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Pathophysiological and nutritional aspects in the etiology and management of gastroesophageal reflux disease

Published online by Cambridge University Press:  24 March 2025

Daniel Ferreira da Silva Open the ORCID record for Daniel Ferreira da Silva [Opens in a new window] ,
Rayana Líbia Vieira Lima Open the ORCID record for Rayana Líbia Vieira Lima [Opens in a new window] ,
Pedro Carrera-Bastos Open the ORCID record for Pedro Carrera-Bastos [Opens in a new window] ,
Damien Ribeiro Maia  and
Paulo Marconi Linhares Mendonça
Daniel Ferreira da Silva*
Affiliation:
Federal University of Ceará, Multidisciplinary Residency Program in Diabetes Care, Walter Cantídio University Hospital, Rua Coronel Nunes de Melo, s/n, Rodolfo Teófilo - Bloco dos Ambulatórios (Ilhas) - 1o andar, CEP 60430-270, Fortaleza, Ceará, Brazil
Rayana Líbia Vieira Lima
Affiliation:
Federal University of Ceará, Multidisciplinary Residency Program in Diabetes Care, Walter Cantídio University Hospital, Rua Coronel Nunes de Melo, s/n, Rodolfo Teófilo - Bloco dos Ambulatórios (Ilhas) - 1o andar, CEP 60430-270, Fortaleza, Ceará, Brazil
Pedro Carrera-Bastos
Affiliation:
Center for Primary Health Care Research, Department of Clinical Sciences, Lund University, 205 02 Malmö, Sweden Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, 28670 Madrid, Spain Centro de Estudios Avanzados en Nutrición (CEAN), 11007 Cádiz, Spain
Damien Ribeiro Maia
Affiliation:
Federal University of Ceara, Faculty of Law, Rua Meton de Alencar, s/n – Centro, CEP 60035-160, Fortaleza, Ceará, Brazil
Paulo Marconi Linhares Mendonça
Affiliation:
Federal Institute of Education, Science and Technology of Ceará - Limoeiro do Norte Campus, Rua Estevão Remígio, 1145, Monsenhor Otávio, CEP 62930-000, Limoeiro do Norte, Ceará, Brazil
*
Corresponding author: Daniel Ferreira da Silva; Email: danielferreiranutricionista@gmail.com
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Abstract

Gastroesophageal reflux disease (GERD) is a prevalent condition observed across various medical specialties, including gastroenterology, otorhinolaryngology, surgery and primary care. Despite the routine prescription of proton pump inhibitors, some patients fail to experience adequate symptom relief. This review delves into the multifactorial mechanisms of reflux, which extend beyond hydrochloric acid to include pepsin, bile acids and trypsin. These factors significantly contribute to mucosal injury in GERD and are influenced by dietary composition. Moreover, dietary patterns with anti-inflammatory properties, such as the Mediterranean and dietary approaches to stop hypertension diets, have shown potential in GERD managing, particularly in the context of obesity–an important risk factor.

Keywords

Gastroesophageal refluxObesityDietary patternsEsophagitis

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Type
Review
Information
British Journal of Nutrition , Volume 133 , Issue 8 , 28 April 2025 , pp. 1057 - 1070
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Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of The Nutrition Society

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References

Yim, M, Chiou, EH & Ongkasuwan, J (2016) Otolaryngologic manifestations of gastroesophageal reflux. Curr Treat Options Pediatr 2, 236–245.CrossRefGoogle Scholar
Clarrett, DM & Hachem, C (2019) Gastroesophageal reflux disease (GERD). Mo Med 115, 214–218.Google Scholar
Eusebi, LH, Ratnakumaran, R, Yuan, Y, et al. (2018) Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis. Gut 67, 430–440.CrossRefGoogle ScholarPubMed
Nirwan, JS, Hasan, SS, Babar, ZUD, et al. (2020) Global prevalence and risk factors of Gastro-Oesophageal Reflux Disease (GORD): systematic review with meta-analysis. Sci Rep 10, 5814.CrossRefGoogle ScholarPubMed
Johnston, N, Dettmar, PW, Strugala, V, et al. (2013) Laryngopharyngeal reflux and GERD. Ann N Y Acad Sci 1300, 71–79.CrossRefGoogle ScholarPubMed
Lazarini, P & da Silva, L (2007) Laryngopharyngeal reflux disease: review Acta Otorrinolaringol 25, 190–196.Google Scholar
Mayo-Yáñez, M, Viña-Vázquez, S, Lechien, JR, et al. (2023) Involvement of laryngopharyngeal reflux in ocular diseases: a state-of-the-art review. J Voice 37, 586–597.CrossRefGoogle Scholar
Parasa, S & Sharma, P (2013) Complications of gastro-oesophageal reflux disease. Best Pract Res Clin Gastroenterol 27, 433–442.CrossRefGoogle ScholarPubMed
Gyawali, CP & Fass, R (2018) Management of gastroesophageal reflux disease. Gastroenterology 154, 302–318.CrossRefGoogle ScholarPubMed
Li, Y, Xu, G, Zhou, B, et al. (2022) Effects of acids, pepsin, bile acids, and trypsin on laryngopharyngeal reflux diseases: physiopathology and therapeutic targets. Eur Arch Oto-Rhino-Laryngology 279, 2743–2752.CrossRefGoogle ScholarPubMed
Mermelstein, J, Chait Mermelstein, A & Chait, MM (2018) Proton pump inhibitor-refractory gastroesophageal reflux disease: challenges and solutions. Clin Exp Gastroenterol 11, 119–134.CrossRefGoogle ScholarPubMed
Fossmark, R, Martinsen, TC & Waldum, HL (2019) Adverse effects of proton pump inhibitors—evidence and plausibility. Int J Mol Sci 20, 5203.CrossRefGoogle ScholarPubMed
Newberry, C & Lynch, K (2019) The role of diet in the development and management of gastroesophageal reflux disease: why we feel the burn. J Thorac Dis 11, S1594–601.CrossRefGoogle ScholarPubMed
Hwalla, N & Jaafar, Z (2020) Dietary management of obesity: a review of the evidence. Diagn 11, 24.CrossRefGoogle ScholarPubMed
Hershcovici, T, Mashimo, H & Fass, R (2011) The lower esophageal sphincter. Neurogastroenterol Motil 23, 819–830.CrossRefGoogle ScholarPubMed
de Carlos, F, Cobo, J, Macías, E, et al. (2013) The sensory innervation of the human pharynx: searching for mechanoreceptors. Anat Rec 296, 1735–1746.CrossRefGoogle ScholarPubMed
Sidhu, AS & Lopoulos, GT (2008) Neuro-regulation of lower esophageal sphincter function as treatment for gastroesophageal refl ux disease. World J Gastroenterol 14, 985.CrossRefGoogle Scholar
Chen, J (2016) Ineffective esophageal motility and the vagus: current challenges and future prospects. Clin Exp Gastroenterol 9, 291–299.CrossRefGoogle ScholarPubMed
Rattan, S, Coln, D & Goyal, RK (1976) The mechanism of action of gastrin on the lower esophageal sphincter. Gastroenterology 70, 828–831.CrossRefGoogle ScholarPubMed
Wright, LE & Castell, DO (1975) The adverse effect of chocolate on lower esophageal sphincter pressure. Am J Dig Dis 20, 703–707.CrossRefGoogle ScholarPubMed
Babaei, A & Mittal, R (2018) Cholecystokinin induces esophageal longitudinal muscle contraction and transient lower esophageal sphincter relaxation in healthy humans. Am J Physiology-Gastrointestinal Liver Physiol 315, G734–42.CrossRefGoogle ScholarPubMed
Mittal, RK, Fisher, M, McCallum, RW, et al. (1990) Human lower esophageal sphincter pressure response to increased intra-abdominal pressure. Am J Physiology-Gastrointestinal Liver Physiol 258, G624–30.CrossRefGoogle ScholarPubMed
Argüero, J & Sifrim, D (2024) Pathophysiology of gastro-oesophageal reflux disease: implications for diagnosis and management. Nat Rev Gastroenterol Hepatol 21, 282–293.CrossRefGoogle ScholarPubMed
Campagnolo, A, Priston, J, Thoen, R, et al. (2013) Laryngopharyngeal reflux: diagnosis, treatment, and latest research. Int Arch Otorhinolaryngol 18, 184–191.Google ScholarPubMed
Runggaldier, D, van Schie, B, Marti, S, et al. (2023) Current possibilities and challenges in the treatment of laryngopharyngeal reflux. HNO 71, 294–303.CrossRefGoogle ScholarPubMed
Jodorkovsky, D, Katzka, DA & Gyawali, CP (2023) A perspective on the clinical relevance of weak or nonacid reflux. Neurogastroenterol Motil 35, e14671.CrossRefGoogle ScholarPubMed
Boeckxstaens, GE & Smout, A (2010) Systematic review: role of acid, weakly acidic and weakly alkaline reflux in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 32, 334–343.CrossRefGoogle ScholarPubMed
Kowalik, K & Krzeski, A (2017) The role of pepsin in the laryngopharyngeal reflux. Otolaryngologia Polska 71, 7–13.CrossRefGoogle ScholarPubMed
Nortunen, M, Väkiparta, N, Parkkila, S, et al. (2022) Carbonic anhydrases II, IX, and XII in reflux esophagitis. Dig Dis Sci 67, 1761–1772.CrossRefGoogle ScholarPubMed
Jovov, B, Que, J, Tobey, NA, et al. (2011) Role of E-cadherin in the pathogenesis of gastroesophageal reflux disease. Am J Gastroenterol 106, 1039–1047.CrossRefGoogle ScholarPubMed
Stabenau, KA, Samuels, TL, Lam, TK, et al. (2023) Pepsinogen/Proton pump co-expression in Barrett’s esophageal cells induces cancer-associated changes. Laryngoscope 133, 59–69.CrossRefGoogle ScholarPubMed
Stanforth, KJ, Wilcox, MD, Chater, PI, et al. (2022) Pepsin properties, structure, and its accurate measurement: a narrative review. Ann Esophagus 5, 31–31.CrossRefGoogle Scholar
Al-Janabi, J, Hartsuck, JA & Tang, J (1972) Kinetics and mechanism of pepsinogen activation. J Biol Chem 247, 4628–4632.CrossRefGoogle ScholarPubMed
Gill, GA, Johnston, N, Buda, A, et al. (2005) Laryngeal epithelial defenses against laryngopharyngeal reflux: investigations of E-cadherin, carbonic anhydrase isoenzyme III, and pepsin. Ann Otology, Rhinology Laryngology 114, 913–921.CrossRefGoogle ScholarPubMed
Bardhan, KD, Strugala, V & Dettmar, PW (2012) Reflux revisited: advancing the role of pepsin. Int J Otolaryngol 2012, 1–13.CrossRefGoogle ScholarPubMed
Yin, CY, Zhang, SS, Zhong, JT, et al. (2021) Pepsin and laryngeal and hypopharyngeal carcinomas. Clin Exp Otorhinolaryngol 14, 159–168.CrossRefGoogle ScholarPubMed
Lyros, O, Rafiee, P, Nie, L, et al. (2015) Wnt/β-Catenin signaling activation beyond robust nuclear β-catenin accumulation in nondysplastic Barrett’s esophagus: regulation via Dickkopf-1. Neoplasia 17, 598–611.CrossRefGoogle ScholarPubMed
Yu, F, Yu, C, Li, F, et al. (2021) Wnt/β-catenin signaling in cancers and targeted therapies. Signal Transduct Target Ther 6, 307.CrossRefGoogle ScholarPubMed
Jung, YS & Park, JI (2020) Wnt signaling in cancer: therapeutic targeting of Wnt signaling beyond β-catenin and the destruction complex. Exp Mol Med 52, 183–191.CrossRefGoogle ScholarPubMed
Shi, X, Chen, Z, Yang, Y, et al. (2022) Bile reflux gastritis: insights into pathogenesis, relevant factors, carcinomatous risk, diagnosis, and management. Gastroenterol Res Pract 2022, 1–7.Google ScholarPubMed
Shulpekova, Y, Shirokova, E, Zharkova, M, et al. (2022) A recent ten-year perspective: bile acid metabolism and signaling. Molecules 27, 1983.CrossRefGoogle ScholarPubMed
Zhang, Q, Agoston, AT, Pham, TH, et al. (2019) Acidic bile salts induce epithelial to mesenchymal transition via VEGF signaling in non-neoplastic Barrett’s cells. Gastroenterology 156, 130–144.e10.CrossRefGoogle ScholarPubMed
Sasaki, CT, Hajek, M, Doukas, SG, et al. (2020) The role of bile reflux and its related NF-κB activated pathway in progression of hypopharyngeal squamous cell cancer. Oral Oncol 105, 104668.CrossRefGoogle ScholarPubMed
Zhang, ML, Ran, LQ, Wu, MJ, et al. (2022) NF-κB: a novel therapeutic pathway for gastroesophageal reflux disease? World J Clin Cases 10, 8436–8442.CrossRefGoogle ScholarPubMed
Kandulski, A, Wex, T, Mönkemüller, K, et al. (2010) Proteinase-activated receptor-2 in the pathogenesis of gastroesophageal reflux disease. Am J Gastroenterol 105, 1934–1943.CrossRefGoogle ScholarPubMed
Yoshida, N, Katada, K, Handa, O, et al. (2007) Interleukin-8 production via protease-activated receptor 2 in human esophageal epithelial cells. Int J Mol Med 19, 335–340.Google ScholarPubMed
Lee, JS, Oh, TY, Ahn, BO, et al. (2001) Involvement of oxidative stress in experimentally induced reflux esophagitis and Barrett’s esophagus: clue for the chemoprevention of esophageal carcinoma by antioxidants. Mutat Res/Fundamental Mol Mech Mutagen 480–481, 189–200.CrossRefGoogle ScholarPubMed
Grad, S, Abenavoli, L & L Dumitrascu, D (2016) The effect of alcohol on gastrointestinal motility. Rev Recent Clin Trials 11, 191–195.CrossRefGoogle ScholarPubMed
Pandolfino, JE & Kahrilas, PJ (2000) Smoking and gastro-oesophageal reflux disease. Eur J Gastroenterol Hepatol 12, 837–842.CrossRefGoogle ScholarPubMed
Yang, Y, Lin, JR, Li, YQ, et al. (2023) Effect of body weight and obesity on esophageal function. Physiol Res 72, 525–537.CrossRefGoogle ScholarPubMed
Zhan, J, Yuan, M, Zhao, Y, et al. (2022) Abdominal obesity increases the risk of reflux esophagitis: a systematic review and meta-analysis. Scand J Gastroenterol 57, 131–142.CrossRefGoogle ScholarPubMed
MacFarlane, B (2018) Management of gastroesophageal reflux disease in adults: a pharmacist’s perspective. Integr Pharm Res Pract 7, 41–52.Google ScholarPubMed
Ali, RAR, Hassan, J & Egan, LJ (2022) Review of recent evidence on the management of heartburn in pregnant and breastfeeding women. BMC Gastroenterol 22, 219.CrossRefGoogle ScholarPubMed
Sfara, A & Dumitrașcu, DL (2019) The management of hiatal hernia: an update on diagnosis and treatment. Med Pharm Rep 92, 321.Google ScholarPubMed
Fass, R, McCallum, RW & Parkman, HP (2009) Treatment challenges in the management of gastroparesis-related GERD. Gastroenterol Hepatol (N Y) 5, 4–16.Google ScholarPubMed
Emerenziani, S (2013) Gastro-esophageal reflux disease and obesity, where is the link? World J Gastroenterol 19, 6536.CrossRefGoogle ScholarPubMed
Hampel, H, Abraham, NS & El-Serag, HB (2005) Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med 143, 199.CrossRefGoogle ScholarPubMed
Nocon, M, Labenz, J, Jaspersen, D, et al. (2007) Association of body mass index with heartburn, regurgitation and esophagitis: results of the Progression of Gastroesophageal Reflux Disease study. J Gastroenterol Hepatol 22, 1728–1731.CrossRefGoogle ScholarPubMed
Kröner, PT, Cortés, P & Lukens, FJ (2021) The medical management of gastroesophageal reflux disease: a narrative review. J Prim Care Community Health 12, 215013272110467.CrossRefGoogle ScholarPubMed
Fraser-Moodie, CA, Norton, B, Gornall, C, et al. (1999) Weight loss has an independent beneficial effect on symptoms of gastro-oesophageal reflux in patients who are overweight. Scand J Gastroenterol 34, 337–340.CrossRefGoogle ScholarPubMed
Jacobson, BC, Somers, SC, Fuchs, CS, et al. (2006) Body-Mass Index and symptoms of gastroesophageal reflux in women. N Engl J Med 354, 2340–2348.CrossRefGoogle ScholarPubMed
O’Doherty, MG, Freedman, ND, Hollenbeck, AR, et al. (2012) A prospective cohort study of obesity and risk of oesophageal and gastric adenocarcinoma in the NIH–AARP Diet and Health Study. Gut 61, 1261–1268.CrossRefGoogle ScholarPubMed
Sun, XM (2015) Association between diabetes mellitus and gastroesophageal reflux disease: a meta-analysis. World J Gastroenterol 21, 3085.CrossRefGoogle ScholarPubMed
Fukunaga, S, Mukasa, M, Nakano, D, et al. (2023) Changing from NAFLD to MASLD: similar cumulative incidence of reflux esophagitis between NAFLD and MASLD. Clin Mol Hepatol 30, 121–123.CrossRefGoogle ScholarPubMed
Hsu, CS, Wang, PC, Chen, JH, et al. (2011) Increasing insulin resistance is associated with increased severity and prevalence of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 34, 994–1004.CrossRefGoogle ScholarPubMed
Budiyani, L, Purnamasari, D, Simadibrata, M, et al. (2017) Differences in the insulin resistance levels measured by HOMA-IR between patients with erosive and non-erosive gastroesophageal reflux disease. J ASEAN Fed Endocr Soc 32, 139–144.CrossRefGoogle ScholarPubMed
Krishnasamy, S & Abell, TL (2018) Diabetic gastroparesis: principles and current trends in management. Diabetes Ther 9, 1–42.CrossRefGoogle ScholarPubMed
Egboh, SM & Abere, S (2022) Gastroparesis: a multidisciplinary approach to management. Cureus 14, e21295.Google ScholarPubMed
Magkos, F, Fraterrigo, G, Yoshino, J, et al. (2016) Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity. Cell Metab 23, 591–601.CrossRefGoogle ScholarPubMed
Wu, KL, Kuo, CM, Yao, CC, et al. (2018) The effect of dietary carbohydrate on gastroesophageal reflux disease. J Formosan Med Assoc 117, 973–978.CrossRefGoogle ScholarPubMed
Austin, GL, Thiny, MT, Westman, EC, et al. (2006) A very low-carbohydrate diet improves gastroesophageal reflux and its symptoms. Dig Dis Sci 51, 1307–1312.CrossRefGoogle ScholarPubMed
Pointer, SD, Rickstrew, J, Slaughter, JC, et al. (2016) Dietary carbohydrate intake, insulin resistance and gastro-oesophageal reflux disease: a pilot study in European- and African-American obese women. Aliment Pharmacol Ther 44, 976–988.CrossRefGoogle ScholarPubMed
Gu, C, Olszewski, T, King, KL, et al. (2022) The effects of modifying amount and type of dietary carbohydrate on esophageal acid exposure time and esophageal reflux symptoms: a randomized controlled trial. Am J Gastroenterol 117, 1655–1667.CrossRefGoogle ScholarPubMed
Lakananurak, N, Pitisuttithum, P, Susantitaphong, P, et al. (2024) The efficacy of dietary interventions in patients with gastroesophageal reflux disease: a systematic review and meta-analysis of intervention studies. Nutrients 16, 464.CrossRefGoogle ScholarPubMed
Mulholland, HG, Cantwell, MM, Anderson, LA, et al. (2009) Glycemic index, carbohydrate and fiber intakes and risk of reflux esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma. Cancer Causes Control 20, 279–288.CrossRefGoogle ScholarPubMed
El-Serag, HB (2005) Dietary intake and the risk of gastro-oesophageal reflux disease: a cross sectional study in volunteers. Gut 54, 11–17.CrossRefGoogle ScholarPubMed
Kubo, A, Block, G, Quesenberry, CP, et al. (2009) Effects of dietary fiber, fats, and meat intakes on the risk of Barrett’s esophagus. Nutr Cancer 61, 607–616.CrossRefGoogle ScholarPubMed
Samuthpongtorn, C, Mehta, RS, Ma, W, et al. (2023) Dietary fiber is associated with decreased risk of gastroesophageal reflux symptoms. Clin Gastroenterol Hepatol 22, 653–655.CrossRefGoogle ScholarPubMed
Morozov, S, Isakov, V & Konovalova, M (2018) Fiber-enriched diet helps to control symptoms and improves esophageal motility in patients with non-erosive gastroesophageal reflux disease. World J Gastroenterol 24, 2291–2299.CrossRefGoogle ScholarPubMed
Zhang, M, Hou, ZK, Huang, ZB, et al. (2021) Dietary and lifestyle factors related to gastroesophageal reflux disease: a systematic review. Ther Clin Risk Manag 17, 305–323.CrossRefGoogle ScholarPubMed
Zeng, Q, Ou, L, Wang, W, et al. (2020) Gastrin, cholecystokinin, signaling, and biological activities in cellular processes. Front Endocrinol (Lausanne) 11, 112.CrossRefGoogle ScholarPubMed
Schubert, ML & Rehfeld, JF (2019) Gastric Peptides—Gastrin and Somatostatin. Comprehensive Physiology. Hoboken, NJ: Wiley. p. 197–228.Google Scholar
Soll, AH & Walsh, JH (1979) Regulation of gastric acid secretion. Annu Rev Physiol 41, 35–53.CrossRefGoogle ScholarPubMed
Martinucci, I, Guidi, G, Savarino, EV, et al. (2018) Vegetal and animal food proteins have a different impact in the first postprandial hour of impedance-pH analysis in patients with heartburn. Gastroenterol Res Pract 2018, 1–7.CrossRefGoogle ScholarPubMed
Koeppen, BM & Stanton, BA (2009) Berne & Levy Physiology, update edition, 6th ed. Philadelphia, PA: Elsevier.Google Scholar
Heidarzadeh-Esfahani, N, Soleimani, D, Hajiahmadi, S, et al. (2021) Dietary intake in relation to the risk of reflux disease: a systematic review. Prev Nutr Food Sci 26, 367–379.CrossRefGoogle Scholar
Pehl, C, Waizenhoefer, A, Wendl, B, et al. (1999) Effect of low and high fat meals on lower esophageal sphincter motility and gastroesophageal reflux in healthy subjects. Am J Gastroenterol 94, 1192–1196.CrossRefGoogle ScholarPubMed
Sun, XH, Ke, MY, Wang, ZF, et al. (2004) Effects of two test-meals on transient lower esophageal sphincter relaxation in patients with gastroesophageal reflux disease and mechanism of gastroesophageal reflux. Acta Academiae Medicinae Sinicae 26, 628–633.Google ScholarPubMed
O’Doherty, MG, Freedman, ND, Hollenbeck, AR, et al. (2012) Association of dietary fat intakes with risk of esophageal and gastric cancer in the NIH-AARP diet and health study. Int J Cancer 131, 1376–1387.CrossRefGoogle ScholarPubMed
Symersky, T, Vu, MK, Frölich, M, et al. (2002) The effect of equicaloric medium-chain and long-chain triglycerides on pancreas enzyme secretion. Clin Physiol Funct Imaging 22, 307–311.CrossRefGoogle ScholarPubMed
Vu, MK, Verkijk, M, Muller, ESM, et al. (1999) Medium chain triglycerides activate distal but not proximal gut hormones. Clin Nutr 18, 359–363.CrossRefGoogle Scholar
Hopman, WP, Jansen, JB, Rosenbusch, G, et al. (1984) Effect of equimolar amounts of long-chain triglycerides and medium-chain triglycerides on plasma cholecystokinin and gallbladder contraction. Am J Clin Nutr 39, 356–359.Google ScholarPubMed
Murata, Y, Harada, N, Kishino, S, et al. (2021) Medium-chain triglycerides inhibit long-chain triglyceride-induced GIP secretion through GPR120-dependent inhibition of CCK. iScience 24, 102963.CrossRefGoogle ScholarPubMed
Sutphen, JL & Dillard, VL (1992) Medium chain triglyceride in the therapy of gastroesophageal reflux. J Pediatr Gastroenterol Nutr 14, 38–40.Google ScholarPubMed
Halliwell, B (2024) Understanding mechanisms of antioxidant action in health and disease. Nat Rev Mol Cell Biol 25, 13–33.CrossRefGoogle ScholarPubMed
Gothai, S, Ganesan, P, Park, SY, et al. (2016) Natural phyto-bioactive compounds for the treatment of type 2 diabetes: inflammation as a target. Nutrients 8, 461.CrossRefGoogle ScholarPubMed
Bulut, F, Tetiker, AT, Çelikkol, A, et al. (2023) Low Antioxidant enzyme levels and oxidative stress in Laryngopharyngeal Reflux (LPR) patients. J Voice 37, 924–931.Google ScholarPubMed
Herdiana, Y (2023) Functional food in relation to Gastroesophageal Reflux Disease (GERD). Nutrients 15, 3583.CrossRefGoogle ScholarPubMed
Oliveira, LD, Teixeira, FM & Sato, MN (2018) Impact of retinoic acid on immune cells and inflammatory diseases. Mediators Inflamm 2018, 1–17.CrossRefGoogle ScholarPubMed
Keir, ME, Yi, T, Lu, TT, et al. (2020) The role of IL-22 in intestinal health and disease. J Exp Med 217, e20192195.CrossRefGoogle ScholarPubMed
Wei, HX, Wang, B & Li, B (2020) IL-10 and IL-22 in mucosal immunity: driving protection and pathology. Front Immunol 11, 1315.CrossRefGoogle ScholarPubMed
Maoka, T (2020) Carotenoids as natural functional pigments. J Nat Med 74, 1–16.CrossRefGoogle ScholarPubMed
Hammond, BR & Renzi, LM (2013) Carotenoids. Adv Nutr 4, 474–476.CrossRefGoogle ScholarPubMed
Lukic, M, Segec, A, Segec, I, et al. (2012) The impact of the vitamins A, C and E in the prevention of gastroesophageal reflux disease, Barrett’s oesophagus and oesophageal adenocarcinoma. Coll Antropol 36, 867–872.Google Scholar
Nam, SY, Park, BJ, Cho, YA, et al. (2019) Gender-specific effect of micronutrient on non-erosive reflux disease and erosive esophagitis. J Neurogastroenterol Motil 25, 82–90.CrossRefGoogle ScholarPubMed
Kubo, A, Levin, TR, Block, G, et al. (2008) Dietary antioxidants, fruits, and vegetables and the risk of Barrett’s esophagus. Am J Gastroenterol 103, 1614–1623.CrossRefGoogle ScholarPubMed
Ibiebele, TI, Hughes, MC, Nagle, CM, et al. (2013) Dietary antioxidants and risk of Barrett’s esophagus and adenocarcinoma of the esophagus in an Australian population. Int J Cancer 133, 214–224.CrossRefGoogle Scholar
Sun, J (2010) Vitamin D and mucosal immune function. Curr Opin Gastroenterol 26, 591–595.CrossRefGoogle ScholarPubMed
Martens, PJ, Gysemans, C, Verstuyf, A, et al. (2020) Vitamin D’s effect on immune function. Nutrients 12, 1248.CrossRefGoogle Scholar
Calton, EK, Keane, KN, Newsholme, P, et al. (2015) The impact of vitamin D levels on inflammatory status: a systematic review of immune cell studies. PLoS One 10, e0141770.CrossRefGoogle ScholarPubMed
Hassanshahi, M, Anderson, PH, Sylvester, CL, et al. (2019) Current evidence for vitamin D in intestinal function and disease. Exp Biol Med 244, 1040–1052.CrossRefGoogle Scholar
Marino, R & Misra, M (2019) Extra-skeletal effects of vitamin D. Nutrients 11, 1460.CrossRefGoogle ScholarPubMed
Liu, W, Zhang, L, Xu, HJ, et al. (2018) The anti-inflammatory effects of vitamin D in tumorigenesis. Int J Mol Sci 19, 2736.CrossRefGoogle ScholarPubMed
Shah, S, Islam, MN, Dakshanamurthy, S, et al. (2006) The molecular basis of vitamin D receptor and β-catenin crossregulation. Mol Cell 21, 799–809.CrossRefGoogle ScholarPubMed
El-Sharkawy, A & Malki, A (2020) Vitamin D signaling in inflammation and cancer: molecular mechanisms and therapeutic implications. Molecules 25, 3219.CrossRefGoogle ScholarPubMed
Zhang, YG, Wu, S & Sun, J (2013) Vitamin D, vitamin D receptor and tissue barriers. Tissue Barriers 1, e23118.CrossRefGoogle ScholarPubMed
Rubenstein, JH, McConnell, D, Beer, DG, et al. (2019) Association of vitamin D and parathyroid hormone with Barrett’s esophagus. J Clin Gastroenterol 53, 711–716.CrossRefGoogle ScholarPubMed
Dong, J, Gharahkhani, P, Chow, WH, et al. (2019) No association between vitamin D status and risk of Barrett’s esophagus or esophageal adenocarcinoma: a Mendelian randomization study. Clin Gastroenterol Hepatol 17, 2227–2235.e1.CrossRefGoogle ScholarPubMed
Zhou, Z, Xia, Y, Bandla, S, et al. (2014) Vitamin D receptor is highly expressed in precancerous lesions and esophageal adenocarcinoma with significant sex difference. Hum Pathol 45, 1744–1751.CrossRefGoogle ScholarPubMed
Janmaat, VT, van de Winkel, A, Peppelenbosch, MP, et al. (2015) Vitamin D receptor polymorphisms are associated with reduced esophageal vitamin D receptor expression and reduced esophageal adenocarcinoma risk. Mol Med 21, 346–354.CrossRefGoogle ScholarPubMed
Herrera, E & Barbas, C (2001) Vitamin E: action, metabolismand perspectives. J Physiol Biochem 57, 43–56.CrossRefGoogle Scholar
Asbaghi, O, Sadeghian, M, Nazarian, B, et al. (2020) The effect of vitamin E supplementation on selected inflammatory biomarkers in adults: a systematic review and meta-analysis of randomized clinical trials. Sci Rep 10, 17234.CrossRefGoogle ScholarPubMed
Jiang, Q (2022) Metabolism of natural forms of vitamin E and biological actions of vitamin E metabolites. Free Radic Biol Med 179, 375–387.CrossRefGoogle ScholarPubMed
Zaaboul, F & Liu, Y (2022) Vitamin E in foodstuff: nutritional, analytical, and food technology aspects. Compr Rev Food Sci Food Saf 21, 964–998.CrossRefGoogle ScholarPubMed
Rao, CV & Vijayakumar, M (2008) Effect of quercetin, flavonoids and α-tocopherol, an antioxidant vitamin on experimental reflux oesophagitis in rats. Eur J Pharmacol 589, 233–238.CrossRefGoogle ScholarPubMed
Hao, J, Zhang, B, Liu, B, et al. (2009) Effect of α-tocopherol, N-acetylcysteine and omeprazole on esophageal adenocarcinoma formation in a rat surgical model. Int J Cancer 124, 1270–1275.CrossRefGoogle Scholar
Murphy, SJ, Anderson, LA, Ferguson, HR, et al. (2010) Dietary antioxidant and mineral intake in humans is associated with reduced risk of esophageal adenocarcinoma but not reflux esophagitis or Barrett’s esophagus. J Nutr 140, 1757–1763.CrossRefGoogle ScholarPubMed
Padayatty, SJ, Katz, A, Wang, Y, et al. (2003) Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr 22, 18–35.CrossRefGoogle Scholar
Niki, E (1987) Interaction of ascorbate and α-tocopherol. Ann N Y Acad Sci 498, 186–199.CrossRefGoogle ScholarPubMed
Carr, A & Maggini, S (2017) Vitamin C and immune function. Nutrients 9, 1211.CrossRefGoogle ScholarPubMed
Wu, P, Zhao, XH, Ai, ZS, et al. (2013) Dietary intake and risk for reflux esophagitis: a case-control study. Gastroenterol Res Pract 2013, 1–9.Google ScholarPubMed
Lee, SR (2018) Critical role of zinc as either an antioxidant or a prooxidant in cellular systems. Oxid Med Cell Longev 2018, 9156285.CrossRefGoogle ScholarPubMed
Oteiza, PI (2012) Zinc and the modulation of redox homeostasis. Free Radic Biol Med 53, 1748–1759.CrossRefGoogle ScholarPubMed
Forman, HJ, Zhang, H & Rinna, A (2009) Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med 30, 1–12.CrossRefGoogle ScholarPubMed
Lin, PH, Sermersheim, M, Li, H, et al. (2017) Zinc in wound healing modulation. Nutrients 10, 16.CrossRefGoogle ScholarPubMed
Taccioli, C, Chen, H, Jiang, Y, et al. (2012) Dietary zinc deficiency fuels esophageal cancer development by inducing a distinct inflammatory signature. Oncogene 31, 4550–4558.CrossRefGoogle ScholarPubMed
Ma, J, Li, Q, Fang, X, et al. (2018) Increased total iron and zinc intake and lower heme iron intake reduce the risk of esophageal cancer: a dose-response meta-analysis. Nutr Res 59, 16–28.CrossRefGoogle ScholarPubMed
Liu, C, Liang, D, Jin, J, et al. (2017) Research progress on the relationship between zinc deficiency, related microRNAs, and esophageal carcinoma. Thorac Cancer 8, 549–557.CrossRefGoogle ScholarPubMed
Shafaghi, A, Hasanzadeh, J, Mansour-Ghanaei, F, et al. (2016) The effect of zinc supplementationon the symptoms of gastroesophageal reflux disease; a randomized clinical trial. Middle East J Dig Dis 8, 289–296.CrossRefGoogle ScholarPubMed
Kiełczykowska, M, Kocot, J, Paździor, M, et al. (2018) Selenium – a fascinating antioxidant of protective properties. Adv Clin Exp Med 27, 245–255.CrossRefGoogle ScholarPubMed
Mehdi, Y, Hornick, JL, Istasse, L, et al. (2013) Selenium in the environment, metabolism and involvement in body functions. Molecules 18, 3292–3311.CrossRefGoogle ScholarPubMed
Ahsan, A, Liu, Z, Su, R, et al. (2022) Potential chemotherapeutic effect of selenium for improved canceration of esophageal cancer. Int J Mol Sci 23, 5509.CrossRefGoogle ScholarPubMed
Cai, X, Wang, C, Yu, W, et al. (2016) Selenium exposure and cancer risk: an updated meta-analysis and meta-regression. Sci Rep 6, 19213.CrossRefGoogle ScholarPubMed
Gröber, U, Schmidt, J & Kisters, K (2015) Magnesium in prevention and therapy. Nutrients 7, 8199–8226.CrossRefGoogle ScholarPubMed
de Baaij, JHF, Hoenderop, JGJ & Bindels, RJM (2015) Magnesium in man: implications for health and disease. Physiol Rev 95, 1–46.CrossRefGoogle ScholarPubMed
Nielsen, FH (2018) Dietary magnesium and chronic disease. Adv Chronic Kidney Dis 25, 230–235.CrossRefGoogle ScholarPubMed
Volpe, SL (2013) Magnesium in disease prevention and overall health. Adv Nutr 4, 378S–383S.CrossRefGoogle ScholarPubMed
Dai, Q, Cantwell, MM, Murray, LJ, et al. (2016) Dietary magnesium, calcium: magnesium ratio and risk of reflux oesophagitis, Barrett’s oesophagus and oesophageal adenocarcinoma: a population-based case–control study. Br J Nutr 115, 342–350.CrossRefGoogle ScholarPubMed
Kumar, A, P, N, Kumar, M, et al. (2023) Major phytochemicals: recent advances in health benefits and extraction method. Molecules 28, 887.CrossRefGoogle ScholarPubMed
Zhang, YJ, Gan, RY, Li, S, et al. (2015) Antioxidant phytochemicals for the prevention and treatment of chronic diseases. Molecules 20, 21138–21156.CrossRefGoogle ScholarPubMed
Lee, SE & Park, YS (2021) The emerging roles of antioxidant enzymes by dietary phytochemicals in vascular diseases. Life 11, 199.CrossRefGoogle ScholarPubMed
Zhu, F, Du, B & Xu, B (2018) Anti-inflammatory effects of phytochemicals from fruits, vegetables, and food legumes: a review. Crit Rev Food Sci Nutr 58, 1260–1270.CrossRefGoogle ScholarPubMed
Eggler, AL & Savinov, SN (2013) Chemical and Biological Mechanisms of Phytochemical Activation of NRF2 and Importance in Disease Prevention. 50 Years of Phytochemistry Research. Cham: Springer International Publishing. pp. 121–155.Google Scholar
Saha, S, Buttari, B, Panieri, E, et al. (2020) An overview of Nrf2 signaling pathway and its role in inflammation. Molecules 25, 5474.CrossRefGoogle ScholarPubMed
Cheng, Y, Lu, C & Yen, G (2017) Phytochemicals enhance antioxidant enzyme expression to protect against NSAID-induced oxidative damage of the gastrointestinal mucosa. Mol Nutr Food Res 61, 1600659.CrossRefGoogle ScholarPubMed
Vageli, DP, Doukas, SG, Spock, T, et al. (2018) Curcumin prevents the bile reflux-induced NF-κB-related mRNA oncogenic phenotype, in human hypopharyngeal cells. J Cell Mol Med 22, 4209–4220.CrossRefGoogle ScholarPubMed
Rasyid, A, Rahman, ARA, Jaalam, K, et al. (2002) Effect of different curcumin dosages on human gall bladder. Asia Pac J Clin Nutr 11, 314–318.CrossRefGoogle ScholarPubMed
Wang, P, Song, M, Eliassen, AH, et al. (2023) Optimal dietary patterns for prevention of chronic disease. Nat Med 29, 719–728.CrossRefGoogle ScholarPubMed
Schulze, MB, Martínez-González, MA, Fung, TT, et al. (2018) Food based dietary patterns and chronic disease prevention. BMJ 361, k2396.CrossRefGoogle ScholarPubMed
García-Montero, C, Fraile-Martínez, O, Gómez-Lahoz, AM, et al. (2021) Nutritional components in western diet v. Mediterranean Diet at the gut microbiota–immune system interplay. Implications for health and disease. Nutrients 13, 699.CrossRefGoogle Scholar
Khodarahmi, M, Azadbakht, L, Daghaghzadeh, H, et al. (2016) Evaluation of the relationship between major dietary patterns and uninvestigated reflux among Iranian adults. Nutr 32, 573–583.CrossRefGoogle ScholarPubMed
Davis, C, Bryan, J, Hodgson, J, et al. (2015) Definition of the Mediterranean Diet; a literature review. Nutrients 7, 9139–9153.CrossRefGoogle ScholarPubMed
Özenoğlu, A, Anul, N & Özçelikçi, B (2023) The relationship of gastroesophageal reflux with nutritional habits and mental disorders. Hum Nutr Metab 33, 200203.CrossRefGoogle Scholar
Ahmad, S, Moorthy, MV, Demler, OV, et al. (2018) Assessment of risk factors and biomarkers associated with risk of cardiovascular disease among women consuming a Mediterranean Diet. JAMA Netw Open 1, e185708.CrossRefGoogle ScholarPubMed
Shivappa, N (2019) Diet and chronic diseases: is there a mediating effect of inflammation? Nutrients 11, 1639.CrossRefGoogle Scholar
Shivappa, N, Hebert, JR, Anderson, LA, et al. (2017) Dietary inflammatory index and risk of reflux oesophagitis, Barrett’s oesophagus and oesophageal adenocarcinoma: a population-based case–control study. Br J Nutr 117, 1323–1331.CrossRefGoogle ScholarPubMed
Marx, W, Veronese, N, Kelly, JT, et al. (2021) The dietary inflammatory index and human health: an umbrella review of meta-analyses of observational studies. Adv Nutr 12, 1681–1690.CrossRefGoogle ScholarPubMed
Suri, S, Kumar, V, Kumar, S, et al. (2020) DASH dietary pattern: a treatment for non-communicable diseases. Curr Hypertens Rev 16, 108–114.Google ScholarPubMed
Beigrezaei, S, Sasanfar, B, Nafei, Z, et al. (2023) Dietary approaches to stop hypertension (DASH)-style diet in association with gastroesophageal reflux disease in adolescents. BMC Public Health 23, 358.CrossRefGoogle ScholarPubMed
Baroni, L, Bonetto, C, Solinas, I, et al. (2023) Diets including animal food are associated with gastroesophageal reflux disease. Eur J Investig Health Psychol Educ 13, 2736–2746.Google ScholarPubMed
O’Doherty, MG, Cantwell, MM, Murray, LJ, et al. (2011) Dietary fat and meat intakes and risk of reflux esophagitis, Barrett’s esophagus and esophageal adenocarcinoma. Int J Cancer 129, 1493–1502.CrossRefGoogle ScholarPubMed
Fernando, I, Schmidt, KA, Cromer, G, et al. (2022) The impact of low-fat and full-fat dairy foods on symptoms of gastroesophageal reflux disease: an exploratory analysis based on a randomized controlled trial. Eur J Nutr 61, 2815–2823.CrossRefGoogle ScholarPubMed
Rivière, P, Vauquelin, B, Rolland, E, et al. (2021) Low FODMAPs diet or usual dietary advice for the treatment of refractory gastroesophageal reflux disease: an open-labeled randomized trial. Neurogastroenterol Motil 33, e14181.CrossRefGoogle ScholarPubMed
Plaidum, S, Patcharatrakul, T, Promjampa, W, et al. (2022) The effect of Fermentable, Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAP) meals on Transient Lower Esophageal Relaxations (TLESR) in Gastroesophageal Reflux Disease (GERD) patients with overlapping Irritable Bowel Syndrome (IBS). Nutrients 14, 1755.CrossRefGoogle ScholarPubMed
Patcharatrakul, T, Linlawan, S, Plaidum, S, et al. (2021) The effect of rice v. wheat ingestion on postprandial Gastroesophageal Reflux (GER) symptoms in patients with overlapping GERD-Irritable Bowel Syndrome (IBS). Foods 11, 26.CrossRefGoogle Scholar
Alnouri, G, Cha, N & Sataloff, RT (2022) Histamine sensitivity: an uncommon recognized cause of living laryngopharyngeal reflux symptoms and signs—a case report. Ear Nose Throat J 101, NP155–7.CrossRefGoogle ScholarPubMed
Taraszewska, A (2021) Risk factors for gastroesophageal reflux disease symptoms related to lifestyle and diet. Rocz Panstw Zakl Hig 72, 21–28.Google ScholarPubMed
Pan, J, Cen, L, Chen, W, et al. (2019) Alcohol consumption and the risk of gastroesophageal reflux disease: a systematic review and meta-analysis. Alcohol Alcohol 54, 62–69.CrossRefGoogle ScholarPubMed
Hungin, AP, Yadlapati, R, Anastasiou, F, et al. (2024) Management advice for patients with reflux-like symptoms: an evidence-based consensus. Eur J Gastroenterol Hepatol 36, 13–25.CrossRefGoogle ScholarPubMed
Bode, C & Bode, JC (1997) Alcohol’s role in gastrointestinal tract disorders. Alcohol Health Res World 21, 76–83.Google ScholarPubMed
Iriondo-DeHond, A, Uranga, JA, del Castillo, MD, et al. (2020) Effects of coffee and its components on the gastrointestinal tract and the brain–gut axis. Nutrients 13, 88.CrossRefGoogle ScholarPubMed
Nehlig, A (2022) Effects of coffee on the gastro-intestinal tract: a narrative review and literature update. Nutrients 14, 399.CrossRefGoogle ScholarPubMed
Kim, J, Oh, SW, Myung, SK, et al. (2014) Association between coffee intake and gastroesophageal reflux disease: a meta-analysis. Dis Esophagus 27, 311–317.CrossRefGoogle ScholarPubMed
Cuomo, R, Savarese, MF, Sarnelli, G, et al. (2008) Sweetened carbonated drinks do not alter upper digestive tract physiology in healthy subjects. Neurogastroenterol Motil 20, 780–789.CrossRefGoogle Scholar
Johnson, T, Gerson, L, Hershcovici, T, et al. (2010) Systematic review: the effects of carbonated beverages on gastro-oesophageal reflux disease. Aliment Pharmacol Ther 31, 607–614.CrossRefGoogle ScholarPubMed
Eslami, O, Shahraki, M, Bahari, A, et al. (2017) Dietary habits and obesity indices in patients with gastro-esophageal reflux disease: a comparative cross-sectional study. BMC Gastroenterol 17, 132.CrossRefGoogle ScholarPubMed
López-Colombo, A, Pacio-Quiterio, MS, Jesús-Mejenes, LY, et al. (2017) Risk factors associated with gastroesophageal reflux disease relapse in primary care patients successfully treated with a proton pump inhibitor. Rev Gastroenterol Mex 82, 106–114.Google ScholarPubMed
Langella, C, Naviglio, D, Marino, M, et al. (2018) New food approaches to reduce and/or eliminate increased gastric acidity related to gastroesophageal pathologies. Nutrition 54, 26–32.CrossRefGoogle ScholarPubMed
Murphy, DW & Castell, DO (1988) Chocolate and heartburn: evidence of increased esophageal acid exposure after chocolate ingestion. Am J Gastroenterol 83, 633–636.Google ScholarPubMed
Fredholm, BB (1984) Gastrointestinal and metabolic effects of methylxanthines. Prog Clin Biol Res 158, 331–354.Google ScholarPubMed
Choe, JW, Joo, MK, Kim, HJ, et al. (2017) Foods inducing typical gastroesophageal reflux disease symptoms in Korea. J Neurogastroenterol Motil 23, 363–369.CrossRefGoogle ScholarPubMed
Fujiwara, Y, Machida, A, Watanabe, Y, et al. (2005) Association between dinner-to-bed time and gastro-esophageal reflux disease. Am J Gastroenterol 100, 2633–2636.CrossRefGoogle ScholarPubMed