Intermittent fasting and dietary supplementation with 2-deoxy-D-glucose improve functional and metabolic cardiovascular risk factors in rats

Hypertension and insulin resistance syndrome are risk factors for cardiovascular disease, and it is therefore important to identify interventions that can reduce blood pressure and improve glucose metabolism. We performed experiments aimed at determining whether intermittent fasting (IF) can improve cardiovascular health and also tested the hypothesis that beneficial effects of IF can be mimicked by dietary supplementation with 2-deoxy-D-glucose (2DG) a non-metabolizable glucose analog. Four-month-old male rats were implanted with telemetry probes to allow continuous monitoring of heart rate, blood pressure, physical activity, and body temperature. Rats were then maintained for 6 months on one of three different dietary regimens: ad libitum feeding, IF, or 2DG supplementation. Rats on the IF regimen consumed 30% less food over time and had reduced body weights compared with rats fed ad libitum, whereas rats on the 2DG regimen did not reduce their food intake and maintained their body weight. Heart rate and blood pressure were significantly decreased within 1 month in rats on IF and 2DG diets and were maintained at reduced levels thereafter. Body temperature was significantly decreased in group IF, but not in group 2DG. Levels of serum glucose and insulin were significantly decreased in rats maintained on IF and 2DG-supplemented diets, suggesting that IF and 2DG diets affect insulin sensitivity in a similar manner. Finally, rats in groups IF and 2DG exhibited increased levels of plasma adrenocorticotropin and corticosterone, indicating that these diets induced a stress response. We conclude that reductions in blood pressure, heart rate, and insulin levels, similar to or greater than those obtained with regular physical exercise programs, can be achieved by IF and by dietary supplementation with 2DG by a mechanism involving stress responses.