Valproic acid (VPA) is a widely used and well-tolerable
antiepileptic drug in epileptic patients. However, VPA has many side effects dose-dependent or non-dose-dependent. It is reported that VPA treatment may lead to
biotin deficiency and low serum and liver tissue
biotinidase enzyme activity (BEA). Major clinical manifestations in
biotin deficiency are
seborrheic dermatitis, dry skin, fine and brittle hair, and
alopecia. We aimed to investigate the effects of
biotin supplementation on serum and liver tissue BEA and
alopecia during VPA
therapy. Rats were randomly divided into 4 groups, each consisted of 15 rats (VPA-B1, VPA-B2, VPA, and control). Except the control group, all groups were administrated VPA dose of 600 mg/kg/d per oral (PO) for 60 days with 12h intervals two divided doses. VPA-B1 was administrated
biotin dose of 6 mg/kg/d and VPA-B2 was administrated
biotin dose of 0.6 mg/kg/d. In the third week of the study, we determined
alopecia in the study groups.
Alopecia was seen in the subjects of 13.3% of VPA-B1 (n=2), 13.3% of VPA-B2 (n=2), and 40% of VPA (n=6). But statistical significant effect on
alopecia by
biotin supplementation was not able to be determined between the study groups. In the control group,
alopecia was not observed. The ratios of
alopecia in the study groups were statistically higher than the control group (p=0.028). Itchiness was more obvious in the study groups compared with the control group. Serum
biotin levels of the
biotin supplemented groups (VPA-B1 and VPA-B2) were higher than the other groups (VPA and control group). Serum
biotin levels of the VPA group were lower than the control group. There were significant decreases in the levels of serum and liver tissue BEA of the study groups compared with the control group. In conclusion we showed that VPA usage reduced the serum and liver tissue BEA and impaired the
biotin utilization by affecting the liver. Partial
biotinidase deficiency may lead to
alopecia. It might be prevented by
biotin supplementation in the patients receiving VPA
therapy. We considered that further studies are necessary to find out the effective and safe
biotin dose.