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Elevated homocysteine levels and low vitamin B12 and folate levels have been associated with deteriorated bone health. This systematic literature review with dose-response meta-analyses summarizes the available scientific evidence on associations of vitamin B12, folate, and homocysteine status with fractures and bone mineral density (BMD). Twenty-seven eligible cross-sectional (n = 14) and prospective (n = 13) observational studies and one RCT were identified. Meta-analysis on four prospective studies including 7475 people showed a modest decrease in fracture risk of 4% per 50 pmol/L increase in vitamin B12 levels, which was borderline significant (RR = 0.96, 95% CI = 0.92 to 1.00).Meta-analysis of eight studies including 11511 people showed an increased fracture risk of 4% per μmol/L increase in homocysteine concentration (RR = 1.04, 95% CI = 1.02 to 1.07). We could not draw a conclusion regarding folate levels and fracture risk, as too few studies investigated this association.Meta-analyses regarding vitamin B12, folate and homocysteine levels, and BMD were possible in female populations only and showed no associations. Results from studies regarding BMD that could not be included in the meta-analyses were not univocal. [ABSTRACT FROM AUTHOR]

Various populations are at increased risk of developing a low vitamin D status, in particular older adults. Whereas sun exposure is considered the main source of vitamin D, especially during summer, dietary contributions should not be underestimated. This study aims to identify food sources of vitamin D that associate most strongly with serum vitamin D concentration. Data of 595 Dutch adults, aged ≥65 years, were analysed. Vitamin D intake was assessed with a food frequency questionnaire and 25-hydroxyvitamin D (25(OH)D) was determined in serum. Associations of total vitamin D intake and vitamin D intake from specific food groups with serum 25(OH)D status were examined by P-for trend analyses over tertiles of vitamin D intake, prevalence ratios (PRs), and spline regression. The prevalence of vitamin D deficiency was high, with 36% of the participants having a 25(OH)D status <50nmol/L. Participants with adequate 25(OH)D concentrations were more likely to be men and more likely to be younger than participants with vitamin D deficiency. Total median vitamin D intake was 4.3μg/day, of which 4.0μg/day was provided by foods. Butter and margarine were the leading contributors to total vitamin D intake with 1.8μg/day, followed by the intake of fish and shellfish with 0.56μg/day. Participants with higher intakes of butter and margarine were 21% more likely to have a sufficient 25(OH)D status after adjustment for covariates (T1 vs. T3: PR 1.0 vs. 1.21 (95%CI: 1.03-1.42), P-for trend 0.02). None of the other food groups showed a significant association with the probability of having a sufficient 25(OH)D status. This study shows that vitamin D intake was positively associated with total serum 25(OH)D concentration, with butter and margarine being the most important contributors to total vitamin D intake., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background and Aims: Hyperhomocysteinemia is associated with arterial stiffness, but underlying pathophysiological mechanisms explaining this association are to be revealed. This study was aimed to explore two potential pathways concerning the one-carbon metabolism. A potential causal effect of homocysteine was explored using a genetic risk score reflecting an individual's risk of having a long-term elevated plasma homocysteine level and also associations with B-vitamin levels were investigated., Methods and Results: Baseline cross-sectional data of the B-PROOF study were used. In the cardiovascular subgroup (n = 567, 56% male, age 72.6 ± 5.6 yrs) pulse wave velocity (PWV) was determined using applanation tonometry. Plasma concentrations of vitamin B12, folate, methylmalonic acid (MMA) and holo transcobalamin (holoTC) were assessed and the genetic risk score was based on 13 SNPs being associated with elevated plasma homocysteine. Associations were examined using multivariable linear regression analysis. B-vitamin levels were not associated with PWV. The genetic risk score was also not associated with PWV. However, the homocysteine-gene interaction was significant (p < 0.001) in the association of the genetic risk score and PWV. Participants with the lowest genetic risk of having long-term elevated homocysteine levels, but with higher measured homocysteine levels, had the highest PWV levels., Conclusion: Homocysteine is unlikely to be causally related to arterial stiffness, because there was no association with genetic variants causing hyperhomocysteinemia, whereas non-genetically determined hyperhomocysteinemia was associated with arterial stiffness. Moreover, the association between homocysteine and arterial stiffness was not mediated by B-vitamins. Possibly, high plasma homocysteine levels reflect an unidentified factor, that causes increased arterial stiffness., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: High plasma homocysteine levels have been associated with incident osteoporotic fractures, but the mechanisms underlying this association are still unknown. It has been hypothesized that homocysteine might interfere with collagen cross-linking in bone, thereby weakening bone structure. Therefore, we wanted to investigate whether plasma homocysteine levels are associated with bone quality parameters, rather than with bone mineral density., Methods: Cross-sectional data of the B-PROOF study (n=1227) and of two cohorts of the Rotterdam Study (RS-I (n=2850) and RS-II (n=2023)) were used. Data on bone mineral density of the femoral neck and lumbar spine were obtained in these participants using dual-energy X-ray assessment (DXA). In addition, participants of B-PROOF and RS-I underwent quantitative ultrasound measurement of the calcaneus, as a marker for bone quality. Multiple linear regression analysis was used to investigate the associations between natural-log transformed plasma levels of homocysteine and bone mineral density or ultrasound parameters., Results: Natural-log transformed homocysteine levels were inversely associated with femoral neck bone mineral density in the two cohorts of the Rotterdam Study (B=-0.025, p=0.004 and B=-0.024, p=0.024). In B-PROOF, no association was found. Pooled data analysis showed significant associations between homocysteine and bone mineral density at both femoral neck (B=-0.032, p=0.010) and lumbar spine (B=-0.098, p=0.021). Higher natural-log transformed homocysteine levels associated significantly with lower bone ultrasound attenuation in B-PROOF (B=-3.7, p=0.009) and speed of sound in both B-PROOF (B=-8.9, p=0.001) and RS-I (B=-14.5, p=0.003), indicating lower bone quality. Pooled analysis confirmed the association between homocysteine and SOS (B=-13.1, p=0.016). Results from ANCOVA-analysis indicate that differences in SOS and BUA between participants having a plasma homocysteine level above or below median correspond to 0.14 and 0.09 SD, respectively., Discussion: In this study, plasma levels of homocysteine were significantly inversely associated with both bone ultrasound parameters and with bone mineral density. However, the size of the associations seems to be of limited clinical relevance and may therefore not explain the previously observed association between plasma homocysteine and osteoporotic fracture incidence., (Copyright © 2014 Elsevier Inc. All rights reserved.)