Dietary Lysine Requirements of Older Adults Stratified by Age and Sex.

BACKGROUND: Current recommendation for lysine in older adults, 30 mg/kg/d, is based on young adult data. Evidence suggests that amino acid requirements may differ between young and old adults with both sex and age having an effect in the elderly. OBJECTIVES: This study aimed to define the lysine requirements in healthy older adults using the indicator amino acid oxidation (IAAO) method with L-[1-13C] phenylalanine as the indicator and to compare the derived estimates based on age: 60-69 y and >70 y. METHODS: Fourteen healthy males and 16 healthy females [>60 y, body mass index (BMI) = 26.3 kg/m2] were randomly assigned to receive 3-7 lysine intakes from 10 to 80 mg/kg/d. Subjects were adapted to a standard liquid diet providing 1.0 g/kg/d protein and adequate energy, for 2 d, with indicator oxidation measurements performed on day 3. The rate of release of 13CO2 from the oxidation of L-[1-13C] phenylalanine was measured in breath. A 2-phase linear mixed-effect model, and parametric bootstrap were used to determine mean lysine requirements and the 95% confidence intervals (CIs). The overlap of the 95% CI between the 2 age groups were used to compare the requirement estimates. The null hypothesis was accepted if the interval contained zero. RESULTS: The mean and upper 95% CI of the lysine requirement for females were 32.9 and 40.9 and 46.2 and 53.7 mg/kg/d for those aged 60-69 y and >70 y, respectively. The mean and upper 95% CI of the lysine requirement for the 2 groups of males were not different so was combined to yield a mean and 95% CI of 32.2 and 38.2 mg/kg/d. CONCLUSIONS: To our knowledge, this is the first study to report on the lysine requirement in adults aged >60 y. These results provide a basis from which the adequacy of diets to meet lysine needs of older adults can be assessed. The trial was registered at clinicaltrials.gov as NCT02008955 (https://clinicaltrials.gov/study/NCT02008955).

Improved long-term outcome of children with congenital diarrhea followed by an intestinal rehabilitation program.

BACKGROUND: Long-term outcomes of congenital diarrheas and enteropathies (CODE) are poorly described. We evaluated the morbidity and mortality of children with CODE followed by an intestinal rehabilitation program (IRP) compared to children with short bowel syndrome (SBS). METHODS: Matched case-control study of children with intestinal failure (IF) due to CODE (diagnosed between 2006 and 2020; N = 15) and SBS (N = 42), matched 1:3, based on age at diagnosis and duration of parenteral nutrition (PN). Nutritional status, growth, and IF-related complications were compared. Survival and enteral autonomy were compared to a nonmatched SBS cohort (N = 177). RESULTS: Fifteen CODE patients (five males, median age 3.2 years) were followed for a median of 2.9 years. Eleven children were alive at the end of the follow-up, and two achieved enteral autonomy. The CODE group had higher median PN fluid and calorie requirements than their matched SBS controls at the end of the follow-up (83 vs. 45 mL/kg/day, p = 0.01; 54 vs. 30.5 kcal/kg/day, p < 0.01), but had similar rates of growth parameters, intestinal failure associated liver disease (IFALD), central venous catheter (CVC) complications and nephrocalcinosis. Kaplan-Meier (KM) analyses of 10-year survival and enteral autonomy were significantly lower in CODE patients compared to the nonmatched SBS population (60% vs. 89% and 30% vs. 87%, respectively; log-rank p < 0.008). CONCLUSIONS: Despite higher PN needs in CODE, rates of IF complications were similar to matched children with SBS. Enteral autonomy and survival rates were lower in CODE patients. Treatment by IRP can mitigate IF-related complications and improve CODE patient's outcome.

Length of Adaptation Has No Effect on the Threonine Requirement Determined in Healthy Young Adult Males Using the Indicator Amino Acid Oxidation Method.

BACKGROUND: The indicator amino acid oxidation (IAAO) method is minimally invasive; therefore, it is applicable to study the amino acid (AA) requirements of individuals in various age groups. However, the accuracy of this method has been criticized because of the 8 h (1 d) protocol, which has been suggested to be too short an adaptation time for estimating AA requirements. OBJECTIVES: The IAAO method was used to determine whether 3 or 7 d of adaptation to each threonine intake alters the threonine requirement in adult men compared to 1 d of adaptation. METHODS: Eleven healthy adult men (19-35 y, body mass index (BMI) 23.4 in kg⋅m-2) were studied at 6 threonine intakes; each intake was studied over a 9 d period. Following 2 d of pre-adaptation to adequate protein intake (1.0 g·kg-1⋅d-1), subjects received experimental diets containing the randomly assigned test threonine intake (5, 10, 15, 20, 25, or 35 mg·kg-1·d-1) for 7 d. IAAO studies were performed on days 1, 3, and 7 of adaptation to the experimental diet. The rate of release of 13CO2 from the oxidation of L-[1-13C]phenylalanine (F13CO2) was measured, and the threonine requirement was determined by applying mixed-effect change-point regression to the F13CO2 data in R version 4.0.5. The 95% confidence interval (CI) was calculated using parametric bootstrap, and the requirement estimates on days 1, 3, and 7 were compared using analysis of variance (ANOVA). RESULTS: The mean threonine requirements (upper, lower 95% CI) for days 1, 3, and 7 were 10.5 (5.7, 15.9), 10.6 (7.5, 13.7), and 12.1 (9.2, 15.0 mg·kg-1·d-1), respectively; and these requirements were not statistically different (P = 0.213). CONCLUSIONS: We demonstrated that the short, 8 h IAAO protocol results in a threonine requirement that is not statistically different from that obtained on days 3 or 7 of adaptation in healthy adult males. This trial was registered at www. CLINICALTRIALS: gov as NCT04585087.

Amino acid oxidation methods to determine amino acid requirements: do we require lengthy adaptation periods?

Determination of indispensable amino acid (IAA) requirements necessitates a range of intakes of the test IAA and monitoring of the physiological response. Short-term methods are the most feasible for studying multiple intake levels in the same individual. Carbon oxidation methods measure the excretion of 13CO2 in breath from a labelled amino acid (AA) in response to varying intakes of the test AA following a period of adaptation. However, the length of adaptation to each AA intake level has been a source of debate and disagreement among researchers. The assertion of the minimally invasive indicator amino acid oxidation (IAAO) technique is that IAA requirements can be estimated after only a few hours (8 h) of adaptation to each test AA intake, suggesting that adaptation occurs rapidly in response to dietary adjustments. On the contrary, the assertion of most other techniques is that 6-7 d of adaptation is required when determining IAA needs. It has even been argued that a minimum of two weeks is needed to achieve complete adaptation. This review explores evidence regarding AA oxidation methods and whether long periods of adaptation to test IAA levels are necessary when estimating IAA requirements. It was found that the consumption of experimental diets containing lower test IAA intake for greater than 7 d violates the terms of a successful adaptive response. While there is some evidence that short-term 8 h IAAO is not different among different test amino acid intakes up to 7 d, it is unclear whether it impacts assessment of IAA requirements.

Body Composition and Physical Activity in Pediatric Intestinal Failure On and Off Parenteral Nutrition.

OBJECTIVES: Data on the relationship between body composition (BC) and physical activity (PA) in children with intestinal failure (IF) are lacking. The objectives were to collect data on PA and BC in children with IF, both parenterally and enterally fed, and to assess the relationship between PA and BC. METHODS: Cross-sectional study in children 5-18 years with IF including those receiving parenteral nutrition (PN) and those fully enterally fed. PA levels were measured using accelerometry. BC was measured by dual-energy X-ray absorptiometry. Data were compared to age- and sex-matched population norms using t tests. Regression analysis assessed the relationship between BC and PA. RESULTS: Fifty-eight children with IF (38 males), mean (SD) age of 10.0 (3.5) years, 20 dependent on PN were included. Patients with IF had significantly fewer steps per day ( P ≤ 0.001) compared with literature controls, with a mean (SD) of 7,972 (3,008) and 11,749 (1,106), respectively. There were no significant differences between patients receiving PN and those enterally fed, but both groups were significantly less active than literature controls ( P < 0.001). Patients with IF had higher fat mass and lower fat-free mass compared to literature controls ( P = 0.008). PA had a significant effect on BC ( r2 = 0.32, P < 0.001). CONCLUSIONS: Children with IF, those receiving PN and those fully enterally fed, are at risk of decreased PA and altered BC. PA should be part of ongoing rehabilitation and management to optimize outcomes.

Predictors of Social-Emotional Development and Adaptive Functioning in School-Age Children with Intestinal Failure.

OBJECTIVES: Despite a focus on neurocognition in pediatric intestinal failure (IF) to date, we examined social-emotional and adaptive functioning. METHODS: Children (N = 63) in our IF rehabilitation program underwent neuropsychological assessments including caregiver- and teacher-reported questionnaires. Results were compared to norms using z-tests. Caregiver and teacher reports were compared using t tests. Medical and demographic factors were examined in an exploratory manner using correlation and targeted regression analyses, adjusting for gestational age and full-scale IQ. RESULTS: Caregiver and teacher reports indicated poorer executive, internalizing, behavioral, and adaptive functioning compared to norms. Teachers reported more executive dysfunctions than caregivers. Necrotizing enterocolitis diagnosis predicted internalizing emotional problems. Immigrant status predicted poorer social and practical adaptive functioning. Living with biological parents predicted fewer externalizing emotional and behavioral problems. CONCLUSIONS: The group displayed social-emotional and adaptive functioning concerns. Identifying medical and demographic risks can allow for screening and intervention.

Metabolic Availability of Methionine Assessed Using Indicator Amino Acid Oxidation Method, Is Greater when Cooked Lentils and Steamed Rice Are Combined in the Diet of Healthy Young Men.

BACKGROUND: Lentil is considered a high protein source. However, it is low in sulphur amino acids (SAA) and their metabolic availability (MA) is further affected by antinutritional factors in lentils. The combination of lentils with grains such as rice can enhance the protein quality of a lentil-based meal but the MA of SAA in lentils must first be known. OBJECTIVES: The objectives of the current study were to assess the MA of methionine in lentils and to test the effects of consumption of complementing lentils with rice in young adults. METHODS: Five healthy young men [age <30 y, BMI <25 (in kg/m2)] were each studied at 8 or 10 intake amounts of methionine in random order; 4 daily intake amounts of l-methionine: 0.5, 1, 2, and 3 mg.kg-1.d-1 (reference diet), 3 daily intake amounts of methionine from lentils, and 3 daily intake amounts of the mixed meal of lentils + rice (test diets). The MA of methionine and the effects of complementation were assessed by comparing the indicator amino acid oxidation (IAAO) response to varying intakes of methionine in cooked Canadian lentils, and in rice + lentils combined, compared with the IAAO response to l-methionine intakes in the reference protein (crystalline AA mixture patterned after egg protein) using the slope ratio method. l-[1-13C] phenylalanine was used as the indicator. Data were analyzed using the procedure "MIXED" with subject as a random variable, and oxidation day as repeated measure. RESULTS: The MA of methionine from lentils was 69%. Complementation of cooked lentils with rice decreased the oxidation of l-[1-13C] phenylalanine by up to 16% (P < 0.05). CONCLUSIONS: The content and MA of methionine are low in lentils. However, combination of lentils with rice in a 1:1 ratio can improve the protein quality of lentil-based diets, resulting in increased protein synthesis in young healthy adults. This trial was registered at www.clinical trials.gov as NCT03110913.

Bioavailable Lysine Assessed Using the Indicator Amino Acid Oxidation Method in Healthy Young Males is High when Sorghum is Cooked by a Moist Cooking Method.

BACKGROUND: Sorghum is the fifth most consumed cereal grain but limiting in the indispensable amino acid lysine. Complementing sorghum with lentils can improve the quality of sorghum-based diets. However, knowledge of lysine bioavailability in sorghum is lacking. OBJECTIVES: The study objectives were to determine the bioavailability of lysine in sorghum and to assess the effect of complementation of sorghum and lentils in a mixed-meal format. METHODS: We studied 5 healthy young men (≤30 years; BMI <25 kg/m2) in a repeated-measure design using the indicator amino acid oxidation (IAAO) method, with L-[1-13C] phenylalanine as the indicator. Each subject participated in 8 determinations in random order. On the reference diet, subjects received 4 amounts of L-lysine (5, 8, 12, and 15 mg. kg-1 . d-1) from a crystalline amino acid mixture patterned after egg protein. On the test diet, they received 3 levels of lysine (8.2, 12.5, and 15.7 mg. kg-1 . d-1) from sorghum, and on the complementation diet they received 1 level of lysine from a mixed meal of sorghum and lentils. The bioavailability of lysine in sorghum was estimated by comparing the IAAO response to the test diet with the IAAO response to the reference diet using the slope-ratio method. Effectiveness of complementation was assessed by comparing the IAAO response to the mixed meal to the IAAO response to the test protein. RESULTS: The bioavailability of lysine from sorghum was 94%. Upon complementation with lentils, there was a decline in the oxidation of L-[1-13C] phenylalanine by 19% (P < 0.0495), reflecting an improvement in available lysine in the mixed meal due to increased lysine intake. CONCLUSIONS: Although the bioavailability of lysine in sorghum is high, its lysine content is limiting. Complementation with lentils in a 1:1 ratio is recommended to achieve the lysine requirement for adult men consuming a sorghum-based diet. This trial was registered at clinicaltrials.gov as NCT03411005.

Muscle Strength, Agility, and Body Composition in Children With Intestinal Failure on Parenteral Nutrition.

OBJECTIVES: With increasing number of children with intestinal failure (IF) on long-term parenteral nutrition (PN), this study assesses the impact of IF on muscle strength, speed, and agility and body composition (BC), identifying clinical factors that may predict impairment. METHODS: Cross-sectional study in children 5-18 years with IF on PN. Assessments included Bruininks-Oseretsky Test of Motor Proficiency-2 strength and agility subtest (BOT-2), and grip strength. BC data from dual-energy x-ray absorptiometry (DXA) measurements and clinical variables were collected by chart abstraction. Data were compared to age and sex matched controls and population norms. RESULTS: Twenty-one children with IF (14 males), median age 8.33 (IQR: 6.96-11.04) years and 33 controls (20 males), 8.25 (6.67-10.79) years were included. Strength and agility ( P < 0.001) and grip strength ( P = 0.001) differed between groups. Nine of 21 (43%) of children with IF scored >1 standard deviation (SD) below mean on BOT-2 and 13 of 21 (62%) had grip strength >1 SD below mean. DXA measurements showed 10 of 18 (56%) of children had lower fat-free mass (FFM)% and higher fat mass (FM)% than reference norms. Decreased FFM% was associated with lower BOT-2 scores ( r = 0.479; P = 0.044) and grip strength scores >1 SD below mean ( P = 0.047). Additional clinical factors significantly impacting strength and agility included prematurity, height, hospitalizations, sepsis, and small bowel length. CONCLUSIONS: Children with IF are at risk of decreased muscle strength and agility, along with altered BC. Ongoing medical, nutritional, and rehabilitation intervention is vital to optimize outcomes.

Bioavailable Methionine Assessed Using the Indicator Amino Acid Oxidation Method Is Greater When Cooked Chickpeas and Steamed Rice Are Combined in Healthy Young Men.

BACKGROUND: In general, pulse protein is limiting in the indispensable amino acid methionine, and antinutritional factors in pulses can affect methionine bioavailability. Complementation with grains such as rice can improve pulse protein quality, but knowledge of methionine bioavailability in pulses and grains is necessary to correct for available methionine when planning and assessing dietary protein intake. OBJECTIVES: The study objectives were to determine the bioavailability of methionine in rice and chickpeas separately and to assess the effect of complementation of chickpeas and rice. METHODS: Eleven healthy young men (<30 y, BMI <25 kg/m2) were studied in a repeated-measures design using the indicator amino acid oxidation (IAAO) method, with l-[1-13C]phenylalanine as the indicator. Each received 7 or 10 methionine intakes in random order: 4 intakes of l-methionine-0.5, 1, 2, and 3 mg⋅kg-1⋅d-1 (reference diet); 3 intakes of methionine from rice and from chickpeas; and 3 intakes from the mixed meal of chickpeas plus rice (test diets). The bioavailability of methionine and the effect of complementation were assessed by comparing the IAAO response to varying intakes of methionine in rice, in cooked Canadian chickpeas, and in rice plus chickpeas combined compared with the IAAO response to l-methionine intakes in the reference protein (crystalline amino acid mixture patterned after egg protein) using the slope ratio method. RESULTS: The bioavailability of methionine from rice and from chickpeas was 100% and 63%, respectively. Complementation of cooked chickpeas with rice decreased the oxidation of l-[1-13C]phenylalanine by up to 14% (P < 0.05), suggesting an improved protein quality of the combined chickpeas plus rice protein. CONCLUSIONS: When chickpeas are the main protein source in the diet of young adult men, the combination of rice and chickpeas in a 3:1 ratio is recommended to improve dietary protein quality. This trial was registered at clinicaltrials.gov as NCT03339154 and NCT03674736.

Bioavailable Lysine, Assessed in Healthy Young Men Using Indicator Amino Acid Oxidation, is Greater when Cooked Millet and Stewed Canadian Lentils are Combined.

BACKGROUND: Pearl millet is the chief source of energy in the diet in some developing regions, but has a limited amount of indispensable amino acid lysine. Complementation with pulses like lentils can improve the protein quality of millet diets, but the knowledge of lysine bioavailability (BA) in millet and lentils is lacking. OBJECTIVES: The study objectives were to determine the BA of lysine in millet and lentils separately and to assess the effect of complementation of millet and lentils in a mixed meal format. METHODS: We studied 9 healthy young men (≤30 y; BMI <25) in a repeated-measure design using the indicator amino acid oxidation (IAAO) method, with L-[1-13C] phenylalanine as the indicator. Each subject completed 7 or 8 experiments in random order. On the reference diet, subjects received 4 graded levels of L-lysine (5, 8, 12, and 15 mg·kg-1.d-1) from a crystalline amino acid mixture patterned after egg protein; on the test diets, they received 3 levels of lysine (10, 12, and 15 mg·kg-1.d-1) from either steamed millet or stewed lentils; and on the complementation diet, they received 1 level of lysine from a mixed meal of steamed millet and stewed lentils. The BA of lysine and the effect of complementation were assessed by comparing the IAAO responses to the test diets and the complementation diet with the IAAO response to L-lysine intakes in the reference protein, using the slope ratio method. RESULTS: The BA of lysine was 97% from millet and 80% from lentils. Complementation of steamed millet with stewed lentils decreased the oxidation of L-[1-13C] phenylalanine by 27% (P < 0.05), signifying improved quality of the combined millet and lentil protein. CONCLUSIONS: Lysine has high BA but is still limiting in steamed pearl millet. Complementation with lentils in a 2:1 ratio is recommended to meet the lysine and protein requirements for adult men consuming a millet-based diet. This trial was registered at clinicaltrials.gov as NCT03674736 and NCT03339167.

Lysine Bioavailability in School-Age Children Consuming Rice Is Reduced by Starch Retrogradation.

BACKGROUND: Rice is one of the most commonly consumed cereal grains and is part of staple diets in the majority of the world. However, it is regarded as an incomplete protein, with lysine being a limiting amino acid. OBJECTIVES: Our objectives were to determine the bioavailability of lysine in school-age children consuming cooked white rice and to assess the effect of rice starch retrogradation. METHODS: Bioavailability or metabolic availability (MA) of lysine was determined using the indicator amino acid oxidation (IAAO) method in a repeated-measures design. Six healthy school-age children (3 boys, 3 girls) with a mean ± SD age of 6.8 ± 0.98 y randomly received 4 crystalline l-lysine intakes (2, 6, 10, 14 mg · kg-1 · d-1), and 5 rice intakes to provide lysine at 8, 11, or 14 mg · kg-1 · d-1. The 14 mg · kg-1 · d-1 intakes were measured twice as warm rice and once as cold rice (to assess the impact of starch retrogradation on MA). Diets provided protein at 1.5 g · kg-1 · d-1 and calories at 1.7 times the participant's measured resting energy requirement, and were isonitrogenous. Breath samples were collected at baseline and during an isotopic steady state for 13C enrichment measurement. The MA of lysine from rice was determined by comparing the IAAO response of rice with l-lysine using the slope-ratio and single intake methods. Starch retrogradation was characterized using differential scanning calorimetry. RESULTS: MA of lysine in warm rice measured in school-age children was 97.5% and was similar to a repeated rice study (97.1%) within the same study population. MA of lysine was reduced significantly (P < 0.05) to 86.1% when the cooked rice was consumed cold, which corresponded to detectable starch retrogradation. CONCLUSIONS: To our knowledge, this is the first study to measure the MA of lysine from rice in school-age children. Although the bioavailability of lysine from rice is high, it can be reduced by retrogradation of its starch component.This trial was registered at clinicaltrials.gov as NCT04135040.

Dietary Aromatic Amino Acid Requirements During Early and Late Gestation in Healthy Pregnant Women.

BACKGROUND: Phenylalanine and tyrosine (referred to as total aromatic amino acids; TAAs) are essential for protein synthesis, and are precursors for important catecholamines. Current estimated average requirement (EAR) recommendations for TAA during pregnancy are 36 mg·kg-1·d-1, and has not been experimentally determined. OBJECTIVES: The aim was to determine TAA requirements (dietary phenylalanine in the absence of tyrosine) during early and late gestation using the indicator amino acid oxidation (IAAO, with L-[1-13C]leucine) technique. METHODS: Nineteen healthy pregnant women (age 22-38 y) were studied at a range of phenylalanine intakes (5 to 100 mg·kg-1·d-1) in early (13-19 wk) and/or late (33-39 wk) pregnancy for a total of 51 study days. Graded test intakes were provided as 8 hourly isonitrogenous and isocaloric meals. Breath samples were collected for 13C enrichment analysis on an isotope ratio mass spectrometer. A plasma sample was collected and analyzed for phenylalanine and tyrosine concentrations on an amino acid analyzer. The TAA requirement in early and late pregnancy was calculated using 2-phase linear regression crossover analysis that identified breakpoints in 13CO2 production (the requirement) in response to phenylalanine intakes. RESULTS: TAA requirement during early pregnancy was 44 mg·kg-1·d-1 (95% CI: 28.3, 58.8) and during late pregnancy was 50 mg·kg-1·d-1 (95% CI: 36.1, 63.1). In early and late pregnancy, plasma phenylalanine and tyrosine concentrations rose linearly in response to graded phenylalanine intakes. CONCLUSIONS: Our results suggest that the current EAR of 36 mg·kg-1·d-1 for TAAs is underestimated. When compared with results previously determined in nonpregnant adults, early pregnancy requirements were similar (43 compared with 44 mg·kg-1·d-1, respectively). During late pregnancy, a 14% higher TAA requirement was observed when compared with early pregnancy. The results from this study have potential implications for creating gestation stage-specific TAA recommendations.

Protein Quality Assessment of Follow-up Formula for Young Children and Ready-to-Use Therapeutic Foods: Recommendations by the FAO Expert Working Group in 2017.

The FAO of the UN convened an Expert Working Group meeting to provide recommendations related to protein quality evaluation of Follow-up Formula for Young Children (FUF-YC) and Ready-to-Use Therapeutic Foods (RUTFs). The protein and amino acid (AA) scoring patterns for the target age groups were defined and recommendations provided on the use of currently available protein and indispensable AA digestibility data. For FUF-YC, an age category of 1-2.9 y was identified, and a matching protein requirement of 0.86 g · kg-1 · d-1 with corresponding AA requirements were recommended. For RUTF, the protein requirement recommended was 2.82 g · kg-1 · d-1, to achieve a catch-up weight gain of 10 g · kg-1 · d-1 in children recovering from severe acute malnutrition. The AA requirements were factorially derived based on the adult protein requirement for maintenance and tissue AA composition. A flowchart was proposed for the best available methods to estimate digestibility coefficients (of either protein or AAs), in the following order: human, growing pig, and rat true ileal AA digestibility values. Where this is not possible, fecal protein digestibility values should be used. The Expert Working Group recommends the use of the Protein Digestibility Corrected Amino Acid Score (PDCAAS), with existing protein digestibility values, or the Digestible Indispensable Amino Acid Score provided that individual AA digestibility values are available for protein quality evaluation using the latter score. The Group also recommends the use of ileal digestibility of protein or of AAs for plant-based protein sources, recognizing the possible effects of antinutritional factors and impaired gut function. A PDCAAS score of ≥90% can be considered adequate for these formulations, whereas with a score <90%, the quantity of protein should be increased to meet the requirements. Regardless of the protein quality score, the ability of formulations to support growth in the target population should be evaluated. Future research recommendations are also proposed based on the knowledge gaps identified.

Nephrocalcinosis and Renal Dysfunction in Pediatric Intestinal Failure.

BACKGROUND: Outcomes of pediatric intestinal failure (PIF) have improved recently, with other comorbidities, such as increased echogenicity/nephrocalcinosis on ultrasound (US) in long-term survivors now evident. We evaluated the significance of nephrocalcinosis over time in PIF and its impact on renal function. METHODS: Retrospective analysis on a cohort of PIF patients was performed. Presence of nephrocalcinosis and/or increased renal echogenicity (identified on US), estimated glomerular filtration rate (eGFR; ml ·â€Šmin ·â€Š1.73 m2), renal tubular function, PN volume (ml ·â€Škg ·â€Šday) and PN exposure time (hours/day) were reviewed annually over a follow-up period of 2 years. Outcomes in the nephrocalcinosis versus normal US groups were compared. RESULTS: Forty patients (28 boys, median age 2.7 years) were followed for 2 years. Fifteen (38%) had either increased echogenicity or nephrocalcinosis (group 1) at initial US. US were normal in the remaining 25 (62%) on initial assessment (group 2). eGFR did not differ between group 1 and group 2 at baseline (118 vs 133, P = 0.51) and year 2 (130 vs 131, P = 1.00). The percentage of patients with abnormal markers of tubular function was similar in both groups at year 2 (high urine calcium: creatinine 33 versus 30, P = 0.83; high urine calcium: citrate 39 versus 42, P = 0.87; low urine citrate: creatinine 15 versus 17, P = 1.00; high urine oxalate: creatinine 39 versus 25, P = 0.77). CONCLUSIONS: A large proportion of PIF patients with a history of parenteral nutrition (PN) exposure have nephrocalcinosis and/or increased echogenicity on US. Over a 2-year follow-up period, however, these abnormalities had no impact on eGFR or renal tubular function.

Indicator amino acid oxidation protein requirement estimate in endurance-trained men 24 h postexercise exceeds both the EAR and current athlete guidelines.

Despite studies indicating increased protein requirements in strength-trained or endurance-trained (ET) individuals, the Institute of Medicine has concluded that "no additional dietary protein is suggested for healthy adults undertaking resistance or endurance exercise," and the controversy regarding exercise effects on protein requirements continues. The objective of this study was to determine the dietary protein requirement of healthy young ET men (≥1 yr training experience) 24 h post exercise (to minimize any acute effects of the previous training session) by measuring the oxidation of ingested l-[1-13C]phenylalanine to 13CO2 in response to graded intakes of protein (indicator amino acid oxidation technique). Eight men [maximal oxygen consumption 64.1 ml·kg-1·min-1 (SD 3.7)] were each studied 24 h postexercise repeatedly with protein intakes ranging from 0.3 to 3.5 g·kg-1·day-1. Protein was fed as an amino acid mixture based on the protein pattern in egg, except for phenylalanine and tyrosine, which were maintained at constant amounts across all protein intakes. For 2 days before the study day, all participants consumed 1.6 g protein·kg-1·day-1. The estimated average requirement (EAR) for protein was determined by applying a nonlinear mixed-effects change-point regression analysis to F13CO2 (label tracer oxidation in 13CO2 breath), which identified a breakpoint in the F13CO2 in response to the graded amounts of protein. The EAR for protein and the upper 95% confidence interval were 2.1 and 2.6 g·kg-1·day-1, respectively. These data suggest that the protein EAR for ET men 24 h postexercise exceeds the Institute of Medicine EAR and established athlete guidelines by ~3.5- and 1.3-fold, respectively.

Predicting Intestinal Adaptation in Pediatric Intestinal Failure: A Retrospective Cohort Study.

OBJECTIVE: The primary goal in intestinal failure (IF) is adaptation and enteral autonomy (EA). Our goals were to determine the proportion of patients treated for IF by an established intestinal rehabilitation program who achieved EA and to assess the predictors of EA. BACKGROUND: There have been considerable advancements in the management of IF over the last 15 years, children with short bowel syndrome with a reduction in mortality. Several studies have discussed variables that may influence the ability to attain EA; however, majority were written when mortality rates were considerably higher compared with the current contemporary experience. METHODS: A retrospective analysis of infants <12 months with short bowel syndrome referred between 2006 and 2013 (n = 120). Data was collected on IF-related factors and nutritional intake. The cohort was stratified based on achievement of EA. Statistical testing completed using t test, Chi Square, and Cox Proportional Hazards regression (P < 0.05). RESULTS: EA was achieved in 84 (70.0%) patients. Patients who remained parenteral nutrition dependent were more likely to have volvulus (1.2 vs 22.2%, P < 0.001), shorter percent residual small bowel (29.4 vs 68.6%; P < 0.0001) and colon length (64.6 vs 86.0%; P = 0.001), and no ileocecal valve (61.1 vs 29.8%; P = 0.05). Mortality was also decreased in those who achieved EA (4 vs 22%; P = 0.004). Percent residual small bowel (HR = 1.03; 95% CI 1.02-1.03) and colon (HR = 1.01; 95% CI 1.00-1.02) length were positively associated with EA, while number of septic episodes was negatively associated (HR = 0.95; 95% CI 0.91-0.99). CONCLUSION: Seventy percent of infants with IF achieved EA. Residual small and large bowel length were the most important predictors of EA and septic events had a negative impact.

Tryptophan Requirement in School-Age Children Determined by the Indicator Amino Acid Oxidation Method is Similar to Current Recommendations.

BACKGROUND: The requirement for dietary tryptophan in school-age children has never been empirically derived. OBJECTIVE: The objective of our study was to determine the tryptophan requirement of school-age children using the indicator amino acid oxidation technique. METHODS: Volunteer healthy school-age children, between 8 and 12 y, were enrolled and the oxidation of l-[13C]-phenylalanine to 13CO2 measured in response to graded intakes of dietary tryptophan. Seven children (3 boys, 4 girls) participated in the study and received randomly assigned tryptophan intakes ranging from 0.5 to 9.75 mg.kg-1.d-1 for a total of 36 studies. The diets provided energy at 1.5 times each subject's resting energy expenditure and were isocaloric. Protein was provided as an amino acid mixture on the basis of the egg protein pattern, and phenylalanine and tyrosine were maintained constant across the protein intake concentrations at 25 and 40 mg.kg-1.d-1. All subjects were adapted for 2 d before the study day to a protein intake of 1.5 g.kg-1.d-1. The mean tryptophan requirement was determined by applying a mixed-effect change-point regression analysis to F13CO2 (label tracer oxidation in 13CO2 breath) which identified a breakpoint in the F13CO2 in response to graded amounts of tryptophan. RESULTS: The mean [estimated average requirement (EAR)] and upper 95% CI, (approximating the RDA) of tryptophan requirements were estimated to be 4.7 and 6.1 mg.kg-1.d-1, respectively. CONCLUSION: Our results are similar to the current recommended EAR and RDA of 5 and 6 mg.kg-1.d-1 for healthy growing children based on the factorial calculation. Clinical Trials Registration No. NCT02018588.

The Phenylalanine Requirement of Elderly Men and Women Measured by Direct 13C Carbon Oxidation Method Is Similar to That of Young Adults.

BACKGROUND: The phenylalanine requirement of the elderly is not known. Current recommendations are based on studies in young adults and are derived from a combined estimate of the total aromatic amino acids, phenylalanine, and tyrosine. OBJECTIVES: The purpose of this study was to determine the dietary phenylalanine requirement of adults aged >65 y, using the direct amino acid oxidation method, by measuring the oxidation of l-[1-13C]phenylalanine to 13CO2 in response to graded phenylalanine intakes in the presence of excess tyrosine. METHODS: Twelve subjects (6 men, 6 women), aged 73.8 ± 6.7 y (mean ± SD) and with a BMI (in kg/m2) of 26.4 ± 4.8 and 25.2 ± 4.4 for men and women, respectively, were randomized to phenylalanine intakes ranging from 7.20 to 40.0 mg .kg-1 .d-1 for a total of 66 studies. Study diets were isocaloric and isonitrogenous, providing protein and energy at 1.0 g .kg-1 .d-1 and 1.5 × resting energy expenditure (REE), respectively. Protein was provided as an amino acid mixture patterned after egg protein, with an excess of tyrosine and alanine to balance the nitrogen as phenylalanine intakes were varied. Two days prior to the study day, subjects were adapted to a milkshake diet providing protein at 1.0 g.kg-1 .d-1 and energy at 1.7 × REE. The mean phenylalanine requirement was determined using biphase linear regression analysis, which identified a breakpoint in the F13CO2 in response to graded phenylalanine intakes. RESULTS: The mean and upper 95% CIs (approximating the recommended dietary allowance) of phenylalanine requirements were estimated to be 9.03 and 15.9 mg.kg-1 .d-1, respectively. CONCLUSION: These results are similar to previously derived estimates of 9.1 and 13.6 mg.kg-1 .d-1 in young adult men and suggest that higher protein needs of the elderly to stimulate similar muscle protein synthesis rates as young adults are not driven by an increased requirement for phenylalanine. This trial was registered at clinicaltrials.gov as NCT02971059.