Alginates are neutral polysaccharide polymers isolated from brown seaweed (Phacophycae
) and are classified as dietary fiber. They are constituted by a proportion of D-mannuroic and L-glucuronic acids. In the presence of gastric acid, alginates precipitate and form a gel. One of the most interesting characteristics is due to the presence of sodium or potassium bicarbonate that, in the presence of gastric acid is converted to a dioxide which, when entrapped in the gel, converts it into a foam that floats on the surface of the gastric contents[12
]. Thus, thanks to their unique mechanism, alginate-based raft-forming formulations have been marketed worldwide for > 40 years under various brand names for the symptomatic treatment of GERD, and many studies have reported their efficacy[12,38,39
]. However, the majority of these studies have assessed only the control of symptoms without objective evaluation of the effect of these drugs on abnormal reflux by means of pH-monitoring, and and even less using impedance-pH testing that is available in the clinical setting since few years.
Therefore, in our prospective study we evaluated the effect of a new alginate raft-forming formulation, Faringel, in a group of 40 patients with GERD who underwent 24 h MII-pH testing after a reflux-provocative meal. Our results showed that this alginate-based formulation is able to reduce the number of acid refluxes and the esophageal exposure time below pH 4.0. Moreover, it is able to decrease significantly, in both the right lateral and supine decubitus position, the number of acid reflux events and their proximal migration. Finally, all patients also reported a lower number of symptoms after treatment, including both heartburn and regurgitation, although the effect on the latter was less evident.
The patients evaluated in the present study were truly representative of the GERD population. Indeed, they had typical reflux symptoms (i.e., heartburn and regurgitation), abnormal acid exposure time, and/or evidence of mucosal breaks at upper GI endoscopy. We opted to include patients with these characteristics in order to be sure of excluding those with functional heartburn. Moreover, we preferred not to enroll patients with normal acid exposure and positive symptom association (i.e., hypersensitive esophagus) for reducing possible confounding factors such as visceral hyperalgesia, overlap with functional disease, autonomic dysfunction and concomitant psychiatric illness that have been more associated with the above condition[40-43
]. Finally, a recent report has suggested caution about overinterpretation of symptom indexes in reflux monitoring, thus supporting our decision to exclude patients with hypersensitive esophagus in order to avoid confusion[44
Previously, Chatfield has reported a comparison of alginate preparation with placebo for the symptomatic relief of reflux esophagitis[39
]. In this multicenter randomized double-blind study, alginate was superior to placebo in reducing symptom severity and increasing symptom-free days. Interestingly, the placebo group recorded a larger number of dropouts due to side effects. This means that alginate is safe and provides better relief of symptoms. An older study that simultaneously used pH-telemetry and X-rays demonstrated that pH within the raft is approximately neutral, while the pH of the gastric contents beneath the raft remains acidic (pH 1-2)[45
]. These data are important because they explain why the alginate formulation is effective in controlling heartburn in the supine decubitus position, as observed in this study, and probably also during the night-time. More recently, using impedance-pH monitoring, we showed a reduction of acid reflux episodes and proximal migration of the refluxate and thereby a relevant decrease of GERD-related symptoms compared with baseline after sodium alginate administration[7
]. However, the results of the latter study were less marked than those of the current investigation, probably because patients were enrolled only on the basis of symptoms without objective documentation of GERD, either by endoscopy or pH monitoring. Moreover, in the previous study, tolerability was not evaluated.
The good control of acid reflux confirms the results obtained in previous studies performed with pH-metry[7,14,46,47
] or scintigraphic methods[48,49
], and represents the main mechanism of the quick and effective relief of heartburn in reflux patients. In a recent study, the positive effect of sodium alginate in reducing acid refluxes has been confirmed using simultaneously stepwise pH pull-throughs, high-resolution manometry and fluoroscopy[15
]. In fact, Kwiatek et al[15
] have shown that alginate can also eliminate or displace the “acid-pocket”, which is a phenomenon seen in the proximity of the esophagogastric junction and is the likely origin of postprandial acid reflux in GERD patients.
Another interesting characteristic of sodium alginate has been emphasized by Manabe et al[50
] in NERD patients, who are known to have a lower response rate to PPIs than patients with ERD when gauged by relief of heartburn. In this study, patients who received omeprazole combined with sodium alginate recorded longer symptom relief compared with those receiving omeprazole alone. They concluded that sodium alginate is useful in combination with PPI therapy and has to be considered for treating NERD patients who do not respond completely to PPIs. Also, in our investigation, we evaluated NERD patients and found similar results on symptom relief in this particular group of GERD patients, although we did not study Faringel as an add-on therapy.
It is likely that the positive effect of sodium alginate in controlling GERD-related symptoms is due to a whole equilibrium between raft-forming alginate and antacid substances. Faringel is constituted from sodium alginate and sodium carbonate. A previously published study has shown that, if two different antacid substances are present (e.g., Algicon Liquid), an effective reflux suppressing raft cannot form because a large amount of antacid prevents the raft formation by neutralizing the gastric acid required to react with alginate. Faringel and Gaviscon formulation consist of sodium alginate and sodium carbonate, and they have a lower acid-neutralizing capacity and a complete raft-forming gel reaction[13,47,49
]. These studies have shown that a large amount of antacids is not required for strong raft formation and effective reflux suppression.
On the contrary, various findings suggest that alginate is less effective in reducing nonacid than acid reflux. In our study alginate increased significantly the number of nonacid reflux events compared with baseline. The number of total reflux episodes decreased slightly but significantly in the right lateral decubitus position, whereas no difference was found in the supine decubitus position. Similarly, Zentilin et al[7
] have shown no action of alginate on nonacid reflux events. Surprisingly, in our study, the number of nonacid reflux episodes almost doubled after drug intake in 50% of patients. Probably the antacid effect of sodium alginate reduces acid reflux, but seems to increase nonacidic reflux.
Finally, our study shows that the percentage of proximal migration of reflux events decreased significantly both in the right lateral and supine decubitus positions compared with baseline, thus stopping one of the main determinants by which reflux causes symptoms[51-53
]. These results confirm our previous findings with a different sodium alginate formulation, although the study was performed in a smaller sample of patients and without a clear documentation of GERD[7
]. These investigations performed with impedance-pH monitoring technique permitted us to assess the ability of sodium alginate to reduce the proximal extension of refluxed material. The raft obtained with alginate represents a cork in the zone of the LES that prevents any gastric material migration into the esophagus independently of the patient decubitus. This beneficial effect could help in controlling not only typical, but especially extraesophageal symptoms. In particular, the Faringel formulation adds to alginate able to control GERD related typical symptoms a large number of vegetal extracts, which have the potential to promote healing of pharyngoesophageal mucosal lesions. The anti-flogistic properties of Faringel are due to herbs such as Propolis, A. vera
, and Calendula
. Eamlamnam et al[54
] have observed that A. vera
treatment induces a complete reduction in leukocyte adherence and tumor necrosis factor-α levels combined with elevated interleukin-10 levels, which are able to promote healing of gastric ulcers in male Sprague-Dawley rats. Propolis and A. vera
have also demonstrated pain-killing effects[55
]. Moreover, experimental studies have shown that C. officinalis
has anti-inflammatory and antibacterial activities as well as angiogenic and fibroblastic properties acting in a positive way on the inflammatory and proliferative phase of the healing process[20
]. Thus, we can speculate that all these data on the anti-inflammatory properties of the herbal components of Faringel may be relevant for extraesophageal reflux-related symptoms in which a flogistic component seems to be more evident[56
In conclusion, our findings demonstrated that Faringel formulation is well tolerated and highly effective in controlling, or at least reducing, heartburn in GERD patients by modifying the number of acid reflux episodes and lowering the proximal migration of reflux events. It was less effective in controlling nonacid reflux and regurgitation. Its action in reducing the proximal extension of reflux events and the combined presence of natural substances (Calendula, Aloe, honey) that favor mucosal healing could be useful to improve GERD-related extraesophageal symptoms.