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).

Supplementation with (6S)-5-methyltetrahydrofolic acid appears as effective as folic acid in maintaining maternal folate status while reducing unmetabolised folic acid in maternal plasma: a randomised trial of pregnant women in Canada.

Folic acid supplementation is recommended during pregnancy to support healthy fetal development; (6S)-5-methyltetrahydrofolic acid ((6S)-5-MTHF) is available in some commercial prenatal vitamins as an alternative to folic acid, but its effect on blood folate status during pregnancy is unknown. To address this, we randomised sixty pregnant individuals at 8-21 weeks' gestation to 0·6 mg/d folic acid or (6S)-5-MTHF × 16 weeks. Fasting blood specimens were collected at baseline and after 16 weeks (endline). Erythrocyte and serum folate were quantified via microbiological assay (as globally recommended) and plasma unmetabolised folic acid (UMFA) via LC-MS/MS. Differences in biochemical folate markers between groups were explored using multivariable linear/quantile regression, adjusting for baseline concentrations, dietary folate intake and gestational weeks. At endline (n 54), the mean values and standard deviations (or median, inter-quartile range) of erythrocyte folate, serum folate and plasma UMFA (nmol/l) in those supplemented with (6S)-5-MTHF v. folic acid, respectively, were 1826 (sd 471) and 1998 (sd 421); 70 (sd 13) and 78 (sd 17); 0·5 (0·4, 0·8) and 1·3 (0·9, 2·1). In regression analyses, erythrocyte and serum folate did not differ by treatment group; however, concentrations of plasma UMFA in pregnancy were 0·6 nmol/l higher (95 % CI 0·2, 1·1) in those supplementing with folic acid as compared with (6S)-5-MTHF. In conclusion, supplementation with (6S)-5-MTHF may reduce plasma UMFA by ∼50 % as compared with supplementation with folic acid, the biological relevance of which is unclear. As folate is currently available for purchase in both forms, the impact of circulating maternal UMFA on perinatal outcomes needs to be determined.

Children Aged 5-6 Years in Vancouver, Canada Meet Dietary Recommendations for Folate and Vitamin B12 but not Choline.

BACKGROUND: Choline, folate, and vitamin B12 are required for growth and development, but there is limited information on the intakes and relationships to biomarkers of status in children. OBJECTIVES: The objective of this study was to determine the choline and B-vitamin intakes and relationship to biomarkers of status in children. METHODS: A cross-sectional study was conducted in children (n = 285, aged 5-6 y) recruited from Metro Vancouver, Canada. Dietary information was collected by using 3 24-h recalls. Nutrient intakes were estimated by using the Canadian Nutrient File and United States Department of Agriculture database for choline. Supplement information was collected by using questionnaires. Plasma biomarkers were quantified by using mass spectrometry and commercial immunoassays, and relationships to dietary and supplement intake were determined by using linear models. RESULTS: Daily dietary intakes of choline, folate, and vitamin B12 were [mean (SD)] 249 (94.3) mg, 330 (120) DFE µg, and 3.60 (1.54) µg, respectively. Top food sources of choline and vitamin B12 were dairy, meats, and eggs (63%-84%) and for folate, were grains, fruits, and vegetables (67%). More than half of the children (60%) were consuming a supplement containing B-vitamins, but not choline. Only 40% of children met the choline adequate intake (AI) recommendation for North America (≥250 mg/d); 82% met the European AI (≥170 mg/d). Less than 3% of children had inadequate folate and vitamin B12 total intakes. Some children (5%) had total folic acid intakes above the North American tolerable upper intake level (UL; >400 µg/d); 10% had intakes above the European UL (>300 µg/d). Dietary choline intake was positively associated with plasma dimethylglycine, and total vitamin B12 intake was positively associated with plasma B12 (adjusted models; P < 0.001). CONCLUSIONS: These findings suggest that many children are not meeting the dietary choline recommendations, and some children may have excessive folic acid intakes. The impact of imbalanced one-carbon nutrient intakes during this active period of growth and development requires further investigation.

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.

Is a Lower Dose of More Bioavailable Iron (18-mg Ferrous Bisglycinate) Noninferior to 60-mg Ferrous Sulfate in Increasing Ferritin Concentrations While Reducing Gut Inflammation and Enteropathogen Detection in Cambodian Women? A Randomized Controlled Noninferiority Trial.

BACKGROUND: Global guidelines recommend untargeted iron supplementation for women in regions of anemia prevalence ≥40%, such as Cambodia. However, the potential harms of untargeted iron on the gut have not been rigorously studied in women and likely vary depending on iron dose and form. OBJECTIVES: We investigated if a lower dose of a highly bioavailable iron amino acid chelate was as effective as the standard dose of iron salts in increasing ferritin concentrations and whether any differences were observed in gut inflammation or enteropathogen detection. METHODS: A double-blind, randomized placebo-controlled noninferiority trial was conducted in Cambodia. Nonpregnant women (n = 480, 18-45 y) were randomly assigned to 60-mg ferrous sulfate, 18-mg ferrous bisglycinate, or placebo for 12 wk. Nonfasting blood and stool specimens were collected at baseline and 12 wk. Ferritin and fecal calprotectin were measured with an ELISA. A molecular assay was used to detect 11 enteropathogens in a random subset of n = 100 women. Generalized linear mixed-effects models were used to estimate the adjusted mean difference in ferritin concentrations at 12 wk (primary outcome), as compared with our 'a priori' noninferiority margin of 20 µg/L. RESULTS: Baseline anemia and iron deficiency prevalence was low (17% and 6%, respectively). The adjusted mean difference in ferritin concentrations between the iron groups was 14.6 (95% confidence interval [CI]: 7.6, 21.6) µg/L. Mean ferritin concentration at 12 wk was higher in the ferrous sulfate (99 [95% CI: 95, 103] µg/L, P < 0.001) than in ferrous bisglycinate (84 [95% CI: 80, 88] µg/L) and placebo groups (78 [95% CI: 74, 82] µg/L). No differences in fecal calprotectin concentrations or enteropathogen detection were observed across groups at 12 wk. CONCLUSIONS: Ferrous bisglycinate (18-mg) was not as effective as ferrous sulfate (60-mg) in increasing ferritin concentrations and did not differentially influence biomarkers of gut health in this predominantly iron-replete population of Cambodian women. This trial was registered at clinicaltrials.gov registry as NCT04017598.

Characterization of Priestia megaterium S1, a polymer degrading gut microbe isolated from the gut of Tenebrio molitor larvae fed on Styrofoam.

This study reveals that Tenebrio molitor larvae are fed with two different feeds i.e., barley bran along with Styrofoam, and barley bran without Styrofoam, the survival percentage of mealworms shows 86 and 89%, respectively. Five isolates namely S1, S2, S3, S4, and S5 were isolated from the gut of Styrofoam-feeding Tenebrio molitor larvae and tested for Hydrophobicity percentage, clear zone assay and turbidity measurement. S1 isolate showed best (turbidity percentage of 19.65%, 13.54% hydrophobicity percentage, and 37% zone of clearance) when compared to other isolates, respectively. 16S rRNA characterization of S1 isolate revealed that the isolate belongs to Priestia megaterium S1(ON024787). Biodegradation of PE and PS beads by Priestia megaterium S1 makes physical and structural changes over 180 days, after microbial adhesion to the beads. Growth parameters have shown that the Priestia megaterium S1 thrives more effectively in the pH (6.5), temperature (28 °C) and at 1.5% LDPE/HDPE/PS concentration there is maximum utilization of carbon and a high percentage survival rate. Significant colonization of the isolate after 30 days over beads of LDPE (52.47%), HDPE (49.26%), and PS (48.11%), respectively. Experimental data revealed that Priestia megaterium S1 have PE and PS beads degradation capacity, proven by weight loss studies, at 6th-month percentage weight loss of LDPE (36.1%), HDPE (31.9%), and PS (28.6%), the percentage loss of carbon and hydrogen shows higher when compared to control. One month Biological Oxygen Demand (BOD) showed that LDPE (7.4 mg/l), HDPE (7.2 mg/l), PS (6.7 mg/l), and simultaneous studies on CO2 evolution over LDPE treatment is 5.05 g/l, HDPE (4.26 g/l), and PS (3.91 g/l), respectively. Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscope (SEM) prove the occurrence of biodegradation on the surface of beads. This work highlights that Priestia megaterium S1 plays a vital role in effectively degrading PE and PS beads.

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.

An evidence review and nutritional conceptual framework for pre-eclampsia prevention.

Pre-eclampsia is a serious complication of pregnancy, and maternal nutritional factors may play protective roles or exacerbate risk. The tendency to focus on single nutrients as a risk factor obscures the complexity of possible interactions, which may be important given the complex nature of pre-eclampsia. An evidence review was conducted to compile definite, probable, possible and indirect nutritional determinants of pre-eclampsia to map a nutritional conceptual framework for pre-eclampsia prevention. Determinants of pre-eclampsia were first compiled through an initial consultation with experts. Second, an expanded literature review was conducted to confirm associations, elicit additional indicators and evaluate evidence. The strength of association was evaluated as definite relative risk (RR) < 0·40 or ≥3·00, probable RR 0·40-0·69 or 1·50-2·99, possible RR 0·70-0·89 or 1·10-1·49 or not discernible RR 0·90-1·09. The quality of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluation. Twenty-five nutritional factors were reported in two umbrella reviews and twenty-two meta-analyses. Of these, fourteen were significantly associated with pre-eclampsia incidence. Higher serum Fe emerged as a definite nutritional risk factors for pre-eclampsia incidence across populations, while low serum Zn was a risk factor in Asia and Africa. Maternal vitamin D deficiency was a probable risk factor and Ca and/or vitamin D supplementation were probable protective nutritional factors. Healthy maternal dietary patterns were possibly associated with lower risk of developing pre-eclampsia. Potential indirect pathways of maternal nutritional factors and pre-eclampsia may exist through obesity, maternal anaemia and gestational diabetes mellitus. Research gaps remain on the influence of household capacities and socio-cultural, economic and political contexts, as well as interactions with medical conditions.

Determining ideal balance among branched-chain amino acids in medical formula for Propionic Acidemia: A proof of concept study in healthy children.

BACKGROUND: Propionic Acidemia (PROP) is an inherited metabolic disorder, with defect in the enzyme propionyl-CoA carboxylase (PCC) which catalyzes catabolism of two of the branched-chain amino acids (BCAA), valine, isoleucine. Nutritional management in PROP depends on dietary protein restriction and consumption of medical formula depleted of the offending amino acids. Recently, concerns have been raised about medical formula due to imbalanced content of BCAA (high leucine - another BCAA, and no valine/isoleucine), which negatively impacts plasma concentrations of BCAA, and growth in children with PROP. OBJECTIVES AND METHODS: To determine an optimal BCAA ratio at which total body protein synthesis is optimized in healthy children using the indicator amino acid oxidation method (oxidation of L-13C-Phenylalanine to 13CO2). This was accomplished by reducing leucine intake gradually from the current high dose in medical formula, in order to compare protein synthesis, under different BCAA ratios. RESULTS: A total of 8 healthy children were studied, completing 42 study days. Significant differences in F13CO2 with different BCAA ratios were found. BCAA ratio (leucine: isoleucine: valine) 1:0:0 was associated with the highest F13CO2 (low protein synthesis) compared to other ratios. By reducing leucine intake, and isoleucine and valine at minimum PROP recommendations, BCAA ratio between1:0.26:0.28 to 1:0.35:0.4 was associated with optimal protein synthesis. CONCLUSION: BCAA ratio of 1:0:0, present in medical formula limited total body protein synthesis. A balanced BCAA ratio was found between 1:0.26:0.28 and 1:0.35:0.4 (leucine:isoleucine:valine). Future research is needed to test this optimal BCAA ratio for optimizing protein synthesis in patients with PROP. SYNOPSIS: The article describes a proof-of-concept study done on healthy school-aged children testing different ratios of branched chain amino acid (BCAA, leucine:isoleucine:valine), in order to determine an optimal ratio at which total body protein synthesis is improved and has implications for dietary management of children with Propionic Acidemia (PROP).

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.

Calcium for pre-eclampsia prevention: A systematic review and network meta-analysis to guide personalised antenatal care.

BACKGROUND: Calcium supplementation reduces the risk of pre-eclampsia, but questions remain about the dosage to prescribe and who would benefit most. OBJECTIVES: To evaluate the effectiveness of high (≥1 g/day) and low (<1 g/day) calcium dosing for pre-eclampsia prevention, according to baseline dietary calcium, pre-eclampsia risk and co-interventions, and intervention timing. SEARCH STRATEGY: CENTRAL, PubMed, Global Index Medicus and CINAHL, from inception to 2 February 2021, clinical trial registries, reference lists and expert input (CRD42018111239). SELECTION CRITERIA: Randomised controlled trials of calcium supplementation for pre-eclampsia prevention, for women before or during pregnancy. Network meta-analysis (NMA) also included trials of different calcium doses. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted published data. The meta-analysis employed random-effects models and the NMA, a Bayesian random-effects model, to obtain direct and indirect effect estimates. MAIN RESULTS: The meta-analysis included 30 trials (N = 20 445 women), and the NMA to evaluate calcium dosage included 25 trials (N = 15 038). Calcium supplementation prevented pre-eclampsia similarly with a high dose (RR 0.49, 95% CI 0.36-0.66) or a low dose (RR 0.49, 95% CI 0.36-0.65). By NMA, high-dose (vs low-dose) calcium did not differ in effect (RR 0.79, 95% CI 0.43-1.40). Calcium was similarly effective regardless of baseline pre-eclampsia risk, vitamin D co-administration or timing of calcium initiation, but calcium was ineffective among women with adequate average baseline calcium intake. CONCLUSIONS: Low- and high-dose calcium supplementation are effective for pre-eclampsia prevention in women with low calcium intake. This has implications for population-level implementation where dietary calcium is low, and targeted implementation where average intake is adequate. TWEETABLE ABSTRACT: A network meta-analysis of 25 trials found that low-dose calcium supplementation (<1 g/day) is as effective as high-dose calcium supplementation (≥1 g/day) in halving the risk of pre-eclampsia when baseline calcium intake is low.

Maternal nutritional risk factors for pre-eclampsia incidence: findings from a narrative scoping review.

BACKGROUND: Pre-eclampsia is a leading cause of maternal mortality and morbidity that involves pregnancy-related stressors on the maternal cardiovascular and metabolic systems. As nutrition is important to support optimal development of the placenta and for the developing fetus, maternal diets may play a role in preventing pre-eclampsia. The purpose of this scoping review is to map the maternal nutritional deficiencies and imbalances associated with pre-eclampsia incidence and discuss evidence consistency and linkages with current understandings of the etiology of pre-eclampsia. METHODS: A narrative scoping review was conducted to provide a descriptive account of available research, summarize research findings and identify gaps in the evidence base. Relevant observational studies and reviews of observational studies were identified in an iterative two-stage process first involving electronic database searches then more sensitive searches as familiarity with the literature increased. Results were considered in terms of their consistency of evidence, effect sizes and biological plausibility. RESULTS: The review found evidence for associations between nutritional inadequacies and a greater risk of pre-eclampsia. These associations were most likely mediated through oxidative stress, inflammation, maternal endothelial dysfunction and blood pressure in the pathophysiology of pre-eclampsia. Maternal nutritional risk factors for pre-eclampsia incidence with the strongest consistency, effect and biological plausibility include vitamin C and its potential relationship with iron status, vitamin D (both on its own and combined with calcium and magnesium), and healthy dietary patterns featuring high consumption of fruits, vegetables, whole grains, fish, seafood and monounsaturated vegetable oils. Foods high in added sugar, such as sugary drinks, were associated with increased risk of pre-eclampsia incidence. CONCLUSION: A growing body of literature highlights the involvement of maternal dietary factors in the development of pre-eclampsia. Our review findings support the need for further investigation into potential interactions between dietary factors and consideration of nutritional homeostasis and healthy dietary patterns. Further research is recommended to explore gestational age, potential non-linear relationships, dietary diversity and social, cultural contexts of food and meals.

Pre-eclampsia is a condition of high blood pressure during the second half of pregnancy with signs of damage to another organ system, often the liver and kidneys. It is a serious and potentially deadly disease and is the second top cause of deaths related to pregnancy and childbirth globally. Though the exact cause of pre-eclampsia is unclear, researchers have discovered that pre-eclampsia develops through abnormal development of the placenta, which is the interface between the growing baby and the mother in the womb. The placenta helps to transfer nutrients, oxygen and waste between the mother and fetus. Nutrition has important roles to play in the development of the placenta and certain vitamins and minerals have clinical properties that may help prevent pre-eclampsia. We conducted a review to summarize observational studies on maternal nutritional risk factors associated with the development of pre-eclampsia. Promising maternal dietary factors that fit with current understandings of how pre-eclampsia develops include vitamin C and its potential relationship with iron, calcium and vitamin D. Healthy dietary patterns with high consumption of fruits, vegetables, whole grains, fish and seafood and monounsaturated vegetable oils are likely beneficial. Foods high in added sugar, such as sugary drinks, may be linked to higher rates of developing pre-eclampsia. Instead of focusing on single nutrient deficiencies, our findings support a broader approach to explore interrelationships between dietary factors and balanced healthy dietary intake for the prevention of pre-eclampsia.

A discussion on the 'dispensable' amino acids.

PURPOSE OF REVIEW: Recently, the concept of dietary dispensable amino acids has been increasingly challenged, as more indirect and direct (experimental) evidence has pointed to the need for them in the diet during specific life stages or disease states. Here, we discuss the classification of amino acids, methods to assess the needs for dispensable amino acids with experimental evidence from our recent studies, and highlight the role of specific dispensable amino acids in metabolism and health. RECENT FINDINGS: There exist differences among the dispensable amino acids to act as effective nitrogen sources in humans. Glycine, a dispensable amino acid is conditionally indispensable in later stages of human pregnancy. SUMMARY: The so-called 'dispensable' amino acids are quantitatively nearly 75% of the daily protein needs in humans. In certain life-stages and diseases, there is a dietary demand for the dispensable amino acids. Future well-designed studies are required to identify the dietary demand for these amino acids, which will certainly be useful for dietary management in specific diseases and to maintain health across all life-stages.

Glycine, a Dispensable Amino Acid, Is Conditionally Indispensable in Late Stages of Human Pregnancy.

BACKGROUND: Recently, we showed that there are higher protein, lysine, and phenylalanine requirements in late stages of pregnancy compared with early stages. Animal studies have suggested an increased dietary need for specific dispensable amino acids in pregnancy; whether such a need exists in human pregnancies is unknown. OBJECTIVE: The objective of the current study was to examine whether healthy pregnant women at midgestation (20-29 wk) and late gestation (30-40 wk) have a dietary demand for glycine, a dispensable amino acid, using the indicator amino acid oxidation method and measurement of plasma 5-oxoproline concentrations. METHODS: Seventeen healthy women (aged 26-36 y) randomly received different test glycine intakes (range: 5-100 mg·kg-1·d-1) during each study day in midgestation (∼26 wk, n = 17 observations in 9 women) and late gestation (∼35 wk, n = 19 observations in 8 women). Diets were isocaloric with energy at 1.7 × resting energy expenditure. Protein was given as a crystalline amino acid mixture based on egg protein composition at current estimated average requirement (EAR; 0.88 g·kg-1·d-1). Breath samples were collected at baseline and isotopic steady state to measure oxidation of L-[1-13C]phenylalanine to 13CO2 (F13CO2). Plasma was collected at the sixth hour of the study day. Linear regression crossover analysis and simple linear regression were used to assess responses in F13CO2 and plasma 5-oxoproline concentrations to different glycine intakes. RESULTS: No statistically significant responses were observed in midgestation. However, in late gestation, lower glycine intakes resulted in higher rates of F13CO2 (suggesting low protein synthesis) with a breakpoint for phenylalanine oxidation at >37 mg glycine·kg-1·d-1 and higher plasma 5-oxoproline (suggesting low glycine availability) with a breakpoint >27 mg glycine·kg-1·d-1. CONCLUSIONS: The findings suggest that glycine should be considered a "conditionally" indispensable amino acid during late gestation, especially when protein intakes are at 0.88 g·kg-1·d-1, the current EAR. This trial was registered at clinicaltrials.gov as NCT02149953.

Tolerable amounts of amino acids for human supplementation: summary and lessons from published peer-reviewed studies.

Amino acid supplementation may be indicated to correct for insufficient amino acid intake in healthy individuals, and in specific physiological or pathophysiological situations. However, there is a concern to not supplement beyond the tolerable upper intake level (UL) by determining parameters of no-observed-adverse-effect level (NOAEL) or lowest-observed-adverse-effect level (LOAEL) for each amino acid. Since the NOAEL and LOAEL values are at least one order of magnitude different when comparing the values obtained in rats and humans, the aim of this review is to evaluate to what extent the amino acid UL measured in the rat model, when referenced to the dietary usual consumption (UC) and dietary requirement (RQ) for indispensable amino acids, may be used as an approximation of the UL in humans. This review then compares the ratios of the NOAEL or LOAEL over UC and RQ in the rat model with the same ratios calculated in humans for the nine amino acids (arginine, serine, glycine, histidine, leucine, lysine, methionine, phenylalanine, and tryptophan) for which this comparison can be done. From the calculations made, it appears that for these 9 amino acids, the calculated ratios for rats and humans, although rather different for several amino acids, remains for all of them in the same order of magnitude. For tryptophan, tyrosine, and valine, the ratios calculated in rats are markedly different according to the sex of animals, raising the view that it may be also the case in humans.

The missing focus on women's health in the First 1,000 days approach to nutrition.

The First 1,000 Days approach highlights the time between conception and a child's second birthday as a critical period where adequate nutrition is essential for adequate development and growth throughout the child's life and potentially onto their own offspring. Based on a review of relevant literature, this commentary explores the First 1,000 Days approach with a maternal lens. While the primary objective of the First 1,000 Days approach to nutrition is to reduce child malnutrition rates, particularly chronic undernutrition in the form of stunting, interventions are facilitated through mothers in terms of promoting healthy behaviours such as exclusive breast-feeding and attention to her nutritional status during pregnancy and lactation. Though these interventions were facilitated through women, women's health indicators are rarely tracked and measured, which we argue represents a missed opportunity to strengthen the evidence base for associations between maternal nutrition and women's health outcomes. Limited evidence on the effects of dietary interventions with pregnant and lactating mothers on women's health outcomes hinders advocacy efforts, which then contributes to lower prioritisation and less research.

Methionine Nutrition and Metabolism: Insights from Animal Studies to Inform Human Nutrition.

Methionine is a nutritionally indispensable amino acid, and is unique among indispensable amino acids due to its sulfur atom. Methionine is involved in cysteine synthesis via the transsulfuration pathway, which is rate limiting for the key antioxidant molecule, glutathione. Methionine is also the primary methyl donor in the body through S-adenosylmethionine via the transmethylation pathway, which is involved in the synthesis of several key metabolites including creatine and phosphatidylcholine. Methionine can also be remethylated from homocysteine, in the presence of betaine via choline and/or folate. Thus methionine demands from a dietary perspective are regulated not only by the presence of cysteine in the body, but also by the demands in vivo for the various metabolites formed from it, and also by the presence of these compounds in foods. Indeed, methionine, cysteine, and the various methyl donors/acceptors vary in human foods, and thus regulate methionine availability, especially under conditions of growth and development. Much of our understanding of methionine nutrition and metabolism arises from experiments in animal models. This is because most animal feed formulations are plant-based and plant sources are relatively low in methionine and cysteine amounts. Thus, this brief review will touch on some broad aspects of human methionine nutrition, including requirements in different life stages, disease, and bioavailability, with some examples from the insights/lessons learned from experiments initially conducted in animals.

Dispensable Amino Acids, except Glutamine and Proline, Are Ideal Nitrogen Sources for Protein Synthesis in the Presence of Adequate Indispensable Amino Acids in Adult Men.

BACKGROUND: Nutritionally, there is a dietary requirement for indispensable amino acids (IAAs) but also a requirement for nitrogen (N) intake for the de novo synthesis of the dispensable amino acids (DAAs). It has been suggested that there might be a dietary requirement for specific DAAs. OBJECTIVES: Experiment 1 tested whether 9 of the DAAs (Ala, Arg, Asn, Asp, Gln, Glu, Gly, Pro, Ser) are ideal N sources using the indicator amino acid oxidation (IAAO) technique. Experiment 2 examined whether there is a dietary requirement for Glu in adult men. METHODS: Seven healthy men (aged 20-24 y) participated in 11 or 2 test diet intakes, in experiment 1 and 2, respectively, in a repeated measures design. In experiment 1, a base diet consisting of the IAA provided at the RDA was compared with test intakes with the base diet plus addition of individual DAAs to meet a 50:50 ratio of IAA:DAA on an N basis. In experiment 2, the diets corresponded to the amino acid pattern present in egg protein, in which all Glu and Gln was present as Glu, or removed, with Ser used to make the diets isonitrogenous. On each study day the IAAO protocol with l-[1-13C]phenylalanine was used to measure whole-body protein synthesis. RESULTS: In experiment 1, repeated measures ANOVA with post hoc multiple comparisons showed that 7 of the 9 DAAs (Ala, Arg, Asn, Asp, Glu, Gly, Ser) decreased IAAO significantly (P < 0.05) compared with base IAA diet, the exceptions being Gln and Pro. In experiment 2, a paired t test did not find significant (P > 0.05) differences in the IAAO in response to removal and replacement of Glu intake. CONCLUSIONS: The results suggest that in healthy men most DAAs are ideal N sources for protein synthesis, in the presence of adequate IAAs, and that endogenous synthesis of Glu is sufficient.Registered clinicaltrials.gov identifier: NCT02009917.