Background: The problems of adherence to energy restriction in humans are well known. Objective: To compare the feasibility and effectiveness of intermittent continuous energy (IER) with continuous energy restriction (CER) for weight loss, insulin sensitivity and other metabolic disease risk markers. Design: Randomized comparison of a 25% energy restriction as IER (B2710 kJ/day for 2 days/week) or CER (B6276 kJ/day for 7 days/week) in 107 overweight or obese (mean ( ± s.d.) body mass index 30.6 ( ± 5.1) kg m À2 ) premenopausal women observed over a period of 6 months. Weight, anthropometry, biomarkers for breast cancer, diabetes, cardiovascular disease and dementia risk; insulin resistance (HOMA), oxidative stress markers, leptin, adiponectin, insulin-like growth factor (IGF)-1 and IGF binding proteins 1 and 2, androgens, prolactin, inflammatory markers (high sensitivity C-reactive protein and sialic acid), lipids, blood pressure and brain-derived neurotrophic factor were assessed at baseline and after 1, 3 and 6 months. Results: Last observation carried forward analysis showed that IER and CER are equally effective for weight loss: mean (95% confidence interval ) weight change for IER was À6.4 (À7.9 to À4.8) kg vs À5.6 (À6.9 to À4.4) kg for CER (P-value for difference between groups ¼ 0.4). Both groups experienced comparable reductions in leptin, free androgen index, high-sensitivity C-reactive protein, total and LDL cholesterol, triglycerides, blood pressure and increases in sex hormone binding globulin, IGF binding proteins 1 and 2. Reductions in fasting insulin and insulin resistance were modest in both groups, but greater with IER than with CER; difference between groups for fasting insulin was À1.2 (À1.4 to À1.0) mU ml À1 and for insulin resistance was À1.2 (À1.5 to À1.0) mU mmol À1 l À1 (both P ¼ 0.04). Conclusion: IER is as effective as CER with regard to weight loss, insulin sensitivity and other health biomarkers, and may be offered as an alternative equivalent to CER for weight loss and reducing disease risk.

Intermittent energy restriction may result in greater improvements in insulin sensitivity and weight control than daily energy restriction (DER). We tested two intermittent energy and carbohydrate restriction (IECR) regimens, including one which allowed ad libitum protein and fat (IECR þ PF). Overweight women (n 115) aged 20 and 69 years with a family history of breast cancer were randomised to an overall 25 % energy restriction, either as an IECR (2500 -2717 kJ/d, , 40 g carbohydrate/d for 2 d/week) or a 25 % DER (approximately 6000 kJ/d for 7 d/week) or an IECR þ PF for a 3-month weight-loss period and 1 month of weight maintenance (IECR or IECR þ PF for 1 d/week). Insulin resistance reduced with the IECR diets (mean 20·34 (95 % CI 2 0·66, 2 0·02) units) and the IECR þ PF diet (mean 2 0·38 (95 % CI 20·75, 2 0·01) units). Reductions with the IECR diets were significantly greater compared with the DER diet (mean 0·2 (95 % CI 2 0·19, 0·66) mU/unit, P¼0·02). Both IECR groups had greater reductions in body fat compared with the DER group (IECR: mean 2 3·7 (95 % CI 22·5, 24·9) kg, P¼0·007; IECR þ PF: mean 23·7 (95 % CI 2 2·8, 24·7) kg, P¼0·019; DER: mean 22·0 (95 % CI 21·0, 3·0) kg). During the weight maintenance phase, 1 d of IECR or IECR þ PF per week maintained the reductions in insulin resistance and weight. In the short term, IECR is superior to DER with respect to improved insulin sensitivity and body fat reduction. Longer-term studies into the safety and effectiveness of IECR diets are warranted.Key words: Intermittent energy restriction: Low-carbohydrate diets: Weight loss: Daily energy restriction: Insulin resistanceThe global health burden of obesity-related conditions such as diabetes, CVD, dementia and certain cancers, including breast cancer, may be reduced by weight loss and the associated improvements in insulin sensitivity. The difficulties of achieving and sustaining weight loss by energy restriction are well known (1) . Even when reduced weights are maintained, metabolic benefits achieved with weight loss are often attenuated because of non-compliance or adaptation (2 -4) . Effective dietary interventions are needed that promote long-term adherence and sustained beneficial effects on metabolic and disease markers. Such interventions need to be palatable and satiating, meet minimal nutritional requirements, promote loss of fat and preserve lean body mass, ensure long-term safety, be simple to administer and monitor and have widespread public health utility. Multiple dietary approaches have been studied that vary in macronutrient composition (5) and the degree of energy restriction (6) . These typically achieve long-term 5 % weight loss in

BACKGROUND: Breast cancer diagnosis may be a teachable moment for lifestyle behaviour change and to prevent adjuvant therapy associated weight gain. We assessed the acceptability and effectiveness of two weight control programmes initiated soon after breast cancer diagnosis to reduce weight amongst overweight or obese women and prevent gains in normal-weight women. METHODS: Overweight or obese (n = 243) and normal weight (n = 166) women were randomised to a three-month unsupervised home (home), a supervised community weight control programme (community) or to standard written advice (control). Primary end points were change in weight and body fat at 12 months. Secondary end points included change in insulin, cardiovascular risk markers, quality of life and cost-effectiveness of the programmes. RESULTS: Forty-three percent of eligible women were recruited. Both programmes reduced weight and body fat: home vs. control mean (95% CI); weight −2.3 (−3.5, −1.0) kg, body fat −1.6 (−2.6, −0.7) kg, community vs. control; weight −2.4 (−3.6, −1.1) kg, body fat −1.4 (−2.4, −0.5) kg (all p < 0.001). The community group increased physical activity, reduced insulin, cardiovascular disease risk markers, increased QOL and was cost-effective. CONCLUSIONS: The programmes were equally effective for weight control, but the community programme had additional benefits. CLINICAL TRIAL REGISTRATION: ISRCTN68576140

BackgroundObservational studies suggest weight loss and energy restriction reduce breast cancer risk. Intermittent energy restriction (IER) reduces weight to the same extent as, or more than equivalent continuous energy restriction (CER) but the effects of IER on normal breast tissue and systemic metabolism as indicators of breast cancer risk are unknown.MethodsWe assessed the effect of IER (two days of 65 % energy restriction per week) for one menstrual cycle on breast tissue gene expression using Affymetrix GeneChips, adipocyte size by morphometry, and systemic metabolism (insulin resistance, lipids, serum and urine metabolites, lymphocyte gene expression) in 23 overweight premenopausal women at high risk of breast cancer. Unsupervised and supervised analyses of matched pre and post IER biopsies in 20 subjects were performed, whilst liquid and gas chromatography mass spectrometry assessed corresponding changes in serum and urine metabolites in all subjects after the two restricted and five unrestricted days of the IER.ResultsWomen lost 4.8 % (±2.0 %) of body weight and 8.0 % (±5.0 %) of total body fat. Insulin resistance (homeostatic model assessment (HOMA)) reduced by 29.8 % (±17.8 %) on the restricted days and by 11 % (±34 %) on the unrestricted days of the IER. Five hundred and twenty-seven metabolites significantly increased or decreased during the two restricted days of IER. Ninety-one percent of these returned to baseline after 5 days of normal eating. Eleven subjects (55 %) displayed reductions in energy restriction-associated metabolic gene pathways including lipid synthesis, gluconeogenesis and glycogen synthesis. Some of these women also had increases in genes associated with breast epithelial cell differentiation (secretoglobulins, milk proteins and mucins) and decreased collagen synthesis (TNMD, PCOLCE2, TIMP4). There was no appreciable effect of IER on breast gene expression in the other nine subjects. These groups did not differ in the degree of changes in weight, total body fat, fat cell size or serum or urine metabolomic markers. Corresponding gene changes were not seen in peripheral blood lymphocytes.ConclusionThe transcriptional response to IER is variable in breast tissue, which was not reflected in the systemic response, which occurred in all subjects. The mechanisms of breast responsiveness/non-responsiveness require further investigation.Trial registrationISRCTN77916487 31/07/2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0714-4) contains supplementary material, which is available to authorized users.