Carnitine deficiency in premature infants receiving total parenteral nutrition: effect of L-carnitine supplementation. Are Bilirubin and Plasma Lipid Profiles of Premature Infants Dependent on the Lipid Emulsion Infused? Plasma and tissue levels of lipids, fatty acids and plasma carnitine in neonates receiving a new fat emulsion Parenteral nutrition in preterm neonates with and without carnitine supplementation Effects of high carnitine supplementation on substrate utilization in low-birth-weight infants receiving total parenteral nutrition. Lack of Effect of L-Carnitine Supplementation on Weight Gain in Very Preterm Infants
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 result ed 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 Summary The effect of a lipid emulsion containing longchain triglycerides ( LCT ) and supplemented with L-carnitine on plasma lipids and bilirubin in premature neonates on total parenteral nutrition was compared to that of lipid emulsions containing either LCT or a mixture of LCT and medium-chain triglycerides ( MCT ) . In a double-blind r and omized study 49 premature neonates received one of the three fat emulsions , given intravenously , over 16–20 h daily for 6 days . Plasma carnitine levels increased significantly in the supplemented group only ; the addition of carnitine did not seem to affect any of the parameters studied . Mean plasma triglycerides rose by 193 and 199 % in the carnitine-supplemented and the LCT groups , respectively , and by 314 % in the MCT/LCT group . On the sixth day of the study free fatty acids were significantly higher in the MCT/LCT group than in the other two groups . Plasma phospholipids and free cholesterol increased ( p < 0.05 ) progressively in all groups and were correlated ( r = 0.74 , p < 0.001 ) . At the end of the 6-day study all groups showed a similar decline in free and total bilirubin levels despite the significant increase in plasma lipids and free fatty acids result ing from the stepwise increase in lipid load . No correlation was found between free fatty acids and free bilirubin . Since hyperbilirubinemia and hypertriglyceridemia appear to be clinical ly independent factors , the infusion of lipids should not be withheld from jaundiced infants on total parenteral nutrition This study was undertaken to compare Intralipid ® with a new fat emulsion containing gamma‐linolenic acid and carnitine , named Pediatric Fat Emulsion 4501 , in neonates with regard to lipid and carnitine metabolism over a short period of total parenteral nutrition . There were 10 neonates in each group and they tolerated the total parenteral nutrition well . In spite of the gamma‐linolenic acid supplementation in the new emulsion , arachidonic acid decreased significantly in plasma lipid esters and adipose tissue in both groups after 5 d of treatment . Also , there was a decrease in plasma docosahexaenoic acid which was more pronounced in the treatment group . The relative percentage values of linoleic and linolenic acids in adipose tissue were increased , indicating that newborns have a rapid accretion of fatty acids . Plasma triglycerides were effectively cleared during the periods without fat infusion . In the group that received Pediatric Fat Emulsion 4501 the means of both free and total plasma carnitine concentrations increased significantly , whereas they tended to decrease in the Intralipid ® group 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 r and om 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 Parenterally fed preterm neonates are known to be at risk for carnitine deficiency . We studied substrate utilization in low-birth-weight infants receiving total parenteral nutrition ( TPN ) with ( A ) and without ( B ) supplementation of 48 mg carnitine.kg-1.d-1 on days 4 - 7 ( birth weights 1334 + /- 282 vs 1318 + /- 248 g , gestational age 32 + /- 2 vs 32 + /- 2 wk , A vs B , respectively ) . TPN consisted of 11 g glucose.kg-1.d-1 and 2.4 g.kg-1.d-1 of both protein and fat . Plasma carnitine concentrations at day 7 were for free carnitine 11.8 + /- 5.0 vs 164 + /- 56 mumol/L and for acyl carnitine 3.8 + /- 2.0 vs 33.9 + /- 15.4 mumol/L , respectively . Indirect calorimetry at day 7 showed a higher fat oxidation ( 0.21 , -0.31 to + 0.60 vs 1.18 , 0.70 to 1.95 g. kg-1.d-1 , respectively , P less than 0.02 , median and interquartile range ) in group B and a higher protein oxidation ( 0.37 , 0.30 - 0.43 vs 0.63 , 0.53 - 0.88 g.kg-1.d-1 , P less than 0.001 ) . The time to regain birth weight was also higher in group B ( 7 , 5.5 - 9 vs 9 , 7 - 14 d , P less than 0.05 ) . Carnitine supplementation and calorie intake were the best explanatory variables for metabolic rate ( R2 = 0.45 , P less than 0.002 ) . We conclude that carnitine supplementation of TPN in this dosage does not seem advisable OBJECTIVE Carnitine transfer across the placenta occurs predominantly during the third trimester . Unless L-carnitine is provided , very preterm infants develop carnitine deficiency . Although breast milk and infant formulas contain L-carnitine , parenteral nutrition solutions do not routinely provide L-carnitine . We hypothesized that prolonged L-carnitine supplementation in very preterm infants would improve weight gain and shorten length of stay in the hospital . STUDY DESIGN The study was a double-blind parallel placebo-controlled  r and omized clinical trial . Eligible patients were < 29 weeks of gestation , < 72 hours of age , and did not have a potentially life-threatening congenital malformation or hereditary metabolic disorder . Patients were stratified by gestational age ( 23 to 256/7 and 26 to 286/7 weeks ) , and r and omized to receive , either L-carnitine at a dose of 50 μmol/kg/day , or placebo . Carnitine was provided intravenously until the infants tolerated 16 ml/day of feeds . The sample size was calculated to have 80 % power to detect a 10 % increase in weight gain from birth until 36 weeks of postmenstrual age or discharge from the hospital . Secondary outcome variables included food efficiency ( defined as weight gain divided by caloric intake ) , weight gain at 4 weeks of age , time to regain birth weight and length of stay . RESULTS Among the 63 infants enrolled in the trial , 32 were r and omized to L-carnitine and 31 to placebo . L-Carnitine supplementation did not significantly affect average daily weight gain from birth until 36 weeks or hospital discharge , or any of the secondary outcome variables . CONCLUSION Prolonged supplementation of L-carnitine did not improve long-term weight gain in very preterm infants
Among infants supplemented with carnitine , there was no evidence of effect on weight gain , lipid utilization or ketogenesis .
REVIEW ER 'S CONCLUSIONS We found no evidence to support the routine supplementation of parenterally fed neonates with carnitine
BACKGROUND Carnitine , a quaternary amino acid , plays an important role in the oxidation of long chain fatty acids .
Both breast milk and infant formulas contain carnitine .
However , it is not routinely provided in parenteral nutrition solutions .
Non supplemented parenterally fed infants have very low tissue carnitine levels .
The clinical significance of this is uncertain .
Carnitine deficiency may be an etiological factor in the limited ability of premature babies to utilize parenteral lipid .
In vitro studies have suggested that fatty acid oxidation is impaired when the tissue carnitine levels fall below 10 % of normal .
Therefore relative carnitine deficiency may impair fatty acid oxidation , thus reducing the available energy and impairing growth .
OBJECTIVES The primary aim of this review is to determine whether carnitine supplementation of parenterally fed neonates will improve weight gain .
The secondary aims are to determine the effect on lipid tolerance and ketogenesis .