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ABSTRACT: The objective of this study was to determine the Ile requirement in early (d 39 to 61) and late (d 89 to 109) pregnancy using the indicator AA oxidation method. The same 7 Large White × Landrace sows in their fourth parity were used in early and late pregnancy. Each sow received 6 diets based on corn, corn starch and sugar in both early and late pregnancy at constant feed allowances (2.5 kg/d). Diets provided Ile at 20,40, 60, 80,100, and 120% of the Ile requirement (6.2 g/d based on the 1998 NRC) in early and 60, 80, 100, 140, 160, and 180% in late pregnancy. After determination of (13)C background in expired CO2 and plasma free Phe for 1.5 h when confined in respiration chambers, sows were fed the tracer, L[1-(13)C]Phe, a rate of 2.0 mg/(kg BW·h) over 4 h divided into eight 30-min meals. Expired CO2 and plasma free Phe were analyzed for (13)C enrichment above background. Requirements were determined as the breakpoint in 2-phase nonlinear models. Sow BW was 246.5 kg in early and 271.6 kg in late pregnancy. Daily gain of the 6 sows was similar in early (344 g/d) and late pregnancy (543 g/d). During pregnancy, sow maternal gain was 19.1 ± 4.4 kg and litters of 17.7 ± 0.8 piglets weighed 22.6 ± 0.9 kg at birth. The Ile requirement was 3.6 ± 1.2 g/d (P = 0.001) in early pregnancy with a Phe retention (-0.59 g/d) and energy retention (-0.31 MJ/d) that were not different from zero. This indicates that the fourth parity sows had requirements close to maintenance in early pregnancy. The Ile requirement in late pregnancy was 9.7 ±1.9 g/d (P = 0.001) when sows retained 3.30 g/d of Phe and -1.45 MJ/d of energy. The greater Ile requirement in late pregnancy was probably caused by the increased conceptus growth after d 70 of pregnancy. Phenylalanine flux, oxidation, and non-oxidative disposal increased (P < 0.1) from early to late pregnancy, but body protein breakdown did not. Phenylalanine oxidation, non-oxidative disposal, and retention increased (P < 0.01) with increasing Ile intake in early pregnancy but were not affected by Ile intake in late pregnancy. Body protein breakdown did not respond to Ile intake in early or late pregnancy. Although energy retention was similar in early and late pregnancy, the respiratory quotient decreased (P = 0.047) from early (1.05) to late pregnancy (0.98), indicating lipid mobilization in late pregnancy when Ile was at or above the requirement. The results of this study show that the Ile requirement of sows increases from early to late pregnancy.
Journal of Animal Science 05/2013; · 2.10 Impact Factor
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ABSTRACT: Current AA recommendations for sows are to provide a fixed amount of AA intake throughout gestation; however, the demand for nutrients changes from maternal lean tissue in early gestation (EG) to fetal and mammary growth in late gestation (LG). The objective of this study was to determine the Lys requirement in EG (d 24 to 45) and LG (d 86 to 110) using the indicator AA oxidation method with simultaneous determination of heat production. Each of 7 Large White x Landrace sows received 6 diets in random order in both EG and LG. Three semi-synthetic diets (14.0 MJ ME/kg) based on corn were formulated and mixed to produce a base diet (60% of the 1998 NRC Lys requirement) and high diets for EG and LG (150 and 185% of the 1998 NRC Lys requirements, respectively). The 6 test diets provided Lys intakes of 7.5 to 19.3 g/d in EG and 8.1 to 23.7 g/d in LG. Sows were placed in respiration chambers and expired air and blood were collected every 30 min for 5.5 h. The tracer AA, L-[1-(13)C]Phe, was given orally at a rate of 2 mg/(kg BWh) over the last 4 h, divided into eight 0.5-h meals. Expired air was measured for (13)CO(2) enrichment and plasma for L-[1-(13)C]Phe enrichment and free Lys concentration. Background (13)CO(2) was subtracted from plateau (13)CO(2) enrichment. Requirements were determined using a 2-phase nonlinear model. Mean maternal gain in gestation (43.7 kg; pooled SE, 1.2 kg), litter size (14.6 total born piglets; pooled SE, 0.8), and litter weight (19.4 kg; pooled SE, 0.9 kg) did not differ between parities. Sow weight gain and BW was greater (P = 0.001) in LG (d 86 to 110) than EG (d 24 to 45). Lysine requirement was 9.4 and 17.4 g/d in EG and LG, respectively. Phenylalanine retention in LG was maximized at a Lys intake of 17.7 g/d. Heat production was greater (P = 0.069) and energy retention lower (P = 0.019) in LG compared to EG. Energy retention in LG was not different from zero. Quantitative Phe kinetics in EG were not affected by Lys intake. In LG, Phe retention increased with Lys intake (P = 0.004), while Phe oxidation decreased (P = 0.005). The Lys requirement was determined to be lower than current recommendations in EG and greater than current recommendations in LG. To meet the change in requirements, diets with increased lysine content are needed in LG. Increasing the feed allowance in LG is necessary to maintain a positive energy balance throughout gestation.
Journal of Animal Science 10/2012; · 2.10 Impact Factor
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ABSTRACT: Current AA recommendations for sows are to provide a fixed amount of AA intake throughout gestation based on the assumption that there is a constant demand for AA; however, the demand for nutrients changes from maternal lean tissue in early gestation to fetal and mammary growth in late gestation. The objective of this study was to determine the Thr requirement in early (d 35 to 53 and 25 to 55 for Exp. 1 and 2, respectively) and late (d 92 to 110 and 81 to 111 for Exp. 1 and 2, respectively) gestation using the indicator AA oxidation (IAAO) method with l-[1-(13)C]Phe as the tracer AA. A total of 14 multiparous sows were used: 6 in Exp. 1 and 8 in Exp. 2. Each sow received each of 6 diets in random order in both early and late gestation. A basal diet was formulated to contain Thr at 60% of the 1998 NRC recommendation in Exp. 1 and 20 and 60% of the 1998 NRC in Exp. 2 for early and late gestation, respectively. Crystalline l-Thr was added to create additional diets with approximately 10% incremental increases in Thr. Sows were placed in respiration chambers, and expired air and blood were collected every 30 min for 5.5 h. Tracer Phe [mg/(kg of BW·h)] was given orally over the last 4 h divided into eight 0.5-h meals. Expired air and plasma were measured for (13)CO(2) enrichment and free Thr concentration, respectively. Background (13)CO(2) was subtracted from plateau (13)CO(2) enrichment. Data were analyzed using a 2-phase nonlinear Mixed model. The overall litter size and litter weight were 13.5 ± 3.1 and 20.5 ± 3.9 kg, respectively. Based on IAAO, the Thr requirement in early gestation was 6.1 g/d (R(2) = 0.59, Exp. 1) and 5.0 g/d (R(2) = 0.71, Exp. 2). In late gestation, the Thr requirement based on IAAO was 13.6 g/d (R(2) = 0.60, Exp. 1) and 12.3 g/d (R(2) = 0.58, Exp. 2). Based on plasma Thr, the Thr requirement in early gestation was 7.0 g/d (R(2) = 0.90, Exp. 1) and 3.9 g/d (R(2) = 0.90, Exp. 2). In late gestation, the Thr requirement based on plasma Thr was 10.5 g/d (R(2) = 0.67, Exp. 2). There was a linear response to increasing Thr intake in late gestation in Exp. 1. Feeding a single amount of AA throughout gestation results in overfeeding AA in early gestation and underfeeding AA in late gestation. The 2-fold increase in Thr requirement in the last third of gestation suggests that phase feeding sows in gestation will more closely meet the demands for nutrients and that the requirement for essential AA in gestating sows should be re-evaluated in early and late gestation separately.
Journal of Animal Science 01/2011; 89(1):93-102. · 2.10 Impact Factor
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ABSTRACT: Although AA requirements for the mean in a population of growing pigs are well established, there are no direct estimates of their variability within the population. The indicator AA oxidation method allows repeated measurements in a short period of time so that the AA requirement can be determined for individual pigs. The objective was to determine the Lys requirement in individual pigs to derive a first estimate of the population mean requirement and its variability. Nine individually housed barrows (15 to 18 kg) were surgically implanted with venous catheters for isotope infusion. Pigs were offered, in random order, isonitrogenous and isoenergetic diets with one of seven Lys concentrations (4.8 to 15.5 g of Lys/kg diet, as-fed basis). The pigs were fed twice daily, except for study days when they received one-half of the daily allowance in eight equal hourly meals. After a validated minimum adaptation period, indicator (Phe) oxidation was determined for each dietary Lys level during a 4-h primed, constant infusion of L-[1-(14C)]Phe at a rate of 464 kBq/h. The Lys requirement was calculated using a two-phase linear regression crossover analysis within individual pigs. For each pig, Phe oxidation decreased linearly (P < 0.02) as the dietary Lys concentration increased until the requirement was reached; thereafter, Phe oxidation was not different. The true ileal digestible Lys requirement ranged from 7.5 to 10.6 g/kg of diet (as-fed basis) for the nine animals. The mean requirement for all pigs was 9.1 g/d (CV, 11.6%) or 93.9% (CV, 9.8%) of the predicted (NRC, 1998) requirement based on each pig's mean BW and energy intake. The measured and predicted requirements did not differ. The indicator AA oxidation method gave values for Lys requirement similar to conventional methods. The short (< 3 wk) experimental period allows, for the first time, the estimate of population variability, which provides for more accurate calculation of the effect of altering Lys intake on herd performance and production economics. This method is suitable to use with all dietary indispensable AA.
Journal of Animal Science 12/2005; 83(11):2535-42. · 2.10 Impact Factor
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ABSTRACT: A low resting metabolic rate (RMR) has been proposed as a possible cause for the increased body fat commonly seen in women compared with men. Absolute RMR is higher in men, but whether RMR adjusted for lean body mass (LBM) remains higher is unresolved. The objective of the present study was to determine whether RMR adjusted for various body composition factors differed between healthy adult men and women. Thirty men years, BMI and twenty-eight women years, BMI were included in the analyses. RMR was measured by open-circuit indirect calorimetry for 60 min. Extracellular water (ECW) was measured by corrected Br(-) space and total body water (TBW) by 2H dilution. LBM was estimated as TBW/0.732. Intracellular water (ICW) was calculated as TBW-ECW, and body cell mass (BCM) as ICW/0.732. Men were heavier and had higher BMI, LBM, BCM and ECW, but less fat mass. Absolute RMR was higher in men than women v. P<0.0001). This difference became non-significant when RMR was adjusted for LBM by ANCOVA v. P=0.2191), but remained significant when adjusted for BCM v. P=0.0249). Fat mass explained a significant amount of variation in RMR in women (r(2) 0.28, P=0.0038), but not in men (r(2) 0.03, P=0.3301). The relationships between body fat and the various subcompartments of BCM and RMR require further elucidation.
British Journal Of Nutrition 01/2002; 86(6):641-6. · 3.01 Impact Factor
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ABSTRACT: Despite early evidence suggesting that dietary cysteine has a sparing effect on methionine requirements, some recent reports question the existence of a measurable sparing capacity.
The goal of the present study was to determine whether dietary cysteine could reduce the requirement for methionine in men consuming diets with and without cysteine.
Six men were randomly assigned to receive graded intakes of methionine while fed a diet containing either no exogenous cysteine or an excess of cysteine (21 mg x kg(-1) x d(-1)). The methionine requirement was determined by measuring the oxidation of L-[1-13C]phenylalanine to 13CO2 and estimated by using a linear regression crossover analysis.
The mean and population-safe (upper limit of the 95% CI) methionine requirements in the absence of exogenous cysteine were found to be 12.6 and 21 mg x kg(-1) x d(-1), respectively. The mean and population-safe methionine requirements in the presence of excess dietary cysteine were found to be 4.5 and 10.1 mg x kg(-1) x d(-1), respectively, representing a cysteine sparing effect of 64% in a comparison of mean methionine requirements and of 52% in a comparison of population-safe methionine intakes. Furthermore, the difference between population-safe intakes with and without dietary cysteine establishes a safe cysteine intake of 10.9 mg x kg(-1) x d(-1) in the presence of adequate methionine intakes.
Our data suggest that dietary cysteine can reduce the exogenous requirement for methionine in men. These results strongly support the existence of a cysteine sparing effect in humans.
American Journal of Clinical Nutrition 01/2002; 74(6):761-6. · 6.67 Impact Factor
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ABSTRACT: Determining the sulfur amino acid (SAA) requirements of humans has remained elusive because of the complex nature of SAA metabolism. Current recommendations are based on nitrogen balance studies.
The goal of the present study was to determine the methionine requirement of men fed a diet devoid of cysteine (total SAA requirement).
Six men were randomly assigned to receive 6 graded intakes of methionine: 0, 6.5, 13.0, 19.5, 26.0, and 32.0 mg x kg(-1) x d(-1). The total SAA requirement was determined by measuring the oxidation of L-[1-13C]phenylalanine to 13CO2 (F(13)CO2)). The mean total SAA requirement was estimated with use of a linear regression crossover analysis, which identified a breakpoint of the F(13)CO2 response to methionine intake.
On the basis of the mean measures of F(13)CO2, the mean requirement and population-safe intake (upper limit of the 95% CI) of total SAAs were found to be 12.6 and 21 mg x kg(-1) x d(-1), respectively.
Although the mean SAA requirement is consistent with current guidelines for the total SAA intake, the population-safe intake is substantially higher than the currently recommended total SAA intake.
American Journal of Clinical Nutrition 01/2002; 74(6):756-60. · 6.67 Impact Factor
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ABSTRACT: Patients with cystic fibrosis (CF) and pancreatic insufficiency (PI) commonly have vitamin K deficiency, and those with CF-associated liver disease (CFLD) have universal vitamin K deficiency. We evaluated the effectiveness of an oral fat-soluble vitamin combination (ADEKs) to treat patients with vitamin K deficiency.
Patients with PI and CF (mean age, 15 years; range, 0.6 to 46 years) including 6 with advanced CFLD were prospectively enrolled in a study of a fat-soluble vitamin combination taken on a daily basis. None had received vitamin K supplementation for at least 4 months before the study. Fat-soluble vitamin combination supplementation was given for a minimum of 4 months; the mean vitamin K intake was 0.18 mg/d (SD = 0.1, range, 0 to 0.3). The primary outcome was change in plasma PIVKA-II (prothrombin in vitamin K absence).
Before supplementation 58 (81%) of 72 patients had abnormal PIVKA-II levels (>2.9 ng/mL). After supplementation 29 (40%) had abnormal PIVKA-II levels (P =.001). All 6 patients with advanced CFLD had abnormal PIVKA-II levels (median, range of 20.8, 5.5 to 55 ng/mL) before treatment, which corrected to normal in 50% (4.1, 2.1 to 65 ng/mL). Four patients, 2 with CFLD, had a prolonged prothrombin time (>13.5 seconds) at both time periods.
An oral fat-soluble vitamin combination with a modest amount of vitamin K can, as a daily supplement, improve the PIVKA-II levels in patients with PI and CF.
Journal of Pediatrics 06/2001; 138(6):851-5. · 4.11 Impact Factor
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ABSTRACT: The currently accepted total aromatic amino acid requirement for adults is based on nitrogen balance measurements in individuals who received their intake of aromatic amino acids solely as phenylalanine.
The objective of this study was to determine the requirement for the amino acid tyrosine in healthy men receiving an adequate, but not excessive, intake of phenylalanine (9 mg x kg(-1) x d(-1)).
The effect of a graded intake of tyrosine was determined in 6 healthy men consuming energy-sufficient diets containing 1 g protein x kg(-1) x d(-1). The tyrosine requirement was determined by using indicator amino acid oxidation methodology with L-[1-13C]lysine as the indicator. Subjects were studied at each of 7 tyrosine intakes.
A graded intake of tyrosine had no effect on lysine flux. The mean tyrosine requirement was determined from the response of the oxidation of L-[1-13C]lysine to breath 13CO2. A 2-phase linear regression crossover analysis of breath 13CO2 identified the breakpoint and upper 95% confidence limit, which represents the mean and safe intakes, to be 6.0 and 7.0 mg x kg(-1) x d(-1), respectively.
The safe intake of total aromatic amino acids calculated from the present results for tyrosine and our previous estimate for phenylalanine is estimated to be 21 mg x kg(-1) x d(-1). This intake is 1.5 times the currently recommended total aromatic amino acid intake of the FAO/WHO/UNU (1985), 14 mg x kg(-1) x d(-1). Furthermore, the absolute aromatic amino acid requirement may be dependent on the proportional balance of these amino acids in the diet.
American Journal of Clinical Nutrition 03/2001; 73(2):276-82. · 6.67 Impact Factor
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ABSTRACT: Although tyrosine is considered indispensable during the neonatal period, its poor solubility has limited its inclusion in parenteral amino acid solutions to less than 1% of total amino acids. Dipeptides of tyrosine are highly soluble, have been shown to be well used and safe in animal models and humans, and, therefore, may be used as an effective means of providing tyrosine in the parenterally fed neonate. The goal of the present study was to determine the tyrosine requirement of the parenterally fed neonate receiving graded intakes of glycyl-L-tyrosine as a source of tyrosine. Thirteen infants receiving adequate energy (340 +/- 38 kJ. kg(-1).d(-1)) and protein (2.4 +/- 0.4 g.kg(-1).d(-1)) were randomized to receive parenteral nutrition with one of five graded levels of glycyl-L-tyrosine. The mean requirement and safe level of intake were estimated using a 1-(13)C-phenylalanine tracer and linear regression cross-over analysis that identified a break point in the response of label appearance in breath CO(2) (F(13)CO(2)) and phenylalanine oxidation to graded tyrosine intake. Based on the mean estimates of whole-body phenylalanine oxidation, the tyrosine mean requirement and safe level of intake were found to be 74 mg.kg(-1). d(-1) and 94 mg.kg(-1).d(-1), respectively. This represents 3.1 and 3.9% of total amino acids, respectively, considerably higher than levels found in present commercially available pediatric amino acid solutions. These data raise concern regarding the adequacy of aromatic amino acid intake in the parenterally fed neonate.
Pediatric Research 02/2001; 49(1):111-9. · 2.70 Impact Factor
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ABSTRACT: Kinetics studies in neonates are important to establish the requirement for amino acids and to understand the mechanisms of normal and altered metabolism. During kinetics experiments, plasma amino acid concentrations should be in steady state. Our objective was to determine whether 12 h of fasting, after parenteral or enteral feeding, resulted in a steady state in concentrations of amino acids. Two-day-old piglets were implanted with catheters (d 0), and randomly assigned to either intragastric (i.g., n = 6) or i.v. (n = 6) feeding. On d 5, piglets were fasted for 12 h. During the first 2 h, plasma concentrations of almost all amino acids declined except asparagine (i.g. and i.v.), tyrosine (i.v.), and glycine (i.v.), which increased. Only i.g. glycine did not change. Between 2 and 12 h, the only indispensable amino acids that did not change were phenylalanine (i.v.) and histidine (i.g. and i.v.). The branched-chain amino acids increased during this period (i.v. and i.g.). The greatest change was tyrosine, increasing 13% (i.v.) and 32% (i.g.) per hour. After 12 h of refeeding, glycine, serine, threonine, and asparagine concentrations were lower than baseline (p<0.05) in the i.v. group. In i.g. fed piglets, only threonine remained below baseline (p<0.05), and arginine was greater than baseline (p<0.05). Differences between i.v. and i.g. may be the result of impaired small intestinal metabolism secondary to parenteral feeding. In neonatal pigs, most plasma amino acids were unstable during 12 h of fasting. Thus, kinetics studies that require a steady state must be conducted in the fed state.
Pediatric Research 12/2000; 48(5):701-7. · 2.70 Impact Factor
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ABSTRACT: The amino acid requirements of the parenterally fed neonate are poorly defined. Newborn infants are at risk for amino acid deficiency and toxicity, due to lack of small intestinal metabolism and metabolic immaturity. We discuss recent evidence that identifies inadequacies of commercial amino acid solutions with respect to the balance and quantity of aromatic amino acids, and sulphur amino acids. We present data demonstrating that impaired small intestinal metabolism (or lack of first pass metabolism) alters the whole body requirement for methionine, threonine, and arginine, and discuss the potential adverse effects of excess or inadequate parenteral amino acid intake.
Current Opinion in Clinical Nutrition and Metabolic Care 08/2000; 3(4):299-304. · 4.38 Impact Factor
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ABSTRACT: In a previous study in piglets fed identical diets intravenously, intraportally or intragastrically, we determined that small intestinal atrophy affects nitrogen metabolism to a greater extent than liver by-pass. Because whole-body amino acid homeostasis is dependent on interorgan metabolism, we also measured the free amino acid concentrations in liver, small intestinal mucosa and kidney in order to study alterations in amino acid metabolism within these organs. Piglets (n = 15; 2-4 d old) were fed identical diets continuously for 8 d via gastric (IG), portal (IP) or central venous (IV) catheters. Concentrations of all measured amino acids were affected by route of feeding in one or more organs. In particular, urea cycle amino acid concentrations were altered in plasma and mucosa of IV and IP pigs, suggesting that arginine synthesis by an atrophied gut may have been limited. Furthermore, most indispensable amino acid concentrations were lower in IP pigs for all organs vs. IG pigs; however, except for phenylalanine, plasma concentrations of these amino acids were not different, demonstrating the liver's "smoothing" capability. Gut atrophy in both IV and IP pigs resulted in significantly lower concentrations of all indispensable amino acids compared with IG pigs. Alterations of all amino acids in various organs due to route of feeding suggest that more detailed analyses of regulatory mechanisms and amino acid interactions on interorgan amino acid metabolism are necessary for all amino acids.
Journal of Nutrition 06/2000; 130(5):1261-6. · 3.92 Impact Factor
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ABSTRACT: The threonine dehydrogenase (TDG) pathway is a significant route of threonine degradation, yielding glycine in experimental animals, but has not been accurately quantitated in humans. Therefore, the effect of a large excess of dietary threonine, given either as free amino acid (+Thr) or as a constituent of protein (+P-Thr), on threonine catabolism to CO(2) and to glycine was studied in six healthy adult males using a 4-h constant infusion of L-[1-(13)C]threonine and [(15)N]glycine. Gas chromatography-combustion isotope ratio mass spectrometry was used to determine [(13)C]glycine produced from labeled threonine. Threonine intakes were higher on +Thr and +P-Thr diets compared with control (126, 126, and 50 micromol x kg(-1) x h(-1), SD 8, P < 0.0001). Threonine oxidation to CO(2) increased threefold in subjects on +Thr and +P-Thr vs. control (49, 45, and 15 micromol x kg(-1) x h(-1), SD 6, P < 0.0001). Threonine conversion to glycine tended to be higher on +Thr and +P-Thr vs. control (3.5, 3.4, and 1.6 micromol x kg(-1) x h(-1), SD 1.3, P = 0.06). The TDG pathway accounted for only 7-11% of total threonine catabolism and therefore is a minor pathway in the human adult.
AJP Endocrinology and Metabolism 06/2000; 278(5):E877-84. · 4.75 Impact Factor
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ABSTRACT: This study evaluated the effect of varying levels of tyrosine intake on the estimation of phenylalanine hydroxylation. Healthy men were fed 1 g protein kg(-1) x d(-1) for a 2-day period. On the third day, subjects consumed a formula diet containing 1 g protein kg(-1) x d(-1) hourly over 10 hours, and primed hourly oral doses of L-[15N]phenylalanine and L-[3,3-2H2]tyrosine for the last 6 hours. Each subject was studied at 7 levels of tyrosine intake (3.0, 4.5, 6.0, 7.5, 9.0, 10.5, and 12.0 mg x kg(-1) x d(-1)) at a constant intake of phenylalanine (9 mg x kg(-1) x d(-1), 4.55 micromol x kg(-1) x h(-1)). Phenylalanine hydroxylation was estimated from the ratio of plasma amino acid isotope enrichment of [15N]phenylalanine and [15N]tyrosine and the tyrosine flux estimated from [2H2]tyrosine enrichment. Phenylalanine and tyrosine fluxes showed no significant response to alterations in the intake of tyrosine. Linear regression analysis showed a significant response such that the rate of phenylalanine hydroxylation decreased as tyrosine intake increased (R2 = .21; P = .003). The mean rates of phenylalanine hydroxylation were 3.89 to 8.06 micromol x kg(-1) x h(-1). Given model uncertainties, the apparent protein breakdown observed at tyrosine intake levels less than 10.5 mg x kg(-1) x d(-1), and the significant differences observed between the present data and our prior data, we cannot estimate the tyrosine requirement with any degree of certainty with the present hydroxylation results.
Metabolism 05/2000; 49(4):444-9. · 2.66 Impact Factor
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ABSTRACT: Threonine is an indispensable amino acid with a complex degradative pathway. Use of the indicator amino acid oxidation technique should provide an estimate of the threonine requirement that is not affected by its metabolic pathway.
Our objective was to determine the requirement for threonine in men by using the indicator amino acid oxidation method and to provide statistical estimates of the population mean and 95% CIs of the threonine requirement. We hypothesized that the current World Health Organization estimate of the threonine requirement, 7 mg*kg(-)(1)*d(-)(1) (based on nitrogen balance studies), is too low.
Six healthy men each received 6 different threonine intakes while consuming an energy-sufficient diet with 1.0 g L-amino acid mixture*kg(-)(1)*d(-)(1). The effect of graded alterations in dietary threonine intake on phenylalanine flux and oxidation was studied by using L-[1-(13)C]phenylalanine as the indicator amino acid.
The results of two-phase linear regression crossover analysis showed that the mean threonine requirement, based on indicator oxidation, was 19.0 mg*kg(-)(1)*d(-)(1) with an upper safe intake of 26.2 mg*kg(-)(1)*d(-)(1).
This is the first application of the indicator amino acid oxidation technique in humans to study the requirement for an indispensable amino acid with a complex degradative pathway. We found that the upper safe intake for 95% of the population is almost 4-fold higher than the current World Health Organization estimate.
American Journal of Clinical Nutrition 04/2000; 71(3):757-64. · 6.67 Impact Factor
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ABSTRACT: Cystic fibrosis related diabetes mellitus is an increasingly recognized problem as survival in patients with cystic fibrosis improves. In a 5 year retrospective study of 627 children and adults attending Toronto cystic fibrosis clinics, we identified 57 (9%) patients with cystic fibrosis related diabetes mellitus; four (1.3%) of 301 children (<18 years) and 53 (16%) of 326 adults. The development of this complication of cystic fibrosis is associated with increased mortality, deteriorations in both respiratory and nutritional status, and the development of late microvascular, but not macrovascular, diabetic complications. Unfortunately, systematic review of the literature provides few well designed studies that provide sound evidence for clinical practice. Recommendations are therefore often based on anecdote, rather than physiological or outcomes research. Dietary therapy combines the principles of the dietary management of both cystic fibrosis and diabetes mellitus, but emphasizes the need for a high energy diet (> 100% of recommended daily intake) in patients with cystic fibrosis related diabetes mellitus. The importance of calories from fat is emphasized, with no restriction on total carbohydrate intake. Insulin intake mirrors carbohydrate intake. Routine dietary therapy is straightforward, but challenges occur due to both complications of cystic fibrosis and advancing disease. If a patient with cystic fibrosis related diabetes mellitus is malnourished, overnight enteral tube feeding is often used, with an adjusted insulin regimen. There is a great need for both physiological and outcomes research to provide sound scientific evidence for the dietary treatment of cystic fibrosis related diabetes mellitus.
Clinical Nutrition 04/2000; 19(2):87-93. · 3.73 Impact Factor
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ABSTRACT: Tyrosine (Tyr) is an essential amino acid in phenylketonuria (PKU) because of the limited hydroxylation of phenylalanine (Phe) to Tyr. The recommended intakes for Tyr in PKU are at least five times the recommended phenylalanine intakes. This suggests that Phe and Tyr contribute approximately 20 and 80%, respectively, of the aromatic amino acid (AAA) requirement (REQ). In animals and normal humans, dietary Tyr was shown to spare 40-50% of the Phe requirement, proportions that reflect dietary and tissue protein composition. We tested the hypothesis that the Tyr REQ in PKU would account for 45% of the total AAA REQ by indicator amino acid oxidation (IAAO). Tyr REQ was determined in five children with PKU by examining the effect of varying dietary Tyr intake on lysine oxidation and the appearance of (13)CO(2) in breath (F(13)CO(2)) under dietary conditions of adequate energy, protein (1.5 g x kg(-1) x day(-1)), and phenylalanine (25 mg x kg(-1) x day(-1)). Lysine oxidation and F(13)CO(2) were determined using a primed 4-h oral equal-dose infusion of L-[1-(13)C]lysine. Lysine oxidation and F(13)CO(2) decreased linearly as Tyr intake increased, to a break point that was interpreted as the mean dietary Tyr requirement (16.3 and 19.2 mg x kg(-1) x day(-1), respectively). At Tyr intakes of >16.3 and 19.2 mg x kg(-1) x day(-1), lysine oxidation and F(13)CO(2), respectively, were low and constant. This represents 40.4 and 44.4%, respectively, of the total AAA intake. The current recommendations for Tyr intake in PKU patients appear to be overestimated by a factor of approximately 5. This study is the first application of the IAAO technique in a pediatric population and in humans with an inborn error of metabolism.
AJP Endocrinology and Metabolism 02/2000; 278(2):E195-201. · 4.75 Impact Factor
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A Moran,
D Hardin,
D Rodman,
H F Allen,
R J Beall,
D Borowitz,
C Brunzell,
P W Campbell,
S E Chesrown,
C Duchow, [......],
D J Klein,
Z Madhun, P B Pencharz,
A L Quittner,
M K Robbins,
T Schindler,
K Schissel,
S J Schwarzenberg,
V A Stallings,
W B Zipf
Diabetes Research and Clinical Practice 09/1999; 45(1):61-73. · 2.75 Impact Factor
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ABSTRACT: Patients with cystic fibrosis (CF) are at risk of developing vitamin K deficiency because of pancreatic insufficiency, hepatobiliary disease, or both.
Our objective was to determine the prevalence of vitamin K deficiency in unsupplemented patients with CF and to identify risk factors that might be associated with the deficiency.
Ninety-eight patients with CF-83 who were pancreatic insufficient (age: 15.2 +/- 10.7 y; range: 0.6-45.8 y), 15 who were pancreatic sufficient (age: 26.2 +/- 11.6 y; range: 6.5-45.3 y), and 62 healthy individuals (age: 16.2 +/- 12. 8 y; range: 1-45 y)-were studied prospectively. None had taken vitamin K supplements. Eight pancreatic-insufficient patients had advanced CF-associated liver disease. Plasma prothrombin in vitamin K absence (PIVKA-II) was measured by immunoassay. All control subjects had PIVKA-II concentrations <3 microg/L.
Seventy-eight percent of pancreatic-insufficient patients had PIVKA-II concentrations >/=3 microg/L (22.8 +/- 35.7 microg/L). All patients with CF-associated liver disease had abnormal PIVKA-II concentrations. The mean PIVKA-II concentration of pancreatic-insufficient patients with liver disease was greater than that of those without liver disease (46.6 +/- 65.3 compared with 15. 3 +/- 26.1 microg/L; P < 0.05). Five pancreatic-sufficient patients had mildly elevated PIVKA-II concentrations. Six (7%) pancreatic insufficient patients (3 with CF-associated liver disease) had mildly prolonged prothrombin time but no clinical bleeding. There was no correlation between PIVKA-II concentrations and severity of fat malabsorption or antibiotic use.
Vitamin K deficiency is common in unsupplemented patients with CF and pancreatic insufficiency and routine supplementation should be considered in all of these patients.
American Journal of Clinical Nutrition 09/1999; 70(3):378-82. · 6.67 Impact Factor
