Raft-Forming Agents. Raft-forming reflux suppressants have been used to treat GERD for more than 30 years (Hampson 2010). Raft-formers are combinations of a gel-forming fiber (e.g., alginate or pectin) with an antacid buffer (commonly sodium or potassium bicarbonate). When the combination reaches the stomach, chemical reactions cause the release of carbon dioxide bubbles. These bubbles become trapped in the gelled fiber, converting it into a foam that floats on the surface of the stomach contents (hence “raft-forming” agent). Several studies have demonstrated that rafts reduce GERD symptoms by mechanisms independent of acid reduction. They can either move into the esophagus ahead of the stomach contents during reflux (protecting it from exposure) or may act as a barrier to reflux episodes (Mandel 2000). A recent multicenter study of patients with mild to moderate GERD symptoms demonstrated that an alginate-based raft-forming agent was as effective as the PPI omeprazole at reaching an initial heartburn-free period and reducing reflux pain (Pouchain 2012).
The properties of raft-forming agents can be modified by adding calcium salts, which can cross-link fibers and form stiffer gels (Mandel 2000). Raft-formers are most effective when taken after the heaviest meal of the day. If taken with a meal, they can mix with stomach contents and fail to form a “raft” (Mandel 2000).
Melatonin. Melatonin is a hormone most often associated with the sleep cycle, but is found at levels hundreds of times higher in the gut than in the brain (Werbach 2008). Animal trials of melatonin for GERD symptoms have found it to be not only effective in preventing acid-induced esophageal damage, but also damage caused by digestive enzymes and bile (Konturek 2007). Two human trials have investigated supplemental melatonin on GERD symptoms. In the first, 176 patients on a 6 mg melatonin /multi-nutrient combination were compared to 175 patients on a PPI (20 mg omeprazole). The effects were measured by the length of time it took for the patients to become asymptomatic (defined as no heartburn or regurgitation) for 24 hours. All patients in the melatonin group reported improvement in GERD symptoms compared to two-thirds in the PPI group. Relief was reached faster in the melatonin (7 days) vs. PPI (9 days) group, with a much lower incidence of side effects (Pereira 2006). A second study compared 3 groups of 9 GERD patients, each on a different regimen (3 mg melatonin, 20 mg omeprazole, or both) to a group of healthy control subjects. Heartburn and gastric pain were decreased after four weeks and completely resolved after eight weeks in all treatment groups. However, only the two melatonin groups had significant improvements in LES function (Kandil 2010).
Deglycyrrhizinated Licorice (DGL) Extract. Licorice root is a time-honored treatment for digestive ulcers, and modern research continues to confirm its ability to heal the tissues of the digestive tract. Some of the mechanisms behind this remarkable ability are now well understood. Compounds from the licorice plant increase the concentration of prostaglandins at the site of erosive lesions, causing increased mucous secretion and cell proliferation to aid healing. Licorice can also inhibit production of pro-inflammatory cytokines such as interleukins, tumor necrosis factor, and nuclear factor kappa-B; and is a powerful oxidative stress modulator. These properties contribute to its ability to protect the delicate lining of the gastrointestinal tract (Baker 1994; Furusawa 2009; Asl 2008; Aly 2005).
A compound found in unrefined licorice root, glycyrrhizin, may cause side effects in high doses including bloating, high blood pressure, low blood potassium levels, hormonal changes, and diarrhea. When these compounds are removed from licorice root, the product is called deglycyrrhizinated licorice, or DGL. DGL retains the gastrointestinal healing properties of the licorice while avoiding most side effects (Larkworthy 1975; Isbrucker 2006).
Research has shown that DGL extract is an effective treatment for indigestion. In a randomized controlled trial, 50 subjects with functional dyspepsia were randomized to receive a placebo or 75 mg of a patented DGL extract twice daily for 30 days. At 15 and 30 days, subjects taking the GutGard reported significant decreases in total symptom scores compared with those taking placebo. The GutGard recipients also showed significant improvement on a standardized dyspepsia assessment index compared with placebo recipients. GutGard was found to be safe and was well tolerated by all subjects (Raveendra 2012).
Mineral carbonates (calcium, magnesium, and potassium). Calcium and magnesium carbonate, and potassium bicarbonate, neutralize stomach acidity and have been used in antacid preparations for many years (Maton 1999; Gold Standard 2002). Magnesium and calcium carbonate interact with hydrochloric acid in the stomach to form chloride salts, water, carbon dioxide, hydrogen, and other benign products (GCSE Bitesize 2014; The American Society of Health-System Pharmacists 2016).
By neutralizing stomach acid, antacid mineral carbonates decrease irritation of the delicate lining of the gastrointestinal tract. Antacids also inhibit the activity of the gastric enzyme pepsin, and this action may also protect against damage to ulcerated or eroded gastrointestinal lining (Gold Standard 2009). Importantly for those suffering from GERD, antacids such as calcium and magnesium carbonate neutralize acid in the esophagus; and chewable calcium carbonate has a relatively long duration of action. Chewable calcium carbonate has demonstrated an ability to improve contraction of the esophagus, resulting in increased clearance of acid (McRorie 2014; Robinson 2002; Rodriguez-Stanley 2004). Calcium carbonate has a rapid onset of action and is capable of relieving GERD symptoms in minutes (Robinson 2002).