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FJ
EXPRESS SUMMARY ARTICLE The Full-length version of this article is also available, published online April 22, 2003 as doi:10.1096/fj.02-0996fje. |
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Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, Maryland, USA
2Correspondence: National Institute on Aging, GRC 4F01, 5600 Nathan Shock Dr., Baltimore, MD 21224, USA. E-mail: mattsonm{at}grc.nia.nih.gov
SPECIFIC AIMS
Experiments were designed to test the hypothesis that intermittent fasting (IF) can improve cardiovascular risk factors in adult rats and that such effects can be mimicked by dietary supplementation with 2-deoxy-D-glucose (2DG), an analog of glucose that inhibits glycolysis. The studies were based on the concept that intermittent fasting is a metabolic stress that can improve cardiovascular function and enhance glucose metabolism.
PRINCIPAL FINDINGS
1. Rats maintained on an intermittent fasting feeding regimen exhibit reduced body weight and decreased body temperature, blood pressure (BP), and heart rate (HR) compared with rats fed ad libitum (Fig. 1
)
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2. Rats maintained on a diet supplemented with 2DG did not reduce their food intake nor lose body weight but did exhibit significant decreases in blood pressure and heart rate (Fig. 1)
3. Blood glucose and insulin levels were significantly reduced in rats maintained on IF and 2DG-supplemented diets compared with rats fed ad libitum (Table 1)
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4. The beneficial effects of IF and 2DG supplementation on cardiovascular risk parameters were associated with a stress response, suggesting that periodic metabolic stress results in adaptive beneficial responses of cells in the cardiovascular system
5. The magnitudes of the decreases in BP and HR and in insulin and glucose levels in rats maintained on IF or 2DG-supplemented diets were as great as or greater than those previously reported to be achieved with regular aerobic exercise programs
CONCLUSIONS AND SIGNIFICANCE
Even though overeating is a major cause of cardiovascular disease and its associated morbidity and mortality, it has proved difficult for many people to reduce their food intake. The present study was aimed at understanding how dietary restriction improves cardiovascular health and to determine whether such beneficial effects might be mimicked without a reduction in food intake. We documented striking improvements in cardiovascular risk factors in rats maintained on an IF regimen; generally, similar changes occurred in rats fed a diet supplemented with 2DG. The reductions in BP and HR and in plasma levels of insulin and glucose in rats on the IF diet were even greater than those achieved with regular physical exercise programs in previous studies. Because increased BP and insulin levels are risk factors for cardiovascular disease and stroke, the ability of IF to reduce BP and insulin levels suggests that IF may reduce the risk of these diseases.
The present findings also provide novel insight into the mechanism whereby dietary restriction increases life span and reduces the incidence of various age-related diseases. We found that IF and 2DG supplementation each induced a neuroendocrine stress response (Fig. 2
). Because previous studies have shown that IF induces cellular stress responses in a variety of tissues throughout the body, it seems likely that such a stress responses increase the resistance of cells to disease. The latter mechanism of action of IF therefore appears to be similar to the mechanism whereby physical exercise improves the function (and resistance to damage and disease) of skeletal muscle, the heart, and blood vessels. IF and caloric restriction are known to decrease levels of oxidative damage to cells; oxidative damage is believed to contribute to the pathogenesis of a variety of disorders, including cardiovascular disease, cancers, diabetes, and neurodegenerative disorders. The present findings provide a scientific basis for tests of the effects of IF and dietary supplements that mimic IF in humans and for the development of novel approaches for preventing and treating cardiovascular disease and diabetes.
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FOOTNOTES
1 To read the full text of this article, go to http://www.fasebj.org/cgi/doi/10.1096/fj.02-0996fje; to cite this article, use FASEB J. (April 22, 2003) 10.1096/fj.02-0996fje 
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