Incorporation of 3.3 g sodium propionate per 50 g available carbohydrate portion of bread reduced acutely the blood glucose response area in six healthy volunteers by 47.6 +/- 12.1% Similarly, in vitro digestibility was reduced by 47.4 +/- 1.1% (P less than 0.01). One week of dietary supplementation with 9.9 g sodium propionate in bread/d reduced the blood glucose area in comparison with standard propionate-free bread by 38.0 +/- 8.7% (P less than 0.05), but increased fecal bulk by 28.3 +/- 8.7% (P less than 0.05) and anaerobic microflora by 0.564 +/- 0.165 X 10(6)/g feces (P less than 0.05), specifically as bifidobacteria. Day-long breath hydrogen concentrations did not increase after 1 wk on propionate bread but methane production increased in the three methane producers. Although lipid changes were not significant, five subjects showed reduced high-density-lipoprotein and increased triglyceride concentrations, both of which correlated with increased fecal weight (P less than 0.05). Because propionate reduces the rate of starch digestion, studies using oral propionate must take into account its action as an enzyme inhibitor.