One consequence of our modular approach is that the resultant cyclical EFMs are contained within a module, limiting the size of substrate cycles that can be discovered. Previously, Gebauer and coworkers reported a median cyclical EFM length of 35 reactions for a genome-scale human metabolic network, with some cycles spanning up to 100 reactions. In this study, the longest cyclical EFM spanned 13 reactions. The median length of a cyclical EFM ranges from 2 to 8, depending on the module. We did not find a significant correlation between mean cyclical EFM length and module size, suggesting that larger modules may not necessarily possess longer cyclical EFMs (Figure 3). For module # 141,811 (boxed in Figure 3), which is the largest module analyzed for EFMs in this study, the distribution of cyclical EFM lengths is bi-modal (Additional file 1: Figure S1). Multi-model distribution of cyclical EFM lengths was also reported previously [8].