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

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 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 ß: 2.49; 95% CI 1.75, 3.24; P < 0.001), supplement use (ß: 81.72; 95% CI: 66.01, 97.43; P < 0.001), fortified food (ß: 12.49; 95% CI: 2.08, 22.91; P = 0.019), and EGRac (ß: -65.81; 95% CI: -99.08, -32.54; P < 0.001), along with BMI (ß: -1.81; 95% CI: -3.31, -0.30; P = 0.019). CONCLUSIONS: 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).

Modelling the impact of mandatory folic acid fortification of bread or flour in Ireland on the risk of occurrence of NTD-affected pregnancies in women of childbearing age and on risk of masking vitamin B12 deficiency in older adults.

PURPOSE: The rate of neural tube defects (NTDs) in Europe has remained similar since the 1990s despite folic acid supplement recommendations (400 µg/day) for women of childbearing age. Mandatory folic acid fortification of staple foods has proved effective for reducing the prevalence of NTDs in over 80 countries. This study estimated the impact of addition of folic acid to bread or flour in the Republic of Ireland on reducing the risk of occurrence of NTD-affected pregnancies and the possible risk of masking (undiagnosed) vitamin B12 deficiency in older adults. METHODS: Analyses were based on the Irish National Adult Nutrition Survey (2008-2010). Folic acid fortification was modelled using DaDiet© software. Estimates were made of the increase in average daily folic acid intake in women (18-50 years) and the risk of exceeding the tolerable upper intake level (UL) of 1000 µg for folic acid in adults over 50 years of age. RESULTS: The fortification scenarios examined would reduce the risk of NTD-affected pregnancies by 8-32%, corresponding to an increase of 39-152 µg in the mean daily folic acid intake of WCBA. The risk of masking anaemia associated with vitamin B12 deficiency in older adults would be negligible as the probability of exceeding the UL for folic acid, even by a small amount, is very low (≤ 0.2%). CONCLUSIONS: These levels of addition of folic acid to bread or flour would effectively reduce the risk of NTDs while allowing safe consumption of folic acid at current levels from other fortified foods and supplements.

Impact of voluntary fortification and supplement use on dietary intakes and biomarker status of folate and vitamin B-12 in Irish adults.

BACKGROUND: Ireland has traditionally operated a liberal policy of voluntary fortification, but little is known about how this practice, along with supplement use, affects population intakes and status of folate and vitamin B-12. OBJECTIVE: The aim was to examine the relative impact of voluntary fortification and supplement use on dietary intakes and biomarker status of folate and vitamin B-12 in Irish adults. DESIGN: Folic acid and vitamin B-12 from fortified foods and supplements were estimated by using brand information for participants from the cross-sectional National Adult Nutrition Survey 2008-2010. Dietary and biomarker values were compared between 6 mutually exclusive consumption groups formed on the basis of folic acid intake. RESULTS: The consumption of folic acid through fortified foods at low, medium, and high levels of exposure [median (IQR) intakes of 22 (13, 32), 69 (56, 84), and 180 (137, 248) µg/d, respectively]; from supplements [203 (150, 400) µg/d]; or from both sources [287 (220, 438) µg/d] was associated with significantly higher folate intakes and status compared with nonconsumption of folic acid (18% of the population). Median (IQR) red blood cell (RBC) folate increased significantly from 699 (538, 934) nmol/L in nonconsumers to 1040 (83, 1390) nmol/L in consumers with a high intake of fortified foods (P < 0.001), with further nonsignificant increases in supplement users. Supplement use but not fortification was associated with significantly higher serum vitamin B-12 concentrations relative to nonconsumers (P < 0.001). Two-thirds of young women had suboptimal RBC folate for protection against neural tube defects (NTDs); among nonconsumers of folic acid, only 16% attained optimal RBC folate. CONCLUSIONS: The consumption of voluntarily fortified foods and/or supplement use was associated with significantly higher dietary intakes and biomarker status of folate in Irish adults. Of concern, the majority of young women remain suboptimally protected against NTDs.