Erythrocyte Glutathione Reductase Activation Coefficient Research Articles

Risk factors for anaemia among women and their young children hospitalised with suspected thiamine deficiency in northern Lao PDR.

Anaemia among women and young children remains a major public health concern. This secondary study describes the anaemia prevalence among young hospitalised children and their mothers in northern Lao People's Democratic Republic and explores possible nutritional causes and risk factors for anaemia. Hospitalised children (ages 21 days to <18 months) with clinical symptoms suggestive of thiamine deficiency disorders were eligible along with their mothers. Venous blood was collected for determination of haemoglobin, ferritin, soluble transferrin receptor (sTfR), retinol-binding protein (RBP), erythrocyte glutathione reductase activation coefficient (EGRac), thiamine diphosphate (ThDP) and acute phase proteins. Risk factors for anaemia were modelled using minimally adjusted logistic regression controlling for age. Haemoglobin results were available for 436 women (mean ± SD age 24.7 ± 6.4 years; 1.6% pregnant) and 427 children (4.3 ± 3.5 months; 60.3% male). Anaemia prevalence (Hb < 120 g/L for nonpregnant women and <110 g/L for pregnant women and children) was 30.7% among women and 55.2% among children. In bivariate analyses, biomarkers significantly associated with anaemia in women were ferritin, sTfR, RBP, EGRacand ThDP. Other risk factors for women were lower BMI, mid-upper arm circumference < 23.5 cm, lower education, lower socioeconomic index, food insecurity, Hmong ethnicity, not/rarely having attended antenatal care, not having taken antenatal iron-containing supplements and not meeting minimum dietary diversity. Risk factors for anaemia among children were older age, male sex, stunting, sTfR, ThDPand alpha-1-acid-glycoprotein. Anaemia was common among women and their hospitalised children and was associated with micronutrient deficiencies and socioeconomic,dietary and health care-seeking risk factors, suggesting that multiple strategies are required to prevent anaemia among women and children.

Vitamin B-6 and riboflavin, their metabolic interaction, and relationship with MTHFR genotype in adults aged 18–102 years

The generation of the active form of vitamin B-6, pyridoxal 5'-phosphate (PLP), in tissues is dependent upon riboflavin as flavin mononucleotide, but whether this interaction is important for maintaining vitamin B-6 status is unclear. To investigate vitamin B-6 and riboflavin status, their metabolic interaction, and relationship with methylenetetrahydrofolate reductase (MTHFR) genotype in adulthood. Data from 5612 adults aged 18-102 y were drawn from the Irish National Adult Nutrition Survey (NANS; population-based sample) and the Trinity-Ulster Department of Agriculture (TUDA) and Genovit cohorts (volunteer samples). Plasma PLP and erythrocyte glutathione reductase activation coefficient (EGRac), as a functional indicator of riboflavin, were determined. Older (≥65 y) compared with younger (<65 y) adults had significantly lower PLP concentrations (P<0.001). A stepwise decrease in plasma PLP was observed across riboflavin categories, from optimal (EGRac ≤1.26), to suboptimal (EGRac: 1.27-1.39), to deficient (EGRac ≥1.40) status, an effect most pronounced in older adults (mean±SEM: 76.4±0.9 vs 65.0±1.1 vs 55.4±1.2nmol/L; P<0.001). In individuals with the variant MTHFR 677TT genotype combined with riboflavin deficiency, compared with non-TT (CC/CT) genotype participants with sufficient riboflavin, we observed PLP concentrations of 52.1±2.9 compared with 76.8±0.7nmol/L (P<0.001). In participants with available dietary data (i.e., NANS cohort, n = 936), PLP was associated with vitamin B-6 intake (nonstandardized regression coefficient β: 2.49; 95% CI 1.75, 3.24; P<0.001), supplement use (β: 81.72; 95% CI: 66.01, 97.43; P<0.001), fortified food (β: 12.49; 95% CI: 2.08, 22.91; P=0.019), and EGRac (β: -65.81; 95% CI: -99.08, -32.54; P<0.001), along with BMI (β: -1.81; 95% CI: -3.31, -0.30; P=0.019). These results are consistent with the known metabolic dependency of PLP on flavin mononucleotide (FMN) and suggest that riboflavin may be the limiting nutrient for maintaining vitamin B-6 status, particularly in individuals with the MTHFR 677TT genotype. Randomized trials are necessary to investigate the PLP response to riboflavin intervention within the dietary range. The TUDA study and the NANS are registered at www.ClinicalTrials.gov as NCT02664584 (27 January 2016) and NCT03374748 (15 December 2017), respectively.Clinical Trial Registry details: Trinity-Ulster-Department of Agriculture (TUDA) study, ClinicalTrials.gov no. NCT02664584 (January 27th 2016); National Adult Nutrition Survey (NANS), ClinicalTrials.gov no. NCT03374748 (December 15th 2017).

Impact of the MTHFR C677T polymorphism on blood pressure and related central haemodynamic parameters in healthy adults.

BackgroundThe C677T polymorphism in the gene‐encoding methylenetetrahydrofolate reductase (MTHFR) is associated with an increased risk of hypertension and cardiovascular disease. Riboflavin, the MTHFR cofactor, is an important modulator of blood pressure (BP) in adults homozygous for this polymorphism (TT genotype). The effect of this genetic variant on BP and related central haemodynamic parameters in healthy adults has not been previously investigated and was examined in this study.MethodsBrachial BP, central BP and pulse wave velocity (PWV, SphygmoCor XCEL) were measured in adults aged 18–65 years prescreened for MTHFR genotype. Riboflavin status was assessed using the erythrocyte glutathione reductase activation coefficient assay.ResultsTwo hundred and forty‐two adults with the MTHFR 677TT genotype and age‐matched non‐TT (CC/CT) genotype controls were identified from a total cohort of 2546 adults prescreened for MTHFR genotype. The TT genotype was found to be an independent determinant of hypertension (p = 0.010), along with low‐riboflavin status (p = 0.002). Brachial systolic and diastolic BP were higher in TT versus non‐TT adults by 5.5 ± 1.2 and 2.4 ± 0.9 mmHg, respectively (both p < 0.001). A stronger phenotype was observed in women, with an almost 10 mmHg difference in mean systolic BP in TT versus non‐TT genotype groups: 134.9 (95% confidence interval [CI] 132.1–137.6) versus 125.2 (95% CI 122.3–128.0) mmHg; p < 0.001. In addition, PWV was faster in women with the TT genotype (p = 0.043).ConclusionThis study provides the first evidence that brachial and central BP are significantly higher in adults with the variant MTHFR 677TT genotype and that the BP phenotype is more pronounced in women.

No Association Between Riboflavin and Choline Status in a Sample of Canadian and Malaysian Women of Reproductive Age

ObjectivesRiboflavin and choline are essential nutrients that are metabolically inter-related and play major roles in one-carbon metabolism. Betaine can donate a methyl group to homocysteine, forming dimethylglycine (DMG) and methionine in the liver and kidney. Betaine is synthesized from choline in two irreversible reactions, the first of which is catalyzed by flavin adenine dinucleotide (FAD), a cofactor formed from riboflavin. In animal models, riboflavin status has been shown to influence choline and its metabolites betaine and DMG but there are no human studies. Here we examine whether riboflavin status modifies plasma choline, betaine, and DMG concentrations in healthy women (19–45 y).MethodsFasting blood was collected from 206 Canadian and 210 Malaysian women between 2015 and 2016. Riboflavin status was assessed using a functional biomarker, erythrocyte glutathione reductase activity coefficient (EGRac). Plasma choline, betaine, and DMG were determined by LCLC MS/MS. Plasma folate and vitamin B12 were determined using the microbiological method and an immune assay, respectively. General linear models were used to assess the independent relationship between EGRac and each of the choline metabolites with adjustment for potential confounders.Results71% of Malaysian women had EGRac ≥1.40 compared to 40% of Canadian women. Betaine, DMG, and vitamin B12 concentrations were significantly higher among Malaysian women compared to Canadian women (40.6 vs. 37.0 mmol/L, 2.7 vs. 2.4 mmol/L and 360 vs. 307 pmol/L, respectively). There were no significant associations between EGRac or riboflavin deficiency (defined as EGRac ≥1.40) and choline or its’ metabolites after adjustments for age, ethnicity, body mass index, plasma folate, and vitamin B12. In the adjusted models, plasma choline was positively associated with vitamin B12 concentrations (B = 0.002, 95% CI: 0.000, 0.003) and plasma betaine was positively associated with plasma folate (B = 0.18, 95%CI: 0.07, 0.29) and vitamin B12 (B = 0.011, 95%CI: 0.002, 0.020).ConclusionsOverall, riboflavin status was not associated with choline and its metabolites in Canadian and Malaysian women.Funding SourcesDairy Farmers of Canada, Saudi Arabian Cultural Bureau in Canada, and BC Children's Hospital Research Institute.

Daily supplementation of a multiple micronutrient powder improves folate but not thiamine, riboflavin, or vitamin B12 status among young Laotian children: a randomized controlled trial

PurposeTo assess the effects of intervention with a daily multiple micronutrient powder (MNP) on thiamine, riboflavin, folate, and B12 status among young Laotian children.MethodsChildren (n = 1704) aged 6–23 mo, participating in a double-blind placebo-controlled randomized trial were individually randomized to receive daily either MNP (containing 0.5 mg of thiamine, 0.5 mg riboflavin, 150 μg folic acid, and 0.9 μg vitamin B12 along with 11 other micronutrients) or placebo and followed for ~ 36 weeks. In a randomly selected sub-sample of 260 children, erythrocyte thiamine diphosphate (eThDP), plasma folate and B12 concentrations, and erythrocyte glutathione reductase activation coefficient (EGRac; riboflavin biomarker) were assessed at baseline and endline.ResultsThere was no treatment effect on endline eThDP concentrations (110.6 ± 8.9 nmol/L in MNP vs. 109.4 ± 8.9 nmol/L in placebo group; p = 0.924), EGRac (1.46 ± 0.3 vs. 1.49 ± 0.3; p = 0.184) and B12 concentrations (523.3 ± 24.6 pmol/L vs. 515.9 ± 24.8 pmol/L; p = 0.678). Likewise, the prevalence of thiamine, riboflavin, and B12 deficiencies did not differ significantly between the two groups. However, endline folate concentration was significantly higher in the MNP compared to the placebo group (28.2 ± 0.8 nmol/L vs 19.9 ± 0.8 nmol/L, respectively; p < 0.001), and correspondingly, the prevalence of folate deficiency was significantly lower in the MNP group (1.6% vs 17.4%; p = 0.015).ConclusionsCompared to a placebo, daily MNP for 9 months increased only folate but not thiamine, riboflavin, or B12 status in young Laotian children.Trial registrationThe trial was registered at www.clinicaltrials.gov (NCT02428647) on April 29 2015.

Effectiveness of a fortified drink in improving B vitamin biomarkers in older adults: a controlled intervention trial

BackgroundOlder adults are reported to have sub-optimal B vitamin status; targeted food-based solutions may help to address this. The objectives of the OptiAge food intervention study were to develop and investigate the effectiveness of a B vitamin-fortified drink in improving B vitamin biomarkers in older Irish adults with a primary outcome of change in the B vitamin biomarker status.MethodsA double-blinded randomised controlled trial was performed in parallel at University College Dublin and Ulster University. Participants aged > 50 years were recruited following screening for exclusion criteria (i.e. taking medications known to interfere with B vitamin metabolism, supplements containing B vitamins, consuming > 4 portions of B vitamin-fortified foods per week or diagnosed with gastrointestinal, liver or pulmonary disease). Recruited participants meeting the inclusion criteria were randomised (by sex and study centre) to receive daily for 16 weeks either B vitamin-fortified or placebo drinks as developed by Smartfish, Norway. Each B vitamin-fortified drink (200 ml) contained 200 µg folic acid, 10 µg vitamin B12, 10 mg vitamin B6 and 5 mg riboflavin, while the placebo was an identical, isocaloric formulation without added B vitamins. Fasting blood samples were collected pre- and post-intervention which were used to measure the primary outcome of change in B vitamin biomarker levels.ResultsA total of 95 participants were randomised, of which 81 commenced the trial. Of these, 70 completed (37 in the active and 33 in the placebo groups). Intention to treat (ITT) analysis of the B vitamins demonstrated a significant improvement in all B vitamin biomarkers in the active compared to placebo groups: p < 0.01 for each of serum folate, serum vitamin B12 and plasma pyridoxal 5′-phosphate (vitamin B6) and the functional riboflavin biomarker, erythrocyte glutathione reductase activation coefficient (EGRac). Correspondingly, a significant lowering of serum homocysteine from 11.9 (10.3–15.1) µmol/L to 10.6 (9.4–13.0) µmol/L was observed in response to the active treatment (P < 0.001). Similar results were seen in a per-protocol analysis.ConclusionsThe results demonstrate that a B vitamin-fortified drink was effective in optimising B vitamin status, making this a useful intervention option to improve B vitamin status in older adults.Trial registration ISRCTN, ISRCTN61709781—Retrospectively registered, https://www.isrctn.com/ISRCTN61709781

Dietary Riboflavin Intake and Riboflavin Status in Young Adult Women Living in Metro Vancouver, Canada.

ABSTRACTBackgroundNutrition surveys suggest that <10% of Canadian adults have inadequate riboflavin intakes. However, biochemical riboflavin deficiency [erythrocyte glutathione reductase activity coefficient (EGRac) ≥1.40] has been reported in 41% of young adult women living in Metro Vancouver. Canadian Chinese ethnicity comprise >25% of Vancouver's population and are postulated to have poorer riboflavin status than those of European ethnicity because they could be less likely to consume dairy products and fortified wheat.ObjectivesThe objectives of this study were to determine dietary riboflavin intake and food sources, and to assess the association between riboflavin intake and status in young women of European (n = 107) and Chinese (n = 91) ethnicities living in Metro Vancouver, Canada.MethodsThis was a cross-sectional study conducted in women (aged 19–45 y). Women were healthy, not pregnant or breastfeeding, of European or Chinese ethnicities, and not taking riboflavin-containing supplements for the past 4 mo. Dietary riboflavin intake was assessed using the past-year Diet History Questionnaire II, and riboflavin status (EGRac) was measured in fasting venous blood samples.ResultsOnly 7% of participants had dietary riboflavin intakes below the Estimated Average Requirement (0.9 mg/d), but 40% of women had biochemical riboflavin deficiency (EGRac ≥1.40). Although more Canadian women of European ethnicity than Chinese ethnicity had biochemical riboflavin deficiency (46% and 34%; P < 0.001), median dietary riboflavin intake did not differ (1.73 and 1.82 mg/d; P = 0.587). Dairy products and vegetables contributed the most to riboflavin intake. Energy-adjusted dietary riboflavin intake was inversely associated with EGRac (B = −0.04, 95% CI: −0.07, −0.01). However, after further adjustment the relation was not significant.ConclusionsOverall, women of reproductive age living in Metro Vancouver, Canada, had a low prevalence of inadequate dietary riboflavin intake despite the high prevalence of apparent biochemical riboflavin deficiency.

A 2-Year Randomized Controlled Trial With Low-Dose B-Vitamin Supplementation Shows Benefits on Bone Mineral Density in Adults With Lower B12 Status.

Folate, vitamins B12, B6, and riboflavin are required for one-carbon metabolism and may affect bone health, but no previous randomized trial has investigated all four nutrients in this context. We investigated the effect of low-dose B-vitamins for 2 years on bone mineral density (BMD) in a dual-centered, 2-year randomized controlled trial (RCT) in adults aged ≥50 years. Eligible participants not consuming B-vitamin supplements or fortified foods >4times weekly were randomized to receive daily either combined folic acid (200 μg), vitamin B12 (10 μg), vitamin B6 (10 mg), and riboflavin (5mg), or "active" placebo, whereby both the intervention and placebo groups received vitamin D (10 μg). BMD was assessed before and after intervention using dual-energy X-ray absorptiometry (DXA) scanning of the total hip, femoral neck, and lumbar spine (L1 to L4). Of 205 eligible participants randomized, 167 completed the trial in full. B-vitamin intervention resulted in increases in serum folate (p < 0.001), serum B12 (p < 0.001), and plasma pyridoxal-5-phosphate (p < 0.001) and decreases in functional biomarkers of B-vitamin status, erythrocyte glutathione reductase activation coefficient (p < 0.001), serum methylmalonic acid (MMA; p < 0.001), and serum total homocysteine (p < 0.001). B-vitamin intervention had no overall effect on BMD, which declined in both treatment groups by approximately 1% (ranging from -0.7% to -1.4%). However, in participants with lower baseline B12 status (serum B12 <246 pmol/L or MMA ≥0.22 μmol/L), B-vitamin intervention reduced the 2-year BMD decline versus placebo: adjusted mean (95% confidence interval [CI]) change of -0.003 (-0.008, 0.002) versus -0.015 (-0.021, -0.010)g/cm2 at the total hip and -0.004 (-0.010, 0.001) versus -0.013 (-0.018, -0.007)g/cm2 at the femoral neck. In conclusion, the findings indicate that although low-dose B-vitamin intervention for 2 years had no overall effect on BMD, improving B-vitamin status appears to have specific benefits for bone health in adults with lower B12 status. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Riboflavin Is an Important Determinant of Vitamin B-6 Status in Healthy Adults

Riboflavin is required to generate the active form of vitamin B-6 (pyridoxal 5'-phosphate; PLP) in tissues, but the relevance of this metabolic interaction for nutritional status of vitamin B-6 is unclear because riboflavin biomarkers are rarely measured in human studies. The purpose of this study was to identify the determinants of biomarkers of vitamin B-6 and riboflavin status and to examine the relationship between these nutrients in healthy adults. Multiple linear regression was performed on observational data in 407 healthy adults aged 18-92 y who did not use B-vitamin supplements. Vitamin B-6 status was assessed by plasma PLP concentrations and erythrocyte glutathione reductase activation coefficient (EGRac) was used as a functional indicator of riboflavin status. Dietary intakes of vitamin B-6 and riboflavin were below the average requirements in 10% and 29% of participants, respectively. Suboptimal status of vitamin B-6 (PLP ≤30.0nmol/L) was more prevalent in adults aged ≥60 y than in younger participants (i.e., 14% compared with 5%), whereas a high proportion (i.e., overall 37%) of both age groups had deficient riboflavin status (EGRac ≥1.40). In multiple regression analysis, EGRac (P=0.019) was a significant determinant of plasma PLP, along with dietary vitamin B-6 intake (P=0.003), age (P<0.001), BMI (kg/m2) (P=0.031), and methylenetetrahydrofolate reductase gene (MTHFR) genotype (P<0.001).Significant determinants of EGRac were dietary riboflavin intake (P<0.001), age (P<0.001)and MTHFR genotype (P=0.020). Plasma PLP showed a stepwise decrease across riboflavin status categories from optimal (EGRac ≤1.26) to low (EGRac 1.27-1.39) to deficient status (P=0.001), independent of dietary vitamin B-6 intake. The findings are consistent with the known metabolic dependency of vitamin B-6 on riboflavin status and indicate that riboflavin may be the limiting nutrient, particularly in older people, for maintaining adequate vitamin B-6 status.

Nutritional Status of Obese Taiwanese Before Bariatric-Metabolic Surgery and Their Serum 25-Hydroxyvitamin D Concentrations for Maximal Suppression of Parathyroid Hormone.

This is the first report from Taiwan using laboratory tests to assess nutritional status of patients with obesity before bariatric-metabolic surgery. Moreover, the 25(OH)D threshold for maximal suppression of parathyroid hormone (PTH) was evaluated to offer a reference value for preoperative nutritional care. Inclusion criteria were Taiwanese, 18-65years old, and with BMI ≥ 27.5kg/m2 awaiting bariatric-metabolic surgery. Anthropometric data and blood samples were collected before surgery. Serum concentrations of protein; vitamins B1, B12, folate, A, D, and E; calcium; iron; zinc; copper; selenium; PTH; and erythrocyte glutathione reductase activity coefficient (vitamin B2 status) were measured. For 52 participants with a mean BMI 37.6 ± 6.4kg/m2, vitamin D deficiency (25(OH)D < 20ng/mL) and insufficiency (20 < 25(OH)D < 30ng/mL) were at 73 and 22% prevalence, respectively. Secondary hyperparathyroidism (PTH≧65pg/mL) was 24% and hypocalcemia was 50% (ionized Ca < 4.5mg/dL). Deficiency of other nutrients was sporadic (< 10%) or nil. When participants were stratified according to 25(OH)D concentrations (< 10, 10-15, 15-20, and ≥ 20ng/mL), PTH increased at 25(OH)D < 10ng/mL (β = 48.34, p = 0.001) after adjusting for age, gender, and BMI. For patients with obesity before bariatric-metabolic surgery, vitamin D/calcium deficiency was the only nutritional issue that needs to be addressed in Taiwan. However, a lower cutoff point of 25(OH)D, i.e., 10ng/mL, for vitamin D deficiency may be considered for patients before surgery. ClinicalTrials.gov Identifier: NCT03915158.

The Homozygous Hemoglobin EE Variant Is Associated with Poorer Riboflavin Status in Cambodian Women of Reproductive Age

Riboflavin is required for erythropoiesis, which is increased in people with hemoglobinopathies due to increased hemolysis and erythrocyte turnover. Dietary intake and status of riboflavin is poor in Cambodia, where hemoglobinopathies are common. We assessed the association between genetic hemoglobin disorders and riboflavin status in women of reproductive age in Cambodia. Venous blood samples from 515 Cambodian women of reproductive age, 18-45 y, were analyzed for biomarker status of riboflavin [erythrocyte glutathione reductase activation coefficient (EGRac)], genetic hemoglobin (Hb) disorders, and hematological indices. Linear regression analysis was used to estimate the association between EGRac with Hb, ferritin, and Hb genotypes. EGRac was log transformed in the analyses, and the regression coefficients represent the geometric mean differences. Genetic Hb disorders were present in 57% of the population, with the homozygous hemoglobin E variant (Hb EE) occurring in ∼10% of women (n=53). Deficient (EGRac ≥1.40) or marginal riboflavin status (EGRac ≥1.30 and <1.40) was observed in 92% (n=475) of women. The variant Hb EE genotype was associated with 18% (95% CI: 9%, 28%) higher geometric mean EGRac values than the normal Hb AA genotype (P<0.001). Although riboflavin biomarker deficiency or marginal status is widely prevalent in Cambodian women, lower riboflavin status was observed more frequently in women with the Hb EE genotype than in women with normal Hb AA. The relation between genetic Hb disorders and riboflavin warrants further investigation. This trial was registered at clinicaltrials.gov as NCT01593423 and NCT02481375.

Homocysteine, the methylenetetrahydrofolate reductase 677C>T polymorphism and hypertension: effect modifiers by lifestyle factors and population subgroups.

Evidence linking fasting plasma total homocysteine (tHcy) and methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype with hypertension is inconsistent. Differences in B vitamin status, other lifestyle factors or their consideration in analyses might explain this. We investigated these associations in the absence of mandatory fortification with folic acid and B vitamin supplement use. A cross-sectional study was conducted in 788 adults, aged 18-75 years, randomly selected from three Catalonian town population registers. Fasting plasma folate, cobalamin, tHcy, erythrocyte folate, erythrocyte glutathione reductase activation coefficient (EGRAC, functional riboflavin status indicator; increasing EGRAC indicates worsening riboflavin status), MTHFR 677C>T and solute carrier family 1 (SLC19A1) 80 G>A genotypes were determined. Medical history and lifestyle habits were recorded. Principal tHcy determinants differed between women (age, plasma folate, plasma cobalamin, cigarettes/d) and men (MTHFR 677TT genotype, plasma folate, plasma cobalamin and CT genotype). The MTHFR 677C>T polymorphism-tHcy association (β standardised regression coefficients) was stronger in male smokers (0·52, P < 0·001) compared with non-smokers (0·21, P = 0·001) and weaker in participants aged >50 years (0·19, P = 0·007) compared with ≤50 years (0·31, P < 0·001). Hypertension was more probable in the third tHcy tertile compared with other tertiles (OR 1·9; 95 % CI 1·2, 3·0), and in participants aged ≤50 years, for the MTHFR 677TT genotype compared with the CC genotype (OR 4·1; 95 % CI 1·0, 16·9). EGRAC was associated with increased probability of hypertension in participants aged >50 years (OR 6·2; 95 % CI 1·0, 38·7). In conclusion, moderately elevated tHcy and the MTHFR 677CT genotype were associated with hypertension. The MTHFR 677C>T genotype-hypertension association was confined to adults aged ≤50 years.

Plasma riboflavin concentration as novel indicator for vitamin-B2 status assessment: suggested cutoffs and its association with vitamin-B6 status in women

AbstractRiboflavin (vitamin B2), as the coenzymes flavin mononucleotide (FMN) and flavin dinucleotide (FAD), is essential for oxidation-reduction reactions and energy metabolism. Riboflavin also interacts with vitamin B12, B6 and folate in one-carbon metabolism, and is required for the conversion of dietary vitamin B6 forms to the coenzyme pyridoxal 5’-phosphate (PLP). Biochemical riboflavin status is rarely measured given the lack of convenient and accessible biomarkers. The current gold-standard marker is erythrocyte glutathione reductase activation coefficient (EGRac) that involves laborious sample processing. High prevalence of riboflavin deficiency (EGRac ≥ 1.4) and suboptimal status (EGRac of 1.3–1.39) have been reported in the UK and Ireland; yet the functional significance is unclear. Plasma riboflavin concentration may serve as an alternative indicator; its association with related metabolites has not yet been investigated. Secondary analysis was conducted to determine the change-point of plasma riboflavin with EGRac, to derive a reference interval for plasma riboflavin, and to determine the association of riboflavin status with plasma PLP, using data of 223 older adult women from a cross-sectional study. Fasting blood samples and sociodemographic, anthropometric and dietary data were available for a convenience sample of 223 older adult women. Plasma PLP and related metabolites were quantified using isotope-dilution liquid chromatography-tandem mass spectrometry. The change-point (95% CI) between EGRac and plasma riboflavin occurred at plasma riboflavin concentration of 26.5 (20.5; 32.5) nmol/L (with EGRac of 1.25). The median (IQR) plasma riboflavin concentration was 15.7 (11.2, 23.8); and the upper and lower limits (90%CI) of the central 95% reference interval were 6.70 (6.33, 7.79) and 64.2 (55.0, 74.6) nmol/L, respectively. Plasma PLP (geometric mean (95%CI)) was significantly lower in women with riboflavin deficiency, 54.0 (46.8, 62.2) nmol/L (n = 64), and suboptimal riboflavin status, 56.1 (48.9, 64.3) nmol/L (n = 48), compared to those with riboflavin adequacy, 135 (112, 161) nmol/L (n = 110). Plasma PLP was positively associated with plasma riboflavin concentration after adjustment for total B6 intake, age, ethnicity, BMI, education, household income and C-reactive protein concentration [β (95% CI) = 1.92 (.670, 3.17) nmol/L; p = 0.003]; a significant interaction between plasma riboflavin and total dietary B6 intake was observed (p = 0.024). In conclusion, we are presenting for the first time a reference range for plasma riboflavin concentration and its change-point with EGRac in healthy women. Vitamin B6 status is strongly associated with riboflavin status; more research is needed to elucidate this relationship in a larger sample and ideally intervention study.

Investigation of Blood Pressure during the First Trimester of Pregnancy in relation to the MTHFR C677T Polymorphism

AbstractThe common C677T polymorphism in the MTHFR gene encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase is implicated in hypertension and hypertension in pregnancy. Hypertension affects up to 15% of all pregnancies and has been identified as a leading cause of maternal and neonatal morbidity and mortality worldwide. We previously reported higher systolic and diastolic blood pressure (BP) in non-pregnant women with the variant MTHFR 677TT genotype compared to CT/CC genotypes. In addition, randomised controlled trials (RCTs) in non-pregnant hypertensive adults from our Centre demonstrated that supplemental riboflavin (co-factor for MTHFR) lowers BP specifically in those with the TT genotype. However, the role of this common folate polymorphism and its interaction with riboflavin during pregnancy remains unclear. The aim of this study was to investigate the impact of MTHFR genotype and riboflavin status on BP in pregnancy. Data were generated from the ongoing Optimal Nutrition for the Prevention of Hypertension (OptiPREG) project. Pregnant women were recruited at the end of the first trimester from antenatal clinics in Northern Ireland and in the Republic of Ireland. Participants were screened for MTHFR genotype and BP was measured according to current clinical guidelines. Biomarker status of riboflavin was determined using the erythrocyte glutathione reductase activation coefficient (EGRac), a functional assay with higher EGRac values representing a lower status. Overall, 117 (11.6%) participants were identified with the variant MTHFR 677TT genotype. Both systolic and diastolic BP decreased from 8th to 16th gestational week (GW), however, this typical BP pattern was not observed in the TT genotype group. After adjusting for maternal age, GW and body mass index, women with the TT genotype at 12th GW had higher mean systolic (P 0.035) and diastolic (P 0.034) BP. When the results at the 12th GW were stratified by riboflavin status, the BP phenotype owing to this polymorphism was evident only among women with lower status (i.e. EGRac &gt; 1.30), with mean (SEM) systolic BP of 120.4 (3.1) mmHg compared to 112.6 (2.5) mmHg in those with higher status (EGRac ≤ 1.30) within the TT genotype group; in contrast, low versus high riboflavin status had no impact on BP in CT/CC genotype groups. These results suggest that MTHFR genotype influences BP during pregnancy and that riboflavin can exert an important modulating effect on BP in women with TT genotype. An RCT is required to fully investigate the role of MTHFR genotype and its interactive effect with riboflavin in BP during pregnancy.

Relationship of obesity with B vitamin status: analysis of NDNS data from UK women of reproductive age

AbstractPre-pregnancy obesity is associated with a 2-fold increased risk of Neural Tube Defects (NTD), an effect not explained by lower dietary folate intake, or non-use of folic acid supplements (as recommended globally to women before and in early pregnancy for NTD prevention). While the exact mechanism linking NTD and obesity is poorly understood, it is possible that a compromised status or metabolism of folate and/or of the closely related micronutrients (vitamin B12, B6 and riboflavin) may be involved. To date however, this hypothesis has not been adequately explored. This study therefore aimed to investigate the relationship of obesity with folate and related B vitamin biomarkers in a representative cohort of non-pregnant UK women of reproductive age. Data were accessed from the most recent UK National Diet and Nutrition Survey (NDNS; Years 7–8; 2015–16), a rolling cross-sectional survey designed to gather information from a representative sample of the UK population on nutrient intakes, food consumption and nutritional status. Data for women aged 16–45 years (non B vitamin supplement users; n 364), were extracted on: anthropometry (height, weight, body mass index [BMI] and waist circumference [WC]), dietary intakes of B vitamins and biomarkers for serum and red blood cell folate, vitamin B12 (total serum B12 and holotranscobalamin), vitamin B6 (plasma pyridoxal-5-phosphate [PLP]) and riboflavin (erythrocyte glutathione reductase activation coefficient EGRAac]). Prevalence of overweight and obesity (i.e. BMI: 25–30kg/m2 and &gt; 30kg/m2) was 28% and 22% respectively, whilst abdominal obesity (i.e. WC &gt; 88cm) was present in 31% of the women. Total serum B12 (r -0.215, P 0.012) and PLP (r -0.270, P 0.002) were negatively correlated with WC, with similar, albeit weaker, correlations found for BMI. Correspondingly, women with abdominal obesity compared to those without, had a lower status of total serum B12 (Median values of: 212 v 249 v pmol/L; P 0.049), B6 (31.5 v 40.5 nmol/L; P 0.002) and EGRac (1.43 v 1.36; P 0.031). No differences in B vitamin dietary intake were observed by categories of abdominal obesity. Abdominal obesity may be a risk factor for low status of both vitamins B12 and B6, independently of dietary intake. Further investigation to elucidate the potential underlying mechanism is warranted. These findings also highlight the importance of taking abdominal obesity into account, in addition to BMI, when examining possible adverse impacts of obesity on micronutrient status.

The association between the whole blood riboflavin level and the occurrence, development and prognosis of esophageal squamous cell carcinoma

Objective: To investigate the association between the whole blood riboflavin level and the occurrence, development and prognosis of esophageal squamous cell carcinoma (ESCC) in China. Methods: From March 2014 to September 2018, ESCC patients from three hospitals (the Affiliated Hospital of Medical College of Shantou University, Shantou Central Hospital in Southern Chaoshan area and First Affiliated Hospital of Zhengzhou University in Northern Taihang Mountain) were selected as a case group; non-esophageal patients who had a physical examination were selected as a control group. The case and control group were paired by age (±5 years) and a 1:1 ration. A total of 1 528 subjects were enrolled including 764 patients in the case group and 764 patients in the control group. About 3-5 ml venous blood samples were collected, and the erythrocyte glutathione reductase activity coefficient (GRAC) was measured to assess the whole blood riboflavin level. A multivariate conditional logistic regression model was used to analyze the association between the GRAC and the risk of ESCC. The association between the GRAC and the prognosis of ESCC was analyzed by using Cox proportional risk regression model based on 288 patients with complete survival data. They were divided into two groups, the high GRAC group (GRAC≥7.87) group and the low GRAC group (GRAC<7.87) according to the strongest correlation between the total survival time, survival outcome and GRAC (GRAC=7.87). Results: Among the 1 528 patients, 958 patients were from Southern Chaoshan area, including 479 patients in the case group with an average age about (59.90±9.34) years and 479 patients in the control group with an average age about (59.55±8.77) years. Other 570 patients were from Northern Taihang Mountain area, including 285 patients in the case group with an average age (58.39±5.19) years and 285 patients in the control group with an average age about (58.74±4.57) years. The multivariate conditional logistic regression showed that the OR (95%CI) of the GRAC and the risk of ESCC was 1.009 (0.998-1.019). The Cox proportional hazard regression model analysis showed that the HR (95%CI) of the high GRAC group was 1.712 (1.034-2.824) compared with the low GRAC group in the 50-70 years group. Conclusion: The whole blood riboflavin level might not be associated with the occurrence of ESCC. The high whole blood riboflavin level would be more beneficial to the prognosis of ESCC patients aged 50-70 years.

Suboptimal Biochemical Riboflavin Status Is Associated with Lower Hemoglobin and Higher Rates of Anemia in a Sample of Canadian and Malaysian Women of Reproductive Age

Riboflavin is required for several redox reactions. Clinical riboflavin deficiency occurs mainly in low-income countries, where it is associated with anemia. The functional significance of suboptimal riboflavin status in different populations and its role in anemia is not well understood. We assessed the biomarker status of riboflavin and its association with hemoglobin concentration and anemia in women living in Vancouver, Canada, and Kuala Lumpur, Malaysia. Healthy nonpregnant, nonbreastfeeding women (19-45 y) were recruited from Canada ( n=206) and Malaysia (n=210) via convenience sampling. Fasting blood was collected to assess riboflavin status [erythrocyte glutathione reductase activity coefficient (EGRac)], hematological indicators, soluble transferrin receptor (sTfR), ferritin, vitamin A, folate, and vitamin B-12 concentrations. Linear and logistic regression models were used to assess the association of riboflavin status with hemoglobin concentration and anemia. EGRac (mean±SD) values were higher, indicating poorer riboflavin status, in Malaysian compared with Canadian women (1.49±0.17 compared with 1.38±0.11). Likewise, riboflavin biomarker deficiency (EGRac≥1.40) was significantly more prevalent among Malaysians than Canadians (71% compared with 40%). More Malaysian than Canadian women were anemic (hemoglobin <120 g/L; 18% compared with 7%). With use of linear regression (pooled sample; n=416), EGRac values were negatively associated with hemoglobin concentration (r=-0.18; P<0.001). This relation remained significant (P=0.029) after adjusting for age, parity, ethnicity, vitamin B-12, folate, sTfR, ferritin, and vitamin A. Women with riboflavin deficiency (EGRac≥1.40) were twice as likely to present with anemia (adjusted OR:2.38; 95% CI: 1.08, 5.27) compared with women with EGRac<1.40. Biochemical riboflavin deficiency was observed in Canadian and Malaysian women, with higher rates of deficiency among Malaysian women. Deficient biomarker status of riboflavin was a weak but significant predictor of hemoglobin and anemia, suggesting that the correction of riboflavin deficiency may potentially play a small protective role in anemia, but this requires further investigation.

P3566Ambulatory blood pressure response to riboflavin supplementation in adults with the C677T polymorphism in the folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR)

Abstract Background Epidemiological evidence suggests that the C677T polymorphism in the folate metabolising enzyme MTHFR is associated with a 24–87% increased risk of hypertension. Riboflavin (a cofactor for MTHFR) can modify this phenotype, as demonstrated in a series of RCTs, at this centre. ABPM measures BP over 24hrs and provides a more reliable assessment of an individual's BP compared to clinic BP. Aim To investigate the effect of riboflavin supplementation on BP (by ABPM) in adults with the MTHFR 677TT genotype. Methods Adults (n=3462) were recruited and screened for the MTHFRTT genotype and those eligible (n=81), were stratified by baseline SBP and randomised to receive riboflavin (10mg/day/16weeks) or placebo. Riboflavin status was measured using the erythrocyte glutathione reductase activation coefficient (EGRac) assay and clinic and ABPM were measured in accordance with clinical guidelines. Results Mean 24hr, daytime and night-time SBP was 6mmHg higher (p&lt;0.05) in adults with the TT v CC genotype. BP response to riboflavin was strongly dependent on baseline BP. In participants with a baseline SBP≥125mmHg, riboflavin resulted in a significant BP lowering in daytime SBP (Table). Day-time SBP response to riboflavin Treatment Placebo P-value Age 48.6 (11.3) 47.8 (12.0) 0.823 Male n (%) 17 (73.9) 12 (46.2) 0.093 BMI 28.8 (3.8) 27.2 (3.1) 0.131 Riboflavin status (EGRac)† Pre 1.33 (1.28–1.38) 1.29 (1.24–1.34) Post 1.20 (1.14–1.25) 1.31 (1.25–1.36) &lt;0.001 Change −0.12 0.02 Daytime BP (mmHg)‡ Pre 137.1 (132.7–141.3) 134.7 (130.3–139.1) Post 133.0 (128.9–138.1) 134.8 (130.6–139.1) 0.036 Change −3.8 −0.2 ANCOVA, adjusting for sex. †Higher EGRac values indicate lower riboflavin status; ‡mean of participant daytime/awake hrs personalised for each participant. Conclusion This is the first study to show, using ABPM, that riboflavin supplementation, targeted at adults with the MTHFR 677TT genotype, results in significant lowering of mean, day and night BP. Given the frequency of this genotype worldwide (approximately 10%, but as high as 30% in some populations) these findings could offer a personalised approach for BP management in at-risk sub-populations. Acknowledgement/Funding This work was supported by DSM Nutritional Products, Ltd and Wellcome Trust-Wolfston Northern Ireland Clinical Research Facility are acknowledged

B-vitamins in Relation to Depression in Older Adults Over 60 Years of Age: The Trinity Ulster Department of Agriculture (TUDA) Cohort Study

ObjectivesMental health disorders are major contributors to disease burden in older people. Deficient status of folate and the metabolically related B vitamins may be implicated in these conditions. This study aimed to investigate folate, vitamin B12, vitamin B6, and riboflavin in relation to depression and anxiety in aging and also considered the role of fortified foods as a means of optimizing B-vitamin status and potentially reducing the risk of these mental health disorders. DesignThe Trinity Ulster Department of Agriculture (TUDA) aging study was a cross-sectional cohort study. Setting and ParticipantsCommunity-dwelling adults (n = 5186; ≥60 years) recruited from 2 jurisdictions within the island of Ireland from 2008 to 2012. MeasuresDepression and anxiety were assessed using the Centre for Epidemiological Studies Depression (CES-D) and the Hospital Anxiety and Depression (HAD) scales, respectively. The following B-vitamin biomarkers were measured: red blood cell folate, serum total vitamin B12, plasma pyridoxal-5-phosphate (PLP; vitamin B6), and erythrocyte glutathione reductase activation coefficient (EGRac; riboflavin). ResultsBiomarker values in the lowest 20% of status for folate (odds ratio [OR] 1.79; 95% CI 1.23-2.61), vitamin B6 (OR 1.45, 95% CI 1.01-2.06), or riboflavin (OR 1.56, 95% CI 1.10-2.00), but not vitamin B12, were each associated with an increased risk of depression (CES-D score ≥16). Correspondingly, B vitamin–fortified foods if consumed daily were associated with a reduced risk of depression (OR 0.54, 95% CI 0.41-0.70). A deficient status of vitamin B6 (OR 1.73, 95% CI 1.07-2.81), but not other vitamins, was associated with increased anxiety. Conclusions/ImplicationsBetter B-vitamin status may have a role in impacting positively on mental health in older adults. Regular intake of fortified foods can provide a means of optimizing B-vitamin status and thus could contribute to reducing depression. If confirmed by a randomized trial, these results may have implications for nutrition and mental health policy, and thus quality of life, in older people.

Adequate vitamin B12 and riboflavin status from menus alone in residential care facilities in the Lower Mainland, British Columbia.

Older adults have potential increased risk of nutrient deficiencies because of age-related decreased dietary intake and malabsorption; it is important to ensure nutrient needs are met to avoid adverse health outcomes. B vitamins are of particular interest: vitamin B12 deficiency can cause irreversible neurodegeneration; there is mandatory folic acid fortification in Canada; and suboptimal riboflavin status has been reported among older adults in the United Kingdom. In this exploratory secondary analysis study we assessed vitamin B12 and riboflavin biochemical status (via microparticle enzyme immunoassay and erythrocyte glutathione reductase activity coefficient (EGRac), respectively), and the vitamin B12, riboflavin, and folate content of menus served to a convenience sample of older adults (≥65 years) from 5 residential care facilities within the Lower Mainland of British Columbia, Canada. Diet was assessed from customized 28-day cycle meal plans. Participants (n = 207; 53 men and 154 women) were aged 86 ± 7 years, largely of European descent (92%), and nonsmokers (95%). The menus served had a low prevalence of inadequacy for vitamin B12 and riboflavin (only 4% and 1% of menus contained less than the estimated average requirement (EAR), respectively), but 93% contained less than the EAR for folate. Mean ± SD serum total vitamin B12 concentration was 422 ± 209 pmol/L, and EGRac was 1.30 ± 0.19. The majority of older adults in residential care were provided with adequate vitamin B12 and riboflavin menu amounts, and only 5% were vitamin B12 deficient (<148 pmol/L). However, 26% were riboflavin deficient (EGRac ≥ 1.4), which may warrant further investigation.