Protocol development in integrative medicine is not typically a simple process. Individuals require individualized care, and what works for one patient may not work for another.

To establish these protocols, we first developed a Rating Scale that could be used to discern the rigor of evidence supporting a specific nutrient’s therapeutic effect.

The following protocols were developed using only A through C-quality evidence.

Qualifying studies
Minimum requirements
Systematic review or meta-analysis of human trials
RDBPC human trials
2+ studies and/or 1 study with 50 + subjects
RDBPC human trials
1 study

Gastroesophageal reflux disease (GERD), marked by symptoms of heartburn and effortless regurgitation, is one of the most common gastrointestinal concerns globally, (Savarino 2018) with an estimated prevalence in North America between 18 to 28%. (Sandhu 2018) Left unmanaged, GERD can lead to the histological changes found in Barrett’s esophagus, which may lead to esophageal adenocarcinoma. (Sharp 2013) Common causes of GERD include dysbiosis, reduced gastrointestinal (GI) transit time, and various dietary triggers (e.g., alcohol, tomato products, spicy foods, and high-fat foods), which may impact lower esophageal sphincter (LES) tone, leading to upward displacement of stomach contents and causing the hallmark symptoms of epigastric pain and effortless regurgitation. (Ahuja 2019)(Waller 2011)

There are a variety of therapeutics that may benefit symptoms of GERD. For example, melatonin is produced in the local tissues of the esophagus and stomach and may positively influence the protective mucous lining that may protect against GERD. (Majka 2018) Licorice derivatives may help to form a mechanical barrier against reflux. (Young 1986) Peppermint has mixed results on smooth muscle tone in the esophagus and stomach but may ultimately reduce symptoms of GERD. (Khalaf 2019)(Pimentel 2001)(Setright 2017) Various B vitamins may both reduce esophageal irritation and the negative progression of GERD. (Sharp 2013) Finally, certain probiotic strains may help reduce symptoms of GERD by improving gastrointestinal transit time. (Waller 2011)

Based on current research findings, the ingredients in the protocol below have been associated with improved health outcomes in patients experiencing gastroesophageal reflux disorder.


3–6 mg before sleep for 40 days to allow for optimal regression of symptoms (Kandil 2010)(Pereira 2006)

  • 3 mg of melatonin before sleep was found to be associated with a significant reduction in signs and symptoms of GERD, such as increased lower esophageal sphincter tone and reduced epigastric pain, both without and with omeprazole (the latter being an additive effect), noting a greater effect of omeprazole versus melatonin when given individually. (Kandil 2010)
  • After-dinner supplementation of 6 mg of melatonin, along with vitamins B6 and B12, folic acid, methionine, tryptophan, and betaine, was associated with a complete regression of symptoms in 100% of 176 individuals, versus 66% of the omeprazole group, after 40 days. (Pereira 2006)
  • Melatonin has been found to be secreted by GI mucosal cells at concentrations 100 to 400 times blood plasma levels. Melatonin may strengthen the esophageal and gastric mucosal barriers to irritants from endogenous or exogenous production. (Majka 2018) Additionally, melatonin has been found to be associated with quicker healing of stomach ulcers. (Celinski 2011)
Melatonin in the Fullscript catalog

Licorice (Glycyrrhiza glabra)

Dose variable based on each form; duration 8 weeks (Young 1986)

  • Carbenoxelone, a synthetic derivative of licorice (Ahuja 2019) administered four times a day (after meals and before sleep) along with alginate and antacid, was associated with an 82% improvement in GERD symptom grades compared to 63% in the alginate and antacid group. The carbenoxelone group was noted to achieve healing 50% faster over the 8 weeks. (Young 1986)
  • A gum (GutsyGum™) containing a proprietary blend of licorice, antacid, papain, and apple cider vinegar was given to 24 participants post-meal and was associated with a significant reduction in heartburn and acid reflux scores compared to placebo. (Brown 2015)
  • Licoflavone, a component of licorice, was found to significantly reduce gastric ulcers through its anti-inflammatory effects on arachidonic acid and histamine, particularly in the group of rodents given a moderate dose. (Yang 2017)
  • Deglycyrrhizinated licorice (DGL), a formulation that doesn’t induce the blood pressure-raising effects of licorice, (Ahuja 2019) was examined along with slippery elm and peppermint and was found to significantly improve symptoms of gastric and intestinal irritation with greater effects than are commonly reported with antacids. Unfortunately, the study didn’t explicitly distinguish between GERD, dyspepsia, and other ailments such as irritable bowel syndrome (IBS) and Crohn’s disease. (Setright 2017)
Licorice in the Fullscript catalog

Peppermint oil

180 mg, 3 times a day, for minimum 4 weeks (Cash 2016)(Rösch 2002)

  • Peppermint oil with slippery elm versus peppermint with slippery elm and DGL were examined, and both groups were found to significantly improve symptoms of gastric and intestinal irritation, with greater effects than are commonly reported with antacids. Unfortunately, the study didn’t explicitly distinguish between GERD, dyspepsia, and other ailments such as IBS and Crohn’s disease. (Setright 2017)
  • A herbal combination product (STW-5) containing peppermint, licorice, and seven other herbs was found to be primarily associated with improvements in epigastric pain and acid regurgitation, with 83 of 138 participants in the treatment group reporting improvements in their symptoms from severe to mild or absent, compared to only 33 of 135 participants in the control group. (Melzer 2004)
  • Patients need to take caution, as a direct peppermint infusion of 160 mL over 20 minutes 10 cm above the lower esophageal sphincter induced intense heartburn in patients with GERD (and only a cold sensation in patients without GERD). (Banovcin 2019) However, in two trials on diffuse esophageal spasm (DES), peppermint oil improved DES and didn’t impact lower esophageal sphincter tone. (Khalaf 2019)(Pimentel 2001)
Peppermint oil in the Fullscript catalog

B complex

Variable based on each B vitamin and form

    • In a sample of 960 participants, intakes of vitamin B2, vitamin B6, and folate were inversely proportionally to the risk of reflux esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma. (Sharp 2013)
    • Long-term proton pump inhibitor (PPI) usage was significantly associated with lower levels of serum vitamin B12 and was proposed as a mechanism for the presence of increased fracture risk in those taking PPIs long-term. (Lewis 2014). With lower B12, homocysteine levels may also rise, possibly elevating cardiovascular disease risk. (Arturo J Martí-Carvajal 2017) A 2017 Cochrane review found that supplementation of vitamins B6, B9, and/or B12 (to reduce homocysteine levels) was associated with a 10% reduced risk of stroke, with a low dose and a high dose likely having similar benefits. (Arturo J Martí-Carvajal 2017)
    • A combination supplement containing vitamin B6, folic acid, vitamin B12, methionine, betaine, l-tryptophan, and melatonin was associated with a complete regression of symptoms in 100% of 176 individuals, versus 66% of the omeprazole group, after 40 days. (Pereira 2006)


B complex in the Fullscript catalog


4 billion CFU of Lactobacillus reuteri DSM17648 or Bifidobacterium bifidum  daily for approximately 4 weeks (Ismail 2023)(Cheng 2020)

  • A 2023 randomized, double-blind, placebo-controlled trial demonstrated that incorporating L. reuteri DSM17648 alongside standard H. pylori treatment markedly enhances eradication rates to over 90% while also improving gastrointestinal symptoms, including indigestion, constipation, and abdominal pain, and reducing treatment side effects. (Ismail 2023)
  • A 2020 systematic review found 13 prospective studies on GERD and probiotics, with five rated as high-quality randomized controlled trials (RCTs), showing significant reductions in symptoms of regurgitation and heartburn (Cheng 2020), with doses ranging from 1–46 billion CFU of various strains for 1–12 weeks. 
  • Over 3 billion CFUs of B. bifidum were given to 39 participants (40 were given placebo) in an RCT for 4 weeks, where B. bifidum supplementation was associated with a significantly higher relief rate for postprandial discomfort and epigastric pain scores. (Gomi 2018)
  • B. lactis, when supplemented for two weeks at a dose of 17 billion CFUs, was found to be associated with reduced regurgitation and improved whole-gut transit time in 54 participants compared to placebo. (Waller 2011)
Probiotics in the Fullscript catalog


The Fullscript Integrative Medical Advisory team has developed or collected these protocols from practitioners and supplier partners to help health care practitioners make decisions when building treatment plans. By adding this protocol to your Fullscript template library, you understand and accept that the recommendations in the protocol are for initial guidance and may not be appropriate for every patient.

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  1. Ahuja, A., & Ahuja, N. K. (2019). Popular Remedies for Esophageal Symptoms: a Critical Appraisal. Current Gastroenterology Reports, 21(8), 39. 
  2. Banovcin, P., Duricek, M., Zatko, T., Liptak, P., Hyrdel, R., & Kollarik, M. (2019). The infusion of menthol into the esophagus evokes cold sensations in healthy subjects but induces heartburn in patients with gastroesophageal reflux disease (GERD). Diseases of the Esophagus: Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E, 32(11).
  3. Brown, R., Sam, C. H. Y., Green, T., & Wood, S. (2015). Effect of GutsyGum(tm), A Novel Gum, on Subjective Ratings of Gastro Esophageal Reflux Following A Refluxogenic Meal. Journal of Dietary Supplements, 12(2), 138–145.
  4. Cash, B. D., Epstein, M. S., & Shah, S. M. (2016). A Novel Delivery System of Peppermint Oil Is an Effective Therapy for Irritable Bowel Syndrome Symptoms. Digestive Diseases and Sciences, 61(2), 560–571.
  5. Celinski, K., Konturek, P. C., Konturek, S. J., Slomka, M., Cichoz-Lach, H., Brzozowski, T., & Bielanski, W. (2011). Effects of melatonin and tryptophan on healing of gastric and duodenal ulcers with Helicobacter pylori infection in humans. Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society, 62(5), 521–526.
  6. Cheng, J., & Ouwehand, A. C. (2020). Gastroesophageal Reflux Disease and Probiotics: A Systematic Review. Nutrients, 12(1).
  7. Ismail, N. I., Nawawi, K. N. M., Hsin, D. C. C., Hao, K. W., Mahmood, N. R. K. N., Chearn, G. L. C., Wong, Z., Tamil, A. M., Joseph, H., & Ali, R. a. R. (2023). Probiotic containing Lactobacillus reuteri DSM 17648 as an adjunct treatment for Helicobacter pylori infection: A randomized, double‐blind, placebo‐controlled trial. Helicobacter, 28(6).
  8. Kandil, T. S., Mousa, A. A., El-Gendy, A. A., & Abbas, A. M. (2010). The potential therapeutic effect of melatonin in Gastro-Esophageal Reflux Disease. BMC Gastroenterology, 10, 7.
  9. Khalaf, M. H. G., Chowdhary, S., Elmunzer, B. J., Elias, P. S., & Castell, D. (2019). Impact of Peppermint Therapy on Dysphagia and Non-cardiac Chest Pain: A Pilot Study. Digestive Diseases and Sciences, 64(8), 2214–2218.
  10. Lewis, J. R., Barre, D., Zhu, K., Ivey, K. L., Lim, E. M., Hughes, J., & Prince, R. L. (2014). Long-term proton pump inhibitor therapy and falls and fractures in elderly women: a prospective cohort study. Journal of Bone and Mineral Research: The Official Journal of the American Society for Bone and Mineral Research, 29(11), 2489–2497.
  11. Majka, J., Wierdak, M., Brzozowska, I., Magierowski, M., Szlachcic, A., Wojcik, D., Kwiecien, S., Magierowska, K., Zagajewski, J., & Brzozowski, T. (2018). Melatonin in Prevention of the Sequence from Reflux Esophagitis to Barrett’s Esophagus and Esophageal Adenocarcinoma: Experimental and Clinical Perspectives. International Journal of Molecular Sciences, 19(7).
  12. Martí-Carvajal, A. J., Solà, I., Lathyris, D., & Dayer, M. (2017). Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database of Systematic Reviews, 8, CD006612.
  13. Pereira, R. de S. (2006). Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: comparison with omeprazole. Journal of Pineal Research, 41(3), 195–200.
  14. Pimentel, M., Bonorris, G. G., Chow, E. J., & Lin, H. C. (2001). Peppermint oil improves the manometric findings in diffuse esophageal spasm. Journal of Clinical Gastroenterology, 33(1), 27–31.
  15. Rösch, W., Vinson, B., & Sassin, I. (2002). A randomised clinical trial comparing the efficacy of a herbal preparation STW 5 with the prokinetic drug cisapride in patients with dysmotility type of functional dyspepsia. Zeitschrift Fur Gastroenterologie, 40(6), 401–408.
  16. Sandhu, D. S., & Fass, R. (2018). Current Trends in the Management of Gastroesophageal Reflux Disease. Gut and Liver, 12(1), 7–16.
  17. Savarino, E., Bredenoord, A. J., Fox, M., Pandolfino, J. E., Roman, S., Gyawali, C. P., & International Working Group for Disorders of Gastrointestinal Motility and Function. (2018). Advances in the physiological assessment and diagnosis of GERD. Nature Reviews. Gastroenterology & Hepatology, 15(5), 323.     
  18. Setright Russell. (n.d.). Prevention of symptoms of gastric irritation (GERD) using two herbal formulas: An observational study. Journal of the Australian Traditional-Medicine Society, 23(2), 68–71.
  19. Sharp, L., Carsin, A.-E., Cantwell, M. M., Anderson, L. A., Murray, L. J., & FINBAR Study Group. (2013). Intakes of dietary folate and other B vitamins are associated with risks of esophageal adenocarcinoma, Barrett’s esophagus, and reflux esophagitis. The Journal of Nutrition, 143(12), 1966–1973.
  20. Waller, P. A., Gopal, P. K., Leyer, G. J., Ouwehand, A. C., Reifer, C., Stewart, M. E., & Miller, L. E. (2011). Dose-response effect of Bifidobacterium lactis HN019 on whole gut transit time and functional gastrointestinal symptoms in adults. Scandinavian Journal of Gastroenterology, 46(9), 1057–1064.
  21. Yang, Y., Wang, S., Bao, Y.-R., Li, T.-J., Yang, G.-L., Chang, X., & Meng, X.-S. (2017). Anti-ulcer effect and potential mechanism of licoflavone by regulating inflammation mediators and amino acid metabolism. Journal of Ethnopharmacology, 199, 175–182.
  22. Young, G. P., Nagy, G. S., Myren, J., Kronborg, I. J., Logan, K. R., Reed, P. I., & Hopper, J. L. (1986). Treatment of reflux oesophagitis with a carbenoxolone/antacid/alginate preparation. A double-blind controlled trial. Scandinavian Journal of Gastroenterology, 21(9), 1098–1104.