Protein-quality evaluation of complementary foods in Indian children

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

The impact of obesity-associated glycine deficiency on the elimination of endogenous and exogenous metabolites via the glycine conjugation pathway

BackgroundGlycine is an integral component of the human detoxification system as it reacts with potentially toxic exogenous and endogenously produced compounds and metabolites via the glycine conjugation pathway for urinary excretion. Because individuals with obesity have reduced glycine availability, this detoxification pathway may be compromised. However, it should be restored after bariatric surgery because of increased glycine production.ObjectiveTo examine the impact of obesity-associated glycine deficiency on the glycine conjugation pathway. We hypothesize that the synthesis rates of acylglycines from endogenous and exogenous sources are significantly reduced in individuals with obesity but increase after bariatric surgery.MethodsWe recruited 21 participants with class III obesity and 21 with healthy weight as controls. At baseline, [1,2-13C2] glycine was infused to study the glycine conjugation pathway by quantifying the synthesis rates of several acylglycines. The same measurements were repeated in participants with obesity six months after bariatric surgery. Data are presented as mean ± standard deviation, and p-value< 0.05 is considered statistically significant.ResultsBaseline data of 20 participants with obesity were first compared to controls. Participants with obesity were significantly heavier than controls (mean BMI 40.5 ± 7.1 vs. 20.8 ± 2.1 kg/m2). They had significantly lower plasma glycine concentration (168 ± 30 vs. 209 ± 50 μmol/L) and slower absolute synthesis rates of acetylglycine, isobutyrylglycine, tigylglycine, isovalerylglycine, and hexanoylglycine. Pre- and post-surgery data were available for 16 participants with obesity. Post-surgery BMI decreased from 40.9 ± 7.3 to 31.6 ± 6.0 kg/m2. Plasma glycine concentration increased from 164 ± 26 to 212 ± 38 μmol/L) and was associated with significantly higher rates of excretion of acetylglycine, isobutyrylglycine, tigylglycine, isovalerylglycine, and hexanoylglycine. Benzoic acid (a xenobiotic dicarboxylic acid) is excreted as benzoylglycine; its synthesis rate was significantly slower in participants with obesity but increased after bariatric surgery.ConclusionObesity-associated glycine deficiency impairs the human body’s ability to eliminate endogenous and exogenous metabolites/compounds via the glycine conjugation pathway. This impairment is ameliorated when glycine supply is restored after bariatric surgery. These findings imply that dietary glycine supplementation could treat obesity-associated metabolic complications due to the accumulation of intramitochondrial toxic metabolites.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT04660513, identifier NCT04660513

Branched-Chain Amino Acid Oxidation Is Elevated in Adults with Morbid Obesity and Decreases Significantly after Sleeve Gastrectomy

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One-carbon metabolism in children with marasmus and kwashiorkor

BACKGROUND: Kwashiorkor is a childhood syndrome of edematous malnutrition. Its precise nutritional precipitants remain uncertain despite nine decades of study. Remarkably, kwashiorkor\u27s disturbances resemble the effects of experimental diets that are deficient in one-carbon nutrients. This similarity suggests that kwashiorkor may represent a nutritionally mediated syndrome of acute one-carbon metabolism dysfunction. Here we report findings from a cross-sectional exploration of serum one-carbon metabolites in Malawian children. METHODS: Blood was collected from children aged 12-60 months before nutritional rehabilitation: kwashiorkor (N = 94), marasmic-kwashiorkor (N = 43) marasmus (N = 118), moderate acute malnutrition (N = 56) and controls (N = 46). Serum concentrations of 16 one-carbon metabolites were quantified using LC/MS techniques, and then compared across participant groups. FINDINGS: Twelve of 16 measured one-carbon metabolites differed significantly between participant groups. Measured outputs of one-carbon metabolism, asymmetric dimethylarginine (ADMA) and cysteine, were lower in marasmic-kwashiorkor (median µmol/L (± SD): 0·549 (± 0·217) P = 0·00045 & 90 (± 40) P \u3c 0·0001, respectively) and kwashiorkor (0·557 (± 0·195) P \u3c 0·0001 & 115 (± 50) P \u3c 0·0001), relative to marasmus (0·698 (± 0·212) & 153 (± 42)). ADMA and cysteine were well correlated with methionine in both kwashiorkor and marasmic-kwashiorkor. INTERPRETATION: Kwashiorkor and marasmic-kwashiorkor were distinguished by evidence of one-carbon metabolism dysfunction. Correlative observations suggest that methionine deficiency drives this dysfunction, which is implicated in the syndrome\u27s pathogenesis. The hypothesis that kwashiorkor can be prevented by fortifying low quality diets with methionine, along with nutrients that support efficient methionine use, such as choline, requires further investigation. FUNDING: The Hickey Family Foundation, the American College of Gastroenterology, the NICHD, and the USDA/ARS

Sulfur amino acid metabolism in children with severe childhood undernutrition: cysteine kinetics

Sulfur amino acid metabolism in children with severe childhood undernutrition: cysteine kinetics 1,2,3 Farook Jahoor, Asha Badaloo, Marvin Reid and Terrence Forrester 1 From the US Department of Agriculture, Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX (FJ), and the Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston, Jamaica (AB, MR, and TF) Background: Children with edematous but not nonedematous severe childhood undernutrition (SCU) have lower plasma and erythrocyte-free concentrations of cysteine, the rate-limiting precursor of glutathione synthesis. We propose that these lower cysteine concentrations are due to reduced production secondary to slower de novo synthesis plus decreased release from protein breakdown. Objective: We aimed to measure cysteine production, de novo synthesis, and the rate of cysteine release from protein breakdown in children with SCU. Design: Cysteine flux, de novo synthesis, and release from protein breakdown were measured in 2 groups of children with edematous (n =3D 11) and nonedematous (n =3D 11) SCU when they were infected and malnourished (clinical phase 1), when they were still severely malnourished but no longer infected (clinical phase 2), and when they had recovered (clinical phase 3). Results: In clinical phase 1, cysteine production and its release from protein breakdown were slower in both groups of children than were the values in the recovered state. These kinetic variables were significantly slower, however, in the children with edematous SCU than in those with nonedematous SCU. De novo cysteine synthesis in clinical phase 1 was faster than the rate at recovery in the edematous SCU group, and there were no significant differences between the groups at any clinical phase. Conclusion: These findings suggest that cysteine production is reduced in all children with SCU because of a decreased contribution from protein breakdown and not from decreased de novo synthesis. The magnitude of this reduction, however, is much greater in children with edematous SCU than in those with nonedematous SCU. Key Words: Cysteine kinetics \u95 edematous severe childhood undernutrition \u95 nonedematous severe childhood undernutritio

Synthesis of hepatic secretory proteins in normal adults consuming a diet marginally adequate in protein

The plasma concentration and hepatic synthesis rates of albumin, transthyretin, very low-density lipoprotein apolipoprotein B-100 (VLDL-apoB-100), high-density lipoprotein apolipoprotein A-1, fibrinogen, ?1-antitrypsin, and haptoglobin were measured in six normal adults before and after consuming a protein intake of 0.6 g · kg body wt-1 · day-1 for 7 days. The synthesis of hepatic proteins was measured from the incorporation of [2H5]- phenylalanine, following prime/continuous infusion, using plasma VLDL-apoB-100 isotopic enrichment to represent the precursor pool. Synthesis of albumin declined by 50% (P < 0.001) following the lower-protein diet, VLDL-apoB-100 declined by 20% (P < 0.001), and apoA-1 declined by 16% (P < 0.05). By contrast, synthesis increased for fibrinogen (50%, P < 0.05) and haptoglobin (90%, P < 0.001). This pattern of change, with decreased synthesis of nutrient transport proteins and increased formation of acute-phase proteins, suggestive of a low-grade inflammatory response, was accompanied by increased plasma concentration of the inflammatory cytokine interleukin 6 (30%, P < 0.05). The pattern of change in the synthesis of hepatic secretory proteins following 7 days on the low-protein diet may be of functional relevance for lipid transport and the capacity to cope with stress

Endogenous glycine and tyrosine production is maintained in adults consuming a marginal-protein diet

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·kg-1·d-1) to a marginal intake (0.75 g·kg-1·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

Response of hepatic proteins to the lowering of habitual dietary protein to the recommended safe level of intake

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·kg–1·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·kg–1·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·kg–1·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