FREE CARNITINE LEVELS AND DIETARY HABITS AMONG

FREE CARNITINE LEVELS AND DIETARY HABITS AMONG

249
Epileptologia, 2008, 16: 249-259
Free carnitine levels and dietary habits among
epileptic patients treated with valproate monotherapy
Stężenie wolnej karnityny i nawyki dietetyczne u pacjentów z padaczką
leczonych walproinianami w monoterapii
Antiepileptic Outpatient Clinic, Provincial Hospital No 2, 35-301 Rzeszów, Lwowska 60, Poland
2 Rinnekoti Research Centre, Kumputie 1, 02980 Espoo, Finland
3 Department of Food Chemistry and Nutrition, Medical College Jagiellonian University,
30-688 Krakow, Medyczna 9, Poland
4 Henryk Niewodniczański Institute of Nuclear Physics,
31-432 Kraków, Radzikowskiego 152, Poland
5 Department of Clinical Sciences, Pharmacology & Toxicology,
ELTDK, 00014 University of Helsinki, Finland
1
Streszczenie
Wstęp. Kwas walproinowy (VPA) jest pochodną kwasów
tłuszczowych, która może powodować zmniejszenie
stężenia karnityny, niezbędnej do betaoksydacji. Takie
zmiany wykazano głównie u dzieci oraz upośledzonych
umysłowo pacjentów leczonych z powodu padaczki.
Cel. Ocena, czy występuje zmniejszenie stężenia wolnej karnityny w surowicy (sfC) dorosłych pacjentów leczonych z powodu padaczki VPA (monoterapia), i czy
są korelacje między dietą pacjentów a tymi możliwymi zmianami.
Materiał i metody. U 21 pacjentów leczonych z powodu padaczki jedynie VPA oraz u 21 osób grupy kontrolnej oceniono na czczo stężenie sfC. Pacjenci oraz osoby z grupy kontrolnej wypełnili kwestionariusze dotyczące zwyczajów żywieniowych.
Wyniki. Nie wykazano statystycznie istotnej różnicy
w stężeniu sfC między grupą badaną a kontrolną, chociaż średnia wartość sfC była nieco mniejsza w grupie
pacjentów leczonych VPA. W całej grupie pacjentów
nie wykazano korelacji między stężeniem VPA a stężeniem sfC. Natomiast stwierdziliśmy istotną korelację między stężeniem VPA a stężeniem sfC u pacjentów płci męskiej. Częstość spożycia mleka i ryb nie korelowała ze stężeniem sfC ani w grupie pacjentów, ani
w grupie kontrolnej. Częstość spożywania mięsa miała
znaczący wpływ na stężenie sfC w obu grupach rozpatrywanych razem.
Wnioski. W związku z długoletnim leczeniem padaczki
wskazane jest branie pod uwagę możliwego działania
ubocznego stosowania VPA, jak zmniejszenie stężenia
Summary
Introduction. Valproic acid (VPA) is the derivative of
fatty acids, which can cause the reduction of the level of carnitine necessary for beta-oxidation. These
changes were primarily demonstrated among children and mentally impaired patients with epilepsy.
Objective. To evaluate if there is any decrease of concentration of serum free carnitine (sfC) during VPA monotherapy of adult patients with epilepsy and if there is
any correlation between patient diets and such possible changes.
Materials and methods. Fasting sfC and VPA levels
were evaluated in 21 patients with epilepsy receiving
VPA monotherapy as well as in 21 control subjects. The
questionnaires about dietary habits of the patients and
controls were completed.
Results. There was no statistically significant difference
in sfC levels between study and control groups, although
the mean value was slightly lower in patients with VPA
therapy. In the entire group of patients, no correlation
between the concentration of VPA and concentration of
sfC has been observed. However, the significant correlation between VPA concentration and sfC for male patients has been found. The frequency of milk and fish
consumption did not correlate with the free serum carnitine level neither in the patients group, nor in controls. The frequency of meat consumption had significant impact on sfC concentration in both groups taken together.
Conclusions. Due to a long-time treatment of epilepsy, it
is advisable to take into account possible adverse effect
Praca wpłynęła 12.11.2008 r.
Received November 12, 2008.
Prace oryginalne • Original papers
Elżbieta Płonka-Półtorak 1, Joanna Chłopicka 3, Paweł Zagrodzki 3,4, Markku Partinen 2,
Pekka Kaipainen2, Faik Atroshi 5, Tuomas Westermarck 2
250
Elżbieta Płonka-Półtorak et al.
sfC. Dotyczy to zwłaszcza mężczyzn leczonych dużymi
dawkami VPA i rzadko spożywających mięso.
Słowa kluczowe: Karnityna – Kwas walproinowy – Nawyki dietetyczne – Padaczka
of VPA therapy, as in case of reduced level of sfC. That
particularly concerns male patients treated with higher doses of VPA and rarely consuming meat.
Key words: L-carnitine – Valproic acid – Dietary habits
– Epilepsy
Prace oryginalne • Original papers
Introduction
V
alproic acid (2-propylvaleric acid, 2-propylpentanoic acid, VPA), an eight-carbon branched-chain fatty acid, is one of the
most widely used antiepileptic drugs. The
decrease of concentration of carnitine in the
serum of patients treated with VPA due to
epilepsy, especially in children (Castro-Gago et al., 1998; Opala et al., 1991; Laub et al.,
1986), and in patients with mental disability (Coppola et al., 2006; Sakemi et al., 1992;
Matsui et al., 1991) was verified in numerous studies.
L-carnitine (3-ydroxy-4-(trimethylam-moniobutanoatec), the key factor in mitochondrial beta oxidation of fatty acids, is synthesized in the liver, kidneys and brain from essential amino acids - lysine and methionine.
The vitamins C, B6, PP, and iron take part in
the synthesis of L-carnitine (Vaz et al., 2002).
More than 95% of the body’s total carnitine
store exists within the skeletal muscle tissue.
It is secreted and reabsorbed by the kidneys
(Rebouche and Engel, 1984).
The basic function of L-carnitine is transporting the long-chain fatty acids into the
mitochondrial matrix for beta-oxidation to
provide cellular energy. Moreover, carnitine
takes part in transport of the products of oxidation of very long-chain fatty acids from
peroxysomes into mitochondria and in removing from mitochondria medium and
short-chain fatty acids, which can be toxic
in higher concentrations.
L-carnitine modulates the rise in intrami-
tochondrial acyl-CoA/CoA ratio, which triggers the inhibition of many intramitochondrial enzymes involved in glucose and amino acid catabolism. As a donor of acetyl
group, it participates in synthesis of neurotransmitter acetylcholine. It also takes part
in reactions of detoxication, including removal of various drugs, and in chelation of
iron (Arrigoni-Martelli and Caso, 2001).
The concentration of L-carnitine in plasma
is between 30 and 90 mmol/l depending on
age and sex. Women have lower L-carnitine
concentration in plasma in comparison to
men, what may be a result of the regulative
influence of sex hormones (Vaz et al., 2002;
Opalka et al., 2001). In the body, L-carnitine
is found as a free compound or bound with
acyl esters, which form 25% of L-carnitine
in the serum.
The main sources of L-carnitine in the
diet are meat and dairy products. Large
amounts are contained in mutton, beef, pork
and fish products. The lowest carnitine content in meats has been detected in poultry.
Vegetables and fruit contain little or no carnitine, cereals have been found to be very low
in carnitine too. The average required carnitine intake for an adult is 15 mg.The adequate diet should cover 75% of the daily requirement for L-carnitine, while the remainder is synthesized endogenically (Czeczot
and Scibior, 2005). The carnitine content in
everyday diet is highly variable: people who
eat more beef can take in up to 300 mg of car-