A Study on the Liver Toxicity Induced by Ketogenic Diet in Rats

Moon, Jin Soo; Kim, Dong Wook

Abstract

PURPOSE: Ketogenic diet(KD) remains a therapy in search of explanation although it is an established treatment for patients with intractable epilepsy. The mechanisms underlying its anticonvulsant action remain poorly understood. Furthermore, its possible side effects have not been investigated systematically. The present study was designed to investigate untoward side effects of KD on liver in rats.
METHODS
A KD([fat]:[protein+carbohydrate] ratio of 4.3:1) was administered to male Sprague-Dawley rats, while control animals were fed a standard rodent chow for treatment period of either 3(KD n=5 vs. control n=4) or 5(KD n= 4 vs. control n=5) weeks. Dietary treatment was initiated at postnatal 3 weeks. At the end of treatment, blood beta-hydroxybutyrate(BHB) was assayed and then the animals were sacrificed for liver and blood sampling. Their livers were examined to evaluate fatty changes using oil red O technique. Serum levels of AST, ALT, alkaline phosphatase, and total bilirubin were assayed.
RESULTS
The mean(+/-SEM) blood BHB levels in the KD group were significantly higher than those of the control group in animals treated for 3(5.9+/-0.1 vs. 0.6+/-0.1 mM, P<0.001) or 5(4.1+/-0.3 vs. 0.4+/-0.1 mM, P<0.001) weeks. Very distinct fatty changes were noticed microscopically in liver specimens of all rats treated with KD for either 3 or 5 weeks. Serum ALT levels were also significantly higher in the KD group than in the control in both 3(87.6+/-12.1 vs. 37.0+/-3.7 IU/L, P<0.01) and 5(118.5+/-2.9 vs. 31.6+/-2.6 IU/L, P<0.001) weeks treatment periods. In animals treated for 5 weeks, serum AST levels were also significantly(P<0.01) higher in the KD group(205.0+/-29.5 IU/L) than in the control(99.2+/-5.4 IU/L), whereas in animals treated for 3 weeks, no significant differences were noticed in AST levels between the two groups(133.2+/-11.7 vs. 122.8+/-13.1 IU/L, P>0.5). Other biochemical assay results showed no significant differences.
CONCLUSION
This study demonstrates that KD causes some significant changes in the hepatic function and morphology at least in rats. It is well known that KD produces ketosis, i.e. elevated blood levels of ketone bodies, which are generated mainly in the liver. Thus, some changes in the liver, either harmful or beneficial, may easily be suspected. Further basic and/or clinical studies on this issue should be performed in a near future.