Diet, caloric restriction, and the rodent bioassay

The diet can significantly alter the results of toxicity and carcinogenicit y studies. Ad libitum (AL) overfeeding of excessive calories to sedentary a dult rodents is one of the most poorly controlled variables affecting the c urrent rodent bioassay. AL-overfed rodents develop an early onset of advers e metabolic events, endocrine-disruptive degenerative diseases, and tumors that result in early morbidity and mortality. AL food consumption is extrem ely variable, but has a strong correlation with adult body weight, obesity, and survival. AL feeding of diets with modified protein, fiber, and energy content are not as effective as simple, moderate dietary (caloric) restric tion (DR) in controlling these study variables. Moderate DR (70 -75% of adu lt AL) is operationally simple and controls adult body weights, prevents ob esity, and improves health and survival by reducing or delaying diet-relate d endocrine, renal, and cardiac diseases. Moderate DR provides a uniform ro dent model, increases treatment exposure time, and increases the statistica l sensitivity of these chronic bioassays to detect true treatment effects. Feeding a balanced diet by a moderate DR regimen of 70-75% of the maximum, unrestricted adult AL food intake is recommended for conducting well-contro lled toxicity and carcinogenicity studies.