Effect of intermittent fasting and refeeding on insulin action in healthy men

Abstract

Insulin resistance is currently a major health problem. This may be because of a marked decrease in daily physical activity during recent decades combined with constant food abundance. This lifestyle collides with our genome, which was most likely selected in the late Paleolithic era (50,000-10,000 BC) by criteria that favored survival in an environment characterized by fluctuations between periods of feast and famine. The theory of thrifty genes states that these fluctuations are required for optimal metabolic function. We mimicked the fluctuations in eight healthy young men [25.0 +/- 0.1 yr (mean +/- SE); body mass index: 25.7 +/- 0.4 kg/m(2)] by subjecting them to intermittent fasting every second day for 20 h for 15 days. Euglycemic hyperinsulinemic (40 mU.min(-1).m(-2)) clamps were performed before and after the intervention period. Subjects maintained body weight (86.4 +/- 2.3 kg; coefficient of variation: 0.8 +/- 0.1%). Plasma free fatty acid and beta-hydroxybutyrate concentrations were 347 +/- 18 and 0.06 +/- 0.02 mM, respectively, after overnight fast but increased (P < 0.05) to 423 +/- 86 and 0.10 +/- 0.04 mM after 20-h fasting, confirming that the subjects were fasting. Insulin-mediated whole body glucose uptake rates increased from 6.3 +/- 0.6 to 7.3 +/- 0.3 mg.kg(-1).min(-1) (P = 0.03), and insulin-induced inhibition of adipose tissue lipolysis was more prominent after than before the intervention (P = 0.05). After the 20-h fasting periods, plasma adiponectin was increased compared with the basal levels before and after the intervention (5,922 +/- 991 vs. 3,860 +/- 784 ng/ml, P = 0.02). This experiment is the first in humans to show that intermittent fasting increases insulin-mediated glucose uptake rates, and the findings are compatible with the thrifty gene concept.

Effects of intermittent fasting on glucose and lipid metabolism

“…The majority of rodent studies (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) and a small number of human studies (22)(23)(24)(25)(26) have used IER protocols, which completely restrict energy intake (i.e. 100 % energy restriction) every other day, with fasting intervals ranging between 20 and 36 h. However, the long-term sustainability of this alternate day total fasting approach in human subjects is questionable due to the persistent hunger reported (24) .…”

Dietary Interventions to Extend Life Span and Health Span Based on Calorie Restriction

“…For example, overweight participants participating in an 8-week study using IF (participants alternated daily between ad libitum intake and 80% CR) lost weight and increased in measures of pulmonary function, perceived energy, and mood (127). Importantly, several recent short-term interventions have examined IF in nonobese humans (129)(130)(131) and have found significant health benefits that parallel CR, including increased insulin sensitivity (127), upregulation of sirt1 (128), and decreased fat mass (131). Although the potential for IF to confer short-term health benefits to humans seems significant, IF's effects on the aging process are not known.…”

Transcriptome analysis of peripheral blood mononuclear cells in human subjects following a 36 h fast provides evidence of effects on genes regulating inflammation, apoptosis and energy metabolism

“…It is postulated that this pattern of eating better reflects the periods of feast and famine that the human genome has evolved to cope with (Halberg et al 2005). Studies in animals suggest that certain patterns of feeding such as alternate-day fasting may offer similar health benefits to long-term caloric restriction, in terms of increased longevity and reduced risks of developing chronic diseases such as cardiovascular disease (CVD), dementia and certain cancers (Trepanowski et al 2011).…”