Publications by authors named "Alex Brito"

57 Publications

Dietary Intake of Adult Residents in Luxembourg Taking Part in Two Cross-Sectional Studies-ORISCAV-LUX (2007-2008) and ORISCAV-LUX 2 (2016-2017).

Nutrients 2021 Dec 7;13(12). Epub 2021 Dec 7.

Nutrition and Health Research Group, Population Health Department, Luxembourg Institute of Health, 1445 Strassen, Luxembourg.

Background: A balanced diet is an important lifestyle component and has been associated with a reduced risk of chronic diseases.

Objectives: To assess dietary intake of adult residents in Luxembourg taking part in two population-based cross-sectional studies (ORISCAV-LUX, 2007-2008 and ORISCAV-LUX 2, 2016-2017).

Methods: Dietary intake of the study participants (1242 in 2007/08 and 1326 in 2016/17), 25-69 years old, were evaluated using food-frequency questionnaires (134 items in 2007/2008 and 174 items in 2016/2017) according to the French ANSES-CIQUAL food composition database. Both food-group- and nutrient-based analyses were conducted.

Results: Dietary patterns in ORISCAV-LUX 2, 2016-2017, were characterized by an increase in the estimated marginal means (EMM) of the intake of energy, total fat, saturated fatty acids, alcohol, and decreased EMM of total carbohydrates, magnesium, and calcium compared to 2007/08. We also observed an increased EMM of the intake of protein-rich food items and ready-to-eat foods/fast foods, together with a decreased intake of grains, dairy products, and vegetables (all -values <0.05, linear mixed models). The intake of most micronutrients was stable or slightly increased in ORISCAV-LUX 2 vs. ORISCAV-LUX, except for the drop in magnesium and calcium, and generally met recommendations, in particular, EFSA population reference intakes (PRI), except for vitamin D.

Conclusions: Though most micronutrient recommendations were met, nutrient consumption in terms of high energy, total fat, and sodium, as well as low carbohydrates, were not aligned with recommendations for balanced eating.
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http://dx.doi.org/10.3390/nu13124382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706514PMC
December 2021

Metabolites involved in purine degradation, insulin resistance, and fatty acid oxidation are associated with prediction of Gestational diabetes in plasma.

Metabolomics 2021 Nov 27;17(12):105. Epub 2021 Nov 27.

Department of Food Science and Nutrition, California Polytechnic State University, San Luis Obispo, CA, USA.

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.
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http://dx.doi.org/10.1007/s11306-021-01857-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8741304PMC
November 2021

Pharmacokinetic Properties of the Novel Synthetic Cannabinoid 5F-APINAC and Its Influence on Metabolites Associated with Neurotransmission in Rabbit Plasma.

Pharmaceuticals (Basel) 2021 Jul 13;14(7). Epub 2021 Jul 13.

Laboratory of Pharmacokinetics and Metabolomic Analysis, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia.

The strong psychoactive effects of synthetic cannabinoids raise the need for the deeper studying of their neurometabolic effects. The pharmacokinetic properties of 5F-APINAC and its influence on metabolomics profiles associated with neurotransmission were investigated in rabbit plasma. Twelve rabbits divided into three groups received 1-mL 5F-APINAC at 0.1, 1 and 2 mg/kg. The intervention groups were compared with the controls. Sampling was performed at nine time points (0-24 h). Ultra-high-performance liquid chromatography-tandem mass spectrometry was used. The pharmacokinetics were dose-dependent (higher curve at a higher dose) with a rapid biotransformation, followed by gradual elimination within 24 h. The tryptophan concentrations abruptly decreased ( < 0.05) in all tested groups, returning to the basal levels after 6 h. 5-hydroxylindole acetic acid increased ( < 0.05) in the controls, but this trend was absent in the treated groups. The aspartic acid concentrations were elevated ( < 0.001) in the treated groups. L-kynurenine was elevated ( < 0.01) in the intervention groups receiving 1 mg/kg to 2 mg/kg. Dose-dependent elevations ( < 0.01) were found for kynurenic acid, xanthurenic acid and quinolinic acid ( < 0.01), whereas the anthranilic acid trends were decreased ( < 0.01). The indole-3-propionic acid and indole-3-carboxaldehyde trends were elevated ( < 0.05), whereas the indole-3-lactic acid trajectories were decreased ( < 0.01) in the intervention groups. 5F-APINAC administration had a rapid biotransformation and gradual elimination. The metabolites related to the kynurenine and serotonergic system/serotonin pathways, aspartic acid innervation system and microbial tryptophan catabolism were altered.
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http://dx.doi.org/10.3390/ph14070668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308683PMC
July 2021

Gestational long-term hypoxia induces metabolomic reprogramming and phenotypic transformations in fetal sheep pulmonary arteries.

Am J Physiol Lung Cell Mol Physiol 2021 05 24;320(5):L770-L784. Epub 2021 Feb 24.

Lawrence D. Longo, MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California.

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 ( < 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.
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http://dx.doi.org/10.1152/ajplung.00469.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174832PMC
May 2021

Short- and medium-term exposures of diazepam induce metabolomic alterations associated with the serotonergic, dopaminergic, adrenergic and aspartic acid neurotransmitter systems in zebrafish (Danio rerio) embryos/larvae.

Comp Biochem Physiol Part D Genomics Proteomics 2021 06 16;38:100816. Epub 2021 Feb 16.

Laboratory of Pharmacokinetics and Metabolomic Analysis, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia. Electronic address:

Introduction: Diazepam is a well-known psychoactive drug widely used worldwide for the treatment of anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, sleeplessness, agitation, and pre/post-operative sedation. It is part of the benzodiazepine family, substances known to primarily act by binding and enhancing gamma-aminobutyric acid (GABA) receptors. The objective of the present work was to investigate the influence of short and medium-term diazepam exposures on neurotransmitters measured through targeted metabolomics using a zebrafish embryo model.

Methods: Short-term (2.5 h) and medium-term (96 h) exposures to diazepam were performed at drug concentrations of 0.8, 1.6, 16, and 160 μg/L. Intervention groups were compared with a vehicle control group. Each group consisted of 20 zebrafish eggs/larvae. Metabolites related with neurotransmission were determined by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS).

Results: Thirty-six compounds were quantified. Significantly increased tryptophan and serotonin concentrations were found in the intervention groups receiving higher doses of diazepam in 2.5 h exposure (p < 0.05 control versus intervention groups). Tyrosine concentrations were higher (p < 0.05) at higher concentrations in 2.5 h exposure, but lower (p < 0.05) at higher concentrations in 96 h exposure. Both phenylalanine and aspartic acid concentrations were higher (p < 0.05) at higher doses in 2.5 h and 96 h exposure.

Conclusions: Short- and medium-term exposures to diazepam induce dose- and time-dependent metabolomic alterations associated with the serotonergic, dopaminergic/adrenergic, and aspartic acid neurotransmitter systems in zebrafish.
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http://dx.doi.org/10.1016/j.cbd.2021.100816DOI Listing
June 2021

Short- and long-term exposures of the synthetic cannabinoid 5F-APINAC induce metabolomic alterations associated with neurotransmitter systems and embryotoxicity confirmed by teratogenicity in zebrafish.

Comp Biochem Physiol C Toxicol Pharmacol 2021 May 6;243:109000. Epub 2021 Feb 6.

Laboratory of Pharmacokinetics and Metabolomic Analysis, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia. Electronic address:

Introduction: Synthetic cannabinoids are abused substances with strong psychoactive effects. Little is known about the effects on neurotransmission and the toxicity of the second-generation cannabinoid 5F-APINAC. The objective was to assess the influence of short- and long-term exposures of 5F-APINAC on metabolites associated with neurotransmission on zebrafish.

Methods: Short-term ("acute", 4 h) and long-term ("chronic", 96 h) exposures to 5F-APINAC were performed at 0.001, 0.01, 0.1, 1.0 and 10 μM. Intervention groups were compared with a vehicle control. Each group n = 20 zebrafish eggs/larvae. Metabolites related to neurotransmission were determined.

Results: In chronic exposure, larvae exposed to 10 μM 5F-APINAC presented morphological and developmental alterations. GABA had the lowest concentrations at higher exposure in acute (p < 0.01) and chronic (p < 0.001) experiments. Glutamine showed a descending trend in the acute experiment, but an ascending trend in the chronic exposure (p < 0.05). In chronic exposure, tryptophan presented an overall descending trend, but with a neat increase at 10 μM 5F-APINAC (p < 0.001). Tryptamine in acute exposure presented lower (p < 0.05) concentrations at higher doses. Dopamine and acetylcholine presented highest (p < 0.05) concentrations in the acute and chronic exposures, but with a drop at the highest doses in the chronic experiments. In chronic exposure, xanthurenic acid decreased, except for the highest dose. Picolinic acid was increased at the highest doses in the chronic experiment (p < 0.001).

Conclusions: Short- and long-term exposures induced metabolomic alterations associated with the gamma-aminobutyric acid/glutamic acid, dopaminergic/adrenergic, cholinergic neurotransmitter systems, and the kynurenine pathway. Chronic exposure at 10 μM 5F-APINAC was associated with embryotoxicity confirmed by teratogenesis.
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http://dx.doi.org/10.1016/j.cbpc.2021.109000DOI Listing
May 2021

Postprandial Dried Blood Spot-Based Nutritional Metabolomic Analysis Discriminates a High-Fat, High-Protein Meat-Based Diet from a High Carbohydrate Vegan Diet: A Randomized Controlled Crossover Trial.

J Acad Nutr Diet 2021 05 3;121(5):931-941.e2. Epub 2020 Dec 3.

Department of Food Science and Nutrition, Cal Poly Metabolomics Service Center, Center for Health Research, California Polytechnic State University, San Luis Obispo. Electronic address:

Background: Due to the challenges associated with accurate monitoring of dietary intake in humans, nutritional metabolomics (including food intake biomarkers) analysis as a complementary tool to traditional dietary assessment methods has been explored. Food intake biomarker assessment using postprandial dried blood spot (DBS) collection can be a convenient and accurate means of monitoring dietary intake vs 24-hour urine collection.

Objective: The objective of this study was to use nutritional metabolomics analysis to differentiate a high-fat, high-protein meat (HFPM) diet from a high-carbohydrate vegan (HCV) diet in postprandial DBS and 24-hour urine.

Design: This was a randomized controlled crossover feeding trial.

Participants/setting: Participants were healthy young adult volunteers (n = 8) in California. The study was completed in August 2019.

Intervention: The standardized isocaloric diet interventions included an HFPM and an HCV diet. Participants attended 2 intervention days, separated by a 2-week washout.

Main Outcome Measures: During each intervention day, a finger-prick blood sample was collected in the fasting state, 3 hours post breakfast, and 3 hours post lunch. Participants also collected their urine for 24 hours. DBS and urine samples were analyzed by ultra-performance liquid chromatography mass spectrometry to identify potential food intake biomarkers.

Statistical Analyses Performed: Principal component analysis for discriminatory analysis and univariate analysis using paired t tests were performed.

Results: Principal component analysis found no discrimination of baseline DBS samples. In both the postprandial DBS and 24-hour urine, post-HFPM consumption had higher (P < 0.05) levels of acylcarnitines, creatine, and cis-trans hydroxyproline, and the HCV diet was associated with elevated sorbitol (P < 0.05). The HFPM diet had higher concentrations of triacylglycerols with fewer than 54 total carbons in DBS, and 24-hour urine had higher nucleoside mono- and di-phosphates (P < 0.05).

Conclusions: Nutritional metabolomics profiles of postprandial DBS and 24-hour urine collections were capable of differentiating the HFPM and HCV diets. The potential use of postprandial DBS-based metabolomic analysis deserves further investigation for dietary intake monitoring.
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http://dx.doi.org/10.1016/j.jand.2020.10.024DOI Listing
May 2021

Maternal plasma folate concentration is positively associated with serum total cholesterol and low-density lipoprotein across the three trimesters of pregnancy.

Sci Rep 2020 11 19;10(1):20141. Epub 2020 Nov 19.

Graduate Program in Food and Nutrition, Faculty of Nutrition, Universidade Federal de Pelotas, Rua Gomes Carneiro, 1, Pelotas, RS, 96010-610, Brazil.

Increased first-trimester low-density lipoprotein (LDL-C) concentration has been associated with adverse pregnancy outcomes, such as gestational diabetes. The B vitamins folate, B-6, and total B-12 are key for the methyl group-dependent endogenous synthesis of phosphatidylcholine, which is needed for lipoprotein synthesis, e.g., very low-density lipoprotein (VLDL), the precursor of circulating LDL-C. Maternal B-vitamin concentration usually declines across trimesters. Whether changes in maternal B-vitamin concentrations are associated with total cholesterol (TC), triglycerides (TG), and lipoprotein concentrations is unknown. Therefore, we explored the association between plasma folate, vitamin B-6 in the form of pyridoxal 5'-phosphate (PLP), and total B-12 with serum TC, LDL-C, HDL-C, and TG concentrations across trimesters. This secondary analysis used data of a prospective pregnancy cohort study included apparently healthy adult women (n = 179) from Rio de Janeiro, Brazil. The biomarkers were measured in fasting blood samples collected at 5-13, 20-26, and 30-36 weeks of gestation. The associations between B vitamins and lipid concentrations across trimesters were explored using linear mixed-effect models. Among B vitamins, only plasma folate was positively associated with TC (β = 0.244, 95% CI 0.034-0.454) and LDL-C (β = 0.193, 95% CI 0.028-0.357) concentrations. The positive relationship of maternal folate and TC and LDL-C concentrations may indicate the importance of folate as a methyl donor for lipoprotein synthesis during pregnancy.
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http://dx.doi.org/10.1038/s41598-020-77231-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677547PMC
November 2020

Phytochemicals as modifiers of gut microbial communities.

Food Funct 2020 Oct;11(10):8444-8471

Luxembourg Institute of Health, Population Health Department, Nutrition and Health Research Group, 1A-B, rue Thomas Edison, Strassen L-1445, Luxembourg.

A healthy gut microbiota (GM) is paramount for a healthy lifestyle. Alterations of the GM have been involved in the aetiology of several chronic diseases, including obesity and type 2 diabetes, as well as cardiovascular and neurodegenerative diseases. In pathological conditions, the diversity of the GM is commonly reduced or altered, often toward an increased Firmicutes/Bacteroidetes ratio. The colonic fermentation of dietary fiber has shown to stimulate the fraction of bacteria purported to have beneficial health effects, acting as prebiotics, and to increase the production of short chain fatty acids, e.g. propionate and butyrate, while also improving gut epithelium integrity such as tight junction functionality. However, a variety of phytochemicals, often associated with dietary fiber, have also been proposed to modulate the GM. Many phytochemicals possess antioxidant and anti-inflammatory properties that may positively affect the GM, including polyphenols, carotenoids, phytosterols/phytostanols, lignans, alkaloids, glucosinolates and terpenes. Some polyphenols may act as prebiotics, while carotenoids have been shown to alter immunoglobulin A expression, an important factor for bacteria colonization. Other phytochemicals may interact with the mucosa, another important factor for colonization, and prevent its degradation. Certain polyphenols have shown to influence bacterial communication, interacting with quorum sensing. Finally, phytochemicals can be metabolized in the gut into bioactive constituents, e.g. equol from daidzein and enterolactone from secoisolariciresinol, while bacteria can use glycosides for energy. In this review, we strive to highlight the potential interactions between prominent phytochemicals and health benefits related to the GM, emphasizing their potential as adjuvant strategies for GM-related diseases.
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http://dx.doi.org/10.1039/d0fo01483dDOI Listing
October 2020

Plasma metabolomic profile in prostatic intraepithelial neoplasia and prostate cancer and associations with the prostate-specific antigen and the Gleason score.

Metabolomics 2020 06 17;16(7):74. Epub 2020 Jun 17.

Laboratory of Pharmacokinetics and Metabolomic Analysis, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University, 2-4 Bolshaya Pirogovskaya St., Moscow, Russia, 119991.

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.
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http://dx.doi.org/10.1007/s11306-020-01694-yDOI Listing
June 2020

Strengthening the Immune System and Reducing Inflammation and Oxidative Stress through Diet and Nutrition: Considerations during the COVID-19 Crisis.

Nutrients 2020 May 27;12(6). Epub 2020 May 27.

Nutrition and Health Research Group, Population Health Department, Luxembourg Institute of Health, 1A-B, rue Thomas Edison, L-1445 Strassen, Luxembourg.

The coronavirus-disease 2019 (COVID-19) was announced as a global pandemic by the World Health Organization. Challenges arise concerning how to optimally support the immune system in the general population, especially under self-confinement. An optimal immune response depends on an adequate diet and nutrition in order to keep infection at bay. For example, sufficient protein intake is crucial for optimal antibody production. Low micronutrient status, such as of vitamin A or zinc, has been associated with increased infection risk. Frequently, poor nutrient status is associated with inflammation and oxidative stress, which in turn can impact the immune system. Dietary constituents with especially high anti-inflammatory and antioxidant capacity include vitamin C, vitamin E, and phytochemicals such as carotenoids and polyphenols. Several of these can interact with transcription factors such as NF-kB and Nrf-2, related to anti-inflammatory and antioxidant effects, respectively. Vitamin D in particular may perturb viral cellular infection via interacting with cell entry receptors (angiotensin converting enzyme 2), ACE2. Dietary fiber, fermented by the gut microbiota into short-chain fatty acids, has also been shown to produce anti-inflammatory effects. In this review, we highlight the importance of an optimal status of relevant nutrients to effectively reduce inflammation and oxidative stress, thereby strengthening the immune system during the COVID-19 crisis.
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http://dx.doi.org/10.3390/nu12061562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352291PMC
May 2020

Metabolomics Reveals Altered Hepatic Bile Acids, Gut Microbiome Metabolites, and Cell Membrane Lipids Associated with Marginal Vitamin A Deficiency in a Mongolian Gerbil Model.

Mol Nutr Food Res 2020 07 22;64(13):e1901319. Epub 2020 Jun 22.

West Coast Metabolomics Center, University of California, Davis, CA, USA.

Scope: This study is designed to provide a broad evaluation of the impacts of vitamin A (VA) deficiency on hepatic metabolism in a gerbil model.

Methods And Results: After 28 days of VA depletion, male Mongolian gerbils (Meriones unguiculatus) are randomly assigned to experimental diets for 28 days. Groups are fed a white-maize-based diet with ≈50 µL cottonseed oil vehicle either alone (VA-, n = 10) or containing 40 µg retinyl acetate (VA+, n = 10) for 28 days. Liver retinol is measured by high-performance liquid chromatography. Primary metabolomics, aminomics, lipidomics, bile acids, oxylipins, ceramides, and endocannabinoids are analyzed in post-mortem liver samples by liquid chromatography-mass spectrometry.

Results: Liver retinol is lower (p < 0.001) in the VA- versus VA+ group, with concentrations indicating marginal VA deficiency. A total of 300 metabolites are identified. Marginal VA deficiency is associated with lower bile acids, trimethylamine N-oxide, and a variety of acylcarnitines, phospholipids and sphingomyelins (p < 0.05). Components of DNA, including deoxyguanosine, cytidine, and N-carbomoyl-beta-alanine (p < 0.05), are differentially altered.

Conclusions: Hepatic metabolomics in a marginally VA-deficient gerbil model revealed alterations in markers of the gut microbiome, fatty acid and nucleotide metabolism, and cellular structure and signaling.
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http://dx.doi.org/10.1002/mnfr.201901319DOI Listing
July 2020

Relationship between the plasma acylcarnitine profile and cardiometabolic risk factors in adults diagnosed with cardiovascular diseases.

Clin Chim Acta 2020 Aug 4;507:250-256. Epub 2020 May 4.

Laboratory of Pharmacokinetics and Metabolomic Analysis, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow Medical University, Moscow, Russia. Electronic address:

The development of cardiovascular diseases (CVDs) is often asymptomatic. Identification of initial indicators of cardiometabolic disruption may assist in its early detection. The objective was to determine the relationships between plasma acylcarnitines (ACs) and cardiometabolic risk factors in adults with and without CVDs. The AC profile in human plasma of healthy controls [non-CVD group, n = 13)] and individuals diagnosed with CVDs (CVD group, n = 34) were compared. A targeted analysis of 29 ACs was performed using flow injection analysis-tandem mass spectrometry. There were significant direct correlations (p < 0.05) between ACs and cardiometabolic risk factors. Comparing the groups after adjustment for covariates, showed that the ACs that were best differentiated (p < 0.05) between the two groups and that presented "good" diagnostic accuracy were carnitine [30.7 (25.5-37.7) vs. 37.7 (32.3-45.0) µM], the short-chain ACs: acetylcarnitine [8.9 (7.4-10.2) vs. 11.9 (9.2-14.4) µM] and isovalerylcarnitine [0.10 (0.06-0.13) vs. 0.13 (0.10-0.16) µM], and the medium-chain ACs: hexanoylcarnitine [0.04 (0.03-0.05) vs. 0.06 (0.05-0.07) µM] and decenoylcarnitine [0.18 (0.12-0.22) vs. 0.22 (0.17-0.32) µM]. This assessment contributes to the identification of the unique metabolic features exhibited in association with cardiometabolic risk in adults diagnosed with CVD. The altered metabolites have the potential to be used as biomarkers for early detection of CVD.
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http://dx.doi.org/10.1016/j.cca.2020.04.035DOI Listing
August 2020

Plasma Sarcosine Measured by Gas Chromatography-Mass Spectrometry Distinguishes Prostatic Intraepithelial Neoplasia and Prostate Cancer from Benign Prostate Hyperplasia.

Lab Med 2020 Nov;51(6):566-573

Laboratory of Pharmacokinetics and Metabolomic Analysis, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.

Objective: Sarcosine was postulated in 2009 as a biomarker for prostate cancer (PCa). Here, we assess plasma sarcosine as a biomarker that is complementary to prostate-specific antigen (PSA).

Methods: Plasma sarcosine was measured using gas chromatography-mass spectrometry (GC-MS) in adults classified as noncancerous controls (with benign prostate hyperplasia [BPH], n = 36), with prostatic intraepithelial neoplasia (PIN, n = 16), or with PCa (n = 27). Diagnostic accuracy was assessed using receiver operating characteristic curve analysis.

Results: Plasma sarcosine levels were higher in the PCa (2.0 µM [1.3-3.3 µM], P <.01) and the PIN (1.9 µM [1.2-6.5 µM], P <.001) groups than in the BPH (0.9 µM [0.6-1.4 µM]) group. Plasma sarcosine had "good" and "very good" discriminative capability to detect PIN (area under the curve [AUC], 0.734) and PCa (AUC, 0.833) versus BPH, respectively. The use of PSA and sarcosine together improved the overall diagnostic accuracy to detect PIN and PCa versus BPH.

Conclusion: Plasma sarcosine measured by GC-MS had "good" and "very good" classification performance for distinguishing PIN and PCa, respectively, relative to noncancerous patients diagnosed with BPH.
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http://dx.doi.org/10.1093/labmed/lmaa008DOI Listing
November 2020

Low Serum B12 Concentrations Are Associated with Low B12 Dietary Intake But Not with Infection or Abnormal Gastric Function in Rural Mexican Women.

Nutrients 2019 Dec 2;11(12). Epub 2019 Dec 2.

The authors contributed equally to this work..

Background: Gastric function, infection, and vitamin B12 (B12) dietary intake were assessed as predictors of serum B12.

Methods: antibodies, gastric function, B12 dietary intake, and biochemical/hematological parameters were measured in 191 adult women from two rural communities in Querétaro, Mexico.

Results: The overall mean serum B12 concentration was 211 ± 117 pmol/L. The prevalences of low (≤ 148 pmol/L), marginal (148 to 221 pmol/L), and adequate (> 221 pmol/L) serum B12 were 28.4%, 31.1%, and 40.5%, respectively. Seventy-one percent of women tested positive for antibodies. The prevalence of gastric function categories did not differ by serum B12 categories. The odds ratio for having low serum B12 was 2.7 ( = 0.01) for women with an intake below the estimated average requirement, 3.6 ( = 0.01) for those in the lowest tertile of total B12 intake, and 3.0 ( = 0.02) for those in the lowest tertile of B12 intake from animal source foods. Age and B12 intake were predictors of serum B12 concentrations [serum B12 (pmol/L) = 90.060 + 5.208 (B12 intake, µg/day) + 2.989 (age, years).

Conclusions: Low serum B12 concentrations were associated with low B12 dietary intake but not with infection or abnormal gastric function in rural Mexican women.
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http://dx.doi.org/10.3390/nu11122922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950710PMC
December 2019

Readmissions After Acute Hospitalization for Traumatic Brain Injury.

J Surg Res 2019 12 12;244:332-337. Epub 2019 Jul 12.

Division of Trauma, Surgical Critical Care, Burns and Acute Care Surgery, Department of Surgery, University of California San Diego Health, San Diego, California. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jss.2019.06.071DOI Listing
December 2019

Prevalence of low serum vitamin B12 in Mexican children and women: results from the first National Nutrition Survey (1999) as a basis for interventions and progress.

Int J Vitam Nutr Res 2020 Jun 16;90(3-4):325-332. Epub 2019 Apr 16.

USDA, ARS, Western Human Nutrition Research Center, Davis, CA, USA.

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.
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http://dx.doi.org/10.1024/0300-9831/a000579DOI Listing
June 2020

Breast milk provides inadequate amounts of vitamin B12 for predominantly breastfed Guatemalan infants.

Int J Vitam Nutr Res 2020 Oct 16;90(5-6):395-402. Epub 2019 Apr 16.

USDA, ARS, Western Human Nutrition Research Center, Davis, CA, USA.

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.
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http://dx.doi.org/10.1024/0300-9831/a000583DOI Listing
October 2020

Rabbit plasma metabolomic analysis of Nitroproston®: a multi target natural prostaglandin based-drug.

Metabolomics 2018 08 20;14(9):112. Epub 2018 Aug 20.

Laboratory of Pharmacokinetics and Metabolomic Analysis, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University, 2-4 Bolshaya Pirogovskaya St., Moscow, Russia, 119991.

Introduction: Nitroproston® is a novel multi-target drug bearing natural prostaglandin E (PGE) 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: PGE, 13,14-dihydro-15-keto-PGE, PGB, 1,3-GDN and 15-keto-PGE 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.
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http://dx.doi.org/10.1007/s11306-018-1413-1DOI Listing
August 2018

Methods to assess vitamin B12 bioavailability and technologies to enhance its absorption.

Nutr Rev 2018 10;76(10):778-792

United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, Davis, California, USA.

Vitamin B12 (B-12) deficiency is still relatively common in low-, medium-, and high-income countries, mainly because of dietary inadequacy and, to a lesser extent, malabsorption. This narrative review is based on a systematic search of evidence on methods to assess B-12 bioavailability and technologies to enhance its absorption. A total of 2523 scientific articles identified in PubMed and 1572 patents identified in Orbit Intelligence were prescreened. Among the reviewed methods, Schilling's test and/or its food-based version (using cobalamin-labeled egg yolk) were used for decades but have been discontinued, largely because they required radioactive cobalt. The qualitative CobaSorb test, based on changes in circulating holo-transcobalamin before and after B-12 administration, and the 14C-labeled B-12 test for quantitative measurement of absorption of a low-dose radioactive tracer are currently the best available methods. Various forms of B-12 co-formulated with chemical enhancers (ie, salcaprozate sodium, 8-amino caprylate) or supplied via biotechnological methods (ie, microbiological techniques, plant cells expressing cobalamin binding proteins), encapsulation techniques (ie, emulsions, use of chitosan particles), and alternative routes of administration (ie, intranasal, transdermal administration) were identified as potential technologies to enhance B-12 absorption in humans. However, in most cases the evidence of absorption enhancement is limited.
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http://dx.doi.org/10.1093/nutrit/nuy026DOI Listing
October 2018

The Human Serum Metabolome of Vitamin B-12 Deficiency and Repletion, and Associations with Neurological Function in Elderly Adults.

J Nutr 2017 Oct;147(10):1839-1849

USDA Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA.

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.
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http://dx.doi.org/10.3945/jn.117.248278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610547PMC
October 2017

Vitamin B deficiency.

Nat Rev Dis Primers 2017 Jun 29;3:17040. Epub 2017 Jun 29.

Diabetes Unit, King Edward Memorial Hospital, Pune, Maharashtra, India.

Vitamin B (B12; also known as cobalamin) is a B vitamin that has an important role in cellular metabolism, especially in DNA synthesis, methylation and mitochondrial metabolism. Clinical B12 deficiency with classic haematological and neurological manifestations is relatively uncommon. However, subclinical deficiency affects between 2.5% and 26% of the general population depending on the definition used, although the clinical relevance is unclear. B12 deficiency can affect individuals at all ages, but most particularly elderly individuals. Infants, children, adolescents and women of reproductive age are also at high risk of deficiency in populations where dietary intake of B12-containing animal-derived foods is restricted. Deficiency is caused by either inadequate intake, inadequate bioavailability or malabsorption. Disruption of B12 transport in the blood, or impaired cellular uptake or metabolism causes an intracellular deficiency. Diagnostic biomarkers for B12 status include decreased levels of circulating total B12 and transcobalamin-bound B12, and abnormally increased levels of homocysteine and methylmalonic acid. However, the exact cut-offs to classify clinical and subclinical deficiency remain debated. Management depends on B12 supplementation, either via high-dose oral routes or via parenteral administration. This Primer describes the current knowledge surrounding B12 deficiency, and highlights improvements in diagnostic methods as well as shifting concepts about the prevalence, causes and manifestations of B12 deficiency.
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http://dx.doi.org/10.1038/nrdp.2017.40DOI Listing
June 2017

Micronutrient Status among Pregnant Women in Zinder, Niger and Risk Factors Associated with Deficiency.

Nutrients 2017 Apr 26;9(5). Epub 2017 Apr 26.

Program in International and Community Nutrition, Department of Nutrition, University of California, Davis, CA 95616, USA.

Anemia and micronutrient (MN) deficiencies in pregnant women are associated with adverse pregnancy outcomes. In Niger, 58.6% of pregnant women are anemic; however, MN statuses are unknown. The study objectives were to estimate the prevalence of MN deficiencies among pregnant women in Zinder, Niger and explore associated risk factors. Pregnant women living in randomly selected rural villages ( = 88) were included. Capillary and venous blood samples ( = 770) were analyzed for hemoglobin (Hb) and plasma ferritin, soluble transferrin receptor (sTfR), zinc (pZn), retinol binding protein (RBP), folate and vitamin B. C-reactive protein and alpha-1-acid glycoprotein were measured to adjust for inflammation. The prevalence of MN deficiencies in pregnant woman was high, indicative of a severe public health problem. Prevalence of iron deficiency was 20.7% and 35.7%, by ferritin (<15 µg/L) and sTfR (>8.3 mg/L), respectively. In total, 40.7% of women had low pZn (<50 µg/dL), 79.7% had marginal RBP (<1.32 µmol/L), 44.3% of women had low folate (<10 nmol/L) and 34.8% had low B concentrations (<148 pmol/L). Common risk factors associated with MN status included gravidity, mid-upper-arm circumference, geophagy, malaria, and result of the woman's last pregnancy. Interventions to promote the strengthening of antenatal care, and access and adherence to nutrition and health interventions are critical among pregnant women in this population.
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http://dx.doi.org/10.3390/nu9050430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452160PMC
April 2017

Association between early pregnancy vitamin D status and changes in serum lipid profiles throughout pregnancy.

Metabolism 2017 05 12;70:85-97. Epub 2017 Feb 12.

Rio de Janeiro Federal University, Josué de Castro Nutrition Institute, Department of Social and Applied Nutrition, Avenida Carlos Chagas Filho, 373 - CCS - Bloco J, Suite 29, Cidade Universitária - Ilha do Fundão, Rio de Janeiro, RJ, 21941-590, Brazil. Electronic address:

Objective: To evaluate the associations between first trimester 25-hydroxyvitamin D [25(OH)D] status and changes in high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC), triglyceride (TG) concentrations, TG/HDL-c, and TC/HDL-c ratios throughout pregnancy. We hypothesized that first trimester 25(OH)D inadequacy is associated with lower concentrations of HDL-c and higher LDL-c, TC, TG, TG/HDL-c, and TC/HDL-c ratios throughout pregnancy.

Methods: A prospective cohort study with 3 visits at 5-13 (baseline), 20-26, and 30-36 gestational weeks, recruited 194 pregnant women attending a public health care center in Rio de Janeiro, Brazil. Plasma 25(OH)D concentrations were measured in the first trimester using liquid chromatography-tandem mass spectrometry. 25(OH)D concentrations were classified as adequate (≥75nmol/L) or inadequate (<75nmol/L). Serum TC, HDL-c, and TG concentrations were measured enzymatically. Crude and adjusted longitudinal linear mixed-effects models were employed to evaluate the association between the first trimester 25(OH)D status and changes in serum lipid concentrations throughout pregnancy. Confounders adjusted for in the multiple analysis were age, homeostatic model assessment (HOMA), early pregnancy BMI, leisure time physical activity before pregnancy, energy intake, and gestational age.

Results: At baseline, 69% of the women had inadequate concentrations of 25(OH)D. Women with 25(OH)D inadequacy had higher mean LDL-c than those with adequate concentrations (91.3 vs. 97.5mg/dL; P=0.064) at baseline. TC, HDL-c, LDL-c TG, TG/HDL-c ratios, and TC/HDL-c ratios, increased throughout pregnancy independently of 25(OH)D concentrations (ANOVA for repeated measures P<0.001). The adjusted models showed direct associations between the first trimester 25(OH)D status and changes in TC (β=9.53; 95%CI=1.12-17.94), LDL-c (β=9.99; 95% CI=3.62-16.36) concentrations, and TC/HDL-c ratios (β=0.16; 95% CI=0.01-0.31) throughout pregnancy.

Conclusions: Inadequate plasma 25(OH)D concentrations during early pregnancy were associated with more pronounced changes of TC, LDL-c concentrations, and TC/HDL-c ratios throughout pregnancy. Changes in these cardiovascular markers suggest the importance of ensuring adequate vitamin D status at the beginning of pregnancy.
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http://dx.doi.org/10.1016/j.metabol.2017.02.004DOI Listing
May 2017

Changes in plasma concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D during pregnancy: a Brazilian cohort.

Eur J Nutr 2018 Apr 28;57(3):1059-1072. Epub 2017 Mar 28.

Nutritional Epidemiology Observatory, Josué de Castro Nutrition Institute, Rio de Janeiro Federal University, Avenida Carlos Chagas Filho, 373, CCS, Bloco J, 2° andar, Cidade Universitária-Ilha do Fundão, Rio de Janeiro, 21941-902, Brazil.

Purpose: To characterize the physiological changes in 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)D] 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)D 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 (β = 0.869; 95% CI 0.723-1.014; P < 0.001) and 1,25(OH)D (β = 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)D 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)D in comparison to women with sufficiency.
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http://dx.doi.org/10.1007/s00394-017-1389-zDOI Listing
April 2018

Vitamin B-6 Status in Unsupplemented Pregnant Women Is Associated Positively with Serum Docosahexaenoic Acid and Inversely with the n-6-to-n-3 Fatty Acid Ratio.

J Nutr 2017 02 28;147(2):170-178. Epub 2016 Dec 28.

Food, Nutrition and Health, Faculty of Land and Food Systems, The University of British Columbia, Vancouver, British Columbia, Canada;

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 (β = 0.252, P = 0.012) and inversely associated with serum n-6-to-n-3 (ω-6-to-ω-3) FA ratio (β = -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.
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http://dx.doi.org/10.3945/jn.116.239483DOI Listing
February 2017

Reply to LR Solomon.

Am J Clin Nutr 2016 05;103(5):1379

From the USDA/Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA (AB; LHA, e-mail: Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark (SNF); Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ (JWM); Department of Pathology and Laboratory Medicine, University of California, Davis, CA (JWM, RG); and the Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile (RU).

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http://dx.doi.org/10.3945/ajcn.116.133322DOI Listing
May 2016

Vitamin B-12 treatment of asymptomatic, deficient, elderly Chileans improves conductivity in myelinated peripheral nerves, but high serum folate impairs vitamin B-12 status response assessed by the combined indicator of vitamin B-12 status.

Am J Clin Nutr 2016 Jan 25;103(1):250-7. Epub 2015 Nov 25.

USDA/Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA;

Background: It is uncertain whether vitamin B-12 supplementation can improve neurophysiologic function in asymptomatic elderly with low vitamin B-12 status or whether folate status affects responses to vitamin B-12 supplementation.

Objective: We assessed the effects of a single intramuscular injection of 10 mg vitamin B-12 (which also contained 100 mg vitamin B-6 and 100 mg vitamin B-1) on vitamin B-12 status and neurophysiologic function in elderly community-dwelling Chileans with low serum vitamin B-12 concentrations who were consuming bread fortified with folic acid.

Design: A pretreatment and posttreatment study was conducted in 51 participants (median ± SD age: 73 ± 3 y; women: 47%) with serum vitamin B-12 concentrations <120 pmol/L at screening. Vitamin B-12 status was defined by combining vitamin B-12, plasma total homocysteine (tHcy), methylmalonic acid (MMA), and holotranscobalamin into one variable [combined indicator of vitamin B-12 status (cB-12)]. The response to treatment was assessed by measuring cB-12 and neurophysiologic variables at baseline and 4 mo after treatment.

Results: Treatment increased serum vitamin B-12, holotranscobalamin, and cB-12 (P < 0.001) and reduced plasma tHcy and serum MMA (P < 0.001). Treatment produced consistent improvements in conduction in myelinated peripheral nerves; the sensory latency of both the left and right sural nerves improved on the basis of faster median conduction times of 3.1 and 3.0 ms and 3.3 and 3.4 ms, respectively (P < 0.0001). A total of 10 sensory potentials were newly observed in sural nerves after treatment. Participants with high serum folate at baseline (above the median, ≥33.9 nmol/L) had less improvement in cB-12 (P < 0.001) than did individuals whose serum folate was less than the median concentration (i.e., with a concentration <33.9 nmol/L).

Conclusion: Asymptomatic Chilean elderly with poor vitamin B-12 status displayed improved conductivity in myelinated peripheral nerves after vitamin B-12 treatment and an interaction with folate status, which was detected only with the use of cB-12. This trial was registered at www.controlled-trials.com as ISRCTN02694183.
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http://dx.doi.org/10.3945/ajcn.115.116509DOI Listing
January 2016
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