Keywords

Fibromyalgia; antioxidants; obesity; nutrition

Introduction

Fibromyalgia syndrome (FMS) is an idiopathic form of rheumatism characterized by diffuse nonarticular musculoskeletal pain along with generalized tender body areas such as muscles, tendons, and joints. The chronic pain in fibromyalgia is widespread and mainly affects the neck, shoulders, upper back, arms, and chest. According to American College of Rheumatology criteria, the duration of widespread pain is at least 3 months, and pain on pressure should be 11–18 specific tender points at minimum (White and Harth, 2001; Neumann and Buskila, 2003; Marcus and Deodhar, 2011; Wolfe et al., 1990). FMS is always associated with other complications, especially sleep disturbances, morning stiffness, fatigue after mild physical exertion, paresthesias, cognitive disturbances (especially memory loss), anxiety, tension headaches, irritable bowel syndrome, mitral valve prolapse, primary dysmenorrhea, depression, and psychological disturbance (Branco et al., 2010; Arnold et al., 2006). It is frequently connected with severe functional damage and work inability, and its effects are comparable to those reported for osteoarthritis and other rheumatic disorders (Walker et al., 1997; Hawley and Wolfe, 1991). Approximately 2–2.7% of the world’s population suffers from FMS, and the rate of incidence is higher in younger and middle-aged women, obese people, and aged patients (Queiroz, 2013; Fitzcharles et al., 2013). The prevalence rate of FMS in the United States is 6–15%, with a five times higher incidence among women than men (Jahan et al., 2012). From 40% to 70% of the fibromyalgia patients are suffering from obesity, and increased body mass index (BMI) is correlated with higher levels of fatigue and pain in fibromyalgia (Bennett et al., 2007; Neumann et al., 2008). The level of oxidative stress, type of diet, and nutritional status are also associated factors that increase the risk of FMS (Li and Micheletti, 2011; Arranz et al., 2010; Percival et al., 1997) (Fig. 7.1).

Pathophysiology of Fibromyalgia

The pathophysiology of FMS includes multiple abnormalities and altered mechanisms. The aberrations of the autonomic and central nervous systems, genetic factors, environmental factors, psychological factors, the hypothalamic–pituitary–adrenal (HPA) axis hormones, and oxidative stress are all involved in the pathogenesis of FMS. Abnormalities in several neuroendocrine transmitters—in particular, nerve growth hormone (GH), 5-hydroxytryptamine, cortisol, norepinephrine, and substance P—are reported in FMS (Bradley, 2009; Ozgocmen et al., 2006).

Chronic pain in FMS is a result of central sensitization, abnormal descending inhibitory pain pathways, and altered level of neurotransmitters. Central sensitization is considered the major mechanism involved in chronic pain. It is a result of spontaneous nerve action, enlarged receptive fields, and augmented response to the stimuli conveyed by the primary afferent nerve (Bellato et al., 2012; Ozgocmen et al., 2006). In FMS, central sensitization causes abnormal windup processes, which results in neuronal hyperexcitability in the spinal cord. It is mediated by N-methyl-D-aspartate receptors via nitric oxide (NO) and peroxynitrite pathways and plays a vital role in pain processing (Woolf, 2011; Staud et al., 2001; Staud et al., 2004; Latremoliere and Woolf, 2009). Glial cell activation through various stimuli also plays a significant role in pain processes. The activation of glial cell increases the release of NO, reactive oxygen species, and proinflammatory cytokines and ultimately prolongs neuronal hyperexcitability (Watkins et al., 2001). Several neurotransmitters and modulators are involved in the central sensitization and chronic pain. For example, serotonin and noradrenalin levels in the central nervous system appear to be reduced in FMS and lead to dysfunctional descending pathways, while substance P and glutamate levels are increased in cerebrospinal fluid, which increases pain sensitivity. Alteration of these neurotransmitters also affects sleep and mood in FMS patients (Becker et al., 2011; McCarley, 2007; Raison, 2009). The HPA axis functions abnormally in FMS because of chronic pain-induced stress (Crofford, 2002; Demitrack and Crofford, 1998). Furthermore, hyposecretion of corticotropin-releasing hormone in FMS patients elevates the level of adrenocorticotropic hormone and cortisol in response to stress (Neeck and Crofford, 2000; Riedel et al., 1998; Neeck and Crofford, 2002). The secretion of GH and insulin-like growth factor (IGF-1) is also decreased. Inadequate secretion of GH and IGF-1 are significant factors of sleep disturbance in FMS patients (Prinz et al., 1995; Van Cauter et al., 1998). Genetic modifications such as nucleotide polymorphism in various genes such as the serotonin transporter (5-HTT) gene, the catechol-O-methyltransferase gene, and dopamine D4 receptor gene are also reported in FMS. Environmental factors such as infections caused by various viruses such as the human immunodeficiency virus, parvoviruses, the hepatitis C virus, and some bacteria also play important roles in pathogenesis by activating glial cells and releasing cytokines (Rivera et al., 1997; Leventhal et al., 1991; Buskila et al., 1990; Nicolson et al., 1999; Furr and Marriott, 2012).

Fibromyalgia and Obesity

Obesity is defined as a complex disease with immoderate deposition of fat in adipose tissue (Ravussin and Swinburn, 1992; Ursini et al., 2011). It can be considered a major risk factor for the development of several medical problems such as hypertension, respiratory diseases, type 2 diabetes, gout, strokes, osteoarthritis, and musculoskeletal disorders, including fibromyalgia (Must and Strauss, 1999). BMI is considered worldwide as an important measure of obesity and is divided into three classes: a BMI <25 kg/m² is considered as normal weight status, a BMI of 25–30 kg/m² is categorized as overweight, and a BMI >30 is considered obese (Gremese et al., 2014). Physical dysfunction and musculoskeletal pain have been more commonly observed in obese individuals. Several clinical reports also revealed relationships between fibromyalgia and obesity (Peltonen et al., 2003; Hooper et al., 2007; De Sá Pinto et al., 2006). Yunus and coworkers examined a connection between fibromyalgia and obesity in 211 female patients and demonstrated significant correlation between BMI and fibromyalgia (Yunus et al., 2002). Neumann and coworkers evaluated the link between fibromyalgia symptoms (physical activity, muscle tenderness, and quality of life) and obesity in 100 FMS female patients. The result showed negative correlation between quality of life, tenderness threshold, and BMI and positive correlation between obesity and physical dysfunction. In the same study, pain sensitivity was found to be high in obese FMS patients (Neumann et al., 2008). Similar outcomes were obtained by Kim et al. and Timmerman et al. in their study conducted on 888 patients and 179 women suffering from FMS, respectively (Kim et al., 2012; Timmerman et al., 2013). Findings from a few more studies showed that low levels of physical exercise in overweight and obese patients increases the risk of FMS development (Mork et al., 2010; Vincent et al., 2014). Furthermore, FMS was found to be more common in obese and overweight twins than nonobese twins (Wright et al., 2010). All of these reported studies indicate a strong correlation between fibromyalgia and obesity.

Symptoms of FMS and Obesity

Obesity deleteriously affects the musculoskeletal system. Mechanical loading, inflammation, and psychological status are three major mechanisms involved in obesity-related musculoskeletal pain (Vincent et al., 2013; Messier et al., 2005; Kaur, 2014; Marcus, 2004). Mechanical loading is responsible for anabolic stimulus to the bone and improves bone strength, size, and shape by improving tissue density (Turner and Robling, 2004). Obesity induces joint pain by increasing mechanical loading on the musculoskeletal system. It subsequently reduces strength to control loading on cartilaginous areas of the joint and affects alignment of the joints. Furthermore, loading may increase toward a small cross-sectional area of the joint and cause tissue damage (Andriacchi et al., 2004). Axial joints are also victim of central obesity and cause back pain (Menegoni et al., 2009). Tissues such as tendons, cartilages, and fascia are also affected by obesity (Wearing et al., 2006). Recent evidence suggests that in obese person adipocytes enlarge and cause alteration in systemic metabolism (Greenberg and Obin, 2006). Furthermore increases in BMI and fat volume also cause adiposopathy and increased tissue pain because more macrophages are able to enter adipose tissue (Seaman, 2013). The release of several inflammatory markers such as C-reactive proteins, cytokines, and interleukins (specifically IL-6) is higher in obese individuals suffering from chronic musculoskeletal pain compared to lean individuals (Deere et al., 2012; Briggs et al., 2013). Cytokines are known to play a role in diverse clinical processes and phenomena such as fatigue, fever, sleep, pain, stress, and aching (Wallace, 2006). Increases in the release of these inflammatory markers also increases pain severity (Bas et al., 2014). Obesity also alters functions of the HPA axis and increases cortisol levels (Okifuji et al., 2009). Psychological factors also play a major role in severity of pain in obese patients, who have more fear of movement and thus are more inactive and lethargic, which ultimately increases multisite pain (Vincent et al., 2010; Seaman, 2013). Obesity is also associated with insomnia, sleep disturbances, and excessive daytime sleepiness, creating a major risk for sleep apnea. It has also been reported that sleep duration is inversely propositional to BMI while daytime sleepiness in directly proportional to BMI. Obesity reduces sleep duration and quality of sleep in fibromyalgia patients (Hargens et al., 2013; Dixon et al., 2001; Watenpaugh, 2009; St-Onge et al., 2009; Algul et al., 2009; De Araújo et al., 2015). Okifuji and coworkers observed similar outcomes in their study conducted on 215 patients suffering from fibromyalgia. The pain sensitivity was high in obese patients along with poor sleep quality and reduced physical strength (Okifuji et al., 2010). Aparicio and coworkers found that weight status affected fibromyalgia symptoms in 175 and 177 women suffering from fibromyalgia, which showed increased levels of anxiety, fatigue, stiffness, morning tiredness, and depression in overweight and obese patients compared to nonobese patients. Furthermore, the quality of life, motor agility, cardiorespiratory fitness, and upper-body flexibility was damaged more in obese patients (Aparicio et al., 2011; Aparicio et al., 2013; Aparicio et al., 2014).

Based on the fact that obesity is playing an important role in pathophysiology of fibromyalgia, many studies have been carried out by various groups of researchers that showed positive improvement in the symptoms of fibromyalgia after weight reduction. In 2005, Shapiro and coworkers investigated the relationship between BMI and FMSs in 42 obese women to determine the effect of behavioral weight-loss treatment in these patients. The outcome of the 20-week treatment showed significant reduction in FMS and pain interference and improved the patients’ quality of life (Shapiro et al., 2005). Evidence showed that weight loss through bariatric surgery in obese subjects reduced FMS up to 92% and also improved musculoskeletal health in obese people (Hooper et al., 2007; Saber et al., 2008).

A randomized controlled trial was also carried out using 86 obese fibromyalgia patients to study the effect of weight loss in improving the FMS. After a 6-month dietary weight loss program, significant improvement was observed in terms of quality of life, improved sleep quality, reduced depression, and reduced tender-point count. The C-reactive protein and interleukin-6 level were also reduced after weight-loss treatment (Senna et al., 2012). There is evidence for the beneficial role of exercise in obese fibromyalgia patients to reduce fatigue because exercise leads to increased resistin and IGF-1 levels in serum that are inversely proportional to fatigue (Bjersing et al., 2013) (Fig. 7.2).

Role of Diet and Micronutrients in Fibromyalgia

The eating habits, type of food, and nutritional level of the diet play significant role in the improvement of fibromyalgia symptoms along with pharmacological therapies (Batista et al., 2015; Arranz et al., 2012). It has been reported that nutritional factors are associated with immune and inflammatory processes and can modify the symptoms of FMS (Henderson and Panush, 1999). According to the Brazilian Rheumatology Society, nutrients play a potential role in FMS. Increased consumption of salt, sugar, fat, and alcohol worsens the symptoms of FMS while increased intake of fruits, vegetables, fluids, and fibers have beneficial effects for FMS patients. In addition, nutritional supplementation of micronutrients such as magnesium, iodine, calcium, manganese, iron, thiamine, vitamin D, melatonin, malic acid, thiamine, and sources of tryptophan are important in improving fibromyalgia symptoms (Batista et al. 2015; Arranz et al., 2010).

Summary

FMS is a rheumatic disease that affects the quality of life of people around the world. Its etiology is unknown, but various scientific and nonscientific reports show the strong involvement of obesity and lowered nutritional levels of antioxidants and essential micronutrients in its pathophysiology. Furthermore, current therapies used to treat fibromyalgia symptoms include not only pharmacological agents but also physical activities and other alternative regimens (i.e., weight-loss programs, diet modifications, and the use of antioxidant and micronutrient supplements).

The assessed clinical data showed that obesity plays a major role in FMS. The severity of symptoms in obese people is more than in nonobese fibromyalgia patients. Various clinical studies demonstrated improvement in the FMS after the use of weight-loss programs and nutritional intervention of vegetarian and vegan diets rich in antioxidants. Nevertheless, more complete and detailed studies are required to confirm the positive effects of these diets on FMS. Some nutritional deficiencies have been suggested to be involved in FMS, although detailed clinical reports on these are lacking. Few studies have been carried out that point to nutritional deficiencies of magnesium, iodine, selenium, iron, thiamine, and manganese as linked with FMS or related conditions such as chronic pain syndrome and hypothyroidism. The importance of some micronutrients in FMS has been evaluated in some studies with positive outcome. This suggests that more detailed and specific investigations are required in FMS patients to understand the beneficial effect of the cited nutrients. In conclusion, current dietary advice is necessary for FMS patients so they can maintain normal weight and enjoy the nutritional benefits of micronutrients that will reduce the severity of their symptoms.