Reducing daily food intake by the equivalent of just a couple of cookies, or around 300 calories, over 2 years leads not only to improvements in body composition but a range of cardiometabolic risk factors that could result in reductions in the incidence of cardiovascular disease, the results of an innovative study suggest.
The Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) trial is a phase 2 study involving more than 200 normal to slightly overweight but otherwise healthy individuals up to aged50 years.
They were assigned to a personalized calorie restriction diet combined with individual and group counseling sessions aimed at reducing energy intake by 25%, or an ad libitum control group, who continued with their normal diet.
William E. Kraus, MD, Duke University School of Medicine, Durham, North Carolina, and colleagues report that individuals in the intervention group actually achieved an average reduction in energy intake of almost 12% over 2 years, with an average weight loss of 7.5 kg (approximately 16.5 lbs).
This was associated with significant improvements in lipid levels over baseline, as well as better insulin sensitivity, metabolic syndrome scores, and C-reactive protein levels. The research, published online July 11 in Lancet Diabetes & Endocrinology, showed that, in comparison, there were no significant changes in individuals assigned to their normal diet.
So the significant cardiometabolic improvements seen in the study were achieved despite the majority of patients in the intervention group not even hitting their targets for energy intake and weight reduction.
“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 observed in a press release by 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.”
He singled out as strengths the large sample size, careful measurement of energy intake and expenditure, relatively high retention and compliance rates, and detailed data on biomarkers of aging and cardiometabolic risk.
Fat Loss Accounted for 70% of Weight Loss in Intervention Group
Kraus and colleagues explain that severe calorie restriction has a “powerful protective effect” against atherosclerotic risk factors such as carotid artery intimal-media thickening (IMT), reduced left ventricular diastolic function, and poor heart rate variability, they note.
However, the impact of longer term calorie restriction on cardiometabolic risk factors in younger, healthy adults is less clear.
The researchers therefore conducted CALERIE, a randomized controlled trial involving individuals from three US clinical centers who were normal weight or slightly overweight, defined as a body mass index (BMI) of 22.0-27.9 kg/m2.
Men aged 21-50 years and premenopausal women aged 21-47 years were included. Participants were randomized in a 2:1 ratio to a calorie restriction intervention aimed at reducing calorie intake by 25% or to ad libitum control group.
Overall, 218 participants were randomized to the intervention (n = 143) or control group (n = 75). The average age of participants was 38 years, and approximately 70% were women. Over 75% were white, and 11% to 15% were African American.
Participants in the calorie restriction group were prescribed a 25% restriction in calorie intake based on energy requirements estimated from doubly labeled water measurements over a 4-week period at baseline. A prescribed diet was chosen from six eating plans, modified to suit cultural preference.
Individuals were then fed three meals per day, every day, at their clinical center for 1 month, during which they were instructed on the basis of calorie restriction. In addition, an in-house meal was provided alongside intensive group and individual behavioral counseling once a week for the first 24 weeks of the study.
Those assigned to the control group continued their regular diet and received no specific dietary intervention or counseling. They were followed every 3 months.
The degree of weight loss achieved by each participant was assessed and compared against a trajectory at the end of year 1, followed by weight loss maintenance for the remaining 12 months.
Energy intake in the calorie restriction group was reduced by a mean of 19.5% over the first 6 months, then crept back up to a mean reduction of 9.1% after 6 months, to average 11.9% over the 2 years of the study.
There was no change in average daily energy intake in the control group.
Compared with baseline, individuals in the intervention group experienced a reduction in weight of 8.4 kg at 1 year and 7.5 kg at 2 years (P < .001).
Although participants in the control group achieved a small degree of weight loss at 1 year, there was no significant change at 2 years.
Similar results were seen for BMI, percentage body fat, fat mass, and fat-free mass, with individuals in the calorie restriction group having significant reductions over baseline at years 1 and 2 (P < .001 for all), but no significant changes recorded in the control group (ad libitum diet).
The team calculated that, overall, fat loss at 2 years accounted for 71% of the weight loss seen in the calorie restriction group.
Improvements in Lipids, CRP, and Insulin Sensitivity
The results also showed that, compared with baseline, the calorie restriction intervention was associated with significant reductions in low-density lipoprotein cholesterol (LDL-C) levels, triglycerides, and total cholesterol to high-density lipoprotein cholesterol (HDL-C) ratio at 1 and 2 years (P < .001).
Individuals in the intervention group also had significant increases in HDL-C levels from baseline at both year 1 and 2 (P < .001).
Again, there were no significant differences in lipoprotein levels versus baseline in participants assigned to the ad libitum group.
For between-group comparisons, the intervention was associated with significant improvements versus controls in LDL-C levels, triglycerides, and total cholesterol to HDL-C ratio at 1 and 2 years, and HDL-C levels at 2 years.
Finally, the researchers looked at a range of other cardiometabolic risk factors and found that calorie restriction led to a series of improvements over the control group across the study period.
Specifically, the intervention was associated with greater insulin sensitivity over the ad libitum diet at 2 years (P < .0001), as well as significant reductions in high-sensitivity C-reactive protein (CRP) levels (P = .012), and a significantly lower metabolic syndrome score (P < .0001).
Researchers say the exact mechanism by which calorie restriction benefits health is not clear, but Kraus notes, “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.”
Nevertheless, “These data…indicate that inexpensive and safe dietary interventions, such as moderate calorie restriction, can be implemented early in life to optimize cardiometabolic health and reduce the lifetime risk of developing some of the most common, disabling, and expensive chronic diseases.”
Long-Term Calorie Restriction Is Hard in Obesogenic Environment
Hu writes in his editorial that previous studies have shown even modest weight gain of around 5 kg during young and middle adulthood is associated with a significantly increased risk of type 2 diabetes, cardiovascular disease, obesity-related cancer, and premature death.
The new study results, although encouraging, nevertheless underline the “challenges” of achieving “long-term calorie restriction in free-living populations.”
He adds that there are other approaches to weight loss, such as intermittent energy restriction or fasting, carbohydrate restriction, and the Mediterranean diet, to name a few.
“Improving the food environment by making healthy food choices more accessible, affordable, and the norm while reducing the accessibility of ultra-processed and highly palatable foods is essential to supporting healthy food choices and behavior,” Hu writes.
“To this end, policy solutions including sugar taxes, financial incentives for producing and purchasing healthy foods, food labeling, and better regulation of food marketing are needed to improve the global food environment.”
The study was supported by the National Institute on Aging (NIA) and National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health (NIH), NIA/NIH Cooperative Agreement, NIH General Clinical Research Center, Diabetes Research Training Center, and NIH Clinical Nutrition Research Unit. Hu has reported receiving grants from the NIH, research support from the California Walnut Commission, honoraria for lectures from Metagenics and Standard Process, and honoraria from Diet Quality Photo Navigation.