EvidenceAlerts

Kraus WE, Bhapkar M, Huffman KM, et al. 2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial. Lancet Diabetes Endocrinol. 2019 Sep;7(9):673-683. doi: 10.1016/S2213-8587(19)30151-2. Epub 2019 Jul 11. (Original study)
Abstract

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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Ratings
Discipline Area Score
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Special Interest - Obesity -- Physician 6 / 7
Public Health 6 / 7
Endocrine 5 / 7
Comments from MORE raters

Endocrine rater

The study gave evidence that moderate caloric restriction in healthy young and middle-aged and non obese persons improves multiple cardiometabolic risk factors.

Family Medicine (FM)/General Practice (GP) rater

The article shows that moderate calorie restriction, in healthy non obese people, causing about 7kg loss of weight over 2 years, resulted in significant improvement in measurements of cardiovascular risk across a wide range of factors from blood pressure to lipids. This is important for individuals and general public health.

Public Health rater

It's interesting to see a study of longer term weight loss. However, still just intermediary outcomes, and strict calorie restriction is unlikely to be widely adopted by normal weight adults unless it gives significant health benefits.

Public Health rater

This is another piece of evidence that calorie restriction works in humans as well to reduce cardiometabolic risk factors and hopefully prolong human survival without disease.

Special Interest - Obesity -- Physician rater

This is a good study. I would like to see the Phase 3 study with a longer duration of study involving more patients looking at cardiovascular outcomes.
Comments from EvidenceAlerts subscribers

Dr. Sreeram Parupudi (9/1/2019 2:52 PM)

Excellent study and encouraging outcomes! Although not addressed by this study, I wonder whether this would be the same or better when applied to non-obese patients with diabetes 🤔.