Special Issue "B-Vitamins and One-Carbon Metabolism"

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (15 September 2016).

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Prof. Dr. Kristina Pentieva
E-Mail Website
Guest Editor
School of Biomedical Sciences, Ulster University, Northern Ireland, BT52 1SA, UK
Fax: +44 28 703 249 65
Interests: B-vitamin requirements and recommendations for intake in humans; B-vitamins in health and disease; B-vitamins and epigenetics; food folate bioavailability; food folate analysis; food fortification; functional foods
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Special Issue Information

Dear Colleagues,

Folate, vitamin B12, vitamin B6 and riboflavin have a key role as coenzymes in one-carbon metabolism which in turn is essential for a broad range of fundamental physiological processes including RNA and DNA synthesis, cell division, tissue growth and methylation. Deficiencies or imbalance of B-vitamins, as well as genetic polymorphisms and environmental factors, are shown to disturb the normal function of one-carbon metabolism with adverse effects on human health. Although a vast volume of research has already been conducted in this area, there are still significant gaps in our knowledge that require further investigations. This Special Issue of Nutrients invites submission of manuscripts, original research or reviews of the scientific literature, focused on novel findings in relation to B-vitamins and one-carbon metabolism in terms of: metabolic roles and molecular mechanisms; gene-nutrient interactions; fetal growth and programing; risk of disease (birth defects and pregnancy related conditions, cancer, cardiovascular disease and hypertension, neuropsychiatric disease, osteoporosis); health effects of B-vitamin supplementation and food fortification.

Dr. Kristina Pentieva
Guest Editor

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Keywords

  • One-carbon metabolism
  • Folate
  • Vitamin B12
  • Vitamin B6
  • Riboflavin
  • Homocysteine
  • DNA methylation
  • Pregnancy
  • Neural tube defects
  • Cancer
  • Cardiovascular disease
  • Hypertension
  • Neuropsychiatric diseases
  • Folic acid and B-vitamin food fortification

Published Papers (26 papers)

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Open AccessArticle
South Asian Ethnicity Is Related to the Highest Risk of Vitamin B12 Deficiency in Pregnant Canadian Women
Nutrients 2017, 9(4), 317; https://doi.org/10.3390/nu9040317 - 23 Mar 2017
Cited by 8
Abstract
Vitamin B12 (B12) adequacy during pregnancy is crucial for maternal health and optimal fetal development; however, suboptimal B12 status has been reported in pregnant Canadian women. Methylmalonic acid (MMA) is a sensitive indicator of B12 status. Since few studies have measured MMA during [...] Read more.
Vitamin B12 (B12) adequacy during pregnancy is crucial for maternal health and optimal fetal development; however, suboptimal B12 status has been reported in pregnant Canadian women. Methylmalonic acid (MMA) is a sensitive indicator of B12 status. Since few studies have measured MMA during pregnancy in Canadian women, the objective of this study was to evaluate B12 status in pregnant women living in Metro Vancouver, using both plasma total B12 and MMA. We recruited a convenience sample of 320 pregnant women between 20 and 35 gestational weeks from local healthcare facilities. Plasma total B12 concentrations indicative of deficiency (<148 pmol/L) and suboptimal B12 status (148–220 pmol/L) were found in 18% and 33% of the women, respectively. Normal plasma MMA concentration (<210 nmol/L) was observed in 82% of all women. Gestational age was a strong predictor of plasma total B12 and MMA concentration, and South Asian ethnicity of B-12 deficiency and MMA concentrations. Overall, there was a high discrepancy between the prevalence of B12 inadequacy depending on the biomarker used. Independently, however, South Asian women were at particular risk for B12 deficiency, likely due to lower animal source food intake. Further study of this vulnerable group and performance testing of B12 biomarkers is warranted. Full article
(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism) Printed Edition available
Open AccessArticle
Correlations between Maternal, Breast Milk, and Infant Vitamin B12 Concentrations among Mother–Infant Dyads in Vancouver, Canada and Prey Veng, Cambodia: An Exploratory Analysis
Nutrients 2017, 9(3), 270; https://doi.org/10.3390/nu9030270 - 12 Mar 2017
Cited by 7
Abstract
Vitamin B12 plays an essential role in fetal and infant development. In regions where animal source food consumption is low and perinatal supplementation is uncommon, infants are at risk of vitamin B12 deficiency. In this secondary analysis, we measured total vitamin B12 concentrations [...] Read more.
Vitamin B12 plays an essential role in fetal and infant development. In regions where animal source food consumption is low and perinatal supplementation is uncommon, infants are at risk of vitamin B12 deficiency. In this secondary analysis, we measured total vitamin B12 concentrations in maternal and infant serum/plasma and breast milk among two samples of mother–infant dyads in Canada (assessed at 8 weeks post-partum) and in Cambodia (assessed between 3–27 weeks post-partum). Canadian mothers (n = 124) consumed a daily vitamin B12-containing multiple micronutrient supplement throughout pregnancy and lactation; Cambodian mothers (n = 69) were unsupplemented. The maternal, milk, and infant total vitamin B12 concentrations (as geometric means (95% CI) in pmol/L) were as follows: in Canada, 698 (648,747), 452 (400, 504), and 506 (459, 552); in Cambodia, 620 (552, 687), 317 (256, 378), and 357 (312, 402). The majority of participants were vitamin B12 sufficient (serum/plasma total B12 > 221 pmol/L): 99% and 97% of mothers and 94% and 84% of infants in Canada and Cambodia, respectively. Among the Canadians, maternal, milk, and infant vitamin B12 were all correlated (p < 0.05); only maternal and infant vitamin B12 were correlated among the Cambodians (p < 0.001). Full article
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Open AccessArticle
Voluntary Folic Acid Fortification Levels and Nutrient Composition of Food Products from the Spanish Market: A 2011–2015 Update
Nutrients 2017, 9(3), 234; https://doi.org/10.3390/nu9030234 - 05 Mar 2017
Cited by 5
Abstract
Introduction. Folic acid (FA) is a synthetic compound commonly added for voluntary fortification of food products in many European countries. In our country, food composition databases (FCDB) lack comprehensive data on FA fortification practices and this is considered a priority research need when [...] Read more.
Introduction. Folic acid (FA) is a synthetic compound commonly added for voluntary fortification of food products in many European countries. In our country, food composition databases (FCDB) lack comprehensive data on FA fortification practices and this is considered a priority research need when undergoing nutritional assessment of the population. Methods. A product inventory was collected and updated by visiting retail stores in Madrid Region, conducting online supermarket searches, and by the provision of food label information by manufacturers. Euro-FIR FCDB guidelines for data compilation and harmonization were used. Results. The FCDB, compiled between 2011 and 2015, includes FA as well as macro and micronutrient data from 338 fortified foodstuffs. As compared to previous FCDB updates (May 2010), 37 products have ceased to declare added FA in their labels, mainly yogurt and fermented milk products. The main food subgroup is ‘breakfast cereals’ (n = 95, 34% of total). However, the highest average FA fortification levels per recommended serving were observed in the ‘milk, milk products, and milk substitutes’ group at ≥35% FA Nutrient Reference Values (NRV, 200 µg, EU Regulation 1169 of 2011) (60–76.3 µg FA per 200 mL). Average contribution to the FA NRV per food group and serving ranged between 16%–35%. Conclusion. Our data show a minor decrease in the number of FA fortified products, but vitamin levels added by manufacturers are stable in most food groups and subgroups. This representative product inventory comprises the main FA food source from voluntary fortification in our country. It is therefore a unique compilation tool with valuable data for the assessment of dietary intakes for the vitamin. Full article
(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism) Printed Edition available
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Open AccessArticle
Sex-Specific Muscular Maturation Responses Following Prenatal Exposure to Methylation-Related Micronutrients in Pigs
Nutrients 2017, 9(1), 74; https://doi.org/10.3390/nu9010074 - 18 Jan 2017
Cited by 3
Abstract
Supplementation of micronutrients involved in DNA methylation, particularly during pregnancy, is recommended because of its impacts on human health, but further evidence is needed regarding the effects of over-supplementation and differences between sexes. Here, a porcine model was used to assess effects of [...] Read more.
Supplementation of micronutrients involved in DNA methylation, particularly during pregnancy, is recommended because of its impacts on human health, but further evidence is needed regarding the effects of over-supplementation and differences between sexes. Here, a porcine model was used to assess effects of maternal supplementation with one-carbon-cycle compounds during prenatal and postnatal stages on offspring muscle development. Sows received either a standard diet (CON) or a standard diet supplemented with folate, B6, B12, methionine, choline, and zinc (MET) throughout gestation. Myogenesis-, growth-, and nutrient utilization-related transcript expression was assessed using quantitative PCR. Organismal phenotype and gene expression effects differed significantly between males and females. Male MET-offspring showed increased fetal weight during late pregnancy but decreased live weight postnatally, with compensatory transcriptional responses comprising myogenic key drivers (Pax7, MyoD1, myogenin). In contrast, female weights were unaffected by diet, and mRNA abundances corresponded to a phenotype of cellular reorganization via FABP3, FABP4, SPP1 and Insulin-like Growth Factor-signaling. These findings in an animal model suggest that supplementation during pregnancy with methylation-related micronutrients can promote sex-specific myogenic maturation processes related to organismal growth and muscle metabolism. The usage of maternal dietary supplements should be more carefully considered regarding its ability to promote fetal and postnatal health. Full article
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Open AccessArticle
B-Vitamin Intake and Biomarker Status in Relation to Cognitive Decline in Healthy Older Adults in a 4-Year Follow-Up Study
Nutrients 2017, 9(1), 53; https://doi.org/10.3390/nu9010053 - 10 Jan 2017
Cited by 14
Abstract
Advancing age can be associated with an increase in cognitive dysfunction, a spectrum of disability that ranges in severity from mild cognitive impairment to dementia. Folate and the other B-vitamins involved in one-carbon metabolism are associated with cognition in ageing but the evidence [...] Read more.
Advancing age can be associated with an increase in cognitive dysfunction, a spectrum of disability that ranges in severity from mild cognitive impairment to dementia. Folate and the other B-vitamins involved in one-carbon metabolism are associated with cognition in ageing but the evidence is not entirely clear. The hypothesis addressed in this study was that lower dietary intake or biomarker status of folate and/or the metabolically related B-vitamins would be associated with a greater than expected rate of cognitive decline over a 4-year follow-up period in healthy older adults. Participants (aged 60–88 years; n = 155) who had been previously screened for cognitive function were reassessed four years after initial investigation using the Mini-Mental State Examination (MMSE). At the 4-year follow-up assessment when participants were aged 73.4 ± 7.1 years, mean cognitive MMSE scores had declined from 29.1 ± 1.3 at baseline to 27.5 ± 2.4 (p < 0.001), but some 27% of participants showed a greater than expected rate of cognitive decline (i.e., decrease in MMSE > 0.56 points per year). Lower vitamin B6 status, as measured using pyridoxal-5-phosphate (PLP; <43 nmol/L) was associated with a 3.5 times higher risk of accelerated cognitive decline, after adjustment for age and baseline MMSE score (OR, 3.48; 95% CI, 1.58 to 7.63; p < 0.05). Correspondingly, lower dietary intake (0.9–1.4 mg/day) of vitamin B6 was also associated with a greater rate of cognitive decline (OR, 4.22; 95% CI, 1.28–13.90; p < 0.05). No significant relationships of dietary intake or biomarker status with cognitive decline were observed for the other B-vitamins. In conclusion, lower dietary and biomarker status of vitamin B6 at baseline predicted a greater than expected rate of cognitive decline over a 4-year period in healthy older adults. Vitamin B6 may be an important protective factor in helping maintain cognitive health in ageing. Full article
(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism) Printed Edition available
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Open AccessArticle
Methionine and Choline Supply during the Periparturient Period Alter Plasma Amino Acid and One-Carbon Metabolism Profiles to Various Extents: Potential Role in Hepatic Metabolism and Antioxidant Status
Nutrients 2017, 9(1), 10; https://doi.org/10.3390/nu9010010 - 29 Dec 2016
Cited by 19
Abstract
The objective of this study was to profile plasma amino acids (AA) and derivatives of their metabolism during the periparturient period in response to supplemental rumen-protected methionine (MET) or rumen-protected choline (CHOL). Forty cows were fed from −21 through 30 days around parturition [...] Read more.
The objective of this study was to profile plasma amino acids (AA) and derivatives of their metabolism during the periparturient period in response to supplemental rumen-protected methionine (MET) or rumen-protected choline (CHOL). Forty cows were fed from −21 through 30 days around parturition in a 2 × 2 factorial design a diet containing MET or CHOL. MET supply led to greater circulating methionine and proportion of methionine in the essential AA pool, total AA, and total sulfur-containing compounds. Lysine in total AA also was greater in these cows, indicating a better overall AA profile. Sulfur-containing compounds (cystathionine, cystine, homocystine, and taurine) were greater in MET-fed cows, indicating an enriched sulfur-containing compound pool due to enhanced transsulfuration activity. Circulating essential AA and total AA concentrations were greater in cows supplied MET due to greater lysine, arginine, tryptophan, threonine, proline, asparagine, alanine, and citrulline. In contrast, CHOL supply had no effect on essential AA or total AA, and only tryptophan and cystine were greater. Plasma 3-methylhistidine concentration was lower in response to CHOL supply, suggesting less tissue protein mobilization in these cows. Overall, the data revealed that enhanced periparturient supply of MET has positive effects on plasma AA profiles and overall antioxidant status. Full article
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Open AccessArticle
Folate and Vitamin B12-Related Biomarkers in Relation to Brain Volumes
Nutrients 2017, 9(1), 8; https://doi.org/10.3390/nu9010008 - 24 Dec 2016
Cited by 3
Abstract
Aim: We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B12 status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin B12 supplementation with participants who did not. Methods: Participants of [...] Read more.
Aim: We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B12 status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin B12 supplementation with participants who did not. Methods: Participants of the B-PROOF study (n = 2919) were assigned to 400 µg folic acid and 500 µg vitamin B12, or a placebo. After two years of intervention, T1-weighted magnetic resonance imaging (MRI) scans were made in a random subsample (n = 218) to obtain grey and white matter volume, and total brain volume (TBV). Plasma homocysteine, serum folate, vitamin B12, holotranscobalamin, and methylmalonic acid concentrations were measured. Results: Multiple linear regression analyses showed inverse associations between plasma homocysteine with TBV (β = −0.91, 95% CI −1.85–0.03; p = 0.06) and between serum folate and TBV (β = −0.20, 95% CI −0.38, −0.02; p = 0.03). No significant associations were observed for serum vitamin B12 and holotranscobalamin. Fully adjusted ANCOVA models showed that the group that received B-vitamins had a lower TBV (adjusted mean 1064, 95% CI 1058–1069 mL) than the non-supplemented group (1072, 95% CI 1067–1078 mL, p = 0.03). Conclusions: Results were contradictory, with higher Hcy levels associated with lower TBV, but also with higher folate levels associated with lower TBV. In addition, the lack of a baseline measurement withholds us from giving recommendations on whether folic acid and vitamin B12 supplementation will be beneficial above and beyond normal dietary intake for brain health. Full article
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Open AccessArticle
Vitamin B12 Status among Pregnant Women in the UK and Its Association with Obesity and Gestational Diabetes
Nutrients 2016, 8(12), 768; https://doi.org/10.3390/nu8120768 - 01 Dec 2016
Cited by 18
Abstract
Background: To evaluate vitamin B12 and folate status in pregnancy and their relationship with maternal obesity, gestational diabetes mellitus (GDM), and offspring birthweight. Methods: A retrospective case-control study of 344 women (143 GDM, 201 no-GDM) attending a district general hospital and that had [...] Read more.
Background: To evaluate vitamin B12 and folate status in pregnancy and their relationship with maternal obesity, gestational diabetes mellitus (GDM), and offspring birthweight. Methods: A retrospective case-control study of 344 women (143 GDM, 201 no-GDM) attending a district general hospital and that had B12 and folate levels measured in the early 3rd trimester was performed. Maternal history including early pregnancy body mass index (BMI) and neonatal data (birthweight, sex, and gestational age) was recorded for all subjects. Results: 26% of the cohort had B12 levels <150 pmol/L (32% vs. 22% in the two groups respectively, p < 0.05) while 1.5% were folate deficient. After adjusting for confounders, 1st trimester BMI was negatively associated with 3rd trimester B12 levels. Women with B12 insufficiency had higher odds of obesity and GDM (aOR (95% CI) 2.40 (1.31, 4.40), p = 0.004, and 2.59 (1.35, 4.98), p = 0.004, respectively), although the latter was partly mediated by BMI. In women without GDM, the lowest quartile of B12 and highest quartile of folate had significantly higher adjusted risk of fetal macrosomia (RR 5.3 (1.26, 21.91), p = 0.02 and 4.99 (1.15, 21.62), p = 0.03 respectively). Conclusion: This is the first study from the UK to show that maternal B12 levels are associated with BMI, risk of GDM, and additionally may have an independent effect on macrosomia. Due to the increasing burden of maternal obesity and GDM, longitudinal studies with B12 measurements in early pregnancy are needed to explore this link. Full article
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Open AccessArticle
Validation of Folate-Enriched Eggs as a Functional Food for Improving Folate Intake in Consumers
Nutrients 2016, 8(12), 777; https://doi.org/10.3390/nu8120777 - 30 Nov 2016
Cited by 4
Abstract
Functional foods enriched with folate may be beneficial as a means of optimizing folate status in consumers. We recently developed novel eggs enriched with folate through folic acid supplementation of the hen’s feed, but their potential to influence consumer folate status is unknown [...] Read more.
Functional foods enriched with folate may be beneficial as a means of optimizing folate status in consumers. We recently developed novel eggs enriched with folate through folic acid supplementation of the hen’s feed, but their potential to influence consumer folate status is unknown because the natural folate forms incorporated into the eggs may not necessarily be retained during storage and cooking. This study aimed to determine the stability of natural folates in folate-enriched eggs under typical conditions of storage and cooking. Total folate was determined by microbiological assay following tri-enzyme treatment in folate-enriched eggs and un-enriched (barn and free-range) on the day they were laid, after storage (up to 27 days) and after using four typical cooking methods (boiling, poaching, frying, scrambling) for different durations. On the day of laying, the folate content of enriched eggs was found to be significantly higher than that of un-enriched barn or free-range eggs (mean ± SD; 123.2 ± 12.4 vs. 41.2 ± 2.8 vs. 65.6 ± 18.5 µg/100 g; p < 0.001). Storage at refrigerator and room temperature for periods up to the Best Before date resulted in no significant losses to the folate content of folate-enriched eggs. Furthermore, folate in enriched eggs remained stable when cooked by four typical methods for periods up to the maximum cooking time (e.g., 135 ± 22.5, 133.9 ± 23.0 and 132.5 ± 35.1; p = 0.73, for raw, scrambled for 50 s and scrambled for 2 min, respectively). Thus, natural folates in folate-enriched eggs remain highly stable with little or no losses following storage and cooking. These findings are important because they demonstrate the feasibility of introducing folate-enriched eggs into the diet of consumers as functional foods with enriched folate content. Further studies will confirm their effectiveness in optimizing the biomarker folate status of consumers. Full article
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Open AccessArticle
Impact of Pre-Pregnancy BMI on B Vitamin and Inflammatory Status in Early Pregnancy: An Observational Cohort Study
Nutrients 2016, 8(12), 776; https://doi.org/10.3390/nu8120776 - 30 Nov 2016
Cited by 4
Abstract
Maternal nutrition and inflammation have been suggested as mediators in the development of various adverse pregnancy outcomes associated with maternal obesity. We have investigated the relation between pre-pregnancy BMI, B vitamin status, and inflammatory markers in a group of healthy pregnant women. Cobalamin, [...] Read more.
Maternal nutrition and inflammation have been suggested as mediators in the development of various adverse pregnancy outcomes associated with maternal obesity. We have investigated the relation between pre-pregnancy BMI, B vitamin status, and inflammatory markers in a group of healthy pregnant women. Cobalamin, folate, pyridoxal 5′-phosphate, and riboflavin; and the metabolic markers homocysteine, methylmalonic acid, and 3-hydroxykynurenine/xanthurenic acid ratio (HK/XA); and markers of cellular inflammation, neopterin and kynurenine/tryptophan ratio (KTR) were determined in pregnancy week 18 and related to pre-pregnancy body mass index (BMI), in 2797 women from the Norwegian Mother and Child Cohort Study (MoBa). Pre-pregnancy BMI was inversely related to folate, cobalamin, pyridoxal 5′-phosphate (PLP), and riboflavin (p < 0.001), and associated with increased neopterin and KTR levels (p < 0.001). Inflammation seemed to be an independent predictor of low vitamin B6 status, as verified by low PLP and high HK/XA ratio. A high pre-pregnancy BMI is a risk factor for low B vitamin status and increased cellular inflammation. As an optimal micronutrient status is vital for normal fetal development, the observed lower B vitamin levels may contribute to adverse pregnancy outcomes associated with maternal obesity and B vitamin status should be assessed in women with high BMI before they get pregnant. Full article
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Open AccessArticle
Dietary B Vitamins and a 10-Year Risk of Dementia in Older Persons
Nutrients 2016, 8(12), 761; https://doi.org/10.3390/nu8120761 - 26 Nov 2016
Cited by 11
Abstract
B vitamins may lower the risk of dementia, yet epidemiological findings, mostly from countries with folic acid fortification, have remained inconsistent. We evaluated in a large French cohort of older persons the associations between dietary B vitamins and long-term incident dementia. We included [...] Read more.
B vitamins may lower the risk of dementia, yet epidemiological findings, mostly from countries with folic acid fortification, have remained inconsistent. We evaluated in a large French cohort of older persons the associations between dietary B vitamins and long-term incident dementia. We included 1321 participants from the Three-City Study who completed a 24 h dietary recall, were free of dementia at the time of diet assessment, and were followed for an average of 7.4 years. In Cox proportional hazards models adjusted for multiple potential confounders, including overall diet quality, higher intake of folate was inversely associated with the risk of dementia (p for trend = 0.02), with an approximately 50% lower risk for individuals in the highest compared to the lowest quintile of folate (HR = 0.47; 95% CI 0.28; 0.81). No association was found for vitamins B6 and B12. In conclusion, in a large French cohort with a relatively low baseline folate status (average intake = 278 µg/day), higher folate intakes were associated with a decreased risk of dementia. Full article
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Open AccessArticle
Effects of Two-Year Vitamin B12 and Folic Acid Supplementation on Depressive Symptoms and Quality of Life in Older Adults with Elevated Homocysteine Concentrations: Additional Results from the B-PROOF Study, an RCT
Nutrients 2016, 8(11), 748; https://doi.org/10.3390/nu8110748 - 23 Nov 2016
Cited by 13
Abstract
Lowering elevated plasma homocysteine (Hcy) concentrations by supplementing vitamin B12 and folic acid may reduce depressive symptoms and improve health-related quality of life (HR-QoL) in older adults. This study aimed to test this hypothesis in a randomized controlled trial. Participants (N [...] Read more.
Lowering elevated plasma homocysteine (Hcy) concentrations by supplementing vitamin B12 and folic acid may reduce depressive symptoms and improve health-related quality of life (HR-QoL) in older adults. This study aimed to test this hypothesis in a randomized controlled trial. Participants (N = 2919, ≥65 years, Hcy concentrations ≥12 µmol/L) received either 500 µg vitamin B12 and 400 µg folic acid daily or placebo for two years. Both tablets contained 15 µg vitamin D3. Depressive symptoms were measured with the Geriatric Depression Scale-15 (GDS-15). HR-QoL was assessed with the SF-12 Mental and Physical component summary scores and the EQ-5D Index score and Visual Analogue Scale. Differences in two-year change scores were analyzed with Analysis of Covariance (ANCOVA). Hcy concentrations decreased more in the intervention group, but two-year change scores of the GDS-15 and three of four HR-QoL measures did not differ between groups. The EQ-5D Index score declined less in the intervention group than in the placebo group (mean change 0.00 vs. −0.02, p = 0.004). In conclusion, two-year supplementation with vitamin B12 and folic acid in older adults with hyperhomocysteinemia showed that lowering Hcy concentrations does not reduce depressive symptoms, but it may have a small positive effect on HR-QoL. Full article
(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism) Printed Edition available
Open AccessArticle
Organ-Specific Gene Expression Changes in the Fetal Liver and Placenta in Response to Maternal Folate Depletion
Nutrients 2016, 8(10), 661; https://doi.org/10.3390/nu8100661 - 22 Oct 2016
Cited by 6
Abstract
Growing evidence supports the hypothesis that the in utero environment can have profound implications for fetal development and later life offspring health. Current theory suggests conditions experienced in utero prepare, or “programme”, the fetus for its anticipated post-natal environment. The mechanisms responsible for [...] Read more.
Growing evidence supports the hypothesis that the in utero environment can have profound implications for fetal development and later life offspring health. Current theory suggests conditions experienced in utero prepare, or “programme”, the fetus for its anticipated post-natal environment. The mechanisms responsible for these programming events are poorly understood but are likely to involve gene expression changes. Folate is essential for normal fetal development and inadequate maternal folate supply during pregnancy has long term adverse effects for offspring. We tested the hypothesis that folate depletion during pregnancy alters offspring programming through altered gene expression. Female C57BL/6J mice were fed diets containing 2 mg or 0.4 mg folic acid/kg for 4 weeks before mating and throughout pregnancy. At 17.5 day gestation, genome-wide gene expression was measured in male fetal livers and placentas. In the fetal liver, 989 genes were expressed differentially (555 up-regulated, 434 down-regulated) in response to maternal folate depletion, with 460 genes expressed differentially (250 up-regulated, 255 down-regulated) in the placenta. Only 25 differentially expressed genes were common between organs. Maternal folate intake during pregnancy influences fetal gene expression in a highly organ specific manner which may reflect organ-specific functions. Full article
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Open AccessFeature PaperArticle
Maternal Folate Status and the BHMT c.716G>A Polymorphism Affect the Betaine Dimethylglycine Pathway during Pregnancy
Nutrients 2016, 8(10), 621; https://doi.org/10.3390/nu8100621 - 09 Oct 2016
Cited by 4
Abstract
The effect of the betaine: homocysteine methyltransferase BHMT c.716G>A (G: guanosine; A: adenosine) single nucleotide polymorphism (SNP) on the BHMT pathway is unknown during pregnancy. We hypothesised that it impairs betaine to dimethylglycine conversion and that folate status modifies its effect. We studied [...] Read more.
The effect of the betaine: homocysteine methyltransferase BHMT c.716G>A (G: guanosine; A: adenosine) single nucleotide polymorphism (SNP) on the BHMT pathway is unknown during pregnancy. We hypothesised that it impairs betaine to dimethylglycine conversion and that folate status modifies its effect. We studied 612 women from the Reus Tarragona Birth Cohort from ≤12 gestational weeks (GW) throughout pregnancy. The frequency of the variant BHMT c.716A allele was 30.8% (95% confidence interval (CI): 28.3, 33.5). In participants with normal-high plasma folate status (>13.4 nmol/L), least square geometric mean [95% CI] plasma dimethylglycine (pDMG, µmol/L) was lower in the GA (2.35 [2.23, 2.47]) versus GG (2.58 [2.46, 2.70]) genotype at ≤12 GW (p < 0.05) and in the GA (2.08 [1.97, 2.19]) and AA (1.94 [1.75, 2.16]) versus GG (2.29 [2.18, 2.40]) genotypes at 15 GW (p < 0.05). No differences in pDMG between genotypes were observed in participants with possible folate deficiency (≤13.4 nmol/L) (p for interactions at ≤12 GW: 0.023 and 15 GW: 0.038). PDMG was lower in participants with the AA versus GG genotype at 34 GW (2.01 [1.79, 2.25] versus 2.44 [2.16, 2.76] and at labour, 2.51 [2.39, 2.64] versus 3.00 [2.84, 3.18], (p < 0.01)). Possible deficiency compared to normal-high folate status was associated with higher pDMG in multiple linear regression analysis (β coefficients [SEM] ranging from 0.07 [0.04], p < 0.05 to 0.20 [0.04], p < 0.001 in models from early and mid-late pregnancy) and the AA compared to GG genotype was associated with lower pDMG (β coefficients [SEM] ranging from −0.11 [0.06], p = 0.055 to −0.23 [0.06], p < 0.001). Conclusion: During pregnancy, the BHMT pathway is affected by folate status and by the variant BHMT c.716A allele. Full article
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Open AccessArticle
Intakes of Folate and Vitamin B12 and Biomarkers of Status in the Very Old: The Newcastle 85+ Study
Nutrients 2016, 8(10), 604; https://doi.org/10.3390/nu8100604 - 28 Sep 2016
Cited by 11
Abstract
Very old adults are at increased risk of folate and vitamin B12 deficiencies due to reduced food intake and gastrointestinal absorption. The main aim was to determine the association between folate and vitamin B12 intake from total diets and food groups, and status. [...] Read more.
Very old adults are at increased risk of folate and vitamin B12 deficiencies due to reduced food intake and gastrointestinal absorption. The main aim was to determine the association between folate and vitamin B12 intake from total diets and food groups, and status. Folate or vitamin B12 intakes (2 × 24 h multiple pass recalls) and red blood cell (RBC) folate or plasma vitamin B12 (chemiluminescence immunoassays) concentrations were available at baseline for 731 participants aged 85 from the Newcastle 85+ Study (North-East England). Generalized additive and binary logistic models estimated the associations between folate and vitamin B12 intakes from total diets and food groups, and RBC folate and plasma B12. Folate intake from total diets and cereal and cereal products was strongly associated with RBC folate (p < 0.001). Total vitamin B12 intake was weakly associated with plasma vitamin B12 (p = 0.054) but those with higher intakes from total diets or meat and meat products were less likely to have deficient status. Women homozygous for the FUT2 G allele had higher concentrations of plasma vitamin B12. Cereals and cereal products are a very important source of folate in the very old. Higher intakes of folate and vitamin B12 lower the risk of “inadequate” status. Full article
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Open AccessArticle
Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats
Nutrients 2016, 8(10), 594; https://doi.org/10.3390/nu8100594 - 23 Sep 2016
Cited by 12
Abstract
Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) [...] Read more.
Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet. Full article
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Open AccessArticle
Association of Vitamin B12 with Pro-Inflammatory Cytokines and Biochemical Markers Related to Cardiometabolic Risk in Saudi Subjects
Nutrients 2016, 8(9), 460; https://doi.org/10.3390/nu8090460 - 06 Sep 2016
Cited by 10
Abstract
Background: This study aimed to examine the relationship between changes in systemic vitamin B12 concentrations with pro-inflammatory cytokines, anthropometric factors and biochemical markers of cardiometabolic risk in a Saudi population. Methods: A total of 364 subjects (224 children, age: 12.99 ± 2.73 (mean [...] Read more.
Background: This study aimed to examine the relationship between changes in systemic vitamin B12 concentrations with pro-inflammatory cytokines, anthropometric factors and biochemical markers of cardiometabolic risk in a Saudi population. Methods: A total of 364 subjects (224 children, age: 12.99 ± 2.73 (mean ± SD) years; BMI: 20.07 ± 4.92 kg/m2 and 140 adults, age: 41.87 ± 8.82 years; BMI: 31.65 ± 5.77 kg/m2) were studied. Fasting blood, anthropometric and biochemical data were collected. Serum cytokines were quantified using multiplex assay kits and B12 concentrations were measured using immunoassay analyzer. Results: Vitamin B12 was negatively associated with TNF-α (r = −0.14, p < 0.05), insulin (r = −0.230, p < 0.01) and HOMA-IR (r = −0.252, p < 0.01) in all subjects. In children, vitamin B12 was negatively associated with serum resistin (r = −0.160, p < 0.01), insulin (r = −0.248, p < 0.01), HOMA-IR (r = −0.261, p < 0.01). In adults, vitamin B12 was negatively associated with TNF-α (r = −0.242, p < 0.01) while positively associated with resistin (r = 0.248, p < 0.01). Serum resistin was the most significant predictor for circulating vitamin B12 in all subjects (r2 = −0.17, p < 0.05) and in children (r2 = −0.167, p < 0.01) while HDL-cholesterol was the predictor of B12 in adults (r2 = −0.78, p < 0.05). Conclusions: Serum vitamin B12 concentrations were associated with pro-inflammatory cytokines and biochemical markers of cardiometabolic risks in adults. Maintaining adequate vitamin B12 concentrations may lower inflammation-induced cardiometabolic risk in the Saudi adult population. Full article
(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism) Printed Edition available
Open AccessArticle
Prevalence and Predictors of Low Vitamin B6 Status in Healthy Young Adult Women in Metro Vancouver
Nutrients 2016, 8(9), 538; https://doi.org/10.3390/nu8090538 - 01 Sep 2016
Cited by 3
Abstract
Low periconceptional vitamin B6 (B6) status has been associated with an increased risk of preterm birth and early pregnancy loss. Given many pregnancies are unplanned; it is important for women to maintain an adequate B6 status throughout reproductive years. There is limited data [...] Read more.
Low periconceptional vitamin B6 (B6) status has been associated with an increased risk of preterm birth and early pregnancy loss. Given many pregnancies are unplanned; it is important for women to maintain an adequate B6 status throughout reproductive years. There is limited data on B6 status in Canadian women. This study aimed to assess the prevalence of B6 deficiency and predictors of B6 status in young adult women in Metro Vancouver. We included a convenience sample of young adult non-pregnant women (19–35 years; n = 202). Vitamin B6 status was determined using fasting plasma concentrations of pyridoxal 5’-phosphate (PLP). Mean (95% confidence interval) plasma PLP concentration was 61.0 (55.2, 67.3) nmol/L. The prevalence of B6 deficiency (plasma PLP < 20 nmol/L) was 1.5% and that of suboptimal B6 status (plasma PLP = 20–30 nmol/L) was 10.9%. Body mass index, South Asian ethnicity, relative dietary B6 intake, and the use of supplemental B6 were significant predictors of plasma PLP. The combined 12.4% prevalence of B6 deficiency and suboptimal status was lower than data reported in US populations and might be due to the high socioeconomic status of our sample. More research is warranted to determine B6 status in the general Canadian population. Full article
(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism) Printed Edition available

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Open AccessReview
Pyridoxine (Vitamin B6) and the Glutathione Peroxidase System; a Link between One-Carbon Metabolism and Antioxidation
Nutrients 2017, 9(3), 189; https://doi.org/10.3390/nu9030189 - 24 Feb 2017
Cited by 12
Abstract
Vitamin B6 (B6) has a central role in the metabolism of amino acids, which includes important interactions with endogenous redox reactions through its effects on the glutathione peroxidase (GPX) system. In fact, B6-dependent enzymes catalyse most reactions of [...] Read more.
Vitamin B6 (B6) has a central role in the metabolism of amino acids, which includes important interactions with endogenous redox reactions through its effects on the glutathione peroxidase (GPX) system. In fact, B6-dependent enzymes catalyse most reactions of the transsulfuration pathway, driving homocysteine to cysteine and further into GPX proteins. Considering that mammals metabolize sulfur- and seleno-amino acids similarly, B6 plays an important role in the fate of sulfur-homocysteine and its seleno counterpart between transsulfuration and one-carbon metabolism, especially under oxidative stress conditions. This is particularly important in reproduction because ovarian metabolism may generate an excess of reactive oxygen species (ROS) during the peri-estrus period, which may impair ovulatory functions and early embryo development. Later in gestation, placentation raises embryo oxygen tension and may induce a higher expression of ROS markers and eventually embryo losses. Interestingly, the metabolic accumulation of ROS up-regulates the flow of one-carbon units to transsulfuration and down-regulates remethylation. However, in embryos, the transsulfuration pathway is not functional, making the understanding of the interplay between these two pathways particularly crucial. In this review, the importance of the maternal metabolic status of B6 for the flow of one-carbon units towards both maternal and embryonic GPX systems is discussed. Additionally, B6 effects on GPX activity and gene expression in dams, as well as embryo development, are presented in a pig model under different oxidative stress conditions. Full article
(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism) Printed Edition available
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Open AccessReview
Nutrients in Energy and One-Carbon Metabolism: Learning from Metformin Users
Nutrients 2017, 9(2), 121; https://doi.org/10.3390/nu9020121 - 10 Feb 2017
Cited by 11
Abstract
Metabolic vulnerability is associated with age-related diseases and concomitant co-morbidities, which include obesity, diabetes, atherosclerosis and cancer. Most of the health problems we face today come from excessive intake of nutrients and drugs mimicking dietary effects and dietary restriction are the most successful [...] Read more.
Metabolic vulnerability is associated with age-related diseases and concomitant co-morbidities, which include obesity, diabetes, atherosclerosis and cancer. Most of the health problems we face today come from excessive intake of nutrients and drugs mimicking dietary effects and dietary restriction are the most successful manipulations targeting age-related pathways. Phenotypic heterogeneity and individual response to metabolic stressors are closely related food intake. Understanding the complexity of the relationship between dietary provision and metabolic consequences in the long term might provide clinical strategies to improve healthspan. New aspects of metformin activity provide a link to many of the overlapping factors, especially the way in which organismal bioenergetics remodel one-carbon metabolism. Metformin not only inhibits mitochondrial complex 1, modulating the metabolic response to nutrient intake, but also alters one-carbon metabolic pathways. Here, we discuss findings on the mechanism(s) of action of metformin with the potential for therapeutic interpretations. Full article
(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism) Printed Edition available
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Open AccessReview
Potential Links between Impaired One-Carbon Metabolism Due to Polymorphisms, Inadequate B-Vitamin Status, and the Development of Alzheimer’s Disease
Nutrients 2016, 8(12), 803; https://doi.org/10.3390/nu8120803 - 10 Dec 2016
Cited by 17
Abstract
Alzheimer’s disease (AD) is the major cause of dementia and no preventive or effective treatment has been established to date. The etiology of AD is poorly understood, but genetic and environmental factors seem to play a role in its onset and progression. In [...] Read more.
Alzheimer’s disease (AD) is the major cause of dementia and no preventive or effective treatment has been established to date. The etiology of AD is poorly understood, but genetic and environmental factors seem to play a role in its onset and progression. In particular, factors affecting the one-carbon metabolism (OCM) are thought to be important and elevated homocysteine (Hcy) levels, indicating impaired OCM, have been associated with AD. We aimed at evaluating the role of polymorphisms of key OCM enzymes in the etiology of AD, particularly when intakes of relevant B-vitamins are inadequate. Our review indicates that a range of compensatory mechanisms exist to maintain a metabolic balance. However, these become overwhelmed if the activity of more than one enzyme is reduced due to genetic factors or insufficient folate, riboflavin, vitamin B6 and/or vitamin B12 levels. Consequences include increased Hcy levels and reduced capacity to synthetize, methylate and repair DNA, and/or modulated neurotransmission. This seems to favor the development of hallmarks of AD particularly when combined with increased oxidative stress e.g., in apolipoprotein E (ApoE) ε4 carriers. However, as these effects can be compensated at least partially by adequate intakes of B-vitamins, achieving optimal B-vitamin status for the general population should be a public health priority. Full article
(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism) Printed Edition available
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Open AccessReview
Metformin Treatment and Homocysteine: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Nutrients 2016, 8(12), 798; https://doi.org/10.3390/nu8120798 - 09 Dec 2016
Cited by 13
Abstract
The aim of this systematic review is to assess whether metformin could change the concentration of serum homocysteine (Hcy) with and without simultaneous supplementation of B-group vitamins or folic acid. A literature search was conducted in PubMed, EmBase, and Cochrane Central Register of [...] Read more.
The aim of this systematic review is to assess whether metformin could change the concentration of serum homocysteine (Hcy) with and without simultaneous supplementation of B-group vitamins or folic acid. A literature search was conducted in PubMed, EmBase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials (RCTs) reporting the concentration of serum Hcy in metformin-treated adults. Meta-analysis was applied to assess the association between metformin and the changes of Hcy concentration. Twelve publications were included in this study. In the overall analysis, metformin administration was not statistically associated with the change of Hcy when compared with the control treatment (mean difference (MD), 0.40 μmol/L; 95% confidence interval (CI), −0.07~0.87 μmol/L, p = 0.10). In the subgroup analysis, metformin was significantly associated with an increased concentration of Hcy in the absence of exogenous supplementation of folic acid or B-group vitamins (MD, 2.02 μmol/L; 95% CI, 1.37~2.67 μmol/L, p < 0.00001), but with a decreased concentration of serum Hcy in the presence of these exogenous supplementations (MD, −0.74 μmol/L; 95% CI, −1.19~−0.30 μmol/L, p = 0.001). Therefore, although the overall effect of metformin on the concentration of serum Hcy was neutral, our results suggested that metformin could increase the concentration of Hcy when exogenous B-group vitamins or folic acid supplementation was not given. Full article
(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism) Printed Edition available
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Open AccessReview
Vitamin B12 among Vegetarians: Status, Assessment and Supplementation
Nutrients 2016, 8(12), 767; https://doi.org/10.3390/nu8120767 - 29 Nov 2016
Cited by 48
Abstract
Cobalamin is an essential molecule for humans. It acts as a cofactor in one-carbon transfers through methylation and molecular rearrangement. These functions take place in fatty acid, amino acid and nucleic acid metabolic pathways. The deficiency of vitamin B12 is clinically manifested in [...] Read more.
Cobalamin is an essential molecule for humans. It acts as a cofactor in one-carbon transfers through methylation and molecular rearrangement. These functions take place in fatty acid, amino acid and nucleic acid metabolic pathways. The deficiency of vitamin B12 is clinically manifested in the blood and nervous system where the cobalamin plays a key role in cell replication and in fatty acid metabolism. Hypovitaminosis arises from inadequate absorption, from genetic defects that alter transport through the body, or from inadequate intake as a result of diet. With the growing adoption of vegetarian eating styles in Western countries, there is growing focus on whether diets that exclude animal foods are adequate. Since food availability in these countries is not a problem, and therefore plant foods are sufficiently adequate, the most delicate issue remains the contribution of cobalamin, which is poorly represented in plants. In this review, we will discuss the status of vitamin B12 among vegetarians, the diagnostic markers for the detection of cobalamin deficiency and appropriate sources for sufficient intake, through the description of the features and functions of vitamin B12 and its absorption mechanism. Full article
(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism) Printed Edition available
Open AccessReview
Nutrition, One-Carbon Metabolism and Neural Tube Defects: A Review
Nutrients 2016, 8(11), 741; https://doi.org/10.3390/nu8110741 - 23 Nov 2016
Cited by 19
Abstract
Neural tube defects (NTDs) are a group of severe congenital malformations, induced by the combined effects of genes and the environment. The most valuable finding so far has been the protective effect of folic acid supplementation against NTDs. However, many women do not [...] Read more.
Neural tube defects (NTDs) are a group of severe congenital malformations, induced by the combined effects of genes and the environment. The most valuable finding so far has been the protective effect of folic acid supplementation against NTDs. However, many women do not take folic acid supplements until they are pregnant, which is too late to prevent NTDs effectively. Long-term intake of folic acid–fortified food is a good choice to solve this problem, and mandatory folic acid fortification should be further promoted, especially in Europe, Asia and Africa. Vitamin B2, vitamin B-6, vitamin B-12, choline, betaine and n-3 polyunsaturated fatty acids (PUFAs) can also reduce the NTD risk by interacting with the one-carbon metabolism pathway. This suggest that multivitamin B combined with choline, betaine and n-3 PUFAs supplementation may have a better protective effect against NTDs than folic acid alone. Genetic polymorphisms involved in one-carbon metabolism are associated with NTD risk, and gene screening for women of childbearing age prior to pregnancy may help prevent NTDs induced by the risk allele. In addition, the consumption of alcohol, tea and coffee, and low intakes of fruit and vegetable are also associated with the increased risk of NTDs, and should be avoided by women of childbearing age. Full article
(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism) Printed Edition available
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Open AccessReview
Causes, Consequences and Public Health Implications of Low B-Vitamin Status in Ageing
Nutrients 2016, 8(11), 725; https://doi.org/10.3390/nu8110725 - 16 Nov 2016
Cited by 26
Abstract
The potential protective roles of folate and the metabolically related B-vitamins (vitamins B12, B6 and riboflavin) in diseases of ageing are of increasing research interest. The most common cause of folate and riboflavin deficiencies in older people is low dietary intake, whereas low [...] Read more.
The potential protective roles of folate and the metabolically related B-vitamins (vitamins B12, B6 and riboflavin) in diseases of ageing are of increasing research interest. The most common cause of folate and riboflavin deficiencies in older people is low dietary intake, whereas low B12 status is primarily associated with food-bound malabsorption, while sub-optimal vitamin B6 status is attributed to increased requirements in ageing. Observational evidence links low status of folate and the related B-vitamins (and/or elevated concentrations of homocysteine) with a higher risk of degenerative diseases including cardiovascular disease (CVD), cognitive dysfunction and osteoporosis. Deficient or low status of these B-vitamins alone or in combination with genetic polymorphisms, including the common MTHFR 677 C → T polymorphism, could contribute to greater disease risk in ageing by causing perturbations in one carbon metabolism. Moreover, interventions with the relevant B-vitamins to optimise status may have beneficial effects in preventing degenerative diseases. The precise mechanisms are unknown but many have been proposed involving the role of folate and the related B-vitamins as co-factors for one-carbon transfer reactions, which are fundamental for DNA and RNA biosynthesis and the maintenance of methylation reactions. This review will examine the evidence linking folate and related B-vitamins with health and disease in ageing, associated mechanisms and public health implications. Full article
(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism) Printed Edition available
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Open AccessReview
Novel Approaches to Investigate One-Carbon Metabolism and Related B-Vitamins in Blood Pressure
Nutrients 2016, 8(11), 720; https://doi.org/10.3390/nu8110720 - 11 Nov 2016
Cited by 3
Abstract
Hypertension, a major risk factor for heart disease and stroke, is the world’s leading cause of preventable, premature death. A common polymorphism (677C→T) in the gene encoding the folate metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR) is associated with increased blood pressure, and there is [...] Read more.
Hypertension, a major risk factor for heart disease and stroke, is the world’s leading cause of preventable, premature death. A common polymorphism (677C→T) in the gene encoding the folate metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR) is associated with increased blood pressure, and there is accumulating evidence demonstrating that this phenotype can be modulated, specifically in individuals with the MTHFR 677TT genotype, by the B-vitamin riboflavin, an essential co-factor for MTHFR. The underlying mechanism that links this polymorphism, and the related gene-nutrient interaction, with hypertension is currently unknown. Previous research has shown that 5-methyltetrahydrofolate, the product of the reaction catalysed by MTHFR, appears to be a positive allosteric modulator of endothelial nitric oxide synthase (eNOS) and may thus increase the production of nitric oxide, a potent vasodilator. Blood pressure follows a circadian pattern, peaking shortly after wakening and falling during the night, a phenomenon known as ‘dipping’. Any deviation from this pattern, which can only be identified using ambulatory blood pressure monitoring (ABPM), has been associated with increased cardiovascular disease (CVD) risk. This review will consider the evidence linking this polymorphism and novel gene-nutrient interaction with hypertension and the potential mechanisms that might be involved. The role of ABPM in B-vitamin research and in nutrition research generally will also be reviewed. Full article
(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism) Printed Edition available
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