Could Intermittent Energy Restriction and Intermittent Fasting Reduce Rates of Cancer in Obese, Overweight, and Normal-Weight Subjects? A Summary of Evidence.

Animal studies and human observational data link energy restriction (ER) to reduced rates of carcinogenesis. Most of these studies have involved continuous energy restriction (CER), but there is increasing public and scientific interest in the potential health and anticancer effects of intermittent energy restriction (IER) or intermittent fasting (IF), which comprise periods of marked ER or total fasting interspersed with periods of normal eating. This review summarizes animal studies that assessed tumor rates with IER and IF compared with CER or ad libitum feed consumption. The relevance of these animal data to human cancer is also considered by summarizing available human studies of the effects of IER or IF compared with CER on cancer biomarkers in obese, overweight, and normal-weight subjects. IER regimens that include periods of ER alternating with ad libitum feed consumption for 1, 2, or 3 wk have been reported to be superior to CER in reducing tumor rates in most spontaneous mice tumor models. Limited human data from short-term studies (≤6 mo) in overweight and obese subjects have shown that IER can lead to greater improvements in insulin sensitivity (homeostasis model assessment) than can CER, with comparable reductions in adipokines and inflammatory markers and minor changes in the insulin-like growth factor axis. There are currently no data comparing IER or IF with CER in normal-weight subjects. The benefits of IER in these short-term trials are of interest, but not sufficient evidence to recommend the use of IER above CER. Longer-term human studies of adherence to and efficacy and safety of IER are required in obese and overweight subjects, as well as normal-weight subjects.

Harvie MN ，Howell T 《-》

Intermittent v. continuous energy restriction: differential effects on postprandial glucose and lipid metabolism following matched weight loss in overweight/obese participants.

Antoni R ，Johnston KL ，Collins AL ，Robertson MD ... -  《-》

Matched Weight Loss Through Intermittent or Continuous Energy Restriction Does Not Lead To Compensatory Increases in Appetite and Eating Behavior in a Randomized Controlled Trial in Women with Overweight and Obesity.

Continuous energy restriction (CER) is purported to be problematic because of reductions in fat-free mass (FFM), compensatory motivation to overeat, and weakened satiety. Intermittent energy restriction (IER) is an alternative behavioral weight loss (WL) strategy that may mitigate some of these limitations. The objective of the DIVA study was to compare the effects of CER and IER on appetite when the degree of WL (≥5%) is matched. Women with overweight/obesity (BMI 25.0-34.9 kg/m2; age 18-55 y) were recruited for this controlled-feeding RCT via CER (25% daily energy restriction) or IER (alternating ad libitum and 75% energy restriction days). Probe days were conducted at baseline and post-intervention to assess body composition, ad libitum energy intake and subjective appetite in response to a fixed-energy breakfast, and eating behavior traits. After baseline measurements, participants were allocated to CER (n = 22) or IER (n = 24). Per protocol analyses (≥5% WL within 12 wk) were conducted with use of repeated measures ANOVA. Thirty of 37 completers reached ≥5% WL [CER (n = 18): 6.3 ± 0.8% in 57 ± 16 d, IER (n = 12): 6.6 ± 1.1% in 67 ± 13 d; % WL P = 0.43 and days P = 0.10]. Fat mass [-3.9 (95% CI: -4.3, -3.4) kg] and FFM [-1.3 (95% CI: -1.6, -1.0) kg] were reduced post-WL (P < 0.001), with no group differences. Self-selected meal size decreased post-WL in CER (P = 0.03) but not in IER (P = 0.19). Hunger AUC decreased post-WL (P < 0.05), with no group differences. Satiety quotient remained unchanged and was similar in both groups. Both interventions improved dietary restraint, craving control, susceptibility to hunger, and binge eating (P < 0.001). Controlled ≥5% WL via CER or IER did not differentially affect changes in body composition, reductions in hunger, and improvements in eating behavior traits. This suggests that neither CER nor IER lead to compensatory adaptations in appetite in women with overweight/obesity. This trial was registered at clinicaltrials.gov as NCT03447600.

Beaulieu K ，Casanova N ，Oustric P ，Turicchi J ，Gibbons C ，Hopkins M ，Varady K ，Blundell J ，Finlayson G ... -  《-》

Intermittent energy restriction is comparable to continuous energy restriction for cardiometabolic health in adults with central obesity: A randomized controlled trial; the Met-IER study.

Short bouts of severe energy restriction may have additional, beneficial cardiometabolic effects beyond that of weight loss. We aimed to assess the short-term effects of intermittent fasting on insulin sensitivity and related cardiometabolic mechanisms. This parallel arm, randomized controlled trial compared the short-term effects of intermittent and continuous energy restriction (IER and CER) diets on markers of cardiometabolic health in individuals with central obesity, aiming for equivalent weight loss on both diets. Outcomes were assessed in non-smoking men and women (35-75 y), following 4-wk IER (48 h 600 kcal/d followed by 5-day healthy eating advice) or CER diets (-500 kcal/d healthy eating advice). The primary outcome was the revised quantitative insulin sensitivity check index (R-QUICKI), an indirect estimate of insulin sensitivity. Secondary outcomes included ambulatory blood pressure (ABP), indicators of sympathetic activity (heart rate variability (HRV) and normetanephrine), and markers of glucose homeostasis/insulin resistance, adiposity, lipids and inflammation. Forty-three participants completed the study. Reductions in body weight were equivalent in both groups: mean loss (%) -2.6; 95% CI -3.3, -1.9 and -2.9; -3.6, -2.1 for CER and IER, respectively, P = 0.464). R-QUICKI increased following IER and CER, with no between-diet differences (overall mean increase (%) 6.6; 3.6, 9.6). Fasting plasma glucose concentrations decreased after CER but not after IER (mean difference CER-IER - 4.8% (0.7, 8.9), P < 0.05) and fasting plasma non-esterified fatty acid concentrations were lower after IER compared to CER (mean difference CER-IER 0.15 mmol/L (0.06, 0.24), P < 0.005). There were no differences in lipids, adipokine/inflammatory markers, ABP or HRV between diets. Short-term CER or IER diets are comparable in their effects on most markers of cardiometabolic risk, although adaptive changes in glucose and fatty acid metabolism occur. This study is registered at clinicaltrials.gov as NCT02679989.

Pinto AM ，Bordoli C ，Buckner LP ，Kim C ，Kaplan PC ，Del Arenal IM ，Jeffcock EJ ，Hall WL ... -  《-》

The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women.

Harvie MN ，Pegington M ，Mattson MP ，Frystyk J ，Dillon B ，Evans G ，Cuzick J ，Jebb SA ，Martin B ，Cutler RG ，Son TG ，Maudsley S ，Carlson OD ，Egan JM ，Flyvbjerg A ，Howell A ... -  《-》