Biochemical parameters and their association with response to ketogenic dietary therapies

Schoeler NE, Bell G, Yuen A, Kapelner AD, Heales SJ, Cross JH, Sisodiya S. An examination of biochemical parameters and their association with response to ketogenic dietary therapies. Epilepsia. 2017 Apr 3. doi: 10.1111/epi.13729. [Epub ahead of print]

Abstract

OBJECTIVE:

In the absence of specific metabolic disorders, accurate predictors of response to ketogenic dietary therapies (KDTs) for treating epilepsy are largely unknown. We hypothesized that specific biochemical parameters would be associated with the effectiveness of KDT in humans with epilepsy. The parameters tested were β-hydroxybutyrate, acetoacetate, nonesterified fatty acids, free and acylcarnitine profile, glucose, and glucose-ketone index (GKI).

METHODS:

Biochemical results from routine blood tests conducted at baseline prior to initiation of KDT and at 3-month follow-up were obtained from 13 adults and 215 children with KDT response data from participating centers. One hundred thirty-two (57%) of 228 participants had some data at both baseline and 3 months; 52 (23%) of 228 had data only at baseline; 22 (10%) of 228 had data only at 3 months; and 22 (10%) of 228 had no data. KDT response was defined as ≥50% seizure reduction at 3-month follow-up.

RESULTS:

Acetyl carnitine at baseline was significantly higher in responders (p < 0.007). It was not associated with response at 3-month follow-up. There was a trend for higher levels of free carnitine and other acylcarnitine esters at baseline and at 3-month follow-up in KDT responders. There was also a trend for greater differences in levels of propionyl carnitine and in β-hydroxybutyrate measured at baseline and 3-month follow-up in KDT responders. No other biochemical parameters were associated with response at any time point.

SIGNIFICANCE:

Our finding that certain carnitine fractions, in particular baseline acetyl carnitine, are positively associated with greater efficacy of KDT is consistent with the theory that alterations in energy metabolism may play a role in the mechanisms of action of KDT.

Physicians designed this study to test the hypothesis that specific biochemical parameters would be associated with the effectiveness of ketogenic dietary therapies (KDTs) in humans with epilepsy. The finding that specific carnitine fractions are positively associated with greater efficacy of KDT is consistent with the theory that alterations in energy metabolism may play a role in the mechanisms of action of KDT, specifically baseline acetyl carnitine.

Methods

The physicians obtained biochemical results from routine blood tests conducted at baseline prior to initiation of KDT and at 3-month follow-up from 13 adults and 215 children with KDT response data from participating centers.

At both baseline and 3 months, 132 (57%) of 228 participants had some data; 52 (23%) of 228 had data only at baseline; 22 (10%) of 228 had data only at 3 months, and 22 (10%) of 228 had no data.

They defined KDT response as ≥50% seizure reduction at 3-month follow-up.

Results

At baseline, acetyl carnitine was significantly higher in responders (p < 0.007) and it was not associated with response at 3-month follow-up.

In KDT responders, there was a trend for higher levels of free carnitine and other acylcarnitine esters at baseline and at 3-month follow-up.

Also, in KDT responders, there was a trend for greater differences in levels of propionyl carnitine and in β-hydroxybutyrate measured at baseline and 3-month follow-up.

At any time point, no other biochemical parameters were associated with response.

https://www.mdlinx.com/neurology/medical-news-article/2017/04/05/ketogenic-dietary-therapies-epilepsy/7121830/?category=latest&page_id=1