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Intermittent Fasting and Metabolic Health: From Religious Fast to Time-Restricted Feeding.
Hoddy, KK, Marlatt, KL, Çetinkaya, H, Ravussin, E
Obesity (Silver Spring, Md.). 2020;(Suppl 1):S29-S37
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Abstract
Over the past 10 to 15 years, intermittent fasting has emerged as an unconventional approach to reduce body weight and improve metabolic health beyond simple calorie restriction. In this review, we summarize findings related to Ramadan and Sunnah fasting. We then discuss the role of caloric restriction not only as an intervention for weight control, but importantly, as a strategy for healthy aging and longevity. Finally, we review the four most common intermittent fasting (IF) strategies used to date for weight management and to improve cardiometabolic health. Weight loss is common after IF but does not appear to be different than daily caloric restriction when compared directly. IF may also provide additional cardiometabolic benefit, such as insulin sensitization, that is independent from weight loss. While no specific fasting regimen stands out as superior at this time, there is indeed heterogeneity in responses to these different IF diets. This suggests that one dietary regimen may not be ideally suited for every individual. Future studies should consider strategies for tailoring dietary prescriptions, including IF, based on advanced phenotyping and genotyping prior to diet initiation.
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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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Energy Restriction and Colorectal Cancer: A Call for Additional Research.
Castejón, M, Plaza, A, Martinez-Romero, J, Fernandez-Marcos, PJ, Cabo, R, Diaz-Ruiz, A
Nutrients. 2020;(1)
Abstract
: Colorectal cancer has the second highest cancer-related mortality rate, with an estimated 881,000 deaths worldwide in 2018. The urgent need to reduce the incidence and mortality rate requires innovative strategies to improve prevention, early diagnosis, prognostic biomarkers, and treatment effectiveness. Caloric restriction (CR) is known as the most robust nutritional intervention that extends lifespan and delays the progression of age-related diseases, with remarkable results for cancer protection. Other forms of energy restriction, such as periodic fasting, intermittent fasting, or fasting-mimicking diets, with or without reduction of total calorie intake, recapitulate the effects of chronic CR and confer a wide range of beneficial effects towards health and survival, including anti-cancer properties. In this review, the known molecular, cellular, and organismal effects of energy restriction in oncology will be discussed. Energy-restriction-based strategies implemented in colorectal models and clinical trials will be also revised. While energy restriction constitutes a promising intervention for the prevention and treatment of several malignant neoplasms, further investigations are essential to dissect the interplay between fundamental aspects of energy intake, such as feeding patterns, fasting length, or diet composition, with all of them influencing health and disease or cancer effects. Currently, effectiveness, safety, and practicability of different forms of fasting to fight cancer, particularly colorectal cancer, should still be contemplated with caution.
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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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Intermittent fasting as a nutrition approach against obesity and metabolic disease.
Zhu, S, Surampudi, P, Rosharavan, B, Chondronikola, M
Current opinion in clinical nutrition and metabolic care. 2020;(6):387-394
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Abstract
PURPOSE OF REVIEW Intermittent fasting has been proposed as a potential nutrition approach against obesity and metabolic disease. Although data from studies in rodents convincingly support the antiobesity and cardiometabolic benefits of intermittent fasting, its effects in human health are still debatable. RECENT FINDINGS Recent studies have examined the effect of two intermittent fasting approaches, that is, alternate day fasting (ADF) and time-restricted eating (TRE), on weight loss and cardiometabolic risk factors. ADF seems to be an equally effective weight loss approach to caloric restriction, but adherence to ADF is more challenging. ADF improves cardiometabolic risk factors, whereas it may have superior metabolic benefits compared to caloric restriction in people with insulin resistance. TRE with ad libitum food intake is well tolerated and induces 2-4% weight loss in approximatively 3 months. Additionally, TRE may have metabolic benefits particularly in people with metabolically abnormal obesity even without weight loss. SUMMARY Intermittent fasting is a promising nutritional approach against obesity and its related metabolic diseases. Further research is needed to: i) establish the long-term effectiveness of TRE in weight loss and metabolic health, ii) improve the long-term adherence to ADF and investigate its weight loss independent effects in metabolic health, and iii) determine the mechanisms underlying the potential cardiometabolic benefits of intermittent fasting in humans.
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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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Rationale and protocol for a randomized controlled trial comparing daily calorie restriction versus intermittent fasting to improve glycaemia in individuals at increased risk of developing type 2 diabetes.
Teong, XT, Liu, K, Hutchison, AT, Liu, B, Feinle-Bisset, C, Wittert, GA, Lange, K, Vincent, AD, Heilbronn, LK
Obesity research & clinical practice. 2020;(2):176-183
Abstract
BACKGROUND Intermittent fasting (IF) is proposed as a viable alternative to moderate calorie restriction (CR) for weight loss and metabolic health, but few long term randomized trials have been conducted. This protocol paper describes the rationale and detailed protocol for DIRECT study (Daily versus Intermittent Restriction of Energy: Controlled Trial to Reduce Diabetes Risk), comparing long term effectiveness of IF versus CR on metabolic health in individuals who are at increased risk of developing type 2 diabetes. METHODS Anticipated 260 non-diabetic men and women aged 35-75 years, BMI 25-50 kg/m2 with score ≥12 on the Australian Diabetes Risk (AUSDRISK) calculator will be recruited into this open-label, multi-arm, parallel group sequential randomized controlled trial. Participants will be randomized to one of three groups for 18 months: IF (30% of energy needs on fast days), CR (70% of energy needs daily), or standard care (SC) group. All participants will visit the clinic fortnightly for weight assessments during active intervention phase (6 months), followed by a 12-month follow-up phase. IF and CR groups will receive further diet counselling by dietitian. Two primary outcomes are the changes in glycated haemoglobin (HbA1c) and postprandial glucose area under the curve (AUC) at week 24 post-randomization. Secondary outcomes include changes in weight, body composition via dual-energy X-ray absorptiometry, gastro-intestinal hormones, cardiovascular risk factors, and dietary record by a smartphone-based application. DISCUSSION This study will provide substantial evidence as to whether IF is an effective nutrition intervention for glycaemic control in a population at risk of developing type 2 diabetes.
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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).