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ERGO2: A Prospective, Randomized Trial of Calorie-Restricted Ketogenic Diet and Fasting in Addition to Reirradiation for Malignant Glioma.
Voss, M, Wagner, M, von Mettenheim, N, Harter, PN, Wenger, KJ, Franz, K, Bojunga, J, Vetter, M, Gerlach, R, Glatzel, M, et al
International journal of radiation oncology, biology, physics. 2020;(4):987-995
Abstract
PURPOSE ERGO2 is the first randomized clinical trial on a calorically restricted ketogenic diet (KD) and intermittent fasting (KD-IF) in addition to reirradiation for recurrent malignant gliomas. METHODS AND MATERIALS Fifty patients were randomized 1:1 to reirradiation combined with either a calorically unrestricted diet or KD-IF. The KD-IF schedule included 3 days of KD (21-23 kcal/kg/d), followed by 3 days of fasting and again 3 days of KD. Primary endpoint was progression-free survival (PFS) at 6 months (PFS6). Secondary endpoints were PFS, local PFS, overall survival (OS), frequency of epileptic seizures, rate of ketosis and quality of life. RESULTS Four patients quit the trial before treatment and 3 patients stopped KD-IF prematurely. Of the 20 patients who completed KD-IF, 17 patients developed ketosis at day 6 and glucose levels declined significantly. KD-IF was well-tolerated with a modest weight loss of -2.1 ± 1.8 kg. No severe adverse events attributable to the diet occurred. PFS6 was not significantly different between the 2 groups (KD-IF: 20%; calorically unrestricted diet: 16%). Similarly, no difference in PFS, local PFS6, or OS was observable. Explorative analysis revealed that patients in the KD-IF group who had a glucose level of less than the median (83.5 mg/dL) on day 6 had significantly longer PFS and OS compared with those above the median (P < .05). CONCLUSIONS KD-IF is feasible and effective in inducing ketosis in heavily pretreated patients with recurrent glioma. However, the short schedule reported here failed to increase the efficacy of reirradiation. CLINICALTRIALS. GOV NUMBER NCT01754350.
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Intermittent fasting 5:2 diet: What is the macronutrient and micronutrient intake and composition?
Scholtens, EL, Krebs, JD, Corley, BT, Hall, RM
Clinical nutrition (Edinburgh, Scotland). 2020;(11):3354-3360
Abstract
BACKGROUND & AIM: Intermittent fasting (IF) is a dietary intervention that has been investigated as an alternative weight-loss diet due to conventional approaches having poor long-term adherence. However, the macronutrient and micronutrient intake and composition of IF diets have been overlooked. The primary aim of this study was to describe the macronutrient and micronutrient intake of individuals following the 5:2 intermittent fasting diet (IF 5:2). METHODS Thirty eight overweight and obese participants were included from two previous studies of IF 5:2. The participants selected included 27 males and 11 females, with and without Type 2 Diabetes. The dietary intervention, IF 5:2, consisted of two days per week fasting, either consecutive or non-consecutive, and five days per week of habitual intake. Prospectively completed 4-day estimated food records were used to assess macronutrient and micronutrient intake at baseline and week six. The 4-day records were weighted to give a mean daily intake during IF 5:2. RESULTS During IF 5:2 the median (25th, 75th quartile) daily macronutrient composition was 22 (19, 24)% from protein, 33 (29, 37)% from fat and 39 (36, 43)% from carbohydrates. The intake (g/d) of carbohydrates and fibre decreased significantly from baseline to week six (p < 0.001) as well as on fasting days compared to non-fasting days (p < 0.001). The intake of calcium, zinc, magnesium and potassium were lower than recommended guidelines. Sodium intake exceeded the suggested daily target. On fasting days, the percent of total energy from protein significantly increased from 21% to 25% (p = 0.02). Despite intake being unrestricted on non-fasting days the energy intake decreased by week six when compared with baseline. CONCLUSION The composition of IF 5:2 was a high protein, moderate fat, low carbohydrate diet with a low fibre intake. Some micronutrients have lower than recommended intake. However, overall IF 5:2 is a safe acceptable weight-loss diet strategy.
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Impact of intermittent vs. continuous energy restriction on weight and cardiometabolic factors: a 12-month follow-up.
Headland, ML, Clifton, PM, Keogh, JB
International journal of obesity (2005). 2020;(6):1236-1242
Abstract
BACKGROUND AND OBJECTIVE Intermittent energy restriction continues to gain popularity as a weight loss strategy; however, data assessing it's long-term viability is limited. The objective of this study was to follow up with participants 12 months after they had completed a 12-month dietary intervention trial involving continuous energy restriction and two forms of intermittent energy restriction; a week-on-week-off energy restriction and a 5:2 programme, assessing long-term changes on weight, body composition, blood lipids and glucose. SUBJECTS AND METHODS 109 overweight and obese adults, aged 18-72 years, attended a 12-month follow-up after completing a 12-month dietary intervention involving three groups: continuous energy restriction (1000 kcal/day for women and 1200 kcal/day for men), week-on-week-off energy restriction (alternating between the same energy restriction as the continuous group for one week and one week of habitual diet), or 5:2 (500 kcal/day on modified fast days each week for women and 600 kcal/day for men). The primary outcome was weight change at 24 months from baseline, with secondary outcomes of change in body composition, blood lipids and glucose. RESULTS For the 109 individuals who completed the 12-month follow-up (82 female, 15 male, mean BMI 33 kg/m2), weight decreased over time with no differences between week-on and week-off and continuous energy restriction or 5:2 and continuous energy restriction with -4.5 ± 4.9 kg for continuous energy restriction, -2.8 ± 6.5 kg for week-on, week-off and -3.5 ± 5.1 kg for 5:2. Total cholesterol reduced over time and glucose, HDL, LDL and triglycerides were unchanged. DISCUSSION AND CONCLUSION Intermittent energy restriction was as successful in achieving modest weight loss over a 24-month period as continuous energy restriction.
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Effect of intermittent compared to continuous energy restriction on weight loss and weight maintenance after 12 months in healthy overweight or obese adults.
Headland, ML, Clifton, PM, Keogh, JB
International journal of obesity (2005). 2019;(10):2028-2036
Abstract
BACKGROUND AND OBJECTIVE Intermittent energy restriction (IER) is an alternative to continuous energy restriction (CER) for weight loss. There are few long-term trials comparing efficacy of these methods. The objective was to compare the effects of CER to two forms of IER; a week-on-week-off energy restriction and a 5:2 program, during which participants restricted their energy intake severely for 2 days and ate as usual for 5 days, on weight loss, body composition, blood lipids, and glucose. SUBJECTS AND METHODS A one-year randomized parallel trial was conducted at the University of South Australia, Adelaide, Australia. Participants were 332 overweight and obese adults, ages 18-72 years, who were randomized to 1 of 3 groups: CER (4200 kJ/day for women and 5040 kJ/day for men), week-on-week-off energy restriction (alternating between the same energy restriction as the continuous group for one week and one week of habitual diet), or 5:2 (2100 kJ/day on modified fast days each week for women and 2520 kJ/day for men, the 2 days of energy restriction could be consecutive or non-consecutive). Primary outcome was weight loss, and secondary outcomes were changes in body composition, blood lipids, and glucose. RESULTS For the 146 individuals who completed the study (124 female, 22 male, mean BMI 33 kg/m2) mean weight loss, and body fat loss at 12 months was similar in the three intervention groups, -6.6 kg for CER, -5.1 kg for the week-on, week-off and -5.0 kg for 5:2 (p = 0.2 time by diet). Discontinuation rates were not different (p = 0.4). HDL-cholesterol rose (7%) and triglycerides decreased (13%) at 12 months with no differences between groups. No changes were seen for fasting glucose or LDL-cholesterol. DISCUSSION AND CONCLUSION The two forms of IER were not statistically different for weight loss, body composition, and cardiometabolic risk factors compared to CER.
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The effect of intermittent compared with continuous energy restriction on glycaemic control in patients with type 2 diabetes: 24-month follow-up of a randomised noninferiority trial.
Carter, S, Clifton, PM, Keogh, JB
Diabetes research and clinical practice. 2019;:11-19
Abstract
AIMS: We investigated the effects of intermittent compared to continuous energy restriction on glycaemic control in patients with type 2 diabetes mellitus. METHODS Adults (N = 137) with type 2 diabetes (mean [SD] HbA1c level, 7.3% (56 mmol/mol) [1.3%] [14.2 mmol/mol]) were randomised to one of two diets for 12 months. The intermittent group (n = 70) followed a 2100-2500 kJ (500-600 kcal) diet 2 non-consecutive days/week and their usual diet for 5 days/week. The continuous group (n = 67) followed a 5000-6300 kJ (1200-1500 kcal) diet for 7 days/week. Follow-up occurred at 24 months, 12 months after the completed intervention. The primary outcome was change in HbA1c and the secondary outcome was weight loss. RESULTS Intention-to-treat analysis showed an increase in mean [SEM] HbA1c level at 24 months in both the continuous and intermittent groups (0.4% [0.3%] vs 0.1% [0.2%] respectively; P = 0.32) (4.4 [3.3 mmol/mol] vs 1.1 [2.2 mmol/mol]; P = 0.32), with a between-group difference of 0.3% (90% CI, -0.31 to 0.83%) (3.3 mmol/mol [90% CI, -3.2 to 9.1 mmol/mol]) outside the prespecified boundary of ± 0.5% (5.5 mmol/mol), so statistical equivalence was not shown. Weight loss was maintained (P < 0.001) at -3.9 kg [1.1 kg] in both groups at 24 months, with a between-group difference of 0.07 kg (90% CI, -2.5 to 2.6 kg) outside the prespecified boundary of ±2.5 kg. There were no significant differences between groups in body composition, fasting glucose levels, lipid levels, or total medication effect score at 24 months, which remained less than baseline. CONCLUSIONS In this prospective analysis weight loss was maintained but despite this HbA1c increased to above baseline levels in both groups.
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Compensatory mechanisms activated with intermittent energy restriction: A randomized control trial.
Coutinho, SR, Halset, EH, Gåsbakk, S, Rehfeld, JF, Kulseng, B, Truby, H, Martins, C
Clinical nutrition (Edinburgh, Scotland). 2018;(3):815-823
Abstract
BACKGROUND & AIMS Strong compensatory responses, with reduced resting metabolic rate (RMR), increased exercise efficiency (ExEff) and appetite, are activated when weight loss (WL) is achieved with continuous energy restriction (CER), which try to restore energy balance. Intermittent energy restriction (IER), where short spells of energy restriction are interspaced by periods of habitual energy intake, may offer some protection in minimizing those responses. We aimed to compare the effect of IER versus CER on body composition and the compensatory responses induced by WL. METHODS 35 adults (age: 39 ± 9 y) with obesity (BMI: 36 ± 4 kg/m2) were randomized to lose a similar weight with an IER (N = 18) or a CER (N = 17) diet over a 12 week period. Macronutrient composition and overall energy restriction (33% reduction) were similar between groups. Body weight/composition, RMR, fasting respiratory quotient (RQ), ExEff (10, 25, and 50 W), subjective appetite ratings (hunger, fullness, desire to eat, and prospective food consumption (PFC)), and appetite-regulating hormones (active ghrelin (AG), cholecystokinin (CCK), total peptide YY (PYY), active glucagon-like peptide-1 (GLP-1), and insulin) were measured before and after WL. RESULTS Changes in body weight (≈12.5% WL) and composition were similar in both groups. Fasting RQ and ExEff at 10 W increased in both groups. Losing weight, either by IER or CER dieting, did not induce significant changes in subjective appetite ratings. RMR decreased and ExEff at 25 and 50 W increased (P < 0.001 for all) in IER group only. Basal and postprandial AG increased (P < 0.05) in IER group, whereas basal active GLP-1 decreased (P = 0.033) in CER group only. Postprandial CCK decreased in both groups (P = 0.0012 and P = 0.009 for IER and CER groups, respectively). No between group differences were apparent for any of the outcomes. CONCLUSIONS The technique used to achieve energy restriction, whether it is continuous or intermittent, does not appear to modulate the compensatory mechanisms activated by weight loss. CLINICAL TRIAL REGISTRATION NUMBER NCT02169778 (the study was registered in clinicaltrial.gov).
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Is two days of intermittent energy restriction per week a feasible weight loss approach in obese males? A randomised pilot study.
Conley, M, Le Fevre, L, Haywood, C, Proietto, J
Nutrition & dietetics: the journal of the Dietitians Association of Australia. 2018;(1):65-72
Abstract
AIM: The 5:2 diet (two non-consecutive days of 2460 KJ (600 calories) and 5 days of ad libitum eating per week) is becoming increasingly popular. This pilot study aimed to determine whether the 5:2 diet can achieve ≥5% weight loss and greater improvements in weight and biochemical markers than a standard energy-restricted diet (SERD) in obese male war veterans. METHODS A total of 24 participants were randomised to consume either the 5:2 diet or a SERD (2050 KJ (500 calorie) reduction per day) for 6 months. Weight, waist circumference (WC), fasting blood glucose, blood lipids, blood pressure and dietary intake were measured at baseline, 3 and 6 months by a blinded investigator. RESULTS After 6 months, participants in both groups significantly reduced body weight (P = <0.001), WC (P = <0.001) and systolic blood pressure (P = 0.001). Mean weight loss was 5.3 ± 3.0 kg (5.5 ± 3.2%) for the 5:2 group and 5.5 ± 4.3 kg (5.4 ± 4.2%) for the SERD group. Mean WC reduction for the 5:2 group was 8.0 ± 4.5 and 6.4 ± 5.8 cm for the SERD group. There was no significant difference in the amount of weight loss or WC reduction between diet groups. There was no significant change in diastolic blood pressure, fasting blood glucose or blood lipids in either dietary group. CONCLUSIONS Results suggest that the 5:2 diet is a successful but not superior weight loss approach in male war veterans when compared to a SERD. Future research is needed to determine the long-term effectiveness of the 5:2 diet and its effectiveness in other population groups.
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Effect of Intermittent Compared With Continuous Energy Restricted Diet on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Noninferiority Trial.
Carter, S, Clifton, PM, Keogh, JB
JAMA network open. 2018;(3):e180756
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IMPORTANCE Intermittent energy restriction is an alternative weight loss method that is becoming popular; however, to date, there are no long-term clinical trials of intermittent energy restriction in patients with type 2 diabetes. OBJECTIVE To compare the effects of intermittent energy restriction (2 days per week) with those of continuous energy restriction on glycemic control and weight loss in patients with type 2 diabetes during a 12-month period. DESIGN, SETTING, AND PARTICIPANTS Adult participants (N = 137) with type 2 diabetes were randomized 1:1 to parallel diet groups (intermittent energy restriction [n = 70] or continuous energy restriction [n = 67]) between April 7, 2015, and September 7, 2017, at the University of South Australia. Medications likely to cause hypoglycemia were reduced at baseline according to the medication management protocol. INTERVENTIONS An intermittent energy restriction diet (500-600 kcal/d) followed for 2 nonconsecutive days per week (participants followed their usual diet for the other 5 days) or a continuous energy restriction diet (1200-1500 kcal/d) followed for 7 days per week for 12 months. MAIN OUTCOMES AND MEASURES The primary outcome was change in hemoglobin A1c (HbA1c) level, with equivalence prespecified by a 90% CI margin of ±0.5%. The secondary outcome was weight loss with equivalence set at ±2.5 kg (±1.75 kg for fat mass loss and ±0.75 kg for fat-free mass loss). All other outcomes were tested for superiority. RESULTS Of the 137 randomized participants (77 women and 60 men; mean [SD] age, 61.0 [9.1] years; mean [SD] body mass index, 36.0 [5.8] [calculated as weight in kilograms divided by height in meters squared]; and mean [SD] HbA1c level, 7.3% [1.3%]), 97 completed the trial. Intention-to-treat analysis showed similar reductions in mean (SEM) HbA1c level between the continuous and intermittent energy restriction groups (-0.5% [0.2%] vs -0.3% [0.1%]; P = .65), with a between-group difference of 0.2% (90% CI, -0.2% to 0.5%) meeting the criteria for equivalence. Mean (SEM) weight change was similar between the continuous and intermittent energy restriction groups (-5.0 [0.8] kg vs -6.8 [0.8] kg; P = .25), but the between-group difference did not meet the criteria for equivalence (-1.8 kg; 90% CI, -3.7 to 0.07 kg), nor did the between-group difference in fat mass (-1.3 kg; 90% CI, -2.8 to 0.2 kg) or fat-free mass (-0.5 kg; 90% CI, -1.4 to 0.4 kg). There were no significant differences between groups in final step count, fasting glucose levels, lipid levels, or total medication effect score at 12 months. Effects did not differ using completers analysis. Hypoglycemic or hyperglycemic events in the first 2 weeks of treatment were similar between the continuous and intermittent energy restriction groups (mean number [SEM] of events, 3.2 [0.7] vs 4.9 [1.4]; P = .28), affecting 35% of participants (16 of 46) using sulfonylureas and/or insulin. CONCLUSIONS AND RELEVANCE Intermittent energy restriction is an effective alternative diet strategy for the reduction of HbA1c and is comparable with continuous energy restriction in patients with type 2 diabetes. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12615000383561.
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Investigation into the acute effects of total and partial energy restriction on postprandial metabolism among overweight/obese participants.
Antoni, R, Johnston, KL, Collins, AL, Robertson, MD
The British journal of nutrition. 2016;(6):951-9
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The intermittent energy restriction (IER) approach to weight loss involves short periods of substantial (75-100 %) energy restriction (ER) interspersed with normal eating. This study aimed to characterise the early metabolic response to these varying degrees of ER, which occurs acutely and prior to weight loss. Ten (three female) healthy, overweight/obese participants (36 (SEM 5) years; 29·0 (sem 1·1) kg/m2) took part in this acute three-way cross-over study. Participants completed three 1-d dietary interventions in a randomised order with a 1-week washout period: isoenergetic intake, partial 75 % ER and total 100 % ER. Fasting and postprandial (6-h) metabolic responses to a liquid test meal were assessed the following morning via serial blood sampling and indirect calorimetry. Food intake was also recorded for two subsequent days of ad libitum intake. Relative to the isoenergetic control, postprandial glucose responses were increased following total ER (+142 %; P=0·015) and to a lesser extent after partial ER (+76 %; P=0·051). There was also a delay in the glucose time to peak after total ER only (P=0·024). Both total and partial ER interventions produced comparable reductions in postprandial TAG responses (-75 and -59 %, respectively; both P<0·05) and 3-d energy intake deficits of approximately 30 % (both P=0·015). Resting and meal-induced thermogenesis were not significantly affected by either ER intervention. In conclusion, our data demonstrate the ability of substantial ER to acutely alter postprandial glucose-lipid metabolism (with partial ER producing the more favourable overall response), as well as incomplete energy-intake compensation amongst overweight/obese participants. Further investigations are required to establish how metabolism adapts over time to the repeated perturbations experienced during IER, as well as the implications for long-term health.
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Efficacy of fasting and calorie restriction (FCR) on mood and depression among ageing men.
Hussin, NM, Shahar, S, Teng, NI, Ngah, WZ, Das, SK
The journal of nutrition, health & aging. 2013;(8):674-80
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OBJECTIVE An intervention study on the FCR (Fasting and Calorie Restriction) dietary regime was carried out to determine its efficacy in improving mood states and depression status among ageing men. SUBJECTS A total of 32 healthy males (Mean±SD), aged 59.7±6.3 years, with a BMI of 26.7±2.2 kg/m2 were recruited to the study. METHOD Participants were randomized to either the FCR group (and were instructed to follow a calorie restricted dietary regime with intermittent fasting) or to the control group (in which individuals were asked to maintain their current lifestyle), for a 3 month period. Mood was assessed using the Profile of Mood States and depression was assessed using Beck Depression Inventory-II and Geriatric Depression Scale-15 at baseline, week 6 and week 12 of the intervention. RESULTS A total of 31 subjects completed the study (n=16, FCR and n=15, control). Significant decreases in tension, anger, confusion and total mood disturbance and improvements in vigor were observed in participants in the FCR group compared to the control group (p<0.05). No significant changes in mean depression scores were observed. Weight, BMI and percent body fat were reduced by 3.8%, 3.7% and 5.7% respectively in the FCR group. CONCLUSIONS Our findings show that a FCR dietary regime is effective in improving mood states and nutritional status among ageing men.