Influence of metabolic fuel on the13C/12C ratio of breath CO2

Natural differences in 13C/12C ratios of various metabolic fuels can produce systematic changes in the 13C/12C ratio of breath CO2, and therefore introduce errors into 13CO2 breath tests. To gain insight into the potential problem, we compared 13C/12C ratios of plasma macronutrients to those of breath CO2 under conditions that should alter the percentages of carbohydrate and lipid being oxidized. In rats, 48 h of starvation decreased the 13C/12C ratio of breath CO2 by 3.5%. At this time the 13C/12C ratio of breath CO2 was very similar to that of plasma lipids. In humans, 30 min of heavy exercise increased the breath 13CO2/12CO2 ratio by 1.3%. These changes in breath 13C/12C ratios could be predicted from 13C/12C ratios of plasma macronutrients and the percentage of carbon dioxide derived from each macronutrient, but only when compared within the same populations. For example, the 13C/12C ratios of plasma macronutrients of residents of Chicago, Illinois (USA) and Tokyo (Japan) differed by 1-3%. An empirical correction of 13CO2 breath test data is recommended when breath tests are run under conditions that will change metabolic fuel utilization.