Vitamin B12 Biomarker Responses to Supplementation

Summary

The aim of the study is to investigate the response of recognized biomarkers of vitamin B12 status to intervention with supplemental vitamin B12 at doses within and beyond the range of typical dietary intakes in younger and older adults.

Study design: A double-blind randomized controlled trial in healthy adults aged 18 years and over will be conducted. Apparently healthy individuals will be recruited from the staff and student population at Ulster University, Coleraine, and the surrounding local community. Those interested in the study will provide informed consent. Individuals suffering from chronic conditions, those taking medications interfering with folate or vitamin B12 metabolism or B vitamin supplements, and women who are pregnant will be excluded from participation. Potential participants will provide a non-fasting blood sample and those with plasma creatinine concentration \> 130 µmol/L, those with hypochlorhydria (diagnosed serologically by pepsinogen I to Pepsinogen II ratio \< 3) and those with the 677C→T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene will also be excluded from the study. In addition, participants aged 60 years and over who score \<25 on the Folstein's Mini-Mental State Examination (a cognitive function screening test) will be excluded to reduce the risk of including participants with impaired cognitive function and thus reduced ability to comply with the study requirements, including compliance with the intervention trial and recall of food intake.

All eligible participants will undergo a pre-treatment phase with 400 µg/day folic acid (FA) for 11 weeks. At the end of this phase, participants will provide a non-fasting blood sample (baseline sample) and will be stratified within each age category (\<60 years and ≥60 years) according to their homocysteine concentrations and subsequently randomized from each stratum (in a 1:1:1:1 allocation ratio) to one of the four treatments for 16 weeks: 400 µg/day FA + placebo, 400 µg/day FA + 2 µg/day vitamin B12, 400 µg/day FA + 10 µg/day vitamin B12 or 400 µg/day FA + 50 µg/day vitamin B12. A non-fasting blood sample will be collected at the end of the intervention. Biomarkers of vitamin B12 and folate will be measured in blood samples collected at baseline and post-intervention. The intervention will be conducted on a staggered basis and both study participants and researchers will be blinded to the treatment allocations. Dietary intake of participants will be assessed using a four-day food diary based on 2 weekday and 2 weekend day intakes in combination with a food frequency questionnaire particularly focused on intakes of foods fortified with vitamin B12 and FA.

Conditions

• Healthy

Interventions

DIETARY_SUPPLEMENT

Folic Acid

400µg Folic Acid per day for 16 weeks

DIETARY_SUPPLEMENT

2 µg Vitamin B12

2 µg Vitamin B12 per day for 16 weeks

DIETARY_SUPPLEMENT

10 µg Vitamin B12

10 µg Vitamin B12 per day for 16 weeks

DIETARY_SUPPLEMENT

50 µg Vitamin B12

50 µg Vitamin B12 per day for 16 weeks

Sponsors & Collaborators

• University of Dublin, Trinity College

  collaborator OTHER

• University of Bergen

  collaborator OTHER

• University of Ulster

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2004-10-01

Primary Completion

2006-12-12

Completion

2006-12-12

Countries

• United Kingdom

Study Locations