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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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Very Low Calorie Diets for Weight Loss in Obese Older Adults-A Randomized Trial.
Haywood, CJ, Prendergast, LA, Purcell, K, Le Fevre, L, Lim, WK, Galea, M, Proietto, J
The journals of gerontology. Series A, Biological sciences and medical sciences. 2017;(1):59-65
Abstract
BACKGROUND Obesity contributes to disability in older adults, and this is offset by weight loss and exercise. Very Low Calorie Diets (VLCDs) achieve rapid weight loss; however, these have not been rigorously evaluated in older people. METHODS A randomized trial was conducted from August 2012 through December 2015. The intervention was 12 weeks of thrice weekly exercise combined with either healthy eating advice (Ex/HE), hypocaloric diet (Ex/Diet), or VLCD (Ex/VLCD). Outcomes were physical function, measured by 6-minute walk test (6MWT) and De Morton Mobility Index (DEMMI). Other measures were body composition measured by Dual Energy X-Ray Absorptiometry, and nutritional parameters (albumin, vitamins B12 and D, ferritin and folate). RESULTS 36, 40, and 41 participants were randomized to Ex/HE, Ex/Diet, and Ex/VLCD, respectively. At 12 weeks, weight was reduced by 3.7, 5.1, and 11.1% (p < .01), respectively. Ex/VLCD had significant reduction in fat (16.8%), lean mass (4.8%), and bone mineral density (1.2%), but increased relative lean mass (3.8%). DEMMI improved by 14.25, 14.25, and 13.75 points in Ex/HE, Ex/Diet, and Ex/VLCD, respectively; however, there was no between-group difference (p = .30). 6MWT improved by 53.1, 64.7, and 84.4 meters in Ex/HE, Ex/Diet, and Ex/VLCD (p = .18). Post hoc stratification for gender and adjustment for initial physical function and type 2 diabetes only revealed significant between-group differences for men in the 6MWT, with improvement by 57.8, 77.8, and 140.3 meters in Ex/HE, Ex/Diet, and Ex/VLCD, respectively (p = .01). Improvements in nutritional parameters were seen in Ex/VLCD, but not in Ex/HE and Ex/Diet. The VLCD was well tolerated. CONCLUSIONS VLCDs have potential in the treatment of obesity in older persons; of particular benefit is improvement in nutritional status. The gait speed improvement observed in men warrants further investigation.
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Change in the Rate of Biological Aging in Response to Caloric Restriction: CALERIE Biobank Analysis.
Belsky, DW, Huffman, KM, Pieper, CF, Shalev, I, Kraus, WE
The journals of gerontology. Series A, Biological sciences and medical sciences. 2017;(1):4-10
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Biological aging measures have been proposed as proxies for extension of healthy life span in trials of geroprotective therapies that aim to slow aging. Several methods to measure biological aging show promise but it is not known if these methods are sensitive to changes caused by geroprotective therapy. We conducted analysis of two proposed methods to quantify biological aging using data from a recently concluded trial of an established geroprotector, caloric restriction. We obtained data from the National Institute on Aging CALERIE randomized trial through its public-access biobank (https://calerie.duke.edu/). The CALERIE trial randomized N = 220 nonobese adults to 25% caloric restriction (n = 145; 11.7% caloric restriction was achieved, on average) or to maintain current diet (n = 75) for 2 years. We analyzed biomarker data collected at baseline, 12-, and 24-month follow-up assessments. We applied published biomarker algorithms to these data to calculate two biological age measures, Klemera-Doubal Method Biological Age and homeostatic dysregulation. Intent-to-treat analysis using mixed-effects growth models of within-person change over time tested if caloric restriction slowed increase in measures of biological aging across follow-up. Analyses of both measures indicated caloric restriction slowed biological aging. Weight loss did not account for the observed effects. Results suggest future directions for testing of geroprotective therapies in humans.
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The effects of intermittent compared to continuous energy restriction on glycaemic control in type 2 diabetes; a pragmatic pilot trial.
Carter, S, Clifton, PM, Keogh, JB
Diabetes research and clinical practice. 2016;:106-112
Abstract
AIMS: Weight loss improves glycaemic control in type 2 diabetes mellitus (T2DM). However, as achieving and maintaining weight loss is difficult, alternative strategies are needed. Our primary aim was to investigate the effects of intermittent energy restriction (IER) compared to continuous energy restriction (CER) on glycated haemoglobin A1c (HbA1c). Secondary aims were to assess effects on weight loss, body composition, medication changes and subjective measures of appetite. Using a 2-day IER method, we expected equal improvements to HbA1c and weight in both groups. METHOD Sixty-three overweight or obese participants (BMI 35.2±5kg/m2) with T2DM (HbA1c 7.4±1.3%) (57mmol/mol) were randomised to a 2-day severe energy restriction (1670-2500kJ/day) with 5days of habitual eating, compared to a moderate CER diet (5000-6500kJ/day) for 12weeks. RESULTS At 12weeks HbA1c (-0.7±0.9% P<0.001) and percent body weight reduction (-5.9±4% P<0.001) was similar in both groups with no group by time interaction. Similar reductions were also seen for medication dosages, all measures of body composition and subjective reports of appetite. CONCLUSIONS In this pilot trial, 2days of IER compared with CER resulted in similar improvements in glycaemic control and weight reduction offering a suitable alternative treatment strategy.
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Can an intensive diet and exercise program prevent knee pain among overweight adults at high risk?
White, DK, Neogi, T, Rejeski, WJ, Walkup, MP, Lewis, CE, Nevitt, MC, Foy, CG, Felson, DT, ,
Arthritis care & research. 2015;(7):965-71
Abstract
OBJECTIVE It is unclear whether an intensive program of weight loss combined with exercise prevents the onset of knee pain among those at high risk. We examined whether an intensive lifestyle intervention (ILI) prevents incident knee pain compared with a diabetes mellitus support and education (DSE) comparison group among overweight adults with diabetes mellitus. METHODS We conducted a secondary analysis of the Action for Health in Diabetes (Look AHEAD) study, which is a randomized intervention trial of adults who were obese and had type 2 diabetes mellitus starting in 2001. We studied a subcohort of 2,889 subjects who reported no knee pain at baseline but were at high risk due to obesity. Risk ratios (RRs) were calculated to examine the association of ILI versus DSE with incident knee pain at year 1 and year 4. All analyses were adjusted for potential confounders. RESULTS Age, sex, and body mass index were similar among ILI and DSE participants with no knee pain at baseline. At year 1, ILI participants were 15% less likely to develop knee pain compared with DSE participants (RR 0.85, 95% confidence interval 0.74-0.98). At year 4, this difference decreased to 5% and was no longer statistically significant. CONCLUSION An ILI of diet and exercise may prevent the development of knee pain among those at high risk in the short term. Health care providers may consider recommending diet and exercise as a means to prevent the development of knee pain among those at high risk.
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Calorie Restriction and Matched Weight Loss From Exercise: Independent and Additive Effects on Glucoregulation and the Incretin System in Overweight Women and Men.
Weiss, EP, Albert, SG, Reeds, DN, Kress, KS, Ezekiel, UR, McDaniel, JL, Patterson, BW, Klein, S, Villareal, DT
Diabetes care. 2015;(7):1253-62
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OBJECTIVE It is not known whether calorie restriction (CR) has additive benefits to those from exercise (EX)-induced weight loss. We hypothesized that weight loss from CR and EX (CREX) improves insulin sensitivity more than matched weight loss induced by EX or CR alone and that the incretin system may be involved in adaptations to CR. RESEARCH DESIGN AND METHODS Sedentary, overweight men and women (n = 52, 45-65 years of age) were randomized to undergo 6-8% weight loss by using CR, EX, or CREX. Glucose, insulin, C-peptide, insulin sensitivity, and incretin hormones (glucagon-like peptide 1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) were measured during frequently sampled oral glucose tolerance tests (FSOGTTs). Incretin effects on insulin secretion were measured by comparing insulin secretion rates from the FSOGTTs to those from a glycemia-matched glucose infusion. RESULTS Despite similar weight losses in all groups, insulin sensitivity index values increased twofold more in the CREX group (2.09 ± 0.35 μM/kg/pM × 100) than in the CR (0.89 ± 0.39 μM/kg/pM × 100) and EX (1.04 ± 0.39 μM/kg/pM × 100) groups. Postprandial GLP-1 concentrations decreased only in the CR group (P = 0.04); GIP concentrations decreased in all groups. Incretin effects on insulin secretion were unchanged. CONCLUSIONS CR and EX have additive beneficial effects on glucoregulation. Furthermore, the adaptations to CR may involve reductions in postprandial GLP-1 concentrations. These findings underscore the importance of promoting both CR and EX for optimal health. However, because data from participants who withdrew from the study and from those who did not adhere to the intervention were excluded, the results may be limited to individuals who are capable of adhering to a healthy lifestyle intervention.
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Diet and physical exercise in psoriasis: a randomized controlled trial.
Naldi, L, Conti, A, Cazzaniga, S, Patrizi, A, Pazzaglia, M, Lanzoni, A, Veneziano, L, Pellacani, G, ,
The British journal of dermatology. 2014;(3):634-42
Abstract
BACKGROUND Increased body mass index and weight gain are risk factors for psoriasis, and the prevalence of obesity in patients with psoriasis is higher than in the general population. Limited data exist regarding the role of diet in psoriasis. OBJECTIVES To assess the impact of a dietary intervention combined with physical exercise for weight loss on improving psoriasis in overweight or obese patients. METHODS This study included 303 overweight or obese patients with moderate-to-severe chronic plaque psoriasis who did not achieve clearance after 4 weeks of continuous systemic treatment. They were randomized to receive either a 20-week quantitative and qualitative dietary plan associated with physical exercise for weight loss or simple informative counselling at baseline about the utility of weight loss for clinical control of psoriatic disease. The main outcome was any reduction of the Psoriasis Area and Severity Index (PASI) from baseline to week 20. RESULTS Intention-to-treat analysis showed a median PASI reduction of 48% (95% confidence interval 33.3-58.3%) in the dietary intervention arm and 25.5% (95% confidence interval 18.2-33.3%) in the information-only arm (P = 0.02). Among secondary outcomes, PASI score reduction of ≥ 50% significantly differed between study arms (49.7% with dietary intervention vs. 34.2% with information only, P = 0.006). The weight-loss target (a ≥ 5% reduction from baseline) was reached by 29.8% of patients in the dietary intervention arm compared with 14.5% in the information-only arm (P = 0.001). CONCLUSIONS A 20-week dietetic intervention associated with increased physical exercise reduced psoriasis severity in systemically treated overweight or obese patients with active psoriasis.
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Intensive weight loss intervention in older individuals: results from the Action for Health in Diabetes Type 2 diabetes mellitus trial.
Espeland, MA, Rejeski, WJ, West, DS, Bray, GA, Clark, JM, Peters, AL, Chen, H, Johnson, KC, Horton, ES, Hazuda, HP, et al
Journal of the American Geriatrics Society. 2013;(6):912-922
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OBJECTIVES To compare the effects of 4 years of intensive lifestyle intervention on weight, fitness, and cardiovascular disease risk factors in older and younger individuals. DESIGN Randomized controlled clinical trial. SETTING Sixteen U.S. clinical sites. PARTICIPANTS Individuals with type 2 diabetes mellitus: 1,053 aged 65 to 76 and 4,092 aged 45 to 64. INTERVENTIONS An intensive behavioral intervention designed to promote and maintain weight loss through caloric restriction and increased physical activity was compared with diabetes mellitus support and education. MEASUREMENTS Standardized assessments of weight, fitness (based on graded exercise testing), and cardiovascular disease risk factors. RESULTS Over 4 years, older individuals had greater intervention-related mean weight losses (6.2%) than younger participants (5.1%; interaction P = .006) and comparable relative mean increases in fitness (0.56 vs 0.53 metabolic equivalents; interaction P = .72). These benefits were seen consistently across subgroups of older adults formed according to many demographic and health factors. Of a panel of age-related health conditions, only self-reported worsening vision was associated with poorer intervention-related weight loss in older individuals. The intensive lifestyle intervention produced mean increases in high-density lipoprotein cholesterol (2.03 mg/dL; P < .001) and decreases in glycated hemoglobin (0.21%; P < .001) and waist circumference (3.52 cm; P < .001) over 4 years that were at least as large in older as in younger individuals. CONCLUSION Intensive lifestyle intervention targeting weight loss and increased physical activity is effective in overweight and obese older individuals to produce sustained weight loss and improvements in fitness and cardiovascular risk factors.
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Diet-induced weight loss in obese children with asthma: a randomized controlled trial.
Jensen, ME, Gibson, PG, Collins, CE, Hilton, JM, Wood, LG
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2013;(7):775-84
Abstract
BACKGROUND Obesity is highly prevalent in asthmatic children and associated with worse clinical outcomes. Energy restriction to induce weight loss in asthmatic children has not been investigated in a randomized controlled trial (RCT). OBJECTIVE To assess if (1) weight loss can be achieved in obese asthmatic children using a dietary intervention; and (2) changes in asthma outcomes occur following diet-induced weight loss. METHODS In a 10-week pilot RCT, obese asthmatic children, aged 8-17 years, were randomized to a wait-list control (WLC) (n = 15) or dietary-intervention group (DIG) (n = 13). Lung function, Asthma Control Questionnaire (ACQ) score, and sputum and systemic inflammation were assessed at baseline and post-intervention. (Australian New Zealand Clinical Trials Registry: ACTRN12610000955011). RESULTS Body mass index (BMI) z-score reduced significantly in the DIG vs. the WLC (-0.2 [-0.4, -0.1] vs. 0.0 [-0.1, 0.0], P = 0.014). Expiratory reserve volume (ERV) increased significantly within the DIG, but not compared to the WLC (0.7 [0.0, 1.0] L vs. 0.3 [0.0, 0.8] L, P = 0.355). ACQ improved significantly in the DIG, compared to the WLC (-0.4 [-0.7, 0.0] vs. 0.1 [0.0, 0.6], P = 0.004). Airway and systemic inflammation did not change within the DIG. In comparison, C-Reactive Protein (CRP) increased significantly in the WLC (-0.4 [-0.5, 0.4] vs. 0.7 [-0.1, 1.9], P = 0.037). Change (∆) in BMI z-score correlated with ∆CRP (r = 0.47, P = 0.012) and ∆exhaled nitric oxide (eNO) (r = 0.46, P = 0.034), and ∆ACQ was associated with ∆CRP (r = 0.43, P = 0.029). CONCLUSION AND CLINICAL RELEVANCE Dietary intervention can induce acute weight loss in obese asthmatic children with subsequent improvements in static lung function and asthma control. Systemic and airway inflammation did not change following weight loss. However, changes in BMI z-score were associated with changes in airway and systemic inflammation and this requires further investigation in a larger RCT. This is the first weight loss RCT conducted in obese asthmatic children. Diet-induced weight loss can achieve significant improvements in clinical outcomes for obese children with asthma.
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Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE Phase 2) screening and recruitment: methods and results.
Stewart, TM, Bhapkar, M, Das, S, Galan, K, Martin, CK, McAdams, L, Pieper, C, Redman, L, Roberts, S, Stein, RI, et al
Contemporary clinical trials. 2013;(1):10-20
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The Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE) study is a systematic investigation of sustained 25% calorie restriction (CR) in non-obese humans. CALERIE is a multicenter (3 clinical sites, one coordinating center), parallel group, randomized controlled trial. Participants were recruited, screened, and randomized to the CR or control group with a 2:1 allocation. Inclusion criteria included ages 21-50 years for men and 21-47 years for women, and a body mass index (BMI) of 22.0 ≤ BMI < 28.0 kg/m(2). Exclusion criteria included abnormal laboratory markers, significant medical conditions, psychiatric/behavioral problems, and an inability to adhere to the rigors of the evaluation/intervention schedule. A multi-stage screening process (telephone screen and 3 in-clinic visits) was applied to identify eligible participants. Recruitment was effective and enrollment targets were met on time. 10,856 individuals contacted the clinical sites, of whom 9787 (90%) failed one or more eligibility criteria. Of the 1069 volunteers who started the in-clinic screening, 831 (78%) were either ineligible or dropped. 238 volunteers were enrolled (i.e., initiated the baseline evaluations), 220 were randomized, and 218 started the assigned intervention (2% from the first screening step). This study offered lessons for future multi-center trials engaging non-disease populations. Recruitment strategies must be tailored to specific sites. A multi-disciplinary screening process should be applied to address medical, physical, and psychological/behavioral suitability of participants. Finally, a multi-step screening process with simple criteria first, followed by more elaborate procedures has the potential to reduce the use of study resources.