Long-Term Calorie Restriction Impact on Cardiovascular Health


A recent phase 2 trial found that caloric intake can improve biomarkers for heart disease, cancer, and cognitive decline — even among patients with a healthy BMI.

Even among healthy patients, calorie restriction over an extended period of time could be an effective way to improve cardiovascular health.

A recent trial examining caloric restriction in patients over a 2-year period found that patients managed to sustain a 10% drop in weight and see improvements in markers linked to metabolic disease and heart disease. 

“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,” said lead author William Kraus, MD, a cardiologist and distinguished professor of medicine at Duke “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.”

The 2 years of calorie restriction and cardio metabolic risk (CALERIE) trial was a multi center, randomized controlled trial that involved 238 participants between the ages of 21 and 50 years old. Between May 8, 2008 and Feb. 26, 2010, 218 of the 238 were randomly assigned in a 2:1 ratio to a 25% calorie restriction diet (143, 66%) or an ad libitum control diet (75, 34%).

Investigators evaluated marker and risk factor responses including 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 in an intention-to-treat population.

Upon analyses, investigators found that individuals randomized into the calorie restriction group achieved a mean reduction in calorie intake of 11.9% and sustained a mean weight reduction of 7.5 kg — of which, 71% was fat mass loss. In the ad libitum control group, the mean reduction in calorie intake was 0.8% and individuals had a mean weight gain of 0.1 kg.

Investigators noted that calorie restriction caused a persistent and significant reduction from baseline to 2 years of all measured cardiometabolic risk factors, which includes change scores in LDL-C, total cholesterol to HDL-C ratio, and systolic and diastolic blood pressure. Additionally, calorie restriction resulted in significant improvement in C-reactive protein, insulin sensitivity index, and metabolic syndrome score compared to the control.

“There’s something about caloric restriction, some mechanism we don’t yet understand that results in these improvements,” Krause said. “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.”

In an invited commentary, Frank Hu, MD, PhD, of the Harvard TH Chan School of Public Health, called the trial groundbreaking. 

“The CALERIE trial is groundbreaking in several respects. It is the first long-term calorie restriction intervention in non-obese young and middle-aged participants with a large sample size,” Hu explained. 

“The trial collected detailed time-course data for biomarkers of ageing and cardiometabolic risk factors. The calorie restriction intervention was previously shown to be safe without adverse effects on quality of life,” Hu continued. 

This study, titled “2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial,” is published in The Lancet: Diabetes & Endocrinology.

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