ENERGY RESTRICTION AND OXIDATIVE DNA-DAMAGE IN HUMANS

The cancer-preventive effect of energy restriction in rodents has been related to a decrease in oxidative damage to DNA, We have investigate d the effect of energy restriction on the rate of oxidative DNA modifi cation estimated from the urinary excretion of the repair product, 8-o xo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), in healthy, normal weight men, Before and after 10 weeks on a diet containing 80 (n = 16) or 100 % (n = 8) of the estimated weight-maintaining energy, resting metaboli c rate (RMR) was measured and 24-h urine was collected for 8-oxodG det ermination by HPLC. During the study, the weight loss was 10 and 2.5% of the initial weight, mostly in terms of fat, and the RMR decreased b y 13 and 8% in the energy-restricted and control groups, respectively, With the use of t tests there was no significant difference within or between groups with respect to 8-oxodG excretion, However, if RMR was included as a covariate in multifactorial ANOVA, an average relative 17% (2-31%; 95% confidence interval) increase in 8-oxodG excretion in the energy-restricted group was significantly different from the corre sponding value of the control group (P < 0.02). In the energy-restrict ed group the change in 8-oxodG excretion was correlated closely with t he decrease in RMR (r = 0.63; P = 0.013). In the present study, 20% en ergy restriction for 10 weeks did not reduce oxidative DNA damage; we question a beneficial effect on cancer risk in normal weight humans, M oreover, the data suggest that unless the metabolic rate decreases cor respondingly, energy restriction may even increase the rate of oxidati ve DNA modification in humans, This apparently complex effect of energ y restriction on oxidative DNA damage warrants additional investigatio n.