Life Extension Update
Human calorie restriction study supports benefits demonstrated in other species
The results of a study published in the April 5, 2006 issue of the Journal of the American Medical Association (JAMA) provide preliminary evidence in humans that calorie restriction may provide some of the benefits seen in animals in which the dietary regimen has been administered.
In the Comprehensive Assessment of the Long Term effects of Reducing Intake of Energy (CALERIE) study, Leonie K. Heilbronn, PhD, of Louisiana State University, in Baton Rouge, and colleagues randomized 48 healthy but overweight, sedentary men and women to six months of one of the following regimens: a weight maintenance diet, a calorie restricted diet which provided 25 percent fewer calories than baseline energy requirements, a diet restricted by 12.5 percent of baseline calorie requirements plus an exercise program designed to expend an additional 12.5 percent, or a very low calorie diet which consisted of 890 calories per day until 15 percent of the subject’s body weight was lost, followed by a weight maintenance diet. Weight was measured weekly, and average body temperature, 24 hour energy expenditure, blood levels of insulin, glucose, thyroid hormones, DHEA sulfate, protein carbonyls (associated with cellular aging), and DNA damage were assessed at the beginning of the study and at its conclusion.
After six months, individuals on the weight maintenance diet had lost 1 percent of their body weight, in contrast with the calorie restricted group who lost 10.4 percent, the calorie restriction with exercise group who lost 10 percent, and the very low calorie group who lost 13.9 percent. Fasting insulin levels significantly declined in all restricted groups after six months, while glucose and DHEA sulfate remained unchanged. Sedentary 24 hour energy expenditure, thyroid hormone levels and DNA damage decreased after six months in these three groups as well. Body temperature was lowered in the calorie restriction and calorie restriction plus exercise groups, but not in the groups that were assigned to the weight maintenance or very low calorie diets.
In summary, the authors write, "Our results indicate that prolonged calorie restriction caused: (1) a reversal in 2 of 3 previously reported biomarkers of longevity (fasting insulin level and core body temperature); (2) a metabolic adaptation (decrease in energy expenditure larger than expected on the basis of loss of metabolic mass) associated with lower thyroid hormone concentrations; and (3) a reduction in DNA fragmentation, reflecting less DNA damage. “
In an accompanying editorial, Luigi Fontana, MD, PhD, observed, ”The most important contributions from this study for enhancing current understanding of the effects of calorie restriction on aging relate to the calorie restriction-mediated reductions in core body temperature, serum T3 levels, and oxidative damage to DNA, as reflected by a reduction in DNA fragmentation. The oxidative stress hypothesis of aging is currently one of the most accepted explanations for how aging occurs at the biochemical and cellular level . . . The study by Heilbronn et al is the first to report a significant decline in DNA damage in response to calorie restriction in humans.”
How long we live may not be determined by what we eat so much as how much we eat. Of all the potential anti-aging approaches, none have so far shown the promise of caloric restriction. Over the past 75 years, many studies have shown that caloric restriction extends life span in a wide variety of species, from invertebrates to rodents, to mammals. So far, no long-term studies have been completed in primates or conducted in humans because of the sheer length of any proposed study (perhaps a century or more for human studies!). However, several ongoing studies are looking at caloric restriction in primates, and the early results are promising.
Although life span CRON studies have not been conducted on humans, there is anecdotal evidence and short-term data to suggest that CRON might work in humans as well. For example, the island of Okinawa has up to 40 times as many centenarians as does the rest of Japan. The caloric intake of adult Okinawans is 20 percent lower than their mainland counterparts. Children in Okinawa consume only about 60 percent of the recommended intake of food as their mainland counterparts (Kagawa Y 1978). The longevity of this subpopulation may be because of their restricted diet, although other factors cannot be ruled out.
Similarly, data from the Baltimore Longitudinal Study of Aging suggests that long-lived humans exhibit some of the same physiological and biochemical changes that accompany caloric restriction in animals. Survival rates are highest in those with low body temperatures and low levels of circulating insulin (Roth GS et al 2002). In addition, levels of serum dehydroepiandrosterone (DHEA), a presumed longevity marker (Kalimi M et al 1999), are also higher in long-lived individuals (Roth GS et al 2002). In primates undergoing CRON, DHEA levels are also conserved (Lane MA et al 1997).
Recent studies at the BioMarker Pharmaceuticals laboratory have shown that a nutrient formula from the Life Extension Foundation that contains extracts of grape seed and skin, a whole red grape resveratrol extract, vitamin C, and calcium (from calcium ascorbate) can produce many of the gene expression effects found in mice on CRON. Studies funded by the Life Extension Foundation at the Chinese Academy of Sciences in Beijing have shown that this formula can improve the strength and coordination of pomace flies (D melanogaster ) afflicted with a motor disorder that is similar to Parkinson’s disease in humans. This formula can protect mitochondria (the energy-generating power plants in the cell) isolated from rat livers from damage caused by exposure to carcinogens (unpublished data). A life span study with this formula is underway at the BioMarker Pharmaceuticals laboratory.
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