This study provides Class I evidence that 2-year supplementation with folic acid and vitamin B12 in hyperhomocysteinemic elderly people does not affect cognitive performance.

Aims: To systematically review the literature on daily losses and bioavailability of vitamin B12. These estimates could be used for deriving recommendations on vitamin B12 intake for adults and elderly. Methods: We identified publications on daily vitamin B12 losses (July 2011) and publications on the bioavailability of vitamin B12 from foods or diets (June 2010) in MEDLINE, EMBASE and the Cochrane Library. Results: A pooled analysis of five studies (52 subjects) showed that 0.13 ± 0.03% of the total body store is lost per day. Absorption of vitamin B12 ranged from 4.5 (dose of 38 µg from consumption of liver) to 83% (dose of 3.0 µg from consumption of mutton meat). Data from eight studies including 83 subjects suggested that the amount of vitamin B12 absorbed from food (A_i) increased with increasing doses of vitamin B12 (D_i) as described by the equation: ln(A_i) = 0.7694 * ln(D_i) - 0.9614. Conclusion: Daily vitamin B12 losses in apparently healthy adults and elderly probably range from 1.4 to 5.1 µg. Vitamin B12 intakes needed to compensate for these losses seem to range from 3.8 to 20.7 µg. More evidence is needed on the relationships between biochemical markers of vitamin B12 status, vitamin B12 body store and long-term health outcomes to evaluate whether current recommendations on vitamin B12 intake (1.4-3 µg) need to be changed.

The obtained dose-response estimate between vitamin B-12 intake and status provides complementary evidence to underpin recommendations for a vitamin B-12 intake of populations.

This version is distributed under a non-commencial no derivatives Creative Commons (CC-BY-NC-ND) user license, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited and not used for commercial purposes. Further, the restriction applies that if you remix, transform, or build upon the material, you may not distribute the modified material. (25(OH)D) and cognitive performance was examined. Secondly, we assessed 6 whether there was evidence for an interplay between 25(OH)D and glucose 7 homeostasis in the association with cognitive performance. 8 9 Design, Setting and Participants: Associations were studied using cross-10 sectional data of 776 (3 domains) up to 2722 (1 domain) Dutch community-11 dwelling older adults, aged ≥65 years. Results: The overall median MMSE score was 29 synthesis, choline acetyltransferase activity, and amyloid clearance (reviewed 52 in 2-4 ). Finally, besides these direct pathways between vitamin D and cognitive 53 performance, one might also think of indirect pathways. For instance, vitamin 54 D deficiency has been associated with glucose intolerance 6 . Glucose 55 intolerance on its turn has been related to both vascular damage and 56 cognitive decline 7 . Accordingly, it may be that the potential favourable effect 57 of vitamin D on cognitive performance can be partially explained by its 58 beneficial effect on glucose tolerance. It may also be that glucose tolerance 59 biologically interacts with vitamin D. Therefore, it may be that the potential 60 association between vitamin D and cognitive function appears to be stronger 61 5 in persons with glucose intolerance than in their glucose tolerant counterparts. 62These possible pathways, however, have only been examined in a few 63 studies [8][9][10][11][12] . 64 65 So far, results from observational studies 1,[8][9][10][11][13][14][15][16][17][18] Biochemical analyses 142Blood samples were drawn in the morning when the participants were fasted 143 or had consumed a restricted breakfast. Samples were stored at -80 ˚C until 144 determination. Serum 25(OH)D was measured by isotope dilution -online 145 9 solid phase extraction liquid chromatography -tandem mass spectrometry 146 (ID-XLC-MS/MS) 28 . Plasma glucose concentrations were analysed using a 147 hexokinase method (Gluco-quant, Roche Diagnostics). Insulin levels were 148 determined using an immunometric assay (ADVIA Centaur immunoassay 149 system, Siemens Medical Solutions Diagnostics). Creatinine concentration 150 was measured using the enzymatic colorimetric Roche CREA plus assay. 151 152Covariates 153 Height was measured at baseline with a stadiometer to the nearest 0.1 cm. 154Weight was measured to the nearest 0.5 kg with a calibrated analogues scale. association with cognitive performance was tested. In case of significant 213 findings, data was also presented stratified. 214 12 A P-value of <0.05 was used to determine statistical significance. Analyses 215 were performed using the statistical package SAS, version 9.1 (S...

Higher serum 25(OH)D and lower plasma glucose are associated with larger gray matter volume, but not white matter or total brain volume, in a population of Dutch adults aged ≥65 y. This trial was registered at clinicaltrials.gov as NCT00696514.

Aim: We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B12 status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin B12 supplementation with participants who did not. Methods: Participants of the B-PROOF study (n = 2919) were assigned to 400 µg folic acid and 500 µg vitamin B12, or a placebo. After two years of intervention, T1-weighted magnetic resonance imaging (MRI) scans were made in a random subsample (n = 218) to obtain grey and white matter volume, and total brain volume (TBV). Plasma homocysteine, serum folate, vitamin B12, holotranscobalamin, and methylmalonic acid concentrations were measured. Results: Multiple linear regression analyses showed inverse associations between plasma homocysteine with TBV (β = −0.91, 95% CI −1.85–0.03; p = 0.06) and between serum folate and TBV (β = −0.20, 95% CI −0.38, −0.02; p = 0.03). No significant associations were observed for serum vitamin B12 and holotranscobalamin. Fully adjusted ANCOVA models showed that the group that received B-vitamins had a lower TBV (adjusted mean 1064, 95% CI 1058–1069 mL) than the non-supplemented group (1072, 95% CI 1067–1078 mL, p = 0.03). Conclusions: Results were contradictory, with higher Hcy levels associated with lower TBV, but also with higher folate levels associated with lower TBV. In addition, the lack of a baseline measurement withholds us from giving recommendations on whether folic acid and vitamin B12 supplementation will be beneficial above and beyond normal dietary intake for brain health.

In this study we observed a significant association between vitamin B12 intake and vitamin B12 biomarkers and between the biomarkers. The observed inflections for total B12 and holoTC with MMA and tHcy could indicate cut-off levels for further testing for B12 deficiency and determining subclinical B12 deficiency.