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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 ± 1.2 nmol/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 ±0.7 nmol/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).

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 foods4 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 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/cm

The 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.Brachial 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.Two 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).This 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.

Background The main mode of transportation in Ireland remains travel by car. Transport mobility is important for older adults in accessing shops, healthcare, services, community and in maintaining relationships. Cessation of driving is associated with negative effects on mental health, loneliness and physical health. We aimed to explore factors associated with driving status in older adults living in an urban environment. Methods Study included adults aged greater than 65 years attending a geriatric outpatient service in an urban environment and recruited as part of the TUDA (Trinity Ulster, Department of Agriculture) study. We excluded those with a MMSE (Mini-Mental State Exam) less than 24 as we aimed to include only non-dementia patients. Physical frailty was measured with the Timed Up and Go (TUG) and depression with the Center for Epidemiological Studies Depression scale (CES-D). Factors associated with driving status were explored in multinomial regression models. Results 1978 adults, mean age 77.7 ± 7.1 years, 76.0% were female. 35.5% were current drivers but this differed by age category 45.9% (65–75 years), 25% (75–85 years) and 12.5% (85+ years). 28.1% were past drivers. Positive independent predictors of current driving were younger age (P Conclusion One third of patients attending a geriatric outpatients in an urban environment were currently driving which is much lower than in the general older Irish population. However, our study included frail adults living in more deprived socioeconomic areas and had a high proportion of females who had never learned to drive. Furthermore, access to urban public transport may be a factor. Non-drivers were more likely to have depression and report loneliness independent of other factors highlighting its negative impact.

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

Whilst chronic kidney disease has been associated with cognitive impairment, the association between reduced estimated Glomerular Filtration Rate (eGFR) and domain-specific cognitive performance is less clear and may represent an important target for the promotion of optimal brain health in older adults.Participants aged60 years from the Trinity-Ulster-Department of Agriculture study underwent detailed cognitive assessment using the Mini-Mental State Examination (Mini-Mental State Examination (MMSE)), Frontal Assessment Battery (FAB) and Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Poisson and linear regression models assessed the relationship between eGFR strata and cognitive performance.In 4887 older adults (73.9 ± 8.3 years; 67.7% female), declining eGFR strata was associated with greater likelihood of error on the MMSE/FAB and poorer overall performance on the RBANS. Following robust covariate adjustment, findings were greatest for GFR45 ml/ml/1.73 mReduced kidney function was associated with poorer global and domain-specific neuropsychological performance. Associations were strongest with eGFR45 ml/min/1.73 m