Previous studies have reported that calorie-restricted diets could prolong the lives of rodents and other short-lived species, but, until now, no such human study has been undertaken to investigate the effects of such diets on markers of human aging.
The Comprehensive Assessment of the Long Term Effects of Reducing Intake of Energy (CALERIE) study, published in the new issue of the Journal of the American Medical Association (Vol. 295, pp. 1539-1548), followed 48 middle-aged, overweight, non-obese men and women eating one of four calorie-controlled diets for six months.
The participants (21 men, 27 women) were randomly assigned to eat one of four diets: control (weight maintenance diet); calorie restriction (calorie intake reduced by 25 per cent of normal); calorie restriction with exercise (calorie intake reduced by 12.5 per cent, energy expenditure increased by 12.5 per cent); very low-calorie diet (890 kilocalories per day until 15 per cent weight loss and then weight maintenance diet).
After six months, the control group had a measured weight loss of about 1 per cent. The three intervention groups, as expected, lost significantly more weight. Both the calorie restriction and calorie restriction with exercise groups lost about 10 per cent during the trial, while the low-calorie group lost on average 14 per cent, in keeping with the design study.
Weight loss was not the primary focus of the study however, and positive results for the calorie restriction were observed for markers of aging.
"Our results indicate that prolonged calorie restriction caused a reversal in two of three previously reported biomarkers of longevity (fasting insulin level and core body temperature)… and a reduction in DNA fragmentation, reflecting less DNA damage," wrote lead author Leonie Heilbronn from Louisiana State University.
"We are the first to report a significant decline in DNA damage following six months of calorie restriction in non-obese men and women," stressed Heilbronn.
One of the most widely accepted theories on aging is that reactive oxygen species (ROS) attack, amongst other things, DNA, affect normal cell function and lead to again and, potentially, the development of cancer.
No changes were recorded in other markers of longevity, including dehydroepiandrosterone sulfate (DHEAS) levels, or in fasting glucose levels, which have been measured in both primates and longer-lived men, an inconsistency suggested to be due to the short duration of the CALERIE study.
Interestingly, a 'metabolic adaptation' (a change in the use of energy) was observed and occurred in the first three months of the trial, with no further changes at the end of the trial.
"The metabolic adaptation in the calorie restriction with exercise group was similar to that observed in the calorie restriction group, suggesting that energy deficit rather than calorie restriction itself is driving the decrease in energy expenditure," said Heilbronn.
In an accompanying editorial, Luigi Fontana from Washington University School of Medicine welcomed the study as adding a considerable amount of information to the current understanding of the subject.
"It is anticipated that the study by Heilbronn et al will stimulate additional investigation of the effects of calorie restriction in humans," said Fontana.
Dr. Fontana called for longer-term studies with larger sample populations to measure changes to hormones, metabolism and gene expression caused by such diets.
"Although it is not likely that many individuals would adopt a calorie-restricted diet, the value of these studies is that they suggest possible mechanisms of aging in humans and points of intervention to modify the effects of aging," concluded Fontana.
The call for more study was echoed by Helen Stracey, a registered dietitian on behalf of the British Dietetic Association.
"It is true that calorie restriction increases longevity in rats, this has been proved," Stracey told NutraIngredients.com.
"This study is in humans but unfortunately the sample size is too small (46 people counting the drop outs) for us to conclude anything and in particular extrapolate anything to the general population. The conclusion is that larger studies of longer duration are needed to determine if calorie restriction attenuates the aging process."