Subject Index to Volume 5

Background: Previous investigations have shown that plasma free choline decreases during long distance running.

Objective: This study was undertaken to determine if body choline status changes during a marathon run and whether performance is thereby adversely affected.

Design: Twenty-three accomplished marathon runners 25 to 49 years of age were studied before and after the 1997 Houston-Methodist Marathon. Fasting blood and five-hour urine samples were obtained in the morning, 14 days prior to the race, immediately after the race and approximately 48 hours after completion of the race. Runners were asked to predict their finish times two weeks prior to the race. Performance was indicated by the ratio of predicted to actual time.

Results: Both plasma free and phospholipid-bound choline concentrations as well as urinary free choline concentration decreased immediately following the race (19.2±4.5 to 14.6±4.2 nmol/mL, p=0.005, and 2565.2±516.4 to 2403.4±643.0 nmol/mL, p=0.068, respectively) and, except for the phospholipid-bound choline, rebounded towards baseline after 48 hours (15.6±3.2 and 2299.9±426.7 nmol/mL), although plasma concentrations remained significantly below baseline. Plasma free and phospholipid-bound choline concentrations were significantly correlated (r=0.46, p=0.0001), although urinary free choline concentration was not correlated with either. There was no correlation between plasma free, phospholipid-bound or urinary free choline concentration and actual finish time or the ratio of predicted to actual finish time. However, the percent decrease in urinary free choline concentration was significantly correlated with the ratio of predicted to actual time (r=0.47, p=0.036). No relationship was seen between this ratio and the percent decrease in either plasma free or phospholipid-bound choline concentrations immediately after the race.

Conclusion: Our finding of both decreased free and phospholipid-bound choline suggests the decrease in choline status is related to accelerated choline metabolism or enhanced choline uptake by tissues rather than decreased hepatic choline release. The role of choline supplementation during endurance running requires further investigation.     

The effect of lecithin supplementation on plasma choline concentrations during a marathon

BACKGROUND: Previous studies have shown that plasma and urinary free choline concentrations decrease significantly during a marathon, and that these decreases may be associated with decreased performance. OBJECTIVE: In a pilot study, we sought to determine whether lecithin supplementation prior to a marathon would maintain plasma free and urinary choline concentrations and improve performance versus placebo. METHODS: 12 accomplished marathon runners, males (7) and females (5), 21 to 50 years of age were randomized to receive lecithin (4 capsules BID; PhosChol 900) or placebo beginning one day prior to the 2000 Houston-Methodist Health Care Marathon. The lecithin supplement provided approximately 1.1 g of choline on a daily basis (2.2 g total). Runners estimated finish time based on recent performance and training. Fasting, pre- and post-marathon plasma and a five-hour urine collection were analyzed for free choline and plasma for phospholipid-bound choline. Pre-race predicted, as well as the actual finish time, were recorded. RESULTS: All subjects completed the marathon. Plasma free choline decreased significantly in the placebo group and increased significantly in the lecithin group (9.6 +/- 3.6 to 7.0 +/- 3.6 nmol/mL vs. 8.0 +/- 1.2 to 11.7 +/- 3.6 nmol/mL, p = 0.001 for the delta between groups). No significant changes in plasma phospholipid-bound choline concentration were observed. There was a non-significant decrease in urine free choline in both groups. Actual finish time was 256.3 +/- 46.3 minutes for the lecithin group vs. 240.8 +/- 62.0 for the placebo group and the actual:predicted time was 1.03 +/- 0.06 (lecithin) and 1.07 +/- 0.08 (placebo), p = 0.36. CONCLUSION: Short-term lecithin supplementation prior to a marathon maintains normal plasma free choline concentration during the race, but failed to improve performance.     

The Effect of Lecithin Supplementation on Plasma Choline Concentrations During a Marathon

Background: Previous studies have shown that plasma and urinary free choline concentrations decrease significantly during a marathon, and that these decreases may be associated with decreased performance.

Objective: In a pilot study, we sought to determine whether lecithin supplementation prior to a marathon would maintain plasma free and urinary choline concentrations and improve performance versus placebo.

Methods: 12 accomplished marathon runners, males (7) and females (5), 21 to 50 years of age were randomized to receive lecithin (4 capsules BID; PhosChol 900) or placebo beginning one day prior to the 2000 Houston-Methodist Health Care Marathon. The lecithin supplement provided approximately 1.1 g of choline on a daily basis (2.2 g total). Runners estimated finish time based on recent performance and training. Fasting, pre- and post-marathon plasma and a five-hour urine collection were analyzed for free choline and plasma for phospholipid-bound choline. Pre-race predicted, as well as the actual finish time, were recorded.

Results: All subjects completed the marathon. Plasma free choline decreased significantly in the placebo group and increased significantly in the lecithin group (9.6 ± 3.6 to 7.0 ± 3.6 nmol/mL vs. 8.0 ± 1.2 to 11.7 ± 3.6 nmol/mL, p = 0.001 for the Δ between groups). No significant changes in plasma phospholipid-bound choline concentration were observed. There was a non-significant decrease in urine free choline in both groups. Actual finish time was 256.3 ± 46.3 minutes for the lecithin group vs. 240.8 ± 62.0 for the placebo group and the actual:predicted time was 1.03 ± 0.06 (lecithin) and 1.07 ± 0.08 (placebo), p = 0.36.

Conclusion: Short-term lecithin supplementation prior to a marathon maintains normal plasma free choline concentration during the race, but failed to improve performance.     

Choline deficiency is associated with increased risk for venous catheter thrombosis

BACKGROUND: Patients with intestinal failure who require long-term parenteral nutrition (PN) develop catheter thrombosis as a complication. This patient group may also develop choline deficiency because of a defect in the hepatic transsulfuration pathway in the setting of malabsorption. This study was undertaken to determine whether choline deficiency is a risk factor for development of catheter thrombosis. METHODS: Plasma free and phospholipid-bound choline concentrations were measured in a group of 41 patients that required long-term PN. Episodes of catheter thrombosis from onset of PN to the time of blood testing were recorded. RESULTS: Sixteen (39%) patients developed catheter thrombosis, and 5 of these had recurrent catheter thrombosis. Plasma free choline was 7.7 +/- 2.7 nmol/mL in patients with no history of catheter thrombosis and 6.2 +/- 1.7 nmol/mL in patients with previous catheter thrombosis (p = .076 by Wilcoxon rank-sum test). The partial correlation between plasma free choline concentration and the frequency of clots after controlling for catheter duration was r = -0.33 (p = .038). The relative risk for catheter thrombosis in subjects with a plasma free choline concentration <8 nmol/mL was 10.0, 95% confidence interval (1.134-88.167). Plasma phospholipid-bound choline concentration was 2191.7 +/- 679.0 nmol/mL in patients with previous catheter thrombosis and 2103.3 +/- 531.2 nmol/mL in patients without history of catheter thrombosis (p = NS). CONCLUSION: Choline deficiency is a significant risk factor for development of catheter thrombosis in patients with intestinal failure who require PN.     

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.     

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.     

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.     

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.     

Dietary folate intake, blood folate status, and urinary folate catabolite excretion in Korean women of childbearing age

This study assessed folate intake, folate concentrations in plasma and erythrocytes, plasma total homocysteine (tHcy) concentrations, and urinary excretion of folate metabolites in Korean women of childbearing age. A total of 36 women voluntarily participated in this study. Precise dietary intake for 3 consecutive days was determined by weighing all foods consumed, and folate intake was calculated with a computer-aided dietary analysis system. Folate concentrations in plasma and erythrocytes were determined via microbiological methods and in plasma by HPLC. Urine excreted over the same period of time was collected and assayed for folate catabolites, para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (ApABG) by reverse-phase HPLC after affinity chromatography. The mean folate intake was 206.9+/-90.8 mug DFE/d, and the mean concentrations in plasma and erythrocytes were 10.5+/-3.7 and 249.9+/-77.8 ng/mL, respectively. Erythrocyte folate concentration was low in 2.8% of the subjects (<140 ng/mL) and was marginal in 5.5% (140-156 ng/mL). The mean plasma tHcy concentration was 12.7+/-0.2 nmol/mL, and 11% of the subjects evidenced hyperhomocysteinemia (>/=15 nmol/mL). The mean urinary excretion levels of pABG and ApABG were 10.7+/-3.8 and 89.1+/-19.5 nmol/d, respectively. The means of folate reserve and folate turnover rate were 26.2+/-11.6 and 10.5+/-3.9, respectively. We noted positive relationships between folate intake and the folate concentrations in plasma and erythrocytes, as well as the urinary excretions of ApABG and total folate catabolites. In addition, the erythrocytic folate concentrations were positively associated with the urinary excretions of ApABG and total folate catabolites. In conclusion, the folate status of Korean women of childbearing age was marginally deficient with inadequate concentrations of erythrocyte folate and elevated plasma tHcy, largely due to insufficient folate intake. The marginally deficient folate status was confirmed by the low excretion of folate catabolites in urine.     

Plasma choline concentration in humans fed parenterally

Choline is an essential nutrient for some mammals; it is used for membrane and neurotransmitter synthesis. We analyzed plasma samples, obtained periodically during TPN therapy, for choline concentration. Malnourished patients referred to a nutrition support service were prospectively assigned to be treated with daily infusions of amino acids with, and without, supplemental daily infusions of lipid emulsion for a period of 1 wk. After the first week, all subjects received intravenous lipid, and most were offered enteral food supplements. Initial plasma choline concentrations in the 25 malnourished patients were significantly lower than those measured in plasma samples from 23 hospitalized patients known to be eating well (6.5 +/- 0.6 vs 9.7 +/- 0.7 nmol/ml; mean +/- SEM; p less than 0.001). During the first week of TPN therapy, plasma choline concentrations in the lipid-restricted group tended to decrease (from 7.3 +/- 1.0 to 4.7 +/- 0.5 nmol/ml; mean +/- SEM; p less than 0.05), while in the lipid-supplemented group plasma choline tended to increase (from 5.6 +/- 0.5 to 6.2 +/- 0.7 nmol/ml; mean +/- SEM; p less than 0.05). Plasma choline concentration increased during wk 2-4, when all patients were treated with lipid emulsions, and some were offered enteral foods. We conclude that malnourished humans who eat no choline have diminished stores of plasma (and possibly tissue) choline.     

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.     

The significance of plasma lysophospholipids in patients with renal failure on hemodialysis

Abnormal phospholipid metabolism may play an important role in the progression of atherosclerosis in renal failure. We analyzed plasma phospholipid and lysophospholipid contents and fatty acid composition in the phospholipids of 18 patients with renal failure on hemodialysis (HD) and compared the levels with those of healthy controls. HD patients had a notably higher molar ratio of the plasma lysophosphatidylcholine (lysoPC)/phosphatidylcholine (PC) distributed from 0.072 to 0.207, and the control group showed a ratio lower than 0.150. Plasma phosphatidylethanolamine (PE) concentration significantly increased in HD patients compared with control subjects. A much higher level of plasma lysophosphatidic acid (lysoPA) (1.41 +/- 0.16 nmol/mL) was observed in HD patients compared with controls (0.54 +/- 0.08 nmol/mL). A strong correlation was found between plasma lysoPA and lysoPC concentrations (r = 0.609, p < 0.01) in HD patients. Serum inorganic phosphate (P) concentration was associated with the abnormal plasma lysoPC/PC, PE, and lysoPA levels in HD patients. Important decreases in eicosapentaenoic acid (EPA) of plasma PC and of dietary intake were observed in HD patients. Plasma thiobarbituric acid reactive substance (TBARS) concentration was negatively correlated with the amount of vitamin E intake in both subjects. These findings demonstrated the specific characteristics of the abnormal phospholipid metabolism in HD patients. The cause and consequences of elevated lysoPC/PC molar ratio and lysoPA in the plasma of HD patients remain to be established.     

Plasma B-6 vitamer changes following a 50-km ultra-marathon

The purpose of this study was to measure plasma B-6 vitamers, and other factors which may affect the plasma concentrations of these vitamers under extreme physical conditions. Blood samples were drawn from 8 men and 3 women (43.7 +/- 8.6 years) 30 min prior to the start of a 50-km ultramarathon race (pre), and at 5 (PST) and 60 (PST60) min post race. HPLC was used to measure plasma pyridoxal 5O-phosphate (PLP), pyridoxal (PL), pyridoxine (PN), and 4-pyridoxic acid (4-PA). Plasma glucose, albumin, lactate, and alkaline phosphatase activity, as well as hematocrit, and hemoglobin levels were measured. Food and liquid intake was assessed during the run. There was a significant (p <.001) decrease in the plasma PLP concentration between pre and PST, with a mean decrease of 12.9 +/- 8.8 nmol/L (31% decrease). At PST60, there was a further decrease in plasma PLP concentration bringing the total decrease to 17.9 nmol/L (44%). The plasma TB6 concentration also decreased after the run, but the mean decrease was only 13.5 nmol/L (pre to PST60). PL increased 25% after the run, and did not change further at PST60. The mean plasma 4-PA concentration increased 21% post run and decreased to just below the pre-run value 1 hr post race. The plasma PLP decrease measured in the current study is not consistent with what has previously been reported during shorter length endurance studies.     

Aging does not impair the anabolic response to a protein-rich meal

BACKGROUND: Sarcopenia is a debilitating condition afflicting the elderly that may be facilitated by insufficient or ineffectual intake of dietary protein. We previously showed that free-form essential amino acids acutely stimulate muscle protein synthesis in both the young and the elderly. However, the ability of an actual protein-rich food to stimulate anabolism in the young and the elderly has not been explored. OBJECTIVE: We aimed to characterize changes in plasma amino acid concentrations and to quantify muscle protein synthesis in healthy young (41 +/- 8 y old; n = 10) and elderly (70 +/- 5 y old; n = 10) persons after ingestion of a 113-g (4-oz) serving of lean beef. DESIGN: Venous blood samples and vastus lateralis muscle biopsy samples were obtained during a primed (2.0 mumol/kg) constant infusion (0.08 mumol.kg(-1).min(-1)) of l-[ring-(13)C(6)] phenylalanine. Plasma amino acid concentrations were measured and a mixed-muscle fractional synthesis rate (FSR) was calculated during the premeal period and for 5 h after beef ingestion. RESULTS: Mixed-muscle FSR increased by approximately 51% in both the elderly (mean +/- SE measurements: 0.072 +/- 0.004%/h and 0.108 +/- 0.006%/h before and after the meal, respectively) and the young (0.074 +/- 0.005%/h and 0.113 +/- 0.005%/h before and after the meal, respectively) after beef ingestion (P < 0.001). Plasma amino acid concentrations peaked at approximately 100 min after beef ingestion in both age groups but were substantially higher in the elderly (2185 +/- 134 nmol/mL compared with 1403 +/- 96 nmol/mL; P < 0.001). CONCLUSION: Despite differences in the concentration of amino acids in the plasma precursor pool, aging does not impair the ability to acutely synthesize muscle protein after ingestion of a common protein-rich food.     

Studies of the reversible binding of biotin to human plasma

In this study we sought to determine the extent of the reversible binding of [3H]biotin to macromolecules (presumably proteins) of human plasma under physiologic conditions during physiologic time intervals ranging from minutes to days. Fresh, heparinized human plasma and [3H]biotin were incubated in 5% CO2, 95% N2 at 37 degrees C. After reaching equilibrium, free biotin was separated from bound biotin by centrifugal ultrafiltration (1500 x g for 60 min) using membranes with a molecular weight cutoff of 30,000. In a sample from a single individual, we detected a mean retentate:ultrafiltrate ratio of 1.20 +/- 0.03 (mean +/- SD, n = 14 determinations). In a group of 10 healthy adults, the mean retentate:ultrafiltrate ratio was 1.17 +/- 0.02; thus, approximately 8% of the biotin in the combined pool of free and reversibly bound biotin is bound. No consistent change in retentate:ultrafiltrate ratio was detected for total biotin concentrations ranging between 500 fmol/mL and 2 nmol/mL, but the ratio decreased to 1.1 at 400 nmol of biotin per mL. Thus, the biotin-binding system of human plasma appears to be a low affinity, high capacity system. A similar biotin-binding system was detected in experiments with purified human serum albumin. These results provide evidence that the majority of added [3H]biotin does not bind to plasma protein under physiologic conditions. To the extent that added [3H]biotin can be assumed to reflect reversible binding of endogenous unlabeled biotin, we infer that endogenous, reversibly bound biotin can account for no more than one-tenth of the increase in biotin detected after acid hydrolysis of plasma.     

Food intake and electrolyte status of ultramarathoners competing in extreme heat

OBJECTIVE: To relate changes in laboratory indices to dietary intake during extremely prolonged running and to determine if dietary intake influences the ability of runners to finish an 160 km trail race. METHODS: We monitored intake and serum chemistries of 26 runners competing in an 160 km foot race in temperatures which peaked at 38 degrees C. Blood was drawn pre-, mid- and post-race. Dietary intake and incidence of gastrointestinal distress or changes in mental status were determined by interview with runners approximately every 13 km. Twenty-three runners completed at least 88 kms and, of these 23 runners, 13 finished 160 km in a mean time of 26.2 +/- 3.6 hours. RESULTS: Finishers ingested nearly 30,000 J, 19.4 +/- 8.1 L of fluid and 16.4 +/- 9.5 g of sodium (Na). Sodium and fluid intake per hour was estimated to be 0.6 g/hour and 0.7 L/hour, respectively. Electrolyte intake during the first half of the race was similar between those that finished the race and those that did not. Finishers ingested fluid at a greater rate than non-finishers (p = 0.01) and tended to meet their caloric needs more closely than did non-finishers (p = 0.09). Body weight was unchanged over time (ANOVA, p = 0.52). Serum Na concentration tended to fall from 143 to 140 mEq/L during the race (p = 0.06), and was inversely correlated with weight loss (p = 0.009). Serum Na concentration was lower mid-race in runners experiencing changes in mental status than in runners without changes (p = 0.04). Fluid intake was inversely correlated with serum Na concentrations (p = 0.04). Most of the runners experienced nausea or vomiting; these symptoms were not related to serum sodium concentration. Hyponatremia (<135 mEq/L) was seen in one runner at 88 kms, but resolved by 160 km. Urinary sodium excretion decreased (p = 0.002) as serum aldosterone concentration increased pre- to post-race (p < 0.001). From start to finish of the race plasma volume increased by 12%. CONCLUSIONS: Food and fluid was ingested at a greater rate than described previously. Runners consumed adequate fluid to maintain body weight although dietary sodium fell far short of the recommended 1 g/hour. The rate of fluid intake was greater in finishers than in non-finishers, and finishers tended to more nearly meet their energy needs. Maintenance of body mass despite large exercise energy expenditures in extreme heat is consistent with fluid overload during a running event lasting more than 24 hours in hot and humid conditions.     

Alcohol intake and methylenetetrahydrofolate reductase polymorphism modify the relation of folate intake to plasma homocysteine

BACKGROUND: Folate intake increases plasma folate and reduces total homocysteine (tHcy) concentrations, which may lower coronary artery disease (CAD) and cancer risks. Folate metabolism may be altered by alcohol intake and 2 common polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, 677C-->T and 1298A-->C. OBJECTIVE: We examined whether the associations between folate intake and plasma folate and tHcy concentrations were modified by alcohol intake or variations in the MTHFR gene. DESIGN: We conducted a cross-sectional analysis among 988 women by using multivariate linear regression models to estimate mean plasma tHcy and folate concentrations. Folate intake was the sum of food and supplemental sources. RESULTS: We observed an inverse association between folate intake and tHcy, which was modified by alcohol intake (P for interaction = 0.04) and MTHFR677 genotype (P for interaction = 0.05) but not by MTHFR1298 genotype (P for interaction = 0.97). In the lowest quintile of folate intake, moderate drinkers (>/=15 g alcohol/d) had significantly higher tHcy concentrations (15.2 +/- 2.9 nmol/mL) than did light drinkers (11.3 +/- 0.7 nmol/mL) and nondrinkers (11.0 +/- 0.8 nmol/mL). However, the reduction in tHcy between the highest and lowest quintiles of folate intake was significantly greater in moderate drinkers (-6.6 nmol/mL) than in light drinkers (-2.3 nmol/mL) and nondrinkers (-2.1 nmol/mL). The elevated tHcy in women with low folate intake who also consumed moderate amounts of alcohol was even higher (22.4 +/- 4.8 nmol/mL) in the presence of the variant MTHFR677 allele. The positive association between folate intake and plasma folate was somewhat modified by alcohol intake (P for interaction = 0.08) but not by either MTHFR genotype. CONCLUSIONS: Moderate alcohol intake and low MTHFR activity have adverse effects on tHcy, but those effects may be overcome by sufficient folate intake.     

Short-term vitamin E supplementation before marathon running: a placebo-controlled trial.

Gastrointestinal complaints and occult bleeding have been commonly described in marathon runners. We hypothesized that these complaints may arise from intestinal ischemia caused by the shunting of blood away from the splanchnic circulation during endurance racing followed by reperfusion injury. Studies in animal models have suggested prophylactic vitamin E supplementation may prevent this type of injury. We sought to determine if prerace vitamin E supplementation would prevent intestinal ischemia/reperfusion injury in humans. Forty subjects who planned to complete the 1996 Houston-Tennaco Marathon were randomized to receive vitamin E (1000 IU daily) or placebo (soya lecithin) for 2 wk before the race in a double-blinded trial. Inclusion criteria included no use of non-steroidal anti-inflammatory drugs (NSAIDs) within 24 d of the race or vitamin or mineral supplements containing vitamins C or E or selenium within 30 d of the race. Subjects were studied 2 wk before the race and immediately following the race. Blood was obtained for serum vitamin E and total lipid and salicylate concentrations. A solution of lactulose (5 g) and mannitol (2 g) was consumed and urine was collected for 6 h. Aliquots were assayed for lactulose and mannitol concentration. Stool samples were tested for occult blood and following the race subjects rated their nausea, abdominal pain, and cramping on a 1-5 scale. Twenty-six subjects (24 male, 2 female) completed the marathon. Finish times ranged between 2 h 43 min and 5 h 28 min. All subjects had heme-negative stool prerace and four developed heme-positive stool postrace, with no difference between vitamin E and placebo groups (Fisher's exact = 0.63). All had non-detectable salicylate concentrations pre- and postrace. Serum vitamin E concentration increased in botPP = 0.02 in the vitamin E group and 1.45 +/- 0.40 to 1.66 +/- 0.48 mg/dL in the placebo group, P = 0.02). However, the serum vitamin E: total lipid ratio increased significantly in the vitamin E-supplemented group (0.0022 +/- 0.0002 to 0.0051 +/- 0.0015, P = 0.02), but not in the placebo group (P = 0.25). Overall, the urinary lactulose:mannitol ratio increased from 0.03 +/- 0.02 to 0.06 +/- 0.08 postrace (P = 0.06) without difference between vitamin E or placebo groups. Intestinal permeability increased significantly more in those who developed occult bleeding. More subjects in the placebo group developed abdominal cramping (Fisher's exact = 0.04) and abdominal pain (Fisher's exact = 0.06), although there was no difference in severity between groups. There was no difference in the incidence of nausea and no diarrhea was reported by any subject. Intestinal permeability tends to increase and occult gastrointestinal bleeding occurs during endurance running, suggesting the occurrence of intestinal ischemia/reperfusion injury. Prerace supplementation with the antioxidant vitamin E had no effect on performance, intestinal injury, occult bleeding, or the severity of postrace gastrointestinal complaints. Vitamin E supplementation was associated with a decreased incidence of these complaints but had no effect on their severity.     

Serum free carnitine and total triglycerid levels in children with iron deficiency anemia

Iron deficiency anemia and hyperlipidemia are common public health problems in Turkey. The connection between iron and lipid metabolisms has not been clarified yet. The aim of the study was to determine the effect of iron deficiency on carnitine and lipid metabolism. Study group was consisted of 70 children (mean age 14.7 +/- 1.3 months) suffering from iron deficiency anemia and 20 healthy children (mean age 13.7 +/- 1.2 months) attended to outpatient clinics of Cumhuriyet University, Sivas were enrolled the study as the control group. Assessments of serum free carnitine concentrations, total triglyceride, total cholesterol and VLDL levels were made in both groups. The mean serum free carnitine concentration was significantly lower than the control group (18.9 +/- 0.43 nmol/ml and 45.9 +/- 1.47 nmol/ml respectively, t = 17.5 p < 0.01). Results of our study also indicated higher serum total triglyceride, total cholesterol and VLDL levels in iron deficient patients than the healthy controls. Regression analyses indicated a negative correlation between serum free carnitine and total triglyceride levels in iron deficient patients. This study confirms that iron deficiency anemia may be linked to the endogenous carnitine synthesis in pediatric age group, and thus hyperlipidemia appears to be a risk factor for premature cardiovascular diseases.     

Hypermanganesemia in long-term intravenous nutrition and chronic liver disease

BACKGROUND: Hypermanganesemia and cholestatic liver disease are both recognized complications of long-term IV nutrition. Manganese is primarily excreted in bile, and recent studies have indicated that manganese toxicity may play a role in the pathogenesis of IV nutrition-associated cholestasis. METHODS: Whole blood and plasma manganese concentrations were measured in patients receiving long-term home IV nutrition (HIN, n = 30). Whole blood manganese concentrations also were measured in patients with chronic liver disease (CLD, n = 10) and control subjects (n = 10). RESULTS: Whole blood manganese concentrations of all CLD patients were within the reference interval (73 to 210 nmol/L) and were not different from those of the control group (151 +/- 44 nmol/L, CLD vs 155 +/- 35 nmol/L, control; not significant), despite the presence of cholestasis. In contrast, whole blood manganese concentration was increased (>210 nmol/L) in 26 patients, and plasma manganese concentration increased (>23 nmol/L) in 23 of the patients receiving HIN. None of the patients exhibited neurologic signs of manganese toxicity. There was no correlation between whole blood manganese concentrations and markers of cholestasis, IV manganese intake, or duration of HIN. However, plasma manganese concentration correlated both with average weekly IV manganese intake (r = .44, p = .02) and with gamma-glutamyl transferase (r = .43, p = .02) and alkaline phosphatase activities (r = .55, p = .003). CONCLUSIONS: Cholestatic liver disease does not appear to contribute to increased whole blood manganese concentrations in patients not receiving HIN. Plasma manganese concentrations in patients receiving HIN reflect recent manganese exposure and impaired excretion where cholestasis is present. The lack of relationship between plasma and whole blood manganese concentrations suggests that factors other than manganese intake and excretion affect intracellular concentrations.