Dataset Information

Effect of Vitamin B12 and Folic Acid Supplementation on Bone Mineral Density and Quantitative Ultrasound Parameters in Older People with an Elevated Plasma Homocysteine Level: B-PROOF, a Randomized Controlled Trial.

ABSTRACT: High plasma homocysteine (Hcy) levels are associated with increased osteoporotic fracture incidence. However, the mechanism remains unclear. We investigated the effect of Hcy-lowering vitamin B12 and folic acid treatment on bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) parameters. This randomized, double-blind, placebo-controlled trial included participants aged ≥65 years with plasma Hcy levels between 12 and 50 µmol/L. The intervention comprised 2-year supplementation with either a combination of 500 µg B12, 400 µg folic acid, and 600 IU vitamin D or placebo with 600 IU vitamin D only. In total, 1111 participants underwent repeated dual-energy X-ray assessment and 1165 participants underwent QUS. Femoral neck (FN) BMD, lumbar spine (LS) BMD, calcaneal broadband ultrasound attenuation (BUA), and calcaneal speed of sound (SOS) were assessed. After 2 years, FN-BMD and BUA had significantly decreased, while LS-BMD significantly increased (all p < 0.01) and SOS did not change in either treatment arm. No statistically significant differences between the intervention and placebo group were present for FN-BMD (p = 0.24), LS-BMD (p = 0.16), SOS (p = 0.67), and BUA (p = 0.96). However, exploratory subgroup analyses revealed a small positive effect of the intervention on BUA at follow-up among compliant persons >80 years (estimated marginal mean 64.4 dB/MHz for the intervention group and 61.0 dB/MHz for the placebo group, p = 0.04 for difference). In conclusion, this study showed no overall effect of treatment with vitamin B12 and folic acid on BMD or QUS parameters in elderly, mildly hyperhomocysteinemic persons, but suggests a small beneficial effect on BUA in persons >80 years who were compliant in taking the supplement.

SUBMITTER: Enneman AW

PROVIDER: S-EPMC4415946 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Effect of Vitamin B12 and Folic Acid Supplementation on Bone Mineral Density and Quantitative Ultrasound Parameters in Older People with an Elevated Plasma Homocysteine Level: B-PROOF, a Randomized Controlled Trial.

Enneman Anke W AW Swart Karin M A KM van Wijngaarden Janneke P JP van Dijk Suzanne C SC Ham Annelies C AC Brouwer-Brolsma Elske M EM van der Zwaluw Nikita L NL Dhonukshe-Rutten Rosalie A M RA van der Cammen Tischa J M TJ de Groot Lisette C P G M LC van Meurs Joyce J Lips Paul P Uitterlinden André G AG Zillikens M Carola MC van Schoor Natasja M NM van der Velde Nathalie N

Calcified tissue international 20150225 5

High plasma homocysteine (Hcy) levels are associated with increased osteoporotic fracture incidence. However, the mechanism remains unclear. We investigated the effect of Hcy-lowering vitamin B12 and folic acid treatment on bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) parameters. This randomized, double-blind, placebo-controlled trial included participants aged ≥65 years with plasma Hcy levels between 12 and 50 µmol/L. The intervention comprised 2-year supplementation w ...[more]

PMID: 25712255

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Project description:BackgroundMegaloblastic anemia (MBA), also known as macrocytic anemia, is a type of anemia characterized by decreased number of RBCs as well as the presence of unusually large, abnormal and poorly developed erythrocytes (megaloblasts), which fail to enter blood circulation due to their larger size. Lack of vitamin-B12 (VB12) and / or folate (Vitamin-B9, VB9) with elevated homocysteine is the key factor responsible for megaloblastic anemia. Prior studies have demonstrated the induction of apoptosis in these abnormal under-developed erythrocytes. However, it is not clear whether this apoptosis induction is due to elevated p53 level or due to any other mechanism. Furthermore, it is also not fully known whether decreased vitamin-B12 and / or folate are responsible for apoptosis induction mediated by p53 in pre-erythroblasts.MethodsLevels of serum VB9, VB12 and homocysteine in 50 patients suffering from MBA were compared with 50 non-megaloblastic anemia control subjects, who were referred by the clinicians for bone marrow examination for medical conditions other than MBA. Next, we have measured the p53 expression in the paraffin embedded blocks prepared from bone marrow biopsy, using immunohistochemistry, and the expression levels correlated with VB9 and VB12 levels.ResultsOut of 50 MBA patients 40 (80%) and 44 (88%) subjects had very low VB12 and VB9 levels respectively. In contrast, only 2 (4%) and 12 (24%) non-megaloblastic anemia controls, out of 50 subjects, had low VB12 and VB9 respectively. Correlating with low vitamin B9 and B12, the homocysteine levels were high in 80% cases. But, only 20% non-megaloblastic controls exhibited high homocysteine in plasma. Immunohistochemical analysis for p53 expression showed a significantly high level of expression in MBA cases and no-or very low-expression in control subjects. Our correlation studies comparing the VB12 and VB9 levels with p53 expression concludes unusually high p53 levels in patients suffering from VB12 and VB9 deficiency induced MBA compared to control subjects not suffering from MBA.ConclusionTumor protein p53 is the key protein expressed heavily in the bone marrow biopsies of patients suffering from VB12 and VB9 deficiency induced MBA but not in control subjects. Hence, p53 expression could be used as a surrogate marker for confirming the VB9 and VB12 induced MBA.

Project description:ObjectivesTo identify the cost-effectiveness of four policy options related to folic acid supplements after considering the side effects of masking vitamin B12 (B12) deficiency in primary stroke prevention for hypertensive patients in China.Study designA cost-effectiveness analysis.MethodsFour policies were considered: Policy A, Do nothing to address folate status in hypertensive patients at risk for stroke; Policy B, Folate supplementation without pre-screening for vitamin B12 deficiency; Policy C, Folate supplementation with pre-screening all patients for B12 deficiency and add B12 supplements if B12 is deficient; and Policy D, Folate supplementation only for those whose folate is deficient, pre-screen all patients for both B12 and folate deficiencies and add B12 supplements if B12 is deficient. A decision tree with a five-year period of intervention based on the China Stroke Primary Prevention Trial (CSPPT) from the Chinese healthcare system perspective estimated incremental cost-effectiveness ratio (ICER) for Policy B, Policy C and Policy D vs. Policy A.ResultsAt a willingness to pay (WTP) threshold of 3 times the national GDP per capita ($38,198), Policy B was not cost-effective compared to Policy A, with an ICER of $47,968 per QALY due to QALYs lost introduced by the delayed diagnosis of B12 deficiency and the potentially underestimated costs associated with treating neuropathy. However, Policy C and Policy D were cost-effective compared to Policy A, with an ICER of $32,615 and $20,287 per QALY, respectively. A probabilistic sensitivity analysis showed that there would be a 72.7% and 83.5% chance that the additional cost of Policy C and Policy D, compared with Policy A, was at or below the WTP threshold.ConclusionsFolate supplementation with integrated screening for B12 and folate deficiencies is considered the most cost-effective strategy for primary stroke prevention in hypertensive elderly patients in China. Future research should focus on advancing precision medicine to assess the feasibility and cost-effectiveness of nationwide implementation across diverse sub-populations within the context of integrated screening, ensuring efficient and tailored public nutrition strategy delivery.

Dataset Information

Effect of Vitamin B12 and Folic Acid Supplementation on Bone Mineral Density and Quantitative Ultrasound Parameters in Older People with an Elevated Plasma Homocysteine Level: B-PROOF, a Randomized Controlled Trial.

Publications

Effect of Vitamin B12 and Folic Acid Supplementation on Bone Mineral Density and Quantitative Ultrasound Parameters in Older People with an Elevated Plasma Homocysteine Level: B-PROOF, a Randomized Controlled Trial.

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