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Volume: The Esophageal Mucosa
Chapter: Antacids

Antacids and alginate-containing preparations: what is their mechanism of action and their place in the management of GERD?

C. Scarpignato, G. Gimbo (Parma)

S. Bruley des Varannes, J.-P. Galmiche (Nantes)

Although the pathogenesis of gastroesophageal reflux disease (GERD) is multifactorial [1], the damaging power of the refluxed material depends primarily on gastric acid secretion and the nature of refluxate is acid in most of patients with GERD [2]. As a consequence, until the 80s, the medical treatment of GERD consisted mainly of antacids and lifestyle modifications [3]. During the last decade new drugs have been developed, including very potent inhibitors of gastric acid secretion and more effective prokinetic agents [4]. However, in many countries, antacids and alginate containing preparations still remain the mainstay of treatment for patients with heartburn and the so-called "reflux-like dyspepsia".

Antacids are among the most widely used medicines. Often, to be sure, they are taken as a result of self-diagnosis and self-treatment (being available as over-the-counter drugs), and the trigger for buying and taking an antacid is not based on structural abnormalities, but on symptoms. Patients take antacids, as well as alginates, to feel better rather than to heal esophageal lesions.

This paper will summarize the pharmacology of both kinds of preparations and discuss their role in the medical treatment of GERD.


Antacids are preparations that are primarily designed to neutralize gastric acid. The proliferation of antacid formulations includes combinations and varying proportions of a number of basic materials, in an attempt to produce improved neutralization characteristics with lowered untoward effects. Currently, the American Hospital Formulary lists over 120 antacid preparations, composed of single ingredients or mixtures, in every conceivable combination. Similarly, the British National Formulary and the French Pharmacopeia contain 58 and 64 formulations, respectively, many of these being very similar.

The chemistry of each antacid is unique [5,6]. On the basis of their biological properties, they can be divided as systemic (i.e., sodium salts), nonsystemic (calcium, magnesium and aluminum salts), and complex antacids (Fig. 1). Most prescribed antacids contain a mixture of aluminum and magnesium salts. Precise methods of preparation and presentation are important because they influence the physico-chemical properties and the therapeutic effects of antacids.

Pharmacological properties of antacids

The pharmacological actions of antacids are summarized in Table 1 [1,7]. Besides the neutralization of hydrogen ions present in gastric secretion, the increase in lower esophageal sphincter pressure (LESP) [8], which is independent of gastrin release [9], could - on theoretical grounds - contribute to the observed reduction of esophageal exposure to acid [10]. An increase in LESP, however, becomes evident only when intragastric pH is kept over 6 [8], a pH level only seldom reached with the common used schedules of antacids. It is worth mentioning that their effect on gastric pH is of short duration; antacids ingested in the fasting state reduce acidity for only approximately 30 min because of their rapid gastric emptying [5]. When antacids (30


Fig. 1. Classification of antacids.

Table 1. .Pharmacological actions of antacids

• Neutralization of hydrogen ions present in gastric secretion and reduction of their concentration in the refluxed material

• Mucosal protection

• Adsorption and inactivation of pepsin

• Binding of bile salts

• Increase of LESP independently from gastrin release

• Inhibition of gastric emptying rate, mainly dependent on aluminum content

ml) are given 1 and 3 h after the meal, gastric pH is kept above 2.0 for only 3 h [11]. The second dose of antacid, given when most of the meal has left the stomach, is slightly less effective than the first one. Moreover, it must be pointed out that acid secretion actually increases while antacids are in the stomach; however, as long as the antacid remains in the stomach, acid can be neutralized. The nocturnal gastric acidity (which normally reaches its peak after midnight) is not adequately controlled by antacids, even when given at bedtime.

Could antacids reduce the esophageal exposure to acids?

Ten years ago, Galmiche's team [12] performed an elegant study comparing an aluminum-magnesium-hydroxide-containing antacid (Dimalan®) with two widely employed histamine H2-antagonists (cimetidine and ranitidine) in patients with symptomatic gastroesophageal reflux (GER). These were randomly allocated to one of the following therapeutic schedules:

- antacid 15 ml 1 h after meals and at bedtime;

- cimetidine 200 mg after meals and 400 mg at bedtime; and

- ranitidine 150 mg bid.

A standard 3-h postprandial pH test without treatment was also performed in all patients before entering the trial and a postprandial acid reflux score was then calculated. When compared to pretreatment levels of esophageal acidity, the three drugs were found to be almost equally effective in reducing the postprandial pH score. However, comparison of the results from the 20 h pH study showed that during the night H2-blockers (especially ranitidine) were clearly more efficacious than the antacid, in decreasing the time of exposure of the esophageal mucosa to low pH levels.

Are antacids capable of relieving heartburn?

Although the degree by which acidity must be reduced to relieve heartburn is not yet clearly established [13], a study by Smith and co-workers [14] showed that a solution of pH over 2.5, infused into the esophagus, may not cause pain even if it is of low pH (e.g., pH 3).

The analgesic effect of a liquid antacid (30 ml aluminum and magnesium hydroxides in vitro, buffering capacity 144 µmol) on episodes of heartburn, has been

studied by Meyer et al. [15] in 20 chronically symptomatic GER patients (Fig. 2). Their first study compared the effect of single doses of antacid and placebo on two spontaneous heartburn episodes. The second trial compared single doses of the same antacid and placebo on acid induced heartburn. Lastly, antacid and placebo were given on demand for multiple heartburn episodes. In all these studies, antacid and placebo resulted in nonstatistically different degrees of pain relief. Moreover, esophageal pH monitoring during the Bernstein test was not correlated with the degree of pain relief after either antacid or placebo.

Is there any healing effect of antacids on esophageal lesions?

Clinical investigations with antacids on GERD patients concern their effects on both symptoms (heartburn, regurgitation, dysphagia) of GERD and esophageal lesions. As shown in Table 2, there are few published trials [16-19] in which antacids and true placebo were compared. It is evident that a significant symptomatic relief was seldom reported and that an improvement of esophageal lesions was never revealed by endoscopy.

Based on the present knowledge, it should therefore be concluded that antacids are of little, if any, therapeutic value in GERD.

Alginate-containing drugs

These pharmaceutical preparations, of which the most widely known is Gaviscon®, contain alginic acid combined with small doses of antacids. Commercial antireflux


Figure 2. .Effect of antacids on spontaneous and acid-induced heartburn in patients with GERD. Each column represents the percentage of patients symptom-free 30 min after administration of either placebo or antacid (drawn from data in [15]).

Table 2. .Placebo-controlled trials with antacid preparations in GERD



Control therapy

Symptomatic improvement

Endoscopic improvemnt

Furman et al. [16]





Graham and Patterson [17]





Grove et al. [18]





Weberg and Berstad [19]





NE = not evaluated.

preparations use a wide range of alginate materials. It is difficult to correlate their properties with those of alginate, since the alginate used is rarely specified by the manufacturer and a wide range of particulates are added to many formulations (e.g., particulate antacids). Even in the same formulation, the composition varies greatly from country to country (Table 3). This is the case with liquid Gaviscon®, which is manufactured under license by different pharmaceutical companies. An interesting study [20] compared four international preparations of liquid Gaviscon® and found that each formulation possesses markedly different raft strength (Fig. 3) and neutralization profiles.

Alginate-containing preparations: how do they work?

Scintigraphic studies have clearly established that Gaviscon® floats on the surface of the gastric pool, providing a mechanical barrier to reflux at the cardia. Using a dual-isotope scintigraphic technique, Malmud and Fisher [21] as well as McKay et al. [22], showed that most of the ingested alginic acid is located in the upper half of the stomach, in both normal subjects and patients with GER (Fig. 4). In those subjects in whom reflux did occur after treatment with alginic acid, the labeled compound refluxed preferentially compared with the liquid contents of the stomach. Therefore, when reflux occurs, this viscous foam first contacts the esophageal mucosa. Compared with antacids, alginate containing preparations float and show a selective retention in the fundus [6].

Optimal dosing in relation to meal intake is needed for alginate to be completely effective (Table 4). To ensure gastric floatation, antireflux agents must indeed be given 30 min after the meal.

Table 3. .Composition of the liquid Gaviscon® formulations in various countries [20]






Sodium alginate

500 mg

500 mg

267 mg

500 mg

Sodium bicarbonate

267 mg



170 mg

Aluminum hydroxide


200 mg

63.3 mg

1 g

Magnesium carbonate


275 mg


Calcium carbonate

150 mg

aQuoted as 60 mg of sodium/10 ml which is equivalent to 219 mg of sodium bicarbonate/10 ml.


Figure 3. .Raft strengths of the minimum recommended doses of liquid Gaviscon® available in four different countries (from [20]).

Effect of alginate-containing preparations on esophageal exposure to acid

Stanciu and Bennett [23] first showed a significant decrease in the number of reflux episodes and in the percentage time during which the esophageal pH was in the acidic range after the administration of eight tablets per day of an alginate containing preparation (Gaviscon®). Antacid alone (Gaviscon® without alginate) had no effect


Figure 4. .Dual isotope scintigraphic evaluation of an alginate containing preparation (Algicon®). Patients with symptomatic GERD were given 300 ml 99mTc labelled milk (blue) followed by 10 ml suspension of 113mIn-labeled alginate (red) (from [22]).

Table 4. .Alginate-containing preparations: optimal dosing in relation to meals

• Antireflux preparations must be given 30 min after a meal to ensure gastric floatation.

• When the antireflux agent is taken on an empty stomach, the formation sinks to the base of the greater curvature and 50% is emptied within 20 min after administration.

• When the formulation is taken 30 min before, the antireflux agent does not float on a meal ingested subsequently. It will be diluted with the fluid from the meal and thus emptied ahead of the meal without forming a raft.

on esophageal pH. By using postprandial and 24-h intraesophageal pH-metry, respectively, Dudicourt et al. [24], Branicki et al. [25] and Castell et al. [26] confirmed this finding and clearly showed that Gaviscon® is more effective in controlling GER in upright than in supine position (Fig. 5). This finding is not unexpected if one takes into account that gastric emptying of Gaviscon® is strongly influenced by posture. Bennett et al. [27], indeed, demonstrated in healthy volunteers that this raft-forming alginate formulation emptied faster than food in subjects lying on their left sides and slower in subjects lying on their right sides. The recently developed Algicon® behaves quite similarly [28]. More recently, Washington [29] used an esophageal pH probe, coupled with a small GAMMA-detector strapped to the chest wall and, by using a radiolabeled meal, was able to show that 20 ml of liquid Gaviscon®, administered 30 min after the meal, significantly reduced the amount of both acid and food reflux into the esophagus.

Alginate-containing preparations: clinical efficacy in GERD

The clinical efficacy of Gaviscon® has not been definitively established by large placebo-controlled trials [30-32]. The studies in which Gaviscon® appeared superior


Figure 5. .Upright reflux time (min) and numbers of reflux episodes after a high-fat meal in 10 subjects following administration of an alginic acid-antacid formulation vs. equal strength antacid (redrawn from [26]).

Table 5. .Controlled trials with alginate containing preparations



Control therapy

Symptomatic improvement

Endoscopic improvement

Barnardo et al. [30]





Beeley and Warner [31]





Grossman et al. [32]





Stanciu and Bennett [23]





McHardy [33]





Scobie [34]





Chevrel [35]





Graham et al. [36]





NE = not evaluated.

to placebo concerned symptoms without information regarding endoscopic or histological findings (Table 5).

In some studies, Gaviscon® was compared with antacids [33-36]. These trials did not show any statistically significant difference between these two drugs, in terms of symptom relief and improvement of lesions [37] but, as pointed out previously, efficacy of antacids themselves remains controversial.

On the whole, clinical experience in general practice suggests that alginates (Gaviscon®) or alginate-antacid preparations (Algicon®) are very effective for the relief of heartburn [38-40], but their efficacy in the healing of esophagitis is at least doubtful.

Antacids and alginates for GERD: are they useful?

In clinical practice, there is generally a consensus to apply a stepwise strategy for the treatment of GERD [4]. In patients with mild symptoms and no lesions at endoscopy (or only an erythema of mucosa), lifestyle modifications and antacids are still recommended as the classical "phase 1" therapy. However, for symptom relief, alginate-containing preparations should certainly be preferred to pure antacids. In France, for instance, a large multicenter trial [38], performed in primary care patients with typical heartburn, showed that about 92% of patients were asymptomatic after a 2-week treatment with an alginate-antacid preparation; moreover, even in those incompletely relieved by treatment, endoscopy showed no or mild esophageal lesions in 60% of them. Antacids or antacid/alginates, however, should not be used alone in severe GERD, when there are persistent or nocturnal symptoms, grade 2 or more esophagitis and/or marked sphincter incompetence with consequent complications.


The authors are indebted to Miss Sabina Cavagni for her invaluable help in checking the references and her diligence in the preparation of the manuscript.


1. Scarpignato C. Pharmacological bases of the medical treatment of gastroesophageal reflux disease. Dig Dis Sci 1988;6: 117-148.

2. Mittal RK, Reuben A, Whitney JO et al. Do bile acids reflux into the esophagus? A study in normal subjects and patients with gastroesophageal reflux disease. Gastroenterology 1987;92:371-375.

3. Richter JE. Gastroesophageal reflux disease: a review of medical therapy. In: Castell DO, Wu WC, Ott DJ (eds) Gastroesophageal Reflux Disease: Pathogenesis, Diagnosis, Therapy. Mount Kisco N.Y.: Futura Publishing, 1985;221-241.

4. Scarpignato C, Galmiche JP. Short-term treatment of reflux oesophagitis: A clinical pharmacological approach. In: Tytgat GN (ed) The Medical Management of Oesophageal Reflux Disease. London: Royal Society of Medicine, 1990;60-80.

5. Peterson WL, Richardson CT. Pharmacology and side effects of drugs used to treat peptic ulcer. In: Sleisenger MH, Fordtran JS (eds) Gastrointestinal Disease. Pathophysiology, Diagnosis and Management, 3rd edn. Philadelphia: WB Saunders Company, 1983;708-725.

6. Washington N. Handbook of Antacids and Anti-reflux Agents. Boca Raton: CRC Press, 1991.

7. Scarpignato C, Galmiche JP Antacids and alginates in the treatment of gastroesophageal reflux disease: How do they work and how much are they clinically useful? In: Scarpignato C (ed) Advances in Drug Therapy of Gastroesophageal Reflux Disease. Basel: Karger, 1992;153-181.

8. Higgs RH, Smyth RD, Castell DO. Gastric alkalinization: effect on lower esophageal sphincter pressure and serum gastrin N Engl J Med 1974;291:486-490.

9. McCallum LS, Kline M, Sturdevant RAL Studies on the mechanism of the lower esophageal sphincter pressure response to alkali ingestion in man. Gastroenterology 1975;68:948.

10. Galmiche JP, Scarpignato C. Pharmacodynamic assessment of drugs in gastroesophageal reflux disease: an overview. In: Tytgat GNJ (ed) Medical Management of Esophageal Disease London: Royal Society of Medicine, 1990;12-33.

11. Deering TB, Malagelada JR. Comparison of an H2-receptor antagonist and a neutralizing antacid on postprandial acid delivery into duodenum patients with duodenal ulcer. Gastroenterology 1977;73:11-14.

12. Desechalliers JP, Galmiche JP, Touchais JY et al. Ranitidine, cimetidine, antacids and gastroesophageal reflux: results of a 20-h esophageal pH study. Int J Clin Pharm Res 1984;4:217-222.

13. Scarpignato C, Galmiche JP Antacids and alginates in the treatment of gastroesophageal reflux disease: How do they work and how much are they clinically useful? In: Scarpignato C (ed) Advances in Drug Therapy of Gastroesophageal Reflux Disease. Basel: Karger, 1992;129-152.

14. Smith JL, Opekun AR, Larkai E et al. Sensitivity of the esophageal mucosa to pH in gastroesophageal reflux disease. Gastroenterology 1989:96:683-689.

15. Meyer C, Berenzweig H, Kuljian B et al. Controlled trial of antacid (AA) versus placebo (P) on relief of heartburn Gastroenterology 1979;76:A1201.

16. Furman D, Mensh R, Winan G et al. A double-blind trial comparing high dose liquid antacid to placebo and cimetidine in improving symptoms and objective parameters in gastroesophageal reflux Gastroenterology 1982;82:1062.

17. Graham DY, Patterson DJ. Double-blind comparison of liquid antacid and placebo in the treatment of symptomatic reflux esophagitis. Dig Dis Sci 1983;28:559-564.

18. Grove O, Bekker C, Jeppe-Hansen MG et al. Ranitidine and high dose antacid in reflux esophagitis. A randomized placebo-controlled trial. Scand J Gastroenterol 1985;20:457-461.

19. Weberg R, Berstad A. Symptomatic effect of a low-dose antacid regimen in reflux esophagitis. Scand J Gastroenterol 1989; 24:401-406

20. Washington N, Washington C, Wilson CO et al. What is "Liquid Gaviscon"? A comparison of four international formulations. Int J Pharmaceut 1986;34:105-109.

21. Malmud LS, Fisher MS. Scintigraphic detection of gastroesophageal reflux. In: Alavi A, Arger PH (eds) Multiple Image Procedures, vol 3. New York: Grune & Stratton, 1980;97-119.

22. McKay AP, Wraight EP, Hunter JO. The alginate raft: a scintigraphic evaluation. Br J Clin Pract 1989;43(suppl 66):20-24.

23. Stanciu C, Bennett JR. Alginate/antacid in the reduction of gastroesophageal reflux. Lancet 1974;1:109-111.

24. Dudicourt JC, Hemery P, Gignoux C et al. Reduction du reflux gastro-oesophagien postprandial par 1'alginate de sodium suspension. Etude pH-métrique multicentrique chez 21 malades. Nouv Presse Med 1988;17:683-685.

25. Branicki FJ, Evans DF, Jones JA et al. A controlled trial of liquid Gaviscon in gastro-oesophageal reflux using a portable pH-sensitive radiotelemetry system. J Ambul Monit 1988;1:61-72.

26. Castell DO, Dalton CB, Becker D, Sinclair J, Castell JA. Alginic acid decreases postprandial upright gastroesophageal reflux. Comparison with equal-strength antacid. Dig Dis Sci 1992;37:589-593.

27. Bennett CE, Hardy JG, Wilson CG. The influence of posture on the gastric emptying of antacids. Int J Pharmaceut 1984; 21:341-347.

28. Devis G, de Rop H, Peters O. Twenty-four-hour oesophageal pH monitoring of reflux episodes: Effect of Algicon. Br J Clin Pract 1989;43(suppl 66):15-17.

29. Washington N. Investigation into the barrier action of an alginate gastric reflux suppressant, liquid Gaviscon*. Drug Inv 1990;2:23-30.

30. Barnardo DE, Lancaster-Smith M, Strickland ID et al. A double-blind controlled trial of "Gaviscon" in patients with symptomatic gastroesophageal reflux Curr Med Res Opin 1975,3:388-391.

31. Beeley M, Warner JO. Medical treatment of symptomatic hiatus hernia with low-density compounds Curr Med Res Opin 1972:1:63-69.

32. Grossman AE, Klotz AP, Rhodes JB et al. Reflux esophagitis: a comparison of old and new medical management. J Kans Med Soc 1973:74:423-424.

33. McHardy G. A multicentric, randomized clinical trial of Gaviscon in reflux esophagitis. Southern Med J 1978;71(suppl l):16-21.

34. Scobie BA. Endoscopically controlled trial of alginate and antacid in reflux oesophagitis. Med J Aust 1976;627-628.

35. Chevrel B. A comparative crossover study on the treatment of heartburn and epigastric pain: Liquid Gaviscon and a magnesium-aluminium antacid gel. J Int Med Res 1980;8:300.

36. Graham DY, Lanza F, Dorsch ER. Symptomatic reflux oesophagitis: a double-blind controlled comparison of antacids and alginate. Curr Ther Res 1977;22:653-658.

37. Tytgat GNJ. Drug therapy of reflux oesophagitis: an update. Scand J Gastroenterol 1989:24(suppl 168):38-49.

38. Bigard MA, Colin R, Galmiche JP, Rampal P, de Meynard C. Evolution des symptômes de reflux gastro-oesophagicn (RGO) après 2 semaines de traitement par alginate-antiacide. Facteurs prédictifs et données endoscopiques chez les non-répondeurs. Gastroenterol Clin Biol 1990:14:A110.

39. Ward AE. Comparative study of Algicon versus Gaviscon in symptomatic gastroesophageal reflux. Br J Clin Pract 1989: 43(suppl 66):52-55.

40. Maxton DG, Miller JP, Whorwell PJ et al. A study of Algicon, an antacid alginate preparation in patients with reflux oesophagitis. Br J Clin Pract 1988:42:368-371.

Publication date: May 1994 OESO©2015