Effect of SNPs in the BCMO1 Enzyme (BETASNP2)

October 5, 2015 updated by: Newcastle-upon-Tyne Hospitals NHS Trust

Effect of SNPs in the Beta-carotene 15, 15'-Monooxygenase (BCMO1) Enzyme on Retinol Formation and Beta-carotene Plasma Responses

Summary:

Chronic intake of foods low in vitamin A (retinol) and provitamin A forming an unbalanced diet with little variety is common in young individuals in the United Kingdom (UK) population and can lead to subclinical micronutrient deficiency. Provitamin A sources such as β-carotene are cleaved centrally by the β-carotene 15,15'-monooxygenase (BCMO1) into retinal, the precursor of retinol. However, the amount of β-carotene and retinol produced after ingestion of β-carotene is highly variable between healthy individuals, with approximately 40% of the subjects being classified as low responders. Several stable isotope studies have shown a large disparity between the most efficient converters and the most inefficient converters of β-carotene with variations of up to 8-fold. It is possible that differences in β-carotene response may be due to single nucleotide polymorphisms (SNPs) in genes involved in aspects of β-carotene conversion. Previous work has shown that carriers of both, the 379V and 267S+379V BCMO1 variant alleles had a reduced ability to convert β-carotene. More importantly, 44% of the western population have the 379V haplotype. A high percentage of the Western population may therefore not be able to achieve adequate vitamin A intake if dietary β-carotene is a major source of their vitamin A intake. This is of particular relevance to vegetarians, to young individuals aged 19-24 years who have lower intakes of preformed retinol than any other age group, and to pregnant women. The aim of this study is to establish whether the maximum recommended dose for β-carotene of 7mg/day by the British Expert Committee on Vitamins and Minerals (EVM) can overcome the SNP effect in the BCMO1 enzyme.

Hypothesis:

The investigators hypothesize that the current maximum recommended intake of 7 mg of β-carotene per day cannot overcome the low convertor phenotype in BCMO1 to fulfill vitamin A requirements in these people.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

85

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Tyne & Wear
      • Newcastle upon Tyne, Tyne & Wear, United Kingdom, NE1 4LP
        • Newcastle NIHR Clinical Research Facility, Royal Victoria Infirmary

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 41 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Healthy individual.
  • Female.
  • Between 18 and 45 years of age.
  • Caucasian.
  • BMI between 18 and 30 kg/m2.
  • Subject willing and able to give written informed consent.

Exclusion Criteria:

  • Smoking.
  • Diabetes.
  • Gastrointestinal diseases.
  • Renal and hepatic diseases.
  • Hyperlipidaemia.
  • Preformed dietary retinol intake above 60% of reference nutrient intake (RNI) values.
  • Recreational drug use.
  • Multi-vitamin consumption.
  • Pregnancy.
  • Menopause.
  • Allergy or sensitivity to study products or ingredients.
  • Blood donation 3 months prior to screening.
  • Participation in other clinical study 4 weeks prior to study start.
  • Suspected inability or unwillingness to comply with study procedures.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Supplement A
Beta-carotene 7mg formulation A
Dietary supplement: Beta-carotene
Other: Supplement B
Beta-carotene 7mg formulation B
Dietary supplement: Beta-carotene
Other: Supplement C
Beta-carotene 7mg formulation C
Dietary supplement: Beta-carotene

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Area under the plasma concentration versus time curve (AUC) of beta-carotene
Time Frame: Pharmacokinetic measures (0,1,4,36,46,57,60 days post-dose)
Pharmacokinetic measures (0,1,4,36,46,57,60 days post-dose)
Area under the plasma concentration versus time curve (AUC) of [13C]retinol
Time Frame: Pharmacokinetic measures (0,1,2,3,4,8,10,22,36,46,57,58,59,60,64,66,78,92,113 days post-dose)
Pharmacokinetic measures (0,1,2,3,4,8,10,22,36,46,57,58,59,60,64,66,78,92,113 days post-dose)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Newcastle-upon-Tyne Hospitals NHS Trust

Collaborators

Newcastle University
DSM Nutritional Products, Inc.

Investigators

  • Principal Investigator: Georg Lietz, PhD, Newcastle University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2012

Primary Completion (Actual)

September 1, 2014

Study Completion (Actual)

September 1, 2014

Study Registration Dates

First Submitted

October 21, 2014

First Submitted That Met QC Criteria

October 23, 2014

First Posted (Estimate)

October 27, 2014

Study Record Updates

Last Update Posted (Estimate)

October 6, 2015

Last Update Submitted That Met QC Criteria

October 5, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2011-01-18-BETASNP2
  • REC 11/NE/0211 (Other Identifier: National Research Ethics Service (NRES))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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