The history of acid inhibition.

In ancient times, acids were not understood in the modem chemical sense but merely as bitter sour liquids [1]. Some foods were thought acidic, and if the stomach had an ulcer, everything acrid was to be avoided and soothing remedies such as starch and milk used. Antacids neutralize, rather than inhibit, acid secretion but could not be rationally prescribed until acids were understood in the modern chemical sense. Hydrochloric acid has been known since the early fifteenth century, thought to be in the stomach by Paracelsus in the sixteenth and by Van Helmont in the seventeenth century, but it was not until 1823 that Prout definitively identified free hydrochloric acid in the gastric juice of man and animals and made quantitative measurements of its concentration. Antacids became widely used only this century, especially in association with Sippytype diets for ulcers [2]. As recently as the 1960s, orthodox gastroenterologists believed that gastric acidity was reduced by minimizing the amount of acid-stimulating foods such as protein and increasing the amount of acid-inhibiting foods such as fats. It was thought that gastrin release was reduced by limiting meals to 150 ml to prevent antral distension and by forbidding secretagogues such as meat juices, coffee, caffeine-containing beverages and alcohol. Moreover, since the patient on such a diet might become frustrated and then hypersecrete acid if he saw normal meals that were forbidden, patients were not allowed to join the family at meal times [2]. Certainly doctors have used antacids for thousands of years to treat patients' symptoms, and both doctors and patients have generally been satisfied with this treatment. Half the adults in the United States have used antacids, and a quarter have taken two or more doses per month. Doctors are even more convinced than patients of the helpfulness of antacids in relieving symptoms. Nevertheless, there is little evidence in the doubleblind, randomized controlled trials that antacids do relieve ulcer symptoms, and in the conventional doses, they are probably no more than a logical placebo [3]. By contrast, antacids have now been shown repeatedly to be more effective than placebo in healing duodenal ulcers, in the range of efficacy of H2 blockade. Although the classical study used over a 1000 mmol/day, lower doses have been tried and in further trials were found effective down to around 200 mmol/day [3, 4].