Intriguing gastrointestinal properties of bismuth: a folk remedy brought into the realm of clinical and investigative medicine.

Abstract

Bismuth subsalicylate (BSS), the use of which was first recorded in 1733, is highly regarded by practitioners of alternative medicine as well as by well-meaning grandmothers, clinicians and basic scientists (1). In 1900, a pink, winter-green flavoured liquid preparation of BSS, the forerunner to Pepto-Bismol (BSS) (Procter & Gamble, Ohio), was called ‘mixture cholera infantum’. Unlike previous concoctions, this mixture was proven to be a successful treatment for cholera infantum. This product, which gained in popularity steadily, was also effective against ‘summer complaint’, characterized by acute gastroenteritis. Current therapeutic uses of bismuth salts based on clinical evidence include control of odour in ostomy patients, prophylaxis against travellers’ diarrhea, and treatment of various bacterial and viral induced diarrheas, dyspepsia, peptic ulcer disease as well as nonsteriodal anti-inflammatory drug-induced upper-gastrointestinal (GI) injury (2,3). The present love affair with bismuth stems partly from observations that treatment of peptic ulcers with this inexpensive compound results in a lower rate of relapse than that obtained with H2 blockers. This is due to a direct antibacterial action of bismuth on Helicobacter pylori as well as to interference with the epithelial attachment of this organism. A Canadian, randomized clinical trial using colloidal bismuth subcitrate (CBS), together with metronidazole and tetracycline, achieved an eradication rate of 86% (4). This treatmentregimen is no longer first-line therapy for H pylori because the pooled data fall just below the 80% cut-off. It has been shown both in vitro and in vivo that bismuth in combination with ranitidine or clarithromycin has a synergistic rather than an additive effect against H pylori (5). In addition, recent preliminary in vitro evidence suggests that bismuth can prevent the resistance of H pylori to metronidazole – an increasing concern for treating physicians. Approval was recently obtained in Canada for a two-week regimen of ranitidine bismuth citrate plus clarythromycin, which achieves eradication rates comparable to those obtained with ‘triple therapy’ (5). Details regarding actual dosages and duration of treatment for the various helicobacter eradication regimens can be obtained from the Canadian Helicobacter Pylori Consensus Conference (6). The Dalhousie Helicobacter Pylori Study Group has a definite interest in bismuth compounds. The synthesis of novel bismuth compounds by Dr Neil Burford was spurred on by the realization that the exact chemical structures of both CBS and BSS are unknown. A collaborative study indicated that different bismuth compounds have markedly different in vitro activities against H pylori (7). In a separate study of experimental ulcers in a rat model not involving helicobacter infection, the same group demonstrated that ulcer healing properties depend on the chemical structure of the bismuth compound used (8,9). In a study of colitis in the rat, this group also showed that both BSS and CBS had efficacy in healing colitis (10). This result concurs with results from