Volume 5 • Number 3 • 2000 HELICOBACTER © Blackwell Science, Inc. 1083-4389/00/$15.00/169 169–175 169 Double-Blind Comparison of Absorbable Colloidal Bismuth Subcitrate and Nonabsorbable Bismuth Subnitrate in the Eradication of Helicobacter pylori and the Relief of Nonulcer Dyspepsia Mark W. Whitehead,* Rosemary H. Phillips,* Christine E. Sieniawska, † H. Trevor Delves, † Paul T. Seed, ‡ Richard P.H. Thompson,* and Jonathan J. Powell* *Gastrointestinal Laboratory, The Rayne Institute, St Thomas’ Hospital, London; † School of Medicine, University of Southampton, Southampton General Hospital, Southampton; and ‡ Department of Public Health Sciences, GKT School of Medicine, ABSTRACT King’s College, London Background. Bismuth is widely used for the eradication of H. pylori, especially in developing countries, al- though there are concerns over its neurotoxicity. Whether bismuth has to be absorbed in humans to act against H. pylori is not known. In this study, we compared “ab- sorbable” (colloidal bismuth subcitrate) and “nonab- sorbable” (bismuth subnitrate) bismuth as part of triple therapy in the eradication of H. pylori. Materials and Methods. A double-blind, randomized, placebo-controlled trial was carried out with 120 H. pylori–positive patients with nonulcer dyspepsia. Group CBS + Ab (n = 35) received colloidal bismuth subcit- rate (one tablet qds), amoxicillin (500 mg qds), and metronidazole (400 mg tds). Group BSN + Ab (n = 35) received bismuth subnitrate (two tablets tds) and the same antibiotics. Group Ab (n = 35) received placebo bismuth (two tablets tds) and the antibiotics. Group BSN (n = 15) received bismuth subnitrate (two tablets tds) and placebo antibiotics. Bismuth was taken for 4 weeks and the antibiotics for the first 2 weeks. H. pylori eradication, side effects, compliance, pre- and post- treatment symptom scores, and bismuth absorption were assessed. Results. H. pylori eradication was 69%, 83%, 31%, and 0% in CBS + Ab, BSN + Ab, Ab, and BSN, respec- tively. Side effects, compliance, and symptom relief were similar in all groups, but blood bismuth levels were significantly greater in CBS + Ab than the other three groups. Conclusion. The efficacy of bismuth-based therapies as part of triple therapy in the eradication of H. pylori is unrelated to absorption. Hence, the use of effective but poorly absorbed bismuth preparations should be en- couraged for bismuth-based eradication therapies. D espite their declining use in the Western world, bismuth-based therapies still are widely used in other regions for eradication of Helicobacter pylori [1–4]. Bismuth compounds have been used for many years for the treatment of gastrointesti- nal symptoms [5] and were among the first to be used in the treatment of H. pylori infection, al- though with limited success as monotherapy [6] and mainly in combination with antibiotics as the more successful triple therapy [7]. A worldwide review of eradication therapies for H. pylori found that bismuth-based triple therapies remain among the most efficacious, with eradication rates of up to 90% [8]. Thus bismuth-based classic triple therapy (bismuth, metronidazole, and either tetra- cycline or amoxicillin), as recommended by the Congress of Gastroenterology in 1990 [9], still is commonly used in developing countries, although less so in Europe and the United States [10], as it is inexpensive and effective. This regimen is also combined with a proton pump inhibitor (PPI) (qua- druple therapy) for the eradication of H. pylori in patients who have failed to respond to triple ther- apy [11]. There are, however, concerns over the long- term safety of bismuth compounds, since the bis- muth ion is neurotoxic and, in the 1970s, pro- longed use of soluble preparations of bismuth caused toxicity [12]. Therefore, newer forms of bismuth are now used, chiefly colloidal bismuth subcitrate (nominal particle size, 5–40 nm diame- ter), bismuth subnitrate, and bismuth subsalicy- Reprint requests to: Jonathan J. Powell, MD, Gastrointes- tinal Laboratory, The Rayne Institute, St. Thoma’s Hospi- tal, London SE1 7EH, United Kingdom.