Recent work shows that increased meal frequency reduces ghrelin responses in sheep. Human research suggests there is an interaction between insulin and ghrelin. The effect of meal frequency on this interaction is unknown. Therefore, we investigated the effect of feeding frequency on insulin and ghrelin responses in human subjects. Five healthy male volunteers were recruited from the general population: age 24 (SEM 2) years, body mass 75·7 (SEM 3·2) kg and BMI 23·8 (SEM 0·8) kg/m 2 . Volunteers underwent three 8-h feeding regimens: fasting (FAST); low-frequency (two) meal ingestion (LOFREQ MEAL ); high-frequency (twelve) meal ingestion (HIFREQ MEAL ). Meals were equi-energetic within trials, consisting of 64 % carbohydrate, 23 % fat and 13 % protein. Total energy intake was equal between feeding trials. Total area under the curve for serum insulin and plasma ghrelin responses did not differ between trials (P.0·05), although the hormonal response patterns to the two meal feeding regimens were different. An inverse relationship was found between serum insulin and plasma ghrelin during the FAST and LOFREQ MEAL trials (P,0·05); and, in the postprandial period, there was a time delay between insulin responses and successive ghrelin responses. This relationship was not observed during the HIFREQ MEAL trial (P.0·05). This study provides further evidence that the postprandial fall in ghrelin might be due, at least partially, to the rise in insulin and that high-frequency feeding may disrupt this relationship.
Ghrelin: Insulin: Feeding frequency: Snacking: AppetiteThe recent escalating obesity trend in man is due to an imbalance between energy intake and energy expenditure (1,2) . Energy intake is influenced by the effect of food's energy density, total energy content and feeding frequency and the extent to which these alter satiety. Of these factors, feeding frequency has received least attention. Epidemiological evidence in human subjects indicates increasing trends in recent years of dietary snacking and increased meal frequency (3,4) and such studies show positive relationships between snacking and increased energy intake and BMI (4) , illustrating the potential importance of investigating feeding frequency.Several gastrointestinal peptides are involved in metabolic processes and are dysregulated in states of metabolic disease (5 -7) . One of these peptides, ghrelin, an orexigenic hormone released by the stomach prior to feeding, has also been implicated in the control of fuel metabolism, appetite and pancreatic insulin release, factors quite central to the onset of metabolic disease (8)