Parenteral nutrition in preterm neonates with and without carnitine supplementation. Effect of intravenous L-carnitine on growth parameters and fat metabolism during parenteral nutrition in neonates. Effects of parenteral L-carnitine supplementation on fat metabolism and nutrition in premature neonates. Carnitine deficiency in premature infants receiving total parenteral nutrition: effect of L-carnitine supplementation. The metabolic effects of oral L-carnitine administration in infants receiving total parenteral nutrition with fat. Randomised controlled trial of L-carnitine as a nutritional supplement in preterm infants. [Carnitine in therapy of placental insufficiency--initial experiences]. L-carnitine supplementation in patients with advanced cancer and carnitine deficiency: a double-blind, placebo-controlled study. Carnitine for the treatment of idiopathic asthenospermia: a randomized, double-blind, placebo-controlled trial.
The effects of carnitine supplementation on fat and glucose metabolism and carnitine balance were studied in 12 preterm neonates receiving full or partial parenteral nutrition (PN) for 5 to 21 days. The gestational age ranged from 27 to 32 weeks and the birth weight from 790 to 2090 g. The neonates were assigned at random to receive either L-carnitine 10 mg/kg (n = 6) or saline (n = 6). In the carnitine group, increased concentrations in plasma of total and free carnitine were observed. Less than 50% of the given dose was recovered in urine. In the placebo group no changes in the total plasma carnitine concentration were seen. In all neonates plasma triglycerides, free fatty acids, glycerol, alanine, 3-hydroxybutyrate (BOB), glucose and lactate were measured at predetermined intervals. The only significant difference between the groups was higher BOB-concentrations in the carnitine group 2 days after the start of parenteral nutrition. Elevated BOB concentrations are an indicator of improved fatty acid oxidation in the carnitine group. In this study, only a temporary effect of the carnitine supplementation was found. To determine whether intravenous carnitine can improve nutritional indices, neonates requiring parenteral nutrition were randomized into carnitine treatment (n = 23) and control (n = 20) groups. Observed plasma lipid indices, carnitine and nitrogen balances, and plasma carnitine concentrations were not different in the prestudy period. Under standardized, steady-state conditions, 0.5 g/kg Intralipid was administered intravenously over 2 hr prior to carnitine administration, after infants received 7 days of 50 mumol/kg/day, and after a second 7 days of 100 mumol/kg/day of continuous intravenous L-carnitine as part of parenteral nutrition. Triglyceride (TGY), free fatty acid (FFA), acetoacetate (AA), beta-hydroxybutyrate (BOB), and plasma carnitine concentrations were measured prior to and at 2, 4, and 6 hr after the initiation of the lipid bolus. Twenty-four-hour urine collections for nitrogen and carnitine balance were obtained on days 7 and 14. Neonates receiving carnitine had significantly greater concentrations of plasma carnitine on days 7 and 14 (p less than 0.001). Greater nitrogen (p less than 0.05) and carnitine (p less than 0.001) balances and weight gain (week 2, p less than 0.05) were found in the carnitine-supplemented group when compared with controls. On day 14, (BOB + AA)/FFA ratios were significantly higher (p less than 0.05), and peak TGY concentrations and 6-hr FFA concentrations were significantly lower (p less than 0.05) in the treatment group. Carnitine supplementation was associated with modest increases in growth and nitrogen accretion possibly by enhancing the neonate's ability to utilize exogenous fat for energy. 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. To investigate whether L-carnitine supplementation may correct nutritional carnitine deficiency and associated metabolic disturbances in premature infants receiving total parenteral nutrition, an intravenous fat tolerance test (1 gm/kg Intralipid over four hours) was performed in 29 premature infants 6 to 10 days of age (15 receiving carnitine supplement 10 mg/kg . day L-carnitine IV, and 14 receiving no supplement). Total carnitine plasma values were normal or slightly elevated in supplemented but decreased in nonsupplemented infants. In both groups, fat infusion resulted in an increase in plasma concentrations of triglycerides, free fatty acids, D-beta-hydroxybutyrate, and short-chain and long-chain acylcarnitine, but total carnitine values did not change. After fat infusion, the free fatty acids/D-beta-hydroxybutyrate ratios were lower and the increase of acylcarnitine greater in supplemented infants of 29 to 33 weeks' gestation than in nonsupplemented infants of the same gestational age. This study provides evidence that premature infants of less than 34 weeks' gestation requiring total parenteral nutrition develop nutritional carnitine deficiency with impaired fatty acid oxidation and ketogenesis. Carnitine supplementation improves this metabolic disturbance. beta-Oxidation, an important pathway in the metabolism of free fatty acids, occurs within the mitochondria in mammals. L-Carnitine is an essential cofactor in the transfer of long-chain fatty acids across the inner mitochondrial membrane. Maintenance of normal carnitine concentrations in whole blood and tissues, either through diet or biosynthesis, would appear necessary for adequate utilization of fat as an energy source. Infants, especially premature ones, without an exogenous dietary source of carnitine, have decreased plasma carnitine levels compared with infants receiving carnitine-supplemented feedings. To determine the importance of carnitine supplementation in a total parenteral nutrition program in infants in which a fat emulsion serves as a major calorie source, the following study was undertaken. Twelve infants receiving total parenteral nutrition (TPN) with fat for seven days were divided into two treatment groups. Group 1 was orally supplemented for seven days with carnitine (70 mumol/l/kg/24 h in 24 mL of 5% dextrose), while the second group received seven days of placebo supplementation (dextrose 5%, 24 cc/24 h). Plasma carnitine levels in the carnitine-supplemented group were significantly higher (29 +/- 8 nmol/mL) than in the control group (12.4 +/- 3.5 nmol/mL) after seven days of treatment. However, clearance of serum triglycerides and free fatty acids was not significantly different between the two groups. Baseline triglyceride levels in the carnitine-supplemented group were 96 +/- 42 mg/dL, increased to 242 +/- 101 mg/dL after the lipid challenge and decreased to 121 +/- 47 mg/dL two hours after the lipid infusion.(ABSTRACT TRUNCATED AT 250 WORDS) To evaluate the effect of L-carnitine supplementation (25 mg/kg/d) on the growth and incidence of hypoglycaemia in preterm infants.
                A double blind, placebo controlled randomised trial, stratified for gestational age, was conducted of 86 preterm infants between 28 and 34 gestational weeks. The median gestational ages in the carnitine group and placebo groups were 30.7 weeks (range 28.0 to 33.6) and 31.4 weeks (range 28.0 to 33.9), respectively. The median birthweights were 1.557 kg (range 0.944 to 2.275) and 1.645 kg (range 0.885 to 2.545), respectively.
                Mean plasma free carnitine concentrations were below values for normal term infants in both groups on day 1 (carnitine group 44.8 mumol/l, placebo group 25.5 mumol/l) in the placebo group on day 7 (50.7 mumol/l), but in neither group on days 14 and 28. Total, free, and acylcarnitine concentrations were significantly increased in both urine and blood in the L-carnitine group. There was no significant difference between the placebo and carnitine supplemented groups in growth rate, as assessed by weight, length, skinfold thickness and head circumference measurements, or in the incidence of episodes of hypoglycaemia.
                The addition of carnitine as a nutritional supplement at a dose of 25 mg/kg/day did not improve growth in our group of preterm infants nor protect them from episodes of hypoglycaemia. Carnitine (3-hydroxy and 4-trimethylaminobutyrate) present in all living cells, plays an important role in the oxidation of fatty acids. It is known that high dose carnitine activates surfactant synthesis. Given to women with imminent premature delivery, its benefit on the post natal period is proved. Own studies showed an increased need of carnitine during pregnancy. Therefore the questions rose if carnitine substitution improves placental insufficiency. 15 pregnant women were treated with 2 x 1 g carnitine orally for one week and with 1 x 1 g carnitine during the following 7 days when their fetus showed a retardation of 1-3 weeks. The control group were 15 untreated patients with the same problems of retardation. The placental insufficiency was diagnosed by fetometry, by blood parameters and the doppler ultrasound flow measurement. In the group of the treated patients 11 out of 15 showed an improvement, in 4 patients no effect of carnitine was seen and in 1 patient the retardation increased. In the control group 8 out of 15 patients showed a spontaneous improvement of fetal growth, 2 women did not have a change in their retardation and 5 patients had to be hospitalized because of increasing placental insufficiency. Inspite of the small number of patients a tendency towards a profit in carnitine treatment for placental insufficiency seems to be real. Carnitine deficiency is prevalent in populations with chronic illness, including cancer. In a recent open-label study, L-carnitine supplementation was well tolerated and appeared to improve fatigue and other outcomes in cancer patients. To further evaluate this finding, adult patients with advanced cancer, carnitine deficiency (free carnitine more than 35 micromol/L for males or less than 25 micromol/L for females, or acyl/free carnitine ratio of more than 0.4), moderate to severe fatigue, and a Karnofsky Performance Status (KPS) score of 50 or more, were randomly assigned to receive either L-carnitine (0.5 g/day for two days, followed by 1g/day for two days, and then 2g/day for 10 days) or placebo. This double-blind phase was followed by an open-label phase, during which all patients received L-carnitine supplementation for two weeks. Outcomes included the fatigue subscale of the Functional Assessment of Cancer Therapy-Anemia (FACT-An), the Linear Analog Scale Assessments (LASA), the Mini-Mental State Exam (MMSE), and the KPS. Twenty-nine patients (12 placebo, 17 L-carnitine) were included in the intent-to-treat (ITT) analysis. From baseline to the end of the double-blind phase, serum total and free L-carnitine increased from 32.9+/-3.8 to 56.6+/-20.5 (P=0.004), and from 22.9+/-19.4 to 45.3+/-17.2 (P=0.004), respectively, in the L-carnitine-treated group, and from 28.2+/-10.2 to 36.2+/-8.7 (P=ns), and from 22.6+/-7.9 to 28.7+/-8.6 (P=ns) in the placebo group, respectively. The planned ITT analysis revealed no significant improvement in any of the study's endpoints, and these negative findings were not different when data from two patients who did not adhere to the protocol were eliminated. However, an exploratory covariate analysis that excluded these two protocol violators and included outcome data from both the double-blind and open-label phases demonstrated significantly improved fatigue on the FACT-An fatigue subscale (P<0.03), and significantly improved FACT-An functional well-being subscale (P<0.03), and KPS (P<0.003), in the group that started with L-carnitine during the double-blind phase. These data do not support the conclusion that L-carnitine in the doses tested reverses cancer-related fatigue in carnitine-deficient patients. However, L-carnitine supplementation does increase L-carnitine serum levels, and the positive findings in an exploratory analysis justify a larger study to determine if this strategy could be of benefit for a subpopulation of cancer patients. To determine the effect of oral carnitine supplementation on the semen parameters of men with idiopathic asthenospermia.
                Prospective, randomized, double-blind placebo-controlled study.
                Academic tertiary referral centers.
                Male patients presenting with infertility and with sperm motility of 10%-50% were selected.
                Patients were randomized to 24-week treatment arms of oral carnitine (2,000 mg L-carnitine and 1,000 mg L-acetyl-carnitine per day) or placebo.
                Sperm motility and total motile sperm counts at baseline, 12 weeks, and 24 weeks. Seminal plasma and sperm free, acetyl, and total L-carnitine levels at baseline and at week 24.
                Twenty-one patients entered the study, with 12 patients in the carnitine arm and 9 in the placebo arm. There were no significant differences in baseline semen parameters between the carnitine and placebo arms. There was no statistically significant or clinically significant increase in motility or total motile sperm counts between baseline, 12 week, or 24 weeks in the carnitine or placebo arms.
                Carnitine supplementation demonstrated no clinically or statistically significant effect on sperm motility or total motile sperm counts in men with idiopathic asthenospermia.
We found no evidence to support the routine supplementation of parenterally fed neonates with carnitine.