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1.
J Proteome Res ; 22(6): 1603-1613, 2023 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-37129248

RESUMEN

Gestational Diabetes Mellitus (GDM) results in complications affecting both mothers and their offspring. Metabolomic analysis across pregnancy provides an opportunity to better understand GDM pathophysiology. The objective was to conduct a metabolomics analysis of first and third trimester plasma samples to identify metabolic differences associated with GDM development. Forty pregnant women with overweight/obesity from a multisite clinical trial of a lifestyle intervention were included. Participants who developed GDM (n = 20; GDM group) were matched with those who did not develop GDM (n = 20; Non-GDM group). Plasma samples collected at the first (10-16 weeks) and third (28-35 weeks) trimesters were analyzed with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Cardiometabolic risk markers, dietary recalls, and physical activity metrics were also assessed. Four medium-chain acylcarnitines, lauroyl-, octanoyl-, decanoyl-, and decenoylcarnitine, significantly differed over the course of pregnancy in the GDM vs Non-GDM group in a group-by-time interaction (p < 0.05). Hypoxanthine and inosine monophosphate were elevated in the GDM group (p < 0.04). In both groups over time, bile acids and sorbitol increased while numerous acylcarnitines and α-hydroxybutyrate decreased (p < 0.05). Metabolites involved in fatty acid oxidation and purine degradation were altered across the first and third trimesters of GDM-affected pregnancies, providing insight into metabolites and metabolic pathways altered with GDM development.


Asunto(s)
Diabetes Gestacional , Embarazo , Femenino , Humanos , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem , Estudios de Casos y Controles , Purinas
2.
Metabolomics ; 19(9): 77, 2023 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-37644353

RESUMEN

INTRODUCTION: Head and neck cancer (HNC) is the fifth most common cancer globally. Diagnosis at early stages are critical to reduce mortality and improve functional and esthetic outcomes associated with HNC. Metabolomics is a promising approach for discovery of biomarkers and metabolic pathways for risk assessment and early detection of HNC. OBJECTIVES: To summarize and consolidate the available evidence on metabolomics and HNC in plasma/serum, saliva, and urine. METHODS: A systematic search of experimental research was executed using PubMed and Web of Science. Available data on areas under the curve was extracted. Metabolic pathway enrichment analysis were performed to identify metabolic pathways altered in HNC. Fifty-four studies were eligible for data extraction (33 performed in plasma/serum, 15 in saliva and 6 in urine). RESULTS: Metabolites with high discriminatory performance for detection of HNC included single metabolites and combination panels of several lysoPCs, pyroglutamate, glutamic acid, glucose, tartronic acid, arachidonic acid, norvaline, linoleic acid, propionate, acetone, acetate, choline, glutamate and others. The glucose-alanine cycle and the urea cycle were the most altered pathways in HNC, among other pathways (i.e. gluconeogenesis, glycine and serine metabolism, alanine metabolism, etc.). Specific metabolites that can potentially serve as complementary less- or non-invasive biomarkers, as well as metabolic pathways integrating the data from the available studies, are presented. CONCLUSION: The present work highlights utility of metabolite-based biomarkers for risk assessment, early detection, and prognostication of HNC, as well as facilitates incorporation of available metabolomics studies into multi-omics data integration and big data analytics for personalized health.


Asunto(s)
Líquidos Corporales , Neoplasias de Cabeza y Cuello , Humanos , Alanina , Glucosa , Neoplasias de Cabeza y Cuello/diagnóstico , Metabolómica
3.
Am J Physiol Lung Cell Mol Physiol ; 320(5): L770-L784, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33624555

RESUMEN

Gestational long-term hypoxia increases the risk of myriad diseases in infants including persistent pulmonary hypertension. Similar to humans, fetal lamb lung development is susceptible to long-term intrauterine hypoxia, with structural and functional changes associated with the development of pulmonary hypertension including pulmonary arterial medial wall thickening and dysregulation of arterial reactivity, which culminates in decreased right ventricular output. To further explore the mechanisms associated with hypoxia-induced aberrations in the fetal sheep lung, we examined the premise that metabolomic changes and functional phenotypic transformations occur due to intrauterine, long-term hypoxia. To address this, we performed electron microscopy, Western immunoblotting, calcium imaging, and metabolomic analyses on pulmonary arteries isolated from near-term fetal lambs that had been exposed to low- or high-altitude (3,801 m) hypoxia for the latter 110+ days of gestation. Our results demonstrate that the sarcoplasmic reticulum was swollen with high luminal width and distances to the plasma membrane in the hypoxic group. Hypoxic animals were presented with higher endoplasmic reticulum stress and suppressed calcium storage. Metabolically, hypoxia was associated with lower levels of multiple omega-3 polyunsaturated fatty acids and derived lipid mediators (e.g., eicosapentaenoic acid, docosahexaenoic acid, α-linolenic acid, 5-hydroxyeicosapentaenoic acid (5-HEPE), 12-HEPE, 15-HEPE, prostaglandin E3, and 19(20)-epoxy docosapentaenoic acid) and higher levels of some omega-6 metabolites (P < 0.02) including 15-keto prostaglandin E2 and linoleoylglycerol. Collectively, the results reveal broad evidence for long-term hypoxia-induced metabolic reprogramming and phenotypic transformations in the pulmonary arteries of fetal sheep, conditions that likely contribute to the development of persistent pulmonary hypertension.


Asunto(s)
Reprogramación Celular , Hipoxia Fetal/fisiopatología , Feto/fisiopatología , Hipoxia/fisiopatología , Metaboloma , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Arteria Pulmonar/fisiopatología , Altitud , Animales , Calcio , Femenino , Edad Gestacional , Embarazo , Ovinos
4.
Metabolomics ; 17(12): 105, 2021 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-34837546

RESUMEN

INTRODUCTION: Gestational diabetes mellitus (GDM) significantly increases maternal and fetal health risks, but factors predictive of GDM are poorly understood. OBJECTIVES: Plasma metabolomics analyses were conducted in early pregnancy to identify potential metabolites associated with prediction of GDM. METHODS: Sixty-eight pregnant women with overweight/obesity from a clinical trial of a lifestyle intervention were included. Participants who developed GDM (n = 34; GDM group) were matched on treatment group, age, body mass index, and ethnicity with those who did not develop GDM (n = 34; Non-GDM group). Blood draws were completed early in pregnancy (10-16 weeks). Plasma samples were analyzed by UPLC-MS using three metabolomics assays. RESULTS: One hundred thirty moieties were identified. Thirteen metabolites including pyrimidine/purine derivatives involved in uric acid metabolism, carboxylic acids, fatty acylcarnitines, and sphingomyelins (SM) were different when comparing the GDM vs. the Non-GDM groups (p < 0.05). The most significant differences were elevations in the metabolites' hypoxanthine, xanthine and alpha-hydroxybutyrate (p < 0.002, adjusted p < 0.02) in GDM patients. A panel consisting of four metabolites: SM 14:0, hypoxanthine, alpha-hydroxybutyrate, and xanthine presented the highest diagnostic accuracy with an AUC = 0.833 (95% CI: 0.572686-0.893946), classifying as a "very good panel". CONCLUSION: Plasma metabolites mainly involved in purine degradation, insulin resistance, and fatty acid oxidation, were altered in early pregnancy in connection with subsequent GDM development.


Asunto(s)
Diabetes Gestacional , Resistencia a la Insulina , Cromatografía Liquida , Ácidos Grasos , Femenino , Humanos , Metabolómica , Embarazo , Purinas , Espectrometría de Masas en Tándem
5.
Metabolomics ; 16(7): 74, 2020 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-32556743

RESUMEN

INTRODUCTION: The metabolic alterations reflecting the influence of prostate cancer cells can be captured through metabolomic profiling. OBJECTIVE: To characterize the plasma metabolomic profile in prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa). METHODS: Metabolomics analyses were performed in plasma samples from individuals classified as non-cancerous control (n = 36), with PIN (n = 16), or PCa (n = 27). Untargeted [26 moieties identified after pre-processing by gas chromatography/mass spectrometry (GC/MS)] and targeted [46 amino acids, carbohydrates, organic acids and fatty acids by GC/MS, and 16 nucleosides and amino acids by ultra performance liquid chromatography-triple quadrupole/mass spectrometry (UPLC-TQ/MS)] analyses were performed. Prostate specific antigen (PSA) concentrations were measured in all samples. In PCa patients, the Gleason scores were determined. RESULTS: The metabolites that were best discriminated (p < 0.05, FDR < 0.2) for the Kruskal-Wallis test with Dunn's post-hoc comparing the control versus the PIN and PCa groups included isoleucine, serine, threonine, cysteine, sarcosine, glyceric acid, among several others. PIN was mainly characterized by alterations on steroidogenesis, glycine and serine metabolism, methionine metabolism and arachidonic acid metabolism, among others. In the case of PCa, the most predominant metabolic alterations were ubiquinone biosynthesis, catecholamine biosynthesis, thyroid hormone synthesis, porphyrin and purine metabolism. In addition, we identified metabolites that were correlated to the PSA [i.e. hypoxanthine (r = - 0.60, p < 0.05; r = - 0.54, p < 0.01) and uridine (r = - 0.58, p < 0.05; r = - 0.50, p < 0.01) in PIN and PCa groups, respectively] and metabolites that were significantly different in PCa patients with Gleason score < 7 and ≥ 7 [i.e. arachidonic acid, median (P25-P75) = 883.0 (619.8-956.4) versus 570.8 (505.6-651.8), respectively (p < 0.01)]. CONCLUSIONS: This human plasma metabolomic assessment contributes to the understanding of the unique metabolic features exhibited in PIN and PCa and provides a list of metabolites that can have the potential to be used as biomarkers for early detection of disease progression and management.


Asunto(s)
Neoplasia Intraepitelial Prostática/metabolismo , Neoplasias de la Próstata/metabolismo , Adulto , Anciano , Biomarcadores de Tumor/sangre , Cromatografía Liquida/métodos , Homólogo de la Proteína Chromobox 5 , Ácidos Grasos/metabolismo , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Masculino , Espectrometría de Masas/métodos , Metaboloma/genética , Metabolómica/métodos , Persona de Mediana Edad , Clasificación del Tumor , Plasma/metabolismo , Antígeno Prostático Específico/análisis , Federación de Rusia
6.
Int J Vitam Nutr Res ; 90(5-6): 395-402, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30987548

RESUMEN

Vitamin B12 (B12) plays in an important role in the development and function of the brain and nervous system, and adequate B12 status is especially important for the normal development of infants. In previous research conducted in Guatemala City we reported a high prevalence of B12 deficiency in lactating women and their infants 3 and 12 months of age, and low B12 concentrations in breast milk. The objective of this study was to assess predictors of serum B12 concentration in predominantly breastfed Guatemalan infants including intake of B12 from breast milk and other foods. Serum B12, breast milk and other food intakes, anthropometry, morbidity and socioeconomic status were assessed in infants 6.7 ± 0.6 months of age (n = 127, 52% female) in peri-urban Guatemala City. Twenty-four percent of infants had deficient B12 status (serum B12 concentration < 148 pmol/L) and 37% had marginal B12 status (148-220 pmol/L). Serum B12 concentrations were negatively correlated with infants' consumption of energy from breast milk (r = -0.37, p = 0.001), and positively correlated with their total consumption of animal source foods, especially cow's milk (r = 0.40, p = 0.001). Based on previously analyzed breast milk B12 concentrations in a nearby community, breast milk provided < 10% of the recommended daily B12 intake for this age. We conclude that there was a high prevalence of B12 deficiency in these Guatemalan infants by 6 months of age. Serum B12 was higher in infants consuming more cow's milk and lower in those consuming more breast milk.


Asunto(s)
Leche Humana , Vitamina B 12 , Animales , Lactancia Materna , Bovinos , Femenino , Guatemala , Humanos , Lactante , Lactancia
7.
Int J Vitam Nutr Res ; 90(3-4): 325-332, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30987554

RESUMEN

Serum samples from the 1999 Mexico National Nutrition Survey (NNS) were analyzed to determine the prevalence of low serum B12 concentrations, identify factors related with low values including B12 intake, and importantly, to provide a baseline for monitoring progress in reducing deficiency. Samples for B12 were available from 488 children and 464 women, a sub-sample of the nationally representative 1999 NNS. The national overall prevalence of low (<200 pg/mL) and marginal (200 to 300 pg/mL) serum B12 was 25.6% and 21.0%, respectively. Adolescent girls had the lowest serum B12 concentrations (325 ± 308 pg/mL) and the prevalence of deficiency was 40% in pregnant women even using a lower cut-point (<135 pg/mL). Residents of rural areas and the South, population groups with poorest socioeconomic status, and illiterate and indigenous women had the lowest serum B12 Children and women who met dietary recommendations for B12 intake had higher serum B12 than those who did not. Overall 45.9% of intakes fell below the Estimated Adequate Requirement. Dietary B12 intake of children and women was directly correlated with serum B12 (r = 0.18, p < 0.001 and r = 0.11, p = 0.0304). The prevalence of marginal and deficient B12 status in 1999 was much higher than the most recently published national data suggesting the success of national policies to improve micronutrient status.


Asunto(s)
Deficiencia de Vitamina B 12 , Vitamina B 12/química , Adolescente , Niño , Femenino , Humanos , México , Encuestas Nutricionales , Embarazo , Prevalencia , Vitamina B 12/metabolismo , Deficiencia de Vitamina B 12/metabolismo
8.
J Surg Res ; 244: 332-337, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31306890

RESUMEN

BACKGROUND: Traumatic brain injury (TBI) is associated with functional deficits, impaired cognition, and medical complications that continue well after the initial injury. Many patients seek medical care at other health care facilities after discharge, rather than returning to the admitting trauma center, making assessment of readmission rates and readmission diagnoses difficult to determine. The objective of this study was to determine the incidence and factors associated with readmission to any acute care hospital after an index admission for TBI. MATERIALS AND METHODS: The Nationwide Readmission Database was queried for all patients admitted with a TBI during the first 3 mo of 2015. Nonelective readmissions for this population were then collected for the remainder of 2015. Patients who died during the index admission were excluded. Demographic data, injury mechanism, type of TBI, the number of readmissions, days from discharge to readmission, readmission diagnosis, and mortality were studied. RESULTS: Of the 15,277 patients with an index admission for TBI, 5296 patients (35%) required at least 1 readmission. Forty percent of readmissions occurred within the first 30 d after discharge from the index trauma admission. The most common primary diagnosis on readmission was SDH, followed by septicemia, urinary tract infection, and aspiration. Readmission rates increased with age, with 75% of readmissions occurring in patients aged >65 y. Initial discharge to a skilled nursing facility (Relative Risk [RR], 1.60) or leaving the hospital against medical advice (RR, 1.59) increased the risk of readmission. Patients with fall as their mechanism of injury and a subdural hematoma were more likely to require readmission compared with other types of mechanisms with TBI (RR, 1.59 and RR, 1.21, respectively; P < 0.001). Notably, the first readmission was to a different hospital for 39.5% of patients and 46.9% of patients had admissions to at least one facility outside that of their original presentation. CONCLUSIONS: Hospital readmission is common for patients discharged after TBI. Elderly patients who fall with resultant subdural hematoma are at especially high risk for complications and readmission. Understanding potentially preventable causes for readmission can be used to guide discharge planning pathways to decrease morbidity in this patient population.


Asunto(s)
Lesiones Traumáticas del Encéfalo/complicaciones , Readmisión del Paciente , Anciano , Anciano de 80 o más Años , Lesiones Traumáticas del Encéfalo/terapia , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad
9.
Metabolomics ; 14(9): 112, 2018 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-30830378

RESUMEN

INTRODUCTION: Nitroproston® is a novel multi-target drug bearing natural prostaglandin E2 (PGE2) and nitric oxide (NO)-donating fragments for treatment of inflammatory and obstructive diseases (i.e., asthma and obstructive bronchitis). OBJECTIVES: To investigate the effects of Nitroproston® administration on plasma metabolomics in vivo. METHODS: Experimental in vivo study randomly assigning the target drug (treatment group) or a saline solution without the drug (vehicle control group) to 12 rabbits (n = 6 in each group). Untargeted (5880 initial features; 1869 negative-4011 positive ion peaks; UPLC-IT-TOF/MS) and 84 targeted moieties (Nitroproston® related metabolites, prostaglandins, steroids, purines, pyrimidines and amino acids; HPLC-QQQ-MS/MS) were measured from plasma at 0, 2, 4, 6, 8, 12, 18, 24, 32 and 60 min after administration. RESULTS: PGE2, 13,14-dihydro-15-keto-PGE2, PGB2, 1,3-GDN and 15-keto-PGE2 increased in the treatment group. Steroids (i.e., cortisone, progesterone), organic acids, 3-oxododecanoic acid, nicotinate D-ribonucleoside, thymidine, the amino acids serine and aspartate, and derivatives pyridinoline, aminoadipic acid and uric acid increased (p < 0.05 AUCROC curve > 0.75) after treatment. Purines (i.e., xanthine, guanine, guanosine), bile acids, acylcarnitines and the amino acids L-tryptophan and L-phenylalanine were decreased. Nitroproston® impacted steroidogenesis, purine metabolism and ammonia recycling pathways, among others. CONCLUSION: Nitroproston®, a multi action novel drug based on natural prostaglandins, altered metabolites (i.e., guanine, adenine, cortisol, cortisone and aspartate) involved in purine metabolism, urea and ammonia biological cycles, steroidogenesis, among other pathways. Suggested mechanisms of action, metabolic pathway interconnections and useful information to further understand the metabolic effects of prostaglandin administration are presented.


Asunto(s)
Dinoprostona/análogos & derivados , Dinoprostona/metabolismo , Óxido Nítrico/metabolismo , Prostaglandinas/metabolismo , Animales , Dinoprostona/sangre , Dinoprostona/química , Metabolómica , Óxido Nítrico/sangre , Óxido Nítrico/química , Prostaglandinas/sangre , Prostaglandinas/química , Conejos
10.
Eur J Nutr ; 57(3): 1059-1072, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28353072

RESUMEN

PURPOSE: To characterize the physiological changes in 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] throughout pregnancy. METHODS: Prospective cohort of 229 apparently healthy pregnant women followed at 5th-13th, 20th-26th, and 30th-36th gestational weeks. 25(OH)D and 1,25(OH)2D concentrations were measured by LC-MS/MS. Statistical analyses included longitudinal linear mixed-effects models adjusted for parity, season, education, self-reported skin color, and pre-pregnancy BMI. Vitamin D status was defined based on 25(OH)D concentrations according to the Endocrine Society Practice Guideline and Institute of Medicine (IOM) for adults. RESULTS: The prevalence of 25(OH)D <75 nmol/L was 70.4, 41.0, and 33.9%; the prevalence of 25(OH)D <50 nmol/L was 16.1, 11.2, and 10.2%; and the prevalence of 25(OH)D <30 nmol/L was 2, 0, and 0.6%, at the first, second, and third trimesters, respectively. Unadjusted analysis showed an increase in 25(OH)D (ß = 0.869; 95% CI 0.723-1.014; P < 0.001) and 1,25(OH)2D (ß = 3.878; 95% CI 3.136-4.620; P < 0.001) throughout pregnancy. Multiple adjusted analyses showed that women who started the study in winter (P < 0.001), spring (P < 0.001), or autumn (P = 0.028) presented a longitudinal increase in 25(OH)D concentrations, while women that started during summer did not. Increase of 1,25(OH)2D concentrations over time in women with insufficient vitamin D (50-75 nmol/L) at baseline was higher compared to women with sufficient vitamin D (≥75 nmol/L) (P = 0.006). CONCLUSIONS: The prevalence of vitamin D inadequacy varied significantly according to the adopted criteria. There was a seasonal variation of 25(OH)D during pregnancy. The women with insufficient vitamin D status present greater longitudinal increases in the concentrations of 1,25(OH)2D in comparison to women with sufficiency.


Asunto(s)
25-Hidroxivitamina D 2/sangre , Calcifediol/sangre , Calcitriol/sangre , Ergocalciferoles/sangre , Fenómenos Fisiologicos Nutricionales Maternos , Complicaciones del Embarazo/sangre , Deficiencia de Vitamina D/sangre , Adulto , Brasil/epidemiología , Estudios de Cohortes , Dieta/efectos adversos , Suplementos Dietéticos , Femenino , Humanos , Estudios Longitudinales , Embarazo , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/etiología , Complicaciones del Embarazo/prevención & control , Prevalencia , Estudios Prospectivos , Estaciones del Año , Autoinforme , Vitamina D/administración & dosificación , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/etiología , Deficiencia de Vitamina D/prevención & control , Adulto Joven
11.
J Nutr ; 147(2): 170-178, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28031376

RESUMEN

BACKGROUND: Vitamin B-6-deficient diets decrease plasma docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) concentrations in healthy adults. These fatty acids (FAs) are important for fetal neurodevelopment, but the relation between vitamin B-6 status and circulating polyunsaturated FAs (PUFAs) during pregnancy is unknown. OBJECTIVE: We sought to assess the relation between plasma pyridoxal 5' phosphate (PLP; the active form of vitamin B-6) and serum DHA, EPA, AA, linoleic acid, eicosadienoic, and α-linolenic acid concentrations during pregnancy. METHODS: A prospective cohort study in 186 healthy pregnant Brazilian women (aged 20-40 y) who were not using supplements was conducted in Rio de Janeiro, Brazil. Participants were enrolled in the first trimester of pregnancy (5-13 gestational weeks) and were followed up twice between 20-26 and 30-36 wk of gestation. Longitudinal linear mixed-effects regression models were used to evaluate the associations between 1) first-trimester PLP and PUFA concentrations across pregnancy and 2) ΔPLP (i.e., difference between third- and first-trimester plasma PLP concentrations) and PUFA concentrations across pregnancy. Models were adjusted for gestational week, first-trimester body mass index, smoking habit, and dietary intakes of vitamin B-6, fish, total fat, and PUFAs. RESULTS: Plasma PLP concentrations (median, IQR) substantially declined during pregnancy from 35.8 nmol/L (28.6-44.3 nmol/L) in the first trimester to 21.0 nmol/L (15.8-26.3 nmol/L) in the second trimester, and 16.8 nmol/L (12.9-20.3 nmol/L) in the third trimester (both P < 0.0001). Changes in plasma PLP concentrations across trimesters were positively associated with serum DHA concentrations (ß = 0.252, P = 0.012) and inversely associated with serum n-6-to-n-3 (ω-6-to-ω-3) FA ratio (ß = -0.010; P = 0.015), after adjustments for confounders. CONCLUSIONS: Maternal vitamin B-6 status during pregnancy was positively associated with the circulating concentration of DHA and inversely associated with n-6:n-3 FAs in Brazilian women who were not taking vitamin supplements. Further study is required to determine the impact of poor vitamin B-6 status on fetal neurodevelopment.


Asunto(s)
Ácidos Docosahexaenoicos/sangre , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-6/sangre , Vitamina B 6/sangre , Adulto , Estudios de Cohortes , Femenino , Humanos , Embarazo , Estudios Prospectivos , Adulto Joven
12.
J Nutr ; 147(10): 1839-1849, 2017 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-28794205

RESUMEN

BACKGROUND: The specific metabolomic perturbations that occur in vitamin B-12 deficiency, and their associations with neurological function, are not well characterized. OBJECTIVE: We sought to characterize the human serum metabolome in subclinical vitamin B-12 deficiency and repletion. METHODS: A before-and-after treatment study provided 1 injection of 10 mg vitamin B-12 (with 100 mg pyridoxine and 100 mg thiamin) to 27 community-dwelling elderly Chileans (∼74 y old) with vitamin B-12 deficiency, as evaluated with serum vitamin B-12, total plasma homocysteine (tHcy), methylmalonic acid (MMA), and holotranscobalamin. The combined indicator of vitamin B-12 status (cB-12) was computed. Targeted metabolites [166 acylcarnitines, amino acids, sugars, glycerophospholipids, and sphingolipids (liquid chromatography-tandem mass spectrometry)], and untargeted metabolites [247 chemical entities (gas chromatography time-of-flight mass spectrometry)] were measured at baseline and 4 mo after treatment. A peripheral nerve score was developed. Differences before and after treatment were examined. For targeted metabolomics, the data from 18 individuals with adequate vitamin B-12 status (selected from the same population) were added to the before-and-after treatment data set. Network visualizations and metabolic pathways are illustrated. RESULTS: The injection increased serum vitamin B-12, holotranscobalamin, and cB-12 (P < 0.001), and reduced tHcy and serum MMA (P < 0.001). Metabolomic changes from before to after treatment included increases (P < 0.001) in acylcarnitines, plasmalogens, and other phospholipids, whereas proline and other intermediaries of one-carbon metabolism-that is, methionine and cysteine-were reduced (P < 0.001). Direct significant correlations (P < 0.05 after the false discovery rate procedure) were identified between acylcarnitines, plasmalogens, phospholipids, lyso-phospholipids, and sphingomyelins compared with vitamin B-12 status and nerve function. Multiple connections were identified with primary metabolites (e.g., an inverse relation between vitamin B-12 markers and tryptophan, tyrosine, and pyruvic, succinic, and citric acids, and a direct correlation between the nerve score and arginine). CONCLUSIONS: The human serum metabolome in vitamin B-12 deficiency and the changes that occur after supplementation are characterized. Metabolomics revealed connections between vitamin B-12 status and serum metabolic markers of mitochondrial function, myelin integrity, oxidative stress, and peripheral nerve function, including some previously implicated in Alzheimer and Parkinson diseases. This trial was registered at www.controlled-trials.com as ISRCTN02694183.


Asunto(s)
Metaboloma , Nervios Periféricos/fisiopatología , Deficiencia de Vitamina B 12/metabolismo , Anciano , Femenino , Humanos , Masculino , Mitocondrias/fisiología , Vitamina B 12/administración & dosificación , Vitamina B 12/sangre , Deficiencia de Vitamina B 12/sangre
14.
Clin Chem Lab Med ; 53(8): 1215-25, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25720072

RESUMEN

BACKGROUND: A novel approach to determine vitamin B12 status is to combine four blood markers: total B12 (B12), holotranscobalamin (holoTC), methylmalonic acid (MMA) and total homocysteine (tHcy). This combined indicator of B12 status is expressed as cB12=log10[(holoTC·B12)/(MMA·Hcy)]-(age factor). Here we calculate cB12 in datasets with missing biomarkers, examine the influence of folate status, and revise diagnostic cut-points. METHODS: We used a database with all four markers (n=5211) plus folate measurements (n=972). A biomarker Z (assumed missing) was plotted versus X (a combination of other markers) and Y (age). Each chart was approximated by a function Ztheor, which predicted the potentially absent value(s). Statistical distributions of cB12 were aligned with physiological indicators of deficiency and used to determine cut-offs. RESULTS: The predictive functions Ztheor allowed assessment of the "incomplete" indicators, 3cB12 (three markers known) and 2cB12 (two markers known). Predictions contained a systematic deviation associated with dispersion along two axes Z and X (and unaccounted by the least squares fit). Increase in tHcy at low serum folate was corrected (cB12+Δfolate) based on the function of Δfolate=log10(Hcyreal/Hcytheor) versus folate. Statistical distributions of cB12 revealed the boundaries of groups with B12 deficiency, i.e., cB12<-0.5. CONCLUSIONS: We provide equations that combine two, three or four biomarkers into one diagnostic indicator, thereby rescaling unmatched data into the same coordinate system. Adjustment of this indicator is required if serum folate is <10 nmol/L and tHcy is measured. Revised cut-points and guidelines for using this approach are provided.


Asunto(s)
Ácido Fólico/sangre , Homocisteína/sangre , Ácido Metilmalónico/sangre , Transcobalaminas/análisis , Vitamina B 12/sangre , Biomarcadores/sangre , Voluntarios Sanos , Humanos
15.
Food Nutr Bull ; 36(2 Suppl): S95-7, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26125199

RESUMEN

This Food and Nutrition Bulletin supplement summarizes updated prevalence data on micronutrient deficiencies in Latin America and the Caribbean (LAC). In order to provide an updated view of micronutrient status in LAC, systematic reviews were performed utilizing national health surveys and research-oriented studies focused on the prevalence of deficiencies of vitamin A, folate, anemia (as a proxy of iron deficiency), and zinc. Results show that the prevalence of vitamin A deficiency has been reduced in many countries, folate deficiency is now almost non-existent, low or marginal vitamin B12 status is still prevalent in most locations, anemia remains a public health problem among children under 6 years of age and women of childbearing age in most surveyed countries, and there is a high prevalence of zinc deficiency in children under 6 years of age and girls and women 12 to 49 years of age. Thus, regardless of improvements in the overall rates of economic growth in LAC, deficiencies of these micronutrients still remain a public health problem.


Asunto(s)
Micronutrientes/deficiencia , Adolescente , Adulto , Región del Caribe/epidemiología , Niño , Preescolar , Femenino , Humanos , Lactante , América Latina/epidemiología , Persona de Mediana Edad , Estado Nutricional , Adulto Joven
16.
Food Nutr Bull ; 36(2 Suppl): S129-38, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26125198

RESUMEN

BACKGROUND: Zinc deficiency affects multiple vital functions in the life cycle, especially growth. Limited information is available on the magnitude of zinc deficiency in Latin America and the Caribbean. OBJECTIVE: To examine the latest available information on both the prevalence of zinc deficiency and the risk of zinc deficiency in Latin America and the Caribbean. METHODS: The prevalence of zinc deficiency was identified through a systematic review looking for the latest available data on serum zinc concentrations from surveys or studies with national representativeness conducted in Latin America and the Caribbean. The risk of zinc deficiency in Latin America and the Caribbean was estimated based on dietary zinc inadequacy (according to the 2011 National Food Balance Sheets) and stunting in children under 5 years of age. RESULTS: Only four countries had available national biochemical data. Mexican, Colombian, Ecuadorian, and Guatemalan children under 6 years of age and women 12 to 49 years of age had a high prevalence of zinc deficiency (19.1% to 56.3%). The countries with the highest risk of zinc deficiency (estimated prevalence of inadequate zinc intake > 25% plus prevalence of stunting > 20%) were Belize, Bolivia, El Salvador, Guatemala, Haiti, Honduras, Nicaragua, and Saint Vincent and the Grenadines. Zinc dietary inadequacy was directly correlated with stunting (r = 0.64, p < .001). CONCLUSIONS: Prevalence data from the four available Latin America and Caribbean national surveys indicate a high prevalence of zinc deficiency in children under 6 years of age and women 12 to 49 years of age. High rates of both estimated zinc dietary inadequacy and stunting were also reported in most Latin America and Caribbean countries.


Asunto(s)
Zinc/deficiencia , Adolescente , Adulto , Belice/epidemiología , Bolivia/epidemiología , Región del Caribe/epidemiología , Niño , Preescolar , Colombia/epidemiología , Dieta , Ecuador/epidemiología , El Salvador/epidemiología , Femenino , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/etiología , Guatemala/epidemiología , Haití/epidemiología , Encuestas Epidemiológicas , Honduras/epidemiología , Humanos , Lactante , América Latina/epidemiología , México/epidemiología , Persona de Mediana Edad , Nicaragua/epidemiología , Estado Nutricional , San Vicente y las Grenadinas/epidemiología , Adulto Joven , Zinc/administración & dosificación
17.
Food Nutr Bull ; 36(2 Suppl): S109-18, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26125196

RESUMEN

UNLABELLED: Background: The current magnitude of folate and vitamin B12 deficiency in Latin America and the Caribbean is uncertain. OBJECTIVE: To summarize data on plasma or serum vitamin B12 and folate concentrations in Latin America and the Caribbean reported since 1990, a period that covers the era before and after the introduction of folic acid fortification. METHODS: A systematic review was conducted in 2012 and updated in 2014. Studies and surveys using biochemical biomarkers and conducted in apparently healthy individuals were identified. RESULTS: Folate deficiency in Latin America and the Caribbean appears not to be a public health problem (prevalence < 5%) after the introduction of folic acid fortification. However, there is some indication that high rates of low or marginal vitamin B12 status remain in most locations and across population groups. CONCLUSIONS: Adding vitamin B12 as a fortificant with folic acid may be the best strategy in areas where vitamin B12 deficiency is an established concern.


Asunto(s)
Deficiencia de Ácido Fólico/epidemiología , Estado Nutricional , Deficiencia de Vitamina B 12/epidemiología , Adolescente , Adulto , Anciano , Región del Caribe/epidemiología , Niño , Preescolar , Femenino , Ácido Fólico/administración & dosificación , Ácido Fólico/sangre , Deficiencia de Ácido Fólico/sangre , Alimentos Fortificados , Humanos , América Latina/epidemiología , Masculino , Embarazo , Vitamina B 12/sangre , Deficiencia de Vitamina B 12/sangre
18.
Food Nutr Bull ; 36(2 Suppl): S119-28, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26125197

RESUMEN

BACKGROUND: In Latin America and the Caribbean, anemia has been a public health problem that affects mainly women of childbearing age and children under 6 years of age. However, the current prevalence of anemia in this region is unknown. OBJECTIVE: To examine the latest available prevalence data on anemia in Latin America and the Caribbean. METHODS: A systematic review was conducted in 2011 and updated in 2014. Studies determining the prevalence of anemia conducted in apparently healthy populations with national or regional representativeness were included in the review. RESULTS: The lowest prevalence rates of anemia among children under 6 years of age were found in Chile (4.0%), Costa Rica (4.0%), Argentina (7.6%), and Mexico (19.9%). In Nicaragua, Brazil, Ecuador, El Panama, and Honduras, anemia was a moderate public health problem, with prevalence ranging Salvador, Cuba, Colombia, the Dominican Republic, Peru, from 20.1% to 37.3%. Anemia was a severe public health problem in Guatemala, Haiti, and Bolivia. The prevalence of anemia among women of childbearing age was lowest in Chile (5.1%). In Colombia, El Salvador, Costa Rica, Nicaragua, Ecuador, Mexico, Peru, Honduras, and Argentina, anemia was a mild public health problem, with prevalence ranging from 7.6% to 18.7%. In Guatemala, Brazil, the Dominican Republic, and Bolivia, anemia was a moderate public health problem, with prevalence ranging from 21.4% to 38.3%. Panama and Haiti had the highest reported prevalence rates (40.0% and 45.5%, respectively), and anemia was considered a severe public health problem in those countries. CONCLUSIONS: Anemia remains a public health problem in children under 6 years of age and women of childbearing age in most Latin America and Caribbean countries for which data are available.


Asunto(s)
Anemia/epidemiología , Adulto , Anemia Ferropénica/epidemiología , Argentina/epidemiología , Bolivia/epidemiología , Brasil/epidemiología , Región del Caribe/epidemiología , Niño , Preescolar , Chile/epidemiología , Colombia/epidemiología , Costa Rica/epidemiología , República Dominicana/epidemiología , Ecuador/epidemiología , Femenino , Guatemala/epidemiología , Haití/epidemiología , Honduras/epidemiología , Humanos , Lactante , América Latina/epidemiología , México/epidemiología , Nicaragua/epidemiología , Panamá/epidemiología , Perú/epidemiología , Embarazo
19.
Food Nutr Bull ; 36(2 Suppl): S98-108, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26125200

RESUMEN

BACKGROUND: In recent decades, the general socioeconomic situation in Latin America and the Caribbean countries has improved, and many vitamin A programs have been implemented in an attempt to reduce vitamin A deficiency in the region. OBJECTIVE: To examine vitamin A status in Latin America and the Caribbean based on serum retinol concentrations and to contrast available data published before and after 1998. METHODS: A systematic review was performed. National surveys or representative studies that reported vitamin A status were selected. RESULTS: Ten national surveys and six representative studies were identified. Data for children under 6 years of age indicate that Guatemala and Nicaragua have practically eradicated vitamin A deficiency (less than 2% prevalence of serum retinol < 20 µg/dL). In Costa Rica, Cuba, El Salvador, and Panama, the prevalence of vitamin A deficiency ranged from 2.8% to 9.4%. In Peru, Honduras, Argentina, Ecuador, and Brazil, vitamin A deficiency is a moderate public health problem (prevalence from 14.0% to 17.4%), while in Colombia, Mexico, and Haiti it is a severe public health problem (prevalence from 24.3% to 32.0%). Disadvantaged groups (indigenous people and those of Afro-Colombian descent) have the highest rates of deficiency. The prevalence of vitamin A deficiency is under 20% in school-children and adult women. When data published before and after 1998 for children under 6 years of age were compared, most Central American countries had a reduction in the prevalence of vitamin A deficiency (p < .05), whereas in South American countries, the prevalence of vitamin A deficiency increased over time (p < .05). CONCLUSIONS: The prevalence of vitamin A deficiency in children under 6 years of age has decreased in many Central American countries, but vitamin A deficiency still remains a public health problem in numerous Latin America and Caribbean countries, especially among disadvantaged and vulnerable groups. Because of issues with the accuracy of the serum retinol biomarker reflecting body stores, these results must be interpreted with caution.


Asunto(s)
Estado Nutricional , Deficiencia de Vitamina A/epidemiología , Vitamina A/sangre , Adulto , Argentina/epidemiología , Brasil/epidemiología , Región del Caribe/epidemiología , América Central/epidemiología , Niño , Preescolar , Colombia/epidemiología , Ecuador/epidemiología , Femenino , Guatemala/epidemiología , Haití/epidemiología , Humanos , Lactante , América Latina/epidemiología , México/epidemiología , Nicaragua/epidemiología , Panamá/epidemiología , Perú/epidemiología , Deficiencia de Vitamina A/prevención & control
20.
Arch Latinoam Nutr ; 64(3): 145-52, 2014 Sep.
Artículo en Español | MEDLINE | ID: mdl-26137790

RESUMEN

The lipid profile is impacted by numerous factors. However, the seasonal variations in this profile have not been well-established in the southern hemisphere. The aim of this study was to determine the seasonal variation of the lipid profile in apparently healthy adults from Santiago, Chile. The study design was observational and prospective, involving 50 healthy volunteers of both genders, aged 23-62 years. The lipid profile was measured at monthly intervals over the course of one year. LDL was significantly higher in winter -spring than in summer- fall (p < 0.01). Conversely, HDL decreases significantly in winter (p < 0.05). We conclude that there are seasonal variations in the serum levels of LDL and HDL. The circannual pattern is characterized by increased levels of LDL in winter-spring and low levels of HDL in winter.


Asunto(s)
Lípidos/sangre , Adulto , Chile , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estaciones del Año , Luz Solar , Temperatura , Triglicéridos/sangre , Adulto Joven
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