BACKGROUND: Zinc is an important nutrient and is necessary to maintain a multitude of physiologic processes. Mineral supplements that provide physiologic doses of zinc may be used when dietary zinc is inadequate. Zinc is also used in pharmacologic doses to treat zinc deficiency and diseases such as Wilson's disease and acrodermatitis enteropathica. Although there are several zinc salts available, they are not equal in solubility, which is thought to be a key factor in zinc absorption. Moreover, the solubility of the salts is affected by pH, which may vary between pH 1 and 7 under various physiologic conditions in the stomach. The objectives of this 2-way 4-phase crossover study were to evaluate the effect of high (> or = 5) and low (< or = 3) intragastric pH on the absorption of zinc from the acetate and oxide salt in young healthy volunteers. METHODS: After a 9-hour fast, 10 healthy subjects (5 males and 5 females) were given a single oral dose of 50 mg of elemental zinc as the acetate or the oxide salt and under either high or low intragastric pH conditions. In all phases, a Heidelberg capsule pH detector-transmitter was used to continuously monitor intragastric pH. During the high pH phases, single oral doses of famotidine 40 mg oral suspension were administered before the zinc to raise the intragastric pH above 5. Intragastric pH < or = 3 was maintained in the low pH phases. RESULTS: The mean plasma zinc area under the curve for zinc acetate at low pH (AL), zinc acetate at high pH (AH), zinc oxide at low pH (OL), and zinc oxide at high pH (OH) were 524, 378, 364, and 66 micrograms x h/dL, respectively. The highest zinc plasma concentrations occurred with the acetate salt at a low intragastric pH, while the lowest plasma concentrations occurred with the oxide salt at a high intragastric pH. The importance of pH to the dissolution of these salts was verified by in vitro tests. Twenty-four-hour urinary zinc excretion was the highest for the AL phase and lowest for the OH phase. CONCLUSION: This study indicates that intragastric pH and salt solubility-dissolution are important in the oral absorption of zinc. Specifically, the oxide salt is not an appropriate zinc salt to use in those patients with elevated intragastric pH.