Vitamin B12 Biomarker Responses to Supplementation

NCT04731948 | Completed

• 1 other identifier: UUREC 04/38
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Vitamin B12; Serum holotranscobalamin; Serum total vitamin B12; Dietary recommendations; Plasma methylmalonic acid; Plasma homocysteine

Outcome Measures

Primary Outcomes (4)

• Vitamin B12 biomarkers

  Serum vitamin B12 concentrations measured by a microbiological L. Leichmannii assay

  Change between screening (before pre-treatment phase), baseline (after pre-treatment phase) and post-intervention (16 weeks)

• Vitamin B12 biomarkers

  Serum holotranscobalamin concentrations measured by a AxSym based immunoassay

  Change between screening (before pre-treatment phase), baseline (after pre-treatment phase) and post-intervention (16 weeks)

• Vitamin B12 biomarkers

  Plasma methylmalonic acid concentrations measured by Gas Chromatography-Mass Spectrometry

  Change between screening (before pre-treatment phase), baseline (after pre-treatment phase) and post-intervention (16 weeks)

• Vitamin B12 biomarkers

  Plasma homocysteine concentrations measured by a fluorescence polarization immunoassay

  Change between screening (before pre-treatment phase), baseline (after pre-treatment phase) and post-intervention (16 weeks)

Secondary Outcomes (6)

• Folate status

  Change between screening (before pre-treatment phase), baseline (after pre-treatment phase) and post-intervention (16 weeks)

• MTHFR C677T polymorphism (rs1801133)

  At screening (before pre-treatment phase)

• Serum Pepsinogen concentrations

  At screening (before pre-treatment phase)

• Plasma creatinine

  At screening (before pre-treatment phase)

• BMI

  At baseline (after pre-treatment phase)

Study Arms (4)

Folic Acid + Placebo

PLACEBO COMPARATOR

400µg Folic Acid per day for 16 weeks after a pre-treatment phase with 400µg FA per day for 11 weeks

Dietary Supplement: Folic Acid

Folic Acid + Vitamin B12 Dose 1

ACTIVE COMPARATOR

400µg Folic Acid + 2 µg Vitamin B12 per day for 16 weeks after a pre-treatment phase with 400µg FA per day for 11 weeks

Dietary Supplement: Folic Acid; Dietary Supplement: 2 µg Vitamin B12

Folic Acid + Vitamin B12 Dose 2

ACTIVE COMPARATOR

400µg Folic Acid + 10 µg Vitamin B12 per day for 16 weeks after a pre-treatment phase with 400µg FA per day for 11 weeks

Dietary Supplement: Folic Acid; Dietary Supplement: 10 µg Vitamin B12

Folic Acid + Vitamin B12 Dose 3

ACTIVE COMPARATOR

400µg Folic Acid + 50 µg Vitamin B12 per day for 16 weeks after a pre-treatment phase with 400µg FA per day for 11 weeks

Dietary Supplement: Folic Acid; Dietary Supplement: 50 µg Vitamin B12

Interventions

Folic Acid DIETARY_SUPPLEMENT

400µg Folic Acid per day for 16 weeks

Folic Acid + Placebo; Folic Acid + Vitamin B12 Dose 1; Folic Acid + Vitamin B12 Dose 2; Folic Acid + Vitamin B12 Dose 3

2 µg Vitamin B12 DIETARY_SUPPLEMENT

2 µg Vitamin B12 per day for 16 weeks

Folic Acid + Vitamin B12 Dose 1

10 µg Vitamin B12 DIETARY_SUPPLEMENT

10 µg Vitamin B12 per day for 16 weeks

Folic Acid + Vitamin B12 Dose 2

50 µg Vitamin B12 DIETARY_SUPPLEMENT

50 µg Vitamin B12 per day for 16 weeks

Folic Acid + Vitamin B12 Dose 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• History of gastrointestinal, hepatic, renal, vascular or haematological diseases, or diabetes;
• Use of medication known to interfere with B12 metabolism (e.g. methotrexate, proton pump inhibitor drugs);
• Use of B vitamin supplements;
• Pregnancy;
• Plasma creatinine concentration \> 130 µmol/L;
• Hypochlorhydria (diagnosed serologically by pepsinogen I to Pepsinogen II ratio \< 3);
• Score of less than 25 on Folstein's Mini-Mental State Examination (a cognitive function screening test; for people aged 60 years and over);
• C→T polymorphism in the MTHFR gene

Sponsors & Collaborators

• University of Ulster: lead
• University of Dublin, Trinity College: collaborator
• University of Bergen: collaborator

Study Sites (1)

Human Intervention Studies Unit, Ulster University

Coleraine, Co.Londonderry, BT52 1SA, United Kingdom

Location

MeSH Terms

Interventions

Folic Acid; Vitamin B 12

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds, 4 or More Rings; Macrocyclic Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A double-blind randomized controlled trial.

Study Record Dates

• First Submitted: January 26, 2021
• First Posted: February 1, 2021
• Study Start: October 1, 2004
• Primary Completion: December 12, 2006
• Study Completion: December 12, 2006
• Last Updated: February 1, 2021

Record last verified: 2021-01

Locations

GB (1)