Bioactive Compounds for Fibromyalgia-like Symptoms: A Narrative Review and Future Perspectives

Abstract

Fibromyalgia (FM) is a prevalent, chronic condition without a cure or reliable therapy. The etiopathogenesis of this syndrome is ambiguous, which has heightened the challenge of discovering treatments to minimize patients' painful symptoms. FM is characterized by diffuse musculoskeletal pain usually accompanied by functional pain syndromes, such as fatigue, sleep disturbances, cognitive difficulties, and mood issues. Currently available treatment options for FM are limited. Recent studies have suggested a potential role for dietary bioactive compounds in FM management. We performed a narrative review to evaluate the existing evidence regarding the dietary bioactive compounds for FM, and we proposed molecular mechanisms on this topic. The inclusion criteria were (i) human, in vivo, or in vitro studies, (ii) studies related to the effect of bioactive compounds on FM-like symptoms, (iii) peer-reviewed literature, and (iv) publications until February 2022 in PubMed and Google Scholar. Exclusion criteria were (i) study designs using CCI, SNI, or SNL models because they are more NP models rather than FM models, and (ii) studies published in a language other than English. Keywords were dietary bioactive compounds, fibromyalgia, cell, animals, humans. Here, we report the effects of commonly consumed bioactive compounds (capsaicin, ginger, curcumin, n-3 PUFA, grape seed extract, naringin, and genistein) on FM-like symptoms in cellular, animal, and human studies. Cellular studies demonstrated that these bioactive compounds reduce pro-inflammatory production and increase antioxidant capacity of neurons or myoblasts that regulate apoptosis/cell survival. Animal studies showed that these regularly consumed bioactive compounds have an effect on FM-like symptoms, as evidenced by decreased pain hypersensitivity and fatigue as well as improved social behaviors. Further studies are warranted to allow meaningful comparison and quantification of the efficacy of these bioactive compounds on FM-like symptoms across studies, in terms of actual changes in antioxidant capacity, pain hypersensitivity, fatigue, and social behaviors. To date, human studies regarding the efficacy of these bioactive compounds on FM-like symptoms are limited and inconclusive. Our review identifies this important knowledge gap and proposes that the development and use of improved preclinical FM models are needed, particularly concerning the usage of female animals to better mimic FM pathophysiology and symptomatology.

Keywords: fibromyalgia; functional food; inflammation; mitochondria; nervous system.

Figure 1

Diagram illustrates the potential actions of the bioactive compounds capsaicin, ginger, curcumin, grape seed extract, n-3 PUFA, naringin, and genistein on fibromyalgia-like symptoms. These compounds not only result in the production of pro-inflammatory cytokines, lipid peroxidation, and oxidative stress, but also result in upregulating antioxidant enzymes capacities in the nervous system, skeletal muscles, and circulatory system. The consequence is mitigation of the progression of fibromyalgia-like symptoms. Abbreviations: AA/EPA, arachidonic acid/eicosapentaenoic acid; CAT, catalase; CK, creatine kinase; CNS, central nervous system; DRG, dorsal root ganglion; GSH, glutathione; IL-1β, interleukin-1β; LA, lactic acid; LDH, lactate dehydrogenase; MAPs, muscle action potentials; MDA, malondialdehyde; MMP-9, matrix metalloproteinase-9; NO, nitric oxide; n-3 PUFA, n-3 polyunsaturated fatty acids; PGE2, prostaglandin E2; PNS, peripheral nervous system; ROS, reactive oxygen species; SDH, succinate dehydrogenase; SOD, superoxide dismutase; T-AOC, total antioxidant capacity; TNF-α, tumor necrosis factor-α; TXB2, thromboxane B2.