Weanling and adult rats differ in fatty acid and carnitine metabolism during sepsis.

Increased oxidation of fat is an important host response to sepsis, and carnitine is essential for long-chain fatty acid oxidation. Because neonates have low levels of carnitine, their ability to respond to a septic insult may be impaired. The purpose of this study was to compare fatty acid and carnitine metabolism in septic weanling (60 to 85 g) and septic adult (285 to 310 g) rats. Sepsis was induced in weanling and adult male Sprague-Dawley rats by cecal ligation and puncture (CLP). The rats were killed 16 hours after CLP or sham operation, and serum glucose, lactate, beta-hydroxybutyrate, fatty acid, carnitine, liver fatty acid, and tissue carnitine levels were measured. The data suggest that during sepsis weanling rats may be more dependent on fatty acid oxidation than adult rats are, as evidenced by their elevated serum fatty acid and acylcarnitine levels, and relative hypoglycemia and hyperketonemia. In addition, although total serum carnitine levels were increased in both adult and weanling septic rats, tissue carnitine levels of weanling rats became significantly depleted during sepsis, unlike in adult rats. This study supports further investigation regarding the role of exogenous carnitine in newborn sepsis.

Effects of parenteral L-carnitine supplementation on fat metabolism and nutrition in premature neonates.

The effects of parenteral L-carnitine supplementation on fat metabolism, nutrient intake, and plasma and erythrocyte carnitine concentrations were studied in 43 very low birth weight infants. Infants were randomly assigned to control or carnitine-supplemented (50 mumol/kg per day) groups within two weight categories: group 1, 750 to 1000 gm, and group 2, 1001 to 1500 gm. Plasma total, free, and acyl carnitine levels, erythrocyte carnitine levels, serum beta-hydroxybutyrate and triglyceride levels, and total fat intake were monitored weekly until 50% of total caloric intake was met enterally. Neonates receiving carnitine had higher plasma carnitine levels than control groups (total carnitine: group 1, 75.2 +/- 22.9 vs 9.6 +/- 2.7 mmol/ml; group 2, 61.6 +/- 31.2 vs 13.0 +/- 9.2 nmol/ml). Levels of beta-OH-butyrate decreased from baseline in control neonates (group 1, 0.12 +/- 0.06 to 0.03 +/- 0.02 mmol/L; group 2, 0.11 +/- 0.03 to 0.05 +/- 0.02 mmol/L); they remained unchanged in supplemented groups. Thus ketogenesis appeared less impaired in infants receiving supplements. Supplemented group 2 tolerated more fat than control group 2; triglyceride levels remained acceptable in all groups. Carnitine group 2 had greater weight gain than control group 2 during the first 2 weeks of life. We conclude that very low birth weight infants requiring prolonged parenteral nutrition have carnitine deficiency with impaired ketogenesis. Parenteral administration of carnitine appears to alleviate this metabolic disturbance.

Reduction of serum carnitine concentrations during anticonvulsant therapy with phenobarbital, valproic acid, phenytoin, and carbamazepine in children.

We determined four carnitine constituents (total and free carnitine and short- and long-chain fatty acid carnitine esters) in serum from 471 patients treated for convulsions with phenobarbital, valproic acid, phenytoin, and/or carbamazepine. The 471 patients were in eight treatment groups; four were treated with monotherapy and four with polytherapy. The means of all four carnitine constituents were significantly reduced in all treatment groups (except for free carnitine in four groups). Total carnitine was reduced by 23% to 48%, free carnitine by 9% to 45%, short-chain fatty acid carnitine by 46% to 64%, and long-chain fatty acid carnitine by 6% to 29%. Patient frequency of reduction for total carnitine was 20% of all patients (10% for free carnitine), 23% of patients receiving valproate (9% for free carnitine), 36% of those receiving phenobarbital (21% for free carnitine), 12% of those receiving phenytoin (8% for free carnitine), and 8% of those receiving carbamazepine (1% for free carnitine). Only for phenobarbital was there an inverse correlation between the serum concentration of the drug and that of carnitine concentration. One patient receiving carbamazepine had a 59% reduction in the total and a 65% reduction in the free carnitine concentration and a fivefold increase in long-chain fatty acid carnitine, values similar to those seen in neonatal lethal carnitine palmitoyl transferase II deficiency. It remains to be determined whether a reduction in serum carnitine values in patients receiving anticonvulsant therapy is of clinical consequence, whether the reduction is present in some patients before the start of therapy, when and by what mechanism carnitine levels may become reduced during therapy, and whether the reduction exists in the solid tissues of these patients.