A Proof-of-Principle, Case-Control Study to Compensate for Potential Carbohydrates in Liquid Antiseizure Drugs in Children on the Ketogenic Diet.

Introduction: Since its creation, patients on ketogenic diet are told to avoid liquid medications due to theoretical concerns of "hidden" carbohydrates. However, switching from liquid to tablet formulations can be problematic, especially for infants and young children. We theorized that increasing the daily ketogenic ratio might compensate for liquid antiseizure drug carbohydrates. Methods: Two tables were created (for 3:1 and 4:1 ketogenic ratios), with variables including daily volume of antiseizure drugs and calories. Cases were those who had their ratio increased and liquid medications continued. Children already on tablet formulations, emergency situations, were primarily those included as controls. Results: From May 2016 through August 2018, 59 children (33 cases and 26 controls) ages 0.3-14 years were started on the classic ketogenic diet. Compensated antiseizure drugs most commonly included levetiracetam, clobazam, and valproate (mean volume 16 mL/d (range: 3-62 mL/d)). Adjusted ratios for younger children and infants on a 3:1 diet ranged from 3.1 to 3.5:1 and older children on a 4:1 diet from 4.2 to 4.7:1. There was no difference between cases and controls in achieving large ketosis (76% vs 77%), weight gain (1.4 vs 1.2 kg), 1 month >50% seizure reduction (52% vs 50%), or >90% seizure reduction (30% vs 35%). Four (12%) cases had zero or small urinary ketosis, which improved when antiseizure drugs were switched to tablets or discontinued. Conclusions: This proof-of-principle study demonstrates feasibility of compensating for carbohydrates in liquid medications by increases in the daily ketogenic ratio. This ratio adjustment protocol may help ease an already complex adjustment to dietary therapy.