Plasma choline in normal newborns, infants, toddlers, and in very-low-birth-weight neonates requiring total parenteral nutrition

Choline deficiency is associated with hepatic abnormalities in adult volunteers and patients administered total parenteral nutrition (TPN). Preliminary investigation has suggested that plasma-free choline concentration (PFCh) is greater in neonatal animals, including humans, than in adults. The aims of this study were to determine the normal PFCh and phospholipid-bound choline concentration (PPLBCh) for newborns, infants, and toddlers and to determine the change during TPN. We also sought to determine the degree of fetal choline extraction, the relation between maternal and newborn plasma choline concentrations, and the relation between plasma choline status and normal newborn length, weight, and gestational age. Blood samples were obtained from 104 full-term newborns in two centers (Ben Taub and Maimonides), 25 mothers, 21 normal infants aged 20.3 +/- 11.8 wk, 12 normal infants aged 62.4 +/- 3.9 wk, and 14 preterm infants (gestational age = 28.9 +/- 2.2 wk) who required TPN. The vein PFChs were 28.1 +/- 13.0 nmol/mL (Ben Taub) and 68.1 +/- 16.9 nmol/mL (Maimonides). The artery PFChs were 27.1 +/- 13.0 nmol/mL (Ben Taub) and 57.9 +/- 11.6 nmol/mL (Maimonides). The vein PPLChs were 1004.7 +/- 246.6 nmol/mL (Ben Taub) and 1121.2 +/- 289.6 nmol/mL (Maimonides). The artery PPLChs were 1065.7 +/- 469.3 nmol/mL (Ben Taub) and 1106.9 +/- 285.8 nmol/mL (Maimonides). The vein-minus-artery differences for PFCh were 1.0 +/- 9.7 nmol/mL (Ben Taub) and 10.2 +/- 10.9 nmol/mL (Maimonides). The vein-minus-artery differences for PPLCh were -51.9 +/- 398.2 nmol/mL (Ben Taub General Hospital, Houston, Texas) and 14.4 +/- 254.3 nmol/mL (Maimonides, New York, New York). Maternal venous PFCh was 8.4 +/- 3.1 nmol/mL. Maternal venous PPLCh was 2592.1 +/- 584.0 nmol/mL (range = 1227.8-3729.0). Maternal venous PFCh correlated with newborn arterial PFCh (r = 0.53, P < 0.05) but not with newborn venous PFCh. No correlation was seen between maternal venous and newborn PPLCh. No significant differences were seen in PPLCh or choline extraction in Ben Taub versus Maimonides patients, although PFCh was significantly greater in the newborns from Maimonides (P < 0.05). The mean venous PFCh and PPLCh in the preterm infants before beginning TPN was 21.2 +/- 6.3 and 1366.8 +/- 339.1 nmol/mL, respectively. Just before initiation of tube feeding (4.0 +/- 2.7 d after TPN had been started), mean venous PFCh and PPLCh was 18.4 +/- 5.3 and 2251.8 +/- 686.9 nmol/mL, respectively. When TPN was discontinued and tube feeding increased to goal, after 10.8 +/- 10.4 d, venous PFCh and PPLCh was 22.6 +/- 8.7 and 2072.5 +/- 540.6 nmol/mL, respectively. Venous PFCh and PPLCh was 13.4 +/- 2.5 and 1827.5 +/- 327.0 nmol/mL, respectively in the older infant group. In conclusion, newborn PFCh is significantly greater than PFCh in adults but falls to adult levels within the first year of life. Low maternal PFCh may be associated with low newborn PFCh. Normal newborn plasma choline status has no bearing on intrauterine growth, although the role of maternal choline deficiency in underweight newborns is unknown. Newborn PPLCh is substantially below that of adults, which suggests its use in membrane synthesis during growth.     

Plasma choline concentrations in children requiring long-term home parenteral nutrition: a case control study.

BACKGROUND: Low plasma free choline concentration has been associated with elevated serum hepatic aminotransferase concentrations and hepatic steatosis in adults who need home parenteral nutrition (HPN). We sought to determine if plasma free choline is similarly reduced in children who need home total parenteral nutrition (TPN). METHODS: We compared the plasma free choline concentration in 21 children who required long-term HPN with 31 normal controls. Patients had received HPN for 75 +/- 13 (SD) months (range 3-206 months). All control children ingested a normal, mixed, nonvegetarian diet. RESULTS: The mean plasma free choline concentration in the children receiving HPN was significantly lower than normal children (6.6 +/- 4.3 vs 8.0 +/- 2.3 nmol/mL, p = .002). Plasma free choline concentration was correlated with age (r = -0.43, p = .049). Using multiple linear regression analysis for age, sex, and squared age (considered in order to account for possible nonlinearity between choline and age), HPN children showed a steady and significant decline in plasma free choline concentration with increased age at the rate of 0.03 nmol/mL per month. Plasma lipid bound choline concentration did not vary with age. No relationship was seen between either plasma free and lipid bound choline concentration and amount of daily IV lipid infusion. A significant negative correlation was observed between plasma free choline concentration and aspartate aminotransferase (AST) and alanine aminostransferase (ALT) (r = -0.72, p = .04 and r = -0.80, p = .02, respectively). CONCLUSION: Our data support the notion that patients who need long-term HPN without significant enteral feeding have a significant risk for the development of choline deficiency with its associated hepatic dysfunction.     

Low plasma free choline is prevalent in patients receiving long term parenteral nutrition and is associated with hepatic aminotransferase abnormalities

Hepatic transaminase abnormalities have been previously reported in patients receiving long term total parenteral nutrition (PN). We sought to determine if such abnormalities are caused by choline deficiency-induced hepatocyte damage. In 41 subjects (19 male, 22 female) aged 45.1 +/- 24.3 years (range 0.1-79 years) who have received PN for 5.5 +/- 4.7 years (range 0.1-14.5 years). We determined plasma free and phospholipid bound choline levels, serum albumin, ALT and AST. We also determined the daily volume of intravenous lipid emulsion received by the patients as well as the concentration of free choline and phospholipid bound choline in the lipid emulsion. Plasma free choline was low in 33 41 subjects (mean 7.15 +/- 2.5 nmol/ml, range 3.3-15.6, normal 11.4 +/- 3.7). Phospholipid bound choline was normal in 34 41 subjects (mean 2157 +/- 620 nmol/ml, range 1026-3887, normal 2364 +/- 774). Elevations in ALT and AST were significantly correlated with plasma free choline (r = -0.34, p = 0.03, r = -0.37, p = 0.02 respectively) but not with phospholipid bound choline. No relationship was found between age, PN duration or daily volume of intravenous lipid and plasma free or phospholipid bound choline. The lipid emulsion contained 24 +/- 6 nmol/ml of free choline and 11 630 +/- 552 nmol/ml of phospholipid bound choline. We conclude that low plasma free choline is prevalent in patients receiving long term PN and this abnormality is associated with elevated serum aminotransferases. Furthermore, intravenous lipid emulsion is an inadequate source of choline for this patient group.     

Plasma ammonia levels in preterm infants receiving parenteral nutrition with crystalline L-amino acids

In order to investigate the severity and incidence of hyperammonemia in preterm infants receiving total parenteral nutrition (TPN) with crystalline L-amino acids having high arginine content (Travasol), we determined the plasma ammonia (PA) levels in a group of 29 preterm infants on TPN, weekly and 1 wk posttherapy. Their mean gestational age was 29.9 +/- 2.6 wk and mean birth weight 1208 +/- 262 g. Thirty five blood samples obtained from 15 preterm infants not on TPN with mean gestational age 32.2 +/- 1.9 wk and a birth weight of 1495 +/- 161 g served as a control. In the parenteral nutrition group the mean PA level (140 +/- 58 micrograms/100 ml) was significantly higher (p less than 0.001) than that in the same group one week post TPN (97 +/- 34 micrograms/100 ml) and in the control group (86 +/- 35 micrograms/100 ml). The incidence of hyperammonemia (greater than 160 micrograms/100 ml) was 30% in the TPN group versus 3% in the controls (p less than 0.01). Maximal PA level during that treatment was 405 versus 216 micrograms/100 ml 1 wk post-TPN versus 163 micrograms/100 ml in the controls. The data show a significant increase in PA levels in preterm infants receiving TPN with Travasol, possibly because of its high glycine content.     

Abnormal liver function in malnourished patients receiving total parenteral nutrition: a prospective randomized study

A prospective study was performed in clinically malnourished patients in which liver function was tested during a 4-week period of total parenteral nutrition (TPN). The purpose was to determine if concomitant intravenous lipid administration would reduce liver function abnormalities noted to occur frequently in patients receiving TPN. Twenty-five patients were randomly assigned to receive either daily infusions of 200 cc of a 20% lipid emulsion with TPN or TPN without lipid for the first week. In the subsequent 3 weeks all patients received daily intravenous lipid. The early lipid treatment group received 0.7 g lipid/kg BW/day and approximately 280 mg of choline/day from the lecithin emulsifier throughout the entire study period. Liver function tests were performed twice in the first week, then weekly thereafter. There were significant (p less than 0.05) elevations in liver function tests in the early lipid treatment group (for aspartate aminotransferase in weeks 1, 2, and 3, and lactic acid dehydrogenase in weeks 2 and 3). Alkaline phosphatase activity was elevated at weeks 2, 3, and 4 for the lipid-treatment group and at week 1 for the lipid-restricted group. The two groups had a similar elevation in gamma-glutamyltransferase activity. Analysis of covariance demonstrated that the overall duration of TPN, and not the presence or absence of intravenous lipid, was significantly related to the elevations in both alkaline phosphatase and gamma-glutamyltransferase (GGT) levels. In contrast, the early intravenous administration of lipid was significantly related to the increase in aspartate aminotransferase levels. The peak increase in AST was noted at day 7 in the lipid-administration group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Abnormal liver function in malnourished patients receiving total parenteral nutrition: a prospective randomized study.

A prospective study was performed in clinically malnourished patients in which liver function was tested during a 4-week period of total parenteral nutrition (TPN). The purpose was to determine if concomitant intravenous lipid administration would reduce liver function abnormalities noted to occur frequently in patients receiving TPN. Twenty-five patients were randomly assigned to receive either daily infusions of 200 cc of a 20% lipid emulsion with TPN or TPN without lipid for the first week. In the subsequent 3 weeks all patients received daily intravenous lipid. The early lipid treatment group received 0.7 g lipid/kg BW/day and approximately 280 mg of choline/day from the lecithin emulsifier throughout the entire study period. Liver function tests were performed twice in the first week, then weekly thereafter. There were significant (p less than 0.05) elevations in liver function tests in the early lipid treatment group (for aspartate aminotransferase in weeks 1, 2, and 3, and lactic acid dehydrogenase in weeks 2 and 3). Alkaline phosphatase activity was elevated at weeks 2, 3, and 4 for the lipid-treatment group and at week 1 for the lipid-restricted group. The two groups had a similar elevation in gamma-glutamyltransferase activity. Analysis of covariance demonstrated that the overall duration of TPN, and not the presence or absence of intravenous lipid, was significantly related to the elevations in both alkaline phosphatase and gamma-glutamyltransferase (GGT) levels. In contrast, the early intravenous administration of lipid was significantly related to the increase in aspartate aminotransferase levels. The peak increase in AST was noted at day 7 in the lipid-administration group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vitamin E status of patients receiving long-term parenteral nutrition: is vitamin E supplementation adequate?

Vitamin E status of eight patients receiving total parenteral nutrition (TPN), including 10 IU of all-racemic alpha-tocopheryl acetate daily and Intralipid 20% (500 mL; 12 mg of RRR-alpha- and 92 mg of RRR-gamma-tocopherols) two to three times per week for 69 +/- 45 (mean +/- SD) months was assessed by measuring plasma and adipose tissue tocopherol concentrations. Plasma alpha-tocopherols of TPN patients were similar to controls (17.5 +/- 6.6 mumol/L vs 22.4 +/- 5.1), whereas gamma-tocopherols were significantly reduced (6.0 +/- 3.1 vs 11.2 +/- 3.6, p less than 0.03). The adipose tissue alpha- and gamma-tocopherol/triglycerides (TG) were similar (369 +/- 215 nmol/mmol vs 452 +/- 228, and 125 +/- 102 vs 140 +/- 130, respectively), but cholesterol/TG were increased in the TPN patients (7.8 +/- 2.5 mumol/mmol vs 5.1 +/- 3.5, p less than 0.05), suggesting that adipose tissue was relatively TG-depleted and tocopherol/cholesterol measurements better reflect vitamin E status. The mean alpha-tocopherol/cholesterol ratios were significantly lower in the TPN patients than the controls (55 +/- 36 vs 106 +/- 63, p less than 0.04). Thus, current vitamin E supplementation of TPN patients seems insufficient for maintenance of adequate tissue stores.     

Enteral nutrition in the early postoperative period: a new semi-elemental formula versus total parenteral nutrition

Several studies have reported that gastrointestinal (GI) intolerance symptoms are the limiting factor to enteral alimentation in the immediate postoperative period and often the reason for resorting to total parenteral nutrition (TPN). We postulated that Reabilan HN (a recently developed small peptide-based formula, in part obtained by enzyme hydrolysis of proteins) might be better absorbed and better tolerated so as to avoid the need for TPN. Accordingly, 19 patients undergoing major abdominal surgery were randomly assigned to receive Reabilan HN via jejunostomy or an equicaloric isonitrogenous TPN regimen. Both were begun 6 hr postoperatively at 25 ml/hr and increased by 25 ml/hr at 12-hr intervals up to the rate providing 1.5 times the calculated REE. GI tolerance to enteral feeding was excellent during the first three postoperative days, allowing the progression of the feeding rate to 99% of goal. During the next 3 days (starting on average 1.7 days after the return of bowel sounds), GI intolerance symptoms required a reduction in feeding rate to 52% on average. Subsequently, the symptoms resolved and the feeding rate reached 96% of goal. Although overall mean daily calorie and nitrogen intakes were lower for the enteral than for the TPN group (79.6 +/- 10.2% vs 94.6 +/- 3.8% of goal; p less than 0.01), the enteral group was nevertheless in positive caloric and nitrogen balance, and maintained similar serum albumin, prealbumin, and plasma transferrin levels. Average daily cost of supplies was $44.36 for enteral vs $102.10 for parenteral nutrition (p less than 0.001). We conclude that enteral feeding using this formula is well tolerated and cost-effective in the immediate postoperative period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relative importance of amino acid infusion as a means of sparing protein in surgical patients

We performed isotopic infusions in 51 surgical patients to investigate the effectiveness of different substrates to conserve protein. All patients were initially studied in the basal state and then the effects of glucose infusion (GL, N = 13), lipid infusion (LIP, N = 11), or amino acid infusion (AA, N = 17) were determined. Ten patients receiving total parenteral nutrition (TPN) were also studied. The basal value for net protein catabolism (NPC) in GL patients was 1.53 +/- 0.4 (SEM) g/kg/day decreasing to 1.39 +/- 0.4 g/kg/day during glucose infusion (p less than 0.01). The basal NPC in the LIP group was 2.04 +/- 0.4 g/kg/day decreasing to 1.72 +/- 0.3 g/kg/day during lipid infusion (p less than 0.01). In the TPN patients the NPC was 0.79 +/- 0.46 g/kg/day whereas in the AA patients the basal value for NPC was 1.37 +/- 0.14 g/kg/day decreasing to -0.77 +/- 0.11 g/kg/day during amino acid infusion (p less than 0.0005). From our study we conclude that: (1) All substrates commonly used in intravenous feeding have the capacity to spare protein. (2) Protein sparing was more pronounced when a balanced amino acid infusion was used than with either glucose or lipid infusion alone. (3) This effect is not solely due to insulin secretion as larger insulin responses were seen with both GL and TPN patients. (4) These results may have implications for peripheral vein feeding with amino acid solutions where there is a contraindication for full TPN or the lack of resources for administering it.     

Levels of plasma lipid peroxides before and after choledocholithotomy in patients with obstructive jaundice.

Plasma lipid peroxide levels were measured in a group of 40 healthy controls and 11 patients with jaundice. In the case of these 11 patients, we checked the plasma lipid peroxide concentrations prior to and after choledocholithotomy. Before choledocholithotomy, there were significantly higher mean concentrations of plasma lipid peroxides and bilirubin in patients with jaundice than in the control cases (11.8 +/- 2.3 vs. 2.0 +/- 0.1 nmol/ml and 10.3 +/- 1.82 vs. 0.7 +/- 0.03 mg/dl, respectively, P < 0.05). In addition, patients with jaundice had lower plasma vitamin E levels in comparison to the controls (8.2 +/- 0.6 vs. 12.2 +/- 0.5 micrograms/ml, P < 0.05). In patients with jaundice, the increased plasma lipid peroxides were clearly related to the serum levels of bilirubin (r = 0.87, P < 0.05). After surgery, the higher plasma levels of lipid peroxide and bilirubin were reduced markedly (11.8 +/- 2.3 vs. 3.7 +/- 0.4 nmol/ml and 10.3 +/- 1.82 vs. 3.1 +/- 0.47 mg/dl, respectively, P < 0.05) with the restoration of bile flow which was associated with improvement in liver function tests. Consequently, these results suggest that there is an involvement of lipid peroxidation in liver cells damaged by obstructive jaundice in patients with cholelithiasis, and that these high plasma lipid peroxide levels may correlate with the severity of the disease.     

Selenium status prior to and during one month total parenteral nutrition in gastroenterological patients: A randomised study of two dosages of Se supplementation

13 consecutive adult gastroenterological patients with non-malignant disease who were candidates for total parenteral nutrition (TPN), and who had mild protein-energy malnutrition (82 +/- 3% of ideal body weight, serum albumin 32 +/- 2 g/l, mean +/- SEM) were found to have, prior to TPN, a Selenium level 50% less than controls (p < 0.001) as assayed by Se and glutathione peroxidase (GSHPx) in plasma and erythrocytes. Compared with other trace metals and minerals, eg, Mn, Zn and Cu, depletion of Selenium was the most marked in this population. Patients were randomised to be supplemented with either 100 or 200 mug/d of sodium-selenite, equal to 32 mug (0.4 mumol) or 64 mug (0.8 mumol) of selenium, in two cross-over periods of TPN, each of two weeks. In this short term study, significant increases in the four measurements of Se status (p < 0.05) were seen in all patients, but there was no difference between those receiving the high or low dose of the element. GSHPx in plasma was normalised within 1 month whereas the increase seen in the erythrocyte pool was consistent with a 4-month half-life. Pooled Se values for patients and controls showed logarithmic correlations between Se and GSHPx in erythrocytes (p < 0.001) and plasma (p < 0.01). Changes in GSHPx provided further evidence of Se depletion in our patients. This study suggests that malnourished gastroenterological patients receiving TPN require Se supplements and that 100 mug (0.4 mumol)/d of sodium-selenite is adequate for most patients since there was no additional benefit from the higher dose of 200 mug (0.8 mumol).     

Thermogenesis from intravenous medium-chain triglycerides

Eighteen hospitalized patients dependent on total parenteral nutrition (TPN) were randomly enrolled into a prospective study comparing intravenous long-chain triglycerides (LCT) with a physical mixture of 75% medium-chain triglycerides (MCT) and 25% LCT. The TPN was given continuously as amino acids and glucose over 5 days with the respective lipid emulsion given intermittently during each day for 10 hr. Indirect calorimetry was measured on each patient before the lipid emulsion was administered in the morning and again 10 hr later near the end of the lipid infusion, on days 1, 3, and 5. Resting energy expenditure, VO2, VCO2, and calculated fat oxidation were shown to increase during MCT infusion but not during LCT administration, (resting energy expenditure 899 +/- 37 to 1085 +/- 40, compared with 978 +/- 23 to 976 +/- 39, kcal/m2 body surface area [BSA]/day, respectively, p less than 0.0002; VO2: 129.9 +/- 5.2 to 157.2 +/- 5.9, compared with 140.9 +/- 3.6 to 141.2 +/- 5.9 ml O2/min/m2 BSA, respectively, p less than 0.0005; and VCO2: 110.7 +/- 4.4 to 127.5 +/- 4.3, compared with 118.3 +/- 2.8 to 118.0 +/- 5.3, ml CO2/min/m2 BSA, respectively, p less than 0.0076; calculated fat oxidation 10.7 +/- 1.5 to 19.3 +/- 2.4, compared with 20.0 +/- 2.7 to 20.0 +/- 3.6, kcal/m2 BSA/hr, respectively, p less than 0.014). Respiratory quotient tended to fall with lipid infusion but did not change statistically. Body temperatures were unaltered by either fat infusion. It is concluded that TPN consisting of MCT causes an increased thermogenesis, most likely through increased fat oxidation, reflective of MCT's property as an obligate fuel. The increased thermogenesis occurs without an increase in body temperature.     

Effects of prolonged, purine-free total parenteral and enteral nutrition on urate homeostasis in man

The influence on human urate homeostasis of prolonged, totally purine-free nutritional support, using total parenteral (TPN) or elemental enteral (EN) nutrition, is not well known. In a prospective study, we measured weekly serum uric acid, renal urate excretion and clearance, together with parameters of hydration, in 58 normally hydrated patients receiving prolonged (15 to 170 days) purine-free TPN (30 patients) or EN (28 patients) for various gastrointestinal disorders. A marked, early and sustained decrease (p less than 0.001) in serum uric acid was observed in TPN (155 +/- 9 mumol/l at day 7 versus 318 +/- 13 mumol/l before nutrition, mean +/- SEM) as well as in EN patients (192 +/- 11 mumol/l at day 7 versus 320 +/- 16 mumol/l before nutrition), together with a significant (p less than 0.01) rise in renal urate clearance. The urate clearance/glomerular filtration rate ratio increased significantly, while there was no significant change in natremia or plasma osmolarity. Serum urate and urate clearance returned to normal within 8 days of refeeding with a normally purine-containing diet. Replacement of TPN by EN or vice versa, or substitution of glucose by fructose resulted in no change in hypouricemia. A 4-day oral supply of purines (125 mg/day) in EN patients was associated with a 53% rise (p less than 0.01) in serum urate. We conclude that prolonged, purine-free TPN and elemental EN are a new cause of marked hypouricemia which is mainly due to increased urate clearance, the mechanism of the latter is still poorly known, but is not related to extracellular volume expansion.     

The effect of 15-hour fat infusions of varying dosage on bilirubin binding to albumin

Intravenous fat emulsions (1, 2, and 3 g/kg) were administered over 15 hr to 20 appropriate for gestational age premature infants with physiologic hyperbilirubinemia to determine the effect of fat infusions on the serum free fatty acid:albumin molar ratio (F/A) and on unbound bilirubin. Significant increases (p less than 0.05) in F/A occurred with each increase in lipid dose in infants less than 30 wk gestation, but not in infants greater than or equal to 30 wk gestation. There was a direct linear correlation (r = 0.65, p less than 0.001) between F/A ratio and unbound bilirubin (estimated fluorometrically by the ratio of albumin-bound bilirubin/reserve bilirubin binding capacity, B/R). The largest increases in unbound bilirubin (albumin-bound bilirubin/reserve bilirubin binding capacity) were seen in infants with F/A greater than 4.0. The gestational age of infants with F/A greater than 4.0 was significantly less (p less than 0.01) than infants with F/A less than 4.0 (28.7 +/- 0.47 vs. 31.1 +/- 0.40 wk, mean +/- SEM). In 10/58 infusions there was a fall in unbound bilirubin, unrelated to birthweight, gestational age, postnatal age, however, during these infusions the end-infusion F/A was greater than or equal to 3.0. We conclude that 1 g/kg of lipid emulsion infused over a 15-hr period has minimal risk of decreasing bilirubin binding in premature infants less than 30 wk gestation. As doses of 2 or 3 g/kg are used, these infants may be at risk of decreased bilirubin binding, due to elevations in the F/A ratio. Monitoring of the F/A ratio may identify infants at risk for decreased bilirubin binding during lipid infusion and provide guidelines for determining the appropriate lipid dose.     

Malnutrition impairs postresection intestinal adaptation

BACKGROUND: Postresection intestinal adaptation is influenced by several factors, including luminal nutrients. Adaptation is impaired in the absence of luminal nutrients, even if the nutrition is maintained via total parenteral nutrition (TPN). Reduced enteral intake also inhibits adaptation if malnutrition is present, but the mechanism has not been completely defined. Our aim was to study the effect of reduced enteral nutrition on adaptation and enterocyte production and death after 50% proximal resection in rats. METHODS: Eighteen Lewis rats underwent either transection (n =6) or 50% proximal resection (n =12). The resected animals either ate ad libitum (n = 6) or were offered 75% of ad libitum intake (n =6). Nutritional status and intestinal adaptation were determined 14 days after surgery. RESULTS: Resected animals receiving 75% normal intake had decreased body weight (89% +/- 4% vs 112% +/- 2% and 112% +/- 1%, p < .05) and serum albumin (2.7 +/- 0.1 vs 3.2 +/- 0.0 g/dL and 3.0 +/- 0.1 g/dL, p < .05) compared with resection with normal intake and transection, respectively. Intestinal weight (0.32 +/- 03 vs 0.22 +/- 0.02 g/cm and 0.19 +/- 0.03 g/cm, p < .05) and diameter (10.5 +/- 0.5 vs 8.5 +/- 1.0 mm and 7.8 +/- 0.8 mm, p < .05) increased after resection alone compared with transection and malnourished resection groups. Gut weight and diameter and villus height were lower in malnourished resected animals than with transection. Crypt cell production rate was significantly lower in the reduced intake animals. Apoptosis was increased in both crypt and villus enterocytes in normally nourished but not malnourished resected animals. Villus apoptosis correlated with villus height. CONCLUSIONS: Intestinal adaptation is impaired by a 25% reduction in enteral nutrients, confirming that both the route and quantity of nutrient intake are important in this process. Both enterocyte production and loss via apoptosis are decreased by reduced enteral intake and malnutrition after resection. The correlation between villus height and apoptosis suggests that the reduced apoptosis reflects the smaller enterocyte number in malnourished animals rather than an adaptive response to maintain intestinal structure.     

Serum vitamin A and E concentrations in pediatric total parenteral nutrition patients

There is uncertainty as to optimal doses of fat soluble vitamins required by pediatric total parenteral nutrition (TPN) patients. We compared serum vitamin A (A) and E (E) concentrations analyzed by HPLC in chronic (greater than 2 weeks) TPN patients aged 1 month to 12 years to values obtained in out-patient surgery patients of the same age. TPN patients received 1500 micrograms of retinol and 2.5 IU of E as alpha-tocopheryl acetate (2.5 ml LyphoMed Multi Vitamin Concentrate). These doses were 214% of the recommended dose of A and 36% for E. Oral intake was minimal in most patients. The results of our study revealed a mean serum A level for TPN patients (N = 29) of 26.0 +/- 15.0 (SD) micrograms/dl vs 25.0 +/- 10.0 (SD) micrograms/dl in controls (N = 52). Mean serum E was 0.63 +/- 0.24 (SD) mg/dl vs 0.89 +/- 0.31 (SD) mg/dl for TPN patients and controls, respectively. There was no consistent trend related to duration of TPN for 23 patients with serial values. Seven (24%) TPN patients had serum A greater than mean + 2 SD of control (p less than 0.01). No values were less than mean - 2 SD. Infants on TPN had a significantly lower mean serum A (22.3 +/- 10.9 micrograms/dl) than TPN patients greater than 1 year of age (34.1 +/- 16.0 micrograms/dl; p less than 0.001). Fifty-two percent of TPN patients vs 26% of control had serum A less than 20 micrograms/dl (p greater than 0.1). For E, one patient had a high value and two patients low values relative to control.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low plasma carnitine in patients on prolonged total parenteral nutrition: association with low plasma lysine

Plasma carnitine levels were determined in 17 patients maintained on long-term total parenteral nutrition (TPN) for a mean (+/- SEM) period of 69 +/- 11 months (range 12-196). All had severe malabsorption and were dependent on intravenous feeding. Plasma carnitine was determined by a modified Cederblad enzymatic method. Mean plasma carnitine was significantly below the mean normal for females (p less than 0.02) and borderline low for males (p = 0.07). In six patients the levels were below the low normal range, and in five others they were at the lowest levels of normal. Of the six patients with normal levels, three had elevated serum creatinine, indicating renal dysfunction which may by itself elevate plasma carnitine. In 10 patients the plasma levels of lysine (a carnitine precursor) were determined and found to be lower than normal (p less than 0.05). Plasma carnitine levels correlated positively with serum albumin (r = 0.62, p less than 0.05), and negatively with serum alkaline phosphatase (r = -0.64, p less than 0.05). Thus, patients maintained on long-term TPN may have low plasma carnitine, which could represent carnitine deficiency. The low plasma carnitine may be related to a deficiency of the carnitine precursor lysine. Further studies are required to determine the significance of the low plasma carnitine and whether carnitine supplementation should be required in long-term TPN.     

Changes in plasma free and phospholipid-bound choline concentrations in chronic hemodialysis patients.

BACKGROUND: Choline deficiency may develop in malnourished patients, those with cirrhosis, and those who require total parenteral nutrition. Previous data has suggested an important role for the kidneys in the maintenance of choline homeostasis. OBJECTIVE: This study was undertaken to determine the change in plasma choline during hemodialysis and to determine if it was lost in the dialysate. DESIGN: Thirteen adult patients (10 men, 3 women) who had required hemodialysis for a mean of 10.8 years were studied. Dialysis was performed 3 times weekly for 4 hours using either a cellulose acetate or polysulfone dialyzer membrane. Venous and arterial blood, and dialysate samples were taken for measurement of plasma free and phospholipid-bound choline concentration before beginning dialysis and after each hour of dialysis. An in vitro system was devised to determine if choline could bind to a significant degree to the dialysis membrane. RESULTS: Plasma free choline concentration was increased above normal (11.7 +/- 3.7 nmol/mL) at baseline and declined progressively during dialysis. In contrast, plasma phospholipid-bound choline concentration increased progressively during dialysis. The decrease in plasma free choline (-1.8 +/- 0.3 nmol/mL(-1)/h(-1); P = 1.6 x 10(-6)) was almost entirely related to that which was removed during dialysis, although the magnitude of the loss was not correlated with the increase in plasma phospholipid-bound choline concentration (125 +/- 20.5 nmol/mL(-1)/h(-1); P < 1.2 x 10(-6)). Patients lost a mean of 246 pmol of free choline during hemodialysis. Choline did not bind to the dialysis membrane. CONCLUSION: Plasma free choline concentration is elevated before dialysis, and choline is lost to a significant degree in the dialysate. Further investigation is necessary to determine whether a transient, dialysis-induced choline deficiency develops, and whether there is a role for choline supplementation in these patients. The choline homeostatic mechanism requires further investigation in renal failure patients.     

Choline deficiency causes reversible hepatic abnormalities in patients receiving parenteral nutrition: proof of a human choline requirement: a placebo-controlled trial

BACKGROUND: Previous studies have shown that plasma free choline concentrations are significantly decreased in many long-term home total parenteral nutrition (TPN) patients. Furthermore, low choline status has been associated with both hepatic morphologic and hepatic aminotransferase abnormalities. A preliminary pilot study suggested choline-supplemented TPN may be useful in reversal of these hepatic abnormalities. METHODS: Fifteen patients (10 M, 5 F) who had required TPN for > or =80% of their nutritional needs were randomized to receive their usual TPN (n = 8), or TPN to which 2 g choline chloride had been added (n = 7) for 24 weeks. Baseline demographic data were similar between groups. Patients had CT scans of the liver and spleen, and blood for plasma free and phospholipid-bound choline, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, gamma glutamyl transferase (GGT), bilirubin, serum lipids, complete blood count (CBC), and chemistry profile obtained at baseline, and weeks 2, 4, 6, 12, 16, 20, 24, and 34. CT scans were analyzed for Hounsfield unit (HU) densities. RESULTS: There were no significant differences in any measured parameters after 2 weeks. However, at 4 weeks, a significant difference in liver HU between groups was observed (13.3+/-5.0 HU [choline] vs 5.8+/-5.2 HU [placebo], p = .04). This significant trend continued through week 24. Recurrent hepatic steatosis and decreased HU were observed at week 34, 10 weeks after choline supplementation had been discontinued. A significant increase in the liver-spleen differential HU was also observed in the choline group (10.6+/-6.2 HU [choline] vs 1.3+/-3.3 HU [placebo], p = .01). Serum ALT decreased significantly (p = .01 to .05) in the choline group vs placebo at weeks 6,12, 20, and 24. Serum AST was significantly decreased in the choline group by week 24 (p = .02). The serum alkaline phosphatase was significantly reduced in the choline group at weeks 2, 12, 20, 24, and 34 (p = .02 to 0.07). Total bilirubin was normal in these patients and remained unchanged during the study. Serum GGT tended to decrease more in the choline group, but the greater decrease was not statistically significant. CONCLUSIONS: Choline deficiency is a significant contributor to the development of TPN-associated liver disease. The data suggest choline is a required nutrient for long-term home TPN patients.     

Hyperkalemia in patients on enteral feeding

The amount of potassium (K) in proprietary enteral feeds varies considerably from 2.7-9.2 mmol K+/g N. It has been suggested that up to 7 mmol K+/g N is required by the anabolic patient. The aim of this study was to determine the effect of a proprietary feed (Triosorbon MCT), containing 6.9 mmol K+/g N, on serum and urinary K in 13 patients requiring nutritional support. Serum electrolytes in all patients and urinary electrolytes in 7 were measured both before feeding commenced and when they had achieved an intake of between 2.4 and 3.0 liter/day (102-127 mmol K+/day) of full strength feed for a period of 1 wk. Ther serum K rose in all patients from 4.2 +/- 0.5 mmol/liter (mean +/- SD) before feeding to 5.1 +/- 0.5 after feeding for 1 wk (p less than 0.001; pair-difference t-test). The daily urinary K excretion rose from 37.8 +/- 24.2 mmol/day to 61.8 +/- 26.6 over the same period (p less than 0.001) The serum urea rose from 4.7 +/- 2.0 mmol/liter to 6.3 +/- 3.2 (p less than 0.05). No significant change was observed in other serum electrolytes, creatinine, or urinary electrolytes. During the whole course of feeding (range 1-11 wk) it was necessary to discontinue Triosorbon in 2 patients whose serum K concentration became elevated to greater than 6 mmol/liter. We conclude that the recommended levels of K intake may be too high and that serum K should be carefully monitored during enteral feeding.