Liadhan McAnena - Academia.edu (original) (raw)
Papers by Liadhan McAnena
Proceedings of the Nutrition Society, 2016
High salt intake (SI) is an established risk factor for several chronic diseases including hypert... more High salt intake (SI) is an established risk factor for several chronic diseases including hypertension, stroke and cardiovascular disease. Less well documented is evidence reporting salt as a potential risk factor for the development of obesity 1-3. Whether or not the relationship between salt and obesity is dependent or independent of energy intake (EI) remains unconfirmed. Consequently, this study aimed to investigate the association between SI and adiposity measures amongst a representative sample of UK adults aged 19-64 years using National Dietary and Nutritional Survey data (NDNS, 2014). Dietary intake from 4-day estimated food diaries and anthropometric measurements (body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR) and % body fat) were examined in relation to measured SI's from 24-hour urinary sodium excretion (NaEx) (n 605; 279 males; 326 females). A significant positive correlation was found between SI and all measures of body composition available, with the strongest correlation for BMI after adjusting for age, gender, smoking, alcohol, misreporting, EI, ethnic group and socioeconomic status (P < 0•001, r = •201). BMI and WC increased significantly across quartiles of sodium density (salt intake/kJ) for both males and females after controlling for misreporting of EI and age (Figure 1).
The Nutrition Handbook for Food Processors, 2002
The American Journal of Clinical Nutrition
Background The generation of the active form of vitamin B-6, pyridoxal 5′-phosphate (PLP), in tis... more Background 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. Objective To investigate vitamin B-6 and riboflavin status, their metabolic interaction, and relationship with methylenetetrahydrofolate reductase (MTHFR) genotype in adulthood. Methods 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. Results 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 ...
Journal of Bone and Mineral Research
ABSTRACTFolate, vitamins B12, B6, and riboflavin are required for one‐carbon metabolism and may a... more ABSTRACTFolate, 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 >4 times weekly were randomized to receive daily either combined folic acid (200 μg), vitamin B12 (10 μg), vitamin B6 (10 mg), and riboflavin (5 mg), 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 seru...
European Journal of Nutrition
Purpose To assess the effects of intervention with a daily multiple micronutrient powder (MNP) on... more Purpose To assess the effects of intervention with a daily multiple micronutrient powder (MNP) on thiamine, riboflavin, folate, and B12 status among young Laotian children. Methods Children (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. Results There 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 ± ...
Additional file 1: Table S1. Impact of B vitamin drinks on B vitamin biomarkers controlling for b... more Additional file 1: Table S1. Impact of B vitamin drinks on B vitamin biomarkers controlling for baseline homocysteine concentrations. Table S2. B vitamin biomarkers at baseline and end of intervention with the drinks (Per protocol analysis). Table S3. Impact of B vitamin drinks on biomarker status controlling for baseline homocysteine concentrations (per-protocol analysis).
Nutrition & Metabolism, 2021
Background Older adults are reported to have sub-optimal B vitamin status; targeted food-based so... more Background Older 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. Methods A 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-fortifie...
The Journal of Nutrition, 2020
Background Riboflavin is required to generate the active form of vitamin B-6 (pyridoxal 5′-phosph... more Background 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. Objectives 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. Methods 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. Results 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 ≤30.0 nmol/...
The American Journal of Clinical Nutrition, 2021
Background Atrophic gastritis (AG) and use of proton pump inhibitors (PPIs) result in gastric aci... more Background Atrophic gastritis (AG) and use of proton pump inhibitors (PPIs) result in gastric acid suppression that can impair the absorption of vitamin B-12 from foods. The crystalline vitamin B-12 form, found in fortified foods, does not require gastric acid for its absorption and could thus be beneficial for older adults with hypochlorhydria, but evidence is lacking. Objectives To investigate associations of AG and PPI use with vitamin B-12 status, and the potential protective role of fortified foods, in older adults. Methods Eligible participants (n = 3299) not using vitamin B-12 supplements were drawn from the Trinity-Ulster and Department of Agriculture cohort, a study of noninstitutionalized adults aged ≥60 y and recruited in 2008–2012. Vitamin B-12 status was measured using 4 biomarkers, and vitamin B-12 deficiency was defined as a combined indicator value < −0.5. A pepsinogen I:II ratio <3 was considered indicative of AG. Results AG was identified in 15% of participan...
Proceedings of the Nutrition Society, 2020
Riboflavin (vitamin B2), as the coenzymes flavin mononucleotide (FMN) and flavin dinucleotide (FA... more Riboflavin (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-p...
Proceedings of the Nutrition Society, 2020
Meta-analyses of epidemiological data report that adults who carry a common polymorphism, the MTH... more Meta-analyses of epidemiological data report that adults who carry a common polymorphism, the MTHFR 677C→T, in the gene encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) have a 40% increased risk of CVD and an 87% increased risk of hypertension. Riboflavin (vitamin B2), in its co-enzymatic form flavin adenine nucleotide (FAD), is required as a co-factor by MTHFR and previous trials in hypertensive patients have shown a blood pressure lowering response to riboflavin supplementation that is specific to individuals homozygous for this polymorphism (TT genotype). Low folate status is commonly reported in adults with the TT genotype however the effect of this genetic variant on riboflavin status has not previously been investigated. The aim of this study, therefore, was to investigate dietary intake and biomarker status of riboflavin by MTHFR genotype in Irish adults using data from the National Adult Nutrition Survey (2008–2010) (www.iuna.net).A 4-day s...
The Journal of Nutrition, 2020
Background Riboflavin is required for erythropoiesis, which is increased in people with hemoglobi... more Background 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. Objective We assessed the association between genetic hemoglobin disorders and riboflavin status in women of reproductive age in Cambodia. Methods 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. Results Genetic Hb disorders were present in 57% of the population, with the homozygous hemoglobin E vari...
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, Jan 24, 2018
Older adults have potential increased risk of nutrient deficiencies due to age-related decreased ... more Older adults have potential increased risk of nutrient deficiencies due to 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 five 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...
Hypertension, 2013
Intervention with riboflavin was recently shown to produce genotype-specific lowering of blood pr... more Intervention with riboflavin was recently shown to produce genotype-specific lowering of blood pressure (BP) in patients with premature cardiovascular disease homozygous for the 677C→T polymorphism (TT genotype) in the gene encoding the enzyme methylenetetrahydrofolate reductase (MTHFR). Whether this effect is confined to patients with high-risk cardiovascular disease is unknown. The aim of this randomized trial, therefore, was to investigate the responsiveness of BP to riboflavin supplementation in hypertensive individuals with the TT genotype but without overt cardiovascular disease. From an available sample of 1427 patients with hypertension, we identified 157 with the MTHFR 677TT genotype, 91 of whom agreed to participate in the trial. Participants were stratified by systolic BP and randomized to receive placebo or riboflavin (1.6 mg/d) for 16 weeks. At baseline, despite being prescribed multiple classes of antihypertensive drugs, >60% of participants with this genotype had f...
Circulation, 2006
Background— Meta-analyses predict that a 25% lowering of plasma homocysteine would reduce the ris... more Background— Meta-analyses predict that a 25% lowering of plasma homocysteine would reduce the risk of coronary heart disease by 11% to 16% and stroke by 19% to 24%. Individuals homozygous for the methylenetetrahydrofolate reductase ( MTHFR ) 677C→T polymorphism have reduced MTHFR enzyme activity resulting from the inappropriate loss of the riboflavin cofactor, but it is unknown whether their typically high homocysteine levels are responsive to improved riboflavin status. Methods and Results— From a register of 680 healthy adults 18 to 65 years of age of known MTHFR 677C→T genotype, we identified 35 with the homozygous (TT) genotype and age-matched individuals with heterozygous (CT, n=26) or wild-type (CC, n=28) genotypes to participate in an intervention in which participants were randomized by genotype group to receive 1.6 mg/d riboflavin or placebo for a 12-week period. Supplementation increased riboflavin status to the same extent in all genotype groups (8% to 12% response in ery...
The Journal of Nutrition, 2019
Background Riboflavin is required for several redox reactions. Clinical riboflavin deficiency occ... more Background 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. Objectives 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. Methods 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 conc...
Proceedings of the Nutrition Society
Pre-pregnancy obesity is associated with a 2-fold increased risk of Neural Tube Defects (NTD), an... more Pre-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 intak...
Circulation, 2005
Background-Meta-analyses predict that a 25% lowering of plasma homocysteine would reduce the risk... more Background-Meta-analyses predict that a 25% lowering of plasma homocysteine would reduce the risk of coronary heart disease by 11% to 16% and stroke by 19% to 24%. Individuals homozygous for the methylenetetrahydrofolate reductase (MTHFR) 677C3 T polymorphism have reduced MTHFR enzyme activity resulting from the inappropriate loss of the riboflavin cofactor, but it is unknown whether their typically high homocysteine levels are responsive to improved riboflavin status. Methods and Results-From a register of 680 healthy adults 18 to 65 years of age of known MTHFR 677C3 T genotype, we identified 35 with the homozygous (TT) genotype and age-matched individuals with heterozygous (CT, nϭ26) or wild-type (CC, nϭ28) genotypes to participate in an intervention in which participants were randomized by genotype group to receive 1.6 mg/d riboflavin or placebo for a 12-week period. Supplementation increased riboflavin status to the same extent in all genotype groups (8% to 12% response in erythrocyte glutathione reductase activation coefficient; PϽ0.01 in each case). However, homocysteine responded only in the TT group, with levels decreasing by as much as 22% overall (from 16.1Ϯ1.5 to 12.5Ϯ0.8 mol/L; Pϭ0.003; nϭ32) and markedly so (by 40%) in those with lower riboflavin status at baseline (from 22.0Ϯ2.9 and 13.2Ϯ1.0 mol/L; Pϭ0.010; nϭ16). No homocysteine response was observed in the CC or CT groups despite being preselected for suboptimal riboflavin status. Conclusions-Although previously overlooked, homocysteine is highly responsive to riboflavin, specifically in individuals with the MTHFR 677 TT genotype. Our findings might explain why this common polymorphism carries an increased risk of coronary heart disease in Europe but not in North America, where riboflavin fortification has existed for Ͼ50 years. (Circulation. 2006;113:74-80.)
Proceedings of the Nutrition Society, 2016
High salt intake (SI) is an established risk factor for several chronic diseases including hypert... more High salt intake (SI) is an established risk factor for several chronic diseases including hypertension, stroke and cardiovascular disease. Less well documented is evidence reporting salt as a potential risk factor for the development of obesity 1-3. Whether or not the relationship between salt and obesity is dependent or independent of energy intake (EI) remains unconfirmed. Consequently, this study aimed to investigate the association between SI and adiposity measures amongst a representative sample of UK adults aged 19-64 years using National Dietary and Nutritional Survey data (NDNS, 2014). Dietary intake from 4-day estimated food diaries and anthropometric measurements (body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR) and % body fat) were examined in relation to measured SI's from 24-hour urinary sodium excretion (NaEx) (n 605; 279 males; 326 females). A significant positive correlation was found between SI and all measures of body composition available, with the strongest correlation for BMI after adjusting for age, gender, smoking, alcohol, misreporting, EI, ethnic group and socioeconomic status (P < 0•001, r = •201). BMI and WC increased significantly across quartiles of sodium density (salt intake/kJ) for both males and females after controlling for misreporting of EI and age (Figure 1).
The Nutrition Handbook for Food Processors, 2002
The American Journal of Clinical Nutrition
Background The generation of the active form of vitamin B-6, pyridoxal 5′-phosphate (PLP), in tis... more Background 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. Objective To investigate vitamin B-6 and riboflavin status, their metabolic interaction, and relationship with methylenetetrahydrofolate reductase (MTHFR) genotype in adulthood. Methods 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. Results 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 ...
Journal of Bone and Mineral Research
ABSTRACTFolate, vitamins B12, B6, and riboflavin are required for one‐carbon metabolism and may a... more ABSTRACTFolate, 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 >4 times weekly were randomized to receive daily either combined folic acid (200 μg), vitamin B12 (10 μg), vitamin B6 (10 mg), and riboflavin (5 mg), 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 seru...
European Journal of Nutrition
Purpose To assess the effects of intervention with a daily multiple micronutrient powder (MNP) on... more Purpose To assess the effects of intervention with a daily multiple micronutrient powder (MNP) on thiamine, riboflavin, folate, and B12 status among young Laotian children. Methods Children (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. Results There 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 ± ...
Additional file 1: Table S1. Impact of B vitamin drinks on B vitamin biomarkers controlling for b... more Additional file 1: Table S1. Impact of B vitamin drinks on B vitamin biomarkers controlling for baseline homocysteine concentrations. Table S2. B vitamin biomarkers at baseline and end of intervention with the drinks (Per protocol analysis). Table S3. Impact of B vitamin drinks on biomarker status controlling for baseline homocysteine concentrations (per-protocol analysis).
Nutrition & Metabolism, 2021
Background Older adults are reported to have sub-optimal B vitamin status; targeted food-based so... more Background Older 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. Methods A 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-fortifie...
The Journal of Nutrition, 2020
Background Riboflavin is required to generate the active form of vitamin B-6 (pyridoxal 5′-phosph... more Background 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. Objectives 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. Methods 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. Results 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 ≤30.0 nmol/...
The American Journal of Clinical Nutrition, 2021
Background Atrophic gastritis (AG) and use of proton pump inhibitors (PPIs) result in gastric aci... more Background Atrophic gastritis (AG) and use of proton pump inhibitors (PPIs) result in gastric acid suppression that can impair the absorption of vitamin B-12 from foods. The crystalline vitamin B-12 form, found in fortified foods, does not require gastric acid for its absorption and could thus be beneficial for older adults with hypochlorhydria, but evidence is lacking. Objectives To investigate associations of AG and PPI use with vitamin B-12 status, and the potential protective role of fortified foods, in older adults. Methods Eligible participants (n = 3299) not using vitamin B-12 supplements were drawn from the Trinity-Ulster and Department of Agriculture cohort, a study of noninstitutionalized adults aged ≥60 y and recruited in 2008–2012. Vitamin B-12 status was measured using 4 biomarkers, and vitamin B-12 deficiency was defined as a combined indicator value < −0.5. A pepsinogen I:II ratio <3 was considered indicative of AG. Results AG was identified in 15% of participan...
Proceedings of the Nutrition Society, 2020
Riboflavin (vitamin B2), as the coenzymes flavin mononucleotide (FMN) and flavin dinucleotide (FA... more Riboflavin (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-p...
Proceedings of the Nutrition Society, 2020
Meta-analyses of epidemiological data report that adults who carry a common polymorphism, the MTH... more Meta-analyses of epidemiological data report that adults who carry a common polymorphism, the MTHFR 677C→T, in the gene encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) have a 40% increased risk of CVD and an 87% increased risk of hypertension. Riboflavin (vitamin B2), in its co-enzymatic form flavin adenine nucleotide (FAD), is required as a co-factor by MTHFR and previous trials in hypertensive patients have shown a blood pressure lowering response to riboflavin supplementation that is specific to individuals homozygous for this polymorphism (TT genotype). Low folate status is commonly reported in adults with the TT genotype however the effect of this genetic variant on riboflavin status has not previously been investigated. The aim of this study, therefore, was to investigate dietary intake and biomarker status of riboflavin by MTHFR genotype in Irish adults using data from the National Adult Nutrition Survey (2008–2010) (www.iuna.net).A 4-day s...
The Journal of Nutrition, 2020
Background Riboflavin is required for erythropoiesis, which is increased in people with hemoglobi... more Background 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. Objective We assessed the association between genetic hemoglobin disorders and riboflavin status in women of reproductive age in Cambodia. Methods 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. Results Genetic Hb disorders were present in 57% of the population, with the homozygous hemoglobin E vari...
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, Jan 24, 2018
Older adults have potential increased risk of nutrient deficiencies due to age-related decreased ... more Older adults have potential increased risk of nutrient deficiencies due to 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 five 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...
Hypertension, 2013
Intervention with riboflavin was recently shown to produce genotype-specific lowering of blood pr... more Intervention with riboflavin was recently shown to produce genotype-specific lowering of blood pressure (BP) in patients with premature cardiovascular disease homozygous for the 677C→T polymorphism (TT genotype) in the gene encoding the enzyme methylenetetrahydrofolate reductase (MTHFR). Whether this effect is confined to patients with high-risk cardiovascular disease is unknown. The aim of this randomized trial, therefore, was to investigate the responsiveness of BP to riboflavin supplementation in hypertensive individuals with the TT genotype but without overt cardiovascular disease. From an available sample of 1427 patients with hypertension, we identified 157 with the MTHFR 677TT genotype, 91 of whom agreed to participate in the trial. Participants were stratified by systolic BP and randomized to receive placebo or riboflavin (1.6 mg/d) for 16 weeks. At baseline, despite being prescribed multiple classes of antihypertensive drugs, >60% of participants with this genotype had f...
Circulation, 2006
Background— Meta-analyses predict that a 25% lowering of plasma homocysteine would reduce the ris... more Background— Meta-analyses predict that a 25% lowering of plasma homocysteine would reduce the risk of coronary heart disease by 11% to 16% and stroke by 19% to 24%. Individuals homozygous for the methylenetetrahydrofolate reductase ( MTHFR ) 677C→T polymorphism have reduced MTHFR enzyme activity resulting from the inappropriate loss of the riboflavin cofactor, but it is unknown whether their typically high homocysteine levels are responsive to improved riboflavin status. Methods and Results— From a register of 680 healthy adults 18 to 65 years of age of known MTHFR 677C→T genotype, we identified 35 with the homozygous (TT) genotype and age-matched individuals with heterozygous (CT, n=26) or wild-type (CC, n=28) genotypes to participate in an intervention in which participants were randomized by genotype group to receive 1.6 mg/d riboflavin or placebo for a 12-week period. Supplementation increased riboflavin status to the same extent in all genotype groups (8% to 12% response in ery...
The Journal of Nutrition, 2019
Background Riboflavin is required for several redox reactions. Clinical riboflavin deficiency occ... more Background 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. Objectives 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. Methods 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 conc...
Proceedings of the Nutrition Society
Pre-pregnancy obesity is associated with a 2-fold increased risk of Neural Tube Defects (NTD), an... more Pre-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 intak...
Circulation, 2005
Background-Meta-analyses predict that a 25% lowering of plasma homocysteine would reduce the risk... more Background-Meta-analyses predict that a 25% lowering of plasma homocysteine would reduce the risk of coronary heart disease by 11% to 16% and stroke by 19% to 24%. Individuals homozygous for the methylenetetrahydrofolate reductase (MTHFR) 677C3 T polymorphism have reduced MTHFR enzyme activity resulting from the inappropriate loss of the riboflavin cofactor, but it is unknown whether their typically high homocysteine levels are responsive to improved riboflavin status. Methods and Results-From a register of 680 healthy adults 18 to 65 years of age of known MTHFR 677C3 T genotype, we identified 35 with the homozygous (TT) genotype and age-matched individuals with heterozygous (CT, nϭ26) or wild-type (CC, nϭ28) genotypes to participate in an intervention in which participants were randomized by genotype group to receive 1.6 mg/d riboflavin or placebo for a 12-week period. Supplementation increased riboflavin status to the same extent in all genotype groups (8% to 12% response in erythrocyte glutathione reductase activation coefficient; PϽ0.01 in each case). However, homocysteine responded only in the TT group, with levels decreasing by as much as 22% overall (from 16.1Ϯ1.5 to 12.5Ϯ0.8 mol/L; Pϭ0.003; nϭ32) and markedly so (by 40%) in those with lower riboflavin status at baseline (from 22.0Ϯ2.9 and 13.2Ϯ1.0 mol/L; Pϭ0.010; nϭ16). No homocysteine response was observed in the CC or CT groups despite being preselected for suboptimal riboflavin status. Conclusions-Although previously overlooked, homocysteine is highly responsive to riboflavin, specifically in individuals with the MTHFR 677 TT genotype. Our findings might explain why this common polymorphism carries an increased risk of coronary heart disease in Europe but not in North America, where riboflavin fortification has existed for Ͼ50 years. (Circulation. 2006;113:74-80.)