JS.(PubMed)
(112) Evaluation of the anti-inflammatory and analgesic effects of green tea (Camellia sinensis) in mice by Mota MA1, Landim JS1, Targino TS1, Silva SF1, Silva SL1, Pereira MR1(PubMed)
(113) Immunomodulatory effects of decaffeinated green tea (Camellia sinensis) on the immune system of rainbow trout (Oncorhynchus mykiss). by Sheikhzadeh N1, Nofouzi K, Delazar A, Oushani AK.(PubMed)
(113a) Treatment of fibromyalgia (fibrositis syndrome): a parallel double blind trial with carisoprodol, paracetamol and caffeine (Somadril comp) versus placebo by Vaerøy H1, Abrahamsen A, Førre O, Kåss E.(PubMed)
(114) Anti-inflammatory and joint protective effects of extra-virgin olive-oil polyphenol extract in experimental arthritis by Rosillo MÁ1, Alcaraz MJ2, Sánchez-Hidalgo M1, Fernández-Bolaños JG3, Alarcón-de-la-Lastra C1, Ferrándiz ML4.(PubMed)
(115) Antinociceptive and anti-inflammatory effects of olive oil (Olea europeae L.) in mice. by Eidi A1, Moghadam-kia S, Moghadam JZ, Eidi M, Rezazadeh S.(PubMed)
(116) Chemistry and health of olive oil phenolics by Cicerale S1, Conlan XA, Sinclair AJ, Keast RS.(PubMed)
(115) Antinociceptive and anti-inflammatory effects of olive oil (Olea europeae L.) in mice. by Eidi A1, Moghadam-kia S, Moghadam JZ, Eidi M, Rezazadeh S.(PubMed)
(116) Chemistry and health of olive oil phenolics by Cicerale S1, Conlan XA, Sinclair AJ, Keast RS.(PubMed)
(117) Omega-3 fatty acids for neuropathic pain: case series by Ko GD1, Nowacki NB, Arseneau L, Eitel M, Hum A.(PubMed)
(118) Effect of omega-3 fatty acids in the management of fibromyalgia syndrome by Ozgocmen S, Catal SA, Ardicoglu O, Kamanli A.(PubMed)
(119) Antioxidant status, lipid peroxidation and nitric oxide in fibromyalgia: etiologic and therapeutic concerns by Ozgocmen S1, Ozyurt H, Sogut S, Akyol O, Ardicoglu O, Yildizhan H.(PubMed)
(120) In vitro fatty acid enrichment of macrophages alters inflammatory response and net cholesterol accumulation by Wang S1, Wu D, Lamon-Fava S, Matthan NR, Honda KL, Lichtenstein AH.(PubMed)
(121) Reduction in dietary omega-6 polyunsaturated fatty acids: eicosapentaenoic acid plus docosahexaenoic acid ratio minimizes atherosclerotic lesion formation and inflammatory response in the LDL receptor null mouse by Wang S1, Wu D, Matthan NR, Lamon-Fava S, Lecker JL, Lichtenstein AH.(PubMed)
(122) In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-kappaB pathway by Comalada M1, Camuesco D, Sierra S, Ballester I, Xaus J, Gálvez J, Zarzuelo A.(PubMed)
(123) Health effects of quercetin: from antioxidant to nutraceutical by Boots AW1, Haenen GR, Bast A.(PubMed)
(124) Red ginseng and vitamin C increase immune cell activity and decrease lung inflammation induced by influenza A virus/H1N1 infection by Kim H1,2, Jang M1, Kim Y1, Choi J1, Jeon J1, Kim J3, Hwang YI1, Kang JS1,2, Lee WJ1.(PubMed)
(125) Ascorbic acid ameliorates oxidative stress and inflammation in dextran sulfate sodium-induced ulcerative colitis in mice by Yan H1, Wang H2, Zhang X3, Li X1, Yu J1.(PubMed)
(126) Amelioration of particulate matter-induced oxidative damage by vitamin c and quercetin in human bronchial epithelial cells by Jin X1, Su R1, Li R2, Song L1, Chen M1, Cheng L3, Li Z4.(PubMed)
(127) Evidence of different mediators of central inflammation in dysfunctional and inflammatory pain--interleukin-8 infibromyalgia and interleukin-1 β in rheumatoid arthritis by Kosek E1, Altawil R2, Kadetoff D3, Finn A4, Westman M2, Le Maître E2, Andersson M5, Jensen-Urstad M6, Lampa J2.(PubMed)
(128) Compounds derived from epigallocatechin-3-gallate (EGCG) as a novel approach to the prevention of viral infections by Hsu S.(PubMed)
(129) Epigallocatechin gallate attenuates fibrosis, oxidative stress, and inflammation in non-alcoholic fatty liver disease rat model through TGF/SMAD, PI3 K/Akt/FoxO1, and NF-kappa B pathways by Xiao J1, Ho CT, Liong EC, Nanji AA, Leung TM, Lau TY, Fung ML, Tipoe GL.(PubMed)
(130) (-)-Epigallocatechin-3-gallate (EGCG) attenuates functional deficits and morphological alterations by diminishing apoptotic gene overexpression in skeletal muscles after sciatic nerve crush injury by Renno WM1, Al-Maghrebi M, Al-Banaw A(PubMed)).
(128) Compounds derived from epigallocatechin-3-gallate (EGCG) as a novel approach to the prevention of viral infections by Hsu S.(PubMed)
(129) Epigallocatechin gallate attenuates fibrosis, oxidative stress, and inflammation in non-alcoholic fatty liver disease rat model through TGF/SMAD, PI3 K/Akt/FoxO1, and NF-kappa B pathways by Xiao J1, Ho CT, Liong EC, Nanji AA, Leung TM, Lau TY, Fung ML, Tipoe GL.(PubMed)
(130) (-)-Epigallocatechin-3-gallate (EGCG) attenuates functional deficits and morphological alterations by diminishing apoptotic gene overexpression in skeletal muscles after sciatic nerve crush injury by Renno WM1, Al-Maghrebi M, Al-Banaw A(PubMed)).
(131) Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals by Chow HH1, Cai Y, Hakim IA, Crowell JA, Shahi F, Brooks CA, Dorr RT, Hara Y, Alberts DS.(PubMed)
(132) Curcumin supplementation likely attenuates delayed onset muscle soreness (DOMS) by Nicol LM1, Rowlands DS, Fazakerly R, Kellett J.(PubMed)
(133) Reduction of delayed onset muscle soreness by a novel curcumin delivery system (Meriva®): a randomised, placebo-controlled trial by Drobnic F1, Riera J1, Appendino G2, Togni S3, Franceschi F3, Valle X4, Pons A5, Tur J5.(PubMed)
(132) Curcumin supplementation likely attenuates delayed onset muscle soreness (DOMS) by Nicol LM1, Rowlands DS, Fazakerly R, Kellett J.(PubMed)
(133) Reduction of delayed onset muscle soreness by a novel curcumin delivery system (Meriva®): a randomised, placebo-controlled trial by Drobnic F1, Riera J1, Appendino G2, Togni S3, Franceschi F3, Valle X4, Pons A5, Tur J5.(PubMed)
(134) The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: A recent update by Ghosh S1, Banerjee S1, Sil PC2.(PubMed)
(135) Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases by Aggarwal BB1, Harikumar KB.(PubMed)
(136) Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature.by Anand P1, Thomas SG, Kunnumakkara AB, Sundaram C, Harikumar KB, Sung B, Tharakan ST, Misra K, Priyadarsini IK, Rajasekharan KN, Aggarwal BB.(PubMed)
(137) Resveratrol nanoparticle system improves dissolution properties and enhances the hepatoprotective effect of resveratrol through antioxidant and anti-inflammatory pathways by Lee CW1, Yen FL, Huang HW, Wu TH, Ko HH, Tzeng WS, Lin CC.(PubMed)
(138) Exploring new ways of regulation by resveratrol involving miRNAs, with emphasis on inflammation by Latruffe N1, Lançon A1, Frazzi R2, Aires V1,3, Delmas D1,3, Michaille JJ1, Djouadi F4, Bastin J4, Cherkaoui-Malki M1.(PubMed)
(139) Resveratrol prevents suppression of regulatory T-cell production, oxidative stress, and inflammation of mice prone or resistant to high-fat diet-induced obesity by Wang B1, Sun J, Li X, Zhou Q, Bai J, Shi Y, Le G.(PubMed)
(140) Resveratrol: a multitargeted agent for age-associated chronic diseases by Harikumar KB1, Aggarwal BB.(PubMed)
(141) Resveratrol engages AMPK to attenuate ERK and mTOR signaling in sensory neurons and inhibits incision-induced acute and chronic pain by Tillu DV1, Melemedjian OK, Asiedu MN, Qu N, De Felice M, Dussor G, Price TJ.(PubMed)
(142) Coadministration of Resveratrol and Rice Oil Mitigates Nociception and Oxidative State in a Mouse Fibromyalgia-Like Model by Peres Klein C1, Rodrigues Cintra M2, Binda N3, Montijo Diniz D3, Gomez MV3, Souto AA4, de Souza AH5.(PubMed)
(143) Boswellia serrata, a potential antiinflammatory agent: an overview by Siddiqui MZ1.(PubMed)
(144) Potentiation of antinociceptive effect of NSAIDs by a specific lipooxygenase inhibitor, acetyl 11-keto-betaboswellic acid by Bishnoi M1, Patil CS, Kumar A, Kulkarni SK.(PubMed)
(144) Potentiation of antinociceptive effect of NSAIDs by a specific lipooxygenase inhibitor, acetyl 11-keto-betaboswellic acid by Bishnoi M1, Patil CS, Kumar A, Kulkarni SK.(PubMed)
(145) Co-administration of 3-Acetyl-11-Keto-Beta-Boswellic Acid Potentiates the Protective Effect of Celecoxib in Lipopolysaccharide-Induced Cognitive Impairment in Mice: Possible Implication of Anti-inflammatory and Antiglutamatergic Pathways by Sayed AS1, El Sayed NS2,3.(PubMed)
(146) Boswellic acid attenuates asthma phenotypes by downregulation of GATA3 via pSTAT6 inhibition in a murine model of asthma by Liu Z1, Liu X1, Sang L1, Liu H1, Xu Q1, Liu Z1.(PubMed)
(147) Anti-inflammatory and analgesic effects of cucurbitacins from Wilbrandia ebracteata by Peters RR1, Farias MR, Ribeiro-do-Valle RM.(PubMed)
(148) Nitric oxide and cyclooxygenase may participate in the analgesic and anti-inflammatory effect of thecucurbitacins fraction from Wilbrandia ebracteata by Peters RR1, Baier Krepsky P, Siqueira-Junior J, da Silva Rocha JC, Marques Bezerra M, de Albuquerque Ribeiro R, de Brum-Fernandes AJ, Rocha Farias M,Castro da Rocha FA, Ribeiro-do-Valle RM(PubMed)
(148) Nitric oxide and cyclooxygenase may participate in the analgesic and anti-inflammatory effect of thecucurbitacins fraction from Wilbrandia ebracteata by Peters RR1, Baier Krepsky P, Siqueira-Junior J, da Silva Rocha JC, Marques Bezerra M, de Albuquerque Ribeiro R, de Brum-Fernandes AJ, Rocha Farias M,Castro da Rocha FA, Ribeiro-do-Valle RM(PubMed)
(149) Cucurbitacins attenuate microglial activation and protect from neuroinflammatory injury through Nrf2/ARE activation and STAT/NF-κB inhibition by Park SY1, Kim YH1, Park G2.(PubMed)
(150) Cucurbitacin R reduces the inflammation and bone damage associated with adjuvant arthritis in lewis rats by suppression of tumor necrosis factor-alpha in T lymphocytes and macrophages by Escandell JM1, Recio MC, Máñez S, Giner RM, Cerdá-Nicolás M, Ríos JL.(PubMed)
(151) Natural products and anti-inflammatory activity. by Yuan G1, Wahlqvist ML, He G, Yang M, Li D.(PubMed)
(152 Free Radicals, Antioxidants in Disease and Health by Lien Ai Pham-Huy,1 Hua He,2 and Chuong Pham-Huy3(PMC)
(153) Superoxide Anion and Its Functions(Beta Forces)
(154) Free radicals and antioxidants in normal physiological functions and human disease by Valko M1, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J.(PubMed)
(155) Free radicals, metals and antioxidants in oxidative stress-induced cancer by Valko M1, Rhodes CJ, Moncol J, Izakovic M, Mazur M.(PubMed)
(153) Superoxide Anion and Its Functions(Beta Forces)
(154) Free radicals and antioxidants in normal physiological functions and human disease by Valko M1, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J.(PubMed)
(155) Free radicals, metals and antioxidants in oxidative stress-induced cancer by Valko M1, Rhodes CJ, Moncol J, Izakovic M, Mazur M.(PubMed)
(156) Clinical implications of oxidative stress and potential role of natural antioxidants in diabetic vascular complications by Ceriello A1, Testa R2, Genovese S3.(PubMed)
(157) Cellular immunity in osteoarthritis: novel concepts for an old disease by Liossis SN1, Tsokos GC.(PubMed)
(158) Free Radicals, Antioxidants in Disease and Health by Lien Ai Pham-Huy,1 Hua He,2 and Chuong Pham-Huy3(PMC)
(157) Cellular immunity in osteoarthritis: novel concepts for an old disease by Liossis SN1, Tsokos GC.(PubMed)
(158) Free Radicals, Antioxidants in Disease and Health by Lien Ai Pham-Huy,1 Hua He,2 and Chuong Pham-Huy3(PMC)
(159) Levels of lipid peroxidation, nitric oxide, and antioxidant vitamins in plasma of patients with fibromyalgia by Akkuş S1, Naziroğlu M, Eriş S, Yalman K, Yilmaz N, Yener M.(PubMed)
(160) Food intake assessment and quality of life in women with fibromyalgia.
[Article in English, Portuguese] by Batista ED1, Andretta A2, Miranda RC3, Nehring J4, Paiva ED2, Schieferdecker ME3.(PubMed)
(161) Exacerbation of soft tissue rheumatism by excess vitamin A: case reviews with clinical vignette by Romano TJ.(PubMed)
(162) Essential role of vitamin C and zinc in child immunity and health by Maggini S1, Wenzlaff S, Hornig D.(PubMed)
(163) New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate by Hae-Suk Kim,a Michael J. Quon,c and Jeong-a Kima,b(PMC)
(164) Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications by Singh BN1, Shankar S, Srivastava RK.(PubMed)
(163) New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate by Hae-Suk Kim,a Michael J. Quon,c and Jeong-a Kima,b(PMC)
(164) Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications by Singh BN1, Shankar S, Srivastava RK.(PubMed)
(165) Total antioxidant capacity and the severity of the pain in patients with fibromyalgia by Altindag O1, Celik H.(PubMed)
(166) Antioxidants in vegan diet and rheumatic disorders by Hänninen1, Kaartinen K, Rauma AL, Nenonen M, Törrönen R, Häkkinen AS, Adlercreutz H, Laakso J.(PubMed)
(167) Muscle pain and serum creatine kinase are not associated with low serum 25(OH) vitamin D levels in patients receiving statins by Kurnik D1, Hochman I, Vesterman-Landes J, Kenig T, Katzir I, Lomnicky Y, Halkin H, Loebstein R.(PubMed)
(168) Effects of vitamin D on patients with fibromyalgia syndrome: a randomized placebo-controlled trial by Wepner F1, Scheuer R2, Schuetz-Wieser B2, Machacek P2, Pieler-Bruha E2, Cross HS3, Hahne J2, Friedrich M2.(PubMed)
(169) The relation between vitamin D deficiency and fibromyalgia syndrome in women by Matthana MH1.(PubMed)
(170) Vitamin D deficiency in women with fibromyalgia in Saudi Arabia by Abokrysha NT1.(PubMed)
(171) Vitamin E and immunity by Moriguchi S1, Muraga M.(PubMed)
(172) Vitamins C and E treatment combined with exercise modulates oxidative stress markers in blood of patients withfibromyalgia: a controlled clinical pilot study by Nazıroğlu M1, Akkuş S, Soyupek F, Yalman K, Çelik Ö, Eriş S, Uslusoy GA.(PubMed)
(173) Total antioxidant capacity and the severity of the pain in patients with fibromyalgia by Altindag O1, Celik H.(PubMed)
(174) Free radicals and antioxidants in primary fibromyalgia: an oxidative stress disorder? by Bagis S1, Tamer L, Sahin G, Bilgin R, Guler H, Ercan B, Erdogan C.(PubMed)
(175) Green tea polyphenol epigallocatechin 3-gallate in arthritis: progress and promise by Ahmed S1.(PubMed)
(176) Antioxidants and inflammatory disease: synthetic and natural antioxidants with anti-inflammatory activity by Geronikaki AA1, Gavalas AM.(PubMed)
(177) Associations between glucosamine and chondroitin supplement use and biomarkers of systemic inflammation by Kantor ED1, Lampe JW, Navarro SL, Song X, Milne GL, White E.(PubMed)
(178) [A role of melatonin in the treatment of low back pain].[Article in Russian] by Kurganova YM, Danilov AB.(PubMed)
(179) Carpal tunnel syndrome, diabetic neuropathy, fibromyalgia, glucosamine and chondroitin, hypnosis in pain management, marijuana for pain by Fishman SM1.(PubMed)
(180) Use of complementary therapies among primary care clinic patients with arthritis by Herman CJ1, Allen P, Hunt WC, Prasad A, Brady TJ.(PubMed)
(181) Sulfur in human nutrition and applications in medicine by Parcell S1.(PubMed)
(182) Taltirelin, a thyrotropin-releasing hormone analog, alleviates mechanical allodynia through activation of descending monoaminergic neurons in persistent inflammatory pain by Eto K1, Kim SK, Nabekura J, Ishibashi H.(PubMed)
(183) 4-Chloro-DL-phenylalanine protects against monocrotaline‑induced pulmonary vascular remodeling and lunginflammation by Bai Y1, Wang HM1, Liu M1, Wang Y1, Lian GC1, Zhang XH1, Kang J2, Wang HL1.(PubMed)
(184) D-phenylalanine and other enkephalinase inhibitors as pharmacological agents: implications for some important therapeutic application by Ehrenpreis S.(PubMed)
(185) Methylsulfonylmethane inhibits NLRP3 inflammasome activation by Ahn H1, Kim J1, Lee MJ1, Kim YJ2, Cho YW3, Lee GS4.(PubMed)
(186) Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. by Kim LS1, Axelrod LJ, Howard P, Buratovich N, Waters RF.(PubMed)
(187) Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study by Debbi EM1, Agar G, Fichman G, Ziv YB, Kardosh R, Halperin N, Elbaz A, Beer Y, Debi R.(PubMed)
(186) Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. by Kim LS1, Axelrod LJ, Howard P, Buratovich N, Waters RF.(PubMed)
(187) Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study by Debbi EM1, Agar G, Fichman G, Ziv YB, Kardosh R, Halperin N, Elbaz A, Beer Y, Debi R.(PubMed)
(188) Methylsulfonylmethane inhibits NLRP3 inflammasome activation by Ahn H1, Kim J1, Lee MJ1, Kim YJ2, Cho YW3, Lee GS4.(PubMed)
(189) Oral coenzyme Q10 supplementation improves clinical symptoms and recovers pathologic alterations in blood mononuclear cells in a fibromyalgia patient by Cordero MD1, Cotán D, del-Pozo-Martín Y, Carrión AM, de Miguel M, Bullón P, Sánchez-Alcazar JA.(PubMed)
(190) Coenzyme q10 regulates serotonin levels and depressive symptoms in fibromyalgia patients: results of a small clinical trial by Alcocer-Gómez E1, Sánchez-Alcázar JA, Cordero MD.(PubMed)
(191) Coenzyme Q10 in salivary cells correlate with blood cells in Fibromyalgia: improvement in clinical and biochemical parameter after oral treatment by Cordero MD1, Santos-García R, Bermejo-Jover D, Sánchez-Domínguez B, Jaramillo-Santos MR, Bullón P.(PubMed)
(192) Effect of coenzyme Q10 evaluated by 1990 and 2010 ACR Diagnostic Criteria for Fibromyalgia and SCL-90-R: four case reports and literature review by Alcocer-Gómez E1, Cano-García FJ, Cordero MD.(PubMed)
(193) Pediatric fibromyalgia by Buskila D1, Ablin J.(PubMed)
(194) Psychological control is a key modulator of fibromyalgia symptoms and comorbidities by Malin K1, Littlejohn GO.(PubMed)
(194) Psychological control is a key modulator of fibromyalgia symptoms and comorbidities by Malin K1, Littlejohn GO.(PubMed)
(195) Systematic review of psychological treatment in fibromyalgia by Lami MJ1, Martínez MP, Sánchez A.(PubMed)
(196) Are psychological treatments effective for fibromyalgia pain? by Thieme K1, Gracely RH.(PubMed)
(197) Gender Differences in Patients with Fibromyalgia Undergoing Cognitive-Behavioral Therapy for Insomnia: Preliminary Data by Lami MJ1, Martínez MP2, Sánchez AI2, Miró E2, Diener FN1, Prados G3, Guzmán MA3.(PubMed)
(198) Psychological pain treatment in fibromyalgia syndrome: efficacy of operant behavioural and cognitive behavioural treatments by Thieme K1, Flor H, Turk DC.(PubMed)(196) Are psychological treatments effective for fibromyalgia pain? by Thieme K1, Gracely RH.(PubMed)
(197) Gender Differences in Patients with Fibromyalgia Undergoing Cognitive-Behavioral Therapy for Insomnia: Preliminary Data by Lami MJ1, Martínez MP2, Sánchez AI2, Miró E2, Diener FN1, Prados G3, Guzmán MA3.(PubMed)
(199) Cognitive behavioural therapies for fibromyalgia. by Bernardy K1, Klose P, Busch AJ, Choy EH, Häuser W(PubMed)
(200) Responder criteria for operant and cognitive-behavioral treatment of fibromyalgia syndrome by Thieme K1, Turk DC, Flor H.(PubMed)
(201) Dysfunctional endogenous analgesia during exercise in patients with chronic pain: to exercise or not to exercise? by Nijs J1, Kosek E, Van Oosterwijck J, Meeus M.(PubMed)
(202) Aquatic exercise training for fibromyalgia by Bidonde J1, Busch AJ, Webber SC, Schachter CL, Danyliw A, Overend TJ, Richards RS, Rader T.(PubMed)
(203) Resistance exercise training for fibromyalgia by Busch AJ1, Webber SC, Richards RS, Bidonde J, Schachter CL, Schafer LA, Danyliw A, Sawant A, Dal Bello-Haas V, Rader T, Overend TJ.(PubMed)
(204) Swimming Improves Pain and Functional Capacity of Patients with Fibromyalgia: A Randomized Controlled Trial by Fernandes G1, Jennings F1, Nery Cabral MV1, Buosi AL1, Natour J2.(PubMed)
(205) Does moderate-to-high intensity Nordic walking improve functional capacity and pain in fibromyalgia? A prospective randomized controlled trial by Mannerkorpi K1, Nordeman L, Cider A, Jonsson G.(PubMed)
(206) Exercise Strengthens Central Nervous System Modulation of Pain in Fibromyalgia by Ellingson LD1, Stegner AJ2,3, Schwabacher IJ4,5, Koltyn KF6, Cook DB7,8.(PubMed)
(207) Physical therapy in the treatment of fibromyalgia by Offenbächer M1, Stucki G.(PubMed)
(207) Physical therapy in the treatment of fibromyalgia by Offenbächer M1, Stucki G.(PubMed)
(208) Mind and body therapy for fibromyalgia by Theadom A1, Cropley M, Smith HE, Feigin VL, McPherson K.(PubMed)
(209) [Physiotherapy and physical therapies for fibromyalgia syndrome. Systematic review, meta-analysis and guideline].[Article in German] by Winkelmann A1, Häuser W, Friedel E, Moog-Egan M, Seeger D, Settan M, Weiss T, Schiltenwolf M; Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften.(PubMed)
(210) A pragmatic community-based intervention of multimodal physiotherapy plus deep water running (DWR) forfibromyalgia syndrome: a pilot study by Cuesta-Vargas AI1, Adams N.(PubMed)
(211) Pharmacotherapy of chronic pain: a synthesis of recommendations from systematic reviews by Kroenke K1, Krebs EE, Bair MJ.(PubMed)
(212) R-Duloxetine and N-Methyl Duloxetine as Novel Analgesics Against Experimental Postincisional Pain. by Wang CF1, Russell G, Wang SY, Strichartz GR, Wang GK.(PubMed)
(213) Milnacipran for pain in fibromyalgia in adults by Cording M1, Derry S, Phillips T, Moore RA, Wiffen PJ.(PubMed)
(214) What are the side effects of analgesics? by Share care
(215) Tricyclic antidepressants and fibromyalgia: what is the mechanism of action? by Lawson K1.(PubMed)
(216) A guide to the understanding and use of tricyclic antidepressants in the overall management of fibromyalgia and other chronic pain syndromes by Godfrey RG1.(PubMed)
(217) Duloxetine and other antidepressants in the treatment of patients with fibromyalgia by Arnold LM1.(PubMed)
(218) Side effects of Tricyclic antidepressants (TCAs) by Mayo Clinic
(219) Gabapentin and pregabalin in the treatment of fibromyalgia: a systematic review and a meta-analysis by Tzellos TG1, Toulis KA, Goulis DG, Papazisis G, Zampeli VA, Vakfari A, Kouvelas D.(PubMed)
(220) Gabapentin for chronic neuropathic pain and fibromyalgia in adults by Moore RA1, Wiffen PJ, Derry S, Toelle T, Rice AS.(PubMed)
(221) side effects of pregabalin by Medicine net
(222) Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia. A randomized, double-blind clinical trial by Carette S1, Bell MJ, Reynolds WJ, Haraoui B, McCain GA, Bykerk VP, Edworthy SM, Baron M, Koehler BE, Fam AG, et al.(PubMed)
(223) The effects of cyclobenzaprine on sleep physiology and symptoms in patients with fibromyalgia by Reynolds WJ1, Moldofsky H, Saskin P, Lue FA.(PubMed)
(224) Cyclobenzaprine side effects by Drug.com
(225) Comparative efficacy and harms of duloxetine, milnacipran, and pregabalin in fibromyalgia syndrome by Häuser W1, Petzke F, Sommer C.(PubMed)
(226) Milnacipran for neuropathic pain and fibromyalgia in adults by Derry S1, Gill D, Phillips T, Moore RA.(PubMed)
(227) Side effects of Milnacipran by LXlist
(228) Compounded pain formulations: what is the evidence? by Asbill S, Sweitzer SM, Spigener S, Romero-Sandoval A.(PubMed)
(229) The use of opioids in fibromyalgia by Ngian GS1, Guymer EK, Littlejohn GO.(PubMed)
(230) Opioid complications and side effects by Benyamin R1, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N, Glaser SE, Vallejo R.(PubMed)
(231) Alternative medical interventions used in the treatment and management of myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia by Porter NS1, Jason LA, Boulton A, Bothne N, Coleman B.(PubMed)
(232) Complementary and alternative medical therapies in fibromyalgia by Sarac AJ1, Gur A.(PubMed)
(233) Fibromyalgia patients report less pain and better quality of life with acupuncture by [No authors listed](PubMed)
(234) Acupuncture for treating fibromyalgia by Deare JC1, Zheng Z, Xue CC, Liu JP, Shang J, Scott SW, Littlejohn G.(PubMed)
(235) Acupuncture for fibromyalgia in primary care: a randomised controlled trial by Vas J1, Santos-Rey K2, Navarro-Pablo R3, Modesto M2, Aguilar I2, Campos MÁ4, Aguilar-Velasco JF5, Romero M4, Párraga P5, Hervás V3, Santamaría O3,Márquez-Zurita C2, Rivas-Ruiz F6.(PubMed)
(236) Acupuncture and Trigger Point Injections for Fibromyalgia: East-West Medicine Case Report by Taw LB, Henry E.(PubMed)
(237) Selenium and magnesium status in fibromyalgia by Eisinger J1, Plantamura A, Marie PA, Ayavou T.(PubMed)
(238) Is magnesium citrate treatment effective on pain, clinical parameters and functional status in patients withfibromyalgia? by Bagis S1, Karabiber M, As I, Tamer L, Erdogan C, Atalay A.(PubMed)
(239) The relationship between serum antioxidant vitamins, magnesium levels, and clinical parameters in patients with primary fibromyalgia syndrome by Sakarya ST1, Akyol Y, Bedir A, Canturk F.(PubMed)
(240) A randomised controlled trial comparing duloxetine and acetyl L-carnitine in fibromyalgic patients: preliminary data by Leombruni P1, Miniotti M1, Colonna F1, Sica C1, Castelli L2, Bruzzone M3, Parisi S3, Fusaro E3, Sarzi-Puttini P4, Atzeni F5, Torta RG1.(PubMed)
(241) Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients by Rossini M1, Di Munno O, Valentini G, Bianchi G, Biasi G, Cacace E, Malesci D, La Montagna G, Viapiana O, Adami S.(PubMed)
(242) Evidence for the efficacy of complementary and alternative medicines in the management of fibromyalgia: a systematic review by De Silva V1, El-Metwally A, Ernst E, Lewith G, Macfarlane GJ; Arthritis Research Campaign working group on complementary and alternative medicines.(PubMed)
(243) Efficacy of the dietary supplement S-adenosyl-L-methionine by Fetrow CW1, Avila JR.(PubMed)
(244) Comparison of manual lymph drainage therapy and connective tissue massage in women with fibromyalgia: a randomized controlled trial by Ekici G1, Bakar Y, Akbayrak T, Yuksel I.(PubMed)
(245) Massage therapy for fibromyalgia: a systematic review and meta-analysis of randomized controlled trials by Li YH1, Wang FY1, Feng CQ1, Yang XF1, Sun YH1.(PubMed)
(246) Effect of a single session of muscle-biased therapy on pain sensitivity: a systematic review and meta-analysis of randomized controlled trials by Gay CW1, Alappattu MJ, Coronado RA, Horn ME, Bishop MD.(PubMed)
(247) Massage therapy has short-term benefits for people with common musculoskeletal disorders compared to no treatment: a systematic review by Bervoets DC1, Luijsterburg PA1, Alessie JJ2, Buijs MJ2, Verhagen AP1.(PubMed)
(248) Complementary and alternative medicine in fibromyalgia and related syndromes by Holdcraft LC1, Assefi N, Buchwald D.(PubMed)
(249) A review of recent clinical trials of the nutritional supplement Chlorella pyrenoidosa in the treatment offibromyalgia, hypertension, and ulcerative colitis by Merchant RE1, Andre CA.(PubMed)
(250) Nutritional supplementation with Chlorella pyrenoidosa for patients with fibromyalgia syndrome: a pilot study by Merchant RE1, Carmack CA, Wise CM.(PubMed)
(251) Management of patients with fibromyalgia using biofeedback: a randomized control trial by Babu AS1, Mathew E, Danda D, Prakash H.(PubMed)
(252) A pilot study of the efficacy of heart rate variability (HRV) biofeedback in patients with fibromyalgia by Hassett AL1, Radvanski DC, Vaschillo EG, Vaschillo B, Sigal LH, Karavidas MK, Buyske S, Lehrer PM.(PubMed)
(253) Efficacy of EMG- and EEG-Biofeedback in Fibromyalgia Syndrome: A Meta-Analysis and a Systematic Review of Randomized Controlled Trials by Glombiewski JA1, Bernardy K, Häuser W.(PubMed)
(254) Effects of Stress and Relaxation on Central Pain Modulation in Chronic Whiplash and Fibromyalgia Patients Compared to Healthy Controls by Coppieters I, Cagnie B, Nijs J1, van Oosterwijck J, Danneels L, De Pauw R, Meeus M2.(PubMed)
(255) Comparison of integrated group therapy and group relaxation training for fibromyalgia by Keel PJ1, Bodoky C, Gerhard U, Müller W.(PubMed)
(256) Mind and body therapy for fibromyalgia by Theadom A1, Cropley M, Smith HE, Feigin VL, McPherson K.(PubMed)
(257) Static magnetic fields for treatment of fibromyalgia: a randomized controlled trial by Alfano AP1, Taylor AG, Foresman PA, Dunkl PR, McConnell GG, Conaway MR, Gillies GT.(PubMed)
(258) Qualitative systemic review of randomized controlled trials on complementary and alternative medicine treatments in fibromyalgia by Baranowsky J1, Klose P, Musial F, Häuser W, Dobos G, Langhorst J.(PubMed)
(259) Natural health product use in Canada: analysis of the National Population Health Survey by Singh SR1, Levine MA.(PubMed)
(260) An open, pilot study to evaluate the potential benefits of coenzyme Q10 combined with Ginkgo biloba extract in fibromyalgia syndrome by Lister RE1.(PubMed)
(261) [Effect of Coenzyme Q10 and Ginkgo biloba on warfarin dosage in patients on long-term warfarin treatment. A randomized, double-blind, placebo-controlled cross-over trial].[Article in Danish]by Engelsen J1, Nielsen JD, Hansen KF.(PubMed)
(262) Herbal Medicine for Low Back Pain: A Cochrane Review by Gagnier JJ1, Oltean H, van Tulder MW, Berman BM, Bombardier C, Robbins CB.(PubMed)
(263) Herbal medicine for low-back pain by Oltean H1, Robbins C, van Tulder MW, Berman BM, Bombardier C, Gagnier JJ.(PubMed)
(264) Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicumannuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract,capsicum frutescens resin, and capsaicin. by[No authors listed](PubMed)
(265) Capsicum pain plaster in chronic non-specific low back pain by Keitel W1, Frerick H, Kuhn U, Schmidt U, Kuhlmann M, Bredehorst A.(PubMed)
(266) Acupuncture for treating fibromyalgia by Deare JC1, Zheng Z, Xue CC, Liu JP, Shang J, Scott SW, Littlejohn G.(PubMed)
(267) Improvement in fibromyalgia symptoms with acupuncture: results of a randomized controlled trial by Martin DP1, Sletten CD, Williams BA, Berger IH.(PubMed)
(268) Acupoint stimulation for fibromyalgia: a systematic review of randomized controlled trials by Cao H1, Li X1, Han M1, Liu J2.(PubMed)
(269) Traditional Chinese Medicine for treatment of fibromyalgia: a systematic review of randomized controlled trials by Cao H1, Liu J, Lewith GT.(PubMed)
(270) Acupuncture for fibromyalgia in primary care: a randomised controlled trial by Vas J1, Santos-Rey K2, Navarro-Pablo R3, Modesto M2, Aguilar I2, Campos MÁ4, Aguilar-Velasco JF5, Romero M4, Párraga P5, Hervás V3, Santamaría O3,Márquez-Zurita C2, Rivas-Ruiz F6.(PubMed)
(271) Using a partially randomized patient preference study design to evaluate the therapeutic effect of acupuncture and cupping therapy for fibromyalgia: study protocol for a partially randomized controlled trial by Cao HJ1, Liu JP, Hu H, Wang NS.(PubMed)
(272) [Combination of acupuncture, cupping and medicine for treatment of fibromyalgia syndrome: a multi-central randomized controlled trial].[Article in Chinese]by Jang ZY1, Li CD, Qiu L, Guo JH, He LN, Yue Y, Li FZ, Qin WY.(PubMed)
(273) Traditional Chinese Medicine for treatment of fibromyalgia: a systematic review of randomized controlled trials by Cao H1, Liu J, Lewith GT.(PubMed)
(274) Traditional Chinese Medicine for treatment of fibromyalgia: a systematic review of randomized controlled trials by Cao H1, Liu J, Lewith GT.(PubMed)
(275) Qigong and fibromyalgia: randomized controlled trials and beyond by Sawynok J1, Lynch M2.(PubMed)
(276) A randomized controlled trial of qigong for fibromyalgia by Lynch M, Sawynok J, Hiew C, Marcon D.(PubMed)
(277) Extension trial of qigong for fibromyalgia: a quantitative and qualitative study by Sawynok J1, Lynch M, Marcon D.(PubMed)
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