A study protocol for a randomized controlled trial of an anti-inflammatory nutritional intervention in patients with fibromyalgia

Ana Rita Silva, Alexandra Bernardo, Maria Fernanda de Mesquita, José Vaz Patto, Pedro Moreira, Maria Leonor Silva, Patrícia Padrão, Ana Rita Silva, Alexandra Bernardo, Maria Fernanda de Mesquita, José Vaz Patto, Pedro Moreira, Maria Leonor Silva, Patrícia Padrão

Abstract

Background: This study aims to analyze the effects of a potentially anti-inflammatory nutritional intervention in disease assessment parameters, inflammatory markers, and quality of life of fibromyalgia (FM) patients.

Methods: A sample of 100 female patients diagnosed with FM, followed up at Portuguese Institute of Rheumatology (IPR) in Lisbon, is being randomly allocated in two groups. Patients in the intervention group are adopting an anti-inflammatory diet, characterized by the exemption of the intake of foods containing gluten, dairy, sugar, and ultra-processed foods, during 3 months. During the first month, a low fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) diet is implemented, along with the anti-inflammatory diet, followed by the reintroduction of all fruits and vegetables over a consecutive period of 2 months. Patients in the control group are adopting a diet based on general recommendations for healthy eating. The outcomes are pain, fatigue, quality of sleep, quality of life, gastrointestinal symptoms, and inflammation. Before and after the 3 months intervention, and also 1 month after beginning the intervention, the following questionnaires are applied: Revised Fibromyalgia Impact Questionnaire, visual analog pain scale, Brief Pain Inventory,visual analog scale from a list of common gastrointestinal and extraintestinal symptoms in FM, Short Form 36, Fatigue Severity Survey, and Pittsburg Sleep Quality Index. Ultra-sensitive serum C-reactive protein, eritrocyte sedimentation rate, and interleukin-8 are determined. Age, physical activity, anthropometric parameters, and body composition are being collected. Student's t test will assess the association between the disease evaluation parameters, the inflammatory markers, and the dietary interventions.

Discussion: The results of this study are expected to determine whether a change in patient nutrition helps to alleviate symptoms, which would optimize medical intervention.

Trial registration: www.ClinicalTrials.gov NCT04007705 . Registered on July 5, 2019.

Keywords: Anti-inflammatory; Diet; FODMAPs; Fibromyalgia; Pain; Quality of life; Randomized controlled trial.

Conflict of interest statement

The authors report no financial or personal conflicts of interest.

Figures

Fig. 1
Fig. 1
Experimental design of the randomized controlled clinical trial. Note: FODMAPs, fermentable oligo-, di-, and monosaccharides and polyols; FIQ-R, Revised Fibromyalgia Impact Questionnaire; SF-36, Short Form 36; EVA-Pain, visual analog pain scale; EVA-GI, visual analog scale from a list of common gastrointestinal and extraintestinal symptoms in FM; BPI, brief pain inventory; PSQI, Pittsburg Sleep Quality Index; FSS, Fatigue Severity Survey; hs-CRP, serum C-reactive protein; ESR, eritrocyte sedimentation rate; IL-8, interleukin-8
Fig. 2
Fig. 2
Schedule of enrolment, interventions, and assessments, according to SPIRIT guidelines. Note: FODMAPs, fermentable oligo-, di-, and monosaccharides and polyols; FIQ-R, Revised Fibromyalgia Impact Questionnaire; SF-36, Short Form 36; EVA-Pain, visual analog pain scale; EVA-GI, visual analogue scale from a list of common gastrointestinal and extraintestinal symptoms in FM; BPI, brief pain inventory; PSQI, Pittsburg Sleep Quality Index; FSS, Fatigue Severity Survey; hs-CRP, serum C-reactive protein; ESR, eritrocyte sedimentation rate; IL-8, interleukin-8

References

    1. Clauw DJ. Fibromyalgia: an overview. Am J Med. 2009;122(12 Suppl):S3–S13. doi: 10.1016/j.amjmed.2009.09.006.
    1. Branco JC, et al. Prevalence of fibromyalgia: a survey in five European countries. Semin Arthritis Rheum. 2010;39(6):448–453. doi: 10.1016/j.semarthrit.2008.12.003.
    1. Branco JC, et al. Prevalence of rheumatic and musculoskeletal diseases and their impact on health-related quality of life, physical function and mental health in Portugal: results from EpiReumaPt- a national health survey. RMD Open. 2016;2(1):e000166. doi: 10.1136/rmdopen-2015-000166.
    1. Wallace DJ, Hallegua DS. Fibromyalgia: the gastrointestinal link. Curr Pain Headache Rep. 2004;8(5):364–368. doi: 10.1007/s11916-996-0009-z.
    1. Atzeni F, et al. Pain in systemic inflammatory rheumatic diseases. Best Pract Res Clin Rheumatol. 2015;29(1):42–52. doi: 10.1016/j.berh.2015.04.016.
    1. Triadafilopoulos G, Simms RW, Goldenberg DL. Bowel dysfunction in fibromyalgia syndrome. Dig Dis Sci. 1991;36(1):59–64. doi: 10.1007/BF01300088.
    1. Carding S, et al. Dysbiosis of the gut microbiota in disease. Microb Ecol Health Dis. 2015;26:26191.
    1. Marsh A, Eslick EM, Eslick GD. Does a diet low in FODMAPs reduce symptoms associated with functional gastrointestinal disorders? A comprehensive systematic review and meta-analysis. Eur J Nutr. 2016;55(3):897–906. doi: 10.1007/s00394-015-0922-1.
    1. Pimentel M, et al. A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing. Ann Rheum Dis. 2004;63(4):450–452. doi: 10.1136/ard.2003.011502.
    1. Goebel A, et al. Altered intestinal permeability in patients with primary fibromyalgia and in patients with complex regional pain syndrome. Rheumatology (Oxford) 2008;47(8):1223–1227. doi: 10.1093/rheumatology/ken140.
    1. Marum AP, et al. A low fermentable oligo-di-mono saccharides and polyols (FODMAP) diet reduced pain and improved daily life in fibromyalgia patients. Scand J Pain. 2016;13:166–172. doi: 10.1016/j.sjpain.2016.07.004.
    1. Clauw DJ. Fibromyalgia and related conditions. Mayo Clin Proc. 2015;90(5):680–692. doi: 10.1016/j.mayocp.2015.03.014.
    1. Feng B, et al. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Neural and neuro-immune mechanisms of visceral hypersensitivity in irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2012;302(10):G1085–G1098. doi: 10.1152/ajpgi.00542.2011.
    1. Alam MS, et al. Interaction of Plasmodium vivax tryptophan-rich antigen PvTRAg38 with band 3 on human erythrocyte surface facilitates parasite growth. J Biol Chem. 2015;290(33):20257–20272. doi: 10.1074/jbc.M115.644906.
    1. Bazzichi L, et al. Cytokine patterns in fibromyalgia and their correlation with clinical manifestations. Clin Exp Rheumatol. 2007;25(2):225–230.
    1. Uceyler N, Hauser W, Sommer C. Systematic review with meta-analysis: cytokines in fibromyalgia syndrome. BMC Musculoskelet Disord. 2011;12:245. doi: 10.1186/1471-2474-12-245.
    1. Sanada K, et al. Effects of non-pharmacological interventions on inflammatory biomarker expression in patients with fibromyalgia: a systematic review. Arthritis Res Ther. 2015;17:272. doi: 10.1186/s13075-015-0789-9.
    1. Cavicchia PP, et al. A new dietary inflammatory index predicts interval changes in serum high-sensitivity C-reactive protein. J Nutr. 2009;139(12):2365–2372. doi: 10.3945/jn.109.114025.
    1. Shivappa N, et al. Designing and developing a literature-derived, population-based dietary inflammatory index. Public Health Nutr. 2014;17(8):1689–1696. doi: 10.1017/S1368980013002115.
    1. Taneja V. Arthritis susceptibility and the gut microbiome. FEBS Lett. 2014;588(22):4244–4249. doi: 10.1016/j.febslet.2014.05.034.
    1. Melnik BC. Milk--the promoter of chronic Western diseases. Med Hypotheses. 2009;72(6):631–639. doi: 10.1016/j.mehy.2009.01.008.
    1. Straub RH. Insulin resistance, selfish brain, and selfish immune system: an evolutionarily positively selected program used in chronic inflammatory diseases. Arthritis Res Ther. 2014;16(Suppl 2):S4. doi: 10.1186/ar4688.
    1. Wahli W, Michalik L. PPARs at the crossroads of lipid signaling and inflammation. Trends Endocrinol Metab. 2012;23(7):351–363. doi: 10.1016/j.tem.2012.05.001.
    1. Suen J, et al. Effect of flavonoids on oxidative stress and inflammation in adults at risk of cardiovascular disease: a systematic review. Healthcare. 2016;4(3):69. doi: 10.3390/healthcare4030069.
    1. Donaldson MS, Speight N, Loomis S. Fibromyalgia syndrome improved using a mostly raw vegetarian diet: an observational study. BMC Complement Altern Med. 2001;1:7. doi: 10.1186/1472-6882-1-7.
    1. Kaartinen K, et al. Vegan diet alleviates fibromyalgia symptoms. Scand J Rheumatol. 2000;29(5):308–313. doi: 10.1080/030097400447697.
    1. Shapiro JR, Anderson DA, Danoff-Burg S. A pilot study of the effects of behavioral weight loss treatment on fibromyalgia symptoms. J Psychosom Res. 2005;59(5):275–282. doi: 10.1016/j.jpsychores.2005.06.081.
    1. Senna MK, et al. Effect of weight reduction on the quality of life in obese patients with fibromyalgia syndrome: a randomized controlled trial. Clin Rheumatol. 2012;31(11):1591–1597. doi: 10.1007/s10067-012-2053-x.
    1. Silva AR, et al. Dietary interventions in fibromyalgia: a systematic review. Ann Med. 2019;51:1–29.
    1. Organization, W.H . Healthy diet. 2018. pp. 1–6.
    1. Calder PC, et al. Inflammatory disease processes and interactions with nutrition. Br J Nutr. 2009;101(Suppl 1):S1–45.
    1. Kontogianni MD, Zampelas A, Tsigos C. Nutrition and inflammatory load. Ann N Y Acad Sci. 2006;1083:214–238. doi: 10.1196/annals.1367.015.
    1. Ruiz-Nunez B, et al. Lifestyle and nutritional imbalances associated with Western diseases: causes and consequences of chronic systemic low-grade inflammation in an evolutionary context. J Nutr Biochem. 2013;24(7):1183–1201. doi: 10.1016/j.jnutbio.2013.02.009.
    1. Zhong D, et al. The role of gut microbiota in the pathogenesis of rheumatic diseases. Clin Rheumatol. 2018;37(1):25–34. doi: 10.1007/s10067-017-3821-4.
    1. Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014;157(1):121–141. doi: 10.1016/j.cell.2014.03.011.
    1. Minihane AM, et al. Low-grade inflammation, diet composition and health: current research evidence and its translation. Br J Nutr. 2015;114(7):999–1012. doi: 10.1017/S0007114515002093.
    1. Hollon J, et al. Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity. Nutrients. 2015;7(3):1565–1576. doi: 10.3390/nu7031565.
    1. Fasano A. Zonulin, regulation of tight junctions, and autoimmune diseases. Ann N Y Acad Sci. 2012;1258:25–33. doi: 10.1111/j.1749-6632.2012.06538.x.
    1. O'Toole A, Korzenik J. Environmental triggers for IBD. Curr Gastroenterol Rep. 2014;16(7):396. doi: 10.1007/s11894-014-0396-y.
    1. Kunz C, Lonnerdal B. Human milk proteins: separation of whey proteins and their analysis by polyacrylamide gel electrophoresis, fast protein liquid chromatography (FPLC) gel filtration, and anion-exchange chromatography. Am J Clin Nutr. 1989;49(3):464–470. doi: 10.1093/ajcn/49.3.464.
    1. Pal S, et al. Milk intolerance, beta-casein and lactose. Nutrients. 2015;7(9):7285–7297. doi: 10.3390/nu7095339.
    1. Brooke-Taylor S, et al. Systematic review of the gastrointestinal effects of A1 compared with A2 beta-casein. Adv Nutr. 2017;8(5):739–748. doi: 10.3945/an.116.013953.
    1. Ul Haq MR, et al. Comparative evaluation of cow beta-casein variants (A1/A2) consumption on Th2-mediated inflammatory response in mouse gut. Eur J Nutr. 2014;53(4):1039–1049. doi: 10.1007/s00394-013-0606-7.
    1. Kim JA, Wei Y, Sowers JR. Role of mitochondrial dysfunction in insulin resistance. Circ Res. 2008;102(4):401–414. doi: 10.1161/CIRCRESAHA.107.165472.
    1. Della Corte KW, et al. Effect of dietary sugar intake on biomarkers of subclinical inflammation: a systematic review and meta-analysis of intervention studies. Nutrients. 2018;10(5):606. doi: 10.3390/nu10050606.
    1. Haroon E, Miller AH. Inflammation effects on brain glutamate in depression: mechanistic considerations and treatment implications. Curr Top Behav Neurosci. 2017;31:173–198. doi: 10.1007/7854_2016_40.
    1. Laudisi F, et al. The food additive maltodextrin promotes endoplasmic reticulum stress-driven mucus depletion and exacerbates intestinal inflammation. Cell Mol Gastroenterol Hepatol. 2019;7(2):457–473. doi: 10.1016/j.jcmgh.2018.09.002.
    1. Guilbaud A, et al. How can diet affect the accumulation of advanced glycation end-products in the human body? Foods. 2016;5(4):84. doi: 10.3390/foods5040084.
    1. Uribarri J, et al. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc. 2010;110(6):911–916. doi: 10.1016/j.jada.2010.03.018.
    1. Teodorowicz M, van Neerven J, Savelkoul H. Food processing: the influence of the maillard reaction on immunogenicity and allergenicity of food proteins. Nutrients. 2017;9(8):835. doi: 10.3390/nu9080835.
    1. Luevano-Contreras C, Chapman-Novakofski K. Dietary advanced glycation end products and aging. Nutrients. 2010;2(12):1247–1265. doi: 10.3390/nu2121247.
    1. Tabrizi R, et al. The effects of resveratrol supplementation on biomarkers of inflammation and oxidative stress among patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials. Food Funct. 2018;9(12):6116–6128. doi: 10.1039/C8FO01259H.
    1. Carlsen MH, et al. The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide. Nutr J. 2010;9:3. doi: 10.1186/1475-2891-9-3.
    1. Herrera E, et al. Aspects of antioxidant foods and supplements in health and disease. Nutr Rev. 2009;67(Suppl 1):S140–S144. doi: 10.1111/j.1753-4887.2009.00177.x.
    1. Organization, W.H . Healthy diet. 2018.
    1. Costa C, et al. Psychometric properties of the Revised Fibromyalgia Impact Questionnaire (FIQR) - a contribution to the Portuguese validation of the scale. Acta Reumatol Port. 2016;41(3):240–250.
    1. Price DD, et al. The validation of visual analogue scales as ratio scale measures for chronic and experimental pain. Pain. 1983;17(1):45–56. doi: 10.1016/0304-3959(83)90126-4.
    1. Boonstra AM, et al. Reliability and validity of the visual analogue scale for disability in patients with chronic musculoskeletal pain. Int J Rehabil Res. 2008;31(2):165–169. doi: 10.1097/MRR.0b013e3282fc0f93.
    1. Valente MAF, Ribeiro JLP, Jensen MP. Further validation of a portuguese version of the brief pain inventory interference scale. Clín Salud. 2012;23(1):89–96. doi: 10.5093/cl2012a6.
    1. Keller S, et al. Validity of the brief pain inventory for use in documenting the outcomes of patients with noncancer pain. Clin J Pain. 2004;20(5):309–318. doi: 10.1097/00002508-200409000-00005.
    1. Bengtsson M, Ohlsson B, Ulander K. Development and psychometric testing of the visual analogue scale for irritable bowel syndrome (VAS-IBS) BMC Gastroenterol. 2007;7:16. doi: 10.1186/1471-230X-7-16.
    1. Bengtsson M, et al. Further validation of the visual analogue scale for irritable bowel syndrome after use in clinical practice. Gastroenterol Nurs. 2013;36(3):188–198. doi: 10.1097/SGA.0b013e3182945881.
    1. Ferreira, P.L., [Development of the Portuguese version of MOS SF-36. Part II --validation tests]. Acta Medica Port. 2000;13(3):119–27.
    1. Fredheim OM, et al. Validation and comparison of the health-related quality-of-life instruments EORTC QLQ-C30 and SF-36 in assessment of patients with chronic nonmalignant pain. J Pain Symptom Manag. 2007;34(6):657–665. doi: 10.1016/j.jpainsymman.2007.01.011.
    1. Laranjeira CA. Translation and adaptation of the fatigue severity scale for use in Portugal. Appl Nurs Res. 2012;25(3):212–217. doi: 10.1016/j.apnr.2010.11.001.
    1. Del Rio Joao KA, et al. Validation of the Portuguese version of the Pittsburgh Sleep Quality Index (PSQI-PT) Psychiatry Res. 2017;247:225–229. doi: 10.1016/j.psychres.2016.11.042.
    1. Slim M, et al. The effects of a gluten-free diet versus a hypocaloric diet among patients with fibromyalgia experiencing gluten sensitivity-like symptoms: a pilot, open-label randomized clinical trial. J Clin Gastroenterol. 2017;51(6):500–507. doi: 10.1097/MCG.0000000000000651.
    1. Vellisca MY, Latorre JI. Monosodium glutamate and aspartame in perceived pain in fibromyalgia. Rheumatol Int. 2014;34(7):1011–1013. doi: 10.1007/s00296-013-2801-5.

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