Zinc salts are effective against pathogens in direct application. Gastroenteritis is strongly attenuated by ingestion of zinc, and this effect could be due to direct antimicrobial action of the zinc ions in the GI tract, or to the absorption of the zinc and re-release from immune cells (all granulocytes secrete zinc), or both. In clinical trials, both zinc gluconate and zinc gluconate glycine (the formulation used in lozenges) have been shown to shorten the duration of symptoms of the common cold. The amount of glycine can vary from two to twenty moles per mole of zinc gluconate. One review of the research found that out of nine controlled experiments using zinc lozenges, the results were positive in four studies, and no better than placebo in five. This review also suggested that the research is characterized by methodological problems, including differences in the dosage amount used, and the use of self-report data. The evidence suggests that zinc supplements may be most effective if they are taken at the first sign of cold symptoms.