Even for the slim, cutting around 300 calories daily improves risk markers

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Data from a two-year Duke Health trial suggests when it comes to cutting your risk for killer ailments such as diabetes and heart disease, there’s always room for improvement. In adults already at a healthy weight or carrying just a few extra pounds, cutting around 300 calories a day significantly improved already good levels of cholesterol, blood pressure, blood sugar and other markers. These are the findings of a randomised, controlled trial of 218 adults under age 50.

The trial, part of an ongoing project with the National Institutes of Health called CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) continues to build on the researchers’ hypothesis that it’s not just weight loss that leads to these improvements, but some more complex metabolic change triggered by eating fewer calories than what’s expended.

“There’s something about caloric restriction, some mechanism we don’t yet understand that results in these improvements,” said the study’s lead author Dr William E Kraus, a cardiologist and distinguished professor of medicine at Duke. “We have collected blood, muscle and other samples from these participants and will continue to explore what this metabolic signal or magic molecule might be.”

For the first month of the trial, participants ate three meals a day that would cut one-fourth of their daily calories to help train them on the new diet. They could choose from six different meal plans that accommodated cultural preferences or other needs.

Participants also attended group and individual counseling sessions for the first six months of the trial, while members of a control group simply continued their usual diet and met with researchers once every six months.

Participants were asked to maintain the 25% calorie reduction for two years. Their ability to do that varied, with the average calorie reduction for all participants being about 12%. Still, they were able to sustain a 10% drop in their weight, 71% of which was fat, the study found. There were numerous improvements in markers that measure risk for metabolic disease. After two years, participants also showed a reduction in a biomarker that indicates chronic inflammation which has also been linked to heart disease, cancer and cognitive decline.

“This shows that even a modification that is not as severe as what we used in this study could reduce the burden of diabetes and cardiovascular disease that we have in this country,” Kraus said. “People can do this fairly easily by simply watching their little indiscretions here and there, or maybe reducing the amount of them, like not snacking after dinner.”

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/m 2) 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, numberNCT00427193.
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.

Authors
William E Kraus, Manjushri Bhapkar, Kim M Huffman, Carl F Pieper, Sai Krupa Das, Leanne M Redman, Dennis T Villareal, James Rochon, Susan B Roberts, Eric Ravussin, John O Holloszy, Luigi Fontana

Duke University Medical Centre material
The Lancet Diabetes & Endocrinology abstract


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