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Effects of 2 years of caloric restriction on oxidative status assessed by urinary F2-isoprostanes: The CALERIE 2 randomized clinical trial.

ABSTRACT: Calorie restriction (CR) without malnutrition slows aging in animal models. Oxidative stress reduction was proposed to mediate CR effects. CR effect on urinary F2-isoprostanes, validated oxidative stress markers, was assessed in CALERIE, a two-year randomized controlled trial. Healthy volunteers (n = 218) were randomized to prescribed 25% CR (n = 143) or ad libitum control (AL, n = 75) stratifying the randomization schedule by site, sex, and BMI. F2-isoprostanes were quantified using LC-MS/MS in morning, fasted urine specimens at baseline, at 12 and 24 months. The primary measure of oxidative status was creatinine-adjusted 2,3-dinor-iPF(2?)-III concentration, additional measured included iPF(2?)-III, iPF2a-VI, and 8,12-iso-iPF2a-VI. Intention-to-treat analyses assessed change in 2,3-dinor-iPF(2?)-III using mixed models assessing treatment, time, and treatment-by-time interaction effects, adjusted for blocking variables and baseline F2-isoprostane value. Exploratory analyses examined changes in iPF(2?)-III, iPF(2?)-VI, and 8,12-iso-iPF(2?)-VI. A factor analysis used aggregate information on F2-isoprostane values. In CR group, 2,3-dinor-iPF(2?)-III concentrations were reduced from baseline by 17% and 13% at 12 and 24 months, respectively; these changes were significantly different from AL group (p < .01). CR reduced iPF(2?)-III concentrations by 20% and 27% at 12 and 24 months, respectively (p < .05). The effects were weaker on the VI-species. CR caused statistically significant reduction in isoprostane factor at both time points, and mean (se) changes were -0.36 (0.06) and -0.31 (0.06). No significant changes in isoprostane factor were at either time point in AL group (p < .01 between-group difference). We conclude that two-year CR intervention in healthy, nonobese men and women reduced whole body oxidative stress as assessed by urinary concentrations of F2-isoprostanes.

SUBMITTER: Il'yasova D

PROVIDER: S-EPMC5847862 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Effects of 2 years of caloric restriction on oxidative status assessed by urinary F2-isoprostanes: The CALERIE 2 randomized clinical trial.

Il'yasova Dora D Fontana Luigi L Bhapkar Manjushri M Pieper Carl F CF Spasojevic Ivan I Redman Leanne M LM Das Sai Krupa SK Huffman Kim M KM Kraus William E WE

Aging cell 20180209 2

Calorie restriction (CR) without malnutrition slows aging in animal models. Oxidative stress reduction was proposed to mediate CR effects. CR effect on urinary F2-isoprostanes, validated oxidative stress markers, was assessed in CALERIE, a two-year randomized controlled trial. Healthy volunteers (n = 218) were randomized to prescribed 25% CR (n = 143) or ad libitum control (AL, n = 75) stratifying the randomization schedule by site, sex, and BMI. F2-isoprostanes were quantified using LC-MS/MS in ...[more]

PMID: 29424490

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Project description:BACKGROUND:For several cardiometabolic risk factors, values considered within normal range are associated with an increased risk of cardiovascular morbidity and mortality. We aimed to investigate the short-term and long-term effects of calorie restriction with adequate nutrition on these risk factors in healthy, lean, or slightly overweight young and middle-aged individuals. METHODS:CALERIE was a phase 2, multicentre, randomised controlled trial in young and middle-aged (21-50 years), healthy non-obese (BMI 22·0-27·9 kg/m2) men and women done in three clinical centres in the USA. Participants were randomly assigned (2:1) to a 25% calorie restriction diet or an ad libitum control diet. Exploratory cardiometabolic risk factor responses to a prescribed 25% calorie restriction diet for 2 years were evaluated (systolic, diastolic, and mean blood pressure; plasma lipids; high-sensitivity C-reactive protein; metabolic syndrome score; and glucose homoeostasis measures of fasting insulin, glucose, insulin resistance, and 2-h glucose, area-under-the curve for glucose, and insulin from an oral glucose tolerance test) analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00427193. FINDINGS:From May 8, 2007, to Feb 26, 2010, of 238 participants that were assessed, 218 were randomly assigned to and started a 25% calorie restriction diet (n=143, 66%) or an ad libitum control diet (n=75, 34%). Individuals in the calorie restriction group achieved a mean reduction in calorie intake of 11·9% (SE 0·7; from 2467 kcal to 2170 kcal) versus 0·8% (1·0) in the control group, and a sustained mean weight reduction of 7·5 kg (SE 0·4) versus an increase of 0·1 kg (0·5) in the control group, of which 71% (mean change in fat mass 5·3 kg [SE 0·3] divided by mean change in weight 7·5 kg [0·4]) was fat mass loss. Calorie restriction caused a persistent and significant reduction from baseline to 2 years of all measured conventional cardiometabolic risk factors, including change scores for LDL-cholesterol (p<0·0001), total cholesterol to HDL-cholesterol ratio (p<0·0001), and systolic (p<0·0011) and diastolic (p<0·0001) blood pressure. In addition, calorie restriction resulted in a significant improvement at 2 years in C-reactive protein (p=0·012), insulin sensitivity index (p<0·0001), and metabolic syndrome score (p<0·0001) relative to control. A sensitivity analysis revealed the responses to be robust after controlling for relative weight loss changes. INTERPRETATION:2 years of moderate calorie restriction significantly reduced multiple cardiometabolic risk factors in young, non-obese adults. These findings suggest the potential for a substantial advantage for cardiovascular health of practicing moderate calorie restriction in young and middle-aged healthy individuals, and they offer promise for pronounced long-term population health benefits. FUNDING:National Institute on Aging and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.

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Effects of 2 years of caloric restriction on oxidative status assessed by urinary F2-isoprostanes: The CALERIE 2 randomized clinical trial.

Publications

Effects of 2 years of caloric restriction on oxidative status assessed by urinary F2-isoprostanes: The CALERIE 2 randomized clinical trial.

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