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Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: a 2-y randomized controlled trial of calorie restriction in nonobese humans.

ABSTRACT: Background: Calorie restriction (CR) retards aging and increases longevity in many animal models. However, it is unclear whether CR can be implemented in humans without adverse effects on body composition.Objective: We evaluated the effect of a 2-y CR regimen on body composition including the influence of sex and body mass index (BMI; in kg/m2) among participants enrolled in CALERIE-2 (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), a multicenter, randomized controlled trial.Design: Participants were 218 nonobese (BMI: 21.9-28.0) adults aged 21-51 y who were randomly assigned to 25% CR (CR, n = 143) or ad libitum control (AL, n = 75) in a 2:1 ratio. Measures at baseline and 12 and 24 mo included body weight, waist circumference, fat mass (FM), fat-free mass (FFM), and appendicular mass by dual-energy X-ray absorptiometry; activity-related energy expenditure (AREE) by doubly labeled water; and dietary protein intake by self-report. Values are expressed as means ± SDs.Results: The CR group achieved 11.9% ± 0.7% CR over 2-y and had significant decreases in weight (-7.6 ± 0.3 compared with 0.4 ± 0.5 kg), waist circumference (-6.2 ± 0.4 compared with 0.9 ± 0.5 cm), FM (-5.4 ± 0.3 compared with 0.5 ± 0.4 kg), and FFM (-2.0 ± 0.2 compared with -0.0 ± 0.2 kg) at 24 mo relative to the AL group (all between-group P < 0.001). Moreover, FFM as a percentage of body weight at 24 mo was higher, and percentage of FM was lower in the CR group than in the AL. AREE, but not protein intake, predicted preservation of FFM during CR (P < 0.01). Men in the CR group lost significantly more trunk fat (P = 0.03) and FFM expressed as a percentage of weight loss (P < 0.001) than women in the CR group.Conclusions: Two years of CR had broadly favorable effects on both whole-body and regional adiposity that could facilitate health span in humans. The decrements in FFM were commensurate with the reduced body mass; although men in the CR group lost more FFM than the women did, the percentage of FFM in the men in the CR group was higher than at baseline. CALERIE was registered at clinicaltrials.gov as NCT00427193.

SUBMITTER: Das SK

PROVIDER: S-EPMC5366044 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: a 2-y randomized controlled trial of calorie restriction in nonobese humans.

Das Sai Krupa SK Roberts Susan B SB Bhapkar Manjushri V MV Villareal Dennis T DT Fontana Luigi L Martin Corby K CK Racette Susan B SB Fuss Paul J PJ Kraus William E WE Wong William W WW Saltzman Edward E Pieper Carl F CF Fielding Roger A RA Schwartz Ann V AV Ravussin Eric E Redman Leanne M LM

The American journal of clinical nutrition 20170222 4

Background: Calorie restriction (CR) retards aging and increases longevity in many animal models. However, it is unclear whether CR can be implemented in humans without adverse effects on body composition.Objective: We evaluated the effect of a 2-y CR regimen on body composition including the influence of sex and body mass index (BMI; in kg/m2) among participants enrolled in CALERIE-2 (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), a multice ...[more]

PMID: 28228420

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Project description:The energy intake necessary to maintain weight and body composition is called the energy requirement for weight maintenance and can be determined by using the doubly labeled water (DLW) method.The objective was to determine the energy requirements of nonobese men and women in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy 2 study.Energy requirements were determined for 217 healthy, weight-stable men and women [aged >21 to <50 y; 70% female, 77% white; body mass index (BMI; in kg/m(2)) 22 to <28; 52% overweight] over 28 d with 2 consecutive 14-d DLW assessments in addition to serial measures of body weight and fat-free mass and fat mass by dual-energy X-ray absorptiometry. Energy intake and physical activity were also estimated by self-report over ?6 consecutive d in each DLW period.Total daily energy expenditure (TDEE) was consistent between the 2 DLW studies (TDEE1: 2422 ± 404 kcal/d; TDEE2: 2465 ± 408 kcal/d; intraclass correlation coefficient = 0.90) with a mean TDEE of 2443 ± 397 kcal/d that was, on average, 20% (580 kcal/d) higher in men than in women (P < 0.0001). The regression equation relating mean TDEE to demographics and weight was as follows: TDEE (kcal/d) = 1279 + 18.3 (weight, kg) + 2.3 (age, y) - 338 (sex: 1 = female, 0 = male); R(2) = 0.57. When body composition was included, TDEE (kcal/d) = 454 + 38.7 (fat-free mass, kg) - 5.4 (fat mass, kg) + 4.7 (age in y) + 103 (sex: 1 = female, 0 = male); R(2) = 0.65. Individuals significantly underreported energy intake (350 kcal/d; 15%), and underreporting by overweight individuals (~400 kcal/d; 16%) was greater (P < 0.001) than that of normal-weight individuals (~270 kcal/d; 12%). Estimates of TDEE from a 7-d physical activity recall and measured resting metabolic rate also suggested that individuals significantly underreported physical activity (~400 kcal/d; 17%; P < 0.0001).These new equations derived over 1 mo during weight stability can be used to estimate the free-living caloric requirements of nonobese adults. This trial was registered at clinicaltrials.gov as NCT00427193.

Project description:IMPORTANCE:Calorie restriction (CR) increases longevity in many species and reduces risk factors for chronic diseases. In humans, CR may improve health span, yet concerns remain about potential negative effects of CR. OBJECTIVE:To test the effect of CR on mood, quality of life (QOL), sleep, and sexual function in healthy nonobese adults. DESIGN, SETTING, AND PARTICIPANTS:A multisite randomized clinical trial (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 [CALERIE 2]) was conducted at 3 academic research institutions. Adult men and women (N?=?220) with body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 22.0 to 28.0 were randomized to 2 years of 25% CR or an ad libitum (AL) control group in a 2:1 ratio favoring CR. Data were collected at baseline, 12 months, and 24 months and examined using intent-to-treat analysis. The study was conducted from January 22, 2007, to March 6, 2012. Data analysis was performed from July 18, 2012, to October 27, 2015. INTERVENTIONS:Two years of 25% CR or AL. MAIN OUTCOMES AND MEASURES:Self-report questionnaires were administered to measure mood (Beck Depression Inventory-II [BDI-II], score range 0-63, higher scores indicating worse mood, and Profile of Mood States [POMS], with a total mood disturbance score range of -32 to 200 and higher scores indicating higher levels of the constructs measured), QOL (Rand 36-Item Short Form, score range 0-100, higher scores reflecting better QOL, and Perceived Stress Scale, score range 0-40, higher scores indicating higher levels of stress), sleep (Pittsburgh Sleep Quality Index [PSQI], total score range 0-21, higher scores reflecting worse sleep quality), and sexual function (Derogatis Interview for Sexual Function-Self-report, total score range 24-188, higher scores indicating better sexual functioning). RESULTS:In all, 218 participants (152 women [69.7%]; mean [SD] age, 37.9 (7.2) years; mean [SD] BMI, 25.1 [1.6]) were included in the analyses. The CR and AL groups lost a mean (SE) of 7.6 (0.3) kg and 0.4 (0.5) kg, respectively, at month 24 (P?<?.001). Compared with the AL group, the CR group had significantly improved mood (BDI-II: between-group difference [BGD], -0.76; 95% CI, -1.41 to -0.11; effect size [ES], -0.35), reduced tension (POMS: BGD, -0.79; 95% CI, -1.38 to -0.19; ES, -0.39), and improved general health (BGD, 6.45; 95% CI, 3.93 to 8.98; ES, 0.75) and sexual drive and relationship (BGD, 1.06; 95% CI, 0.11 to 2.01; ES, 0.35) at month 24 as well as improved sleep duration at month 12 (BGD, -0.26; 95% CI, -0.49 to -0.02; ES, -0.32) (all P?<?.05). Greater percent weight loss in the CR group at month 24 was associated with increased vigor (Spearman correlation coefficient, ??=?-0.30) and less mood disturbance (??=?0.27) measured with the POMS, improved general health (??=?-0.27) measured with the SF-36, and better sleep quality per the PSQI total score (??=?0.28) (all P?<?.01). CONCLUSIONS AND RELEVANCE:In nonobese adults, CR had some positive effects and no negative effects on health-related QOL. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT00427193.

Project description:BackgroundCaloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible for this adaptation are poorly understood.Methods and findingsThe current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young (36.8 +/- 1.0 y), overweight (body mass index, 27.8 +/- 0.7 kg/m(2)) individuals randomized into one of three groups for a 6-mo intervention: Control, 100% of energy requirements; CR, 25% caloric restriction; and CREX, caloric restriction with exercise (CREX), 12.5% CR + 12.5% increased energy expenditure (EE). In the controls, 24-h EE was unchanged, but in CR and CREX it was significantly reduced from baseline even after adjustment for the loss of metabolic mass (CR, -135 +/- 42 kcal/d, p = 0.002 and CREX, -117 +/- 52 kcal/d, p = 0.008). Participants in the CR and CREX groups had increased expression of genes encoding proteins involved in mitochondrial function such as PPARGC1A, TFAM, eNOS, SIRT1, and PARL (all, p < 0.05). In parallel, mitochondrial DNA content increased by 35% +/- 5% in the CR group (p = 0.005) and 21% +/- 4% in the CREX group (p < 0.004), with no change in the control group (2% +/- 2%). However, the activity of key mitochondrial enzymes of the TCA (tricarboxylic acid) cycle (citrate synthase), beta-oxidation (beta-hydroxyacyl-CoA dehydrogenase), and electron transport chain (cytochrome C oxidase II) was unchanged. DNA damage was reduced from baseline in the CR (-0.56 +/- 0.11 arbitrary units, p = 0.003) and CREX (-0.45 +/- 0.12 arbitrary units, p = 0.011), but not in the controls. In primary cultures of human myotubes, a nitric oxide donor (mimicking eNOS signaling) induced mitochondrial biogenesis but failed to induce SIRT1 protein expression, suggesting that additional factors may regulate SIRT1 content during CR.ConclusionsThe observed increase in muscle mitochondrial DNA in association with a decrease in whole body oxygen consumption and DNA damage suggests that caloric restriction improves mitochondrial function in young non-obese adults.

Dataset Information

Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: a 2-y randomized controlled trial of calorie restriction in nonobese humans.

Publications

Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: a 2-y randomized controlled trial of calorie restriction in nonobese humans.

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