Suchergebnisse

The Egyptian government introduced wheat-flour fortification with iron and folic acid to reduce the incidence of neural tube defects, but suspended it for technical reasons. We previously developed novel legume foods with enhanced folate content. In this study, we investigated the efficacy of 12-week intervention with folate-en- hanced foods versus folic acid supplement in improving folate status in Egyptian women. A randomized, parallel intervention trial with two active groups (n = 19, n = 18) and one blinded control group (n = 20) was executed over 12 weeks. Volunteers received either germinated legume foods and orange juice (≈250 μg/d folate) or folic acid supplement (500 μg/d) or apple juice (0 μg/d folate). Folate status was assessed by erythrocyte and plasma folate and total homocysteine (tHcy) at day 0, and after 8 and 12 weeks of intervention. After 12 weeks, mean plasma folate increased by 14 (P < 0.0001) and 12 (P < 0.0001) nmoL in the folic acid and food group, respectively. Erythrocyte folate concentration increased in the folic acid group from 614 to 912 (P < 0.0001) and in the food group from 631 to 914 nmoL (P < 0.0001). After 12 weeks, 90% of subjects in the folic acid group and 70% in the food group had erythrocyte folate concentrations exceeding 906 nmol/L. tHcy concentration was decreased by 20% (P = 0.007) and 18% (P = 0.006) in the folic acid and food group, respectively, but remained unchanged in the control group during intervention. Folate-enhanced foods effectively improve folate status in women of reproductive age. These foods could be used as a complement to folic acid fortification

On behalf of the HELENA Study Group. ; This study aimed to examine the association between vitamin B6, folate and vitamin B12 biomarkers and plasma fatty acids in European adolescents. A subsample from the Healthy Lifestyle in Europe by Nutrition in Adolescence study with valid data on B-vitamins and fatty acid blood parameters, and all the other covariates used in the analyses such as BMI, Diet Quality Index, education of the mother and physical activity assessed by a questionnaire, was selected resulting in 674 cases (43 % males). B-vitamin biomarkers were measured by chromatography and immunoassay and fatty acids by enzymatic analyses. Linear mixed models elucidated the association between B-vitamins and fatty acid blood parameters (changes in fatty acid profiles according to change in 10 units of vitamin B biomarkers). DHA, EPA) and n-3 fatty acids showed positive associations with B-vitamin biomarkers, mainly with those corresponding to folate and vitamin B12. Contrarily, negative associations were found with n-6:n-3 ratio, trans-fatty acids and oleic:stearic ratio. With total homocysteine (tHcy), all the associations found with these parameters were opposite (for instance, an increase of 10 nmol/l in red blood cell folate or holotranscobalamin in females produces an increase of 15·85 Âmol/l of EPA (P value <0·01), whereas an increase of 10 nmol/l of tHcy in males produces a decrease of 2·06 Âmol/l of DHA (P value <0·05). Positive associations between B-vitamins and specific fatty acids might suggest underlying mechanisms between B-vitamins and CVD and it is worth the attention of public health policies. ; The HELENA study received funding from the European Union's Sixth RTD Framework Programme (contract FOODCT-2005-007034). Additional support was obtained from the Spanish Ministry of Education (AGL2007-29784-E/ALI), Axis-Shield Diagnostics Ltd (Oslo, Norway), Abbot Científica S.A. (Spain). This analysis was also supported by the Spanish Ministry of Science and Innovation (JCI-2010-07055) with the contribution of the European Regional Development Fund (FEDER). The first author is supported by a grant from the Spanish Carlos III Health Institute: RD08/0072/0025 (Red SAMID: Maternal, Child Health and Development Research Network). ; Peer Reviewed

AbstractIntroductionDolutegravir‐based antiretroviral therapy (ART) is the preferred antiretroviral treatment for children and adolescents living with HIV. A large surveillance study in Botswana previously raised concerns about an association between pre‐conception dolutegravir and neural tube defects. Before these concerns were subsequently resolved, we set up a sub‐study to look at the effect of dolutegravir on levels of folate and vitamin B12 in children and adolescents within the randomized ODYSSEY trial, as folate and vitamin B12 are known to play a crucial role in neural tube development.MethodsWe conducted the sub‐study among Ugandan ODYSSEY participants and compared folate and vitamin B12 between children randomized to dolutegravir‐based ART (DTG) and non‐dolutegravir‐based standard‐of‐care treatment (SOC). Plasma folate was measured at enrolment and week 4 on stored samples; in addition, plasma and red blood cell (RBC) folate and vitamin B12 were assayed at week ≥96 in prospectively collected samples. RBC mean corpuscular volume (MCV) was measured 24‐weekly in all ODYSSEY participants. Samples analysed in the sub‐study were collected between September 2016 and October 2020.ResultsA total of 229 children aged ≥6 years were included in the sub‐study with median age at trial enrolment of 12.3 (interquartile range [IQR] 9.0, 14.7) years, and CD4 count of 501 (IQR 228, 695); 112 (49%) children were male. Most participants (225/229, 98%) had plasma folate results at enrolment and 214 (93%) children had results available for RBC folate, vitamin B12 and plasma folate at week ≥96. MCV results were analysed on 679 children aged ≥6 years enrolled in ODYSSEY. At week 4, mean plasma folate was significantly higher in the dolutegravir arm than in SOC (difference [DTG‐SOC] 1.6 ng/ml, 95% CI 0.8, 2.3; p<0.001), and this difference persisted to week ≥96 (2.7 ng/ml, 95% CI 1.7, 3.7; p<0.001). Mean RBC folate at ≥96 weeks was also higher in the DTG arm (difference 73 ng/ml, 95% CI 3, 143; p = 0.041). There was no difference in the treatment arms for vitamin B12 levels at ≥96 weeks or change in MCV through trial follow‐up.ConclusionsPlasma and RBC folate levels were higher in children and adolescents receiving dolutegravir‐based ART than on other ART regimens. Further studies are needed to clarify the mechanisms of these interactions and the clinical implications of increased blood folate levels.

On behalf of the HELENA study group: et al. ; [Objectives]: To determine dietary patterns (DPs) and explain the highest variance of vitamin B6, folate, and B12 intake and related concentrations among European adolescents. ; [Methods]: A total of 2173 adolescents who participated in the Healthy Lifestyle in Europe by Nutrition in Adolescence study met the eligibility criteria for the vitamin B intake analysis (46% boys) and 586 adolescents for the biomarkers analysis (47% boys). Two non-consecutive, 24-h, dietary recalls were used to assess the mean intakes. Concentrations were measured by chromatography and immunoassay testing. A reduced rank regression was applied to elucidate the combined effect of food intake of vitamin B and related concentrations. ; [Results]: The identified DPs (one per vitamin B intake and biomarker and by sex) explained a variability between 34.2% and 23.7% of the vitamin B intake and between 17.2% and 7% of the biomarkers. In the reduced rank regression models, fish, eggs, cheese, whole milk and buttermilk intakes were loaded positively for vitamin B intake in both sexes; however, soft drinks and chocolate were loaded negatively. For the biomarkers, a higher variability was observed in the patterns in terms of food loads such as alcoholic drinks, sugars, and soft drinks. Some food items were loaded differently between intakes and biomarkers such as fish products, which was loaded positively for intakes but negatively for plasma folate in girls. ; [Conclusions]: The identified DPs explained up to 34.2% and 17.2% of the variability of the vitamin B intake and plasma concentrations, respectively, in European adolescents. Further studies are needed to elucidate the factors that determine such patterns. ; HELENA study received funding from the European Union's Sixth RTD Framework Programme (Contract FOODCT-2005-007034). Additional support from the Spanish Ministry of Education (AGL2007-29784-E/ALI), Axis-Shield Diagnostics Ltd (Oslo, Norway), Abbot Científica S.A. (Spain). This analysis was also supported by the Spanish Ministry of Science and Innovation (JCI-2010-07055) with the contribution of the European Regional Development Fund (FEDER). The first author is supported by a grant from the Spanish Carlos III Health Institute: RD08/0072/0025 (Red SAMID: Maternal, Child Health and Development Research Network). ; Peer reviewed

Background: Impaired homocysteine me­tabolism (IHM; hyperhomocysteinemia) has been linked with many complex disorders like cardiovascular diseases and immu­nological disturbances. However, studies understanding IHM in light of pro- and anti-atherogeneic markers like Interleukin-17A & -10 (IL-17A & IL-10) and Forkhead box p3 (Foxp3, a master transcription factor) are scarce.Aim: In our present study, we aimed to understand the relation of IHM with plasma IL-17A and IL-10 levels and Foxp3 mRNA expression in peripheral blood mononuclear cells (PBMCs) from an endogamous popula­tion (Jats of Haryana, North India) with high prevalence of IHM without the concur­rence of significant adverse cardiovascular outcomes.Methods: Forty (40) clinically healthy individuals, unrelated up to first cousins, were recruited and were subjected to demographic, physiological and anthropometric profiling, followed by intravenous blood sample collection (fasting) and lipid profiling. Plasma homocysteine levels were estimated and individuals with homocysteine levels ≥ 15umol/L and <15umol/L were categorized as the impaired homocysteine metabolism group (IHM, n=30) and normal homocysteine metabolism group (NHM, n=10) respectively. Plasma folate and vitamin B12 and MTHFR C677T (methylenetetrahydrofolate reductase) polymorphism were detected. Relative mRNA expression of Foxp3 in PBMCs (normalized to 18S) was quantitated using SyBR green technology. Plasma IL-10 & 17 levels were estimated by ELISA assays.Results and Conclusion: None of the physiological, anthropometric and lipid variables were different between the two groups. Foxp3 mRNA expression levels were relatively lower, and plasma IL-10 levels were found to be comparable among IHM and NHM group. However, significantly higher IL-17A levels and relatively high LDL cholesterol levels were present in the IHM group as compared with NHM. Our findings suggest that the Jats of Haryana, North India, exhibiting high levels of homocysteine, might also carry the high IL-17A -pro-atherogenic marker, suggest­ing an increasing burden of pre-morbid condition. This apparently does not reach to significant mortality/morbidity attributed to the counter action or balancing act of IL-10 (an anti-atherogenic marker). This further suggests environment-influenced epigenetic control mechanisms of the tar­geted genes in the present population.Ethn Dis. 2018;28(4):525-530; doi:10.18865/ ed.28.4.525

Wheat bran cereals are an important source of dietary fibre. The aim of the study was to investigate if a high intake (120 g) of fibre rich breakfast cereal (which delivers the UK Government guidelines for fibre intake in one serving but is three-fold higher than the manufacturers recommended serving) has additional potential health benefits compared to the recommended serving (40 g, containing 11 g of dietary fibre). To assess this, the study determined the short chain fatty acid (SCFA) profiles in human faecal, urine and plasma samples after consumption of two different servings of fibre-rich cereal. Inhibition of prostanoid production was measured (ex vivo) in human colonic fibroblast cells after cytokine (IL-1β) inflammation stimulation. Eight healthy volunteers, 18-55 years old; BMI (18-30 kg/m2) consumed the wheat bran-rich "ready to eat cereal", at both the high (120 g) serving and recommended (40 g) serving. Faecal, urine and plasma samples were collected at baseline, throughout the five-hour intervention period and approximately 24 hours following consumption. Faecal butyrate showed the largest increase (p < 0.05) of more than a two-fold change following the consumption of the recommended serving of wheat bran cereal (from 13.95 ± 9.17 to 31.63 ± 20.53 mM) and no significant change following the higher serving (from 21.96 ± 11.03 to 22.9 ± 12.69 mM). ANOVA analysis also found a weak serving effect (p = 0.046) of the portion size (high vs. recommended) only for butyrate in urine 24 hours after consumption of the bran cereal. The physiological nutritionally relevant concentrations of faecal SCFAs, as determined in the volunteers' faecal samples showed significant anti-inflammatory activity or the individual faecal SCFAs; acetate (p < 0.001), propionate (p < 0.001) and butyrate (p < 0.01), as well as in combination. Plasma folate was also increased after consumption of both wheat bran servings and was significant (p = 0.037) at the three-hour time point following consumption of the high wheat ...

Nutritional imbalance is emerging as a causative factor of hearing loss. Epidemiologic studies have linked hearing loss to elevated plasma total homocysteine (tHcy) and folate deficiency, and have shown that folate supplementation lowers tHcy levels potentially ameliorating age-related hearing loss. The purpose of this study was to address the impact of folate deficiency on hearing loss and to examine the underlying mechanisms. For this purpose, 2-mo-old C57BL/6J mice (Animalia Chordata Mus musculus) were randomly divided into 2 groups (n = 65 each) that were fed folate-deficient (FD) or standard diets for 8 wk. HPLC analysis demonstrated a 7-fold decline in serum folate and a 3-fold increase in tHcy levels. FD mice exhibited severe hearing loss measured by auditory brainstem recordings and TUNEL-positive-apoptotic cochlear cells. RT-quantitative PCR and Western blotting showed reduced levels of enzymes catalyzing homocysteine (Hcy) production and recycling, together with a 30% increase in protein homocysteinylation. Redox stress was demonstrated by decreased expression of catalase, glutathione peroxidase 4, and glutathione synthetase genes, increased levels of manganese superoxide dismutase, and NADPH oxidase-complex adaptor cytochrome b-245, α-polypeptide (p22phox) proteins, and elevated concentrations of glutathione species. Altogether, our findings demonstrate, for the first time, that the relationship between hyperhomocysteinemia induced by folate deficiency and premature hearing loss involves impairment of cochlear Hcy metabolism and associated oxidative stress. ; R.M.-V. is supported by a fellowship from the JAE-CSIC predoctoral program. This work was supported by grants from the Ministerio de Ciencia e Innovación (BFU2009-08977 to M.A.P., SAF2011-24391 to I.V.-N., and PS09/01762 to C.M.-A.), the European Union (FP7-AFHELO and TARGEAR to I.V.-N.), U.S. National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (Grant DK056350 to S.H.Z.), and Puleva BioFoods (to I.V.-N., G.V.-M., and M.A.P.). ; Peer Reviewed

Celiac disease (CD) is an autoimmune enteropathy associated with alterations of metabolism. Metabolomics studies, although limited, showed changes in choline, choline-derived lipids, and methionine concentrations, which could be ascribed to alterations in one-carbon metabolism. To date, no targeted metabolomics analysis investigating di erences in the plasma choline/methionine metabolome of CD subjects are reported. This work is a targeted metabolomic study that analyzes 37 metabolites of the one-carbon metabolism in 17 children with CD, treated with a gluten-free diet and 17 healthy control siblings, in order to establish the potential defects in this metabolic network. Our results demonstrate the persistence of defects in the transsulfuration pathway of CD subjects, despite dietary treatment, while choline metabolism, methionine cycle, and folate cycle seem to be reversed and preserved to healthy levels. These findings describe for the first time, a metabolic defect in one-carbon metabolism which could have profound implications in the physiopathology and treatment of CD. ; Junta de Andalucía P12-AGR-2581 ; Spanish Ministry of Science, Innovation, and Universities (Ministerio de Ciencia, Innovacion y Universidades) RTI2018-099200-BI00 ; Generalitat of Catalonia: Agency for Management of University and Research Grants 2017SGR696 ; Department of Health SLT002/16/00250 ; European Union (EU) ; Grant "Investigation grant program by the SPAO" 2020 edition

Osteoporosis is a major health problem, and the economic costs are expected to rise due to an increase in life expectancy throughout the world. Its major consequence is fractures, and especially hip fractures are associated with institutionalization and increased mortality. Homocysteine is an amino acid intermediate formed during the metabolism of methionine. Homocysteinuria is a rare autosomal recessive biochemical abnormality which causes elevated plasma concentrations of homocysteine and severe occlusive vascular disease. In patients with homocysteinuria, there is an increased prevalence of skeletal deformities, including osteoporosis, which is a primary risk factor for hip fracture. The high prevalence of osteoporosis among patients with homocysteinuria suggests that high levels of plasmatic homocysteine may also increase the risk of fractures. Nutritional factors such as vitamins B12, B6, and folate are cofactors in homocysteine metabolism, and vitamin intakes may inversely affect plasma homocysteine levels.

Celiac disease (CD) is an autoimmune enteropathy associated with alterations of metabolism. Metabolomics studies, although limited, showed changes in choline, choline-derived lipids, and methionine concentrations, which could be ascribed to alterations in one-carbon metabolism. To date, no targeted metabolomics analysis investigating differences in the plasma choline/methionine metabolome of CD subjects are reported. This work is a targeted metabolomic study that analyzes 37 metabolites of the one-carbon metabolism in 17 children with CD, treated with a gluten-free diet and 17 healthy control siblings, in order to establish the potential defects in this metabolic network. Our results demonstrate the persistence of defects in the transsulfuration pathway of CD subjects, despite dietary treatment, while choline metabolism, methionine cycle, and folate cycle seem to be reversed and preserved to healthy levels. These findings describe for the first time, a metabolic defect in one-carbon metabolism which could have profound implications in the physiopathology and treatment of CD. ; This research was funded by the Regional Government of Andalusia, Excellence Research Project No P12-AGR-2581, the Spanish Ministry of Science, Innovation, and Universities (Ministerio de Ciencia, Innovación y Universidades, RTI2018-099200-BI00), and the Generalitat of Catalonia: Agency for Management of University and Research Grants (2017SGR696), and Department of Health (SLT002/16/00250) to RP. This study was co-financed by FEDER funds from the European Union ("A way to build Europe"). IRBLleida is a CERCA Programme/Generalitat of Catalonia. It was also partially funded with the grant "Investigation grant program by the SPAO" 2020 edition

Abstract

Aims
Wernicke–Korsakoff syndrome (WKS) is commonly associated with chronic alcohol misuse, a condition known to have multiple detrimental effects on thiamine metabolism. This study was conducted to identify genetic variants that may contribute to the development of WKS in individuals with alcohol dependence syndrome through alteration of thiamine transport into cells.


Methods
Exome sequencing data from a panel of genes related to alcohol metabolism and thiamine pathways were analysed in a discovery cohort of 29 individuals with WKS to identify possible genetic risk variants associated with its development. Variant frequencies in this discovery cohort were compared with European frequencies in the Genome Aggregation Database browser, and those present at significantly higher frequencies were genotyped in an additional cohort of 87 alcohol-dependent cases with WKS and 197 alcohol-dependent cognitively intact controls.


Results
Thirty non-synonymous variants were identified in the discovery cohort and, after filtering, 23 were taken forward and genotyped in the case–control cohort. Of these SLC19A1:rs1051266:G was nominally associated with WKS. SLC19A1 encodes the reduced folate carrier, a major transporter for physiological folate in plasma; rs1051266 is reported to impact folate transport. Thiamine pyrophosphate (TPP) efflux was significantly decreased in HEK293 cells, stably transfected with rs1051266:G, under thiamine deficient conditions when compared with the efflux from cells transfected with rs1051266:A (P = 5.7 × 10−11).


Conclusion
This study provides evidence for the role of genetic variation in the SLC19A1 gene, which may contribute to the development of WKS in vivo through modulation of TPP transport in cells.

Under a Creative Commons license. ; Omega-3 polyunsaturated fatty acids (PUFAs) are essential nutrients well-known for their beneficial effects, among others on cognitive development and maintenance, inflammation and oxidative stress. Previous studies have shown an inverse association between high plasma levels of PUFAs and age-related hearing loss, and the relationship between low serum folate and elevated plasma homocysteine levels and hearing loss. Therefore, we used C57BL/6J mice and long-term omega-3 supplementation to evaluate the impact on hearing by analyzing their auditory brainstem response (ABR) and distortion product otoacustic emissions (DPOAE) thresholds. The omega-3 group showed significantly lower ABR hearing thresholds (∼25 dB SPL) and higher DPOAE amplitudes in mid-high frequencies, when compared to the control group. These changes did not correlate with alterations between groups in plasma homocysteine or serum folate levels as measured by HPLC and a microbiological method, respectively. Ageing in the control group was associated with imbalanced cytokine expression toward increased pro-inflammatory cytokines as determined by RT-qPCR; these changes were prevented by omega-3 supplementation. Genes involved in homocysteine metabolism showed decreased expression during ageing of control animals, and only alterations in Bhmt and Cbs were significantly prevented by omega-3 feeding. Western blotting showed that omega-3 supplementation precluded the CBS protein increase detected in 10 month-old controls, but also produced an increase in BHMT protein levels. Altogether, the results obtained suggest a long term protective role of omega-3 supplementation on cochlear metabolism and progression of hearing loss. ; R.M.V. is a fellow of the JAE-CSIC predoctoral program, and N.V. is supported by FP7-AFHELO. The authors wish to thank the Genomics and Non-invasive Neurofunctional Evaluation facilities (IIBM, CSIC-UAM) for their technical support. This work was supported by grants of the Ministerio de Economía y Competitividad (SAF2011-24391 and SAF2014-53979-R to I.V.N.; BFU2009-08977 to M.A.P.), the European Union (FP7-AFHELO and TARGEAR to I.V.N.) and Puleva-LACTALIS (to I.V.N., G.V.M. and M.A.P.). ; Peer reviewed

Multiple micronutrient deficiencies (MNDs) co‐exist, often because of poor intakes and adversely impact health. Habitual diets were assessed in 300 school children (6–17 years old) recruited from two government schools by simple random sampling. Probability of adequacy (PA) for 11 micronutrients and mean probability of adequacy (MPA) was calculated. Haemoglobin, plasma ferritin, folic acid, vitamin B(12) and C‐reactive protein were estimated. Descriptive statistics and regression analysis were used to estimate magnitude and factors associated with MNDs. The contribution of fortified foods and/or supplements in addressing inadequacies and excessive intakes was modelled. The PA ranged from 0.04 for folate to 0.70 for zinc, and the MPA was 0.27. Prevalence of anaemia (53%), iron deficiency (57%; ID), iron deficiency anaemia (38%; IDA), folate deficiency (24%) and B(12) deficiency (43%) was high. Dietary inadequacy of iron, zinc and a low MPA was associated with anaemia and IDA. Inclusion of double fortified salt (DFS), fortified rice (FR) or iron folic acid (IFA) supplements individually in habitual diet reduced probability of iron inadequacy significantly from 82% to ≤13%. Inclusion of DFS and FR simultaneously led to disappearance of iron inadequacy, but risk of excessive intake increased to 16%. Inclusion of DFS, FR and IFA together increased risk of excess iron intake to 40%. Nevertheless, intakes of folate and B(12) remained inadequate even with FR and/or IFA. These results indicate a high risk of dietary MNDs in children and suggest need for more systematic intake measurements in representative sample and adjustment of iron dosages to avoid excessive intakes.