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1.
Mild intermittent hypoxia exposure induces metabolic and molecular adaptations in men with obesity.
van Meijel, RLJ, Vogel, MAA, Jocken, JWE, Vliex, LMM, Smeets, JSJ, Hoebers, N, Hoeks, J, Essers, Y, Schoffelen, PFM, Sell, H, et al
Molecular metabolism. 2021;:101287
Abstract
OBJECTIVE Recent studies suggest that hypoxia exposure may improve glucose homeostasis, but well-controlled human studies are lacking. We hypothesized that mild intermittent hypoxia (MIH) exposure decreases tissue oxygen partial pressure (pO2) and induces metabolic improvements in people who are overweight/obese. METHODS In a randomized, controlled, single-blind crossover study, 12 men who were overweight/obese were exposed to MIH (15 % O2, 3 × 2 h/day) or normoxia (21 % O2) for 7 consecutive days. Adipose tissue (AT) and skeletal muscle (SM) pO2, fasting/postprandial substrate metabolism, tissue-specific insulin sensitivity, SM oxidative capacity, and AT and SM gene/protein expression were determined. Furthermore, primary human myotubes and adipocytes were exposed to oxygen levels mimicking the hypoxic and normoxic AT and SM microenvironments. RESULTS MIH decreased systemic oxygen saturation (92.0 ± 0.5 % vs 97.1 ± 0.3, p < 0.001, respectively), AT pO2 (21.0 ± 2.3 vs 36.5 ± 1.5 mmHg, p < 0.001, respectively), and SM pO2 (9.5 ± 2.2 vs 15.4 ± 2.4 mmHg, p = 0.002, respectively) compared to normoxia. In addition, MIH increased glycolytic metabolism compared to normoxia, reflected by enhanced fasting and postprandial carbohydrate oxidation (pAUC = 0.002) and elevated plasma lactate concentrations (pAUC = 0.005). Mechanistically, hypoxia exposure increased insulin-independent glucose uptake compared to standard laboratory conditions (~50 %, p < 0.001) and physiological normoxia (~25 %, p = 0.019) through AMP-activated protein kinase in primary human myotubes but not in primary human adipocytes. MIH upregulated inflammatory/metabolic pathways and downregulated extracellular matrix-related pathways in AT but did not alter systemic inflammatory markers and SM oxidative capacity. MIH exposure did not induce significant alterations in AT (p = 0.120), hepatic (p = 0.132) and SM (p = 0.722) insulin sensitivity. CONCLUSIONS Our findings demonstrate for the first time that 7-day MIH reduces AT and SM pO2, evokes a shift toward glycolytic metabolism, and induces adaptations in AT and SM but does not induce alterations in tissue-specific insulin sensitivity in men who are overweight/obese. Future studies are needed to investigate further whether oxygen signaling is a promising target to mitigate metabolic complications in obesity. CLINICAL TRIAL REGISTRATION This study is registered at the Netherlands Trial Register (NL7120/NTR7325).
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2.
Eight weeks of intermittent fasting versus calorie restriction does not alter eating behaviors, mood, sleep quality, quality of life and cognitive performance in women with overweight.
Teong, XT, Hutchison, AT, Liu, B, Wittert, GA, Lange, K, Banks, S, Heilbronn, LK
Nutrition research (New York, N.Y.). 2021;:32-39
Abstract
Human trials that compare intermittent fasting (IF) to calorie restriction (CR) with psychological, behavioral and cognition outcomes are limited. We hypothesized that there would be no difference between CR and IF on perceived eating behaviors, mood, sleep quality, quality of life (QOL) and cognition in women with overweight and obesity. In this prespecified secondary analysis of an open-label, single center, parallel assignment, randomized controlled trial, healthy women with overweight or obesity (N = 46, mean [SD] age 50 [9] years, BMI 32.9 [4.4] kg/m2), without a diagnosed eating disorder and who were randomized into 2 weight loss groups (prescribed 70% of calculated energy requirements as IF or CR) were included. Measurements were assessed in both IF and CR groups following a 12-hour overnight fast during baseline and week 8 and additionally following a 24-hour fast in the IF group only at week 8. We observed that IF produced greater weight and body fat loss than CR (P < .001). We did not detect any statistical difference between groups for the change in dietary restraint, disinhibition, hunger, mood, sleep quality, and QOL. An increase in cognitive performance was found in both IF (P = .036) and CR (P = .006) groups in one of the cognitive tasks, but there was no statistical difference between groups. Perceived eating behaviors, mood, sleep quality and cognitive performance were not changed by an acute 24-hour fast within the IF group (all P > .05). IF may be a viable alternative to CR for weight loss, in the short-term, without adversely impacting eating behaviors, mood, sleep quality, QOL or cognition in healthy women with overweight or obesity. However, larger and long term trials are required.
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3.
Intermittent Fasting and the Possible Benefits in Obesity, Diabetes, and Multiple Sclerosis: A Systematic Review of Randomized Clinical Trials.
Morales-Suarez-Varela, M, Collado Sánchez, E, Peraita-Costa, I, Llopis-Morales, A, Soriano, JM
Nutrients. 2021;(9)
Abstract
Intermittent fasting has become popular in recent years and is controversially presented as a possible therapeutic adjunct. A bibliographic review of the literature on intermittent fasting and obesity, diabetes, and multiple sclerosis was carried out. The scientific quality of the methodology and the results obtained were evaluated in pairs. Intermittent fasting has beneficial effects on the lipid profile, and it is associated with weight loss and a modification of the distribution of abdominal fat in people with obesity and type 2 diabetes as well as an improvement in the control of glycemic levels. In patients with multiple sclerosis, the data available are too scarce to draw any firm conclusions, but it does appear that intermittent fasting may be a safe and feasible intervention. However, it is necessary to continue investigating its long-term effects since so far, the studies carried out are small and of short duration.
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4.
Intermittent fasting and weight loss: Systematic review.
Welton, S, Minty, R, O'Driscoll, T, Willms, H, Poirier, D, Madden, S, Kelly, L
Canadian family physician Medecin de famille canadien. 2020;(2):117-125
Abstract
OBJECTIVE To examine the evidence for intermittent fasting (IF), an alternative to calorie-restricted diets, in treating obesity, an important health concern in Canada with few effective office-based treatment strategies. DATA SOURCES A MEDLINE and EMBASE search from January 1, 2000, to July 1, 2019, yielded 1200 results using the key words fasting, time restricted feeding, meal skipping, alternate day fasting, intermittent fasting, and reduced meal frequency. STUDY SELECTION Forty-one articles describing 27 trials addressed weight loss in overweight and obese patients: 18 small randomized controlled trials (level I evidence) and 9 trials comparing weight after IF to baseline weight with no control group (level II evidence). Studies were often of short duration (2 to 26 weeks) with low enrolment (10 to 244 participants); 2 were of 1-year duration. Protocols varied, with only 5 studies including patients with type 2 diabetes. SYNTHESIS All 27 IF trials found weight loss of 0.8% to 13.0% of baseline weight with no serious adverse events. Twelve studies comparing IF to calorie restriction found equivalent results. The 5 studies that included patients with type 2 diabetes documented improved glycemic control. CONCLUSION Intermittent fasting shows promise for the treatment of obesity. To date, the studies have been small and of short duration. Longer-term research is needed to understand the sustainable role IF can play in weight loss.
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5.
Combined effects of continuous exercise and intermittent active interruptions to prolonged sitting on postprandial glucose, insulin, and triglycerides in adults with obesity: a randomized crossover trial.
Wheeler, MJ, Green, DJ, Cerin, E, Ellis, KA, Heinonen, I, Lewis, J, Naylor, LH, Cohen, N, Larsen, R, Dempsey, PC, et al
The international journal of behavioral nutrition and physical activity. 2020;(1):152
Abstract
BACKGROUND Postprandial glucose, insulin, and triglyceride metabolism is impaired by prolonged sitting, but enhanced by exercise. The aim of this study was to assess the effects of a continuous exercise bout with and without intermittent active interruptions to prolonged sitting on postprandial glucose, insulin, and triglycerides. METHODS Sedentary adults who were overweight to obese (n = 67; mean age 67 yr SD ± 7; BMI 31.2 kg∙m- 2 SD ± 4.1), completed three conditions: SIT: uninterrupted sitting (8-h, control); EX+SIT: sitting (1-h), moderate-intensity walking (30-min), uninterrupted sitting (6.5-h); EX+BR: sitting (1-h), moderate-intensity walking (30- min), sitting interrupted every 30-min with 3-min of light-intensity walking (6.5 h). Participants consumed standardized breakfast and lunch meals and blood was sampled at 13 time-points. RESULTS When compared to SIT, EX+SIT increased total area under the curve (tAUC) for glucose by 2% [0.1-4.1%] and EX+BR by 3% [0.6-4.7%] (all p < 0.05). Compared to SIT, EX+SIT reduced insulin and insulin:glucose ratio tAUC by 18% [11-22%] and 21% [8-33%], respectively; and EX+BR reduced values by 25% [19-31%] and 28% [15-38%], respectively (all p < 0.001 vs SIT, all p < 0.05 EX+SIT-vs-EX+BR). Compared to SIT, EX+BR reduced triglyceride tAUC by 6% [1-10%] (p = 0.01 vs SIT), and compared to EX+SIT, EX+BR reduced this value by 5% [0.1-8.8%] (p = 0.047 vs EX+SIT). The magnitude of reduction in insulin tAUC from SIT-to-EX+BR was greater in those with increased basal insulin resistance. No reduction in triglyceride tAUC from SIT-to-EX+BR was apparent in those with high fasting triglycerides. CONCLUSIONS Additional reductions in postprandial insulin-glucose dynamics and triglycerides may be achieved by combining exercise with breaks in sitting. Relative to uninterrupted sitting, this strategy may reduce postprandial insulin more in those with high basal insulin resistance, but those with high fasting triglycerides may be resistant to such intervention-induced reductions in triglycerides. TRIAL REGISTRATION Australia New Zealand Clinical Trials Registry ( ACTRN12614000737639 ).
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6.
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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7.
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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8.
Rationale for novel intermittent dieting strategies to attenuate adaptive responses to energy restriction.
Sainsbury, A, Wood, RE, Seimon, RV, Hills, AP, King, NA, Gibson, AA, Byrne, NM
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2018;:47-60
Abstract
Eating patterns involving intermittent energy restriction (IER) include 'intermittent fasting' where energy intake is severely restricted for several 'fasting' days per week, with 'refeeding' days (involving greater energy intake than during fasting days) at other times. Intermittent fasting does not improve weight loss compared to continuous energy restriction (CER), where energy intake is restricted every day. We hypothesize that weight loss from IER could be improved if refeeding phases involved restoration of energy balance (i.e. not ongoing energy restriction, as during intermittent fasting). There is some evidence in adults with overweight or obesity showing that maintenance of a lower weight may attenuate (completely or partially) some of the adaptive responses to energy restriction that oppose ongoing weight loss. Other studies show some adaptive responses persist unabated for years after weight loss. Only five randomized controlled trials in adults with overweight or obesity have compared CER with IER interventions that achieved energy balance (or absence of energy restriction) during refeeding phases. Two reported greater weight loss than CER, whereas three reported similar weight loss between interventions. While inconclusive, it is possible that achieving energy balance (i.e. avoiding energy restriction or energy excess) during refeeding phases may be important in realizing the potential of IER.
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9.
Intermittent fasting interventions for treatment of overweight and obesity in adults: a systematic review and meta-analysis.
Harris, L, Hamilton, S, Azevedo, LB, Olajide, J, De Brún, C, Waller, G, Whittaker, V, Sharp, T, Lean, M, Hankey, C, et al
JBI database of systematic reviews and implementation reports. 2018;(2):507-547
Abstract
OBJECTIVE To examine the effectiveness of intermittent energy restriction in the treatment for overweight and obesity in adults, when compared to usual care treatment or no treatment. INTRODUCTION Intermittent energy restriction encompasses dietary approaches including intermittent fasting, alternate day fasting, and fasting for two days per week. Despite the recent popularity of intermittent energy restriction and associated weight loss claims, the supporting evidence base is limited. INCLUSION CRITERIA This review included overweight or obese (BMI ≥25 kg/m) adults (≥18 years). Intermittent energy restriction was defined as consumption of ≤800 kcal on at least one day, but no more than six days per week. Intermittent energy restriction interventions were compared to no treatment (ad libitum diet) or usual care (continuous energy restriction ∼25% of recommended energy intake). Included interventions had a minimum duration of 12 weeks from baseline to post outcome measurements. The types of studies included were randomized and pseudo-randomized controlled trials. The primary outcome of this review was change in body weight. Secondary outcomes included: i) anthropometric outcomes (change in BMI, waist circumference, fat mass, fat free mass); ii) cardio-metabolic outcomes (change in blood glucose and insulin, lipoprotein profiles and blood pressure); and iii) lifestyle outcomes: diet, physical activity, quality of life and adverse events. METHODS A systematic search was conducted from database inception to November 2015. The following electronic databases were searched: MEDLINE, Embase, CINAHL, Cochrane Library, ClinicalTrials.gov, ISRCTN registry, and anzctr.org.au for English language published studies, protocols and trials. Two independent reviewers evaluated the methodological quality of included studies using the standardized critical appraisal instruments from the Joanna Briggs Institute. Data were extracted from papers included in the review by two independent reviewers using the standardized data extraction tool from the Joanna Briggs Institute. Effect sizes were expressed as weighted mean differences and their 95% confidence intervals were calculated for meta-analyses. RESULTS Six studies were included in this review. The intermittent energy restriction regimens varied across studies and included alternate day fasting, fasting for two days, and up to four days per week. The duration of studies ranged from three to 12 months. Four studies included continuous energy restriction as a comparator intervention and two studies included a no treatment control intervention. Meta-analyses showed that intermittent energy restriction was more effective than no treatment for weight loss (-4.14 kg; 95% CI -6.30 kg to -1.99 kg; p ≤ 0.001). Although both treatment interventions achieved similar changes in body weight (approximately 7 kg), the pooled estimate for studies that investigated the effect of intermittent energy restriction in comparison to continuous energy restriction revealed no significant difference in weight loss (-1.03 kg; 95% CI -2.46 kg to 0.40 kg; p = 0.156). CONCLUSIONS Intermittent energy restriction may be an effective strategy for the treatment of overweight and obesity. Intermittent energy restriction was comparable to continuous energy restriction for short term weight loss in overweight and obese adults. Intermittent energy restriction was shown to be more effective than no treatment, however, this should be interpreted cautiously due to the small number of studies and future research is warranted to confirm the findings of this review.
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10.
Is There an Optimal Diet for Weight Management and Metabolic Health?
Thom, G, Lean, M
Gastroenterology. 2017;(7):1739-1751
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Abstract
Individuals can lose body weight and improve health status on a wide range of energy (calorie)-restricted dietary interventions. In this paper, we have reviewed the effectiveness of the most commonly utilized diets, including low-fat, low-carbohydrate, and Mediterranean approaches, in addition to commercial slimming programs, meal replacements, and newly popularized intermittent fasting diets. We also consider the role of artificial sweeteners in weight management. Low-fat diets tend to improve low-density lipoprotein cholesterol the most, while lower-carbohydrate diets may preferentially improve triglycerides and high-density lipoprotein cholesterol. However, differences between diets are marginal. Weight loss improves almost all obesity-related co-morbidities and metabolic markers, regardless of the macronutrient composition of the diet, but individuals do vary in preferences and ability to adhere to different diets. Optimizing adherence is the most important factor for weight loss success, and this is enhanced by regular professional contact and supportive behavioral change programs. Maintaining weight losses in the long term remains the biggest challenge, and is undermined by an "obesogenic" environment and biological adaptations that accompany weight loss.