Abstract

Abstract Objectives Intermittent calorie restriction has emerged as an effective alternative to continuous calorie restriction to impart favorable health benefits. However, there remains a degree of uncertainty about the optimal fasting length to simultaneously improve metabolic flexibility and promote positive behavior-change. While a 16-hr fast is commonly employed, it is possible that a shorter fast could result in similar metabolic benefits and better longer term adherence. Thus, we compared changes in hormone response between two 4-hr time intervals of fasting – 11–15 hrs. vs. 15–19 hrs. Methods Secondary analyses were performed from a 38-hr fasting study that enrolled 24 healthy, European men (18–30 y) with normal body mass index. Participants initiated a fast at 2300, arrived to the laboratory at 0800, and continued fasting in individual rooms. Venous blood was sampled at 13 time-points to measure insulin, glucose, adrenocorticotropin (ACTH), C-peptide, cortisol, and adiponectin via immunoassays. Data were normally distributed without outliers or missing values. Within-group differences were analyzed with paired t-tests. Results Insulin (pmol/L) declined between 11–15 hrs. (7.00; CI = 0.97, 13.02; P = .025), but not 15–19 hrs. (5.67; CI = –0.65, 11.98; P = .076). The decline in C-peptide (nmol/L) was sharper between 11–15 hrs. (0.09; CI = 0.05, 0.13; P = < .001), compared to 15–19 hrs. (0.06; CI = 0.02, 0.09; P = .003). Cortisol (nmol/L) also steeply declined between 11–15 hrs. (60.09; CI = 30.58, 89.59; P = < .001), but slightly increased between 15–19 hrs. (10.75; CI = −33.15, 11.65; P = 0.331). The change in glucose (mmol/L) was not different between 11–15 hrs. (0.02 mmol/L; CI = −0.15, 0.19; P = 0.784), but sharply decreased between 15–19 hrs. (0.24; CI = 0.10, 0.39; P = 0.002). No differences were detected for ACTH or adiponectin. Conclusions Though substrate oxidation was not measured, changes in insulin, C-peptide, cortisol, and glucose were consistent with increased gluconeogenesis during 11–15 hrs. and lipid oxidation during 15–19 hrs. of fasting. Whereas cortisol often declines throughout the day, a slight increase was noted between 15–19 hrs. – evidence of a heightened sympathetic activity. Further study of hormone response during intermittent fasting will inform optimal length to promote health benefits and longer term adherence. Funding Sources None

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