Objective: To investigate the effect of a rye, high-fibre diet (HFD) vs a wheat, low-fibre diet (LFD), meal frequency, nibbling (Nib, seven times a day) or ordinary (Ord, three times a day), and their combined effects on blood glucose, insulin, lipids, urinary C-peptide and ileal excretion of energy, cholesterol and bile acids in humans. Design: LFD period with Nib or Ord meal frequency followed by an HFD diet with Nib or Ord meal frequency in randomized, crossover design. Setting: Outpatients of ileostomy volunteers were called for an investigation in research word. Subjects: A total of 10 subjects (two female subjects, age 34 and 51 y; eight males, mean age 54.4 y, range 43-65 y) participated in the experiment. All subjects were proctocolectomized for ulcerative colitis (mean 16.0 y, range 8-29 y before the study). Intervention: In total, 10 ileostomy subjects started with LFD for 2 weeks, the first week on either Nib (five subjects) or Ord (five subjects) and the second week on the other meal frequencies, in a crossover design, followed by a wash-out week, and continued with HFD period for 2 weeks in the same meal frequency manner. All foods consumed in both Nib or Ord regimens were identical and a high-fibre rye bread was used in the HFD period and a low-fibre wheat bread in the LFD period. Main outcome measures: Day-profiles of blood glucose, insulin and lipids, blood lipids before and after dietary intervention, and excretion of steroids in the effluents and C-peptide in the urine. Results: During the Nib regimen, plasma glucose and insulin peaks were lower at the end of the day with HFD compared with LFD. Urinary C-peptide excretion was significantly higher in the day-time on LFD compared with HFD (LFD-Ord vs HFD-Ord, Po0.01; LFD-Nib vs HFD-Nib, Po0.01). Plasma free-cholesterol, total cholesterol, triglycerides and phospholipids were significantly higher (Po0.05) after LFD than after HFD with the Nib regimen. A higher excretion of energy (Po0.05) and chenodeoxycholic acid (Po0.05) were observed with HFD compared with LFD regardless of meal frequency. A higher daily excretion of cholic acid, total bile acids, cholesterol, net cholesterol and net sterols (Po0.05) was observed on HFD compared with LFD with the Nib regimen. Conclusions: An HFD decreased insulin secretion measured as a decreased excretion of C-peptide in urine and as decreased plasma insulin peaks at the end of the day during a Nib regimen. The smoother glycaemic responses at the end of the day during a Nib regimen may be a consequence of a second meal phenomenon, possibly related to the nature of dietary fibre complex. Contributors: EAL and JXZ were responsible for the study design, conducting the dietary intervention, completing the statistical analysis and writing the paper. PT was responsible for the study design and conducting the dietary intervention of the study. DL was involved in the advisory of writing the paper and the analysis of the blood lipids. PÅ was involved in the concept and planning, and the analysis of the nutrients in the...