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Background: The types of food in complementary feeding of infants and young children are important for growth and development. Food protein quality, as measured by the Digestible Indispensable Amino Acid Score (DIAAS), requires the determination of true ileal digestibility of indispensable amino acids (IAAs) in children., Objectives: First, the aim of this study was to measure the true ileal IAA digestibility of 4 (rice, finger millet, mung bean, and hen egg) commonly consumed complementary foods in children aged <2 y using the dual-isotope tracer method. Second, we calculated the DIAAS of complementary feeding diets and their relation to stunting in a representative Indian rural population., Design: Rice, finger millet, and mung bean were intrinsically labeled with deuterium oxide (2H2O), whereas egg was labeled through oral dosing of hens with a uniformly 2H-labeled amino acid mixture. True ileal IAA digestibility was determined by the dual-isotope tracer technique. The DIAAS of complementary food protein was calculated in children aged 1-3 y from a nationally representative survey to evaluate its relation with stunting., Results: True ileal IAA digestibility was lowest in mung bean (65.2% ± 7.1%), followed by finger millet (68.4 %± 5.3%) and rice (78.5% ± 3.5%), and was highest for egg (87.4% ± 4.0%). There was a significant inverse correlation of complementary food DIAAS with stunting in survey data (r = -0.66, P = 0.044). The addition of egg or milk to nationally representative complementary diets theoretically improved the DIAAS from 80 to 100., Conclusions: The true ileal IAA digestibility of 4 foods commonly consumed in complementary diets showed that the DIAAS was associated with stunting and reinforces the importance of including animal source food (ASF) in diets to improve growth. This trial was registered at http://ctri.nic.in/clinicaltrials/login.php as CTRI/2017/02/007921., (Copyright © American Society for Nutrition 2019.)

Background: Low-quality dietary protein intake and vitamin B-12 deficiency could interact to decrease methionine transmethylation and remethylation rates during pregnancy and may affect epigenetic modifications of the fetal genome. Objective: The objective of this randomized, partially open-labeled intervention trial was to examine the effect of supplemental high-quality protein and vitamin B-12 on third-trimester methionine kinetics in pregnant Indian women with a low vitamin B-12 status. Methods: Pregnant women with low serum vitamin B-12 concentrations (<200 pmol/L) were randomly assigned to 1 of 3 groups: the first group received balanced protein-energy supplementation of 500 mL milk/d plus a 10-μg vitamin B-12 tablet/d (M+B-12 group; n = 30), the second group received milk (500 mL/d) plus a placebo tablet (M+P group; n = 30), and the third group received a placebo tablet alone (P group; n = 33). Third-trimester fasting plasma amino acid kinetics were measured by infusing 1- 13 C,methyl- 2 H 3 -methionine, ring- 2 H 5 -phenylalanine, ring- 2 H 4 -tyrosine,1- 13 C-glycine, and 2,3,3- 2 H 3 , 15 N-serine in a subset of participants. Placental mRNA expression of genes involved in methionine pathways, placental long interspersed nuclear elements 1 (LINE-1) methylation, and promoter methylation levels of vascular endothelial growth factor ( VEGF ) were analyzed. Results: Remethylation rates in the M+B-12, M+P, and P groups were 5.1 ± 1.7, 4.1 ± 1.0, and, 5.0 ± 1.4 μmol ⋅ kg -1 ⋅ h -1 , respectively ( P = 0.057), such that the percentage of transmethylation remethylated to methionine tended to be higher in the M+B-12 group (49.5% ± 10.5%) than in the M+P group (42.3% ± 8.4%; P = 0.053) but neither differed from the P group (44.2% ± 8.1%; P > 0.1). Placental mRNA expression, LINE-1, and VEGF promoter methylation did not differ between groups. Conclusions: Combined vitamin B-12 and balanced protein-energy supplementation increased the homocysteine remethylation rate in late pregnancy. Thus, vitamin B-12 along with balanced protein-energy supplementation is critical for optimal functioning of the methionine cycle in the third trimester of pregnancy in Indian women with low serum vitamin B-12 in early pregnancy. This trial was registered at clinicaltrials.gov as CTRI/2016/01/006578., Competing Interests: 3: Author disclosures: S Devi, A Mukhopadhyay, P Dwarkanath, T Thomas, J Crasta, A Thomas, CN Sheela, JW Hsu, GJ Tang, F Jahoor, and AV Kurpad, no conflicts of interest., (© 2017 American Society for Nutrition.)

Background: In India, the prevalence of low birth weight is high in women with a low body mass index (BMI), suggesting that underweight women are not capable of providing adequate energy and protein for fetal growth. Furthermore, as pregnancy progresses, there is increased need to provide methyl groups for methylation reactions associated with the synthesis of new proteins and, unlike normal-BMI American women, low-BMI Indian women are unable to increase methionine transmethylation and remethylation rates as pregnancy progresses from trimester 1 to 3. This also negatively influences birth weight., Objective: The aim was to determine the effect of dietary supplementation with energy and protein from 12 ± 1 wk of gestation to time of delivery compared with no supplement on pregnancy outcomes, protein kinetics, and the fluxes of the methyl group donors serine and glycine., Methods: Protein kinetics and serine and glycine fluxes were measured by using standard stable isotope tracer methods in the fasting and postprandial states in 24 pregnant women aged 22.9 ± 0.7 y with low BMIs [BMI (in kg/m(2)) ≤18.5] at 12 ± 1 wk (trimester 1) and 30 ± 1 wk (trimester 3) of gestation. After the first measurement, subjects were randomly assigned to either receive the supplement (300 kcal/d, 15 g protein/d) or no supplement., Results: Supplementation had no significant effect on any variable of pregnancy outcome, and except for fasting state decreases in leucine flux (125 ± 7.14 compared with 113 ± 5.06 μmol ⋅ kg(-1) ⋅ h(-1); P = 0.04) and nonoxidative disposal (110 ± 6.97 compared with 101 ± 3.69 μmol ⋅ kg(-1) ⋅ h(-1); P = 0.02) from trimesters 1 to 3, it had no effect on any other leucine kinetic variable or urea, glycine, and serine fluxes., Conclusion: We conclude that in Indian women with a low BMI, supplementation with energy and protein from week 12 of pregnancy to time of delivery does not improve pregnancy outcome, whole-body protein kinetics, or serine and glycine fluxes., (© 2016 American Society for Nutrition.)

Pregnancy and the first two years of life are periods of rapid growth and yet the knowledge of requirements for protein and dietary indispensable amino acids is very limited. The development of carbon oxidation methods opens the way to studies that should fill these important gaps in knowledge.

Background: Evidence suggests that in women with a normal to high body mass index (BMI; in kg/m(2)), the extra amino acids needed during pregnancy are met through reduced oxidation. It is not known whether a woman with a low BMI can make this adaptation successfully., Objective: The objective was to measure and compare leucine kinetic parameters and alanine-nitrogen, glutamine amide-nitrogen, and glycine and cysteine fluxes in Indian women with a low and normal BMI in early and midpregnancy., Design: Fasted- and fed-state kinetics were measured by infusing 1-[(13)C]leucine, [(2)H(2)]cysteine, [(2)H(2)]glycine, [5-(15)N]glutamine, and [(15)N]alanine in groups of 10 women with a low BMI (<18.5) and 10 women with a normal BMI (18.5-25) in the first and second trimesters of pregnancy., Results: Leucine, glutamine, glycine, and cysteine fluxes were faster in women with a low BMI in both trimesters, but there was no difference in alanine flux between groups. This difference was explained in the first trimester by a higher proportion of fat-free mass in low-BMI women. Leucine oxidation and percentage of dietary leucine oxidized were higher in low-BMI women in both trimesters, but nonoxidative disposal was not different between groups., Conclusions: Although they use dietary protein less efficiently, low-BMI women maintain net protein synthesis at the same rate as do normal-BMI women and produce similar quantities of labile nitrogen for the de novo synthesis of other dispensable amino acids such as glycine and cysteine. The extra amino acids required for increased maternal protein synthesis during pregnancy are provided by an overall decrease in amino acid catabolism in women with normal or low BMI.

The plasma concentrations of albumin, HDL apolipoprotein A1 (apoA1), retinol-binding protein (RBP), transthyretin (TTR), haptoglobulin, and fibrinogen were measured, and a stable isotope infusion protocol was used to determine the fractional and absolute synthesis rates of RBP, TTR, and fibrinogen in 12 young adults on three occasions during a reduction of their habitual protein intake from 1.13 to 0.75 g x kg(-1) x day(-1) for 10 days. This study was performed to determine whether healthy adults could maintain the rates of synthesis of selected nutrient transport and positive acute-phase proteins when consuming a protein intake of 0.75 g x kg(-1) x day(-1). During the lower protein intake, the plasma concentration of all the proteins, other than HDL-apoA1, remained unchanged. HDL-apoA1 concentration was significantly reduced (P < 0.05) after 3 days of the lower protein intake, but not at 10 days. The rates of synthesis of RBP and TTR declined significantly (P < 0.05), whereas the rate of synthesis of fibrinogen remained unchanged. The results indicate that, when normal adults consume the recommended safe level of protein, 0.75 g x kg(-1) x day(-1), there is a slower rate of turnover of nutrient transport proteins than on their habitual diet. Hence, healthy individuals consuming this amount of protein may be less able to mount an adequate metabolic response to a stressful stimulus.

Background: The finding that plasma glutathione turnover decreases as dietary protein intake decreases suggests that the safe amount of dietary protein, although sufficient for maintenance of nitrogen balance, may be insufficient for maintenance of cellular glutathione., Objective: Our objective was to determine the effect of the safe protein intake on the erythrocyte glutathione synthesis rate and its relation with urinary 5-L-oxoproline excretion., Design: Erythrocyte glutathione synthesis and urinary 5-L-oxoproline excretion were measured in young adults (6 men and 6 women) by using an infusion of [(13)C(2)]glycine on 3 occasions: initially during the subjects' habitual protein intake (1.13 g.kg(-1).d(-1)) and on days 3 and 10 of consumption of a diet providing the safe protein intake (0.75 g.kg(-1).d(-1))., Results: Compared with baseline values, the fractional synthesis rate of erythrocyte glutathione was significantly lower (P < 0.05) on days 3 and 10 of the diet with the safe protein intake. Urinary 5-L-oxoproline excretion increased significantly (P < 0.05) above baseline by the third day of the diet with the safe protein intake and remained elevated. Erythrocyte glutathione concentrations and absolute synthesis rates decreased by day 3 but recovered to baseline values by day 10. Erythrocyte concentrations of cysteine, methionine, and serine remained unchanged, whereas erythrocyte concentrations of glycine, glutamic acid, and glutamine increased significantly by day 10., Conclusion: During adaptation to the safe amount of dietary protein, there are changes in the concentration and kinetics of erythrocyte glutathione that suggest a reduced antioxidant capacity and possible increased susceptibility to oxidant stress.

Background: Growth failure often precedes secondary infections in HIV-infected infants and children, suggesting that inadequate protein deposition may be an early manifestation of infection by the virus. However, the protein metabolic response elicited by the virus in young children is unknown., Objective: We compared children with HIV infection and age-matched children without HIV infection with regard to whole-body and splanchnic protein kinetics and synthesis of acute phase proteins (APPs)., Design: Whole-body and splanchnic leucine kinetics and fractional and absolute synthesis rates of 2 positive and 4 negative APPs were measured in 6 asymptomatic, HIV-infected children (4 males and 2 females) aged 6-17 mo and 4 uninfected children (3 females and 1 male) aged 7-9 mo who were in the fed state., Results: Compared with the control children, the HIV-infected children had significantly lower dietary energy and protein intakes and leucine balance and significantly faster leucine flux and fractional splanchnic leucine extraction; there was no significant difference between the groups in leucine oxidation rates. The HIV-infected children also had significantly higher plasma concentrations and absolute synthesis rates of the positive APPs and a significantly higher fractional synthesis rate of fibrinogen. The concentrations of 2 of the 4 negative APPs, albumin and HDL apolipoprotein A-I, were significantly lower in the HIV-infected children but were not associated with slower synthesis rates., Conclusions: Children with HIV infection but without secondary infection have reduced protein balance because of an inability to down-regulate protein catabolism. Furthermore, the acute phase protein response elicited by HIV infection is characterized by higher concentrations and synthesis rates of positive APPs without lower concentrations of some negative APPs.

Background: The adequacy of indispensable amino acid supplies has received much attention in studies of protein requirements, but the availability of nitrogen for synthesis and maintenance of the supply of dispensable amino acids has been overlooked., Objective: We aimed to determine whether nitrogen balance and the endogenous supply of the dispensable amino acids glycine and tyrosine can be maintained with a marginal protein intake., Design: Phenylalanine, glycine, and tyrosine kinetics were measured in young adults (6 men, 6 women) on 4 occasions during a reduction in habitual protein intake (1.13 g x kg(-1) x d(-1)) to a marginal intake (0.75 g x kg(-1) x d(-1)) by using a multiple stable-isotope-infusion protocol., Results: During the 10-d period of marginal protein intake, nitrogen excretion fell initially, then remained constant such that nitrogen balance was negative for the first 2 d and then positive or zero thereafter. Whole-body protein degradation and synthesis predicted from phenylalanine kinetics declined significantly (P < 0.05) over the period of marginal protein intake. Despite the reduction in the amount of glycine and tyrosine derived from whole-body proteolysis, the fluxes of glycine and tyrosine were maintained., Conclusions: The results show that adaptation to a marginal intake of dietary protein consisted of an overall reduction in whole-body protein turnover, net protein catabolism, and the rate of nitrogen excretion. The conserved nitrogen was sufficient to maintain the endogenous synthesis and hence the supply of glycine and tyrosine.

The changes in protein metabolism of severe childhood malnutrition are generally perceived as a metabolic adaptation to chronic protein undernutrition. However, severe malnutrition is invariably accompanied by infections which also have profound effects on protein metabolism. This study aimed to distinguish the effect of protein undernutrition from that of an inflammatory stimulus on muscle and plasma protein synthesis rates. Two groups of five piglets consumed diets containing either 23% or 3% protein for 4 wk. They then were infused intravenously with 2H3-leucine before and 48 h after subcutaneous injections of turpentine to measure the fractional synthesis rates (FSR) of muscle protein and both the FSR and the absolute synthesis rates (ASR) of albumin and fibrinogen. Prior to turpentine injection, compared to control piglets, protein-deficient piglets had significantly lower muscle FSR and plasma concentrations of both albumin and fibrinogen, although only albumin had lower FSR and ASR. Turpentine injection decreased muscle FSR but increased the FSR, ASR and plasma concentrations of both albumin and fibrinogen in control piglets. In protein-deficient piglets, the inflammatory stress caused a further decrease in muscle protein FSR and in plasma albumin concentration despite marked increases in albumin FSR and ASR. Fibrinogen FSR, ASR and plasma concentration were increased. We conclude that protein undernutrition and inflammation elicit the same kinetic response in muscle protein but different kinetic responses in plasma proteins. Furthermore, whereas protein deficiency reduces the plasma albumin pool via a reduction in albumin synthesis, inflammation reduces it through a stimulation of catabolism and/or loss from the intravascular space.

To investigate the extent of first-pass intestinal metabolism of dietary amino acids, seven female pigs (28 d old, 8.0 kg) were implanted with arterial, venous, portal and gastric catheters and with an ultrasonic portal blood flow probe. The pigs were fed a milk-based diet once hourly and infused intragastrically with [U-13C]algal protein. On average, 56% of the essential amino acid (EAA) intake appeared in the portal blood. However, the net portal balance of methionine (48% of intake) and threonine (38% of intake) tended (P = 0.08) to be lower than the mean of all EAA. The net portal balance (expressed as a percentage of intake) of alanine (205%), tyrosine (167%) and arginine (137%) exceeded their intake. Net portal outflow of ammonia accounted for 18% of total amino acid nitrogen intake. As a percentage of the enteral tracer input, there was substantial first-pass metabolism of lysine (35%), leucine (32%), phenylalanine (35%) and threonine (61%). However, only 18, 21, 18 and 12% of the total first-pass metabolism of lysine, leucine, phenylalanine and threonine, respectively, were recovered in mucosal protein. We conclude that roughly one third of dietary intake of EAA is consumed in first-pass metabolism by the intestine and that amino acid catabolism by the mucosal cells is quantitatively greater than amino acid incorporation into mucosal protein.

We investigated whether the efficiency of dietary protein utilization for growth increases during the pubertal growth spurt in both nondiabetic and diabetic subjects. We measured leucine oxidation and retention (intake minus oxidation) in orally fed nondiabetic (n = 9) and diabetic (n = 9) human subjects, aged 7-17 yr. Eight subjects were Tanner stage I, and 10 were Tanner stages III-V; groups were not matched for gender. After 3 days of consuming a diet containing approximately 1 g/kg. day protein, subjects drank a commercial liquid nutrition formula, containing L-[1(-13)C]leucine, every 30 min for a total of 6 h to provide 1 g protein/kg. day. Isotopic enrichment of CO2 was used to calculate the fractional leucine oxidation rate and, together with alpha-ketoisocaproate isotopic enrichment, to calculate total leucine oxidation. Leucine oxidation rates decreased with puberty in both nondiabetic subjects (36.0 +/- 10.4 vs. 23.9 +/- 4.2 mumol/kg fat-free mass (FFM).h, prepubertal and pubertal, respectively; P < 0.05) and diabetic (33.6 +/- 4.9% vs. 27.3 +/- 3.4 mumol/kg FFM.h, prepubertal and pubertal, respectively; P < 0.1) subjects. Leucine retention increased with puberty in both nondiabetic (0.27 +/- 3.2 vs. 15.7 +/- 5.3 mumol/kg FFM.h, prepubertal and pubertal, respectively; P < 0.001) and diabetic (1.9 +/- 4.9 vs. 13.2 +/- 4.4 mumol/kg FFM.h, prepubertal and pubertal subjects, respectively; P < 0.05) subjects. The data suggest that the pubertal growth spurt is associated with a marked increase in the efficiency of dietary protein utilization for growth.

Nitrogen balance and whole-body protein turnover were measured in children aged about one year taking diets which provided 1.7 or 0.7 g milk protein/kg/d at three levels of metabolizable energy, 80, 90 and 100 kcal/kg/d. All the children were in positive nitrogen balance at all levels of energy intake on 1.7 g protein/kg/d. Nitrogen equilibrium was maintained on 0.7 g protein/kg/d when the energy intake exceeded 90 kcal/kg/d, but on 80 kcal/kg/d nitrogen balance was negative. Whole-body protein turnover was measured from the enrichment in urinary ammonia following a continuous infusion of 15N-glycine. The variation between individuals on the same diet was significantly greater than the variation within individuals at different levels of energy intake. For the group as a whole protein synthesis on 1.7 g protein/kg/d was 0.74, 0.75 and 0.87 g N/kg/d on 100, 90 and 80 kcal/kg/d respectively; whereas on 0.7 g protein/kg/d it was 0.37, 0.38 and 0.40 g N/kg/d. These results show that over this range of intakes protein synthesis decreased as dietary protein fell, but tended to increase as energy intake fell.