Barret’s Esophagus, Low Carb/Ketogenic Diet and Antioxidants

Posted on September 7, 2023 by Dr. Cheng
  • GERD is the leading cause of Barrett’s esophagus. Elevated oxidative stress is a key underlying biochemical feature (1, 2). Esophageal adenocarcinoma (EAC) is the leading form of esophageal malignancy in the United States and other industrialized countries. The incidence of EAC has increased rapidly over the past four decades. Barrett’s esophagus (BE) is the major precancerous lesion of EAC in which metaplastic columnar epithelium replaces the normal squamous mucosa of the lower esophagus. The main risk factors for BE and EAC are chronic gastroesophageal reflux disease (GERD), obesity, and smoking. During the BE-dysplasia-EAC sequence, esophageal cells bear a huge burden of reactive oxygen species (ROS) accumulation and oxidative stress. Although normal cells have a complete antioxidant mechanism to maintain a balanced anti-tumor physiological response, the antioxidant capacity of tumor cells is compromised due to the anti-oxidative response that promotes tumorigenesis. During tumor progression in the GERD-BE-EAC sequence, the accumulation of ROS induces DNA damage, lipid peroxidation, and protein oxidation. Tumor cells adapt to oxidative stress by generating tumor-promoting antioxidant responses that keep oxidative damage below lethal levels while promoting tumorigenesis, progression, and resistance to therapy (1).
  • Low-carb/ketogenic diet improves gastroesophageal reflux disease (3). A ketogenic diet can improve heartburn symptoms in several ways. Losing weight has been shown to improve heartburn symptoms and acid reflux, and a ketogenic diet is one of the most effective ways to lose weight and maintain a healthy weight. Sugar has pro-inflammatory effects that may make digestive problems worse. Studies show that restricting sugar and carbohydrate intake (low-carb/fat-burning (ketogenic) diets) can improve heartburn symptoms and acid reflux (4, 5). A high-sugar diet requires normal pancreas function. If your pancreas can’t produce enough enzymes to process the excess sugar, the bacteria in your gut can become unbalanced. The result is an overgrowth of opportunistic bacteria that interferes with nutrient absorption and causes gas, bloating, and increased acidity. The ketogenic diet eliminates these grains and starchy carbohydrates that feed opportunistic bacteria (6, 7, 8). Certain carbohydrates, including grains and other starches, also ferment and produce gas, which can stress the lower esophageal sphincter. Some studies have involved interesting measurements, such as the 24-hour esophageal pH probe test, and concluded that ketosis may improve GERD and reflux symptoms. The antioxidant, anti-inflammatory, and nutritious foods commonly found on a ketogenic diet can be very beneficial in managing heartburn symptoms. The best keto foods for gut healing include bone broth, asparagus, garlic, and apple cider vinegar. Fermented foods like sauerkraut and kimchi can nourish the healthy bacteria in your gut and help restore balance. A lack of stomach acid can also cause the contents to back up into the esophagus. Your stomach needs enough acidity to digest food. Many people with acid reflux don’t make enough stomach acid (9).
  • Plasma antioxidants such as selenium, vitamin C, β-cryptoxanthine, and lutein were significantly lower in patients with Barrett’s esophagus (10, 11).
  • Dietary antioxidants, including vitamins C and E, beta-carotene, selenium, and zinc, can inhibit oxidation and prevent Barrett’s esophagus and esophageal cancer (12).
  1. Peng D, Zaika A, Que J, El-Rifai W. The antioxidant response in Barrett’s tumorigenesis: A double-edged sword. Redox Biol. 2021 May;41:101894. doi: 10.1016/j.redox.2021.101894. Epub 2021 Feb 14. PMID: 33621787; PMCID: PMC7907897.
  2. Han D, Zhang C. The Oxidative Damage and Inflammation Mechanisms in GERD-Induced Barrett’s Esophagus. Front Cell Dev Biol. 2022 May 26;10:885537. doi: 10.3389/fcell.2022.885537. PMID: 35721515; PMCID: PMC9199966.
  3. Austin GL, Thiny MT, Westman EC, Yancy WS Jr, Shaheen NJ. A very low-carbohydrate diet improves gastroesophageal reflux and its symptoms. Dig Dis Sci. 2006 Aug;51(8):1307-12. doi: 10.1007/s10620-005-9027-7. Epub 2006 Jul 27. PMID: 16871438.
  4. Ness-Jensen E, Hveem K, El-Serag H, Lagergren J. Lifestyle Intervention in Gastroesophageal Reflux Disease. Clin Gastroenterol Hepatol. 2016 Feb;14(2):175-82.e1-3. doi: 10.1016/j.cgh.2015.04.176. Epub 2015 May 6. PMID: 25956834; PMCID: PMC4636482.
  5. Newberry C, Lynch K. The role of diet in the development and management of gastroesophageal reflux disease: why we feel the burn. J Thorac Dis. 2019 Aug;11(Suppl 12):S1594-S1601. doi: 10.21037/jtd.2019.06.42. PMID: 31489226; PMCID: PMC6702398.
  6. Damiano A, Handley K, Adler E, Siddique R, Bhattacharyja A. Measuring symptom distress and health-related quality of life in clinical trials of gastroesophageal reflux disease treatment: further validation of the Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS). Dig Dis Sci. 2002 Jul;47(7):1530-7. doi: 10.1023/a:1015815102175. PMID: 12141813.
  7. Pointer SD, Rickstrew J, Slaughter JC, Vaezi MF, Silver HJ. Dietary carbohydrate intake, insulin resistance and gastro-oesophageal reflux disease: a pilot study in European- and African-American obese women. Aliment Pharmacol Ther. 2016 Nov;44(9):976-988. doi: 10.1111/apt.13784. Epub 2016 Sep 1. PMID: 27582035; PMCID: PMC5048546.
  8. Can Keto Help Heartburn? – Keto Lifestyle (ketogenic.com)
  9. Wright, J. V., Lenard, L. (2001). Why stomach acid is good for you: Natural relief from heartburn, indigestion, reflux, and GERD. M. Evans.
  10. Kubo A, Levin TR, Block G, Rumore GJ, Quesenberry CP Jr, Buffler P, Corley DA. Dietary antioxidants, fruits, and vegetables and the risk of Barrett’s esophagus. Am J Gastroenterol. 2008 Jul;103(7):1614-23; quiz 1624. doi: 10.1111/j.1572-0241.2008.01838.x. PMID: 18494834; PMCID: PMC2735568.
  11. Clements DM, Oleesky DA, Smith SC, Wheatley H, Hullin DA, Havard TJ, Bowrey DJ. A study to determine plasma antioxidant concentrations in patients with Barrett’s oesophagus. J Clin Pathol. 2005 May;58(5):490-2. doi: 10.1136/jcp.2004.023721. PMID: 15858119; PMCID: PMC1770670.
  12. Kang JH, Luben R, Alexandre L, Hart AR. Dietary antioxidant intake and the risk of developing Barrett’s oesophagus and oesophageal adenocarcinoma. Br J Cancer. 2018 Jun;118(12):1658-1661. doi: 10.1038/s41416-018-0113-y. Epub 2018 May 21. PMID: 29780162; PMCID: PMC6008398
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