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Plasma amino acid pools in the umbilical cord artery show lower 15N natural isotope abundance relative to the maternal venous pools
Abstract
N natural isotope abundance (NIA) is systematically higher in infants’ hair than in that of their mothers at birth. This study aimed to investigate this difference in plasma pools. We compared ¹⁵N NIA values for plasma amino acid (AA) pools (free + protein-bound) in the umbilical cord artery (UCA) and vein (UCV) and in the maternal vein (MV) at birth. This preliminary study included 7 mother–infant dyads. Whole plasma was treated (HCl) to hydrolyze protein. Following derivatization, AAs were separated using gas chromatography and compound-specific ¹⁵N NIA values were measured on-line using an isotope ratio monitoring mass spectrometer. ¹⁵N NIA plasma AA pools in the UCA and UCV were highly correlated to the MV, r ² > 0.89 and r ² > 0.88 (both P < 10⁻⁴) respectively. The full model found a significant effect of sampling compartment (P = 0.02) and AA type (P < 0.0001) on ¹⁵N NIA plasma AA values. ¹⁵N NIA plasma AA was 0.74 ‰ higher (P = 0.01) in the MV than in the UCA. This study indicates that a decrease in ¹⁵N NIA for plasma AA pools occurs in the fetal–placental unit.
Trial registration: ClinicalTrials.gov identifier: NCT00607061.
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Natural abundances of stable nitrogen and carbon isotopes (δ15N and δ13C) can vary with both dietary intake and metabolic (specifically catabolic) state. In low-income countries, weaning is a period of dietary transition from milk to plant-based foods and a high-risk period for malnutrition. We explored how diet and malnutrition impact hair δ15N and δ13C in young children by an observational, cross-sectional study in Cox’s Bazar District, Bangladesh [255 children, 6–59 months with 19.6% wasted (7.1% severely) and 36% stunted (9.8% severely)]. Hair δ15N and δ13C exhibited exponential decreases with age, with the loss of one trophic level (3.3‰ and 0.8‰, respectively) from 6 to 48 months, which we associate with the shift from exclusive breastfeeding to complete weaning. After adjustment for age and breastfeeding status, hair isotopic values were unaffected by wasting but lower in severe stunting (−0.45‰ to −0.6‰, P < 0.01). In this population of young children, whose isotopic values in hair primarily depended on age, we failed to observe any effect of wasting, likely due to opposite, compensating effects between dietary and metabolic changes involved. In contrast, we evidenced low δ15N and δ13C values in severely stunted children that likely indicate chronic exposure to diets low in animal products.
Background: Stable-isotope ratios of carbon (13C/12C, expressed as δ13C) and nitrogen (15N/14N, or δ15N) have been proposed as potential nutritional biomarkers to distinguish between meat, fish, and plant-based foods.
Objective: The objective was to investigate dietary correlates of δ13C and δ15N and examine the association of these biomarkers with incident type 2 diabetes in a prospective study.
Design: Serum δ13C and δ15N (‰) were measured by using isotope ratio mass spectrometry in a case-cohort study (n = 476 diabetes cases; n = 718 subcohort) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)–Norfolk population-based cohort. We examined dietary (food-frequency questionnaire) correlates of δ13C and δ15N in the subcohort. HRs and 95% CIs were estimated by using Prentice-weighted Cox regression.
Results: Mean (±SD) δ13C and δ15N were −22.8 ± 0.4‰ and 10.2 ± 0.4‰, respectively, and δ13C (r = 0.22) and δ15N (r = 0.20) were positively correlated (P < 0.001) with fish protein intake. Animal protein was not correlated with δ13C but was significantly correlated with δ15N (dairy protein: r = 0.11; meat protein: r = 0.09; terrestrial animal protein: r = 0.12, P ≤ 0.013). δ13C was inversely associated with diabetes in adjusted analyses (HR per tertile: 0.74; 95% CI: 0.65, 0.83; P-trend < 0.001], whereas δ15N was positively associated (HR: 1.23; 95% CI: 1.09, 1.38; P-trend = 0.001).
Conclusions: The isotope ratios δ13C and δ15N may both serve as potential biomarkers of fish protein intake, whereas only δ15N may reflect broader animal-source protein intake in a European population. The inverse association of δ13C but a positive association of δ15N with incident diabetes should be interpreted in the light of knowledge of dietary intake and may assist in identifying dietary components that are associated with health risks and benefits.
Fractional synthesis rates (FSR) of tissue proteins (P) are usually measured using labeled amino acid (AA) tracer methods over short periods of time under acute, particular conditions. In this work, we developed a new isotopic approach, by combining the long-term and non-steady-state 15N labeling of AA and P tissue fractions with compartmental modeling, in order to investigate the degree of compartmentation of P turnover in tissues and to estimate long-term FSR values under sustained and averaged nutritional and physiological conditions. We measured the rise-to-plateau kinetics of nitrogen isotopic enrichments (δ(15)N) in both the AA and P fractions of various tissues in rats for 2 months following a slight increase in the diet δ(15)N. From these δ(15)N kinetics, and using a numerical method based on a 2-compartment model, we determined reliable FSR estimates for tissues in which P turnover is adequately represented by such a simple precursor-product model. This was the case for the kidney, liver, plasma and muscle, where the FSR estimates were 103%/d, 101%/d, 58%/d and 11%/d, respectively. Conversely, we identified tissues, namely the skin and small intestine, whose P turnover proved to be too complex to be represented by a simple 2-compartment model, evidencing the higher level of sub-compartmentation of the P and/or AA metabolism in these tissues. The present results support the value of this new approach in gaining both cognitive and practical insights into tissue P turnover, and propose new and integrated FSR values over all individual precursor AA and all diurnal variations in P kinetics.
Depletion of blood glutathione (GSH), a key antioxidant, is known to occur in preterm infants.
Our aim was to determine: 1) whether GSH depletion is present at the time of birth; and 2) whether it is associated with insufficient availability of cysteine (cys), the limiting GSH precursor, or a decreased capacity to synthesize GSH.
Sixteen mothers delivering very low birth weight infants (VLBW), and 16 mothers delivering healthy, full term neonates were enrolled. Immediately after birth, erythrocytes from umbilical vein, umbilical artery, and maternal blood were obtained to assess GSH [GSH] and cysteine [cys] concentrations, and the GSH synthesis rate was determined from the incorporation of labeled cysteine into GSH in isolated erythrocytes ex vivo, measured using gas chromatography mass spectrometry.
Compared with mothers delivering at full term, mothers delivering prematurely had markedly lower erythrocyte [GSH] and [cys] and these were significantly depressed in VLBW infants, compared with term neonates. A strong correlation was found between maternal and fetal GSH and cysteine levels. The capacity to synthesize GSH was as high in VLBW as in term infants.
The current data demonstrate that: 1) GSH depletion is present at the time of birth in VLBW infants; 2) As VLBW neonates possess a fully active capacity to synthesize glutathione, the depletion may arise from inadequate cysteine availability, potentially due to maternal depletion. Further studies would be needed to determine whether maternal-fetal cysteine transfer is decreased in preterm infants, and, if so, whether cysteine supplementation of mothers at risk of delivering prematurely would strengthen antioxidant defense in preterm neonates.
Eight pregnant sheep were infused with two amino acid mixtures of different composition: essential amino acids only and the essentials plus some of the nonessentials. Uterine and umbilical uptakes of amino acids were measured before and during infusion. For most of the amino acids, the infusion increased both maternal plasma concentration and umbilical uptake. However, depending on the infusate composition, the increase in maternal concentration of some amino acids was associated with no change or a significant reduction in umbilical uptake. Data were pooled from this and other, similar studies to test the hypothesis that umbilical uptake of several amino acids can be inhibited by coinfused amino acids. The test consisted of fitting the data, by means of multiple regression analysis, to the linear transformation of a saturation kinetics equation in which uptake is assumed to depend on maternal arterial concentrations. The analysis showed significant inhibitory effects within the neutral essential amino acids group and within the lysine-arginine group, with no demonstrable interaction between the two groups. Uterine uptakes did not show clear evidence of saturability and inhibitory interactions, suggesting a large transport capacity and low transporter affinity on the maternal surface of the trophoblast. We conclude that the transport of any given amino acid from placenta to fetus is a function of both its own maternal concentration and the maternal concentration of inhibitory amino acids.
The stable nitrogen (15N) and carbon (13C) isotopic composition of tissues reflects the isotopic pattern of food sources. We investigated whether the isotopic composition of human hair can be used as a biomarker to predict the dietary intake of animal-derived food. Hair samples were collected from subjects during a 1987-1988 German nutrition survey (VERA) in which dietary information was collected using a 7-d dietary record. Samples of 50 men and 50 women were randomly selected, in addition to 27 samples of subjects with a reported low meat intake. Isotope ratio MS was used to analyze hair bulk and amino acid-specific isotopic composition. Its relation with and feasibility for predicting animal protein intake were tested using regression analysis and cross-tabulation of observed and predicted dietary data and comparison of the individual values for the binary categories of high and low intake. 15N and 13C abundances strongly predicted relative animal protein and meat intake (R2= 0.31, P < 0.01 and R2= 0.20, P <0.01, respectively). Distinct patterns of individual hair amino acid 15N and 13C abundances were observed. In contrast to bulk values, the isotopic abundances in individual amino acids did not show discriminating ability across sex and isotope-specific categories. We conclude that hair 13C values are as predictive for animal protein consumption as hair 15N values. Bulk isotopic abundance of hair can be used as a biomarker for animal protein intake to validate dietary assessment methods provided that the correlation between isotopic abundances and dietary protein intake is verified in dietary intervention studies.
An objective means based on the carbon and nitrogen stable isotope analysis of five hairs per individual is presented for distinguishing between individuals with anorexia nervosa and/or bulimia nervosa from non-clinical individuals (i.e. clinically normal controls). Using discriminant analysis, an algorithm has been developed that provides both sensitivity and specificity of 80% in making diagnoses of individuals with these eating disorders. With further refinements, the results suggest that it may be also possible to distinguish between individuals with anorexia or bulimia. Finally, the study shows the value of conducting blind tests and using larger sample sizes of both control and treatment groups. Both groups are needed to validate the diagnostic value of a method and to provide measures of sensitivity and specificity of any diagnostic test.
Diet is a leading modifiable risk factor for chronic disease, but it remains difficult to measure accurately due to the error and bias inherent in selfreported methods of diet assessment. Consequently, there is a pressing need for more objective biomarkers of diet for use in health research. The stable isotope ratios of light elements are a promising set of candidate biomarkers because they vary naturally and reproducibly among foods, and those variations are captured in molecules and tissues with high fidelity. Recent studies have identified valid isotopic measures of short- and long-term sugar intake, meat intake, and fish intake in specific populations. These studies provide a strong foundation for validating stable isotopic biomarkers in the general US population. Approaches to improve specificity for specific foods are needed; for example, by modeling intake using multiple stable isotope ratios or by isolating and measuring specific molecules linked to foods of interest. Expected final online publication date for the Annual Review of Nutrition Volume 35 is July 17, 2015. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
In the Central European context, the 9th and 10th centuries are well known for rapid cultural and societal changes concerning the development of the economic and political structures of states as well as the adoption of Christianity. A bioarchaeological study based on a subadult skeletal series was conducted to tackle the impact of these changes on infant and young child feeding practices and, consequently, their health in both urban and rural populations. Data on growth and frequency of nonspecific stress indicators of a subadult group aged 0-6 years were analyzed. A subsample of 41 individuals was selected for nitrogen and carbon isotope analyses, applying an intra-individual sampling strategy (bone vs. tooth). The isotopic results attest to a mosaic of food behaviors. In the urban sample, some children may have been weaned during their second year of life, while some others may have still been consuming breast milk substantially up to 4-5 years of age. By contrast, data from the rural sample show more homogeneity, with a gradual cessation of breastfeeding starting after the age of 2 years. Several factors are suggested which may have been responsible for applied weaning strategies. There is no evidence that observed weaning strategies affected the level of biological stress which the urban subadult population had to face compared with the rural subadult population. Am J Phys Anthropol, 2014. © 2014 Wiley Periodicals, Inc.
Background and aims
Nephropathy is a serious long-term complication in type 2 diabetic patients. Few data are available about nitrogen metabolism in diabetic nephropathy. Bulk 15N natural isotopic abundance (NIA) in hair has been shown modified in different pathologies with altered protein metabolism. We have compared bulk 15N NIA in hair proteins in type 2 diabetic patients to look for differences between groups with or without nephropathy.
Methods
Case patients were type 2 diabetic patients with high urinary albumin concentrations (≥20 mg/L or 30 mg/24h on two of three urine collections) and/or an estimated glomerular filtration rate (eGFR) below 60 mL min-1 1.73m-2, according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Control subjects were type 2 diabetic patients of the same geographical origin with long-term diabetes, normo-albuminuria and eGFR above 60 mL min-1 1.73m-2. The bulk 15N NIA values for hair were measured by isotope ratio measurement mass spectrometry coupled with an elemental analyzer.
Results
Thirty-three patients in the nephropathy group and 31 in the control group were included. The mean age of the participants was 69±8 years, and the mean duration of diabetes was 22±8 years. Bulk hair 15N NIA were 8.9±0.7 ‰ in the nephropathy group and 9.0±0.5 ‰ in the control group (p=0.41). Positive correlations were found between bulk hair 15N NIA with eGFR (p<0.01) and with urinary urea concentration (p<0.01), and a negative correlation with the urinary albumin-to-creatinine ratio (p<0.001).
Conclusions
Bulk hair 15N NIA might be an easily available, non-invasive biomarker of nitrogen metabolism in type 2 diabetic patients.
In isotope tracer experiments used in nutritional studies, it is frequently desirable both to determine the (15) N/(14) N ratios of target compounds and to quantify these compounds. This report shows how this can be achieved in a single chromatographic run for protein amino acids using an isotope ratio mass spectrometer.
Protein hydrolysis by acidic digestion was used to release amino acids, which were then derivatized as their N-pivaloyl-O-isopropyl esters. Suitable conditions for sample preparation were established for both hair and milk proteins. The N-pivaloyl-O-isopropyl esters of amino acids were separated by gas chromatography (GC) on a 60 m ZB-WAX column linked via a combustion interface to an isotope ratio mass spectrometer. The (15) N/(14) N ratios were obtained from the m/z 28, 29 and 30 peak intensities and the quantities from the Area All (Vs) integrated peak areas.
It is shown from a five-point calibration curve that both parameters can be measured reliably within the range of 1.0 to 2.0 mg/mL for the major amino acids derived from the hydrolysis of human maternal milk or hair samples. The method was validated in terms of inter-day and inter-user repeatability for both parameters for 14 amino acids. The amino acid percentage composition showed a good correlation with literature values. The method was applied to determine the variability in a population of lactating mothers and their infants.
It has been established that δ(15) N values can be simultaneously determined for a complex mixture of amino acids at variable concentrations. It is shown that the percentage composition obtained correlates well with that obtained by calculation from the protein composition or from literature values. This procedure should provide a significant saving in analysis time, especially in those cases where the GC run-time is necessarily long. It allows the satisfactory determination of the variation within a sample population. Copyright © 2013 John Wiley & Sons, Ltd.
To assess the global effect of preterm birth on fetal metabolism and maternal-fetal nutrient transfer, we used a mass spectrometric based chemical phenotyping approach on cord blood obtained at the time of birth. We sampled umbilical venous, umbilical arterial, and maternal blood from mothers delivering very-low-birth-weight (VLBW, with a median gestational age and weight of 29 weeks, and 1210 grams, respectively) premature or full-term (FT) neonates. In VLBW group, we observed a significant elevation in the levels and maternal-fetal gradients of butyryl-, isovaleryl-, hexanoyl- and octanoyl-carnitines, suggesting enhanced short- and medium chain fatty acid -oxidation in human preterm feto-placental unit. The significant decrease in glutamine-glutamate in preterm arterial cord blood beside lower levels of amino acid precursors of Krebs cycle suggest increased glutamine utilization in the fast growing tissues of preterm fetus with a deregulation in placental glutamate-glutamine shuttling. Enhanced glutathione utilization is likely to account for the decrease in precursor amino acids (serine, betaine, glutamate and methionine) in arterial cord blood. An increase in both the circulating levels and maternal-fetal gradients of several polyamines in their acetylated form (diacetylspermine and acetylputrescine) suggests an enhanced polyamine metabolic cycling in extreme prematurity. Our metabolomics study allowed the identification of alterations in fetal energy, antioxidant defense, and polyamines and purines flux as a signature of premature birth.
A number of biologically active peptides have been proposed to regulate function and differentiation of reproductive organs in an autocrine and/or paracrine fashion. Regulation of the local concentrations of these peptides is one of the important factors influencing their physiological effects on target cells. Membrane-bound cell surface peptidases can activate or inactivate biologically active peptides before peptide factors access their receptors on the cell surface. Aminopeptidase A (EC 3.4.11.7), placental leucine aminopeptidase (EC 3.4.11.3), aminopeptidase-N/CD13 (EC 3.4.11.2), dipeptidyl peptidases IV/CD26 (EC.3.4.14.5), carboxypeptidase-M (EC 3.4.17.12), neutral endopeptidase/CD10 (EC 3.4.24.11) and endothelin converting enzyme-1 (EC 3.4.23) are differentially expressed on the ovary, endometrium and placenta. The inhibition of enzyme activity affects steroid hormone production by granulosa and thecal cells, decidualization of endometrium and migration of extravillous trophoblasts. These findings suggest that membrane-bound cell surface peptidases are local regulators for cellular growth and differentiation in reproductive organs by controlling extracellular concentration of peptide factors. (Reprod Med Biol 2004; 3: 165 –176)
Societal interest in food safety, animal welfare, and environmental quality attributes of food production is increasing, creating a need for reliable indicators of such factors. Here we test the hypothesis that cattle farming systems create unique and meaningful isotopic fingerprints, which can be characterized by analysing cattle tail switch hair. To this end we analysed feeding practices and nutrient fluxes, and sampled hair, feed components and fertilizers from 13 different farms in Upper Bavaria, Germany. The farms represented the range of cattle farming types present in the region and included: conventional confinement dairy, pasture based organic and conventional dairy, suckler cow, and bull and steer and heifer fattening enterprises. Samples were analysed for their carbon
Protein intake in fetal life or infancy may play a key role in determining early growth rate, a determinant of later health and disease. Previous work has indicated that hair isotopic composition is influenced by diet and protein intake.
This study analyzes the isotopic composition of hair obtained from 239 mother/newborn pairs randomly selected within a larger cohort enrolled in a study of pre- and postnatal determinants of the child's development and health. The isotopic compositions in nitrogen (δ(15)N) and in carbon (δ(13)C) were determined by isotope ratio mass spectrometry.
Mother and newborn hair δ(15)N were tightly correlated (Pearson r = 0.88). The mean δ(15)N and δ(13)C values of hair from newborn infants were significantly higher than those for the mothers: 9.7 ± 0.7 vs. 8.8 ± 0.6‰ (P < 0.0001) for δ(15)N and -20.0 ± 0.4 vs. -20.4 ± 0.4‰ (P < 0.0001) for δ(13)C. Maternal hair δ(15)N at parturition was slightly and positively correlated with estimates of protein intake (r = 0.14, P = 0.04).
Hair δ(15)N of the fetus is both highly dependent on and systematically higher than that of the mother. Whether quantitative and qualitative protein intake, disease, or hormonal status alter hair δ(15)N at birth remains to be determined.
A high protein or meat intake might be a risk factor for metabolic disorders. Stable isotopic abundances (SIA) of hair can be used as biomarkers for animal protein intake due to characteristic isotopic patterns of food proteins. We investigated if an additional meat intake (M, 200 g pork fillet/day) or an omission of meat and meat products (NOM) can influence the natural (15)N and (13)C SIA within 4 weeks in hair and plasma of young women. The daily protein intake (means +/- SD) was 1.40 +/- 0.29, 2.25 +/- 0.35, and 1.15 +/- 0.26 g/kg at baseline, during M, and during NOM, respectively. At baseline the animal protein intake correlated with bulk SIA of hair ((15)N: R(2) = 0.416; (13)C: R(2) = 0.664; n = 14). However, isotope ratio mass spectrometry (IRMS) analyses have not shown that hair and plasma SIA were changed significantly after M or NOM. Possible reasons were discussed. Urinary SIA were significantly lower after M than after NOM ((15)N: p = 0.039; (13)C: p = 0.006) and close to those of pork fillet. Characteristic patterns of SIA were measured in individual amino acids (AA) by gas chromatography/combustion isotope ratio mass spectrometry (GC/C/IRMS). The results confirmed considerable differences in SIA between AA (delta(15)N, up to 22 per thousand; delta(13)C, up to 31 per thousand). Plots of (15)N versus (13)C abundances in hair revealed characteristic differences between indispensable and dispensable AA. The intervention-dependent changes of AA-specific SIA were not as clear as expected. Although the AA-specific SIA may reveal more detailed characteristics of physiological conditions, further methodological research is required. We suggest that the SIA of leucine can be potential markers of protein intake. The reliability of SIA as biomarkers of protein intake still have to be tested in longer lasting intervention studies in humans. The results may have implications in the assessment for possible benefits and risks of protein consumption.
The carbon ((13)C/(12)C) and nitrogen ((15)N/(14)N) stable isotope ratios of human hair can be used for the interpretation of dietary habits and nutritional status in contemporary or past populations. Although the results of bulk or segmental isotope ratio analysis of human hair have been used for the reconstruction of an individual's diet for years, only limited data of controlled dietary changes on the carbon and nitrogen isotopic composition of human hair are available. Hair of four individuals, two males and two females, who participated in a dietary change experiment for 28 days was segmentally analysed for delta(13)C and delta(15)N. The dietary change included a change from C3 to C4 plant enriched diets and a simultaneous replacement of terrestrial animal products by marine products. This resulted in an increase in delta(13)C(diet) of +8.5 to +9.9 per thousand and in delta(15)N(diet) of +1.5 to +2.2 per thousand. All subjects showed significant increases in delta(13)C(hair) and delta(15)N(hair) during the dietary change period, although no subject reached a new steady state for either carbon or nitrogen. The change in delta(15)N(hair) was faster than the change in delta(13)C(hair) for all individuals. The magnitude of change of the isotopic composition during the dietary change period could be attributed to the degree of physical activity of the individuals, with a higher physical activity resulting in a faster change.
The degradation of several bioactive peptides and proteins by purified human dipeptidyl peptidase IV is reported. It was hitherto unknown that human gastrin-releasing peptide, human chorionic gonadotropin, human pancreatic polypeptide, sheep prolactin, aprotinin, corticotropin-like intermediate lobe peptide and (Tyr-)melanostatin are substrates of this peptidase. Kinetic constants were determined for the degradation of a number of other natural peptides, including substance P, the degradation of which has been described earlier in a qualitative manner. Generally, small peptides are degraded much more rapidly than proteins. However, the Km-values seem to be independent of the peptide chain length. The influence of the action of dipeptidyl peptidase IV on the biological function of peptides and proteins is discussed.
The transport and metabolism of glutamine (GLN) and glutamate (GLU) during fetal development exhibit unique characteristics that clearly emphasize the importance of the interaction between the placenta and the fetal liver. GLN is delivered into the fetal circulation at a rate that is the highest of all the amino acids. In contrast, approximately 90% of fetal plasma GLU is extracted by the placenta. Conversely, the fetal liver has a large net output of GLU and a net uptake of GLN. We have studied the fluxes of GLU and GLN into and out of the placenta and fetal liver, as well as their interconversion in these organs, during late gestation in sheep. In the fetus, 45% of GLN carbon taken up by the liver exits as GLU; indeed, the production of GLU from GLN is large, approximately 3.7 micromol/(min.kg fetus), and accounts for virtually all of the GLU produced in the fetus. In contrast, only 6% of GLU carbon is converted to GLN in the placenta; most of the fetal plasma GLU taken up by this organ is converted to CO(2). Remarkably, placental GLU uptake accounts for >60% of the fetal plasma GLU disposal rate. In some respects, the net output of GLU from the liver in fetuses replaces the net hepatic glucose output that is characteristic of postnatal life. We also examined GLN and GLU fluxes in pregnant sheep during either dexamethasone-induced or spontaneous parturition. At parturition, a striking reduction in GLU output from the fetal liver occurred, leading to a fall in fetal arterial GLU concentrations and a marked decrease in placental GLU uptake. These changes were progressive as parturition advanced and correlated with a marked decrease in progesterone output from the pregnant uterus.
Carbon (13C/12C) and nitrogen (15N/14N) stable isotope ratios were longitudinally measured in human hair that reflected the period from pre-conception to delivery in 10 pregnant women. There was no significant change in the delta13C results, but all subjects showed a decrease in delta15N values (-0.3 to -1.1 per thousand) during gestation. The mechanisms causing this decrease in hair delta15N have not been fully elucidated. However, since the delta15N values of dietary nitrogen and urea nitrogen are significantly lower compared to maternal tissues, it is hypothesized that the increased utilization of dietary and urea nitrogen for tissue synthesis during pregnancy resulted in a reduction of the steady state diet to a body trophic level effect by approximately 0.5-1 per thousand. An inverse correlation (R2 = 0.67) between hair delta15N and weight gain was also found, suggesting that positive nitrogen balance results in a reduction of delta15N values independent of diet. These results indicate that delta15N measurements have the ability to monitor not only dietary inputs, but also the nitrogen balance of an organism. A potential application of this technique is the detection of fertility patterns in modern and ancient species that have tissues that linearly record stable isotope ratios through time.
While past experiments on animals, birds, fish, and insects have shown changes in stable isotope ratios due to nutritional stress, there has been little research on this topic in humans. To address this issue, a small pilot study was conducted. Hair samples from eight pregnant women who experienced nutritional stress associated with the nausea and vomiting of morning sickness (hyperemesis gravidarum) were measured for carbon (delta13C) and nitrogen (delta15N) stable isotope ratios. The delta13C results showed no change during morning sickness or pregnancy when compared with pre-pregnancy values. In contrast, the delta15N values generally increased during periods of weight loss and/or restricted weight gain associated with morning sickness. With weight gain and recovery from nutritional stress, the hair delta15N values displayed a decreasing trend over the course of gestation towards birth. This study illustrates how delta15N values are not only affected by diet, but also by the nitrogen balance of an individual. Potential applications of this research include the development of diagnostic techniques for tracking eating disorders, disease states, and nitrogen balance in archaeological, medical, and forensic cases.
Carbon ((13)C/(12)C) and nitrogen ((15)N/(14)N) stable isotope ratios were longitudinally measured in fingernail and hair samples from mother-infant pairs where infants were exclusively breastfed (n = 5), breast- and formula-fed (n = 2), or exclusively formula-fed (n = 1) from birth. All exclusively breastfed infants had a dual enrichment in carbon ( approximately 1 per thousand) and nitrogen ( approximately 2-3 per thousand) when compared to maternal values. In contrast, breast- and formula-fed subjects had reduced enrichments compared to exclusively breastfed subjects, and the exclusively formula-fed infant showed no increase in delta(13)C or delta(15)N values. This finding of a carbon trophic level effect in breastfeeding infants suggests that (13)C-enrichments of approximately 1 per thousand in archaeological populations are not necessarily the result of the consumption of C(4)-based weaning foods such as maize or millet. During the weaning process, the delta(13)C results for breastfed infants declined to maternal levels more rapidly than the delta(15)N results. This suggests that delta(13)C values have the potential to track the introduction of solid foods into the diet, whereas delta(15)N values monitor the length of time of breast milk consumption. These findings can be used to refine the isotopic analysis of breastfeeding and weaning patterns in past and modern populations.
The stable-isotopic composition of nitrogen (delta15N) or carbon (delta13C) of body tissues depends on the isotopic composition of food sources and on shifts due to isotopic fractionation during metabolism. As little is known about the effects of pathophysiological conditions we measured delta15N and delta13C values in hair and hair amino acids of patients with cirrhosis (n = 21) and compared the results with those of healthy subjects (n = 100) randomly selected from the 1987-1988 VERA German nutrition survey population. Cirrhosis was reflected in lower hair 15N abundances (6.7 vs. 9.9 per thousand delta15N; P < 0.001) whereas hair 13C abundances did not differ from healthy subjects (-19.4 vs. -19.6 per thousand 13C). Distinct patterns of delta15N and delta13C values were measured in hair amino acids. The delta15N values of phenylalanine were significantly higher in cirrhotics (P < 0.001). With the exception of isoleucine, threonine, and proline all other measured amino acids showed lower delta15N values than healthy subjects (P < 0.001). Lower hair delta15N values were associated with cirrhotic liver disease which suggests that under this condition the altered liver amino acid metabolism affects the nitrogen isotopic composition of the amino acids used for hair protein synthesis. It remains to be determined in controlled studies whether the altered nitrogen isotopic composition directly reflects the pathophysiological condition or is related to differences in dietary protein intake from plant or animal food sources.
Studies in ovine fetus and placenta have pointed to an interaction between the fetal liver and the placenta. The supply of amino acids and carbohydrates depends on this interaction. These studies have led to clinical studies in normal and high-risk pregnancies. The objective of the present review was to compare changes in fetal circulation, in terms of both velocimetry and actual blood flow measurements, and to couple such data with data on the placental transport of amino acids. Flow studies were carried out on the umbilical vein with measurements of time-averaged velocity and venous diameter. A similar approach was used for measurements of ductus venosus flow. Stable-isotope-labeled amino acids were used to study placental transport by the non-steady state approach. The studies of flow showed a marked reduction in umbilical blood flow even when expressed per kilogram fetal body weight in fetal-growth-restricted pregnancies. This may be coupled with an increased ductus venosus shunt, the combination leading to a marked reduction in fetal hepatic blood flow. The placental transport of some amino acids is reduced in fetal-growth-restricted pregnancies. Furthermore, nonglucose carbohydrates and polyols are found in fetal blood, some in concentrations higher than maternal concentrations. There is significant uptake of several polyols and of mannose across the umbilical circulation in normal pregnancies. In conclusion, both perfusion and permeability can now be studied in both normal and high-risk pregnancies.
The mechanisms by which amino acids are transferred across the human placenta are fundamental to our understanding of foetal nutrition. Amino acid transfer across the human placenta is dependent on transport across both the microvillous and basal plasma membranes of the placental syncytiotrophoblast, and on metabolism within the syncytiotrophoblast. Although the principles underlying uptake of amino acids across the microvillous plasma membrane are well understood, the extent to which amino acids are metabolised within human placenta and the mechanisms by which amino acids are transported out of the placenta across the basal plasma membrane are not well understood. Understanding the mechanisms and regulation of amino acid transport is necessary to understand the causes of intrauterine growth restriction in human pregnancy.
Nitrogen balance and δ15N: why you’re not what you eat during nutritional stress
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