title: Effects of high carnitine supplementation on substrate utilization in low-birth-weight infants receiving total parenteral nutrition. Carnitine deficiency in premature infants receiving total parenteral nutrition: effect of L-carnitine supplementation. Randomised controlled trial of L-carnitine as a nutritional supplement in preterm infants 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 Are Bilirubin and Plasma Lipid Profiles of Premature Infants Dependent on the Lipid Emulsion Infused?
abstract: 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 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 AIMS To evaluate the effect of L-carnitine supplementation ( 25 mg/kg/d ) on the growth and incidence of hypoglycaemia in preterm infants . METHODS A double blind , placebo controlled r and omised 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 . RESULTS Mean plasma free carnitine concentrations were below values for normal term infants in both groups on day 1 ( carnitine group 44.8 μmol/l , placebo group 25.5 μmol/l ) in the placebo group on day 7 ( 50.7 μmol/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 . CONCLUSION The addition of carnitine as a nutritional supplement at a dose of 25mg/kg/day did not improve growth in our group of preterm infants nor protect them from episodes of hypoglycaemia 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 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
target: 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: 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 .