Effect of 1 Year Vitamin D or D Plus B-vitamins on Bone Markers in Elderly People (KnoVIB) (KnoVIB)

Effect of 1 Year Vitamin D or D Plus B-vitamins on Bone Markers in Elderly People

The standard recommendation to prevent osteoporosis is to supplement low doses of vitamin D and calcium. Hyperhomocysteinemia has been related to increased risk of osteoporosis.

Study Overview

• Status: Completed
• Conditions: Nutritional Supplement Toxicity
• Intervention / Treatment: Dietary supplement: Vitamin D and Calcium; Dietary supplement: Vitamin D, Calcium, Vitamins B9, B6, B12

Detailed Description

The current study aimed at investigating if homocysteine-lowering effect (low doses of B-vitamins) will add any measurable beneficial effect on bone markers when added to the standard recommendations for prevention of osteoporosis.

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Saarland
    • Homburg, Saarland, Germany, 66424
      • University of Saarland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age> 50 years,
• male and female

Exclusion Criteria:

• renal dysfunction,
• recent stroke or coronary event within the last 3 months,
• current cancer,
• antifolate treatment,
• ileum resection,
• existing B vitamins supplementation,
• megaloblastic anemia,
• osteoporotic patients treated with pharmacological doses of vitamin D or antiosteoporotic drugs.

Termination criteria were:

• indication for a high-dose vitamin B supplementation,
• coronary or vascular event,
• or surgical procedures during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Vitamin D and Calcium; a combination of dietary supplement including "all" 1200 IE Vitamin D3 plus 800 mg Calcium Carbonate	Dietary supplement: Vitamin D and Calcium; a combination of dietary supplement including "all" 1200 IE Vitamin D3 plus 800 mg Calcium Carbonate 1200 IE Vitamin D3 plus 800 mg Calcium Carbonate Arm: Experimental: Vitamin D, Calcium, Vitamins B9, B6, B12 1200 IE Vitamin D3 plus 800 mg Calcium Carbonate plus 0,5mg Folic acid, 50 mg B6, 0,5 mg B12
Experimental: Vitamin D, Calcium, Vitamins B9, B6, B12; a combination of dietary supplement including "all" 1200 IE Vitamin D3 plus 800 mg Calcium Carbonate plus 0,5mg Folic acid, 50 mg B6, 0,5 mg B12	Dietary supplement: Vitamin D, Calcium, Vitamins B9, B6, B12; a combination of dietary supplement including "all" 1200 IE Vitamin D3 plus 800 mg Calcium Carbonate plus 0,5mg Folic acid, 50 mg B6, 0,5 mg B12

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in bone formation markers	Concentrations of bone formation markers in plasma [OC (ng/ml), BAP (U/L)]: are measured: if all are increased indicate enhanced bone formation	baseline, 6 and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in plasma choline and betaine	plasma choline and betaine (all µmol/L): if both increased indicate saving betaine and choline	baseline and aftter 12 months
Changes in global DNA methylation	global DNA methylation [line 1-methylation (expressed as %)]	baseline and after 12 months
Changes in gene-specific gene methylation	After isolating DNA from whole blood, changes in methylation of targeted genes is studied (expressed as %)	baseline and after 12 months
Changes in TMAO	Plasma concentrations of TMAO ((µmol/L) is measured	baseline and after 6 and 12 months
Changes in phospholipid concentration in plasma	Plasma phospholipids ((µmol/L) are measured	baseline and after 12 months
Changes in concentrations of bone resorption markers	concentrations of bone resorption markers [plasma TRAP5b (U/L), urine DPD (nmol//mmol creatinine)]: if both are increased indicate enhanced bone resorption	baseline, 6 and 12 months
Changes in plasma homocysteine concentrations	changes in plasma homocysteine (µmol/L) between the time points	baseline, 6 and 12 months
Changes in plasma levels of folate	changes in serum and whole blood folate (nmol/L)	baseline, 6 and 12 months

Collaborators and Investigators

• Sponsor: Universität des Saarlandes
• Investigators: Principal Investigator: Rima Obeid, PhD, Universität des Saarlandes

Publications and helpful links

General Publications

• Kirsch SH, Herrmann W, Kruse V, Eckert R, Graber S, Geisel J, Obeid R. One year B-vitamins increases serum and whole blood folate forms and lowers plasma homocysteine in older Germans. Clin Chem Lab Med. 2015 Feb;53(3):445-52. doi: 10.1515/cclm-2014-0540.
• Hubner U, Geisel J, Kirsch SH, Kruse V, Bodis M, Klein C, Herrmann W, Obeid R. Effect of 1 year B and D vitamin supplementation on LINE-1 repetitive element methylation in older subjects. Clin Chem Lab Med. 2013 Mar 1;51(3):649-55. doi: 10.1515/cclm-2012-0624.
• Herrmann W, Kirsch SH, Kruse V, Eckert R, Graber S, Geisel J, Obeid R. One year B and D vitamins supplementation improves metabolic bone markers. Clin Chem Lab Med. 2013 Mar 1;51(3):639-47. doi: 10.1515/cclm-2012-0599.
• Obeid R, Hubner U, Bodis M, Graeber S, Geisel J. Effect of adding B-vitamins to vitamin D and calcium supplementation on CpG methylation of epigenetic aging markers. Nutr Metab Cardiovasc Dis. 2018 Apr;28(4):411-417. doi: 10.1016/j.numecd.2017.12.006. Epub 2017 Dec 29.
• Obeid R, Awwad HM, Rabagny Y, Graeber S, Herrmann W, Geisel J. Plasma trimethylamine N-oxide concentration is associated with choline, phospholipids, and methyl metabolism. Am J Clin Nutr. 2016 Mar;103(3):703-11. doi: 10.3945/ajcn.115.121269. Epub 2016 Feb 10.

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: October 21, 2015
• First Submitted That Met QC Criteria: October 22, 2015
• First Posted (Estimate): October 26, 2015

Study Record Updates

• Last Update Posted (Actual): April 4, 2019
• Last Update Submitted That Met QC Criteria: April 2, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin B Complex; Hematinics; Vitamin D; Cholecalciferol; Calcium; Vitamins; Folic Acid; Calcium, Dietary; Ergocalciferols
• Other Study ID Numbers: Vitamins and bone markers