The modification of the ketogenic diet mitigates its stunting effects in rodents

The high-fat and low-carbohydrate ketogenic diet (HFKD) is extensively studied within the fields of numerous diseases, including cancer and neurological disorders. Since most studies incorporate animal models, ensuring the quality of ketogenic rodent diets is important, both in the context of laboratory animal welfare as well as for the accuracy of the obtained results. In this study we implemented a modification to a commonly used ketogenic rodent chow by replacing non-resorbable cellulose with wheat bran. We assessed the effects of month-long treatment with either the unmodified or the modified HFKD on the growth and development of young male rats. Daily body weight, functional performance, and brain morphometric parameters were assessed to evaluate the influence of both applied diets on rodent development. Our results revealed that the unmodified ketogenic chow induced strong side effects that included weakness, emaciation, and brain undergrowth concomitant to growth inhibition. However, application of the ketogenic chow supplemented with wheat bran suppressed these adverse side effects, which was associated with the restoration of insulin-like growth factor 1 and a decrease in corticosterone levels. We have also shown that the advantageous results of the modified HFKD are not species- or sex-specific. Our data indicate that the proposed HFKD modification even allows for its application in young animals, without causing detrimental side effects.