Nutritional recommendations for the treatment of fibromyalgia/Recomendacoes nutricionais para o tratamento da fibromialgia.
Fibromyalgia has an unknown etiology. It is characterized by generalized chronic pain in the locomotor system, in addition to intense fatigue, sleep disorders, paresthesia in the extremities, depression, anxiety, joint stiffness, headache and a feeling of swelling in the hands. (1-3)
There are no laboratory tests to confirm the diagnosis, which is based on the presence of body pain for at least three months, with fatigue, sleep disorders, cognitive changes, mood disorders and other variable-grade somatic symptoms that cannot be explained by the presence of other diseases. (2,4) Generalized pain is defined as the presence of pain in the left and right quadrants of the body, above and below the waist, in addition to axial pain, in which there is involvement of the cervical, thoracic or lumbar spine. For the diagnosis, digital palpation is performed at 18 tender points and it is considered positive when there is pain in at least 11 of these points. (5)
Patients with fibromyalgia may present other associated diagnoses, such as irritable bowel syndrome (6) and hypothyroidism. (7)
The prevalence of fibromyalgia assessed according to the American College of Rheumatology (ACR) criteria for 1990 ranges from 0.66% to 4.4%, and it is more common in women aged 35-60 years. (8) In Brazil, a prevalence of 2.5% of fibromyalgia was found.9 Although the disease is more common in middle-aged people, it also affects children, adolescents and the elderly. (10)
Among the treatments that can be employed, complementary and alternative medicine comprises the use of natural products, vitamins, minerals, probiotics and other dietary supplements. (11)
The science of nutrition presented many advances during the twentieth century, highlighting the discovery of vitamins to bioactive substances in food. Currently, issues such as nutrigenomics and individualized nutritional recommendations are discussed. It is speculated that in the future there may be dietary recommendations for the bioactive substances present in foods considered functional. (12) It is also important to note that considerable advances have been made in enteral and parenteral nutrition therapy, making it possible to support patients for long periods of time. (13,14)
However, there are still many challenges related to nutritional therapy in various diseases, including fibromyalgia. This review aims to find the scientific evidence related to nutrition in fibromyalgia, through an integrative literature review, (15) which is considered a subdivision of the systematic review, along with meta-analysis, systematic review and qualitative review. (16)
The databases Science Direct, Medline Pubmed, Medline Bireme and Scientific Electronic Library Online (Scielo) were consulted in the period from July to September 2016. The descriptors fibromyalgia and nutrition were used, searching for original reviewed articles, as well as guides and consensuses of national and international societies available in their own electronic addresses, considering pharmacological and non-pharmacological treatment, that have been published from 2003 to 2016. In addition to the bases mentioned above, as a search strategy, the Google Scholar site was also used and the list of references of the most recent publications was checked.
As inclusion criterion, articles in Portuguese, Spanish and / or English were selected to provide evidence on the nutritional recommendations for the treatment of fibromyalgia. The steps for the research design are shown in Figure 1. The initial screening of articles consisted in the evaluation of titles and abstracts, seeking to answer the nutritional recommendations for fibromyalgia. Afterwards, a critical reading of the selected articles was carried out to determine which ones met the criteria to be included in the review.
Twenty two scientific articles were selected and five of which were included in the analysis. Four of which were systematic reviews of the literature and one classified as a non-systematic review, in addition to five consensuses of fibromyalgia treatment (Table 1). It is important to note that most of the studies on nutrition related to fibromyalgia contain small numbers of individuals, are not randomized and therefore are not conclusive, and that the systematic reviews selected group the majority of these studies. Thus, articles that were read in full and not included in the critical analysis, because they did not meet the inclusion criteria, were often cited in the discussion. The topics addressed in these articles were oxidative stress and supplementation with coenzyme Q10 (coQ10), (25,27-30,32) body composition and symptoms of fibromyalgia (35,37,39) and vitamin D deficiency and its influence on fibromyalgia. (41-43)
In the systematic review by Arranz et al., (17) the authors reviewed articles on vegetarian diets, rich in antioxidants, although there are few studies and a small number of individuals. As for nutritional status, patients are generally overweight and / or obese, and have micronutrient deficiencies such as selenium, zinc and magnesium, and low levels of branched chain amino acids (BCAA), although it has not been possible to determine if these deficiencies are due to changes in ingestion and influence the etiopathogenesis of fibromyalgia. The authors conclude that a healthy diet for weight maintenance and nutritional supplements is recommended for the best nutritional status, although more studies are needed to understand the potential benefits of nutrition.
On the use of complementary and alternative medicine and nutritional supplementation in the treatment of fibromyalgia, the studies present small samples, are not randomized, and lack placebo or double blind control, most of them presenting limited or insufficient evidence. To date, there is moderate evidence for the use of magnesium, which is essential for ATP synthesis, strong evidence for S-adenosyl-L-methionine (SAM-e) supplementation and limited to Chlorella pyrenoidosa, while anthocyanidins and vegetarian diet have limited evidence. (18)
There is questioning whether the removal of some foods, additives or increased nutrient levels influence the treatment of fibromyalgia, or whether results are due to weight loss caused by restrictive diets. It is hypothesized that monosodium glutamate may contribute to increased obesity but it has not yet been tested in humans. Although the evidence for dietary modifications is restricted, the authors consider that these changes are safer and less expensive than pharmacological therapies and are under the control of the patient, noting that less restrictive diets may achieve greater adherence. (19)
According to Li and Micheletti, (20) most of the studies that relate diet and fibromyalgia are observational and descriptive, which results in low statistical power for vegetarian diets, lack of controls in studies with weight loss and difficult evidence of effects for elimination diets. Although there are reports of patients believing in a relationship between fibromyalgia and diet, more rigorous studies are needed to determine the function of the diet in fibromyalgia or specific dietary recommendations for treatment.
In the systematic review on the use of dietary supplements, such as micronutrients, SAM-e, Chlorella pyrenoidosa and soybeans, favorable results were obtained for these nutritional interventions, although most studies are preliminary or exploratory, and with small samples. (11)
Regarding recommendations for nutritional treatment, the Canadian Consensus (21) proposes that patients should be encouraged to eat balanced and nutritious meals at regular times, maintain good hydration, take multienzyme along with meals when associated with irritable bowel syndrome (IBS), use supplements when needed for treatment. Specific recommendations involve the elimination of those non-tolerated foods in patients with IBS and low-glycemic diet in case of hypoglycemia.
Still according to Canadian recommendations, vitamins are often cofactors that help enzymes in the use of nutrients. The recommended intake is based on the estimated sums required to prevent symptoms of deficiencies and not at optimal levels for chronic diseases. The balanced vitamin profile is helpful. Vitamins C and E ([alpha]-tocopherol) and [beta]-carotene are antioxidants and stimulate the immune system. Vitamins of the B complex reduce stress; folic acid can help in lowering cholesterol. Calcium is involved in hundreds of enzymatic reactions and has increased absorption by vitamin D. Magnesium maleate can reduce fatigue and prevent muscle cramps, patients with fibromyalgia may require extra magnesium maleate compared to the usual ratio of 2:1 of calcium to magnesium. Zinc improves the function of nerve and muscle tissues and is involved in the formation of collagen. (21)
As for the use of supplements, essential fatty acids (EFA) are required for cell membrane integrity and prostaglandin synthesis. Ingestion of foods such as ice water fish, salmon oil and primrose oil may influence blood flow and nerve impulse transmission. Lecithin has function in the nervous and muscular tissues, in the brain and in the circulation; methylsulfonylmethane (MSM) can strengthen connective tissue and reduce joint pain; glucosamine sulfate can reduce pain and improve mobility of joints; glutamine can improve muscle function and promote growth hormone production; procyanidolic oligomer (PCO) can protect muscles and help prevent arthritis and bursitis. (21)
In 2013, the Canadian Guide for the diagnosis and treatment of fibromyalgia was published, which discusses the lack of evidence based on scientific studies, leading to the exclusion of nutritional recommendations from the protocols. Thus, nutritional treatment is not contemplated in the Canadian guide, (4) just as it is not contemplated in the Brazilian Consensus on the Treatment of Fibromyalgia. (22)
Hassett and Gevirtz, (23) in their work on the non-pharmacological treatment of fibromyalgia and the use of complementary and alternative medicine, argue that studies with nutritional supplements should explore individual factors to identify which subgroups of patients may respond better to each type of treatment.
The use of non-pharmacological strategies for the treatment of fibromyalgia is based on the stimulus to patient independence, social support and lifestyle that promote health, psychological assessment and counseling, and the practice of moderate physical activity. (2,4)
The most recent literature has presented discussion about the oxidative stress present in fibromyalgia and the use of antioxidants, the issue of excess body weight and micronutrient deficiency.
Patients with fibromyalgia produce 3.2 times more reactive oxygen species (ROS) than controls, comparable results to patients with rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis and systemic sclerosis, diseases with inflammatory profile. (24) Oxidative stress in fibromyalgia is an accepted fact, but its role in the disease, from a physiological point of view, is unclear, and the mechanism by which it may have an effect on worsening symptoms is still unknown. (25)
The use of antioxidant therapy or stress reduction with administration of antioxidant drugs and control of risk factors, such as smoking cessation, physical activity and diet, can be effective therapy for fatigue. It is possible that oxidative stress is an important mediator in the vicious cycle, aggravating chronic fatigue, if not the primary cause of fatigue. (6)
CoQ10 is present in cell membranes and has the function of transferring electrons from complexes I and II to complex III in the mitochondrial respiratory chain. It presents a critical role in the production of ATP, contains important role in cellular metabolism and limits the production of reactive oxygen species (ROS). It is suggested that CoQ10 is a marker of mitochondrial function. (26)
CoQ10 supplementation induced increased mitochondrial biogenesis and protein expression levels, with increased mitochondrial DNA copy numbers. These results suggest the function of CoQ10 and mitochondrial dysfunction in the pathogenesis of fibromyalgia. Treatment with CoQ10 can be used as an alternative therapy in fibromyalgia and its beneficial effects can be monitored at the cellular level. However, more research is needed to clarify precise mechanisms by which CoQ10 can contribute to pathological and therapeutic processes. (27)
Coenzyme Q10 (CoQ10) supplementation improved sleep and mental alertness, reduced joint pain, headache episodes and intensity, tender points numbers and lipid peroxidation, as well as improving fatigue symptoms, depression and anxiety. (28-30) Mitochondrial dysfunction may be involved in several symptoms observed in fibromyalgia. (31) Studies with CoQ10 involve a small number of individuals and their results cannot be generalized.
In addition to the symptoms of the disease, it is necessary to administer the side effects of drug therapy. Amitriptyline causes increased ROS and reduction in CoQ10 levels, increased lipid peroxidation, and a reduction in mitochondrial mass, suggesting that the treatment aggravated mitochondrial dysfunction in these patients. ATP levels were also decreased, probably because CoQ10 is an essential component of mitochondrial electron transport and is directly involved in ATP biosynthesis. CoQ10 supplementation may prevent or reduce the effects of amitriptyline. (32)
Other effects related to drug treatment may be cited, such as weight gain, edema, constipation and nausea. (33) Increased body mass index (BMI) influences sleep quality, hyperalgesia and quality of life, which may complicate the clinical picture, insofar as physical strength and flexibility are affected, in addition to pain sensitivity, especially in the lower part of the body. (34) Individuals who were overweight or obese presented higher levels of pain, fatigue and stiffness, as well as lower vitality. (35) The establishment of correlations between body composition and variables, such as emotional function, pain, vitality and physical capacity, was not possible. (36) Although fibromyalgia was more common in premenopausal women, the relationship between percentage of body fat and eating disorders was observed in adolescents. (37)
Regarding nutritional status, there is a prevalence of overweight and obesity, which may involve up to 70% of patients with fibromyalgia. (33) Excess weight may increase serum concentrations of C-reactive protein (CRP), which can be reduced with exercise. Serum CRP concentrations, an important indicator of inflammation, are not affected by diet or sleep. (38)
Reduction in BMI improves symptoms of fibromyalgia, such as pain and body dissatisfaction. Weight loss may be responsible for reducing joint pressure, reducing energy demands for tasks, reducing fatigue, and increasing willingness to perform tasks. (39)
Among the major changes in fibromyalgia are the presence of chronic fatigue and depression. In both, the studies demonstrated low serum concentrations of [alpha]-tocopherol, which may indicate the presence of oxidative stress. (6,40)
In a control case study with premenopausal women, it was observed that vitamin D deficiency is not more common in fibromyalgia than in controls. However, there was an association between low concentrations of vitamin D and pain in the patients group, indicating that hypovitaminosis D may have an impact on pain intensity. (41)
As for vitamin D supplementation, there was reduction of pain in the treatment group, with no difference with controls in somatization, depression and anxiety nor in physical or mental health. The authors conclude that the lack of improvement in some fibromyalgia symptoms may be related to both the small sample size and the complexities of the symptoms, which are not related only to vitamin D deficiency. (42)
Women with premenopausal fibromyalgia presented lower concentrations of vitamin D than controls, and also had lower bone mineral density (BMD) in the lumbar region. In patients with severe vitamin D deficiency, there was loss of short-term memory, confusion, mood disorders, sleep disorders, and palpitations. Vitamin D concentrations were inversely related to the visual pain scale, Beck score of depression and bone mineral density (BMD) in the lumbar region. This study concludes that there is a prevalence of vitamin D deficiency among fibromyalgia patients, who will benefit from vitamin D and calcium supplementation, as well as physical activity, along with medical treatment to prevent the development of osteoporosis. (43)
The chronic fatigue syndrome present in fibromyalgia may be aggravated by the sensitivity to non-celiac gluten, recently considered comorbidity of both conditions. In this syndrome, there is the presence of intense fatigue and unexplained cognitive, autonomic and neuroendocrine symptoms, in the last six months, with the possible presence of gastrointestinal symptoms as diagnostic criteria. (44) Sensitivity to non-celiac gluten presents clinical manifestations that overlap with those of fibromyalgia, chronic fatigue and irritable bowel syndrome. (45) Thus, some symptoms of fibromyalgia, such as fatigue, headache and gastrointestinal discomfort, are also common symptoms in individuals with gluten sensitivity. (46) In individuals with fibromyalgia with non-celiac gluten sensitivity, the exclusion of gluten from the diet was related to the remission of the pain criteria, return to work and discontinuation of opioid use, as well as improvement of symptoms such as fatigue, gastrointestinal symptoms, migraine and depression. (47) Similarly, there was reduction of intestinal frequency in individuals with irritable bowel syndrome and dominant diarrhea after exclusion of gluten from the diet. (48)
The exclusion of gluten should be followed by a balanced diet, with the ingestion of whole grains, increase of vegetables and reduction of the energy density of foods, (46) seeking adequate nutrition and dietary balance according to the symptoms, more than the simple exclusion of gluten from the diet. (44) Because of this gluten sensitivity issue potentially having relevant effects on the symptoms of fibromyalgia, the protocol of the first randomized controlled trial was recently published to evaluate the effects of gluten exclusion among fibromyalgia-sensitive patients. (49)
The science of nutrition has made great advances in the last 100 years, although nutrition is considered complementary therapy in the treatment of various diseases. There are no specific nutritional recommendations for the treatment of fibromyalgia. This group of patients should adopt the principles of healthy eating. Reduction of obesity may contribute to decrease pain and improve functional capacity, as well as to reduce inflammatory markers and improve quality of life.
Da Silva AF participated in the design of the article, the bibliographical survey and the preparation of the manuscript. Schieferdecker MEM participated in the design of the article, the preparation of the manuscript and the final revision of the article.
Conflict of interests: The authors declare no conflict of interest.
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Received: March 06, 2017
Reviewed: August 06, 2017
Accepted: August 21, 2017
Alice Freitas da Silva 
Maria Eliana Madalozzo Schieferdecker 
 Universidade Federal de Santa Catarina, Programa de Pos-Graduacao em Nutricao. Florianopolis-SC, Brasil.
 Universidade Federal do Parana, Programa de Pos-Graduacao em Seguranca Alimentar e Nutricional. Curitiba-PR, Brasil
Alice Freitas da Silva
Table 1. Nutritional recommendations for the treatment of fibromyalgia Author Year Methodology Main goal Arranz, 2010 Systematic Relating nutrition Canela and Review from and fibromyalgia Rafecas (17) 1998 to 2008 Holdcraft, 2003 Systematic To find evidence Assefi and Review from regarding the use of Buhwald (18) 1975 to 2002 complementary and alternative medicine in the treatment of fibromyalgia Holton, 2009 Systematic To investigate the Kindler and Review from effects of vegetarian Jones (19) 1986 to 2008 diet, elimination and / or weight loss in fibromyalgia Li and 2011 Review To investigate the Micheletti (20) effects of vegetarian diet, elimination and / or weight loss in fibromyalgia Terhorst et 2011 Systematic To find evidence al. (11) Review from regarding the use of 1950 to 2010 complementary and alternative medicine in the treatment of fibromyalgia Carruthers 2003 Canadian Recommendations and Consensus for the treatment of Sande (21) fibromyalgia Fitzcharles 2013 Canadian Recommendations et al. (4) Consensus for the treatment of fibromyalgia Hassett 2009 Review Recommendations for and non-pharmacological Gevirtz (23) treatment of fibromyalgia: use of complementary and alternative medicine Heymann 2010 Brazilian Recommendations et al. (22) Consensus for the treatment of fibromyalgia Rivera et 2006 Spanish Recommendations al. (2) Consensus for the treatment of fibromyalgia Author Main results Arranz, Presence of Canela and overweight or obesity; Rafecas (17) micronutrient deficiency. Holdcraft, Moderate evidence Assefi and for magnesium Buhwald (18) supplementation, strong for SAM-e supplementation and limited for Chlorella pyrenoidosa supplementation. Holton, There is no evidence for Kindler and dietary restrictions in Jones (19) fibromyalgia. Li and There is an increase Micheletti (20) in pain related to glutamate and aspartame ingestion; there are no dietary recommendations for the treatment of fibromyalgia. Terhorst et Favorable results al. (11) for micronutrient supplementation, SAM-e, Chlorella pyrenoidosa and soybean. Carruthers Indicated balanced and and nutritious diet; authors Sande (21) discuss the role of nutrients. Fitzcharles It does not contemplate et al. (4) nutritional treatment. Hassett To look for individual and factors to define Gevirtz (23) better forms of supplementation. Heymann It does not contemplate et al. (22) nutritional treatment. Rivera et To seek patient self- al. (2) efficacy in treatment.
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|Author:||da Silva, Alice Freitas; Schieferdecker, Maria Eliana Madalozzo|
|Publication:||Demetra: Food, Nutrition & Health|
|Date:||Sep 1, 2017|
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